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Sample records for carcinoma models-in vivo

  1. Design of cholesterol arabinogalactan anchored liposomes for asialoglycoprotein receptor mediated targeting to hepatocellular carcinoma: In silico modeling, in vitro and in vivo evaluation.

    Science.gov (United States)

    Pathak, Pankaj; Dhawan, Vivek; Magarkar, Aniket; Danne, Reinis; Govindarajan, Srinath; Ghosh, Sandipto; Steiniger, Frank; Chaudhari, Pradip; Gopal, Vijaya; Bunker, Alex; Róg, Tomasz; Fahr, Alfred; Nagarsenker, Mangal

    2016-07-25

    We have developed active targeting liposomes to deliver anticancer agents to ASGPR which will contribute to effective treatment of hepatocellular carcinoma. Active targeting is achieved through polymeric ligands on the liposome surface. The liposomes were prepared using reverse phase evaporation method and doxorubicin hydrocholoride, a model drug, was loaded using the ammonium sulphate gradient method. Liposomes loaded with DOX were found to have a particle size of 200nm with more than 90% entrapment efficiency. Systems were observed to release the drug in a sustained manner in acidic pH in vitro. Liposomes containing targeting ligands possessed greater and selective toxicity to ASGPR positive HepG2 cell lines due to specific ligand receptor interaction. Bio-distribution studies revealed that liposomes were concentrated in the liver even after 3h of administration, thus providing conclusive evidence of targeting potential for formulated nanosystems. Tumor regression studies indicated greater tumor suppression with targeted liposomes thereby establishing superiority of the liposomal system. In this work, we used a novel methodology to guide the determination of the optimal composition of the targeting liposomes: molecular dynamics (MD) simulation that aided our understanding of the behaviour of the ligand within the bilayer. This can be seen as a demonstration of the utility of this methodology as a rational design tool for active targeting liposome formulation.

  2. Tamoxifen can reverse multidrug resistance of colorectal carcinoma in vivo

    Institute of Scientific and Technical Information of China (English)

    Li-Zong Shen; Yi-Bing Hua; Xue-Ming Yu; Qing Xu; Tao Chen; Jian-Hua Wang; Wen-Xi Wu

    2005-01-01

    AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER).METHODS: Multidrug resistance was determined by means of semi-quantitative retro-transcription polymerase chain reaction (RT-PCR) to test mdr1 gene mRNA and ER expression was studied by immunohistochemistry. Tumor tissues from three cases of human colon carcinoma, which had mdr1( + )/ER(+ ), mdr1( + )/ER(-), mdr1(-) expressions,were planted subcutaneously in the neck of nude mice to establish three xenograft models. These models were subdivided into four subgroups randomly: Doxorubicin(DOX)-treated group, TAN-treated group, DOX and TAM group and control group. The dimensions of these xenografts were measured after each course of treatment and the xenografts were removed at the end of the experiments for measurements of weight and the variation of mdr1 mRNA level with RT-PCR. In each course, TAM[15 mg/(kg/d)] was administrated orally per day in the first seven days and DOX (3.6 mg/kg) was injected peritoneally on the first day. Data was evaluated by q and ttests.RESULTS: In the animal models with mdr1(-) tumor, the weights and volumes of the planted tumor in DOX group[(39.1±2.29) mg, (31.44±1.61) mm3] and TAM and DOX group [(38.72±2.56) mg, (31.31±1.74) mm3], which were lesser than that of control group [(45.48±3.92) mg,(36.42±2.77) mm3, P = 0.037, P = 0.016 respectively]significantly. In the animal models with mdr1(+)/ER(+)tumor, the weights and volumes of planted tumor were not affected by DOX or TAM treatment; however, in TAM and DOX group [(425.5±28.58) mg, (340.35±22.28) mm3],they were significantly less than that of control group[(634.23±119.41) mg, (507.45±93.34) mm3, P = 0.022,P = 0.045 respectively], which are similar to that in the models with mdr1(+)/ER(-) tumor. No significant changes were found in the expressive level of mdr1 mRNA following these treatments.CONCLUSION: The expression

  3. INVESTIGATION OF THE THERAPEUTIC EFFECT OF EXPRESSION OF TRAIL IN VIVO ON MOUSE HEPATOCELLULAR CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张桂梅; 薛胜利; 张慧; 黎培员; 李东; 冯作化

    2003-01-01

    Objective: To construct an eukaryotic expressing plasmid of mouse TRAIL (mTRAIL), and investigate its ability to induce the apoptosis of hepatocellular carcinoma cells in vitro and in vivo, its inhibitory effect on the growth of hepatocellular carcinoma, and its synergism with pCH510, an eukaryotic expressing plasmid of recombinant human FN polypeptide. Methods: The eukaryotic expressing plasmid of mTRAIL was constructed by RT-PCR and DNA recombination techniques. Gene transfection was performed in vitro and in vivo. The apoptosis rate of hepatocellular carcinoma cells was measured by Flow Cytometry. The apoptosis of hepatocellular carcinoma cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) and histochemistry techniques. The inhibitory effect of gene transfection on solid tumor was observed in mice. Results: The cDNA of mTRAIL was amplified by RT-PCR from the RNA of mouse spleen cells, and cloned into the eukaryotic expressing vector pcDNA3.1. The recombinant plasmid was designated as pX1. The BHK cells transfected with plasmid pX1 could attack H22 hepatocellular carcinoma cells and induce the apoptosis of them. The transfection of plasmid pX1 through injection into mouse muscles could inhibit the growth of hepatocellular carcinoma by inducing the apoptosis of tumor cells. Plasmid pX1 and pCH510 had a synergistic inhibitory effect on the hepatocellular carcinoma growth. Conclusion: Plamid pX1 could be expressed in cells and in vivo in mouse. The expression of pX1 in vivo and in vitro could induce the apoptosis of hepatocellular carcinoma cells and inhibit the growth of hepatocellular carcinoma. Plasmid pX1 and pCH510 had a synergistic inhibitory effect on the hepatocellular carcinoma growth.

  4. Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular carcinoma in vitro and in vivo.

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    Xiang, Jianfeng; Xiang, Yanjie; Lin, Shengming; Xin, Dongwei; Liu, Xiaoyu; Weng, Lingling; Chen, Tao; Zhang, Minguang

    2014-04-01

    Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world whose chemoprevention became increasingly important in HCC treatment. Although the anticancer effects of asparagus constituents have been investigated in several cancers, its effects on hepatocellular carcinoma have not been fully studied. In this study, we investigated the anticancer effects of the deproteinized asparagus polysaccharide on the hepatocellular carcinoma cells using the in vitro and in vivo experimental model. Our data showed that deproteinized asparagus polysaccharide might act as an effective inhibitor on cell growth in vitro and in vivo and exert potent selective cytotoxicity against human hepatocellular carcinoma Hep3B and HepG2 cells. Further study showed that it could potently induce cell apoptosis and G2/M cell cycle arrest in the more sensitive Hep3B and HepG2 cell lines. Moreover, deproteinized asparagus polysaccharide potentiated the effects of mitomycin both in vitro and in vivo. Mechanistic studies revealed that deproteinized asparagus polysaccharide might exert its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. In conclusion, deproteinized asparagus polysaccharide exhibited significant anticancer activity against hepatocellular carcinoma cells and could sensitize the tumoricidal effects of mitomycin, indicating that it is a potential therapeutic agent (or chemosensitizer) for liver cancer therapy.

  5. [Possibility of achieving the Pasteur effect by ascites carcinoma cells in vivo].

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    Tagi-zade, S B; Shapot, V S

    1971-01-01

    Possibility of Pasteur effect in cancer cells in vivo was studied on mice with Ehrlich ascites carcinoma and rats with carcinoma of ovaries++. The experiments were run in two series. In the first series, all animals were saturated with oxygen through inhalation. In this series, part of the animals were given glucose subcutaneously. In the second series, all animals were given oxygen intraperitoneally and some of the animals with carcinoma of ovaries++ were given glucose subcutaneously. Values of inhibition of glycolytic activity in cancer cells under various experimental conditions were estimated through a calculated coefficient. Results of the experiment evidenced that inhalational saturation of animals with oxygen did not inhibit glycolysis of ascites cells in vivo while after intraperitoneal administration of oxygen, coefficient of inhibition of glycolytic activity in mice with Ehrlich ascites++ carcinoma after 45-65 min was 50-615, respectively. Experiments on rats showed that inhibition of glycolytic activity in rats can be revealed during simultaneous administration of oxygen intraperitoneally and of glucose subcutaneously. The authors reached the conclusion that under adequate supply of cancer cells with oxygen respiration can suppress glycolysis at the level of organism as well.

  6. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    International Nuclear Information System (INIS)

    Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-PrkdcScid/J (in the following: NOD-Scid) mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies

  7. In vivo image of radioiodinated IVDU and IVFRU in HSV-TK gene tranduced hepatocellular carcinoma bearing buffalo rat

    International Nuclear Information System (INIS)

    , selective localization of 123I-IVFRU observed. Both compound could be used in imaging HSV-tk gene expression for gene therapy monitoring in MCA-tk tumor model. In HSV-tk tranduced hepatocellular carcinoma bearing buffalo rat model, IVFRU could be used as prognostic marker

  8. In Ovo PET Imaging Of A Human Colorectal Carcinoma Model In Chicken Chorioallantoic Membrane

    OpenAIRE

    Warnock, Geoffrey; Turtoi, Andrei; Blomme, Arnaud; Gonzalez, Arnaud; Bretin, Florian; Bahri, Mohamed Ali; Lemaire, Christian; Seret, Alain; Castronovo, Vincenzo; Luxen, André; Plenevaux, Alain

    2012-01-01

    Aim. The objective of this study was to use in vivo PET/CT imaging as a validation tool for a novel human colorectal carcinoma model being developed in chicken chorioallantoic membrane (CAM). For this initial pilot study a cell line modeling colon cancer was selected and imaged using [18F]fluorodeoxyglucose (FDG). Materials and methods. A window was made in the shell of fertilized chicken eggs and 3x106 SW1222 human colorectal carcinoma cells were implanted at day 10 post-fertilization. On...

  9. Apoptosis inhibitor 5 (API-5; AAC-11; FIF) is upregulated in human carcinomas in vivo

    OpenAIRE

    Koci, Lenka; Chlebova, Katarina; Hyzdalova, Martina; Hofmanova, Jirina; Jira, Miroslav; Kysela, Petr; Kozubik, Alois; Kala, Zdenek; Krejci, Pavel

    2012-01-01

    Apoptosis inhibitor 5 (API-5) is a 55 kDa nuclear protein with potent anti-apoptotic signaling in tumor cells in vitro. In this study, we analyzed the expression of the API-5 protein in vivo in a broad spectrum of human carcinomas, including those of the colon, lung, liver, kidney, pancreas, stomach and esophagus using tumor tissues obtained during tumor resection. The results showed significant upregulation of API-5 expression in biopsies of lung (23%, n=13) and colorectal tumors (33%, n=27)...

  10. Galectin-9 suppresses the growth of hepatocellular carcinoma via apoptosis in vitro and in vivo.

    Science.gov (United States)

    Fujita, Koji; Iwama, Hisakazu; Sakamoto, Teppei; Okura, Ryoichi; Kobayashi, Kiyoyuki; Takano, Jitsuko; Katsura, Akiko; Tatsuta, Miwa; Maeda, Emiko; Mimura, Shima; Nomura, Takako; Tani, Joji; Miyoshi, Hisaaki; Morishita, Asahiro; Yoneyama, Hirohito; Yamana, Yuka; Himoto, Takashi; Okano, Keiichi; Suzuki, Yasuyuki; Niki, Toshiro; Hirashima, Mitsuomi; Masaki, Tsutomu

    2015-01-01

    Galectin-9, a soluble β-galactoside-binding animal lectin, evokes apoptosis in various human cancer cell lines. The galectin-9 antitumor effect against hepatocellular carcinoma (HCC) is, however, unknown. We investigated whether galectin-9 suppresses HCC growth in vitro and in vivo. We assessed the antitumor effect of galectin-9 on HCC cells by conducting WST-8 assay in vitro and xenograft model analysis in vivo. Galectin-9-induced apoptosis was evaluated by FACS and ELISA in vitro and by TUNEL stain in vivo. Cell cycle alteration was profiled by FACS. Caspases were profiled by colorimetry. MicroRNAs related to the galectin-9 antitumor effects were determined using microarrays, and their antitumor effect was confirmed in a transfection study in vitro. The expression levels of the target proteins of the miRNAs extracted above were analyzed by western blot analysis. To summarize the results, galectin-9 inhibited the growth of the HCC cell lines HLE and Li-7 in vitro and Li-7 in vivo inducing apoptosis. Cell cycle turnover was not arrested in HLE and Li-7 cells in vitro. miR-1246 was similarly extracted both in vitro and in vivo, which sensitized Li-7 cells to apoptosis when transfected into the cells. DYRK1A, a target protein of miR-1246 was downregulated in Li-7 cells. Caspase-9 was upregulated in Li-7 cells in vitro and in vivo. In conclusion, galectin-9 inhibited the growth of HCC cells by apoptosis, but not cell cycle arrest, in vitro and in vivo. miR-1246 mediated signals of galectin-9, possibly through miR-1246-DYRK1A-caspase-9 axis. Galectin-9 might be a candidate agent for HCC chemotherapy. PMID:25823465

  11. Combination Gene Therapy for Liver Metastasis of Colon Carcinoma in vivo

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    Chen, Shu-Hsai; Chen, X. H. Li; Wang, Yibin; Kosai, Ken-Ichiro; Finegold, Milton J.; Rich, Susan S.

    1995-03-01

    The efficacy of combination therapy with a "suicide gene" and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombinant adenoviral vectors containing various control and therapeutic genes were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals treated with a control vector or a mouse interleukin 2 vector, those treated with a herpes simplex virus thymidine kinase vector, with or without the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with both vectors developed an effective systemic antitumoral immunity against challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the presence of MCA-26 tumor-specific cytolytic CD8^+ T lymphocytes. The results suggest that combination suicide and cytokine gene therapy in vivo can be a powerful approach for treatment of metastatic colon carcinoma in the liver.

  12. An in vivo cytogenetic analysis of human oral squamous cell carcinoma

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    Abhimanyu Mohanta

    2015-01-01

    Full Text Available Background: Oral cancer ranks in the top three of all cancers in India, which accounts for over 30% of all cancers reported in the country. The micronucleus test (MNT is one of the most widely applied short term tests used in genetic toxicology to evaluate the mutagenicity and carcinogenicity. Aims: The present study aims at an in vivo cytogenetic analysis of human oral squamous cell carcinoma and to assess the applicability of MNT in diagnosing early detection of oral carcinoma. Materials and Methods: Exfoliated scrape smears were collected from the clinically diagnosed 136 patients suffering from oral precancerous and cancerous lesions. The wet fixed smears were stained by adopting Papanicolaou's staining protocol and counter-stained with Giemsa's solution. Results: The frequency of micronucleated cells has been observed to be in increasing order with the increase of the age-groups and from control to precancerous to cancerous cases significantly in both sexes. Conclusion: Micronucleus formation in the oral mucosa could be a biomarker of genetic damage and also a potential onco-indicator in the long run of oral carcinogenesis. Therefore, MNT can be applied for the early detection of oral carcinoma in the human being.

  13. Targeted transferrin-modified polymeric micelles: enhanced efficacy in vitro and in vivo in ovarian carcinoma.

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    Sawant, Rupa R; Jhaveri, Aditi M; Koshkaryev, Alexander; Zhu, Lin; Qureshi, Farooq; Torchilin, Vladimir P

    2014-02-01

    In this study, transferrin (Tf)-modified poly(ethylene glycol)-phosphatidylethanolamine (mPEG-PE) micelles loaded with the poorly water-soluble drug, R547 (a potent and selective ATP-competitive cyclin-dependent kinase (CDK) inhibitor), were prepared and evaluated for their targeting efficiency and cytotoxicity in vitro and in vivo to A2780 ovarian carcinoma cells, which overexpress transferrin receptors (TfR). At 10 mM lipid concentration, both Tf-modified and plain micelles solubilized 800 μg of R547. Tf-modified micelles showed enhanced interaction with A2780 ovarian carcinoma cells in vitro. The involvement of TfR in endocytosis of Tf-modified micelles was confirmed by colocalization studies of micelle-treated cells with the endosomal marker Tf-Alexa488. We confirmed endocytosis of micelles in an intact form with micelles loaded with a fluorescent dye and additionally labeled with fluorescent lipid. The in vitro cytotoxicity and in vivo tumor growth inhibition studies in A2780-tumor bearing mice confirmed the enhanced efficacy of Tf-modified R547-loaded micelles compared to free drug solution and to nonmodified micelles. The results of this study demonstrate the potential application of Tf-conjugated polymeric micelles in the treatment of tumors overexpressing TfR. PMID:24325630

  14. Indole-3-carbinol inhibits nasopharyngeal carcinoma growth through cell cycle arrest in vivo and in vitro.

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    Zhe Chen

    Full Text Available Nasopharyngeal carcinoma is a common malignant tumor in the head and neck. Because of frequent recurrence and distant metastasis which are the main causes of death, better treatment is needed. Indole-3-carbinol (I3C, a natural phytochemical found in the vegetables of the cruciferous family, shows anticancer effect through various signal pathways. I3C induces G1 arrest in NPC cell line with downregulation of cell cycle-related proteins, such as CDK4, CDK6, cyclin D1 and pRb. In vivo, nude mice receiving I3C protectively or therapeutically exhibited smaller tumors than control group after they were inoculated with nasopharyngeal carcinoma cells. The expression of CDK4, CDK6, cyclin D1 and pRb in preventive treatment group and drug treatment group both decreased compared with the control group. We conclude that I3C can inhibit the growth of NPC in vitro and in vivo by suppressing the expression of CDK and cyclin families. The drug was safe and had no toxic effects on normal tissues and organs.

  15. In vivo dose verification for photon treatments of head and neck carcinomas using MOSFET dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Tung, C.J. [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan (China)], E-mail: cjtung@mx.nthu.edu.tw; Wang, L.C. [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan (China); Wang, H.C. [Department of Radiation Oncology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Lee, C.C.; Chao, T.C. [Department of Medical Imaging and Radiological Sciences, Chang Gung University, Kwei-Shan, Taiwan (China)

    2008-02-15

    In vivo dosimetry was performed for the head and neck carcinoma patients during the treatment of a large photon field using MOSFETs. This study followed the protocols recommended by the European Society for Therapeutic Radiology and Oncology. A total of 32 portals belonging to 12 patients were under investigation. Results showed that the deviation between in vivo midline doses and planned target doses was partly due to the manual dose calculations in the treatment planning which used the patient geometric thickness rather than the radiological thickness. Other factors responsible for this deviation included the difficult positioning of MOSFETs on the face mask, the asymmetric positioning of MOSFETs on the left and right sides of the mask, and the asymmetric tissue inhomogeneities with respect to the body midline. To reduce the deviation contributed from these factors, in vivo midline doses were calculated by averaging the results for each bilaterally opposed portals and compared with corresponding planned target doses. This comparison showed that MOSFET dosimeters are suitable for in vivo dosimetry of the present study.

  16. Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo.

    Science.gov (United States)

    Miyoshi, Hisaaki; Kato, Kiyohito; Iwama, Hisakazu; Maeda, Emiko; Sakamoto, Teppei; Fujita, Koji; Toyota, Yuka; Tani, Joji; Nomura, Takako; Mimura, Shima; Kobayashi, Mitsuyoshi; Morishita, Asahiro; Kobara, Hideki; Mori, Hirohito; Yoneyama, Hirohito; Deguchi, Akihiro; Himoto, Takashi; Kurokohchi, Kazutaka; Okano, Keiichi; Suzuki, Yasuyuki; Murao, Koji; Masaki, Tsutomu

    2014-07-01

    Metformin is a commonly used oral anti-hyperglycemic agent of the biguanide family. Recent studies suggest that metformin may reduce cancer risk and improve prognosis. However, the antitumor mechanism of metformin in several types of cancers, including hepatocellular carcinoma (HCC), has not been elucidated. The goal of the present study was to evaluate the effects of metformin on HCC cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with the antitumor effect of metformin in vitro. We used the cell lines Alex, HLE and Huh7, and normal hepatocytes to study the effects of metformin on human HCC cells. In an in vivo study, athymic nude mice bearing xenograft tumors were treated with metformin or left untreated. Tumor growth was recorded after 4 weeks, and the expression of cell cycle-related proteins was determined. Metformin inhibited the proliferation of Alex, HLE and Huh7 cells in vitro and in vivo. Metformin blocked the cell cycle in G0/G1 in vitro and in vivo. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, cyclin E and cyclin-dependent kinase 4 (Cdk4). In addition, microRNA (miRNA) expression was markedly altered by the treatment with metformin in vitro and in vivo. In addition, various miRNAs induced by metformin also may contribute to the suppression of tumor growth. Our results demonstrate that metformin inhibits the growth of HCC, possibly by inducing G1 cell cycle arrest through the alteration of microRNAs. PMID:24806290

  17. Paridis saponins inhibiting carcinoma growth and metastasis in vitro and in vivo.

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    Shuli, Man; Wenyuan, Gao; Yanjun, Zhang; Chaoyi, Ma; Liu, Yang; Yiwen, Li

    2011-01-01

    Paris polyphylla Smith var. yunnanensis extracts, Rhizoma Paridis saponins (RPS) have been found to show strong antitumor activity. However, few studies have yet investigated pulmonary metastasis treatment with this herb. To detail the effective components in RPS and discuss the preliminary mechanism of antitumor effects in vivo and in vitro, a mixture isolated from RPS was investigated. The main constituents were identified as polyphyllin D, formosanin C, dioscin, Paris H, Paris VII and pennogennin 3-O-α-L-rhamnopyranosyl (1→4)-[β-L-rhamnopyranosyl (1→2)]-β-D-glucopyranoside. In our experiments, LA795 cells were exposed to the mixed compounds. Migration inhibition was evaluated by wound healing assay and migration assay in non-cytotoxic dose which was determined by MTT assay. The results demonstrated that the constituent in varying degrees inhibited the migration of the tumor cells in vitro. The mixture also showed antitumor effects on carcinoma in vivo. In conclusion, the mixture is a potent anticancer agent that elicits programmed cell death and inhibits the migration in murine lung adenocarcinoma, both in vitro and in vivo. PMID:21468914

  18. Sulindac Induces Apoptosis and Inhibits Tumor Growth In Vivo in Head and Neck Squamous Cell Carcinoma

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    Mark A. Scheper

    2007-03-01

    Full Text Available Sulindac has antineoplastic effects on various cancer cell lines; consequently, we assessed sulindac's effects on laryngeal squamous cell carcinoma (SCC cells in vitro and in vivo. In vitro, SCC (HEP-2 cells treated with various cyclooxygenase inhibitors or transfected with constitutively active signal transducer and activator of transcription 3 (Stat3 or survivin vectors were analyzed using Western blot analysis, annexin V assay, and cell proliferation assay. In parallel, nude mice injected subcutaneously with HEP-2 cells were either treated intraperitoneally with sulindac or left untreated, and analyzed for tumor weight, survivin expression, and tyrosine-phosphorylated Stat3 expression. In vitro studies confirmed the selective antiproliferative and proapoptotic effects of sulindac, which also downregulated Stat3 and survivin protein expression. Stat3 or survivin forced expression partially rescued the antiproliferative effects of sulindac. In vivo studies showed significant repression of HEP-2 xenograft growth in sulindactreated mice versus controls, with near-complete resolution at 10 days. Additionally, tumor specimens treated with sulindac showed downregulation of phosphorylated tyrosine-705 Stat3 and survivin expression. Taken together, our data suggest, for the first time, a specific inhibitory effect of sulindac on tumor growth and survivin expression in laryngeal cancer, both in vitro and in vivo, in a Stat3-dependent manner, suggesting a novel therapeutic approach to head and neck cancer.

  19. Establishment of VX2 breast carcinoma model in rabbit by injecting tumor mass suspension

    Institute of Scientific and Technical Information of China (English)

    CHEN Jiang-hao; YAO Qing; WANG Ling; LING Rui; ZHANG Ju-liang; WANG Ting; WANG Hui; YANG Hua

    2004-01-01

    Objective: To establish a stable model of VX2 breast carcinoma in rabbit and select the optimal way.Methods: Thirty female New Zealand rabbits were randomly divided into 3 groups with 10 in each. Tumor cell suspensions or tumor mass suspensions were injected into breast tissues of rabbits of group A and B, respectively. Tumor blocks were surgically implanted in rabbit breasts of group C. Tumor formation rate, tumor growth rate, and tumor-bearing survival time was compared, and the histological feature of tumor was observed. Results: Models were established conveniently and successfully in rabbits received injection of tumor mass suspensions. Tumor proliferated rapidly with the biological feature of squamous cell carcinoma. Conclusion: VX2 breast carcinoma model in rabbit was established successfully. Intramammary injection of tumor mass suspension is the best method.

  20. Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Jia He; Xiao-Feng Tang; Qiu-Yan Chen; Hai-Qiang Mai; Zhou-Feng Huang; Jiang Li; Yi-Xin Zeng

    2012-01-01

    Establishing Epstein-Barr virus (EBV)-specific cytolytic T lymphocytes (EBV-CTLs) from peripheral blood mononuclear cells (PBMCs) for adoptive immunotherapy has been reported in EBV-associated malignancies including Hodgkin's lymphoma and nasopharyngeal carcinoma (NPC).In the current study,we performed ex vivo expansion of tumor-infiltrating lymphocytes (TILs) obtained from NPC biopsy specimens with a rapid expansion protocol using anti-CD3 monoclonal antibody (OKT3),recombinanthuman interleukin (IL)-2,and irradiated PBMCs from healthy donors to initiate the growth of TILs.Young TIL cultures comprised of more than 90% of CD3+ T cells,a variable percentage of CD3+CD8+ and CD3+CD4+ T cells,and less than 10% of CD3-CD16+ natural killer cells,a similar phenotype of EBV-CTL cultures from PBMCs.Interestingly,TIL cultures secreted high levels of the Th1 cytokines,interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α),and low levels of the Th2 cytokines,IL-4 and IL10.Moreover,young TILs could recognize autologous EBV-transformed B lymphoblast cell lines,but not autologous EBV-negative blast cells or allogeneic EBV-negative tumor cells.Taken together,these data suggest that ex vivo expansion of TILs from NPC biopsy tissue is an appealing alternative method to establish T cell-based immunotherapy for NPC.

  1. Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy

    Directory of Open Access Journals (Sweden)

    Jiang Li

    2012-06-01

    Full Text Available Establishing Epstein-Barr virus(EBV-specific cytolytic T lymphocytes(EBV-CTLs from peripheral blood mononuclear cells(PBMCs for adoptive immunotherapy has been reported in EBV-associated malignancies including Hodgkin's lymphoma and nasopharyngeal carcinoma(NPC. In the current study, we performed ex vivo expansion of tumor-infiltrating lymphocytes(TILs obtained from NPC biopsy specimens with a rapid expansion protocol using anti-CD3 monoclonal antibody(OKT3, recombinant human interleukin(IL-2, and irradiated PBMCs from healthy donors to initiate the growth of TILs. Young TIL cultures comprised of more than 90% of CD3+ T cells, a variable percentage of CD3+CD8+ and CD3+CD4+ T cells, and less than 10% of CD3-CD16+ natural killer cells, a similar phenotype of EBV-CTL cultures from PBMCs. Interestingly, TIL cultures secreted high levels of the Th1 cytokines, interferon gamma (IFNγ and tumor necrosis factor-alpha (TNF-α, and low levels of the Th2 cytokines, IL-4 and IL-10. Moreover, young TILs could recognize autologous EBV-transformed B lymphoblast cell lines, but not autologous EBV-negative blast cells or allogeneic EBV-negative tumor cells. Taken together, these data suggest that ex vivo expansion of TILs from NPC biopsy tissue is an appealing alternative method to establish T cell-based immunotherapy for NPC.

  2. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes

    Science.gov (United States)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  3. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes.

    Science.gov (United States)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  4. Construction of radiation - induced metastasis model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Kuk; Jang, Su Jin; Kang, Sung Wook; Kim, Jae Sung; Hwang, Sang Gu; Kang, Joo Hyun [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2011-05-15

    In treatment of cancer, distant metastases are important limiting factor because an estimated 50% of all cancer patients will develop metastases, and the metastases are major causing of cancer treatment failure. Recently a few reports indicated {gamma}-radiation induced an increase of invasiveness of several cancer cells. In this study, we had tried to show the possibility that radiation could also induce metastasis in vivo system. To prove our hypothesis, we constructed primary tumor by using C6-TL transfectant cell line expressing HSV1-tk and firefly luciferase (fLuc), and then {gamma}-radiation was treated to xenografts locally. Treatment of {gamma}-radiation to primary C6-TL xenografts of mice reduced size of xenografts and elongated survival of mice than those of mock control mice. But we also show that {gamma}-radiation treatment was followed by the growth of dormant metastases in various organs including lung and intestine after 2-4 weeks of {gamma}-radiation treatment. When bioluminescence imaging indicated growth of tumor in organs in mice, we sacrificed the mice and repeat acquired bioluminescence imaging after repeatedly. These images presented tumor growth locations exactly in organs. Because metastatic tumor candidates have morphology of foci, biopsies were performed for histological analysis or PCR analysis to confirm metastases. In most foci, histological analysis indicated several features of typical cancer tissue and PCR analysis showed present of fLuc gene in metastases. Detection of fLuc gene in metastases indicated these foci were originated from primary C6-TL xenografts, and the results suggest that {gamma}-radiation could promote metastasis in vivo as well as in vitro system. Although we need to understand changes of intracellular signaling or physiological phenomena of the radiation-induced metastasis yet, these results also imply that {gamma}-radiation treatment only to cancer patients need to pay attention carefully, and development of new

  5. Overexpression of the dynein light chain km23-1 in human ovarian carcinoma cells inhibits tumor formation in vivo and causes mitotic delay at prometaphase/metaphase.

    Science.gov (United States)

    Pulipati, Nageswara R; Jin, Qunyan; Liu, Xin; Sun, Baodong; Pandey, Manoj K; Huber, Jonathan P; Ding, Wei; Mulder, Kathleen M

    2011-08-01

    km23-1 is a dynein light chain that was identified as a TGFβ receptor-interacting protein. To investigate whether km23-1 controls human ovarian carcinoma cell (HOCC) growth, we established a tet-off inducible expression system in SKOV-3 cells in which the expression of km23-1 is induced upon doxycycline removal. We found that forced expression of km23-1 inhibited both anchorage-dependent and anchorage-independent growth of SKOV-3 cells. More importantly, induction of km23-1 expression substantially reduced the tumorigenicity of SKOV-3 cells in a xenograft model in vivo. Fluorescence-activated cell sorting analysis of SKOV-3 and IGROV-1 HOCCs demonstrated that the cells were accumulating at G2/M. Phospho-MEK, phospho-ERK and cyclin B1 were elevated, as was the mitotic index, suggesting that km23-1 suppresses HOCCs growth by inducing a mitotic delay. Immunofluorescence analyses demonstrated that the cells were accumulating at prometaphase/metaphase with increases in multipolar and multinucleated cells. Further, although the mitotic spindle assembly checkpoint protein BubR1 was present at the prometaphase kinetochore in Dox+/- cells, it was inappropriately retained at the metaphase kinetochore in Dox- cells. Thus, the mechanism by which high levels of km23-1 suppress ovarian carcinoma growth in vitro and inhibit ovary tumor formation in vivo appears to involve a BubR1-related mitotic delay.

  6. Adenovirus-mediated ING4 expression reduces multidrug resistance of human gastric carcinoma cells in vitro and in vivo.

    Science.gov (United States)

    Mao, Zong-Lei; He, Song-Bing; Sheng, Wei-Hua; Dong, Xiao-Qiang; Yang, Ji-Cheng

    2013-11-01

    Chemotherapy is the primary treatment for both resectable and advanced gastric carcinoma, yet multiple drug resistance (MDR) of gastric carcinoma remains a significant therapeutic obstacle. The development of novel strategies to reduce MDR in gastric carcinoma would yield a better outcome following chemotherapy. ING4, a member of the inhibitor of growth (ING) tumor-suppressor family, possesses antitumor and radiosensitization or chemosensitization effects in a variety of human cancers. The present study investigated the effects and possible mechanisms of action of adenovirus-mediated ING4 (AdVING4) on the reversion of human gastric carcinoma cell MDR in vitro and in vivo in nude mouse xenografts. The data showed that the expression of ING4 mRNA and protein was dramatically downregulated (or lost) in gastric carcinoma SGC7901/CDDP cells after CDDP-induced MDR phenotype and in the parental SGC7901 cells. AdVING4‑induced ING4 expression reversed MDR and induced apoptosis of SGC7901/CDDP cells in vitro and in vivo in the SGC7901/CDDP xenograft tumors. Furthermore, AdVING4 substantially downregulated the expression of MDR-related proteins P-gp and MRP1 and apoptosis‑related proteins Bcl-2 and survivin, but upregulated the expression of apoptosis-related protein Bax in the SGC7901/CDDP xenograft tissues. The reversion effects elicited by AdVING4 on gastric cancer cell MDR were closely associated with the downregulation of ATP-binding cassette transporters and activation of apoptotic pathways. Thus, these findings suggest that AdVING4 may be a feasible modulator for the MDR phenotype of gastric carcinoma cells. PMID:23969950

  7. Selective tropism of liver stem cells to hepatocellular carcinoma in vivo

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the selective tropism of liver stem cells to hepatocellular carcinoma (HCC) in an animal model and its feasibility as a vector to deliver therapeutic genes for targeted therapy of HCC.METHODS: WB-F344, a kind of rat liver stem cell,was infected with recombinant virus to establish a cell line with stable, high-level expressing enhanced green fluorescent protein (EGFP). An animal model of HCC in Wistar rats was established by implanting HCC cells (CBRH7919) combined with an immunosuppressive drug.EGFP labeled liver stem cells were injected into caudal veins of the animals and distribution was observed at different time points after injection. SDF-1 and c-kit expression in non-tumor liver and tumor tissue were analysed by immunohistochemistry for the relationshiop between the expression and migration of liver stem cells.Furthermore, hepatic stem cells were injected via the portal vein, hepatic artery, caudal vein, or directly into the pericancerous liver tissue, respectively, and effects on migration, localization, and proliferation of the hepatic stem cells within the tumor tissue were observed and analyzed.RESULTS: Recombinant adenovirus could deliver the EGFP gene to hepatic stem cells. A new stem cell line,named WB-EGFP, was established that stably expressed EGFP. WB-EGFP cells still showed selective tropism towards HCC and EGFP expression was stable in vivo.According to immunohistochemistry results, SDF-1 may not be related to the mechanisms of tropism of hepatic stem cells. Different application sites affected the distribution of liver stem cells. Injection via the portal vein was superior with regard to selective migration,localization, and proliferation of the hepatic stem cells within the tumor tissue.CONCLUSION: Liver stem cells have the biological behavior of selective migration to HCC in vivo and they could localize and proliferate within HCC tissue stably expressing the target gene. Liver stem cells are a potential tool for a targeted

  8. In vivo confocal microscopy of basal cell carcinoma: a systematic review of diagnostic accuracy.

    Science.gov (United States)

    Kadouch, D J; Schram, M E; Leeflang, M M; Limpens, J; Spuls, P I; de Rie, M A

    2015-10-01

    Basal cell carcinoma (BCC) is the most prevalent type of skin cancer. Histologic analysis of punch biopsy or direct excision specimen is used to confirm clinical diagnosis. In vivo reflectance confocal microscopy (RCM) is a non-invasive imaging modality that could facilitate early diagnosis and minimize unnecessary invasive procedures. We systematically reviewed diagnostic accuracy (sensitivity and specificity) of RCM in diagnosing primary BCCs to judge its usefulness. Eligible studies were reviewed for methodological quality using the QUADAS-2 tool. We used the bivariate random-effects model to calculate summary estimates of sensitivity and specificity. Six studies met the selection criteria and were included for analysis. The meta-analysis showed a summary estimate of sensitivity 0.97 (95% CI, 0.90-0.99) and specificity 0.93 (95% CI, 0.88-0.96). All but one of the QUADAS-2 items showed a high or unclear risk of bias with regards to patient selection. RCM may be a promising diagnostic tool, but the limited number of available studies and potential risk of bias of included studies do not allow us to draw firm conclusions. Future accuracy studies should take these limitations into account. PMID:26290493

  9. Ex vivo hepatic venography for hepatocellular carcinoma in livers explanted for liver transplantation

    Directory of Open Access Journals (Sweden)

    Takatsuki Mitsuhisa

    2011-09-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is supposed to have a venous drainage system to a portal vein, which makes intrahepatic metastasis possible. However, the mechanism of extrahepatic recurrence, including the possibility of a direct route to the systemic circulation from the HCC nodules, remains unclear. Therefore, we performed retrograde hepatic venography for HCC in livers that had been explanted for liver transplantation in order to explore the possible direct connection between the hepatic vein and HCC nodules. Methods Of 105 living-donor liver transplantations (LDLT performed up to July, 2009 at the Department of Surgery, Nagasaki University Hospital, dynamic hepatic venography was performed with contrast media under fluoroscopy for the most recent 13 cases with HCC. The presence of a tumor stain for each HCC case was evaluated and compared with the histological findings of HCC. Results Hepatic venography revealed a tumor stain in 2 of 13 cases (15%. Neither showed any microscopic tumor invasion of HCC into the hepatic vein. In the other 11 cases, there were 4 microscopic portal venous invasions and 2 microscopic hepatic venous invasions. No patients have shown HCC recurrence in follow-up (median period, 13 months. Conclusion Using ex vivo hepatic venography, a direct connection to the hepatic vein from HCC in whole liver was revealed in 2 cases without demonstrated histopathological invasion to hepatic vein for the first time in the literature. The finding suggests that there is direct spillage of HCC cells into the systemic circulation via hepatic vein.

  10. In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog.

    Directory of Open Access Journals (Sweden)

    Haitao Liu

    Full Text Available The synthetic compound 3,5-bis(2-flurobenzylidenepiperidin-4-one (EF24 is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity

  11. Dihydroartemisinin exhibits antitumor activity toward hepatocellular carcinoma in vitro and in vivo.

    Science.gov (United States)

    Zhang, Chris Zhiyi; Zhang, Haitao; Yun, Jingping; Chen, George Gong; Lai, Paul Bo San

    2012-05-01

    Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua L., has been shown to exhibit inhibitory effects on human cancer cells. However, its antitumor ability toward hepatocellular carcinoma (HCC) has not been studied. In this study, we demonstrated that DHA significantly inhibited HCC cell growth in vitro and in vivo via inducing G2/M cell cycle arrest and apoptosis. The induction of p21 and the inhibition of cyclin B and CDC25C contributed to DHA-induced G2/M arrest. DHA-induced apoptosis was associated with mitochondrial membrane depolarization, release of cytochrome c, activation of caspases, and DNA fragmentation. Activation of caspase 9 and caspase 3, but not caspase 8, was detected in DHA-treated cells. Attenuation of apoptosis in cells pretreated with Z-VAD-FMK suggested the involvement of caspase cascade. Furthermore, p53 facilitated apoptosis caused by DHA. Bcl-2 family proteins were also responsible for DHA-induced apoptosis. DHA exposure decreased Mcl-1 expression but increased the levels of Noxa and active Bak. Bak was released from the Mcl-1/Bak complex due to the decline of Mcl-1. Further study revealed that Mcl-1 was rapidly degraded in DHA-treated cells and that DHA-induced apoptosis was largely inhibited by overexpression of Mcl-1 or RNAi-mediated decrease of Bak and Noxa. In a HCC-xenograft mouse model, the intraperitoneal injection of DHA resulted in significant inhibition of HCC xenograft tumors. Taken together, our data, for the first time, demonstrate the potential antitumor activity of DHA in HCC. PMID:22342732

  12. The in vitro and in vivo antitumor effects of clotrimazole on oral squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Juan Wang

    Full Text Available BACKGROUND: Clotrimazole is an antifungal imidazole derivative showing anti- neoplastic effect in some tumors, but its anticancer potential is still unclear in oral squamous cell carcinoma (OSCC. The aim of this study was to evaluate the antitumor effect of clotrimazole, and to investigate the possible mechanism of clotrimazole-mediated antitumor activity in OSCC. METHODOLOGY: In vitro experiments, the cell viability and clonogenic ability of three human OSCC cell lines CAL27, SCC25 and UM1 were detected after clotrimazole treatment by CCK8 assay and colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the involvement of several mediators of apoptosis was examined by western blot analysis. Then, the in vivo antitumor effect of clotrimazole was investigated in CAL27 xenograft model. Immunohistochemistry and western blot analysis were performed to determine the presence of apoptotic cells and the expression of Bcl-2 and Bax in tumors from mice treated with or without clotrimazole. RESULTS: Clotrimazole inhibited proliferation in all three OSCC cell lines in a dose-and time-dependent manner, and significantly reduced the colony formation of OSCC cells in vitro. Clotrimazole caused cell cycle arrest at the G0/G1 phase. In addition, clotrimazole induced apoptosis in OSCC cells, and significantly down-regulated the anti-apoptotic protein Bcl-2 and up-regulated the pro-apoptotic protein Bax. Notably, clotrimazole treatment inhibited OSCC tumor growth and cell proliferation in CAL27 xenograft model. Clotrimazole also markedly reduced Bcl-2 expression and increased the protein level of Bax in tumor tissues of xenograft model. CONCLUSION: Our findings demonstrated a potent anticancer effect of clotrimazole by inducing cell cycle arrest and cellular apoptosis in OSCC.

  13. Thioridazine Sensitizes Esophageal Carcinoma Cell Lines to Radiotherapy-Induced Apoptosis In Vitro and In Vivo

    Science.gov (United States)

    Li, Hongxia; Juan, Li; Xia, Leiming; Wang, Yi; Bao, Yangyi; Sun, Guoping

    2016-01-01

    Background Radiotherapy is one of the primary treatments for esophageal squamous cell carcinoma (ESCC). Identification of novel radio-sensitizing agents will improve the therapeutic outcome of radiotherapy. This study aimed to determine the radio-sensitizing effect of the antipsychotic agent thioridazine in ESCC and explored the underlying mechanisms. Material/Methods ECA-109 and TE-1 ESCC cells were treated with thioridazine and radiotherapy alone and in combination. Cell survival was measured by MTT assay. Cell cycle and apoptosis were monitored by flow cytometry. Western blot analysis was used to analyze the expression of phospho-PI3K, phosphor-AKT, phospho-mTOR, Caspase-3, Caspase-9, Bax, Bcl-2, Bal-xl, Bak, and p53. The xenograft mouse model was used to study the in vivo anticancer effect of thioridazine and irradiation. Results Combined treatment with thioridazine and irradiation significantly reduced viability of ESCC cells compared with thioridazine or irradiation treatment alone. Thioridazine and irradiation treatment induced G0/G1 phases cell cycle arrest through down-regulation of CDK4 and cyclinD1. In addition, thioridazine and irradiation treatment induced apoptosis through up-regulation of cleaved capase-3 and 9, as well as an increase in the expression of Bax and Bak and a decrease in the expression of Bcl-2 and Bcl-xl. Furthermore, thioridazine and irradiation treatment inhibited the PI3K-AKT-mTOR pathway and up-regulated the expression of p53. In xenograft mice, thioridazine and irradiation reduced ESCC tumor growth. Conclusions Thioridazine sensitizes ESCC cells to radiotherapy. Thioridazine may play a role in ESCC radiation therapy as a promising radiosensitizer. PMID:27453171

  14. Antitumor and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Sharada, A.C. [Dept. of Radiobiology, Kasturba Medical Coll., Manipal (India); Solomon, F.E. [Dept. of Radiobiology, Kasturba Medical Coll., Manipal (India); Uma Devi, P. [Dept. of Radiobiology, Kasturba Medical Coll., Manipal (India); Udupa, N. [Coll. of Pharmaceutical Sciences, Manipal (India); Srinivasan, K.K. [Coll. of Pharmaceutical Sciences, Manipal (India)

    1996-06-01

    The antitumor and radiosensitizing effects of withaferin A (WA), a steroidal lactone from Withania somnifera, was studied on Ehrlich ascites carcinoma in vivo. The acute LD{sub 50(14)} for WA in Swiss mice was {proportional_to}80 mg/kg. Twenty-four hours after i.p. inoculation of 10{sup 6} tumor cells, WA was injected i.p. at different dose fractions (5 or 7.5 mg/kg x 8, 10 mg/kg x 5, 20 or 30 mg/kg x 2) with or without abdominal gamma irradiation (RT, 7.5 Gy) after the first drug dose. Increase in life span and tumor-free survival were studied up to 120 days. The drug inhibited tumor growth and increased survival, which was dependent on the WA dose per fraction rather than the total dose. Combination of RT with all the drug schedules increased tumor cure and tumor-free survival, the best effect seen after 2 fractions of 30 mg/kg each. In another experiment WA was given as 2 (40 mg/kg x 2), 3 (30 mg/kg x 3) or 4 (20 mg/kg x 4) fractions at 5, 7 or 10 days after tumor inoculation with or without RT after the first drug dose. At 7 and 10 days after inoculation the drug was effective only at 40 mg/kg x 2, but with RT 30 mg/kg x 3 produced an equal effect (20% survival) on 7 day old tumors. (orig.).

  15. In vivo screening of hepatocellular carcinoma using AC susceptibility of anti-alpha fetoprotein-activated magnetic nanoparticles.

    Directory of Open Access Journals (Sweden)

    Jen-Jie Chieh

    Full Text Available With antibody-mediated magnetic nanoparticles (MNPs applied in cancer examinations, patients must pay at least twice for MNP reagents in immunomagnetic reduction (IMR of in vitro screening and magnetic resonance imaging (MRI of in vivo tests. This is because the high maintenance costs and complex analysis of MRI have limited the possibility of in vivo screening. Therefore, this study proposes novel methods for in vivo screening of tumors by examining the AC susceptibility of bound MNPs using scanning superconducting-quantum-interference-device (SQUID biosusceptometry (SSB, thereby demonstrating high portability and improved economy. The favorable agreement between in vivo tests using SSB and MRI demonstrated the feasibility of in vivo screening using SSB for hepatocellular carcinoma (HCC targeted by anti-alpha fetoprotein (AFP-mediated MNPs. The magnetic labeling was also proved by in vitro tests using SSB and biopsy assays. Therefore, patients receiving bioprobe-mediated MNPs only once can undergo in vivo screening using SSB in the future.

  16. Laser capture microdissection-based in vivo genomic profiling of wound keratinocytes identifies similarities and differences to squamous cell carcinoma

    DEFF Research Database (Denmark)

    Pedersen, Tanja Xenia; Leethanakul, Chidchanop; Patel, Vyomesh;

    2003-01-01

    we present the first analysis of global changes in keratinocyte gene expression during skin wound healing in vivo, and compare these changes to changes in gene expression during malignant conversion of keratinized epithelium. Laser capture microdissection was used to isolate RNA from wound...... reepithelialization. Furthermore, the analyses revealed that the phenotypic resemblance of wound keratinocytes to squamous cell carcinoma is mimicked at the level of gene expression, but notable differences between the two tissue-remodeling processes were also observed. The combination of laser capture...

  17. Inhibition of Oesophageal Squamous Cell Carcinoma Progression by in vivo Targeting of Hyaluronan Synthesis

    Directory of Open Access Journals (Sweden)

    Savani Rashmin C

    2011-03-01

    Full Text Available Abstract Background Oesophageal cancer is a highly aggressive tumour entity with at present poor prognosis. Therefore, novel treatment options are urgently needed. Hyaluronan (HA is a polysaccharide present in the matrix of human oesophageal squamous cell carcinoma (ESCC. Importantly, in vitro ESCC cells critically depend on HA synthesis to maintain the proliferative phenotype. The aim of the present study is (1 to study HA-synthase (HAS expression and regulation in human ESCC, and (2 to translate the in vitro results into a mouse xenograft model of human ESCC to study the effects of systemic versus tumour targeted HAS inhibition on proliferation and distribution of tumour-bound and stromal hyaluronan. Methods mRNA expression was investigated in human ESCC biopsies by semiquantitative real-time RT PCR. Furthermore, human ESCC were xenografted into NMRI nu/nu mice. The effects on tumour progression and morphology of 4-methylumbelliferone (4-MU, an inhibitor of HA-synthesis, and of lentiviral knock down of HA-synthase 3 (HAS3, the main HAS isoform in the human ESCC tissues and the human ESCC cell line used in this study, were determined. Tumour progression was monitored by calliper measurements and by flat-panel detector volume computed tomography (fpVCT. HA content, cellular composition and proliferation (Ki67 were determined histologically. Results mRNA of HAS isoform 3 (HAS3 was upregulated in human ESCC biopsies and HAS3 mRNA was positively correlated to expression of the epidermal growth factor (EGF receptor. EGF was also proven to be a strong inductor of HAS3 mRNA expression in vitro. During the course of seven weeks, 4-MU inhibited progression of xenograft tumours. Interestingly, remodelling of the tumour into a more differentiated phenotype and inhibition of cell proliferation were observed. Lentiviral knockdown of HAS3 in human ESCC cells prior to xenografting mimicked all effects of 4-MU treatment suggesting that hyaluronan produced by

  18. Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats

    OpenAIRE

    Murthy, S; Gautam, M. K.; Shalini Goel; V Purohit; SHARMA, H; Goel, R.K.

    2013-01-01

    Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME) was studied on wound models in rats. BME (25 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound models) or for 21 days or more (excision wound model) in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model), rate of contraction, period of epithelization, histology of skin (excision model), granulation tissue free...

  19. In vivo visualization of expression and function of miR221 in papillary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Joo; Kim, Soon Hag; Jeong, Jae Min; Lee, Dong Soo; Chung, June Key [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    MicroRNA 221 has been known to be one of up-regulated miRNAs in papillary thyroid carcinoma. To evaluate the expression and function of miR221, we measured the quantities of primary or mature miR221 in normal thyroid or papillary cancer cells and examined the gene expression of Gaussian luciferase (Glue) regulated by miR221. Total RNA and small RNA were isolated from normal thyroid cells (HT-ori3) and papillary thyroid cancer cells (NPA, TPC-1). The quantities of primary miR221 or mature miR221 in cells were measured by qRT-PCR. We constructed a CMV/Gluc-3xPT{sub m}iR221 including 3 times repeated perfect target sequences of miR221 in the 3'UTR of Gluc. CMV/Gluc-3xPT{sub m}iR221 was transfected into HT-ori3, NPA, and TPC-1, CMV/Gluc was used as a control. Also, precursor miR221 or anti-miR221 were co-transfected with CMV/Gluc-3xPT{sub m}iR221 into each cells and compared the Gluc activities by luciferase assay and in vivo bioluminescence image. The quantities of primary miR221 of NPA or TPC-1 were 2.24 or 1.5 times more than that of HT-ori3, and quantities of mature miR221 in NPA or TPC-1 were 17 or 7 times more than that of HT-ori3, respectively. Gluc activities in NPA or TPC-1 transfected with CMV/Gluc-3xPT{sub m}iR221 were repressed 2 times or more than those of CMV/Gluc, respectively. Also, Gluc activities in NPA or TPC-1 co-transfected with pre-miR221 and CMV/Gluc-3xPT{sub m}iR221 were repressed 5 times or more down-regulated than those of CMV/Gluc, respectively. The other hand, Gluc activities in NPA or TPC-1 co-transfected with anti-miR221 and CMV/Gluc-3xPT{sub m}iR221 were retrieved as those of CMV/Gluc. In vivo bioluminescence images also showed that Gluc activities were repressed by pre.miR221 and retrieved by anti-miR221. These results suggest that CMV/Gluc-3xPT{sub m}iR221 system may be a useful tool for monitoring the quantities of miR221 and gene regulation by miR221 in a living animal.

  20. In Vivo Selection of Phage for the Optical Imaging of PC-3 Human Prostate Carcinoma in Mice

    Directory of Open Access Journals (Sweden)

    Jessica R. Newton

    2006-09-01

    Full Text Available There is an increasing medical need to detect and spatially localize early and aggressive forms of prostate cancer. Affinity ligands derived from bacteriophage (phage library screens can be developed to molecularly target prostate cancer with fluorochromes for optical imaging. Toward this goal, we used in vivo phage display and a newly described micropanning assay to select for phage that extravasate and bind human PC-3 prostate carcinoma xenografts in severe combined immune deficiency mice. One resulting phage clone (G1 displaying the peptide sequence IAGLATPGWSHWLAL was fluorescently labeled with the near-infrared fluorophore AlexaFluor 680 and was evaluated both in vitro and in vivo for its ability to bind and target PC-3 prostate carcinomas. The fluorescently labeled phage clone (G1 had a tumor-to-muscle ratio of ~30 in experiments. In addition, prostate tumors (PC-3 were readily detectable by optical-imaging methods. These results show proof of principle that diseasespecific library-derived fluorescent probes can be rapidly developed for use in the early detection of cancers by optical means.

  1. Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma

    Science.gov (United States)

    GHITA, MIHAELA A.; CARUNTU, CONSTANTIN; ROSCA, ADRIAN E.; KALESHI, HARILLAQ; CARUNTU, ANA; MORARU, LILIANA; DOCEA, ANCA OANA; ZURAC, SABINA; BODA, DANIEL; NEAGU, MONICA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Superficial basal cell carcinoma (sBCC) is the second most frequent histological type of basal cell carcinoma (BCC), usually requiring a skin biopsy to confirm the diagnosis. It usually appears on the upper trunk and shoulders as erythematous and squamous lesions. Although it has a slow growth and seldom metastasizes, early diagnosis and management are of crucial importance in preventing local invasion and subsequent disfigurement. Dermoscopy is nowadays an indispensable tool for the dermatologist when evaluating skin tumors. Reflectance confocal microscopy (RCM) is a novel imaging technique that allows the non-invasive, in vivo quasi-microscopic morphological and dynamic assessment of superficial skin tumors. Moreover, it offers the advantage of performing infinite repeatable determinations to monitor disease progression and non-surgical treatment for sBCC. Herein, we present three lesions of sBCC evaluated using in vivo and non-invasive imaging techniques, emphasizing the usefulness of combining RCM with dermoscopy for increasing the diagnostic accuracy of sBCC. PMID:27123056

  2. Anti-tumor Effect and Its Mechanisms of Ursolic Acid on Human Esophageal Carcinoma Cell Eca-109 in Vivo

    Institute of Scientific and Technical Information of China (English)

    CHEN Guo-qing; SHEN Yi; DUANG Hong

    2008-01-01

    Objective:To investigate the anti-tumor effect and possible mechanisms of ursolic acid on human esophageal carcinoma in vivo.Methods:A transplanted tumor model by injecting Eca-109 cells into subcutaneous tissue of BALB/c nude mice was established.40 nude mice bearing tumors were randomly divided into 4 groups and 0.2 ml saline or 0.2 ml ursolic acid(25-100 mg·kg-1.d-1)was injected into abdominal cavity respectively once everyday and lasted for fourteen days.The changes of tumor volume were measured continuously and tumor inhibition rate was calculated.The morphological changes of apoptosis were observed by electron microscope.The expressions of COX-2,bcl-2 and Bax protein in transplanted tumors were detected by immunohistochemistry.At last the PGE2 level of transplanted tumors was detected by radioimmunoassay.Results:Treatment of nude mice with 25,50,or 100 mg·kg-1.d-1 of ursolic acid significantly inhibited the growth of the human esophageal carcinoma tumor in nude mice and induced Eca-109 cells apoptosis as demonstrated by electron microscopy analyses.The expressions of COX-2 and bcl-2 in the transplanted tumors were decreased in ursolic acid groups,while the Bax increased.The PGE2 level of transplanted tumors was decreased in ursolic acid groups with a dose-related manner.Conclusion:Ursolic acid has anti-tumor effects against human esophageal carcinoma cells in vivo,which are likely mediated via induction of tumor cell apoptosis and inhibition of COX-2 and PGE2.

  3. Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo.

    Science.gov (United States)

    Miyoshi, Hisaaki; Kato, Kiyohito; Iwama, Hisakazu; Maeda, Emiko; Sakamoto, Teppei; Fujita, Koji; Toyota, Yuka; Tani, Joji; Nomura, Takako; Mimura, Shima; Kobayashi, Mitsuyoshi; Morishita, Asahiro; Kobara, Hideki; Mori, Hirohito; Yoneyama, Hirohito; Deguchi, Akihiro; Himoto, Takashi; Kurokohchi, Kazutaka; Okano, Keiichi; Suzuki, Yasuyuki; Murao, Koji; Masaki, Tsutomu

    2013-12-30

    Metformin is a commonly used oral anti-hyperglycemic agent of the biguanide family. Recent studies suggest that metformin may reduce cancer risk and improve prognosis. However, the antitumor mechanism of metformin in several types of cancers, including hepatocellular carcinoma (HCC), has not been elucidated. The goal of the present study was to evaluate the effects of metformin on HCC cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with the antitumor effect of metformin in vitro. We used the cell lines Alex, HLE and Huh7, and normal hepatocytes to study the effects of metformin on human HCC cells. In an in vivo study, athymic nude mice bearing xenograft tumors were treated with metformin or left untreated. Tumor growth was recorded after 4 weeks, and the expression of cell cycle‑related proteins was determined. Metformin inhibited the proliferation of Alex, HLE and Huh7 cells in vitro and in vivo. Metformin blocked the cell cycle in G0/G1 in vitro and in vivo. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, cyclin E and cyclin-dependent kinase 4 (Cdk4). In addition, microRNA (miRNA) expression was markedly altered by the treatment with metformin in vitro and in vivo. In addition, various miRNAs induced by metformin also may contribute to the suppression of tumor growth. Our results demonstrate that metformin inhibits the growth of HCC, possibly by inducing G1 cell cycle arrest through the alteration of microRNAs. PMID:24378856

  4. Modeling In Vivo Pharmacokinetics and Pharmacodynamics of Moxifloxacin Therapy for Mycobacterium tuberculosis Infection by Using a Novel Cartridge System

    OpenAIRE

    Ginsburg, Amy Sarah; Lee, Jin; Woolwine, Samuel C.; Jacques H Grosset; Hamzeh, Fayez M.; Bishai, William R.

    2005-01-01

    To study the efficacy of moxifloxacin treatment for tuberculosis, we utilized a novel cartridge system to simulate in vivo pharmacokinetics. We found this system to be a robust method for modeling in vivo pharmacokinetics and present data supporting the utility of intermittent moxifloxacin treatment as a component of antituberculosis chemotherapy.

  5. Cellular Redox Status Regulates Emodin-Induced Radiosensitization of Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Huaxin Hou

    2013-01-01

    Full Text Available Here, we report that regulation of cellular redox status is required for radiosensitization of nasopharyngeal carcinoma (NPC cells by emodin. We evaluated emodin’s radiosensitivity-enhancing ability by using NPC cells in vitro and xenografts in vivo. A clonogenic assay was performed to evaluate NPC cell survival and to determine dose modification factors. Flow cytometry, western blot analysis, and in vivo radiation-induced tumor regrowth delay assays were performed to characterize emodin’s effects. Exposure of CNE-1 NPC cells to emodin enhanced their radiosensitivity. HIF-1α expression significantly increased under hypoxic conditions but did not change after treatment with emodin alone. Emodin downregulated mRNA and protein expression of HIF-1α. Cells exposed to radiation and emodin underwent significant cell cycle arrest at the G2/M phase. The percentage of apoptotic cells and reactive oxygen species (ROS levels were significantly higher in the group exposed to emodin and radiation hypoxic group than in the other groups. Compared to the CNE-1 xenografts exposed to radiation alone, CNE-1 xenografts exposed to radiation with emodin showed significantly enhanced radiation effects. Our data suggest that emodin effectively enhanced the radiosensitivity of CNE-1 cells in vitro and in vivo. The mechanism appears to involve ROS generation and ROS-mediated inhibition of HIF-1α expression.

  6. Hyaluronidase enhances the activity of adriamycin in breast cancer models in vitro and in vivo

    OpenAIRE

    Beckenlehner, Karin; Bannke, Silke; Spruss, Thilo; Bernhardt, Günther; Schönenberger, Helmut; Schiess, Wilfried

    1992-01-01

    The effect of hyaluronidase and a combination of hyaluronidase with Adriamycin was investigated on several breast cancer models in vitro and in vivo. In vitro enzyme treatment (using concentrations up to 80,000 IU/1) of murine (MXT-, MXT +/-, and MXT+) and human (MCF-7, ZR-75-1 and T-47-D) breast cancer cell lines did not inhibit tumour cell proliferation (measured by a kinetic crystal violet assay) in either case. Although high-dose hyaluronidase (1.2 x 10(6) IU/kg) was ineffective, when adm...

  7. In vitro and in vivo suppression of hepatocellular carcinoma growth by midkine-antisense oligonucleotide-loaded nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Li-Cheng Dai; Xing Yao; Xiang Wang; Shu-Qiong Niu; Lin-Fu Zhou; Fang-Fang Fu; Shui-Xin Yang; Jin-Liang Ping

    2009-01-01

    AIM: To synthesize antisense oligonucleotides (ASODNs) of midkine (MK), package the ASODNs with nanoparticles, and to inhibit hepatocellular carcinoma (HCC) growth using these nanoparticles.METHODS: HepG2 cell proliferation was analyzed in vitro using the 3-(4,5-dimethythiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2Htetrazolium, inner salt assay. The in vivo activity of nanoparticles delivering the MK-ASODNs was analyzed by histopathological and immunohistochemical staining and quantitative real time polymerase chain reaction (PCR).RESULTS: The in vitro proliferation of HepG2 cells was significantly inhibited by the nanoparticles packaged with MK-ASODNs (NANO-ASODNs). Furthermore, the NANOASODNs significantly inhibited the growth of HCC in the mouse model.

  8. Diagnosing basal cell carcinoma in vivo by near-infrared Raman spectroscopy: a Principal Components Analysis discrimination algorithm

    Science.gov (United States)

    Silveira, Landulfo, Jr.; Silveira, Fabrício L.; Bodanese, Benito; Pacheco, Marcos Tadeu T.; Zângaro, Renato A.

    2012-02-01

    This work demonstrated the discrimination among basal cell carcinoma (BCC) and normal human skin in vivo using near-infrared Raman spectroscopy. Spectra were obtained in the suspected lesion prior resectional surgery. After tissue withdrawn, biopsy fragments were submitted to histopathology. Spectra were also obtained in the adjacent, clinically normal skin. Raman spectra were measured using a Raman spectrometer (830 nm) with a fiber Raman probe. By comparing the mean spectra of BCC with the normal skin, it has been found important differences in the 800-1000 cm-1 and 1250-1350 cm-1 (vibrations of C-C and amide III, respectively, from lipids and proteins). A discrimination algorithm based on Principal Components Analysis and Mahalanobis distance (PCA/MD) could discriminate the spectra of both tissues with high sensitivity and specificity.

  9. Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Danxin; Zhang, Yu; Huang, Jie; Fan, Zirong; Shi, Fengrong; Wang, Senming, E-mail: wsenming@126.com

    2014-01-10

    Highlight: •We first evaluated the effect of salinomycin on nasopharyngeal carcinoma (NPC). •Salinomycin could inhibit Wnt/β-catenin signaling and induce apoptosis in NPC. •So salinomycin may be a good potential candidate for the chemotherapy of NPC. -- Abstract: Salinomycin (Sal) is a polyether ionophore antibiotic that has recently been shown to induce cell death in various human cancer cells. However, whether salinomycin plays a functional role in nasopharyngeal carcinoma (NPC) has not been determined to date. The present study investigated the chemotherapeutic efficacy of salinomycin and its molecular mechanisms of action in NPC cells. Salinomycin efficiently inhibited proliferation and invasion of 3 NPC cell lines (CNE-1, CNE-2, and CNE-2/DDP) and activated a extensive apoptotic process that is accompanied by activation of caspase-3 and caspase-9, and decreased mitochondrial membrane potential. Meanwhile, the protein expression level of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and β-catenin was down-regulated, which showed that the Wnt/β-catenin signaling was involved in salinomycin-induced apoptosis of NPC cells. In a nude mouse NPC xenograft model, the anti-tumor effect of salinomycin was associated with the downregulation of β-catenin expression. The present study demonstrated that salinomycin can effectively inhibit proliferation and invasion, and induce apoptosis of NPC cells in vitro and inhibit tumor growth in vivo, probably via the inhibition of Wnt/β-catenin signaling, suggesting salinomycin as a potential candidate for the chemotherapy of NPC.

  10. Bimodal ex vivo expansion of T cells from patients with head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Junker, Niels; Andersen, Mads Hald; Wenandy, Lynn;

    2011-01-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has proven effective in metastatic melanoma and should therefore be explored in other types of cancer. The aim of this study was to examine the feasibility of potentially expanding clinically relevant quantities of tumor-specific T-cell cu......-cell cultures from TIL from patients with head and neck squamous cell carcinoma (HNSCC) using a more rapid expansion procedure compared with previous HNSCC studies....

  11. Anti-Tumor Effect of Curcumin on Human Cervical Carcinoma HeLa Cells In Vitro and In Vivo

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jing; ZHAO Yong; ZHANG Yan; CHEN Wei

    2007-01-01

    Objective: To investigate the anti-tumor effect of curcumin on human cervical carcinoma HeLa cells in vitro and in vivo. Methods: (1) Human cervical carcinoma cell line HeLa was cultured in vitro. HeLa cells were treated with 5-50μmol/L curcumin for 24. 48, 72 h and the growth inhibition rates of HeLa cells were measured by MTT method. Cell apoptosis was inspected by electron microscopy and flow cytometry (FCM). (2) A transplanted tumor model by injecting HeLa cells into subcutaneous tissue of BABL/C mice was established and its growth curve was measured. 30 BABL/C mice with tumors were divided into 2 groups at random and 0.2 ml saline or 0.2 ml 250 μmol/L curcumin was injected into abdominal cavity respectively once everyday and lasted for ten days. The changes of tumor volume were measured continuously and tumor inhibition rate was calculated. At last the expressions of caspase-3 and bax protein in transplanted tumors were detected by immunohistochemistry. Results: (1) Curcumin inhibited the proliferation of Lela cells on a dose-depending manner. Apoptosis of cells could be observed by FCM. Partial cells presented the characteristic morphological changes of apoptosis under electron microseope. (2) When 1×107 HeLa cells were inoculated for each mouse, 100% of the mice developed growing tumors after seven days. An inhibition effect was observed in treatment group, and the inhibition rate of curcumin was 74.33%. The expressions of caspase-3 and bax in the transplanted tumors were increased in curcumin group. Conclusion: Curcumin is effective as an anti-cancer drug not only in vitro but also in vivo.

  12. In vivo toxicity study of N-1-sulfonylcytosine derivatives and their mechanisms of action in cervical carcinoma cell line.

    Science.gov (United States)

    Kašnar-Šamprec, Jelena; Ratkaj, Ivana; Mišković, Katarina; Pavlak, Marina; Baus-Lončar, Mirela; Kraljević Pavelić, Sandra; Glavaš-Obrovac, Ljubica; Žinić, Biserka

    2012-06-01

    New N-1-sulfonylpyrimidines showed potent growth inhibitory activity against human and mouse tumour cells of different origin. 1-(p-toluenesulfonyl)cytosine (TsC) and 1-(p-toluenesulfonyl)cytosine hydrochloride (TsC × HCl) inhibited the growth of human cervical carcinoma cells (HeLa), and had no significant cytotoxic effects on normal human foreskin fibroblasts (BJ). TsC and TsC × HCl interfered with the HeLa cell cycle progression bringing about the accumulation of G1 phase cells and the induction of apoptosis. Antiproliferative effects of TsC and TsC × HCl were additionally confirmed by investigating de novo synthesis of RNA, DNA and proteins in HeLa cells. Monitoring gene expression using DNA Chip Analysis and quantitative PCR showed that TsC × HCl affects the expression of several cell-cycle regulating genes implying that cell cycle arrest and DNA damage-induced apoptosis might account for the observed cellular effects. In vivo experiments revealed low toxicity of TsC × HCl, as demonstrated by unaltered haematological and metabolic blood parameters. In conclusion, potent antitumour efficacy and low toxicity of new compounds in comparison with the common chemotherapy drug 5-FU make them promising anticancer agents. Additional pre-clinical and clinical studies are warranted to illuminate the mode of action of these newly synthesized compounds in vivo, which would lay the groundwork for their further optimization.

  13. Characterization of 9-nitrocamptothecin liposomes: anticancer properties and mechanisms on hepatocellular carcinoma in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Shunzhen Zheng

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm and zeta potential (∼-11 mV, and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo. CONCLUSIONS/SIGNIFICANCE: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

  14. Modeling in vivo fluorescence of small animals using TracePro software

    Science.gov (United States)

    Leavesley, Silas; Rajwa, Bartek; Freniere, Edward R.; Smith, Linda; Hassler, Richard; Robinson, J. Paul

    2007-02-01

    The theoretical modeling of fluorescence excitation, emission, and propagation within living tissue has been a limiting factor in the development and calibration of in vivo small animal fluorescence imagers. To date, no definitive calibration standard, or phantom, has been developed for use with small animal fluorescence imagers. Our work in the theoretical modeling of fluorescence in small animals using solid modeling software is useful in optimizing the design of small animal imaging systems, and in predicting their response to a theoretical model. In this respect, it is also valuable in the design of a fluorescence phantom for use in in vivo small animal imaging. The use of phantoms is a critical step in the testing and calibration of most diagnostic medical imaging systems. Despite this, a realistic, reproducible, and informative phantom has yet to be produced for use in small animal fluorescence imaging. By modeling the theoretical response of various types of phantoms, it is possible to determine which parameters are necessary for accurately modeling fluorescence within inhomogenous scattering media such as tissue. Here, we present the model that has been developed, the challenges and limitations associated with developing such a model, and the applicability of this model to experimental results obtained in a commercial small animal fluorescence imager.

  15. Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice

    Institute of Scientific and Technical Information of China (English)

    Dao-Ming Liang; Jia-Yong Chen; Yi Zhang; Ping Gan; Jie Lin; An-Bao Chen

    2006-01-01

    AIM: To study effects of recombinant human growth hormone (rhGH) on growth of a human gastric carcinoma cell in vivo.METHODS: Experimental mice were divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model wasestablished successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method.RESULTS: Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%,58.2%, 65.2% and 59.2% in rhGH+L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH+L-OHP group (or L-OHP group ) and control group or rhGH group (P <0.05), whereas there were no significant differences (P >0.05) between L-OHP group and rhGH+L-OHP group and between rhGH group and control group.CONCLUSION: rhGH does not accelerate the proliferation of human gastric cancer cell in vivo.

  16. Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

    Institute of Scientific and Technical Information of China (English)

    Zhao-You Tang; Lun-Xiu Qin; Hui-Chuan Sun; Lu Wang; Jian Zhou; Yah Li; Zeng-Chen Ma; Xin-Da Zhou; Zhi-Quan Wu; Zhi-Ying Lin; Bing-Hui Yang; Fan-Xian Sun; Jian Tian; Sheng-Long Ye; Yin-Kun Liu; Kang-Da Liu; Qiong Xue; Jie Chen; Jing-Lin Xia

    2001-01-01

    Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.``

  17. Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats

    Directory of Open Access Journals (Sweden)

    S. Murthy

    2013-01-01

    Full Text Available Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME was studied on wound models in rats. BME (25 mg/kg was administered orally, once daily for 10 days (incision and dead space wound models or for 21 days or more (excision wound model in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model, rate of contraction, period of epithelization, histology of skin (excision model, granulation tissue free radicals (nitric oxide and lipid peroxidation, antioxidants (catalase, superoxide dismutase, and reduced glutathione, acute inflammatory marker (myeloperoxidase, connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid, and deep connective tissue histology (dead space wound. BME showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation, and early epithelization period with low scar area indicating enhanced healing. Healing effect was further substantiated by decreased free radicals and myeloperoxidase and enhanced antioxidants and connective tissue markers with histological evidence of more collagen formation in skin and deeper connective tissues. BME decreased myeloperoxidase and free radical generated tissue damage, promoting antioxidant status, faster collagen deposition, other connective tissue constituent formation, and antibacterial activity.

  18. Diagnosis of malignant melanoma and basal cell carcinoma by in vivo NIR-FT Raman spectroscopy is independent of skin pigmentation

    DEFF Research Database (Denmark)

    Philipsen, P A; Knudsen, L; Gniadecka, M;

    2013-01-01

    There is a general need for methods to obtain fast in vivo diagnosis of skin tumours. Raman spectroscopy measures molecular structure and may thus have potential as a tool for skin tumour diagnosis. The purpose of this study was to investigate how skin pigmentation influenced the Raman spectra...... and skin tumour diagnostics in vivo. We obtained Raman spectra in vivo from the normal skin of 55 healthy persons with different skin pigmentation (Fitzpatrick skin type I-VI) and in vivo from 25 basal cell carcinomas, 41 pigmented nevi and 15 malignant melanomas. Increased skin pigmentation resulted...... in a higher spectral background caused by fluorescence, which could be removed by background correction. After background correction, we found only a negligible effect of pigmentation on the major spectral bands, and the comparison of the intensity of these bands allowed us to differentiate between normal...

  19. In vivo assessment of the antiproliferative properties of interferon-alpha during immunotherapy: Ki-67 (MIB-1) in patients with metastatic renal cell carcinoma

    DEFF Research Database (Denmark)

    Donskov, F; Marcussen, N; Hokland, M;

    2004-01-01

    The aim of the present study was to investigate the in vivo antiproliferative effect of interferon alpha (IFN-alpha) in patients with metastatic renal cell carcinoma (mRCC). Core needle biopsies of metastatic and/or the primary kidney cancer were obtained before interleukin-2 (IL-2)- and IFN.......016). Baseline or change in Ki-67 LI did not correlate to survival. These data suggest that IFN-alpha in vivo has only modest effect on tumour proliferation in patients with mRCC. Tumour Ki-67 (MIB-1) reactivity after 1 month of immunotherapy appears to be a significant predictor of patient survival....

  20. In vivo nonlinear spectral imaging as a tool to monitor early spectroscopic and metabolic changes in a murine cutaneous squamous cell carcinoma model

    OpenAIRE

    Thomas, Giju; van Voskuilen, Johan; Truong, Hoa; Song, Ji-Ying; Gerritsen, Hans C.; Sterenborg, H. J. C. M.

    2014-01-01

    Timely detection of cutaneous squamous cell carcinoma with non-invasive modalities like nonlinear spectral imaging (NLSI) can ensure efficient preventive or therapeutic measures for patients. In this study, in vivo NLSI was used to study spectral characteristics in murine skin treated with 7, 12-dimethylbenz(a)anthracene. The results show that NLSI could detect emission spectral changes during the early preclinical stages of skin carcinogenesis. Analyzing these emission spectra using simulate...

  1. IN VIVO 1H MAGNETIC RESONANCE SPECTROSCOPY IN EVALUATION OF HEPATOCELLULAR CARCINOMA AND ITS EARLY RESPONSE TO TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION

    Institute of Scientific and Technical Information of China (English)

    Bin Wu; Wei-jun Peng; Pei-jun Wang; Ya-jia Gu; Wen-tao Li; Liang-pin Zhou; Feng Tang; Guo-ming Zhong

    2006-01-01

    Objective To investigate the value of in vivo proton magnetic resonance spectroscopy (MRS) in the assessment of hepatocellular carcinoma (HCC) and monitor its metabolic change shortly after transcatheter arterial chemoembolization (TACE).Methods In this prospective study,28 consecutive patients with large HCC (≥3 cm in diameter) confirmed by fine needle aspiration biopsy were recruited.The 1H MRS of all hepatic lesions and some uninvolved liver parenchyma were performed with 1.5T whole body MR scanner.Among them,15 cases were evaluated again about one week after TACE.The main metabolites such as choline and lipid before and after interventional therapy were measured to assess the early response of the tumor.Results The technical success rate of 1H MRS in liver was high (33/41,80%),closely related to breath motion,location of lesion,and size of voxel.In spectra,the choline compound peak of HCC elevated compared with uninvolved liver parenchyma.After TACE,both the amplitude and the area of choline resonance peak significantly descended (choline-to-lipid ratios from 0.352±0.080 to 0.167±0.030,P=0.026;from 0.205±0.060 to 0.070±0.020,P=0.042,respectively);yet lipid resonance peak ascended.Conclusions In vivo 1H MRS is technically feasible for the evaluation of large focal hepatic lesions,however,the reproducibility and stability are not as good as routine MR scan.1H MRS can monitor the early stage metabolic changes of HCC after TACE but limitation like quantification still exists.

  2. Application of serum protein fingerprinting coupled with artificial neural network model in diagnosis of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Jia-xiang; ZHANG Bo; YU Jie-kai; LIU Jian; YANG Mei-qin; ZHENG Shu

    2005-01-01

    Background Hepatocellular carcinoma tends to present at a late clinical stage with poor prognosis.Therefore, it is urgent to explore and develop a simple, rapid diagnostic method, which has high sensitivity and specificity for hepatocellular carcinoma at an early stage.In this study, the serum proteins in patients with hepatocellular carcinoma or liver cirrhosis and in normal controls were analysed.Surface enhanced laser desorption/ionization time-of-flight mass (SELDI-TOF-MS) spectrometry was used to fingerprint serum protein using the protein chip technique and explore the value of the fingerprint, coupled with artificial neural network, to diagnose hepatocellular carcinoma.Methods Of the 106 serum samples obtained, 52 were from patients with hepatocellular carcinoma, 22 from patients with liver cirrhosis and 32 from healthy volunteers.The samples were randomly assigned into a training group (n=70, 35 patients with hepatocellular carcinoma, 14 with liver cirrhosis, and 21 normal controls) and a testing group (n=36, 17 patients with hepatocellular carcinoma, 8 with liver cirrhosis, and 11 normal controls).An artificial neural network was trained on data from 70 individuals in the training group to develop an artificial neural network diagnostic model and this model was tested.The 36 sera in the testing group were analysed with blind prediction by using the same flowchart and procedure of data collection.The 36 serum protein spectra were clustered with the preset clustering method and the same mass/charge (M/Z) peak values as those in the training group.Matrix transfer was performed after data were output.Then the data were input into the previously built artificial neural network model to get the prediction value.The M/Z peaks of the samples with more than 2000 M/Z were normalized with biomarker wizard of ProteinChip Software version 3.1 for noise filtering.The first threshold for noise filtering was set at 5, and the second was set at 2.The 10% was the minimum

  3. Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lars A Ormandy; Tim F Greten; Anatol F(a)rber; Tobias Cantz; Susanne Petrykowska; Heiner Wedemeyer; Monique H(o)rning; Frank Lehner; Michael P Manns; Firouzeh Korangy

    2006-01-01

    AIM: To analyze the phenotype and function of dendritic cells (DC) from patients with hepatocellular carcinoma (HCC) in order to understand their role in this disease.METHODS: Myeloid dendritic cells were enumerated in peripheral blood of HCC patients. CD80, CD83, CD86 and HLA-DR expression on naive and stimulated myeloid dendritic cells from peripheral blood were analyzed. Myeloid dendritic cells were isolated from peripheral blood and their function was tested. Phagocytosis was analyzed using FITC-dextran beads, peptide specific stimulation, the capacity to stimulate allogeneic T cells and secretion of cytokines upon poly dI:dC was tested.RESULTS: Myeloid dendritic cells were reduced in patients with HCC. No differences in CD80, CD83, CD86 and HLA-DR expression were found on naive and stimulated myeloid dendritic cells from HCC patients and healthy controls. Normal phagocytosis or stimulation of peptide specific T cells was observed in contrast to an impaired allo-stimulatory capacity and a reduced IL-12 secretion.CONCLUSION: Impaired IL-12 production of mDCs in patients could lead to an impaired stimulatory capacity of naive T cells suggesting that IL-12 directed therapies may enhance tumor specific immune responses in HCC patients.

  4. Effect of plumbagin on the radiation induced cytogenetic and cell cycle changes in mouse Ehrlich ascites carcinoma in vivo

    International Nuclear Information System (INIS)

    The effect of plumbagin, a naphthoquinone from the roots of the Indian medicinal plant Plumbago rosea, and cobalt-60 gamma radiation was studied on Ehrlich ascites carcinoma in vivo, taking cytogenetic damage and cell cycle changes as experimental endpoints. Plumbagin (5 mg/kg body wt, Pl) administered intraperitoneally produced a significant increase in the percentage of S-phase as well as G2-M cells with a corresponding decrease in the G1 phase at different post-treatment times. Radiation (7.5 Gy, RT) alone produced the classical G2 block at 1 hr, which persisted with a continuous increase throughout the post-treatment observation period. The combination treatment produced a similar effect as that of RT on G2-M cells, but its effect on the G1 phase was more pronounced than the latter. While Pl treatment produced a small increase in the percentage of labelled S-phase cells, combination treatment significantly reduced the labelled S-phase cells with a corresponding increase in the unlabelled fraction. Drug or radiation alone significantly increased micronuclei induction at various post-treatment times and the combination of the two further enhanced this effect additively. The mechanism of interaction of Pl with radiation in bringing about this effect is not clear. (author)

  5. Homeobox B9 is overexpressed in hepatocellular carcinomas and promotes tumor cell proliferation both in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fangyi [Department of General Surgery, Dalian Municipal Friendship Hospital, No. 8 Sanba Square, Zhongshan District, Dalian 116001 (China); Dong, Lei, E-mail: dlleidong@126.com [Department of Laparoscopic Surgery, First Affiliated Hospital of Dalian Medical University, No. 193 Lianhe Street, Shahekou District, Dalian 116001 (China); Xing, Rong [Department of Pathology and Pathophysiology, Dalian Medical University, No. 9 Lvshunnan Road, Lvshunkou District, Dalian 116044 (China); Wang, Li; Luan, Fengming; Yao, Chenhui [Department of General Surgery, Dalian Municipal Friendship Hospital, No. 8 Sanba Square, Zhongshan District, Dalian 116001 (China); Ji, Xuening [Department of Oncology, Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian 116001 (China); Bai, Lizhi, E-mail: dllizhibai@126.com [Department of Emergency, Zhongshan Hospital of Dalian University, No. 6 Jiefang Street, Zhongshan District, Dalian 116001 (China)

    2014-02-07

    Highlights: • HOXB9 is overexpressed in human HCC samples. • HOXB9 over expression had shorter survival time than down expression. • HOXB9 stimulated the proliferation of HCC cells. • Activation of TGF-β1 contributes to HOXB9-induced proliferation in HCC cells. - Abstract: HomeoboxB9 (HOXB9), a nontransforming transcription factor that is overexpressed in multiple tumor types, alters tumor cell fate and promotes tumor progression. However, the role of HOXB9 in hepatocellular carcinoma (HCC) development has not been well studied. In this paper, we found that HOXB9 is overexpressed in human HCC samples. We investigated HOXB9 expression and its prognostic value for HCC. HCC surgical tissue samples were taken from 89 HCC patients. HOXB9 overexpression was observed in 65.2% of the cases, and the survival analysis showed that the HOXB9 overexpression group had significantly shorter overall survival time than the HOXB9 downexpression group. The ectopic expression of HOXB9 stimulated the proliferation of HCC cells; whereas the knockdown of HOXB9 produced an opposite effect. HOXB9 also modulated the tumorigenicity of HCC cells in vivo. Moreover, we found that the activation of TGF-β1 contributes to HOXB9-induced proliferation activities. The results provide the first evidence that HOXB9 is a critical regulator of tumor growth factor in HCC.

  6. Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

    Institute of Scientific and Technical Information of China (English)

    ZHU Ji-hong; JIN Ning-yi; LI Xiao; SUN Li-li; ZHANG Mu-chun; KAN Shi-fu; LIU Lei; HUANG Hai-yan; YANG Guo-hua; PIAO Bing-guo

    2011-01-01

    Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid cells.To explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein (vFV-Apoptin) to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma(HeLa) cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT) assay,acridine orage/ethidium bromide(AO/EB) and annexin V staining test,respectively.The results show that vFV-Apoptin inhibites the proliferation of HeLa cells in vitro through inducing the apoptosis of HeLa cells,and the inhibition effect of vFV-Apoptin has a dose-effect and time-effect relationship.The results of animal models show that vFV-Apoptin significantly inhibits tumor growth,extends the lifespan of animals and improves the mean survival.Experimental results indicate that vFV-Apoptin has a potential application in the tumor gene therapy.

  7. Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Masaaki Yasukawa

    2016-02-01

    Full Text Available Cisplatin is a commonly used chemotherapeutic drug for treatment of oral carcinoma, and combinatorial effects are expected to exert greater therapeutic efficacy compared with monotherapy. Poly(ADP-ribosylation is reported to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, and genomic stability. Based on these properties, poly(ADP-ribose polymerase (PARP inhibitors are used for treatment of cancers, such as BRCA1/2 mutated breast and ovarian cancers, or certain solid cancers in combination with anti-cancer drugs. However, the effects on oral cancer have not been fully evaluated. In this study, we examined the effects of PARP inhibitor on the survival of human oral cancer cells in vitro and xenografted tumors derived from human oral cancer cells in vivo. In vitro effects were assessed by microculture tetrazolium and survival assays. The PARP inhibitor AZD2281 (olaparib showed synergetic effects with cisplatin in a dose-dependent manner. Combinatorial treatment with cisplatin and AZD2281 significantly inhibited xenografted tumor growth compared with single treatment of cisplatin or AZD2281. Histopathological analysis revealed that cisplatin and AZD2281 increased TUNEL-positive cells and decreased Ki67- and CD31-positive cells. These results suggest that PARP inhibitors have the potential to improve therapeutic strategies for oral cancer.

  8. Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo

    Science.gov (United States)

    Yasukawa, Masaaki; Fujihara, Hisako; Fujimori, Hiroaki; Kawaguchi, Koji; Yamada, Hiroyuki; Nakayama, Ryoko; Yamamoto, Nanami; Kishi, Yuta; Hamada, Yoshiki; Masutani, Mitsuko

    2016-01-01

    Cisplatin is a commonly used chemotherapeutic drug for treatment of oral carcinoma, and combinatorial effects are expected to exert greater therapeutic efficacy compared with monotherapy. Poly(ADP-ribosyl)ation is reported to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, and genomic stability. Based on these properties, poly(ADP-ribose) polymerase (PARP) inhibitors are used for treatment of cancers, such as BRCA1/2 mutated breast and ovarian cancers, or certain solid cancers in combination with anti-cancer drugs. However, the effects on oral cancer have not been fully evaluated. In this study, we examined the effects of PARP inhibitor on the survival of human oral cancer cells in vitro and xenografted tumors derived from human oral cancer cells in vivo. In vitro effects were assessed by microculture tetrazolium and survival assays. The PARP inhibitor AZD2281 (olaparib) showed synergetic effects with cisplatin in a dose-dependent manner. Combinatorial treatment with cisplatin and AZD2281 significantly inhibited xenografted tumor growth compared with single treatment of cisplatin or AZD2281. Histopathological analysis revealed that cisplatin and AZD2281 increased TUNEL-positive cells and decreased Ki67- and CD31-positive cells. These results suggest that PARP inhibitors have the potential to improve therapeutic strategies for oral cancer. PMID:26927065

  9. Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo.

    Science.gov (United States)

    Yasukawa, Masaaki; Fujihara, Hisako; Fujimori, Hiroaki; Kawaguchi, Koji; Yamada, Hiroyuki; Nakayama, Ryoko; Yamamoto, Nanami; Kishi, Yuta; Hamada, Yoshiki; Masutani, Mitsuko

    2016-01-01

    Cisplatin is a commonly used chemotherapeutic drug for treatment of oral carcinoma, and combinatorial effects are expected to exert greater therapeutic efficacy compared with monotherapy. Poly(ADP-ribosyl)ation is reported to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, and genomic stability. Based on these properties, poly(ADP-ribose) polymerase (PARP) inhibitors are used for treatment of cancers, such as BRCA1/2 mutated breast and ovarian cancers, or certain solid cancers in combination with anti-cancer drugs. However, the effects on oral cancer have not been fully evaluated. In this study, we examined the effects of PARP inhibitor on the survival of human oral cancer cells in vitro and xenografted tumors derived from human oral cancer cells in vivo. In vitro effects were assessed by microculture tetrazolium and survival assays. The PARP inhibitor AZD2281 (olaparib) showed synergetic effects with cisplatin in a dose-dependent manner. Combinatorial treatment with cisplatin and AZD2281 significantly inhibited xenografted tumor growth compared with single treatment of cisplatin or AZD2281. Histopathological analysis revealed that cisplatin and AZD2281 increased TUNEL-positive cells and decreased Ki67- and CD31-positive cells. These results suggest that PARP inhibitors have the potential to improve therapeutic strategies for oral cancer. PMID:26927065

  10. Antitumour and antioxidant activity of some Red Sea seaweeds in Ehrlich ascites carcinoma in vivo.

    Science.gov (United States)

    Ahmed, Hanaa H; Hegazi, Muhammad M; Abd-Alla, Howaida I; Eskander, Emad F; Ellithey, Mona S

    2011-01-01

    The antitumour activities of extracts from the Red Sea seaweeds Jania rubens, Sargassum subrepandum, and Ulva lactuca were investigated in an in vivo mice model based on intramuscular injection of Ehrlich ascites tumour cells. In parallel, antioxidant activities were measured. Tumour marker levels, liver biochemical parameters, and hepatic oxidant/antioxidant status were measured to prove the anticancer and antioxidant nature of the algal extracts. Significant decreases in carcinoembryonic antigen (CEA) and a-fetoprotein (AFP) levels, activities of liver enzymes, levels of nitric oxide (NO) and malondialdehyde (MDA), and an increase in total antioxidant capacity (TAC) were recorded in groups treated with the algal extracts. Jania rubens was selected for phytochemical screening of its phytoconstituents. In addition, carotenoids, halides, minerals, lipoidal matters, proteins, and carbohydrates were studied. Furthermore, 7-oxo-cholest-5(6)-en-3-ol (1) and cholesterol (2) were isolated from the dichloromethane fraction. PMID:21950161

  11. Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

    Directory of Open Access Journals (Sweden)

    J. Wang

    2015-03-01

    Full Text Available This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each given daily intraperitoneal injections of vehicle (physiological saline, esculetin (200, 400, or 700 mg·kg-1·day-1, or 5-Fu (200 mg·kg-1·day-1 for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

  12. Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J. [The First Affiliated Hospital, Liaoning Medical University, Jinzhou (China); Key Laboratory of Cardiovascular and Cerebrovascular Drug Research, Liaoning Province, Liaoning Medical University, Jinzhou (China); Lu, M.L.; Dai, H.L.; Zhang, S.P.; Wang, H.X. [Key Laboratory of Cardiovascular and Cerebrovascular Drug Research, Liaoning Province, Liaoning Medical University, Jinzhou (China); Wei, N. [The First Affiliated Hospital, Liaoning Medical University, Jinzhou (China)

    2014-12-12

    This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivo antitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg{sup -1}·day{sup -1}), or 5-Fu (200 mg·kg{sup -1}·day{sup -1}) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC{sub 50} value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

  13. Inhibition of connective tissue growth factor overexpression decreases growth of hepatocellular carcinoma cells in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    JIA Xiao-qin; CHENG Hai-qing; LI Hong; ZHU Yan; LI Yu-hua; FENG Zhen-qing; ZHANG Jian-ping

    2011-01-01

    Background We have previously found that connective tissue growth factor (CTGF) is highly expressed in a rat model of liver cancer.Here,we examined expression of CTGFin human hepatocellular carcinoma (HCC) cells and its effect on cell growth.Methods Real-time PCR was used to observe expression of CTGF in human HCC cell lines HepG2,SMMC-7721,MHCC-97H and LO2.siRNA for the CTGFgene was designed,synthesized and cloned into a Plk0.1-GFP-SP6 vector to construct a lentivirus-mediated shRNA/CTGF.CTGF mRNA and protein expression in HepG2 cells treated by CTGF-specific shRNA was evaluated by real-time PCR and Western blotting.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to evaluate the growth effect,and a colony formation assay was used for observing clonogenic growth.In vivo,tumor cell proliferation was evaluated in a nude mouse model of xenotransplantation.Statistical significance was determined by t test for comparison between two groups,or analysis of variance (ANOVA) for multiple groups.Results Immunohistochemical staining of CTGF was seen in 35 of 40 HCC samples (87.5%).CTGF was overexpressed 5-fold in 20 HCC tissues,compared with surrounding non-tumor liver tissue.CTGF mRNA level was 5-8-fold higher in HepG2,SMMC-7721 and MHCC-97H than in LO2 cells.This indicated that the inhibition rate of cell growth was 43% after knockdown of CTGF expression (P <0.05).Soft agar colony formation assay showed that siRNA mediated knockdown of CTGF inhibited colony formation in soft agar of HepG2 cells (P <0.05).The volume of tumors from CTGF-shRNA-expressing cells only accounted for 35% of the tumors from the scrambled control-infected HepG2 cells (P <0.05).Conclusions CTGF was overexpressed in human HCC cells and downregulation of CTGF inhibited HCC growth in vitro and in vivo.Knockdown of CTGF may be a potential therapeutic strategy for treatment of HCC.

  14. ADENOVIRUS-MEDIATED P53 GENE TRANSFER INCREASES THE THERMOSENSITIVITY OF HUMAN GASTRIC CARCINOMA CELL LINES (IN VITRO AND IN VIVO)

    Institute of Scientific and Technical Information of China (English)

    张珊文; 肖绍文; 吕有勇

    2003-01-01

    Objective: To investigate the effect of adenovirus- mediated p53 (Adp53) transfer on thermosensitivity of human gastric carcinoma cell lines (BGC823). Methods: Two human gastric carcinoma cell lines with different p53 status, BGC823-wtp53 cell (abbreviate W) bearing the wilt-type p53 and BGC823-mutp53 cell (abbreviate M) bearing the mutant p53, were cultured with DMEM medium and were infected with Adp53 at a viral multiplicity of infection of 100 (1:100MOI) for 48h before heating. Cell cycle redistribution and apoptosis of two human gastric carcinoma cell lines in 24h at 37℃ after heat treatment at 42℃ for 2h or 43℃ for 0.5h were analyzed by flow cytometry. Relative tumor volume growth curves were used in a nude mouse tumor model of the two cell lines following hyperthermia at 43℃ for 0.5h after 48h intratumoral injection of 1(108 pfu of Adp53 to evaluate thermoenhancemet effect in vivo. Results: In vitro study showed that both W and M cells infected with Adp53 and treated with heating had strong arrest in G2 (after heating at 42℃ for 2h, 34.0% of original population for W cells and 25.3% of original population for M cells) and produced obvious apoptotic response. The apoptosis rate showed 230% increased (for W cells) and 110% increase (for M cells) compared with heating only control. In vivo study showed that the growth of tumor of both W cells and M cells was significantly delayed by hyperthemia combining with Adp53 as compared to tumors receiving either treatment alone. Conclusion: This study demonstrated that Adp53 transfer increased cellular apoptosis and thermo- sensitivity in vitro and tumor thermosensitivity in vivo independent of cellular intrinsic p53 status. These results support the combined used of p53 gene therapy with hyperthermia in clinical trials.

  15. Effects of TGF-beta signalling inhibition with galunisertib (LY2157299) in hepatocellular carcinoma models and in ex vivo whole tumor tissue samples from patients

    OpenAIRE

    Serova, Maria; Tijeras-Raballand, Annemilaï; Santos, Célia Dos; Albuquerque, Miguel; Paradis, Valerie; Neuzillet, Cindy; Benhadji, Karim A; Raymond, Eric; Faivre, Sandrine; De Gramont, Armand

    2015-01-01

    Galunisertib (LY2157299) is a selective ATP-mimetic inhibitor of TGF-β receptor (TβR)-I activation currently under clinical investigation in hepatocellular carcinoma (HCC) patients. Our study explored the effects of galunisertib in vitro in HCC cell lines and ex vivo on patient samples. Galunisertib was evaluated in HepG2, Hep3B, Huh7, JHH6 and SK-HEP1 cells as well as in SK-HEP1-derived cells tolerant to sorafenib (SK-Sora) and sunitinib (SK-Suni). Exogenous stimulation of all HCC cell lines...

  16. Effect of cisplatin and c-myb antisense phosphorothioate oligodeoxynucleotides combination on a human colon carcinoma cell line in vitro and in vivo.

    OpenAIRE

    Del Bufalo, D; Cucco, C.; C. Leonetti; Citro, G.; D'Agnano, I; M. Benassi; Geiser, T; Zon, G; Calabretta, B; Zupi, G.

    1996-01-01

    We investigated the effect of c-myb antisense phosphorothioate oligodeoxynucleotides [(S)ODNs] and cisplatin (CDDP) combination on the human colon carcinoma cell line LoVo Dx both in vitro and in nude mice bearing LoVo Dx solid tumour. We show that antisense (S)ODN treatment decreases c-myb mRNA and protein expression, induces growth arrest in the G1 phase of the cell cycle, and inhibits cell proliferation. In vivo treatment with c-myb antisense (S)ODNs results in a reduction in tumour growth...

  17. Pancreatic carcinoma, pancreatitis, and healthy controls: metabolite models in a three-class diagnostic dilemma.

    Science.gov (United States)

    Leichtle, Alexander Benedikt; Ceglarek, Uta; Weinert, Peter; Nakas, Christos T; Nuoffer, Jean-Marc; Kase, Julia; Conrad, Tim; Witzigmann, Helmut; Thiery, Joachim; Fiedler, Georg Martin

    2013-06-01

    Metabolomics as one of the most rapidly growing technologies in the "-omics" field denotes the comprehensive analysis of low molecular-weight compounds and their pathways. Cancer-specific alterations of the metabolome can be detected by high-throughput mass-spectrometric metabolite profiling and serve as a considerable source of new markers for the early differentiation of malignant diseases as well as their distinction from benign states. However, a comprehensive framework for the statistical evaluation of marker panels in a multi-class setting has not yet been established. We collected serum samples of 40 pancreatic carcinoma patients, 40 controls, and 23 pancreatitis patients according to standard protocols and generated amino acid profiles by routine mass-spectrometry. In an intrinsic three-class bioinformatic approach we compared these profiles, evaluated their selectivity and computed multi-marker panels combined with the conventional tumor marker CA 19-9. Additionally, we tested for non-inferiority and superiority to determine the diagnostic surplus value of our multi-metabolite marker panels. Compared to CA 19-9 alone, the combined amino acid-based metabolite panel had a superior selectivity for the discrimination of healthy controls, pancreatitis, and pancreatic carcinoma patients [Formula: see text] We combined highly standardized samples, a three-class study design, a high-throughput mass-spectrometric technique, and a comprehensive bioinformatic framework to identify metabolite panels selective for all three groups in a single approach. Our results suggest that metabolomic profiling necessitates appropriate evaluation strategies and-despite all its current limitations-can deliver marker panels with high selectivity even in multi-class settings. PMID:23678345

  18. Telomerase inhibition decreases alpha-fetoprotein expression and secretion by hepatocellular carcinoma cell lines: in vitro and in vivo study.

    Directory of Open Access Journals (Sweden)

    Roula Tahtouh

    Full Text Available Alpha-fetoprotein (AFP is a diagnostic marker for hepatocellular carcinoma (HCC. A direct relationship between poor prognosis and the concentration of serum AFP has been observed. Telomerase, an enzyme that stabilizes the telomere length, is expressed by 90% of HCC. The aim of this study was to investigate the effect of telomerase inhibition on AFP secretion and the involvement of the PI3K/Akt/mTOR signaling pathway. Proliferation and viability tests were performed using tetrazolium salt. Apoptosis was determined through the Annexin V assay using flow cytometry. The concentrations of AFP were measured using ELISA kits. The AFP mRNA expression was evaluated using RT-PCR, and cell migration was evaluated using a Boyden chamber assay. The in vivo effect of costunolide on AFP production was tested in NSG mice. Telomerase inhibition by costunolide and BIBR 1532 at 5 and 10 μM decreased AFP mRNA expression and protein secretion by HepG2/C3A cells. The same pattern was obtained with cells treated with hTERT siRNA. This treatment exhibited no apoptotic effect. The AFP mRNA expression and protein secretion by PLC/PRF/5 was decreased after treatment with BIBR1532 at 10 μM. In contrast, no effect was obtained for PLC/PRF/5 cells treated with costunolide at 5 or 10 μM. Inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP concentration. In contrast, the MAPK/ERK pathway appeared to not be involved in HepG2/C3A cells, whereas ERK inhibition decreased the AFP concentration in PLC/PRF/5 cells. Modulation of the AFP concentration was also obtained after the inhibition or activation of PKC. Costunolide (30 mg/kg significantly decreased the AFP serum concentration of NSG mice bearing HepG2/C3A cells. Both the inhibition of telomerase and the inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP production of HepG2/C3A and PLC/PRF/5 cells, suggesting a relationship between telomerase and AFP expression through the PI3K

  19. Telomerase inhibition decreases alpha-fetoprotein expression and secretion by hepatocellular carcinoma cell lines: in vitro and in vivo study.

    Science.gov (United States)

    Tahtouh, Roula; Azzi, Anne-Sophie; Alaaeddine, Nada; Chamat, Soulaima; Bouharoun-Tayoun, Hasnaa; Wardi, Layal; Raad, Issam; Sarkis, Riad; Antoun, Najibe Abou; Hilal, George

    2015-01-01

    Alpha-fetoprotein (AFP) is a diagnostic marker for hepatocellular carcinoma (HCC). A direct relationship between poor prognosis and the concentration of serum AFP has been observed. Telomerase, an enzyme that stabilizes the telomere length, is expressed by 90% of HCC. The aim of this study was to investigate the effect of telomerase inhibition on AFP secretion and the involvement of the PI3K/Akt/mTOR signaling pathway. Proliferation and viability tests were performed using tetrazolium salt. Apoptosis was determined through the Annexin V assay using flow cytometry. The concentrations of AFP were measured using ELISA kits. The AFP mRNA expression was evaluated using RT-PCR, and cell migration was evaluated using a Boyden chamber assay. The in vivo effect of costunolide on AFP production was tested in NSG mice. Telomerase inhibition by costunolide and BIBR 1532 at 5 and 10 μM decreased AFP mRNA expression and protein secretion by HepG2/C3A cells. The same pattern was obtained with cells treated with hTERT siRNA. This treatment exhibited no apoptotic effect. The AFP mRNA expression and protein secretion by PLC/PRF/5 was decreased after treatment with BIBR1532 at 10 μM. In contrast, no effect was obtained for PLC/PRF/5 cells treated with costunolide at 5 or 10 μM. Inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP concentration. In contrast, the MAPK/ERK pathway appeared to not be involved in HepG2/C3A cells, whereas ERK inhibition decreased the AFP concentration in PLC/PRF/5 cells. Modulation of the AFP concentration was also obtained after the inhibition or activation of PKC. Costunolide (30 mg/kg) significantly decreased the AFP serum concentration of NSG mice bearing HepG2/C3A cells. Both the inhibition of telomerase and the inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP production of HepG2/C3A and PLC/PRF/5 cells, suggesting a relationship between telomerase and AFP expression through the PI3K/Akt/mTOR pathway. PMID:25822740

  20. Comparison of in vitro cell models in predicting in vivo brain entry of drugs.

    Science.gov (United States)

    Hakkarainen, Jenni J; Jalkanen, Aaro J; Kääriäinen, Tiina M; Keski-Rahkonen, Pekka; Venäläinen, Tetta; Hokkanen, Juho; Mönkkönen, Jukka; Suhonen, Marjukka; Forsberg, Markus M

    2010-12-15

    Although several in vitro models have been reported to predict the ability of drug candidates to cross the blood-brain barrier, their real in vivo relevance has rarely been evaluated. The present study demonstrates the in vivo relevance of simple unidirectional permeability coefficient (P(app)) determined in three in vitro cell models (BBMEC, Caco-2 and MDCKII-MDR1) for nine model drugs (alprenolol, atenolol, metoprolol, pindolol, entacapone, tolcapone, baclofen, midazolam and ondansetron) by using dual probe microdialysis in the rat brain and blood as an in vivo measure. There was a clear correlation between the P(app) and the unbound brain/blood ratios determined by in vivo microdialysis (BBMEC r=0.99, Caco-2 r=0.91 and MDCKII-MDR1 r=0.85). Despite of the substantial differences in the absolute in vitro P(app) values and regardless of the method used (side-by-side vs. filter insert system), the capability of the in vitro models to rank order drugs was similar. By this approach, thus, the additional value offered by the true endothelial cell model (BBMEC) remains obscure. The present results also highlight the need of both in vitro as well as in vivo methods in characterization of blood-brain barrier passage of new drug candidates.

  1. Silencing of RhoA and RhoC expression by RNA interference suppresses human colorectal carcinoma growth in vivo

    Directory of Open Access Journals (Sweden)

    Wang Haibo

    2010-09-01

    Full Text Available Abstract Background RhoA and RhoC have been proved to be over-expressed in many solid cancers, including colorectal cancer. The reduction of RhoA and RhoC expression by RNA interference (RNAi resulted growth inhibition of cancer cells. The present study was to evaluate the effect of silencing of RhoA and RhoC expression by RNAi on growth of human colorectal carcinoma (CRC in tumor-bearing nude mice in vivo. Methods To establish HCT116 cell transplantable model, the nude mice were subcutaneously inoculated with 1.0 × 107 HCT116 cells and kept growing till the tumor xenografts reached 5-7 mm in diameter. Then the mice were randomly assigned to three groups(seven mice in each group: (1 normal saline(NS group, (2replication-defective recombinant adenovirus carrying the negative control shRNA (Ad-HK group and (3replication-defective recombinant adenovirus carrying the 4-tandem linked RhoA and RhoC shRNAs (Ad-RhoA-RhoC group. Ad-HK (4 × 108 pfu, 30 ul/mouse, Ad-RhoA-RhoC (4 × 108 pfu, 30 ul/mouse or PBS (30 ul/mouse was injected intratumorally four times once every other day. The weight and volumes of tumor xenografts were recorded. The levels of RhoA and RhoC mRNA transcripts and proteins in tumor xenografts were detected by reverse quantitative transcription polymerase chain reaction (QRT-PCR and immunohistochemical staining respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay was used to detect the death of cells. Results The xenografts in mice could be seen at 5th day from the implantation of HCT116 cells and all had reached 5-7 mm in size at 9th day. After injection intratumorally, the growth speed of tumor xenografts in Ad-RhoA-RhoC group was significantly delayed compared with those in NS and Ad-HK group(P RhoA and RhoC reduced more in Ad-RhoA-RhoC group than those in NS and Ad-HK group. The relative RhoA and RhoC mRNA transcripts were decreased to 48% and 43% respectively (P RhoA and Rho

  2. Expression of E-cadherin in oral epithelial dysplasia and oral squamous cell carcinoma: An in vivo study

    OpenAIRE

    Avadhoot Avadhani; J V Tupkari; Yuwanati, Monal B.

    2011-01-01

    Objectives: There is evidence that E-cadherins may also play a role in progression of dysplasia to cancer. The aim of this study was to investigate the expression of E-cadherin during the process of oral carcinogenesis by comparing their expression in normal and oral dysplastic epithelium (OED) with oral squamous cell carcinoma (OSSC).Materials and methods: The patients who were clinical suspected of having premalignant lesion and oral squamous cell carcinoma were included in the study after ...

  3. Expression of E-cadherin in oral epithelial dysplasia and oral squamous cell carcinoma: An in vivo study

    OpenAIRE

    Yuwanati, Monal B.; J V Tupkari; Avadhani, Avadhoot

    2011-01-01

    Objectives: There is evidence that E-cadherins may also play a role in progression of dysplasia to cancer. The aim of this study was to investigate the expression of E-cadherin during the process of oral carcinogenesis by comparing their expression in normal and oral dysplastic epithelium (OED) with oral squamous cell carcinoma (OSSC). Materials and methods: The patients who were clinical suspected of having premalignant lesion and oral squamous cell carcinoma were included in the study a...

  4. Modeling in vivo corrosion of AZ31 as temporary biodegradable implants. Experimental validation in rats

    International Nuclear Information System (INIS)

    In this paper, two complementary approaches, mathematical modeling and experimental results are combined to identify variables that affect the in vivo biodegradation of magnesium implants. The in vivo corrosion behavior of AZ31 alloy proposed for temporary applications as fixation of bone fractures has been modeled solving the Laplace equation by finite element method (FEM). Bar-shaped AZ31 implants of 1 mm diameter and 20 mm length were inserted in Wistar rat femurs with and without a fracture. The presence of gas around AZ31 implants inside the femurs has been detected in situ at the epiphysis and in fractured areas by computerized tomography (CT). Examining some in vivo conditions, the model confirms that magnesium-alloy devices have different biodegradation behavior, depending on the thickness of electrolyte at the implantation site and can be used for predicting the biodegradation behavior. - Highlights: • Modeling of AZ31 corrosion by solving the Laplace by finite element method • Electrolyte thickness is a key factor in the in vivo corrosion of magnesium alloys. • A critical thickness below which corrosion is focused around impurities is identified. • The critical value is less evident in a material with a high number of impurities. • Experimental and numerical results explain the biodegradation of magnesium implants

  5. Modeling In Vivo Interactions of Engineered Nanoparticles in the Pulmonary Alveolar Lining Fluid

    Directory of Open Access Journals (Sweden)

    Dwaipayan Mukherjee

    2015-07-01

    Full Text Available Increasing use of engineered nanomaterials (ENMs in consumer products may result in widespread human inhalation exposures. Due to their high surface area per unit mass, inhaled ENMs interact with multiple components of the pulmonary system, and these interactions affect their ultimate fate in the body. Modeling of ENM transport and clearance in vivo has traditionally treated tissues as well-mixed compartments, without consideration of nanoscale interaction and transformation mechanisms. ENM agglomeration, dissolution and transport, along with adsorption of biomolecules, such as surfactant lipids and proteins, cause irreversible changes to ENM morphology and surface properties. The model presented in this article quantifies ENM transformation and transport in the alveolar air to liquid interface and estimates eventual alveolar cell dosimetry. This formulation brings together established concepts from colloidal and surface science, physics, and biochemistry to provide a stochastic framework capable of capturing essential in vivo processes in the pulmonary alveolar lining layer. The model has been implemented for in vitro solutions with parameters estimated from relevant published in vitro measurements and has been extended here to in vivo systems simulating human inhalation exposures. Applications are presented for four different ENMs, and relevant kinetic rates are estimated, demonstrating an approach for improving human in vivo pulmonary dosimetry.

  6. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy

    Science.gov (United States)

    Wang, Jianfeng; Lin, Kan; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Huang, Zhiwei

    2015-01-01

    This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800–1800 cm−1) and high-wavenumber (HW)(2800–3600 cm−1) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy. PMID:26243571

  7. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy

    Science.gov (United States)

    Wang, Jianfeng; Lin, Kan; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Huang, Zhiwei

    2015-08-01

    This work aims to evaluate clinical value of a fiber-optic Raman spectroscopy technique developed for in vivo diagnosis of esophageal squamous cell carcinoma (ESCC) during clinical endoscopy. We have developed a rapid fiber-optic Raman endoscopic system capable of simultaneously acquiring both fingerprint (FP)(800-1800 cm-1) and high-wavenumber (HW)(2800-3600 cm-1) Raman spectra from esophageal tissue in vivo. A total of 1172 in vivo FP/HW Raman spectra were acquired from 48 esophageal patients undergoing endoscopic examination. The total Raman dataset was split into two parts: 80% for training; while 20% for testing. Partial least squares-discriminant analysis (PLS-DA) and leave-one patient-out, cross validation (LOPCV) were implemented on training dataset to develop diagnostic algorithms for tissue classification. PLS-DA-LOPCV shows that simultaneous FP/HW Raman spectroscopy on training dataset provides a diagnostic sensitivity of 97.0% and specificity of 97.4% for ESCC classification. Further, the diagnostic algorithm applied to the independent testing dataset based on simultaneous FP/HW Raman technique gives a predictive diagnostic sensitivity of 92.7% and specificity of 93.6% for ESCC identification, which is superior to either FP or HW Raman technique alone. This work demonstrates that the simultaneous FP/HW fiber-optic Raman spectroscopy technique improves real-time in vivo diagnosis of esophageal neoplasia at endoscopy.

  8. In-vivo imaging of oral squamous cell carcinoma by EGFR monoclonal antibody conjugated near-infrared quantum dots in mice

    Directory of Open Access Journals (Sweden)

    Li YD

    2011-08-01

    Full Text Available Kai Yang, Fu-Jun Zhang, Hong Tang, Cheng Zhao, Yu-An Cao, Xiao-Qiang Lv, Dan Chen, Ya-Dong LiDepartment of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing, ChinaObjectives: The purpose of this study was to investigate in-vivo visible imaging of oral squamous cell carcinoma (OSCC by targeting epidermal growth factor receptor (EGFR with near-infrared quantum dots.Materials and methods: Quantum dots with an emission wavelength of 800 nm (QD800 were conjugated to monoclonal antibodies against EGFR, resulting in the probe designated as QD800-EGFR Ab. OSCC cell line (BcaCD885 expressing high levels of EGFR was transplanted subcutaneously into nude mice cheeks to develop an OSCC animal model. QD800-EGFR Ab containing 100 pmol equivalent of QD800 was intravenously injected into the animal model, and in-situ and in-vivo imaging of cheek squamous cell carcinoma was analyzed at 10 different time points.Results and conclusion: In-vivo imaging and immunohistochemical examination of the tumors showed that intravenously injected QD800-EGFR Ab probe could bind EGFR expressed on BcaCD885 cells. Fluorescence signals of BcaCD885 cells labeled with QD800-EGFR Ab probe could be clarly detected, and these fluorescence signals lasted for 24 hours. The most complete tumor images with maximal signal-to-noise ratio were observed from 15 minutes to 6 hours after injection of the probe. To the best of the authors' knowledge, this is the first study that has obtained clear in-situ and in-vivo imaging of head and neck cancer by using QD800-EGFR Ab probe. The authors conclude that the combination of near-infrared quantum dots that are highly penetrating for tissues with EGFR monoclonal antibody has promising prospects in in-vivo imaging of OSCC and development of personalized surgical therapies.Keywords: oral cancer, head and neck cancer, near-infrared fluorescence, visual in-vivo imaging, epidermal growth factor receptor

  9. Modeling In Vivo Interactions of Engineered Nanoparticles in the Pulmonary Alveolar Lining Fluid

    OpenAIRE

    Dwaipayan Mukherjee; Alexandra Porter; Mary Ryan; Stephan Schwander; Kian Fan Chung; Teresa Tetley; Junfeng Zhang; Panos Georgopoulos

    2015-01-01

    Increasing use of engineered nanomaterials (ENMs) in consumer products may result in widespread human inhalation exposures. Due to their high surface area per unit mass, inhaled ENMs interact with multiple components of the pulmonary system, and these interactions affect their ultimate fate in the body. Modeling of ENM transport and clearance in vivo has traditionally treated tissues as well-mixed compartments, without consideration of nanoscale interaction and transformation mechanisms. ENM ...

  10. In vivo antimicrobial activity of marbofloxacin against Pasteurella multocida in a tissue cage model in calves

    Directory of Open Access Journals (Sweden)

    Changfu eCao

    2015-07-01

    Full Text Available Marbofloxacin is a fluoroquinolone specially developed for use in veterinary medicine with broad-spectrum antibacterial activity. The objective of our study was to re-evaluate in vivo antimicrobial activity of marbofloxacin against Pasteurella multocida using subcutaneously implanted tissue cages in calves. Calves were infected by direct injection into tissue cages with Pasteurella multocida(type B, serotype 2, then intramuscularly received a range of marbofloxacin doses 24h after inoculation. The ratio of 24h area under the concentration-time curve divided by the minimum inhibitory concentration or the mutant prevention concentration (AUC24h/MIC or AUC24h/MPC was the pharmacokinetic-pharmacodynamic (PK/PD index that best described the effectiveness of marbofloxacin against Pasteurella multocida (R2=0.8514 by nonlinear regression analysis. Marbofloxacin exhibited a good antimicrobial activity in vivo. The levels of AUC24h/MIC and AUC24h/MPC that produced 50% (1.5log10CFU/mL reduction and 90% (3log10CFU/mL reduction of maximum response were 18.60h and 50.65h, 4.67h and 12.89h by using sigmoid Emax model WINNONLIN software, respectively. The in vivo PK/PD integrated methods by tissue cage model display the advantage of the evaluation of antimicrobial activity and the optimization of the dosage regimen for antibiotics in the presence of the host defenses, especially in target animal of veterinary interest.

  11. In vivo antimicrobial activity of marbofloxacin against Pasteurella multocida in a tissue cage model in calves.

    Science.gov (United States)

    Cao, Changfu; Qu, Ying; Sun, Meizhen; Qiu, Zhenzhen; Huang, Xianhui; Huai, Binbin; Lu, Yan; Zeng, Zhenling

    2015-01-01

    Marbofloxacin is a fluoroquinolone specially developed for use in veterinary medicine with broad-spectrum antibacterial activity. The objective of our study was to re-evaluate in vivo antimicrobial activity of marbofloxacin against Pasteurella multocida using subcutaneously implanted tissue cages in calves. Calves were infected by direct injection into tissue cages with P. multocida(type B, serotype 2), then intramuscularly received a range of marbofloxacin doses 24 h after inoculation. The ratio of 24 h area under the concentration-time curve divided by the minimum inhibitory concentration or the mutant prevention concentration (AUC24 h/MIC or AUC24 h/MPC) was the pharmacokinetic-pharmacodynamic (PK/PD) index that best described the effectiveness of marbofloxacin against P. multocida (R (2) = 0.8514) by non-linear regression analysis. Marbofloxacin exhibited a good antimicrobial activity in vivo. The levels of AUC24 h/MIC and AUC24 h/MPC that produced 50% (1.5log10 CFU/mL reduction) and 90% (3log10 CFU/mL reduction) of maximum response were 18.60 and 50.65 h, 4.67 and 12.89 h by using sigmoid Emax model WINNONLIN software, respectively. The in vivo PK/PD integrated methods by tissue cage model display the advantage of the evaluation of antimicrobial activity and the optimization of the dosage regimen for antibiotics in the presence of the host defenses, especially in target animal of veterinary interest.

  12. Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Luo YL

    2016-07-01

    Full Text Available Yuling Luo, Zhongbing Liu, Xiaoqin Zhang, Juan Huang, Xin Yu, Jinwei Li, Dan Xiong, Xiaoduan Sun, Zhirong Zhong Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan,People’s Republic of ChinaAbstract: The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 µm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger–Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy.Keywords: oleanolic acid, multivesicular liposomes, murine hepatocellular carcinoma, controlled release, cancer therapy

  13. The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma.

    LENUS (Irish Health Repository)

    Bennett, M W

    2012-02-03

    Various cancer cell lines express Fas ligand (FasL) and can kill lymphoid cells by Fas-mediated apoptosis in vitro. FasL expression has been demonstrated in several human malignancies in vivo. We sought to determine whether human esophageal carcinomas express FasL, and whether FasL expression is associated with increased apoptosis of tumor-infiltrating lymphocytes (TIL) in vivo, thereby contributing to the immune privilege of the tumor. Using in situ hybridization and immunohistochemistry, respectively, FasL mRNA and protein were colocalized to neoplastic esophageal epithelial cells in all esophageal carcinomas (squamous, n = 6; adenocarcinoma, n = 2). The Extent of FasL expression was variable, with both FasL-positive and FasL-negative neoplastic regions occurring within tumors. TIL were detected by immunohistochemical staining for the leukocyte common Ag, CD45. FasL expression was associated with a mean fourfold depletion of TIL when compared with FasL-negative areas within the same tumors (range 1.6- to 12-fold, n = 6,p < 0.05). Cell death of TIL was detected by dual staining of CD45 (immunohistochemistry) and DNA strand breaks (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). There was a mean twofold increase in detectable cell death among TIL in FasL-positive areas compared with FasL-negative areas (range 1.6- to 2.4-fold, n = 6, p < 0.05). In conclusion, we demonstrate a statistically significant, quantitative reduction of TIL concomitant with significantly increased TIL apoptosis within FasL-expressing areas of esophageal tumors. Our findings suggest Fas-mediated apoptotic depletion of TIL in response to FasL expression by esophageal cancers, and provide the first direct, quantitative evidence to support the Fas counterattack as a mechanism of immune privilege in vivo in human cancer.

  14. Single cell migration in oral squamous cell carcinoma - possible evidence of epithelial-mesenchymal transition in vivo

    DEFF Research Database (Denmark)

    Jensen, David H; Reibel, Jesper; Mackenzie, Ian C;

    2015-01-01

    carcinomas, their relationship has not been examined in detail. METHODS: Paraffin-embedded tissues from 28 patients with oral squamous cell carcinomas were stained with antibodies to cytokeratin, α-SMA, vimentin, E-cadherin, N-cadherin and Twist and evaluated for their expression in relation to invasive......BACKGROUND: The invasion of cancer cells into the surrounding normal tissue is one of the defining features of cancer. While the phenomena of tumour budding, epithelial-mesenchymal transition and the presence of myofibroblasts have independently been shown to be related to a poor prognosis of oral...

  15. CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

    International Nuclear Information System (INIS)

    Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression

  16. CIAPIN1 gene silencing enhances chemosensitivity in a drug-resistant animal model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.M.; Gao, S.J.; Guo, X.F.; Sun, W.J. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Yan, Z.Q. [Department of Breast Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin (China); Wang, W.X.; Xu, Y.Q.; Lu, D. [Department of Oncology, The Second Affiliated Hospital, Harbin Medical University, Harbin (China)

    2014-03-21

    Overexpression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) contributes to multidrug resistance (MDR) in breast cancer. This study aimed to evaluate the potential of CIAPIN1 gene silencing by RNA interference (RNAi) as a treatment for drug-resistant breast cancer and to investigate the effect of CIAPIN1 on the drug resistance of breast cancer in vivo. We used lentivirus-vector-based RNAi to knock down CIAPIN1 in nude mice bearing MDR breast cancer tumors and found that lentivirus-vector-mediated silencing of CIAPIN1 could efficiently and significantly inhibit tumor growth when combined with chemotherapy in vivo. Furthermore, Western blot analysis showed that both CIAPIN1 and P-glycoprotein expression were efficiently downregulated, and P53 was upregulated, after RNAi. Therefore, we concluded that lentivirus-vector-mediated RNAi targeting of CIAPIN1 is a potential approach to reverse MDR of breast cancer. In addition, CIAPIN1 may participate in MDR of breast cancer by regulating P-glycoprotein and P53 expression.

  17. In vivo 31P magnetic resonance spectroscopy and 1H magnetic resonance imaging of human bladder carcinoma on nude mice: effects of tumour growth and treatment with cis-dichloro-diamine platinum

    DEFF Research Database (Denmark)

    De Certaines, J D; Albrectsen, J; Larsen, V A;

    1992-01-01

    In vivo 31P NMR spectroscopy and 1H NMR imaging were used to examine the bladder T24B carcinoma in nude mice during untreated growth and in response to chemotherapy by Cis-dichloro-diammine-platinum (CDDP) at a dose of 8 mg/kg i.p. Untreated growth was associated with an increase of inorganic pho...

  18. In Vivo Investigation of the Effectiveness of a Hyper-viscoelastic Model in Simulating Brain Retraction

    Science.gov (United States)

    Li, Ping; Wang, Weiwei; Zhang, Chenxi; An, Yong; Song, Zhijian

    2016-07-01

    Intraoperative brain retraction leads to a misalignment between the intraoperative positions of the brain structures and their previous positions, as determined from preoperative images. In vitro swine brain sample uniaxial tests showed that the mechanical response of brain tissue to compression and extension could be described by the hyper-viscoelasticity theory. The brain retraction caused by the mechanical process is a combination of brain tissue compression and extension. In this paper, we first constructed a hyper-viscoelastic framework based on the extended finite element method (XFEM) to simulate intraoperative brain retraction. To explore its effectiveness, we then applied this framework to an in vivo brain retraction simulation. The simulation strictly followed the clinical scenario, in which seven swine were subjected to brain retraction. Our experimental results showed that the hyper-viscoelastic XFEM framework is capable of simulating intraoperative brain retraction and improving the navigation accuracy of an image-guided neurosurgery system (IGNS).

  19. In Vivo Investigation of the Effectiveness of a Hyper-viscoelastic Model in Simulating Brain Retraction.

    Science.gov (United States)

    Li, Ping; Wang, Weiwei; Zhang, Chenxi; An, Yong; Song, Zhijian

    2016-01-01

    Intraoperative brain retraction leads to a misalignment between the intraoperative positions of the brain structures and their previous positions, as determined from preoperative images. In vitro swine brain sample uniaxial tests showed that the mechanical response of brain tissue to compression and extension could be described by the hyper-viscoelasticity theory. The brain retraction caused by the mechanical process is a combination of brain tissue compression and extension. In this paper, we first constructed a hyper-viscoelastic framework based on the extended finite element method (XFEM) to simulate intraoperative brain retraction. To explore its effectiveness, we then applied this framework to an in vivo brain retraction simulation. The simulation strictly followed the clinical scenario, in which seven swine were subjected to brain retraction. Our experimental results showed that the hyper-viscoelastic XFEM framework is capable of simulating intraoperative brain retraction and improving the navigation accuracy of an image-guided neurosurgery system (IGNS). PMID:27387301

  20. Loss of the α2β1 integrin alters human papilloma virus-induced squamous carcinoma progression in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Thuy Tran

    Full Text Available Expression of the α2β1 integrin, a receptor for collagens and laminin, is altered during tumor progression. Recent studies have linked polymorphisms in the α2 integrin gene with oral, squamous cell carcinoma (SCC. To determine the α2β1 integrin's role in SCC progression, we crossed α2-null mice with K14-HPV16 transgenic animals. Pathological progression to invasive carcinoma was evaluated in HPV-positive, α2-null (HPV/KO and HPV-positive, wild-type (HPV/WT animals. α2β1 integrin expression stimulated progression from hyperplasia and papillomatosis to dysplasia with concomitant dermal mast cell infiltration. Moreover, lymph node metastasis was decreased by 31.3% in HPV/KO, compared to HPV/WT, animals. To evaluate the integrin-specific impact on the malignant epithelium versus the microenvironment, we developed primary tumor cell lines. Although transition from dysplasia to carcinoma was unaltered during spontaneous tumor development, isolated primary HPV/KO SCC cell lines demonstrated decreased migration and invasion, compared to HPV/WT cells. When HPV/WT and HPV/KO SCC cells were orthotopically injected into WT or KO hosts, tumor α2β1 integrin expression resulted in decreased tumor latency, regardless of host integrin status. HPV/WT SCC lines failed to demonstrate a proliferative advantage in vitro, however, the HPV/WT tumors demonstrated increased growth compared to HPV/KO SCC lines in vivo. Although contributions of the integrin to the microenvironment cannot be excluded, our studies indicate that α2β1 integrin expression by HPV-transformed keratinocytes modulates SCC growth and progression.

  1. Effect of Non-Anticoagulant N-Desulfated Heparin on Basic Fibroblast Growth Factor Expression, Angiogenesis, and Metastasis of Gastric Carcinoma In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Jin-Lian Chen

    2012-01-01

    Full Text Available Objective. The present study was performed to investigate the effect of N-desulfated heparin on basic fibroblast growth factor (bFGF expression, tumor angiogenesis and metastasis of gastric carcinoma. Methods. Human gastric cancer SGC-7901 tissues were orthotopically implanted into the stomach of NOD SCID mice. Twenty mice were randomly divided into two groups which received either intravenous injection of 0.9% NaCl solution (normal saline group or 10 mg/kg N-desulfated heparin (N-desulfated heparin group twice weekly for three weeks. In vitro, human gastric carcinoma SGC-7901 cells were treated with N-desulfated heparin in different concentration (0.1 mg/mL, 1 mg/mL, N-desulfated heparin group, and treated with medium (control group. Results. In vivo, the tumor metastasis rates were 9/10 in normal saline group and 2/10 in N-desulfated heparin group (P<0.05. The intratumoral microvessel density was higher in normal saline group than in N-desulfated heparin group (P<0.05. bFGF expression in gastric tissue was inhibited by N-desulfated heparin (P<0.05. There was no bleeding in N-desulfated heparin group. In vitro, N-desulfated heparin inhibited significantly bFGF protein and mRNA expression of gastric carcinoma cells (P<0.05. Conclusions. N-desulfated heparin can inhibit the metastasis of gastric cancer through inhibiting tumor bFGF expression and tumor angiogenesis with no obvious anticoagulant activity.

  2. Autoradiographic studies and experiments on partial synchronization of human tumors, especially mammary carcinomas, in vitro and in vivo following xenotransplantation to NU/NU mice

    Energy Technology Data Exchange (ETDEWEB)

    Nord, D.

    1980-08-20

    Human mammary carcinomas were evaluated radiographically in vitro in the native state. Penetration depths up to 552 ..mu..m into the tissue were reached by the incubating medium. The labelling indices for the 3H-thymidine autoradiography lay between 1.5 and 19.3 percent. A correlation of the autoradiographic labelling indices with the findings of a simultaneously performed in vitro sensitivity test against cytostatics could not be proved. There seems to be a relation between the histomorphological tumour image and the proliferation behaviour expressed by the autoradiographic labelling index. Human mammary carcinomas were cultivated as xeno-transplant on thymus-aplastic NU/NU mice in parallel to this investigation. These heterotransplants show a remarkable correlation to the proliferation behaviour of the directly examined human tumours, after an autoradiographic in-vivo-labelling, with index values between 1.5 and 23.8 percent. This parallelism in the biological behaviour represents a further proof for the usefulness of the oncological test model of the NU/NU mouse as a carrier for human carcinomas. The application of this pre-therapeutical test model followed by determination of the synchronization behaviour of three human malignomas after xeno-transplantation onto NU/NU mice. For all three tumous an individual synchronization behaviour could be determined. Therapy attempts followed with cyclophosphomide or ionizing radiation by using the optimal cell-cycle therapy. Therefore an improvement of the therapeutical success by means of pre-therapeutical synchronization of human tumours can be reached in particular cases.

  3. MiR-634 sensitizes nasopharyngeal carcinoma cells to paclitaxel and inhibits cell growth both in vitro and in vivo

    OpenAIRE

    Peng, Xiaowei; Cao, Peiguo; He, Dong; Han, Shuang; Zhou, Jianda; Tan, Guolin; Li, Wei; Yu, Fenghui; Yu, Jianjun; Li, Zan; Cao, Ke

    2014-01-01

    Resistance to chemotherapy is one of the key causal factors in cancer death and increasing evidence has revealed that microRNAs (miRNAs) are involved in chemoresistance in many kinds of human cancers. Paclitaxel has been used for treatment of advanced nasopharyngeal carcinoma (NPC); however, treatment failure often occurs due to development of acquired paclitaxel resistance. In this study, based on miRNA microarray screening and qRT-PCR validation, we found six differentially expressed miRNAs...

  4. Telomerase Inhibition Decreases Alpha-Fetoprotein Expression and Secretion by Hepatocellular Carcinoma Cell Lines: In Vitro and In Vivo Study

    OpenAIRE

    Roula Tahtouh; Anne-Sophie Azzi; Nada Alaaeddine; Soulaima Chamat; Hasnaa Bouharoun-Tayoun; Layal Wardi; Issam Raad; Riad Sarkis; Najibe Abou Antoun; George Hilal

    2015-01-01

    Alpha-fetoprotein (AFP) is a diagnostic marker for hepatocellular carcinoma (HCC). A direct relationship between poor prognosis and the concentration of serum AFP has been observed. Telomerase, an enzyme that stabilizes the telomere length, is expressed by 90% of HCC. The aim of this study was to investigate the effect of telomerase inhibition on AFP secretion and the involvement of the PI3K/Akt/mTOR signaling pathway. Proliferation and viability tests were performed using tetrazolium salt. A...

  5. Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo.

    Science.gov (United States)

    Nagaoka, Akira; Takehara, Hiroaki; Hayashi-Takagi, Akiko; Noguchi, Jun; Ishii, Kazuhiko; Shirai, Fukutoshi; Yagishita, Sho; Akagi, Takanori; Ichiki, Takanori; Kasai, Haruo

    2016-01-01

    Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca(2+) signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD. PMID:27221801

  6. Photodynamic impact induces ischemic tolerance in models in vivo and in vitro

    Science.gov (United States)

    Demyanenko, Svetlana; Sharifulina, Svetlana; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Maria; Zhukovskaya, Ludmila

    2016-04-01

    Ischemic tolerance determines resistance to lethal ischemia gained by a prior sublethal stimulus (i.e., preconditioning). We reproduced this effect in two variants. In vitro the preliminary short (5 s) photodynamic treatment (PDT) (photosensitizer Photosens, 10 nM, 30 min preincubation; laser: 670 nm, 100 mW/cm2) significantly reduced the necrosis of neurons and glial cells in the isolated crayfish stretch receptor, which was caused by following 30-min PDT by 66% and 46%, respectively. In vivo PDT of the rat cerebral cortex with hydrophilic photosensitizer Rose Bengal (i.v. administration, laser irradiation: 532 nm, 60 mW/cm2, 3 mm beam diameter, 30 min) caused occlusion of small brain vessels and local photothrombotic infarct (PTI). It is a model of ischemic stroke. Cerebral tissue edema and global necrosis of neurons and glial cells occurred in the infarction core, which was surrounded by a 1.5 mm transition zone, penumbra. The maximal pericellular edema, hypo- and hyperchromia of neurons were observed in penumbra 24 h after PTI. The repeated laser irradiation of the contralateral cerebral cortex also caused PTI but lesser as compared with single PDT. Preliminary unilateral PTI provided ischemic tolerance: at 14 day after second exposure the PTI volume significantly decreased by 24% than in the case of a single exposure. Sensorimotor deficits in PDT-treated rats was registered using the behavioral tests. The preliminary PTI caused the preconditioning effect.

  7. Effects of TGF-beta signalling inhibition with galunisertib (LY2157299) in hepatocellular carcinoma models and in ex vivo whole tumor tissue samples from patients.

    Science.gov (United States)

    Serova, Maria; Tijeras-Raballand, Annemilaï; Dos Santos, Célia; Albuquerque, Miguel; Paradis, Valerie; Neuzillet, Cindy; Benhadji, Karim A; Raymond, Eric; Faivre, Sandrine; de Gramont, Armand

    2015-08-28

    Galunisertib (LY2157299) is a selective ATP-mimetic inhibitor of TGF-β receptor (TβR)-I activation currently under clinical investigation in hepatocellular carcinoma (HCC) patients. Our study explored the effects of galunisertib in vitro in HCC cell lines and ex vivo on patient samples. Galunisertib was evaluated in HepG2, Hep3B, Huh7, JHH6 and SK-HEP1 cells as well as in SK-HEP1-derived cells tolerant to sorafenib (SK-Sora) and sunitinib (SK-Suni). Exogenous stimulation of all HCC cell lines with TGF-β yielded downstream activation of p-Smad2 and p-Smad3 that was potently inhibited with galunisertib treatment at micromolar concentrations. Despite limited antiproliferative effects, galunisertib yielded potent anti-invasive properties. Tumor slices from 13 patients with HCC surgically resected were exposed ex vivo to 1 µM and 10 µM galunisertib, 5 µM sorafenib or a combination of both drugs for 48 hours. Galunisertib but not sorafenib decreased p-Smad2/3 downstream TGF-β signaling. Immunohistochemistry analysis of galunisertib and sorafenib-exposed samples showed a significant decrease of the proliferative marker Ki67 and increase of the apoptotic marker caspase-3. In combination, galunisertib potentiated the effect of sorafenib efficiently by inhibiting proliferation and increasing apoptosis. Our data suggest that galunisertib may be active in patients with HCC and could potentiate the effects of sorafenib. PMID:26057634

  8. Improved visualization of breast cancer features in multifocal carcinoma using phase-contrast and dark-field mammography: an ex vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Grandl, Susanne; Sztrokay-Gaul, Aniko; Auweter, Sigrid D.; Hellerhoff, Karin [Ludwig-Maximilians-University Hospital Munich, Institute of Clinical Radiology, Munich (Germany); Scherer, Kai; Birnbacher, Lorenz; Willer, Konstantin; Chabior, Michael; Herzen, Julia; Pfeiffer, Franz [Technische Universitaet Muenchen, Department of Physics and Institute of Medical Engineering, Garching (Germany); Mayr, Doris [Ludwig-Maximilians-Universitaet Muenchen, Institute of Pathology, Munich (Germany); Bamberg, Fabian [University Hospital Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany)

    2015-12-15

    Conventional X-ray attenuation-based contrast is inherently low for the soft-tissue components of the female breast. To overcome this limitation, we investigate the diagnostic merits arising from dark-field mammography by means of certain tumour structures enclosed within freshly dissected mastectomy samples. We performed grating-based absorption, absolute phase and dark-field mammography of three freshly dissected mastectomy samples containing bi- and multifocal carcinoma using a compact, laboratory Talbot-Lau interferometer. Preoperative in vivo imaging (digital mammography, ultrasound, MRI), postoperative histopathological analysis and ex vivo digital mammograms of all samples were acquired for the diagnostic verification of our results. In the diagnosis of multifocal tumour growth, dark-field mammography seems superior to standard breast imaging modalities, providing a better resolution of small, calcified tumour nodules, demarcation of tumour boundaries with desmoplastic stromal response and spiculated soft-tissue strands extending from an invasive ductal breast cancer. On the basis of selected cases, we demonstrate that dark-field mammography is capable of outperforming conventional mammographic imaging of tumour features in both calcified and non-calcified tumours. Presuming dose optimization, our results encourage further studies on larger patient cohorts to identify those patients that will benefit the most from this promising additional imaging modality. (orig.)

  9. 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)

    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 G2/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

  10. Improved visualization of breast cancer features in multifocal carcinoma using phase-contrast and dark-field mammography: an ex vivo study

    International Nuclear Information System (INIS)

    Conventional X-ray attenuation-based contrast is inherently low for the soft-tissue components of the female breast. To overcome this limitation, we investigate the diagnostic merits arising from dark-field mammography by means of certain tumour structures enclosed within freshly dissected mastectomy samples. We performed grating-based absorption, absolute phase and dark-field mammography of three freshly dissected mastectomy samples containing bi- and multifocal carcinoma using a compact, laboratory Talbot-Lau interferometer. Preoperative in vivo imaging (digital mammography, ultrasound, MRI), postoperative histopathological analysis and ex vivo digital mammograms of all samples were acquired for the diagnostic verification of our results. In the diagnosis of multifocal tumour growth, dark-field mammography seems superior to standard breast imaging modalities, providing a better resolution of small, calcified tumour nodules, demarcation of tumour boundaries with desmoplastic stromal response and spiculated soft-tissue strands extending from an invasive ductal breast cancer. On the basis of selected cases, we demonstrate that dark-field mammography is capable of outperforming conventional mammographic imaging of tumour features in both calcified and non-calcified tumours. Presuming dose optimization, our results encourage further studies on larger patient cohorts to identify those patients that will benefit the most from this promising additional imaging modality. (orig.)

  11. Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo.

    Science.gov (United States)

    Cai, Xianbin; Hu, Xi; Tan, Xiaojun; Cheng, Weijie; Wang, Qinjia; Chen, Xiaofeng; Guan, Yinghong; Chen, Chong; Jing, Xubin

    2015-01-01

    Esophageal squamous cell carcinomas (ESCC) have become a severe threat to health and the current treatments for ESCC are frequently not effective. Recent epidemiological studies suggest that the anti-hyperglycemic agent metformin may reduce the risk of developing cancer, including ESCC, among diabetic patients. However, the antitumor effects of metformin on ESCC and the mechanisms underlying its cell cycle regulation remain elusive. The findings reported herein show that the anti-proliferative action of metformin on ESCC cell lines is partially mediated by AMPK. Moreover, we observed that metformin induced G0/G1 phase arrest accompanied by the up-regulation of p21CIP1 and p27KIP1. In vivo experiments further showed that metformin inhibited tumor growth in a ESCC xenograft model. Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down-regulation of cyclinD1 are involved in the anti-tumor action of metformin in vivo. In conclusion, metformin inhibits the growth of ESCC cells both in cell cultures and in an animal model. AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are involved in the inhibition of tumor growth that is induced by metformin and cell cycle arrest in ESCC. These findings indicate that metformin has the potential for use in the treatment of ESCC.

  12. Monte Carlo modeling of in vivo protoporphyrin IX fluorescence and singlet oxygen production during photodynamic therapy for patients presenting with superficial basal cell carcinomas

    Science.gov (United States)

    Valentine, Ronan M.; Brown, C. Tom A.; Moseley, Harry; Ibbotson, Sally; Wood, Kenny

    2011-04-01

    We present protoporphyrin IX (PpIX) fluorescence measurements acquired from patients presenting with superficial basal cell carcinoma during photodynamic therapy (PDT) treatment, facilitating in vivo photobleaching to be monitored. Monte Carlo (MC) simulations, taking into account photobleaching, are performed on a three-dimensional cube grid, which represents the treatment geometry. Consequently, it is possible to determine the spatial and temporal changes to the origin of collected fluorescence and generated singlet oxygen. From our clinical results, an in vivo photobleaching dose constant, β of 5-aminolaevulinic acid-induced PpIX fluorescence is found to be 14 +/- 1 J/cm2. Results from our MC simulations suggest that an increase from our typical administered treatment light dose of 75-150 J/cm2 could increase the effective PDT treatment initially achieved at a depth of 2.7-3.3 mm in the tumor, respectively. Moreover, this increase reduces the surface PpIX fluorescence from 0.00012 to 0.000003 of the maximum value recorded before treatment. The recommendation of administrating a larger light dose, which advocates an increase in the treatment time after surface PpIX fluorescence has diminished, remains valid for different sets of optical properties and therefore should have a beneficial outcome on the total treatment effect.

  13. Trans-splicing repair of mutant p53 suppresses the growth of hepatocellular carcinoma cells in vitro and in vivo

    OpenAIRE

    Xingxing He; Fang Liu; Jingjun Yan; Yunan Zhang; Junwei Yan; Haitao Shang; Qian Dou; Qiu Zhao; Yuhu Song

    2015-01-01

    Reactivation of wild-type p53 (wt-p53) function is an attractive therapeutic approach to p53-defective cancers. An ideal p53-based gene therapy should restore wt-p53 production and reduces mutant p53 transcripts simultaneously. In this study, we described an alternative strategy named as trans-splicing that repaired mutant p53 transcripts in hepatocellular carcinoma (HCC) cells. The plasmids which encoded a pre-trans-splicing molecule (PTM) targeting intron 6 of p53 were constructed and then ...

  14. Combined reflectance confocal microscopy-optical coherence tomography for delineation of basal cell carcinoma margins: an ex vivo study

    Science.gov (United States)

    Iftimia, Nicusor; Peterson, Gary; Chang, Ernest W.; Maguluri, Gopi; Fox, William; Rajadhyaksha, Milind

    2016-01-01

    We present a combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) approach, integrated within a single optical layout, for diagnosis of basal cell carcinomas (BCCs) and delineation of margins. While RCM imaging detects BCC presence (diagnoses) and its lateral spreading (margins) with measured resolution of ˜1 μm, OCT imaging delineates BCC depth spreading (margins) with resolution of ˜7 μm. When delineating margins in 20 specimens of superficial and nodular BCCs, depth could be reliably determined down to ˜600 μm, and agreement with histology was within about ±50 μm.

  15. Molecular imaging of EGFR and CD44v6 for prediction and response monitoring of HSP90 inhibition in an in vivo squamous cell carcinoma model

    Energy Technology Data Exchange (ETDEWEB)

    Spiegelberg, Diana; Mortensen, Anja C.; Stenerloew, Bo [Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Selvaraju, Ram K.; Eriksson, Olof [Uppsala University, Preclinical PET Platform, Uppsala (Sweden); Nestor, Marika [Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala (Sweden); Uppsala University, Unit of Otolaryngology and Head and Neck Surgery, Department of Surgical Sciences, Uppsala (Sweden)

    2016-05-15

    Heat shock protein 90 (HSP90) is essential for the activation and stabilization of numerous oncogenic client proteins. AT13387 is a novel HSP90 inhibitor promoting degradation of oncogenic proteins upon binding, and may also act as a radiosensitizer. For optimal treatment there is, however, the need for identification of biomarkers for patient stratification and therapeutic response monitoring, and to find suitable targets for combination treatments. The aim of this study was to assess the response of surface antigens commonly expressed in squamous cell carcinoma to AT13387 treatment, and to find suitable biomarkers for molecular imaging and radioimmunotherapy in combination with HSP90 inhibition. Cancer cell proliferation and radioimmunoassays were used to evaluate the effect of AT13387 on target antigen expression in vitro. Inhibitor effects were then assessed in vivo in mice-xenografts. Animals were treated with AT13387 (5 x 50 mg/kg), and were imaged with PET using either {sup 18}F-FDG or {sup 124}I-labelled tracers for EGFR and CD44v6, and this was followed by ex-vivo biodistribution analysis and immunohistochemical staining. AT13387 exposure resulted in high cytotoxicity and possible radiosensitization with IC{sub 50} values below 4 nM. Both in vitro and in vivo AT13387 effectively downregulated HSP90 client proteins. PET imaging with {sup 124}I-cetuximab showed a significant decrease of EGFR in AT13387-treated animals compared with untreated animals. In contrast, the squamous cell carcinoma-associated biomarker CD44v6, visualized with {sup 124}I-AbD19384 as well as {sup 18}F-FDG uptake, were not significantly altered by AT13387 treatment. We conclude that AT13387 downregulates HSP90 client proteins, and that molecular imaging of these proteins may be a suitable approach for assessing treatment response. Furthermore, radioimmunotherapy targeting CD44v6 in combination with AT13387 may potentiate the radioimmunotherapy outcome due to radiosensitizing effects of

  16. Molecular imaging of EGFR and CD44v6 for prediction and response monitoring of HSP90 inhibition in an in vivo squamous cell carcinoma model

    International Nuclear Information System (INIS)

    Heat shock protein 90 (HSP90) is essential for the activation and stabilization of numerous oncogenic client proteins. AT13387 is a novel HSP90 inhibitor promoting degradation of oncogenic proteins upon binding, and may also act as a radiosensitizer. For optimal treatment there is, however, the need for identification of biomarkers for patient stratification and therapeutic response monitoring, and to find suitable targets for combination treatments. The aim of this study was to assess the response of surface antigens commonly expressed in squamous cell carcinoma to AT13387 treatment, and to find suitable biomarkers for molecular imaging and radioimmunotherapy in combination with HSP90 inhibition. Cancer cell proliferation and radioimmunoassays were used to evaluate the effect of AT13387 on target antigen expression in vitro. Inhibitor effects were then assessed in vivo in mice-xenografts. Animals were treated with AT13387 (5 x 50 mg/kg), and were imaged with PET using either 18F-FDG or 124I-labelled tracers for EGFR and CD44v6, and this was followed by ex-vivo biodistribution analysis and immunohistochemical staining. AT13387 exposure resulted in high cytotoxicity and possible radiosensitization with IC50 values below 4 nM. Both in vitro and in vivo AT13387 effectively downregulated HSP90 client proteins. PET imaging with 124I-cetuximab showed a significant decrease of EGFR in AT13387-treated animals compared with untreated animals. In contrast, the squamous cell carcinoma-associated biomarker CD44v6, visualized with 124I-AbD19384 as well as 18F-FDG uptake, were not significantly altered by AT13387 treatment. We conclude that AT13387 downregulates HSP90 client proteins, and that molecular imaging of these proteins may be a suitable approach for assessing treatment response. Furthermore, radioimmunotherapy targeting CD44v6 in combination with AT13387 may potentiate the radioimmunotherapy outcome due to radiosensitizing effects of the drug, and could potentially

  17. Inhibitory effect of antisense vascular endothelial growth factor RNA on the profile of hepatocellular carcinoma cell line in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Ji-Hui Hao; Ming Yu; Hui-Kai Li; Yu-Rong Shi; Qiang Li; Xi-Shan Hao

    2006-01-01

    AIM: To evaluate the effect of antisense vascular endothelial growth factor (VEGF) RNA (PCMV-FGEV)transfection on the profile of hepatocellular carcinoma (HCC) SMMC-7721 cells in vitro and in vivo.METHODS: SMMC-7721 cells were transfected with PCMV-FGEV antisense, PCMV-VEGF sense and empty vector plasmid encapsulated by lipofectamine as antisense group, sense group and control group respectively. The positive cell clones were selected with G418. The stable transfection and expression of VEGF in the cells were determined by RT-PCR and immunohistochemistry. Cell proliferation was observed by MTT assay. FACS analysis was used to determine the effect of PCMV-FGEV transfection on cell apoptosis. The growth of transfected cells in vivo was also observed in nude mice.RESULTS: VEGFexpression was reduced in SMMC-7721transfected with PCMV-FGEV, which was confirmed by RT-PCR and immunohistochemistry. No effect of PCMVFGEV transfection was found on cell proliferation and cell apoptosis of SMMC-7721 in vitro. The growth of cells transfected with PCMV-FGEV was slow in nude mice and accompanied with obvious apoptosis. The latent time of tumors in the antisense group was 25.0± 1.8d, which was longer than that in sense and control groups (F=19.455, P<0.01). The average tumor weight in antisense group (0.96g±0.28 g) was the smallest among the three groups (F=21.501, P<0.01).CONCLUSION: The expression of VEGF can be inhibited by antisense PCMV-FGEV. Antisense PCMV-FGEV has no effect on cell proliferation and apoptosis of SMMC-7721in vitro but can inhibit tumor growth and induce cell apoptosis in vivo.

  18. Overexpression of NDRG2 Increases Iodine Uptake and Inhibits Thyroid Carcinoma Cell Growth In Situ and In Vivo.

    Science.gov (United States)

    Yin, Anqi; Wang, Chengguo; Sun, Jiachen; Gao, Jianjun; Tao, Liang; Du, Xilin; Zhao, Huadong; Yang, Jiandong; Li, Yan

    2016-01-01

    Medullary thyroid carcinoma (MTC) is an uncommon and highly aggressive tumor of the neuroendocrine system, which derives from the neuroendocrine C cells of the thyroid gland. Except for surgical resection, there are not very many effective systemic treatment options for MTC. N-Myc downstream-regulated gene 2 (NDRG2) had a significantly lower expression in MTC compared with normal thyroid tissue. However, the function of NDRG2 in MTC oncogenesis is largely unknown. In this study, we found that overexpression of NDRG2 inhibited the proliferation of TT cells (human medullary thyroid carcinoma cells) in vitro and suppressed the development of MTC in a nude mouse xenograft model. Further analysis revealed that NDRG2 arrested the cell cycle G0/G1 phase progression and induced TT cell apoptosis. Moreover, NDRG2 overexpression may mediate the antiproliferative effect by reducing cyclin D1 and cyclin E protein levels. We also found aberrant NDRG2-mitigated TT cell migration and invasion in vitro. Sodium/iodide symporter (NIS) mediates active I(-) transport into the thyroid follicular cells, and radionuclide treatment is a promising therapy for MTC. Our current data revealed that NDRG2 overexpression enhanced NIS level in TT cells and increased their iodine uptake in vitro. Furthermore, (99m)TcO4(-) radionuclide imaging of the xenograft tumors indicated that NDRG2 could promote NIS-mediated radionuclide transport. In conclusion, the present study suggested that NDRG2 is a critical molecule in the regulation of MTC biological behavior and a potential promoter in radioactive iodine therapy. PMID:26802650

  19. Induction of cytotoxic T lymphocyte respones in vivo after immunotherapy with dendritic cells in patients with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    JIAN MIN ZUO; LING ZHOU; ZHI JIAN CHEN; DE RUI LI; QI WANG; JIONG YU CHEN; ZHAN WANG; SHU QING YE; YI ZENG

    2006-01-01

    The aim of the present study was to determine the efficacy of immunotherapy with dendritic cells to elicit EBV-specific CTL-immunity in advanced cases of EBV-positive patients with nasopharyngeal carcinoma (NPC) and to determine the safety and toxicity of this preparation. Nine cases of histologically confirmed patients with NPC undergoing treatment with radiological therapy were enrolled in this study. Dendritic cells, generated in vitro from blood monocytes of patients were cultured and matured with cytokines and then infected with recombinant adenovirus vaccine containing EBV-latent membrane protein-2 (Ad-LMP2). On 9 days' cultivation of cells, the matured DCs were harvested, irradiated with 60Co and then injected intradermally to patients with NPC. The injections were performed 3 times totally. After immunization, the CTL responses were assayed by means of cytotoxicity and epitope-specific IFN-γ production. The results of this trial showed that all patients could tolerate this kind of treatment without any side effect, during which marked increase of LMP2-specific CTL-responses could be demonstrated in 5 patients of this group. And the level of IgA/VCA antibody decreased in 8 of 9 patients, thus accounting for a better prognosis for these patients. All patients will be followed up for another one year. At least, the present work shows that intradermal vaccination with autologous DCs infected with recombinant Ad-LMP2 adenovirus is a safe procedure in NPC patients, in which this procedure can enhance the LMP2-specific CTL responses in patients. These data are encouraging to develop more effective vaccine strategies for the treatment of nasopharyngeal carcinoma.

  20. 6-Shogaol induces apoptosis in human hepatocellular carcinoma cells and exhibits anti-tumor activity in vivo through endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Rong Hu

    Full Text Available 6-Shogaol is an active compound isolated from Ginger (Zingiber officinale Rosc. In this work, we demonstrated that 6-shogaol induces apoptosis in human hepatocellular carcinoma cells in relation to caspase activation and endoplasmic reticulum (ER stress signaling. Proteomic analysis revealed that ER stress was accompanied by 6-shogaol-induced apoptosis in hepatocellular carcinoma cells. 6-shogaol affected the ER stress signaling by regulating unfolded protein response (UPR sensor PERK and its downstream target eIF2α. However, the effect on the other two UPR sensors IRE1 and ATF6 was not obvious. In prolonged ER stress, 6-shogaol inhibited the phosphorylation of eIF2α and triggered apoptosis in SMMC-7721 cells. Salubrinal, an activator of the PERK/eIF2α pathway, strikingly enhanced the phosphorylation of eIF2α in SMMC-7721 cells with no toxicity. However, combined treatment with 6-shogaol and salubrinal resulted in significantly increase of apoptosis and dephosphorylation of eIF2α. Overexpression of eIF2α prevented 6-shogaol-mediated apoptosis in SMMC-7721 cells, whereas inhibition of eIF2α by small interfering RNA markedly enhanced 6-shogaol-mediated cell death. Furthermore, 6-shogaol-mediated inhibition of tumor growth of mouse SMMC-7721 xenograft was associated with induction of apoptosis, activation of caspase-3, and inactivation of eIF2α. Altogether our results indicate that the PERK/eIF2α pathway plays an important role in 6-shogaol-mediated ER stress and apoptosis in SMMC-7721 cells in vitro and in vivo.

  1. A novel quinoline, MT477: suppresses cell signaling through Ras molecular pathway, inhibits PKC activity, and demonstrates in vivo anti-tumor activity against human carcinoma cell lines.

    Science.gov (United States)

    Jasinski, Piotr; Welsh, Brandon; Galvez, Jorge; Land, David; Zwolak, Pawel; Ghandi, Lori; Terai, Kaoru; Dudek, Arkadiusz Z

    2008-06-01

    MT477 is a novel thiopyrano[2,3-c]quinoline that has been identified using molecular topology screening as a potential anticancer drug with a high activity against protein kinase C (PKC) isoforms. The objective of the present study was to determine the mechanism of action of MT477 and its activity against human cancer cell lines. MT477 interfered with PKC activity as well as phosphorylation of Ras and ERK1/2 in H226 human lung carcinoma cells. It also induced poly-caspase-dependent apoptosis. MT477 had a dose-dependent (0.006 to 0.2 mM) inhibitory effect on cellular proliferation of H226, MCF-7, U87, LNCaP, A431 and A549 cancer cell lines as determined by in vitro proliferation assays. Two murine xenograft models of human A431 and H226 lung carcinoma were used to evaluate tumor response to intraperitoneal administration of MT477 (33 microg/kg, 100 microg/kg, and 1 mg/kg). Tumor growth was inhibited by 24.5% in A431 and 43.67% in H226 xenografts following MT477 treatment, compared to vehicle controls (p < 0.05). In conclusion, our empirical findings are consistent with molecular modeling of MT477's activity against PKC. We also found, however, that its mechanism of action occurs through suppressing Ras signaling, indicating that its effects on apoptosis and tumor growth in vivo may be mediated by Ras as well as PKC. We propose, therefore, that MT477 warrants further development as an anticancer drug. PMID:17957339

  2. In vivo prediction of anti-tumor effect of 3-bromopyruvate in hepatocellular carcinoma using Tc-99m labeled annexin-v imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won; Yoon, Jung Hwan; Kim, Chung Yang [Seoul National University College of Medicine, Seoul (Korea, Republic of); Cheon, Gi Jeoog; Lee, Tae Sup; Woo, Kwang Sun; Chung, Wee Sup [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2005-07-01

    We have recently demonstrated that hypoxia stimulates hepatocellular carcinoma (HCC) cell growth through hexokinase II induction, and its inhibition induces apoptotic cell death through activating mitochondrial apoptotic signaling cascades. In this study, we were apt to evaluate the antitumoral effect of 3-bromopyruvate (3-BP) on in vivo model of HCC by apoptotic imaging using Tc-99m labeled annexin V. In vivo model of HCC was established in C3H mice intradermally implanted with MH134 cells, a mouse HCC cell line, and 3-BP (0, 5, 10 mg/kg) was subsequently administered intraperitoneally. Tc-99m-HYNIC-annexin V (185 KBq) was injected via tail vein at one and three days after the 3-BP treatment, planar scan was acquired at a hour after the injection using gamma camera. The anti-tumor effect was evaluated by measuring tumor volumes and quantification of apoptotic cells using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Tumor volume was significantly reduced in mice treated with 3-BP in a dose-dependent manner (mean tumor volume 1.07 vs. 0.58 vs. 0.39 cm{sup 3} in 3-BP 0, 5, 10 mg/kg, respectively: p=0.047). The percentage of TUNEL staining-positive cells was significantly increased in 3-BP-treated mice (0.53 vs. 1.40 vs. 1.84% in 3-BP 0, 5, 10 mg/kg, respectively; p=0.018). On Tc-99m-HYNIC annexin V imaging, tumor-to-background uptake ratio (UR) was 1.92 at one day and 4.23 at three days after 3-BP treatment of 5 mg/kg (non-treated tumor showed UR of 2.93). Apoptosis-inducing anti-tumor effect of 3-BP was able to be demonstrated in in vivo model of HCC by apoptotic in vivo imaging using Tc-99m-HYNIC annexin V.

  3. In vivo molecular imaging and radionuclide (131I therapy of human nasopharyngeal carcinoma cells transfected with a lentivirus expressing sodium iodide symporter.

    Directory of Open Access Journals (Sweden)

    Shuo Shi

    Full Text Available Despite recent improvements in the survival rates for nasopharyngeal carcinoma (NPC, novel treatment strategies are required to improve distant metastasis-free survival. The sodium iodine symporter (NIS gene has been applied for in vivo imaging and cancer therapy. In this study, we examined the potential of NIS gene therapy as a therapeutic approach in NPC by performing non-invasive imaging using 125I and 131I therapy in vivo.We constructed a lentiviral vector expressing NIS and enhanced green fluorescent protein (EGFP under the control of the human elongation factor-1α (EF1α promoter, and stably transfected the vector into CNE-2Z NPC cells to create CNE-2Z-NIS cells. CNE-2Z and CNE-2Z-NIS tumor xenografts were established in nude mice; 125I uptake, accumulation and efflux were measured using micro-SPECT/CT imaging; the therapeutic effects of treatment with 131I were assessed over 25 days by measuring tumor volume and immunohistochemical staining of the excised tumors.qPCR, immunofluorescence and Western blotting confirmed that CNE-2Z-NIS cells expressed high levels of NIS mRNA and protein. CNE-2Z-NIS cells and xenografts took up and accumulated significantly more 125I than CNE-2Z cells and xenografts. In vitro, 131I significantly reduced the clonogenic survival of CNE-2Z-NIS cells. In vivo, 131I effectively inhibited the growth of CNE-2Z-NIS xenografts. At the end of 131I therapy, CNE-2Z-NIS xenograft tumor cells expressed higher levels of NIS and caspase-3 and lower levels of Ki-67.Lentiviruses effectively delivered and mediated long-lasting expression of NIS in CNE-2Z cells which enabled uptake and accumulation of radioisotopes and provided a significant therapeutic effect in an in vivo model of NPC. NIS-mediated radioiodine treatment merits further investigation as a potentially effective, low toxicity therapeutic strategy for NPC.

  4. Optical imaging of head and neck squamous cell carcinoma in vivo using arginine-glycine- aspartic acid peptide conjugated near-infrared quantum dots

    Directory of Open Access Journals (Sweden)

    Huang H

    2013-12-01

    Full Text Available Hao Huang, Yun-Long Bai, Kai Yang, Hong Tang, You-Wei WangDepartment of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of ChinaAbstract: Molecular imaging plays a key role in personalized medicine and tumor diagnosis. Quantum dots with near-infrared emission spectra demonstrate excellent tissue penetration and photostability, and have recently emerged as important tools for in vivo tumor imaging. Integrin αvβ3 has been shown to be highly and specifically expressed in endothelial cells of tumor angiogenic vessels in almost all types of tumors, and specifically binds to the peptide containing arginine-glycine-aspartic acid (RGD. In this study, we conjugated RGD with quantum dots with emission wavelength of 800 nm (QD800 to generate QD800-RGD, and used it via intravenous injection as a probe to image tumors in nude mice bearing head and neck squamous cell carcinoma (HNSCC. Twelve hours after the injection, the mice were still alive and were sacrificed to isolate tumors and ten major organs for ex vivo analysis to localize the probe in these tissues. The results showed that QD800-RGD was specifically targeted to integrin αvβ3 in vitro and in vivo, producing clear tumor fluorescence images after the intravenous injection. The tumor-to-background ratio and size of tumor image were highest within 6 hours of the injection and declined significantly at 9 hours after the injection, but there was still a clearly visible tumor image at 12 hours. The greatest amount of QD800-RGD was found in liver and spleen, followed by tumor and lung, and a weak fluorescence signal was seen in tibia. No detectable signal of QD800-RGD was found in brain, heart, kidney, testis, stomach, or intestine. Our study demonstrated that using integrin αvβ3 as target, it is possible to use intravenously injected QD800-RGD to generate high quality images of HNSCC, and the technique offers great potential

  5. Liposomal formulation of α-tocopheryl maleamide: In vitro and in vivo toxicological profile and anticancer effect against spontaneous breast carcinomas in mice

    International Nuclear Information System (INIS)

    The vitamin E analogue α-tocopheryl succinate (α-TOS) is an efficient anti-cancer drug. Improved efficacy was achieved through the synthesis of α-tocopheryl maleamide (α-TAM), an esterase-resistant analogue of α-tocopheryl maleate. In vitro tests demonstrated significantly higher cytotoxicity of α-TAM towards cancer cells (MCF-7, B16F10) compared to α-TOS and other analogues prone to esterase-catalyzed hydrolysis. However, in vitro models demonstrated that α-TAM was cytotoxic to non-malignant cells (e.g. lymphocytes and bone marrow progenitors). Thus we developed lyophilized liposomal formulations of both α-TOS and α-TAM to solve the problem with cytotoxicity of free α-TAM (neurotoxicity and anaphylaxis), as well as the low solubility of both drugs. Remarkably, neither acute toxicity nor immunotoxicity implicated by in vitro tests was detected in vivo after application of liposomal α-TAM, which significantly reduced the growth of cancer cells in hollow fiber implants. Moreover, liposomal formulation of α-TAM and α-TOS each prevented the growth of tumours in transgenic FVB/N c-neu mice bearing spontaneous breast carcinomas. Liposomal formulation of α-TAM demonstrated anti-cancer activity at levels 10-fold lower than those of α-TOS. Thus, the liposomal formulation of α-TAM preserved its strong anti-cancer efficacy while eliminating the in vivo toxicity found of the free drug applied in DMSO. Liposome-based targeted delivery systems for analogues of vitamin E are of interest for further development of efficient and safe drug formulations for clinical trials.

  6. In vitro radionuclide therapy and in vivo scintigraphic imaging of alpha fetoprotein producing hepatocellular carcinoma by targeted sodium iodide symporter gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kwang Il; Lee, Yong Jin; Lee, Tae Sup; Song, Inho; Cheon, Gi Jeong; Lim, Sang Moo; Kang, Joo Hyun [Korea Institute of Radiological and Medical and Medical Sciences, Seoul (Korea, Republic of); Chung, June Key [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    This study aimed to develop a gene expression targeting method for specific imaging and therapy of alpha fetoprotein (AFP) producing hepatocellular carcinoma (HCC) cells, using an adenovirus vector containing the human sodium/iodide symporter (hNIS) gene driven by an AFP enhancer/promoter. The recombinant adenovirus vector, AdAFPhNIS (containing the hNIS gene driven by human AFP enhancer/promoter) was prepared. After in vitro infection by the adenovirus, hNIS gene expression in AFP producing cells and in AFP nonproducing cells was investigated using {sup 125}I uptake assay and semi quantitative reverse transcription polymerase chain reaction (RT-PCR). The killing effect of {sup 131}I vitro clonogenic assay. In addition, tumor bearing mice were intravenously injected with the adenovirus, and scintigraphic images were obtained. The expression of hNIS was efficiently demonstrated by {sup 125}I uptake assay in AFP producing cells, but not in AFP nonproducing cells. AFP producing HCC targeted gene expression was confirmed at the mRNA level. Furthermore, in vitro clonogenic assay showed that hNIS gene expression induced by AdAFPhNIS infection in AFP producing cells caused more sensitivity to {sup 131}I than that in AFP nonproducing cells. Injected intravenously in HuH-7 tumor xenografts mice by adenovirus, the functional hNIS gene expression was confirmed in tumor by in vivo scintigraphic imaging. An AFP producing HCC was targeted with an adenovirus vector containing the hNIS gene using the AFP enhancer/promoter in vitro and in vivo. These findings demonstrate that AFP producing HCC specific molecular imaging and radionuclide gene therapy are feasible using this recombinant adenovirus vector system.

  7. Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine.

    Science.gov (United States)

    Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David L

    2015-10-20

    Aberrant expression of membrane-associated and secreted mucins, as evident in epithelial tumors, is known to facilitate tumor growth, progression and metastasis, and to provide protection against adverse growth conditions, chemotherapy and immune surveillance. Emerging evidence provides support for the oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal tumors, in particular increased or de novo expression of MUC2 and/or MUC5AC, is widely believed to imply an adverse clinicopathological feature. Through formation of viscous gels, too, MUC2 and MUC5AC significantly contribute to the biology and pathogenesis of mucin-secreting gastrointestinal tumors. Here, we investigated the mucin-depleting effects of bromelain (BR) and N-acetylcysteine (NAC), in nine different regimens as single or combination therapy, in in vitro (MKN45, KATOIII and LS174T cell lines) and in vivo (female nude mice bearing intraperitoneal MKN45 and LS174T) settings. The inhibitory effects of the treatment on cancer cell growth and proliferation were also evaluated in vivo. Our results suggest that a combination of BR and NAC with dual effects on growth and mucin products of mucin-expressing tumor cells is a promising candidate towards the development of novel approaches to gastrointestinal malignancies with the involvement of mucin pathology. This capability supports the use of this combination formulation in locoregional approaches for reducing the adverse effects of the aberrantly secreted gel-forming mucins, as in pseudomyxoma peritonei and similar pathologies with ectopic production of mucin. PMID:26436698

  8. H-ras-transformed NRK-52E renal epithelial cells have altered growth, morphology, and cytoskeletal structure that correlates with renal cell carcinoma in vivo.

    Science.gov (United States)

    Best, C J; Tanzer, L R; Phelps, P C; Merriman, R L; Boder, G G; Trump, B F; Elliget, K A

    1999-04-01

    We studied the effect of the ras oncogene on the growth kinetics, morphology, cytoskeletal structure, and tumorigenicity of the widely used NRK-52E rat kidney epithelial cell line and two H-ras oncogene-transformed cell lines, H/1.2-NRK-52E (H/1.2) and H/6.1-NRK-52E (H/6.1). Population doubling times of NRK-52E, H/1.2, and H/6.1 cells were 28, 26, and 24 h, respectively, with the transformed cells reaching higher saturation densities than the parent cells. NRK-52E cells had typical epithelial morphology with growth in colonies. H/1.2 and H/6.1 cell colonies were more closely packed, highly condensed, and had increased plasma membrane ruffling compared to parent cell colonies. NRK-52E cells showed microfilament, microtubule, and intermediate filament networks typical of epithelial cells, while H/1.2 and H/6.1 cells showed altered cytoskeleton architecture, with decreased stress fibers and increased microtubule and intermediate filament staining at the microtubule organizing center. H/1.2 and H/6.1 cells proliferated in an in vitro soft agar transformation assay, indicating anchorage-independence, and rapidly formed tumors in vivo with characteristics of renal cell carcinoma, including mixed populations of sarcomatoid, granular, and clear cells. H/6.1 cells consistently showed more extensive alterations of growth kinetics, morphology, and cytoskeleton than H/1.2 cells, and formed tumors of a more aggressive phenotype. These data suggest that analysis of renal cell characteristics in vitro may have potential in predicting tumor behavior in vivo, and significantly contribute to the utility of these cell lines as in vitro models for examining renal epithelial cell biology and the role of the ras proto-oncogene in signal transduction involving the cytoskeleton.

  9. Effect of host immunity on metastatic potential in renal cell carcinoma: the assessment of optimal in vivo models to study metastatic behavior of renal cancer cells.

    Science.gov (United States)

    Kobayashi, Minoru; Morita, Tatsuo; Chun, Nicole A L; Matsui, Aya; Takahashi, Masafumi; Murakami, Takashi

    2012-04-01

    There has been little information about metastatic behavior of renal cell carcinoma (RCC) cells because human cancers metastasize only rarely in immunodeficient mice. Moreover, it is difficult to know the effect of host immunity on RCC metastasis due to lack of such RCC cells as transplantable in not only xenograft models but also counterparts with intact immunity. Therefore, we scrutinized in vivo metastasis of RCC cells to seek for the optimal preclinical model to study metastatic behavior. The luciferase-expressing three representative human RCC cell lines (Caki-1, A498, and 786-O) and rat ACI-RCC cell which were established in our laboratory were transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice or immunocompetent ACI rats by intracardiac injection as well as orthotopic inoculation. Metastasis was monitored using a bioluminescent imaging technique. Metastasis was rare in the three human RCC cells even when they were directly disseminated into systemic circulation under the condition least susceptible to host immune attack in NOD/SCID mice. In contrast, ACI-RCC cells spontaneously metastasized to pulmonary tissue from orthotopic tumor sites and systemically spread via intracardiac route. Metastases were more extensive when the cells were inoculated into an immunodeficient host, implying suppressive effect of host immunity on colonization of RCC cells. These results suggest that the representative human RCC cells are not adequate resource to study metastasis but that the luciferase-labeled ACI-RCC cell characterized by its luminescent stability, enhanced tumorigenicity, and widespread metastatic potential provides a useful in vivo model for preclinical assessment of cancer progression and potential therapies against RCC.

  10. Swainsonine promotes apoptosis in human oesophageal squamous cell carcinoma cells in vitro and in vivo through activation of mitochondrial pathway

    Indian Academy of Sciences (India)

    Zhaocai Li; Yong Huang; Feng Dong; Wei Li; Li Ding; Gaoshui Yu; Dan Xu; Yuanyuan Yang; Xingang Xu; Dewen Tong

    2012-12-01

    Swainsonine, a natural indolizidine alkaloid, has been reported to have antitumour effects, and can induce apoptosis in human gastric and lung cancer cells. In the present study, we evaluated the antitumour effects of swainsonine on several oesophageal squamous cell carcinoma cells and investigated relative molecular mechanisms. Swainsonine treatment inhibited the growth of Eca-109, TE-1 and TE-10 cells in a concentration-dependent manner as measured by MTT assay. Morphological observation, DNA laddering detection and flow cytometry analysis demonstrated that swainsonine treatment induced Eca-109 cell apoptosis in vitro. Further results showed that swainsonine treatment up-regulated Bax, down-regulated Bcl-2 expression, triggered Bax translocation to mitochondria, destructed mitochondria integrity and activated mitochondria-mediated apoptotic pathway, followed by the release of cytochrome c, which in turn activated caspase-9 and caspase-3, promoted the cleavage of PARP, resulting in Eca-109 cell apoptosis. Moreover, swainsonine treatment inhibited Bcl-2 expression, promoted Bax translocation, cytochrome c release and caspase-3 activation in xenograft tumour cells, resulting in a significant decrease of tumour volume and tumour weight in the swainsonine-treated xenograft mice groups compared with that in the control group. Taken together, this study demonstrated that swainsonine inhibited Eca-109 cells growth through activation of mitochondria-mediated caspase-dependent pathway.

  11. Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

    Directory of Open Access Journals (Sweden)

    Roberta Lotti

    2016-01-01

    Full Text Available Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC originate from alterations in keratinocyte stem cells (KSC gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD and non-RAD (NRAD cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, β1-integrin, while it increases the level of differentiation markers (K10, involucrin. Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in RasG12V-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development.

  12. Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo.

    Science.gov (United States)

    Lotti, Roberta; Palazzo, Elisabetta; Petrachi, Tiziana; Dallaglio, Katiuscia; Saltari, Annalisa; Truzzi, Francesca; Quadri, Marika; Puviani, Mario; Maiorana, Antonino; Marconi, Alessandra; Pincelli, Carlo

    2016-01-01

    Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC) originate from alterations in keratinocyte stem cells (KSC) gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD) and non-RAD (NRAD) cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, β₁-integrin), while it increases the level of differentiation markers (K10, involucrin). Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in Ras(G12V)-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development.

  13. Metformin attenuates the stimulatory effect of a high-energy diet on in vivo LLC1 carcinoma growth.

    Science.gov (United States)

    Algire, Carolyn; Zakikhani, Mahvash; Blouin, Marie-Jose; Shuai, Jian Hua; Pollak, Michael

    2008-09-01

    We investigated the effects of metformin on the growth of lewis lung LLC1 carcinoma in C57BL/6J mice provided with either a control diet or a high-energy diet, previously reported to lead to weight gain and systemic insulin resistance with hyperinsulinemia. Forty-eight male mice were randomized into four groups: control diet, control diet+metformin, high-energy diet, or high-energy diet+metformin. Following 8 weeks on the experimental diets, selected groups received metformin in their drinking water. Three weeks following the start of metformin treatment, mice were injected with 0.5x10(6) LLC1 cells and tumor growth was measured for 17 days. By day 17, tumors of mice on the high-energy diet were nearly twice the volume of those of mice on the control diet. This effect of diet on tumor growth was significantly attenuated by metformin, but metformin had no effect on tumor growth of the mice on the control diet. Metformin attenuated the increased insulin receptor activation associated with the high-energy diet and also led to increased phosphorylation of AMP kinase, two actions that would be expected to decrease neoplastic proliferation. These experimental results are consistent with prior hypothesis-generating epidemiological studies that suggest that metformin may reduce cancer risk and improve cancer prognosis. Finally, these results contribute to the rationale for evaluation of the anti-neoplastic activity of metformin in hyperinsulinemic cancer patients. PMID:18469156

  14. MicroRNA-338-3p suppresses tumor growth of esophageal squamous cell carcinoma in vitro and in vivo.

    Science.gov (United States)

    Li, Xinyu; Li, Zhihong; Yang, Guiyun; Pan, Zhenxiang

    2015-09-01

    Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal squamous cell carcinoma (ESCC) and are crucial in tumorigenesis, among which miR‑338‑3p has been examined to be downregulated in patients with ESCC. However, the role of miR‑338‑3p in ESCC remains to be elucidated. In the present study, the role of miR‑338‑3p on the growth and survival of an ESCC cell line was determined with several in vitro approaches and in nude mouse models. It was determined that miR‑338‑3p expression was frequently downregulated in ESCC tissue compared with corresponding adjacent non‑tumor tissue, and that its expression was significantly correlated with tumor stage and metastasis. Overexpression of miR‑338‑3p in ESCC cells suppressed cell proliferation, colony formation, migration and invasion, and induced cell arrest at the G0/G1 stage and cell apoptosis in vitro. In addition, it was demonstrated that overexpression of miR‑338‑3p significantly suppresses tumor growth of xenograft tumors in mice (PESCC, and its dysregulation may be involved in the initiation and development of human ESCC. In addition, it was suggested that miR‑338‑3p may be a potential therapeutic agent for treatment of ESCC.

  15. In vivo detection of basal cell carcinoma: comparison of a reflectance confocal microscope and a multiphoton tomograph

    Science.gov (United States)

    Ulrich, Martina; Klemp, Marisa; Darvin, Maxim E.; König, Karsten; Lademann, Jürgen; Meinke, Martina C.

    2013-06-01

    The standard diagnostic procedure for basal cell carcinoma (BCC) is invasive tissue biopsy with time-consuming histological examination. To reduce the number of biopsies, noninvasive optical methods have been developed providing high-resolution skin examination. We present direct comparison of a reflectance confocal microscope (RLSM) and a multiphoton tomograph (MPT) for BCC diagnosis. Both systems are applied to nine patients prior to surgery, and the results are analyzed, including histological results. Both systems prove suitable for detecting typical characteristics of BCC in various stages. The RLSM allows large horizontal overview images to be obtained, enabling the investigator to find the regions of interest quickly, e.g., BCC nests. Elongated cells and palisading structures are easily recognized using both methods. Due to the higher resolution, changes in nucleus diameter or cytoplasm could be visualized with the MPT. Therefore, the nucleus diameter, nucleus/cytoplasm ratio, and cell density are estimated for normal and BCC cells using the MPT. The nucleus of elongated BCC cells is significantly longer than other measured normal skin cells, whereas the cell density and nucleus/cytoplasm ratio of BCC cannot be significantly distinguished from granular cells.

  16. In vivo infiltration of mononuclear cells in squamous cell carcinoma of the head and neck correlates with the ability to expand tumour-infiltrating T cells in vitro and with the expression of MHC class I antigens on tumour cells

    DEFF Research Database (Denmark)

    Hald, J; Rasmussen, N; Claesson, Mogens Helweg

    1994-01-01

    A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well with their abi......A series of 18 head and neck squamous cell carcinoma biopsies, 6 primary and 12 recurrent, were investigated for tumour-infiltrating mononuclear cells with monoclonal or polyclonal antibodies. Our results suggest that the number of T cells at the tumour edge in vivo correlates well...... with their ability to expand in vitro in the presence of high-dose interleukin-2 (2000 U/ml). High MHC class I antigen expression on tumour cells was found to be positively correlated with p53 overexpression, suggesting that p53-derived peptides, wild-type or mutated ones, presented by MHC class I antigens......, are potential targets for MHC-restricted cytotoxic T cells in head and neck squamous cell carcinomas. However, lack of correlation between peritumoural T cell infiltration in vivo and T cell expansion in vitro, on the one hand, and p53 overexpression on tumour cells, on the other hand, suggests absence of p53...

  17. Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo.

    Science.gov (United States)

    Liu, Min-Chen; Liu, Lin; Wang, Xia-Rong; Shuai, Wu-Ping; Hu, Ying; Han, Min; Gao, Jian-Qing

    2016-01-01

    The diacid metabolite of norcantharidin (DM-NCTD) is clinically effective against hepatocellular carcinoma (HCC), but is limited by its short half-life and high incidence of adverse effects at high doses. We developed a DM-NCTD-loaded, folic acid (FA)-modified, polyethylene glycolated (DM-NCTD/FA-PEG) liposome system to enhance the targeting effect and antitumor potency for HCC at a moderate dose based on our previous study. The DM-NCTD/FA-PEG liposome system produced liposomes with regular spherical morphology, with mean particle size approximately 200 nm, and an encapsulation efficiency >80%. MTT cytotoxicity assays demonstrated that the DM-NCTD/FA-PEG liposomes showed significantly stronger cytotoxicity effects on the H22 hepatoma cell line than did PEG liposomes without the FA modification (Pkidney was higher than in the normal liposome group. With regard to in vivo antitumor activity, DM-NCTD/FA-PEG liposomes inhibited tumors in H22 tumor-bearing mice better than either free DM-NCTD or DM-NCTD/PEG liposomes (Pnormal mice, as shown by histopathological examination. All these results demonstrate that DM-NCTD-loaded FA-modified liposomes might have potential application for HCC-targeting therapy. PMID:27110110

  18. In vivo validation of a bimodal technique combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy for diagnosis of oral carcinoma

    Science.gov (United States)

    Sun, Yang; Xie, Hongtao; Liu, Jing; Lam, Matthew; Chaudhari, Abhijit J.; Zhou, Feifei; Bec, Julien; Yankelevich, Diego R.; Dobbie, Allison; Tinling, Steven L.; Gandour-Edwards, Regina F.; Monsky, Wayne L.; Gregory Farwell, D.; Marcu, Laura

    2012-11-01

    Tissue diagnostic features generated by a bimodal technique integrating scanning time-resolved fluorescence spectroscopy (TRFS) and ultrasonic backscatter microscopy (UBM) are investigated in an in vivo hamster oral carcinoma model. Tissue fluorescence is excited by a pulsed nitrogen laser and spectrally and temporally resolved using a set of filters/dichroic mirrors and a fast digitizer, respectively. A 41-MHz focused transducer (37-μm axial, 65-μm lateral resolution) is used for UBM scanning. Representative lesions of the different stages of carcinogenesis show that fluorescence characteristics complement ultrasonic features, and both correlate with histological findings. These results demonstrate that TRFS-UBM provide a wealth of co-registered, complementary data concerning tissue composition and structure as it relates to disease status. The direct co-registration of the TRFS data (sensitive to surface molecular changes) with the UBM data (sensitive to cross-sectional structural changes and depth of tumor invasion) is expected to play an important role in pre-operative diagnosis and intra-operative determination of tumor margins.

  19. In vitro and in vivo cytotoxic effects of PRIMA-1 on hepatocellular carcinoma cells expressing mutant p53ser249.

    Science.gov (United States)

    Shi, Hong; Lambert, Jeremy M R; Hautefeuille, Agnes; Bykov, Vladimir J N; Wiman, Klas G; Hainaut, Pierre; Caron de Fromentel, Claude

    2008-07-01

    Hepatocellular carcinoma (HCC) is highly lethal due to limited curative options. In high-incidence regions, such as parts of Africa and Southeastern Asia, >50% of cases carry an AGG to AGT mutation at codon 249 of the TP53 gene, considered as a 'signature' of mutagenesis by aflatoxins. The protein product, p53ser249, may represent a therapeutic target for HCC. The small molecule p53 reactivation and induction of massive apoptosis (PRIMA)-1 has been shown to induce apoptosis in tumour cells by reactivating the transactivation capacity of some p53 mutants. In this study, we have investigated the cytotoxic effects of PRIMA-1 on HCC cells expressing p53ser249. In p53-null Hep3B cells, over-expression of p53ser249 or p53gln248 by stable transfection increased the cytotoxicity of PRIMA-1 at 50 muM. Furthermore, PRIMA-1 treatment delayed the growth of p53ser249-expressing Hep3B cells xenografted in severe combined immunodeficiency mice. However, PRIMA-1 did not restore wild-type DNA binding and transactivation activities to p53ser249 or to p53gln248 in Hep3B cells. Moreover, in PLC/PRF/5, a HCC cell line constitutively expressing p53ser249, small interfering RNA (siRNA) silencing of the mutant increased the cytotoxic effect of PRIMA-1. These apparently contradictory effects can be reconciled by proposing that p53ser249 exerts a gain-of-function effect, which favours the survival of HCC cells. Thus, both inhibition of this effect by PRIMA-1 and removal of the mutant by siRNA can lead to the decrease of survival capacity of HCC cells. PMID:18048389

  20. In vitro and in vivo anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Metformin, which is widely used as an antidiabetic agent, has recently been reported to reduce cancer risk and improve prognosis in certain malignancies. However, the specific mechanisms underlying the effect of metformin on the development and progression of several cancers including oral squamous cell carcinoma (OSCC) remain unclear. In the present study, we investigated the effects of metformin on OSCC cells in vitro and in vivo. OSCC cells treated with or without metformin were counted using a hemocytometer. The clonogenic ability of OSCC cells after metformin treatment was determined by colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the activation of related signaling pathways was examined by immunoblotting. The in vivo anti-tumor effect of metformin was examined using a xenograft mouse model. Immunohistochemistry and TUNEL staining were used to determine the expression of cyclin D1 and the presence of apoptotic cells in tumors from mice treated with or without metformin. Metformin inhibited proliferation in the OSCC cell lines CAL27, WSU-HN6 and SCC25 in a time- and dose-dependent manner, and significantly reduced the colony formation of OSCC cells in vitro. Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which was accompanied by an obvious activation of the AMP kinase pathway and a strongly decreased activation of mammalian target of rapamycin and S6 kinase. Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK) 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells. In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax. Metformin also markedly reduced the expression of cyclin D1 and increased the numbers of apoptotic cells in vivo, thus inhibiting

  1. In vitro and in vivo anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Luo Qingqiong

    2012-11-01

    Full Text Available Abstract Background Metformin, which is widely used as an antidiabetic agent, has recently been reported to reduce cancer risk and improve prognosis in certain malignancies. However, the specific mechanisms underlying the effect of metformin on the development and progression of several cancers including oral squamous cell carcinoma (OSCC remain unclear. In the present study, we investigated the effects of metformin on OSCC cells in vitro and in vivo. Methods OSCC cells treated with or without metformin were counted using a hemocytometer. The clonogenic ability of OSCC cells after metformin treatment was determined by colony formation assay. Cell cycle progression and apoptosis were assessed by flow cytometry, and the activation of related signaling pathways was examined by immunoblotting. The in vivo anti-tumor effect of metformin was examined using a xenograft mouse model. Immunohistochemistry and TUNEL staining were used to determine the expression of cyclin D1 and the presence of apoptotic cells in tumors from mice treated with or without metformin. Results Metformin inhibited proliferation in the OSCC cell lines CAL27, WSU-HN6 and SCC25 in a time- and dose-dependent manner, and significantly reduced the colony formation of OSCC cells in vitro. Metformin induced an apparent cell cycle arrest at the G0/G1 phase, which was accompanied by an obvious activation of the AMP kinase pathway and a strongly decreased activation of mammalian target of rapamycin and S6 kinase. Metformin treatment led to a remarkable decrease of cyclin D1, cyclin-dependent kinase (CDK 4 and CDK6 protein levels and phosphorylation of retinoblastoma protein, but did not affect p21 or p27 protein expression in OSCC cells. In addition, metformin induced apoptosis in OSCC cells, significantly down-regulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulating the pro-apoptotic protein Bax. Metformin also markedly reduced the expression of cyclin D1 and increased

  2. The effectiveness of 125I seed interstitial brachytherapy for transplantation tumor of human pancreatic carcinoma in nude mice: an experiment in vivo

    International Nuclear Information System (INIS)

    (8.1 ± 1.5)%, respectively, and the difference between two groups was statistically significant (P 125I interstitial brachytherapy is an effective treatment for transplantation tumor of human pancreatic carcinoma in nude mice. Its mechanisms include directly killing the tumor cells, inducing tumor cell apoptosis and reducing cell proliferation. Additionally, 125I seeds implantation in vivo tumor is safe for the surrounding organs. (authors)

  3. ANTICANCER STUDY OF HEMATOLOGICAL AND SURVIVAL PERIOD IN BRASSICA RAPA CHINENSIS LINN. USING IN VIVO MODEL IN MICE

    Directory of Open Access Journals (Sweden)

    DHARANI MAYILSAMY

    2016-06-01

    Full Text Available Aim: Dalton’s Lymphoma Ascites (DLA cells are a cancer of the lymphocytes, a type of cell that forms part of the immune system. The present study aims to evaluate the anticancer study of hematological and survival period in brassica rapa chinensis linn. using in vivo model in mice. Methods: Hematological study- The experimental mice were divided to 5 groups. The methanolic extract (800 mg/kg and nanoparticles of methanolic extract (1mg/kg of Brassica rapa Chinensis leaves, was administered to mice of group III and IV respectively. The mice were induced with DLA. Group I mice served as normal control and group II as DLA control. Cyclophosphamide at 3mg/kg b.wt was administered to group V. Survival period- The animals were divided into eight groups, containing six animals in each group. The survival period and change in body weight of these animals, during and after the development were monitored up to 58 days. Results: Treatment with methanolic extract and nanoparticles of methanolic extract of Brassica rapa Chinensis leaves (800, 1mg/kg, orally against Dalton’s Lymphoma Ascites (DLA in mice by the activities of hematological parameters as Hemoglobin (Hb, White blood cell count (WBC, Red blood cell count (RBC & PCV levels in blood and body weight & life span. The extract also enhanced in a dose dependent manner with 3mg dose revealing more defending effect in line with the standard drug, Cyclophosphamide. Conclusion: The observed results indicate that the Brassica rapa Chinensis leaves extract at both the doses were effective in curbing the toxic insult of DLA.

  4. Calcitriol enhances gemcitabine antitumor activity in vitro and in vivo by promoting apoptosis in a human pancreatic carcinoma model system

    Science.gov (United States)

    Yu, Wei-Dong; Ma, Yingyu; Flynn, Geraldine; Muindi, Josephia R; Kong, Rui-Xian; Trump, Donald L

    2010-01-01

    Gemcitabine is the standard care chemotherapeutic agent to treat pancreatic cancer. Previously we demonstrated that calcitriol (1, 25-dihydroxycholecalciferol) has significant anti-proliferative effects in vitro and in vivo in multiple tumor models and enhances the activity of a variety of chemotherapeutic agents. We therefore investigated whether calcitriol could potentiate the cytotoxic activity of gemcitabine in the human pancreatic cancer Capan-1 model system. Isobologram analysis revealed that calcitriol and gemcitabine had synergistic antiproliferative effect over a wide range of drug concentrations. Calcitriol did not reduce the cytidine deaminase activity in Capan-1 tumors nor in the livers of Capan-1 tumor bearing mice. Calcitriol and gemcitabine combination promoted apoptosis in Capan-1 cells compared with either agent alone. The combination treatment also increased the activation of caspases-8, -9, -6 and -3 in Capan-1 cells. This result was confirmed by substrate-based caspase activity assay. Akt phosphorylation was reduced by calcitriol and gemcitabine combination treatment compared to single agent treatment. However, ERK1/2 phosphorylation was not modulated by either agent alone or by the combination. Tumor regrowth delay studies showed that calcitriol in combination with gemcitabine resulted in a significant reduction of Capan-1 tumor volume compared to single agent treatment. Our study suggests that calcitriol and gemcitabine in combination promotes caspase-dependent apoptosis, which may contribute to increased anti-tumor activity compared to either agent alone. PMID:20699664

  5. Genomic amplification upregulates estrogen-related receptor alpha and its depletion inhibits oral squamous cell carcinoma tumors in vivo.

    Science.gov (United States)

    Tiwari, Ankana; Swamy, Shivananda; Gopinath, Kodaganur S; Kumar, Arun

    2015-12-07

    The ESRRA gene encodes a transcription factor and regulates several genes, such as WNT11 and OPN, involved in tumorigenesis. It is upregulated in several cancers, including OSCC. We have previously shown that the tumor suppressor miR-125a targets ESRRA, and its downregulation causes upregulation of ESRRA in OSCC. Upregulation of ESRRA in the absence of downregulation of miR-125a in a subset of OSCC samples suggests the involvement of an alternative mechanism. Using TaqMan(®) copy number assay, here we report for the first time that the genomic amplification of ESRRA causes its upregulation in a subset of OSCC samples. Ectopic overexpression of ESRRA led to accelerated cell proliferation, anchorage-independent cell growth and invasion, and inhibited apoptosis. Whereas, knockdown of ESRRA expression by siRNA led to reduced cell proliferation, anchorage-independent cell growth and invasion, and accelerated apoptosis. Furthermore, the delivery of a synthetic biostable ESRRA siRNA to OSCC cells resulted in regression of xenografts in nude mice. Thus, the genomic amplification of ESRRA is another novel mechanism for its upregulation in OSCC. Based on our in vitro and in vivo experiments, we suggest that targeting ESRRA by siRNA could be a novel therapeutic strategy for OSCC and other cancers.

  6. Re-expression of AKAP12 inhibits progression and metastasis potential of colorectal carcinoma in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Weiwei Liu

    Full Text Available BACKGROUND: AKAP12/Gravin (A kinase anchor protein 12 is one of the A-kinase scaffold proteins and a potential tumor suppressor gene in human primary cancers. Our recent study demonstrated the highly recurrent loss of AKAP12 in colorectal cancer and AKAP12 reexpression inhibited proliferation and anchorage-independent growth in colorectal cancer cells, implicating AKAP12 in colorectal cancer pathogenesis. METHODS: To evaluate the effect of this gene on the progression and metastasis of colorectal cancer, we examined the impact of overexpressing AKAP12 in the AKAP12-negative human colorectal cancer cell line LoVo, the single clone (LoVo-AKAP12 compared to mock-transfected cells (LoVo-CON. RESULTS: pCMV6-AKAP12-mediated AKAP12 re-expression induced apoptosis (3% to 12.7%, p<0.01, migration (89.6±7.5 cells to 31.0±4.1 cells, p<0.01 and invasion (82.7±5.2 cells to 24.7±3.3 cells, p<0.01 of LoVo cells in vitro compared to control cells. Nude mice injected with LoVo-AKAP12 cells had both significantly reduced tumor volume (p<0.01 and increased apoptosis compared to mice given AKAP12-CON. The quantitative human-specific Alu PCR analysis showed overexpression of AKAP12 suppressed the number of intravasated cells in vivo (p<0.01. CONCLUSION: These results demonstrate that AKAP12 may play an important role in tumor growth suppression and the survival of human colorectal cancer.

  7. Experimental study on therapeutic effect of in vivo expression of Cell I-Hep II recombinant polypeptide of fibronectin on murine H22 hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Gui-Mei Zhang; Yan Yang; Bo Huang; Hui Xiao; Dong Li; Zuo-Hua Feng

    2003-01-01

    AIM: To investigate the inhibitory effect of in vivo expression of expressing plasmid pCH510 of recombinant fibronectin polypeptide (CH50) on hepatocellular carcinoma and the improved therapeutic effect of pCH510 in combination with chemotherapeutic agents and Hsp70-H22 hepatocarcinoma antigen peptide on tumor.METHODS: Mice were inoculated with H22 hepatocarcinoma ceils. The chemotactic effect of the expression of plasmid pCH510 on immunocytes was observed after in vivo transfection, tissue slicing and HE staining. Inhibitory effect of transfection with pCH510 on murine tumor originated from different inoculative doses was observed. The inhibitory effect of immediate transfection with pCH510after chemotherapy on tumor was compared with that of transfection 5 days after chemotherapy. The change of function and amount of mouse peritoneal macrophages and the peripheral blood immunocytes resulted from administration of chemotherapeutic agents were detected. The peptides mixture was prepared from H22hepatocarcinoma cells. pCH510 + Hsp70-H22 antigen peptides were injected into tumor-bearing mice with or without chemotherapy, to observe the inhibitory effects on tumor.RESULTS: At the tumor tissue site injected with pCH510,there were a great number of immunocytes which mainly were macrophages, lymphocytes and neutrophils.Transfection of plasmid pCH510 inhibited significantly the murine tumor induced by different inoculative doses. The inhibitory effect was negatively correlated with the inoculative dose. The therapeutic effect was not improved by immediate transfection with pCH510 after chemotherapy, but was significantly improved by transfection with pCH510 5 days after chemotherapy. Chemotherapeutic agent decreased the number of immunocytes and suppressed their activation in vivo. After injection of drug, the amount of immunocytes was the lowest from d 1 to d 3 and returned to normal level on the 10th day. Transfection with plasmid pCH510 alone could inhibit tumor

  8. Antitumor activities of human autologous cytokine-induced killer (CIK) cells against hepatocellular carcinoma cells in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Fu-Sheng Wang; Ming-Xu Liu; Bing Zhang; Ming Shi; Zhou-Yun Lei; Wen-Bing Sun; Qing-You Du; Ju-Mei Chen

    2002-01-01

    AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptiveimmunotherapy for the patients with primary hepatocellularcarcinoma (HCC), we evaluated the proliferation rate,phenotype and the antitumor activity of human CIK cellsfrom healthy donors and HCC patients in vitro and in vivo.METHODS: Peripheral blood mononuclear cells (PBMC) fronhealthy donors and patients with primary HCC were incubatedin vitro and induced into ClK cells in the presence of variouscytokines such as interferon-gamma (IFN-γ), interleukin-1(IL-1), IL-2, and monoclonal antibody (mAb) against CD3.The phenotype and characterization of CIK cells wereidentified by flow cytometric analysis. The cytotoxicity of CIKcells was determined by 51 Cr release assay.RESULTS: The CIK cells were shown to be a heterogeneouspopulation with different cellular phenotypes. Thepercentage of CD3+/CD56+ positive cells, the dominanteffector cells, in total CIK cells from healthy donors andHCC patients, significantly increased from 0.1-0.13 % at day0 to 19.0-20.5 % at day 21 incubation, which suggested thatthe CD3+ CD56+ positive cells proliferated faster than othercell populations of CIK cells in the protocol used in thisstudy. After 28 day in vitro incubation, the ClK cells frompatients with HCC and healthy donors increased by morethan 300-fold and 500-fold in proliferation cell number,respectively. CIK cells originated from HCC patientspossessed a higher in vitro antitumor cytotoxic activity onautologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivoanimal experiment, CIK cells had stronger effects on theinhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate,84.7 % vs 52.8 %, P < 0.05) or PBMC (mean inhibitoryrate, 84.7% vs37.1%, P<0.01).CONCLUSION: Autologous CIK cells are of highly efficientcytotoxic effector cells against primary hepatocellularcarcinoma

  9. Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase.

    Science.gov (United States)

    Algire, Carolyn; Amrein, Lilian; Zakikhani, Mahvash; Panasci, Lawrence; Pollak, Michael

    2010-06-01

    The molecular mechanisms responsible for the association of obesity with adverse colon cancer outcomes are poorly understood. We investigated the effects of a high-energy diet on growth of an in vivo colon cancer model. Seventeen days following the injection of 5x10(5) MC38 colon carcinoma cells, tumors from mice on the high-energy diet were approximately twice the volume of those of mice on the control diet. These findings were correlated with the observation that the high-energy diet led to elevated insulin levels, phosphorylated AKT, and increased expression of fatty acid synthase (FASN) by the tumor cells. Metformin, an antidiabetic drug, leads to the activation of AMPK and is currently under investigation for its antineoplastic activity. We observed that metformin blocked the effect of the high-energy diet on tumor growth, reduced insulin levels, and attenuated the effect of diet on phosphorylation of AKT and expression of FASN. Furthermore, the administration of metformin led to the activation of AMPK, the inhibitory phosphorylation of acetyl-CoA carboxylase, the upregulation of BNIP3 and increased apoptosis as estimated by poly (ADP-ribose) polymerase (PARP) cleavage. Prior work showed that activating mutations of PI3K are associated with increased AKT activation and adverse outcome in colon cancer; our results demonstrate that the aggressive tumor behavior associated with a high-energy diet has similar effects on this signaling pathway. Furthermore, metformin is demonstrated to reverse the effects of the high-energy diet, thus suggesting a potential role for this agent in the management of a metabolically defined subset of colon cancers. PMID:20228137

  10. The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell carcinoma cell growth in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qiang; Song, Xin-mao; Ji, Yang-yang; Jiang, Hui; Xu, Lin-gen, E-mail: drlingenxu@126.com

    2013-11-01

    Highlights: •AZD8055 induces significant cytotoxic effects in cultured HNSCC cells. •AZD8055 blocks mTORC1 and mTORC2 activation in cultured HNSCC cells. •JNK activation is required for AZD8055-induced HNSCC cell death. •AZD8055 inhibits Hep-2 cell growth in vivo, and was more efficient than rapamycin. -- Abstract: The serine/threonine kinase mammalian target of rapamycin (mTOR) promotes cell survival and proliferation, and is constitutively activated in head and neck squamous cell carcinoma (HNSCC). Thus mTOR is an important target for drug development in this disease. Here we tested the anti-tumor ability of AZD8055, the novel mTOR inhibitor, in HNSCC cells. AZD8055 induced dramatic cell death of HNSCC lines (Hep-2 and SCC-9) through autophagy. AZD8055 blocked both mTOR complex (mTORC) 1 and mTORC2 activation without affecting Erk in cultured HNSCC cells. Meanwhile, AZD8055 induced significant c-Jun N-terminal kinase (JNK) activation, which was also required for cancer cell death. JNK inhibition by its inhibitors (SP 600125 and JNK-IN-8), or by RNA interference (RNAi) alleviated AZD8055-induced cell death. Finally, AZD8055 markedly increased the survival of Hep-2 transplanted mice through a significant reduction of tumor growth, without apparent toxicity, and its anti-tumor ability was more potent than rapamycin. Meanwhile, AZD8055 administration activated JNK while blocking mTORC1/2 in Hep-2 tumor engrafts. Our current results strongly suggest that AZD8055 may be further investigated for HNSCC treatment in clinical trials.

  11. In vivo distribution of recombinant interleukin-2-activated autologous lymphocytes administered by intra-arterial infusion in patients with renal cell carcinoma

    International Nuclear Information System (INIS)

    Recombinant interleukin-2 (RIL 2)-activated autologous peripheral blood lymphocytes (PBL) were infused directly into the renal arteries of 3 patients with renal cell carcinoma, and the in vivo distribution of the infused cells was investigated. In vitro studies to define the optimal culture conditions indicated that maximal lymphokine-activated killer activity was observed at around 10-20 days in culture, as judged by the cytotoxicity against fresh allogenic tumor cells. Maximal expression of the interleukin-2 receptor was also obtained at around 10 days. PBL collected by leukopheresis from each patient were thus cultured for 10 days with RIL 2, labeled with 111In-oxine, and then infused directly into the renal artery of the affected kidney via a catheter. Radioactivity in the infused side of the kidneys increased immediately after the infusion but then gradually decreased. Radioactivity in the lungs also rapidly increased within the first hour but then cleared gradually, whereas that in the liver and spleen tended to increase steadily. Nevertheless, at 48 hours, the infused side of the kidneys retained levels of radioactivity comparable to those seen in the liver and spleen, while the levels seen in the lungs were already close to background levels. The radioactivity in the areas corresponding to tumors remained consistently higher than that in the normal parts of the affected kidneys. The direct comparison of the radioactivity distribution pattern with the macroscopic appearance of surgically resected kidneys indicated that the accumulation of radioactivity was indeed selectively associated with the tumor tissues in the kidneys, except for a case in which the tumor was quite necrotic and hypovascular

  12. Flavokawain B inhibits growth of human squamous carcinoma cells: Involvement of apoptosis and cell cycle dysregulation in vitro and in vivo.

    Science.gov (United States)

    Lin, Elong; Lin, Wen-Hsin; Wang, Sheng-Yang; Chen, Chih-Sheng; Liao, Jiuun-Wang; Chang, Hsueh-Wei; Chen, Ssu-Ching; Lin, Kai-Yuan; Wang, Lai; Yang, Hsin-Ling; Hseu, You-Cheng

    2012-04-01

    Flavokawain B is a natural chalcone isolated from the rhizomes of Alpenia pricei Hayata. In the present study, we have investigated the antiproliferative and apoptotic effect of flavokawain B (5-20 μg/ml; 17.6-70.4 μM) against human squamous carcinoma (KB) cells. Exposure of KB cells with flavokawain B resulted in apoptosis, evidenced by loss of cell viability, profound morphological changes, genomic DNA fragmentation and sub-G1 phase accumulation. Apoptosis induced by flavokawain B results in activation of caspase-9, -3 and -8, cleavage of poly ADP ribose polymerase (PARP) and Bid in KB cells. Flavokawain B also down-regulate Bcl-2 with concomitant increase in Bax level, which resulted in release of cytochrome c. Taken together, the induction of apoptosis by flavokawain B involved in both death receptor and mitochondrial pathway. We also observed that flavokawain B caused the G2/M phase arrest that was mediated through reductions in the levels of cyclin A, cyclin B1, Cdc2 and Cdc25C and increases in p21/WAF1, Wee1 and p53 levels. Moreover, flavokawain B significantly inhibits matrix metalloproteinase-9 and urokinase plasminogen activator expression, whereas tissue inhibitor of matrix metalloproteinase-1 and plasminogen activator inhibitor-1 were increased, which are playing critical role in tumor metastasis. In addition, flavokawain B treatment significantly inhibited in vivo growth of human KB cell-derived tumor xenografts in nude mice, which is evidenced by augmentation of apoptotic DNA fragmentation, as detected by in situ terminal deoxynucleotidyl transferase-meditated dUTP nick end-labeling staining. The induction of cell cycle arrest and apoptosis by flavokawain B may provide a pivotal mechanism for its cancer chemopreventive action. PMID:21543203

  13. Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Shirzadi, Zahra [Graduate Program in Biomedical Engineering, Western University, London, Ontario N6A 5B9 (Canada); Sadeghi-Naini, Ali [Department of Medical Biophysics, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Samani, Abbas [Graduate Program in Biomedical Engineering, Western University, London, Ontario N6A 5B9 (Canada); Department of Medical Biophysics, Western University, London, Ontario N6A 5C1 (Canada); Department of Electrical and Computer Engineering, Western University, London, Ontario N6A 5B9 (Canada); Imaging Research Laboratories, Robarts Research Institute (RRI), London, Ontario N6A 5K8 (Canada)

    2013-05-15

    Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The

  14. Automatic application of ICRP biokinetic models in voxel phantoms for in vivo counting and internal dose assessment

    International Nuclear Information System (INIS)

    As part of the improvement of calibration techniques of in vivo counting, the Laboratory of Internal Dose Assessment of the Institute of Radiological Protection and Nuclear Safety has developed a computer tool, 'OEDIPE', to model internal contamination, to simulate in vivo counting and to calculate internal dose. The first version of this software could model sources located in a single organ. As the distribution of the contamination evolves from the time of intake according to the biokinetics of the radionuclide, a new facility has been added to the software first to allow complex heterogeneous source modelling and then to automatically integrate the distribution of the contamination in the different tissues estimated by biokinetic calculation at any time since the intake. These new developments give the opportunity to study the influence of the biokinetics on the in vivo counting, leading to a better assessment of the calibration factors and the corresponding uncertainties. (authors)

  15. Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Liu MC

    2016-04-01

    Full Text Available Min-Chen Liu,1 Lin Liu,1 Xia-Rong Wang,1 Wu-Ping Shuai,2 Ying Hu,3 Min Han,1 Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 3Zhejiang Pharmaceutical College, Ningbo, People’s Republic of China Abstract: The diacid metabolite of norcantharidin (DM-NCTD is clinically effective against hepatocellular carcinoma (HCC, but is limited by its short half-life and high incidence of adverse effects at high doses. We developed a DM-NCTD-loaded, folic acid (FA-modified, polyethylene glycolated (DM-NCTD/FA-PEG liposome system to enhance the targeting effect and antitumor potency for HCC at a moderate dose based on our previous study. The DM-NCTD/FA-PEG liposome system produced liposomes with regular spherical morphology, with mean particle size approximately 200 nm, and an encapsulation efficiency >80%. MTT cytotoxicity assays demonstrated that the DM-NCTD/FA-PEG liposomes showed significantly stronger cytotoxicity effects on the H22 hepatoma cell line than did PEG liposomes without the FA modification (P<0.01. We used liquid chromatography–mass spectrometry for determination of DM-NCTD in tissues and tumors, and found it to be sensitive, rapid, and reliable. In addition, the biodistribution study showed that DM-NCTD liposomes improved tumor-targeting efficiency, and DM-NCTD/FA-PEG liposomes exhibited the highest efficiency of the treatments (P<0.01. Meanwhile, the results indicated that although the active liposome group had an apparently increased tumor-targeting efficiency of DM-NCTD, the risk to the kidney was higher than in the normal liposome group. With regard to in vivo antitumor activity, DM-NCTD/FA-PEG liposomes inhibited tumors in H22 tumor-bearing mice better than either free DM-NCTD or DM-NCTD/PEG liposomes (P<0.01, and induced considerably more significant cellular apoptosis in the tumors, with no obvious toxicity to the tissues

  16. A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo

    International Nuclear Information System (INIS)

    In search of a suitable GSH-depleting agent, a novel copper complex viz., copper N-(2-hydroxyacetophenone) glycinate (CuNG) has been synthesized, which was initially found to be a potential resistance modifying agent and later found to be an immunomodulator in mice model in different doses. The objective of the present work was to decipher the effect of CuNG on reactive oxygen species (ROS) generation and antioxidant enzymes in normal and doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)-bearing Swiss albino mice. The effect of CuNG has been studied on ROS generation, multidrug resistance-associated protein1 (MRP1) expression and on activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). CuNG increased ROS generation and reduced MRP1 expression in EAC/Dox cells while only temporarily depleted glutathione (GSH) within 2 h in heart, kidney, liver and lung of EAC/Dox bearing mice, which were restored within 24 h. The level of liver Cu was observed to be inversely proportional to the level of GSH. Moreover, CuNG modulated SOD, CAT and GPx in different organs and thereby reduced oxidative stress. Thus nontoxic dose of CuNG may be utilized to reduce MRP1 expression and thus sensitize EAC/Dox cells to standard chemotherapy. Moreover, CuNG modulated SOD, CAT and and GPx activities to reduce oxidative stress in some vital organs of EAC/Dox bearing mice. CuNG treatment also helped to recover liver and renal function in EAC/Dox bearing mice. Based on our studies, we conclude that CuNG may be a promising candidate to sensitize drug resistant cancers in the clinic

  17. A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo

    Directory of Open Access Journals (Sweden)

    Efferth Thomas

    2006-11-01

    Full Text Available Abstract Background In search of a suitable GSH-depleting agent, a novel copper complex viz., copper N-(2-hydroxyacetophenone glycinate (CuNG has been synthesized, which was initially found to be a potential resistance modifying agent and later found to be an immunomodulator in mice model in different doses. The objective of the present work was to decipher the effect of CuNG on reactive oxygen species (ROS generation and antioxidant enzymes in normal and doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox-bearing Swiss albino mice. Methods The effect of CuNG has been studied on ROS generation, multidrug resistance-associated protein1 (MRP1 expression and on activities of superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GPx. Results CuNG increased ROS generation and reduced MRP1 expression in EAC/Dox cells while only temporarily depleted glutathione (GSH within 2 h in heart, kidney, liver and lung of EAC/Dox bearing mice, which were restored within 24 h. The level of liver Cu was observed to be inversely proportional to the level of GSH. Moreover, CuNG modulated SOD, CAT and GPx in different organs and thereby reduced oxidative stress. Thus nontoxic dose of CuNG may be utilized to reduce MRP1 expression and thus sensitize EAC/Dox cells to standard chemotherapy. Moreover, CuNG modulated SOD, CAT and and GPx activities to reduce oxidative stress in some vital organs of EAC/Dox bearing mice. CuNG treatment also helped to recover liver and renal function in EAC/Dox bearing mice. Conclusion Based on our studies, we conclude that CuNG may be a promising candidate to sensitize drug resistant cancers in the clinic.

  18. PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcinoma model.

    Directory of Open Access Journals (Sweden)

    Edward Hammond

    Full Text Available PG545 is a clinically relevant heparan sulfate (HS mimetic which, in addition to possessing anti-angiogenic properties, also acts as a heparanase inhibitor which may differentiate its mechanism(s of action from approved angiogenesis inhibitors. The degradation of HS by heparanase has been strongly implicated in cell dissemination and the metastatic process. Thus, the anti-metastatic activity of PG545 has been linked to the enzymatic function of heparanase - the only endoglycosidase known to cleave HS, an important component of the extracellular matrix (ECM which represents a potential avenue for therapeutic intervention for certain metastatic cancer indications. Recent concerns raised about the paucity of overall survival as an endpoint in mouse models of clinically relevant metastasis led us to examine the effect of PG545 on the progression of both primary tumor growth and the spontaneously metastasizing disease in the 4T1 syngeneic breast carcinoma model in a non-surgical and surgical (mastectomy setting. PG545 significantly inhibited primary tumor growth but importantly also inhibited lung metastasis in treated mice, an effect not observed with the tyrosine kinase inhibitor sorafenib. Importantly, PG545 significantly enhanced overall survival compared to vehicle control and the sorafenib group, suggesting PG545's inhibitory effect on heparanase is indeed a critical attribute to induce anti-metastatic activity. In addition to blocking a common angiogenic signalling pathway in tumor cells, the expression of heparanase in the primary tumor and lung was also significantly reduced by PG545 treatment. These results support the ongoing development of PG545 and highlight the potential utility in metastatic disease settings.

  19. Mesenchymal stromal cells from the human placenta promote neovascularization in a mouse model in vivo.

    Science.gov (United States)

    Kinzer, M; Hingerl, K; König, J; Reinisch, A; Strunk, D; Huppertz, B; Lang, I

    2014-07-01

    Cell transplantation is a promising strategy in regenerative medicine for revascularization of ischemic tissues. Based on our observation that placental mesenchymal stromal cells (PMSC) enhance endothelial cell viability in vitro via secretion of angiogenic factors, we asked whether PMSC support vascular growth in vivo. PMSC were isolated from amnion and placental endothelial cells (PLEC) from chorion and either separately or co-transplanted subcutaneously into immune-deficient mice. Co-transplantation resulted in a higher number of perfused human vessels (CD31+/vimentin+) containing mouse glycophorin A+ erythrocytes. Results indicate positive effects of PMSC on neovascularization in vivo, making them attractive candidates to create autologous PMSC/PLEC pairs for research and transplantation.

  20. An Ex Vivo Model in Human Femoral Heads for Histopathological Study and Resonance Frequency Analysis of Dental Implant Primary Stability

    Directory of Open Access Journals (Sweden)

    Pedro Hernández-Cortés

    2014-01-01

    Full Text Available Objective. This study was designed to explore relationships of resonance frequency analysis (RFA—assessed implant stability (ISQ values with bone morphometric parameters and bone quality in an ex vivo model of dental implants placed in human femoral heads and to evaluate the usefulness of this model for dental implant studies. Material and Methods. This ex vivo study included femoral heads from 17 patients undergoing surgery for femoral neck fracture due to osteoporosis (OP (n=7 or for total prosthesis joint replacement due to severe hip osteoarthrosis (OA (n=10. Sixty 4.5×13 mm Dentsply Astra implants were placed, followed by RFA. CD44 immunohistochemical analysis for osteocytes was also carried out. Results. As expected, the analysis yielded significant effects of femoral head type (OA versus OA (P0.5 in all cases, and no significant differences in ISQ values were found as a function of the length or area of the cortical layer (both P>0.08. Conclusion. Although RFA-determined ISQ values are not correlated with morphometric parameters, they can discriminate bone quality (OP versus OA. This ex vivo model is useful for dental implant studies.

  1. Assessment of Full-Eye Response to Osmotic Stress in Mouse Model In Vivo Using Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Yang Ni

    2015-01-01

    Full Text Available NaCl based solutions were applied as osmotic stress agents to alter the hydration state of the mouse eye. Full-eye responses to these osmotic challenges were monitored in vivo using a custom-built optical coherence tomography (OCT with an extended imaging range of 12.38 mm. Dynamic changes in the mouse eye were quantified based on the OCT images using several parameters, including the central corneal thickness (CCT, the anterior chamber depth (ACD, the crystalline lens thickness (LT, the cornea-retina distance (CRD, the iris curvature (IC, and the lens scattering intensity (LSI. Apparent but reversible changes in the morphology of almost all the ocular components and the light transparency of the lens are exhibited. Particularly, the ocular dehydration induced by the hypertonic challenges resulted in a closing of the iridocorneal angle and an opacification of the lens. Our results indicated that the ocular hydration is an important physiological process which might be correlated with various ocular disorders, such as dry eye, cataract, and angle-closure glaucoma, and would affect the biometry and imaging of the eye. OCT uniquely enables the comprehensive study of the dynamic full-eye responses to the ocular hydration in vivo.

  2. Development of multifunctional optical coherence tomography and application to mouse myocardial infarction model in vivo (Conference Presentation)

    Science.gov (United States)

    Jang, Sun-Joo; Park, Taejin; Shin, Inho; Park, Hyun Sang; Shin, Paul; Oh, Wang-Yuhl

    2016-02-01

    Optical coherence tomography (OCT) is a useful imaging method for in vivo tissue imaging with deep penetration and high spatial resolution. However, imaging of the beating mouse heart is still challenging due to limited temporal resolution or penetration depth. Here, we demonstrate a multifunctional OCT system for a beating mouse heart, providing various types of visual information about heart pathophysiology with high spatiotemporal resolution and deep tissue imaging. Angiographic imaging and polarization-sensitive (PS) imaging were implemented with the electrocardiogram (ECG)-triggered beam scanning scheme on the high-speed OCT platform (A-line rate: 240 kHz). Depth-resolved local birefringence and the local orientation of the mouse myocardial fiber were visualized from the PS-OCT. ECG-triggered angiographic OCT (AOCT) with the custom-built motion stabilization imaging window provided myocardial vasculature of a beating mouse heart. Mice underwent coronary artery ligation to derive myocardial infarction (MI) and were imaged with the multifunctional OCT system at multiple time points. AOCT and PS-OCT visualize change of functionality of coronary vessels and myocardium respectively at different phases (acute and chronic) of MI in an ischemic mouse heart. Taken together, the integrated imaging of PS-OCT and AOCT would play an important role in study of MI providing multi-dimensional information of the ischemic mouse heart in vivo.

  3. quercetin抑制肝细胞癌生长的在体实验研究%Quercetin inhibiting growth of hepatocellular carcinoma cells:in vivo experimental study

    Institute of Scientific and Technical Information of China (English)

    黄春龙; 彭伟; 张继红; 邓量; 王小锋

    2015-01-01

    目的:探讨quercetin对肝癌细胞体内生长的抑制作用及机制。  方法:用人肝癌HepG2细胞皮下接种法建立裸鼠移植瘤模型,成瘤后随机分为对照组、quercetin治疗组、5-FU治疗组、5-FU+quercetin联合治疗组,溶剂或药物均1次/d腹腔注射,3周后观察各组移植瘤大小并计算各治疗组的抑瘤率,分别用RT-PCR、Western blot、免疫组化法检测各组移植瘤组织中cyclin D1、cyclin E、增殖细胞核抗原(PCNA)的表达。  结果:与对照组比较,各治疗组移植瘤体积明显减小、移植瘤组织中cyclin D1、cyclin E mRNA和蛋白表达以及PCNA阳性指数均明显降低(均P0.05)。  结论:quercetin能通过下调cyclin D1与cyclin E的表达而抑制肝癌细胞的增殖,且与5-FU联合应用具有协同作用。%Objective: To investigate the inhibitory effect of quercetin on the growth of hepatocellular carcinoma (HCC) cells in vivo and the mechanism. Methods: Tumor xenograft model was established by subcutaneous inoculation of human HCC HepG2 cells into the nude mice. Atfer tumor formation, the tumor-bearing mice were randomly divided into control group, quercetin treatment group, 5-FU treatment group, and quercetin plus 5-FU combination treatment group, and the vehicle or drugs were administered by intraperitoneal injection once daily. At three weeks atfer treatment, the tumor size in each group was observed and the tumor inhibition rate in each treatment group was calculated, and the expressions of cyclin D1, cyclin E and proliferating cell nuclear antigen (PCNA) in the xenogratf tumor tissues were determined by RT-PCR, Western blot and immunohistochemical staining, respectively. Results: Compared with control group, the tumor size was reduced, and the mRNA and protein expressions of cyclin D1 and cyclin E as well as PCNA positive index in tumor tissue were decreased significantly in each treatment group (allP0.05). Conclusion

  4. Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo

    DEFF Research Database (Denmark)

    Ale, Marcel Tutor; Maruyama, Hiroko; Tamauchi, Hidekazu;

    2011-01-01

    Fucoidan is known to exhibit crucial biological activities, including anti-tumor activity. In this study, we examined the influence of crude fucoidan extracted from Sargassum sp. (MTA) and Fucus vesiculosus (SIG) on Lewis lung carcinoma cells (LCC) and melanoma B16 cells (MC). In vitro studies were...

  5. CHARACTERIZATION OF A RAT ORAL SQUAMOUS-CELL CARCINOMA CELL-LINE UHG-RAC-'93 INDUCED BY 4-NITROQUINOLINE-1-OXIDE IN-VIVO

    NARCIS (Netherlands)

    WITJES, M; SCHOLMA, J; VANDRUNEN, E; ROODENBURG, JLN; MESANDER, G; HAGEMEIJER, A; TOMSON, AM

    1995-01-01

    This study describes several characteristics of a cell line, UHG-RaC '93 derived from rat oral squamous cell carcinoma induced by the carcinogen 4-nitroquinoline-1-oxide (4NQO), The cell Line was established from explant cultures without support of fibroblast feeder cells and continued for > 30 pass

  6. Inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma:in vitro andin vivo studies

    Institute of Scientific and Technical Information of China (English)

    Xiang-Bao Yin; Lin-Quan Wu; Hua-Qun Fu; Ming-Wen Huang; Kai Wang; Fan Zhou; Xin Yu; Kai-Yang Wang

    2014-01-01

    Objective:To investigate the inhibitory effect of humanized anti-VEGFR-2ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma bothin vitro andin vivo, which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer.Methods:Humanized anti-VEGFR-2ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology. In this combinedin vitro andin vivo study, the inhibitory effects of anti-VEGFR-2ScFv-As2O3-stealth nanoparticles conjugate on tumor growth, invasion, and metastasis was observed with human liver carcinoma cell lineBel7402 and normal cellL02 byMTT assay,Tanswell assay, Hochest33258 staining, andDNA ladder analysis.The anticancer activity and distribution of anti-VEGFR-2ScFv-As2O3-stealth nanoparticles was then verified in a mouse model ofBel7402 xenografts.Results:Anti-VEGFR-2ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation ofBel7402 in the3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while had almost no effects onL02 cells.And the apoptosis inducing effects were proved byHochest33258 staining andDNA ladder analysis.Transwell assay found that the drug also inhibited the metastasis ability of tumor cells.Furthermore, anti-VEGFR-2ScFv-As2O3-stealth nanoparticles significantly delayed the growth ofBel7402 xenografts after administration(92.9%), followed byAs2O3-stealth nanoparticles, anti-VEGFR-2ScFv, andAs2O3(61.4%,58.8%,20.5%, P<0.05).The concentration ofAs2O3 in anti-VEGFR-2ScFv-As2O3-stealth nanoparticles group was more selectively.Conclusions:Anti-VEGFR-2ScFv-As2O3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent bothin vitro andin vivo and also significantly inhibit angiogenesis.

  7. Effect of histone deacetylase inhibitor on expression of HDAC1 in gallbladder carcinoma cell line and extrahepatic cholangiocarcinoma cell line in vivo and in vitro%组蛋白去乙酰化酶抑制剂对胆囊癌细胞系和肝外胆管癌细胞系HDAC1表达的影响

    Institute of Scientific and Technical Information of China (English)

    王欣; 黄凯; 徐立宁

    2008-01-01

    目的 观察组蛋白去乙酰化酶抑制剂-曲古抑菌素(TSA)在体外和体内对胆囊癌细胞和肝外胆管癌细胞HDAC1表达的影响.方法 用TSA作用于胆囊癌细胞系(Mz-ChA-1)和肝外胆管癌细胞系(QBC939、KMBC、OZ),然后用逆转录-聚合酶链反应(RT-PCR)检测HDAC1之mR-NA的表达变化,用Western blot检测其蛋白的表达变化.将这些细胞接种在裸鼠皮下建立胆囊癌和肝外胆管癌裸鼠种植瘤模型,用免疫组织化学方法 观察TSA在体内对裸鼠种植瘤组织中HDAC1蛋白表达的影响.结果 TSA可以减弱胆囊癌细胞系(Mz-ChA-1)和肝外胆管癌细胞系(QBC939、KMBC、OZ)HDAC1 mRNA和蛋白的表达;TSA作用前后的胆囊癌细胞系(Mz-ChA-1)和肝外胆管癌细胞系(KMBC)裸鼠成瘤组织中的各种蛋白的表达均无变化.结论 TSA在体外可以抑制胆囊癌和肝外胆管癌HDAC1的表达;TSA抑制HDAC1表达的作用可能受到体内环境的影响而消失.%Objective To study the effect of histone deacetylase inhibitor-trichostatin A (TSA) on the HDAC1 expression in gallbladder carcinoma and extrahepatic cholangioearcinoma cells in vivo and in vitro. Methods The cells from gallbladder carcinoma cell line ( Mz-ChA-1 ) and cholangiocarcinoma cell lines (QBC939, KMBC and OZ) were treated with TSA, and the expression of HDAC1 mRNA and protein was detected by RT-PCR assay and Western blot respectively. These cells were subcutaneously transplanted into nude mice to establish the transplanted cholangiocarcinoma and gallbladder carcinoma models. The effect of TSA on the expression of HDAC1 protein in transplanted cancer tissues in vivo was observed. Results TSA could down-regulate the expression of HDAC1 mRNA and protein in gallbladder carcinoma cells and cholangiocarcinoma cells. TSA could not down-or up-regulate the expression of HDAC1 protein in the transplanted biliary tract cancer models in nude mice. Conclusion TSA might down-regulate the expression of HDAC1 in

  8. Particle deposition in a child respiratory tract model: in vivo regional deposition of fine and ultrafine aerosols in baboons.

    Directory of Open Access Journals (Sweden)

    Iolanda Albuquerque-Silva

    Full Text Available To relate exposure to adverse health effects, it is necessary to know where particles in the submicron range deposit in the respiratory tract. The possibly higher vulnerability of children requires specific inhalation studies. However, radio-aerosol deposition experiments involving children are rare because of ethical restrictions related to radiation exposure. Thus, an in vivo study was conducted using three baboons as a child respiratory tract model to assess regional deposition patterns (thoracic region vs. extrathoracic region of radioactive polydisperse aerosols ([d16-d84], equal to [0.15 µm-0.5 µm], [0.25 µm-1 µm], or [1 µm-9 µm]. Results clearly demonstrated that aerosol deposition within the thoracic region and the extrathoraic region varied substantially according to particle size. High deposition in the extrathoracic region was observed for the [1 µm-9 µm] aerosol (72% ± 17%. The [0.15 µm-0.5 µm] aerosol was associated almost exclusively with thoracic region deposition (84% ± 4%. Airborne particles in the range of [0.25 µm-1 µm] showed an intermediate deposition pattern, with 49% ± 8% in the extrathoracic region and 51% ± 8% in the thoracic region. Finally, comparison of baboon and human inhalation experiments for the [1 µm-9 µm] aerosol showed similar regional deposition, leading to the conclusion that regional deposition is species-independent for this airborne particle sizes.

  9. Detection of in situ mammary cancer in a transgenic mouse model: in vitro and in vivo MRI studies demonstrate histopathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, S A; Fan, X; Zamora, M; Foxley, S; River, J; Newstead, G M; Karczmar, G S [Department of Radiology, University of Chicago, 5841 S Maryland Avenue, MC 2026, Chicago, IL 60637 (United States); Conzen, S D [Department of Medicine and Ben May Department for Cancer Research, University of Chicago, 5841 S Maryland Ave, MC 2115, Chicago, IL 60637 (United States); Krausz, T [Department of Pathology, University of Chicago, 5841 S Maryland Avenue, MC 6101, Chicago, IL 60637 (United States)], E-mail: gskarczm@uchicago.edu

    2008-10-07

    Improving the prevention and detection of preinvasive ductal carcinoma in situ (DCIS) is expected to lower both morbidity and mortality from breast cancer. Transgenic mouse models can be used as a 'test bed' to develop new imaging methods and to evaluate the efficacy of candidate preventive therapies. We hypothesized that despite its microscopic size, early murine mammary cancer, including DCIS, might be accurately detected by MRI. C3(1) SV40 TAg female mice (n = 23) between 10 and 18 weeks of age were selected for study. Eleven mice were subjected to in vitro imaging using a T{sub 2}-weighted spin echo sequence and 12 mice were selected for in vivo imaging using a T{sub 1}-weighted gradient echo, a T{sub 2}-weighted spin echo and high spectral and spatial resolution imaging sequences. The imaged glands were carefully dissected, formalin fixed and paraffin embedded, and then H and E stained sections were obtained. The ratio of image-detected versus histologically detected cancers was obtained by reviewing the MR images and H and E sections independently and using histology as the gold standard. MR images were able to detect 12/12 intramammary lymph nodes, 1/1 relatively large ({approx}5 mm) tumor, 17/18 small ({approx}1 mm) tumors and 13/16 ducts distended with DCIS greater than 300 {mu}m. Significantly, there were no false positives-i.e., image detection always corresponded to a histologically detectable cancer in this model. These results indicate that MR imaging can reliably detect both preinvasive in situ and early invasive mammary cancers in mice with high sensitivity. This technology is an important step toward the more effective use of non-invasive imaging in pre-clinical studies of breast cancer prevention, detection and treatment.

  10. Detection of in situ mammary cancer in a transgenic mouse model: in vitro and in vivo MRI studies demonstrate histopathologic correlation

    Science.gov (United States)

    Jansen, S. A.; Conzen, S. D.; Fan, X.; Krausz, T.; Zamora, M.; Foxley, S.; River, J.; Newstead, G. M.; Karczmar, G. S.

    2008-10-01

    Improving the prevention and detection of preinvasive ductal carcinoma in situ (DCIS) is expected to lower both morbidity and mortality from breast cancer. Transgenic mouse models can be used as a 'test bed' to develop new imaging methods and to evaluate the efficacy of candidate preventive therapies. We hypothesized that despite its microscopic size, early murine mammary cancer, including DCIS, might be accurately detected by MRI. C3(1) SV40 TAg female mice (n = 23) between 10 and 18 weeks of age were selected for study. Eleven mice were subjected to in vitro imaging using a T2-weighted spin echo sequence and 12 mice were selected for in vivo imaging using a T1-weighted gradient echo, a T2-weighted spin echo and high spectral and spatial resolution imaging sequences. The imaged glands were carefully dissected, formalin fixed and paraffin embedded, and then H&E stained sections were obtained. The ratio of image-detected versus histologically detected cancers was obtained by reviewing the MR images and H&E sections independently and using histology as the gold standard. MR images were able to detect 12/12 intramammary lymph nodes, 1/1 relatively large (~5 mm) tumor, 17/18 small (~1 mm) tumors and 13/16 ducts distended with DCIS greater than 300 µm. Significantly, there were no false positives—i.e., image detection always corresponded to a histologically detectable cancer in this model. These results indicate that MR imaging can reliably detect both preinvasive in situ and early invasive mammary cancers in mice with high sensitivity. This technology is an important step toward the more effective use of non-invasive imaging in pre-clinical studies of breast cancer prevention, detection and treatment.

  11. 癌相关成纤维细胞对结肠癌生物学行为的影响%Carcinoma-associated fibroblasts effect on biological behavior of colon carcinoma LoVo cells in vivo

    Institute of Scientific and Technical Information of China (English)

    施琳; 隋贵春; 袁宏伟; 韦玄; 贾永峰; 云芬; 孙红; 乌新林

    2016-01-01

    目的 观察人结肠癌相关成纤维细胞(CAFs)在体内对结肠癌LoVo细胞侵袭转移的影响.方法 胶原酶消化法原代培养人结肠CAFs和正常成纤维细胞(NFs);对第3代人结肠CAFs和NFs通过形态学观察和免疫细胞化学染色方法进行鉴定;BALB/c裸鼠随机分3组,实验组将CAFs和NFs分别与结肠癌LoVo细胞按浓度为1×1010/L,以1:1比例混合,以单独注射LoVo细胞为对照组,通过皮下注射和脾脏注射的方法分别建立皮下移植瘤模型和肝转移模型,比较3组间皮下移植瘤的生长速度及肝转移率之间的差异;采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结(SP)法检测3组皮下移植瘤标本中CD31标记的微血管密度(MVD)以探讨CAFs和NFs对肿瘤血管生成的影响.结果 CAFs较NFs特异表达成纤维细胞活化蛋白(FAP)和成纤维细胞特异性蛋白(FSP),两种细胞结蛋白(Desmin)均为阴性表达;CAFs+ LoVo组(CAF干扰组)肿瘤生长速度和体积明显大于NFs+ LoVo组(NF干扰组)和LoVo组(未干扰组,P<0.05);皮下移植瘤CD31免疫组织化学染色显示CAFs+ LoVo组MVD计数为(11.16±2.44)个,NFs+ LoVo组为(7.36±1.52)个,LoVo组为(6.08±1.41)个,CAFs+ LoVo组MVD计数明显多于NFs+ LoVo组和LoVo组(P<0.05),NFs+ LoVo组MVD计数多于LoVo组(P<0.05);CAFs+ LoVo组肝转移率为80%,明显高于NFs+ LoVo组(40%)和LoVo组(20%,P<0.05).结论 人结肠CAFs能够促进结肠癌的侵袭和转移,可能与CAFs促进结肠癌肿瘤血管生成有关.%Objective To investigate the effects of human colon carcinoma-associated fibroblasts (CAFs) on colon cancer cells LoVo invasion and metastasis in vivo.Methods The primary human colon CAFs and normal fibroblasts (NFs) were obtained by digestion methods.Identified the third generation CAFs and NFs cells by morphological observation and immunocytochemistry (ICC) staining.BALB/c nude mice were randomly grouped.Mix CAFs or NFs with colon cancer LoVo cells at a

  12. Viral cross-class serpin inhibits vascular inflammation and T lymphocyte fratricide; a study in rodent models in vivo and human cell lines in vitro.

    Directory of Open Access Journals (Sweden)

    Kasinath Viswanathan

    Full Text Available Poxviruses express highly active inhibitors, including serine proteinase inhibitors (serpins, designed to target host immune defense pathways. Recent work has demonstrated clinical efficacy for a secreted, myxomaviral serpin, Serp-1, which targets the thrombotic and thrombolytic proteases, suggesting that other viral serpins may have therapeutic application. Serp-2 and CrmA are intracellular cross-class poxviral serpins, with entirely distinct functions from the Serp-1 protein. Serp-2 and CrmA block the serine protease granzyme B (GzmB and cysteine proteases, caspases 1 and 8, in apoptotic pathways, but have not been examined for extracellular anti-inflammatory activity. We examined the ability of these cross-class serpins to inhibit plaque growth after arterial damage or transplant and to reduce leukocyte apoptosis. We observed that purified Serp-2, but not CrmA, given as a systemic infusion after angioplasty, transplant, or cuff-compression injury markedly reduced plaque growth in mouse and rat models in vivo. Plaque growth was inhibited both locally at sites of surgical trauma, angioplasty or transplant, and systemically at non-injured sites in ApoE-deficient hyperlipidemic mice. With analysis in vitro of human cells in culture, Serp-2 selectively inhibited T cell caspase activity and blocked cytotoxic T cell (CTL mediated killing of T lymphocytes (termed fratricide. Conversely, both Serp-2 and CrmA inhibited monocyte apoptosis. Serp-2 inhibitory activity was significantly compromised either in vitro with GzmB antibody or in vivo in ApoE/GzmB double knockout mice. Conclusions The viral cross-class serpin, Serp-2, that targets both apoptotic and inflammatory pathways, reduces vascular inflammation in a GzmB-dependent fashion in vivo, and inhibits human T cell apoptosis in vitro. These findings indicate that therapies targeting Granzyme B and/or T cell apoptosis may be used to inhibit T lymphocyte apoptosis and inflammation in response to

  13. Discovery of Fully Human Anti-MET Monoclonal Antibodies with Antitumor Activity against Colon Cancer Tumor Models In Vivo

    Directory of Open Access Journals (Sweden)

    Edward Htun van der Horst

    2009-04-01

    Full Text Available The receptor tyrosine kinase MET is a major component controlling the invasive growth program in embryonic development and in invasive malignancies. The discovery of therapeutic antibodies against MET has been difficult, and antibodies that compete with hepatocyte growth factor (HGF act as agonists. By applying phage technology and cell-based panning strategies, we discovered two fully human antibodies against MET (R13 and R28, which synergistically inhibit HGF binding to MET and elicit antibody-dependent cellular cytotoxicity. Cell-based phosphorylation assays demonstrate that R13 and R28 abrogate HGF-induced activation of MET, AKT1, ERK1/2, and HGF-induced migration and proliferation. FACS experiments suggest that the inhibitory effect is mediated by “locking” MET receptor in a state with R13, which then increases avidity of R28 for the extracellular domain of MET, thus blocking HGF binding without activating the receptor. In vivo studies demonstrate that the combination of R13/28 significantly inhibited tumor growth in various colon tumor xenograft models. Inhibition of tumor growth was associated with induction of hypoxia. Global gene expression analysis shows that inhibition of HGF/MET pathway significantly upregulated the tumor suppressors KLF6, CEACAM1, and BMP2, the negative regulator of phosphatidylinositol-3-OH-kinase PIK3IP1, and significantly suppressed SCF and SERPINE2, both enhancers of proliferation and invasiveness. Moreover, in an experimental metastasis model, R13/28 increased survival by preventing the recurrence of otherwise lethal lung metastases. Taken together, these results underscore the utility of a dual-antibody approach for targeting MET and possibly other receptor tyrosine kinases. Our approach could be expanded to drug discovery efforts against other cell surface proteins.

  14. Simultaneous inactivation of Par-4 and PTEN in vivo leads to synergistic NF-κB activation and invasive prostate carcinoma

    Science.gov (United States)

    Fernandez-Marcos, Pablo J.; Abu-Baker, Shadi; Joshi, Jayashree; Galvez, Anita; Castilla, Elias A.; Cañamero, Marta; Collado, Manuel; Saez, Carmen; Moreno-Bueno, Gema; Palacios, Jose; Leitges, Michael; Serrano, Manuel; Moscat, Jorge; Diaz-Meco, Maria T.

    2009-01-01

    Prostate cancer is one of the most common neoplasias in men. The tumor suppressor Par-4 is an important negative regulator of the canonical NF-κB pathway and is highly expressed in prostate. Here we show that Par-4 expression is lost in a high percentage of human prostate carcinomas, and this occurs in association with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss. Par-4 null mice, similar to PTEN-heterozygous mice, only develop benign prostate lesions, but, importantly, concomitant Par-4 ablation and PTEN-heterozygosity lead to invasive prostate carcinoma in mice. This strong tumorigenic cooperation is anticipated in the preneoplastic prostate epithelium by an additive increase in Akt activation and a synergistic stimulation of NF-κB. These results establish the cooperation between Par-4 and PTEN as relevant for the development of prostate cancer and implicate the NF-κB pathway as a critical event in prostate tumorigenesis. PMID:19470463

  15. Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine

    OpenAIRE

    AMINI, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David L

    2015-01-01

    Aberrant expression of membrane-associated and secreted mucins, as evident in epithelial tumors, is known to facilitate tumor growth, progression and metastasis, and to provide protection against adverse growth conditions, chemotherapy and immune surveillance. Emerging evidence provides support for the oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal tumors, in particular increase...

  16. The Silencing of Pokemon Attenuates the Proliferation of Hepatocellular Carcinoma Cells In Vitro and In Vivo by Inhibiting the PI3K/Akt Pathway

    OpenAIRE

    Chan-Chan Lin; Jing-Ping Zhou; Yun-Peng Liu; Jing-Jing Liu; Xiao-Ning Yang; Amarsanaa Jazag; Zhi-Ping Zhang; Bayasi Guleng; Jian-Lin Ren

    2012-01-01

    Pokemon (POK erythroid myeloid ontogenic factor), which belongs to the POK protein family, is also called LRF, OCZF and FBI-1. As a transcriptional repressor, Pokemon assumes a critical function in cellular differentiation and oncogenesis. Our study identified an oncogenic role for Pokemon in human hepatocellular carcinoma (HCC). We successfully established human HepG2 and Huh-7 cell lines in which Pokemon was stably knocked down. We demonstrated that Pokemon silencing inhibited cell prolifer...

  17. ENMD-1198, a novel tubulin-binding agent reduces HIF-1alpha and STAT3 activity in human hepatocellular carcinoma(HCC cells, and inhibits growth and vascularization in vivo

    Directory of Open Access Journals (Sweden)

    Schlitt Hans J

    2008-07-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC represents a highly vascularized tumor entity and the process of angiogenesis is essential for the growth of HCC. Importantly, the pro-angiogenic transcription factors HIF-1α and STAT3 have been implicated in HCC progression, thus representing interesting targets for molecular targeted therapy. We hypothesized that therapeutic inhibition of HIF-1α could be achieved by using a novel tubulin-binding agent (ENMD-1198. ENMD-1198 is an analog of 2-methoxyestradiol (2ME2 with antiproliferative and antiangiogenic activity. Methods The human HCC cell lines HUH-7 and HepG2 were used for experiments. Effects of ENMD-1198 on constitutive and inducible (hypoxia, growth factors activation of signaling cascades, including HIF-1α and STAT3, were investigated by Western blotting. Changes in VEGF expression were determined by real-time PCR. Effects of ENMD-1198 on cancer cell migration and invasion were evaluated in in vitro-assays. The growth-inhibitory effects of ENMD-1198 (200 mg/kg/day were determined in a subcutaneous tumor model (HUH-7. Results ENMD-1198 inhibited the phosphorylation of MAPK/Erk, PI-3K/Akt and FAK. Moreover, activation of HIF-1α and STAT3 was dramatically reduced by ENMD-1198, which resulted in lower VEGF mRNA expression (P In vivo, treatment with ENMD-1198 led to a significant reduction in tumor growth, tumor vascularization, and numbers of proliferating tumor cells (P Conclusion The novel microtubule destabilizing agent ENMD-1198 is suitable for inhibiting HIF-1α and STAT3 in human HCC cells and leads to reduced tumor growth and vascularization in vivo. Hence, inhibition of HIF-1α and STAT3 could prove valuable for therapy of hepatocellular carcinoma.

  18. The silencing of Pokemon attenuates the proliferation of hepatocellular carcinoma cells in vitro and in vivo by inhibiting the PI3K/Akt pathway.

    Directory of Open Access Journals (Sweden)

    Chan-Chan Lin

    Full Text Available Pokemon (POK erythroid myeloid ontogenic factor, which belongs to the POK protein family, is also called LRF, OCZF and FBI-1. As a transcriptional repressor, Pokemon assumes a critical function in cellular differentiation and oncogenesis. Our study identified an oncogenic role for Pokemon in human hepatocellular carcinoma (HCC. We successfully established human HepG2 and Huh-7 cell lines in which Pokemon was stably knocked down. We demonstrated that Pokemon silencing inhibited cell proliferation and migration. Pokemon knockdown inhibited the PI3K/Akt and c-Raf/MEK/ERK pathways and modulated the expression of various cell cycle regulators in HepG2 and Huh-7 cells. Therefore, Pokemon may also be involved in cell cycle progression in these cells. We confirmed that Pokemon silencing suppresses hepatocellular carcinoma growth in tumor xenograft mice. These results suggest that Pokemon promotes cell proliferation and migration in hepatocellular carcinoma and accelerates tumor development in an Akt- and ERK-signaling-dependent manner.

  19. The silencing of Pokemon attenuates the proliferation of hepatocellular carcinoma cells in vitro and in vivo by inhibiting the PI3K/Akt pathway.

    Science.gov (United States)

    Lin, Chan-Chan; Zhou, Jing-Ping; Liu, Yun-Peng; Liu, Jing-Jing; Yang, Xiao-Ning; Jazag, Amarsanaa; Zhang, Zhi-Ping; Guleng, Bayasi; Ren, Jian-Lin

    2012-01-01

    Pokemon (POK erythroid myeloid ontogenic factor), which belongs to the POK protein family, is also called LRF, OCZF and FBI-1. As a transcriptional repressor, Pokemon assumes a critical function in cellular differentiation and oncogenesis. Our study identified an oncogenic role for Pokemon in human hepatocellular carcinoma (HCC). We successfully established human HepG2 and Huh-7 cell lines in which Pokemon was stably knocked down. We demonstrated that Pokemon silencing inhibited cell proliferation and migration. Pokemon knockdown inhibited the PI3K/Akt and c-Raf/MEK/ERK pathways and modulated the expression of various cell cycle regulators in HepG2 and Huh-7 cells. Therefore, Pokemon may also be involved in cell cycle progression in these cells. We confirmed that Pokemon silencing suppresses hepatocellular carcinoma growth in tumor xenograft mice. These results suggest that Pokemon promotes cell proliferation and migration in hepatocellular carcinoma and accelerates tumor development in an Akt- and ERK-signaling-dependent manner. PMID:23300578

  20. A Catalogue of Altered Salivary Proteins Secondary to Invasive Ductal Carcinoma: A Novel In Vivo Paradigm to Assess Breast Cancer Progression.

    Science.gov (United States)

    Streckfus, Charles F; Bigler, Lenora

    2016-08-01

    The objective of this manuscript is to introduce a catalogue of salivary proteins that are altered secondary to carcinoma of the breast. The catalogue of salivary proteins is a compilation of twenty years of research by the authors and consists of 233 high and low abundant proteins which have been identified by LC-MS/MS mass spectrometry, 2D-gel analysis and by enzyme-linked immunosorbent assay. The body of research suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be useful in the study of breast cancer progress, treatment efficacy and the tailoring of individualized patient care.

  1. Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo

    OpenAIRE

    Xing-Mei Luo; Bin Xu; Min-Li Zhou; Yang-Yang Bao; Shui-Hong Zhou; Jun Fan; Zhong-Jie Lu

    2015-01-01

    In the present study, we investigated the role of GLUT-1 and PI3K/Akt signaling in radioresistance of laryngeal carcinoma xenografts. Volume, weight, radiosensitization, and the rate of inhibition of tumor growth in the xenografts were evaluated in different groups. Apoptosis was evaluated by TUNEL assay. In addition, mRNA and protein levels of GLUT-1, p-Akt, and PI3K in the xenografts were measured. Treatment with LY294002, wortmannin, wortmannin plus GLUT-1 AS-ODN, and LY294002 plus GLUT-1 ...

  2. In vivo anti-tumor effect of hybrid vaccine of dendritic cells and esophageal carcinoma cells on esophageal carcinoma cell line 109 in mice with severe combined immune deficiency

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To develop a fusion vaccine of esophageal carcinoma cells and dendritic cells (DC) and observe its protective and therapeutic effect against esophageal carcinoma cell line 109 (EC109). METHODS: The fusion vaccine was produced by fusing traditional polyethyleneglycol (PEG), inducing cytokine, sorting CD34+ magnetic microbead marker and magnetic cell system (MACS). The liver, spleen and lung were pathologically tested after injection of the fusion vaccine. To study the therapeutic and protective effect of the fusion vaccine against tumor EC109, mice were divided immune group and therapeutic group. The immune group was divided into P, E, D and ED subgroups, immunized by phosphate buffered solution (PBS), inactivated EC109,DC and the fusion vaccine respectively, and attacked by EC109 cells. The tumor size, weight, latent period and mouse survival period were recorded and statistically analyzed. The therapeutic group was divided into four subgroups: P, inactivated EC109,D and ED subgroups, which were attacked by EC109 and then treated with PBS, inactivated EC109,DC,and EC109-DC respectively. Pathology and flow cytometry were also used to study the therapeutic effect of the fusion vaccine against EC109 cells. RESULTS: Flow cytometry showed that the expression of folate receptor (FR), EC109, D Cs (D) in human nasopharyngeal carcinoma cell line (HNE1) (B) was 78.21%,89.50%,and 0.18%,respectively.The fusion cells were highly expressed. No tumor was found in the spleen, lung and liver after injection of the fusion vaccine. Human IgG was tested in peripheral blood lymphocytes (PBL). In the immune group, the latent period was longer in EC109-DC subgroup than in other subgroups, while the tumor size and weight were also smaller than those in ED subgroup. In the therapeutic group, the tumor size and weight were smaller in ED subgroup than in P, inactivated EC109 and DC subgroups. CONCLUSION: Fusion cells are highly expressed not only in FR but also in CD80.The fusion

  3. Human Sulfatase-1 Improves the Effectiveness of Cytosine Deaminase Suicide Gene Therapy with 5-Fluorocytosine Treatment on Hepatocellular Carcinoma Cell Line HepG2 In Vitro and In Vivo

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Yang; Ling Liu; Ping Wang; Sheng-Lin Ma

    2015-01-01

    Background:Human sulfatase-1 (Hsulf-l) is an endosulfatase that selectively removes sulfate groups from heparan sulfate proteoglycans (HSPGs),altering the binding of several growth factors and cytokines to HSPG to regulate cell proliferation,cell motility,and apoptosis.We investigated the role of combined cancer gene therapy with Hsulf-l and cytosine deaminase/5-fluorocytosine (CD/5-FC) suicide gene on a hepatocellular carcinoma (HCC) cell line,HepG2,in vitro and in vivo.Methods:Reverse transcription polymerase chain reaction and immunohistochemistry were used to determine the expression of Hsulf-1 in HCC.Cell apoptosis was observed through flow cytometry instrument and mechanism of Hsulf-1 to enhance the cytotoxicity of 5-FC against HCC was analyzed in HCC by confocal microscopy.We also establish a nude mice model of HCC to address the effect of Hsulf-1 expression on the CD/5-FC suicide gene therapy in vivo.Results:A significant decrease in HepG2 cell proliferation and an increase in HepG2 cell apoptosis were observed when Hsulf-1 expression was combined with the CD/5-FC gene suicide system.A noticeable bystander effect was observed when the Hsulf-1 and CD genes were co-expressed.Intracellular calcium was also increased after HepG2 cells were infected with the Hsulf-1 gene.In vivo studies showed that the suppression of tumor growth was more pronounced in animals treated with the Hsulf-1 plus CD than those treated with either gene therapy alone,and the combined treatment resulted in a significant increase in survival.Conclusions:Hsulf-1 expression combined with the CD/5-FC gene suicide system could be an effective treatment approach for HCC.

  4. Human Sulfatase-1 Improves the Effectiveness of Cytosine Deaminase Suicide Gene Therapy with 5-Fluorocytosine Treatment on Hepatocellular Carcinoma Cell Line HepG2 In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Xiao-Ping Yang

    2015-01-01

    Full Text Available Background: Human sulfatase-1 (Hsulf-1 is an endosulfatase that selectively removes sulfate groups from heparan sulfate proteoglycans (HSPGs, altering the binding of several growth factors and cytokines to HSPG to regulate cell proliferation, cell motility, and apoptosis. We investigated the role of combined cancer gene therapy with Hsulf-1 and cytosine deaminase/5-fluorocytosine (CD/5-FC suicide gene on a hepatocellular carcinoma (HCC cell line, HepG2, in vitro and in vivo. Methods: Reverse transcription polymerase chain reaction and immunohistochemistry were used to determine the expression of Hsulf-1 in HCC. Cell apoptosis was observed through flow cytometry instrument and mechanism of Hsulf-1 to enhance the cytotoxicity of 5-FC against HCC was analyzed in HCC by confocal microscopy. We also establish a nude mice model of HCC to address the effect of Hsulf-1 expression on the CD/5-FC suicide gene therapy in vivo. Results: A significant decrease in HepG2 cell proliferation and an increase in HepG2 cell apoptosis were observed when Hsulf-1 expression was combined with the CD/5-FC gene suicide system. A noticeable bystander effect was observed when the Hsulf-1 and CD genes were co-expressed. Intracellular calcium was also increased after HepG2 cells were infected with the Hsulf-1 gene. In vivo studies showed that the suppression of tumor growth was more pronounced in animals treated with the Hsulf-1 plus CD than those treated with either gene therapy alone, and the combined treatment resulted in a significant increase in survival. Conclusions: Hsulf-1 expression combined with the CD/5-FC gene suicide system could be an effective treatment approach for HCC.

  5. Dys-psychological Stress Effect on Expressions of P53 and NFκBp65 in Human Ovarian Carcinoma In Vivo

    Institute of Scientific and Technical Information of China (English)

    Li-qun Yu; Guo-lan Gao; Fun-jun Liu; Qiong-jing Zeng

    2012-01-01

    Objective:To investigate the dys-psychological stress effect on the growth of subcutaneous xenotransplanted tumor in nude mice bearing human epithelium ovarian carcinoma,and the influence on P53 and NFκBp65 expressions.Methods:The subcutaneous tumor xenografts were established by implanting human epithelium ovarian carcinoma tissues into nude mice and the dys-psychological stress model was established with restraint.The mice were randomized into the following four treatment groups with each group six mice respectively:tumor group (group A),normal saline intraperitoneal injection; tumor with stress group (group B),normal saline intraperitoneal injection;tumor therapy group (group C),cisplatin intraperitoneal injection; and tumor therapy with stress group (group D),cisplatin intraperitoneal injection.The expressions of P53 and NFκBp65 in tumor tissues were determined by Western blotting.Results:The expressions of P53 and NFκBp65 in each restraint group were enhanced compared with the control groups (P<0.05).Conclusion:The dys-psychological stress may induce the high expressions of P53 and NFκBp65 proteins and further promote tumor growth.

  6. A study to evaluate the in-vivo anticancer activity of ethanolic extract of Holoptelea integrifolia leaves against Ehrlich ascites carcinoma model using Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Pramod S. G.

    2016-10-01

    Conclusions: On the basis of the above result it was suggested that, the in-vivo anticancer activity of ethanolic extract of Holoptelea integrifolia leaves possess significant anticancer property with the dose dependent effect. This may probably due to the presence of phytochemicals such as alkaloids, phenols and flavonoids. [Int J Basic Clin Pharmacol 2016; 5(5.000: 1739-1745

  7. 利用体内噬菌体展示技术筛选膀胱癌特异性结合肽%Selection of peptide specifically binding to bladder carcinoma by using phage display in vivo

    Institute of Scientific and Technical Information of China (English)

    罗俊茜; 张帆; 杨晓峰; 罗芳; 刘杰昊; 庞建智; 闫三华; 张小雷

    2015-01-01

    目的:利用体内噬菌体展示技术筛选与人膀胱移行细胞癌特异性结合的小分子多肽。方法:将人膀胱移行细胞癌细胞BIU87接种于裸鼠体内,制备膀胱癌荷瘤小鼠模型,尾静脉注射噬菌体展示环七肽库,然后筛选与膀胱移行细胞癌特异性结合的含外源多肽的噬菌体,经过3轮体内筛选后,免疫组织化学法及ELISA法鉴定单克隆噬菌体对BIU87的亲和力。提取阳性单克隆噬菌体单链DNA进行测序,并推导出外源多肽氨基酸序列,化学合成多肽、制备分子探针后采用激光扫描共聚焦显微镜术及流式细胞术鉴定多肽对膀胱癌细胞和组织的特异性。结果:3轮体内筛选后,噬菌体富集率达到4.334×102倍。免疫组化结果显示,肿瘤组织中噬菌体肽的含量随着每一轮筛选呈增长趋势,且结合逐渐增强,同时由于噬菌体经肝、肾代谢,可见肝脏结合大量非特异性的噬菌体。 ELISA结果显示,随机挑选的30个单克隆噬菌体斑中,有24个阳性噬菌体,其中10个噬菌体对BIU87有较强的亲和力,对其测序并推导出3种多肽序列,重复率最高的序列CSSPIGRHC(8/10)命名为NYZL1。化学合成FITC-C6-NYZL1,通过激光扫描共聚焦显微镜术、流式细胞术均证明多肽NYZL1可以特异性结合膀胱癌细胞。结论:利用体内噬菌体展示技术筛选出了与人膀胱移行细胞癌特异性结合的小分子多肽NYZL1,为膀胱癌早期诊断和靶向治疗提供一定的理论依据。%Objective:To screen the peptide binding to human bladder carcinoma cells specifically by using phage display technology in vivo.Methods: Nude mice were inoculated with bladder carcinoma cells BIU87 for establishing tumor-bearing mice model.The Ph.D.-C7CTM Peptide Library was injected intravenously via tail vein.Then we screened Phage containing exogenous peptides binding to bladder transitional carcinoma cells

  8. Expression of placental protein 14 by the new endometrial cancer cell line MFE-280 in vitro and by endometrial carcinomas in vivo.

    Science.gov (United States)

    Hackenberg, R; Loos, S; Nia, A H; Kunzmann, R; Schulz, K D

    1998-01-01

    MFE-280 endometrial cancer cells express PP14 (placental protein 14) in vitro. PP14 is normally found in the secretory endometrium and in placental tissue. MFE-280 cells, which are tumorigenic in nude mice, were derived from a recurrent, poorly differentiated endometrial carcinoma. The cells were initially grown in suspension culture and later transferred to monolayer cultures. Karyotyping revealed near-diploidy with a complex heterogeneous aberration pattern. MFE-280 cells were positive for the cytokeratins 7, 8, 18 and 19 as well as for vimentin. The expression of PP14 in MFE-280 cells was demonstrated by immunochemistry and reverse transcriptase--polymerase chain reaction. PP14-mRNA was also detected in one out of five endometrial cancer specimen. In tumor tissue the expression of PP14 was not dependent on progestins.

  9. Murine breast carcinoma 4T1 cells are more sensitive to atranorin than normal epithelial NMuMG cells in vitro: Anticancer and hepatoprotective effects of atranorin in vivo.

    Science.gov (United States)

    Solár, Peter; Hrčková, Gabriela; Koptašíková, Lenka; Velebný, Samuel; Solárová, Zuzana; Bačkor, Martin

    2016-04-25

    The aim of this study was to evaluate the anticancer effect of atranorin (ATR) on murine 4T1 breast carcinoma cells and compare its sensitivity with normal mammary epithelial NMuMG cells in vitro. Anti-tumor and hepatoprotective activity of ATR-therapy was examined on mouse model of 4T1-induced cancer disease. ATR significantly reduced clonogenic ability of carcinoma 4T1 cells at the concentration of 75 μM, but clonogenicity of normal NMuMG cells was not affected by any of ATR concentrations tested. Moreover, flow cytometric and BrdU incorporation analysis did not confirm the inhibited entry into S-phase of the cell cyle after ATR incubation, and on the contrary, it induced apoptosis associated with the activation of caspase-3 and PARP cleavage in 4T1 cells. Although ATR did not cause any significant changes in Bcl-xL protein expression in NMuMG cells, an apparent depletion of Bcl-xL protein in 4T1 cells after 48 h ATR therapy was confirmed. Based on this result as well as the result of the total cell number decline, we can conclude that 4T1 cells are more sensitive to ATR therapy than NMuMG cells. ATR administration resulted in significantly longer survival time of BALB/c mice inoculated with 4T1 cells, what was associated with reduced tumor size and the higher numbers of apoptotic 4T1 cells. No differences were recorded in the number of BrdU-positive tumor cells between ATR-treated group and controls. Results indicate that ATR has rather proapoptotic than antiproliferative effect on 4T1 cells in vitro and in vivo and normal NMuMG cells are less sensitive to ATR. Furthermore, our studies revealed protective effect of ATR against oxidative stress in the livers of the tumor-bearing mice.

  10. Murine breast carcinoma 4T1 cells are more sensitive to atranorin than normal epithelial NMuMG cells in vitro: Anticancer and hepatoprotective effects of atranorin in vivo.

    Science.gov (United States)

    Solár, Peter; Hrčková, Gabriela; Koptašíková, Lenka; Velebný, Samuel; Solárová, Zuzana; Bačkor, Martin

    2016-04-25

    The aim of this study was to evaluate the anticancer effect of atranorin (ATR) on murine 4T1 breast carcinoma cells and compare its sensitivity with normal mammary epithelial NMuMG cells in vitro. Anti-tumor and hepatoprotective activity of ATR-therapy was examined on mouse model of 4T1-induced cancer disease. ATR significantly reduced clonogenic ability of carcinoma 4T1 cells at the concentration of 75 μM, but clonogenicity of normal NMuMG cells was not affected by any of ATR concentrations tested. Moreover, flow cytometric and BrdU incorporation analysis did not confirm the inhibited entry into S-phase of the cell cyle after ATR incubation, and on the contrary, it induced apoptosis associated with the activation of caspase-3 and PARP cleavage in 4T1 cells. Although ATR did not cause any significant changes in Bcl-xL protein expression in NMuMG cells, an apparent depletion of Bcl-xL protein in 4T1 cells after 48 h ATR therapy was confirmed. Based on this result as well as the result of the total cell number decline, we can conclude that 4T1 cells are more sensitive to ATR therapy than NMuMG cells. ATR administration resulted in significantly longer survival time of BALB/c mice inoculated with 4T1 cells, what was associated with reduced tumor size and the higher numbers of apoptotic 4T1 cells. No differences were recorded in the number of BrdU-positive tumor cells between ATR-treated group and controls. Results indicate that ATR has rather proapoptotic than antiproliferative effect on 4T1 cells in vitro and in vivo and normal NMuMG cells are less sensitive to ATR. Furthermore, our studies revealed protective effect of ATR against oxidative stress in the livers of the tumor-bearing mice. PMID:26969521

  11. Parotid carcinoma

    DEFF Research Database (Denmark)

    Sørensen, Kristine Bjørndal; Godballe, Christian; de Stricker, Karin;

    2006-01-01

    OBJECTIVES: Our aim is to investigate the expression of kit protein (KIT) and epidermal growth factor receptor (EGFR) in parotid carcinomas in order to correlate the expression to histology and prognosis. Further we want to perform mutation analysis of KIT-positive adenoid cystic carcinomas....... PATIENTS AND METHODS: Formalin-fixed paraffin-embedded sections from 73 patients with parotid gland carcinomas were used for the study. The sections were stained with both KIT and EGFR polyclonal antibodies. Twelve KIT-positive adenoid cystic carcinomas were examined for c-kit mutation in codon 816....... RESULTS: Of all carcinomas 25% were KIT-positive and 79% were EGFR-positive. Ninety-two percentage of the adenoid cystic carcinomas were KIT-positive. None of the adenoid cystic carcinomas had mutations in codon 816 of the c-kit gene. CONCLUSION: Neither KIT- nor EGFR-expression seem to harbour...

  12. Phenotype, functions and fate of adoptively transferred tumor draining lymphocytes activated ex vivo in mice with an aggressive weakly immunogenic mammary carcinoma

    Directory of Open Access Journals (Sweden)

    Bear Harry D

    2010-11-01

    Full Text Available Abstract Background Regression of established tumors can be induced by adoptive immunotherapy with tumor draining lymph node lymphocytes activated with bryostatin and ionomycin. We hypothesized that tumor regression is mediated by a subset of the transferred T lymphocytes, which selectively infiltrate the tumor draining lymph nodes and proliferate in vivo. Results Adoptive transfer of B/I activated tumor draining lymphocytes induces regression of advanced 4T1 tumors, and depletion of CD8, but not CD4 T cells, abrogated tumor regression in mice. The predominant mediators of tumor regression are CD8+ and derived from CD62L- T cells. Transferred lymphocytes reached their peak concentration (10.5% in the spleen 3 days after adoptive transfer and then rapidly declined. Adoptively transferred cells preferentially migrated to and/or proliferated in the tumor draining lymph nodes, peaking at day 5 (10.3% and remained up to day 28. CFSE-stained cells were seen in tumors, also peaking at day 5 (2.1%. Bryostatin and ionomycin-activated cells proliferated vigorously in vivo, with 10 generations evident in the tumor draining lymph nodes on day 3. CFSE-stained cells found in the tumor draining lymph nodes on day 3 were 30% CD8+, 72% CD4+, 95% CD44+, and 39% CD69+. Pre-treatment of recipient mice with cyclophosphamide dramatically increased the number of interferon-gamma producing cells. Conclusions Adoptively transferred CD8+ CD62Llow T cells are the principal mediators of tumor regression, and host T cells are not required. These cells infiltrate 4T1 tumors, track preferentially to tumor draining lymph nodes, have an activated phenotype, and proliferate in vivo. Cyclophosphamide pre-treatment augments the anti-tumor effect by increasing the proliferation of interferon-gamma producing cells in the adoptive host.

  13. Curcumin potentiates the antitumor effects of 5-FU in treatment of esophageal squamous carcinoma cells through downregulating the activation of NF-κB signaling pathway in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Fang Tian; Tianli Fan; Yan Zhang; Yanan Jiang; Xiaoyan Zhang

    2012-01-01

    Although constitutive activation of nuclear factor-kappaB (NF-κB) signaling pathway has been reported in multiple different human tumors,the role of NF-κB pathway in esophageal squamous ceil carcinoma (ESCC) remains illdefined.Abundant sources have provided interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer.In this study,we first analyzed the status of NF-κB pathway in the two ESCC cell lines Eca109 and EC9706,and then further investigated whether curcumin alone or in combination with 5-fluorouracil (5-FU) could modulate NF-κB pathway in vitro and in vivo.The results showed that NF-κB signaling pathway was constitutively activated in the ESCC cell lines.Curcumin suppressed the activation of NF-κB via the inhibition of IκBα phosphorylation,and downregulated the expressions of Bcl-2 and CyclinD1 in ESCC cell lines.Curcumin combined with 5-FU led to the lower cell viability and higher apoptosis than 5-FU treated alone.In a human ESCC xenograft model,curcumin or 5-FU alone reduced the tumor volume,but their combination had the strongest anticancer effects.Besides,curcumin could also inhibit NF-κB signaling pathway through downregulation of the IκBα phosphorylation and induction of cell apoptosis in vivo.Overall,our results indicated that constitutively activated NF-κB signaling pathway exists in the two ESCC cells and the chemopreventive effects of curcumin were associated with downregulation of NF-κB signaling pathway and its downstream genes.

  14. Feedback control of temperature evolution in rabbit kidney in vivo using MRI guided focused ultrasound. Application to renal VX2 carcinoma ablation

    Science.gov (United States)

    Delemazure, A. S.; Salomir, R.; Grenier, N.; Palussière, J.; Deminière, C.; Mougenot, C.; Moonen, C. W.

    2005-03-01

    A significant number of patients with small renal tumours may get benefit from in situ thermo-ablation techniques. Focused ultrasound is a non-invasive approach which offers excellent flexibility. On the other hand, real time MR thermometry is a valuable tool for monitoring and controlling therapy. In this study, coupling of focused ultrasound with PRF-based, respiratory-gated MR thermometry was used to provide temperature feedback control for local hyperthermia in the rabbit kidney. Two heating protocols were initially used in healthy kidneys (medulla and cortex): 1. fixed focal point heating; 2. spiral trajectories of the focal point. Further, five VX2 renal carcinomas were treated with multiple focal point heating in each tumour. Post-treatment MRI follow up and post mortem histology were performed. The shape and size of the lesions (MRI, histology) were compared to the calculated thermal dose map. The standard deviation of the MR thermometry ranged from 0.5°C to 1°C. The temperature controller matched the objective curve with approximately 1°C precision (fixed focal point mode). Several technical and physiological difficulties for spiral heating could not be overcome with the available setup. Thermal ablation with temperature feedback control in healthy and tumour bearing kidney was demonstrated to be feasible and effective, despite specific challenges (deep seated organ, respiratory motion, high blood perfusion).

  15. DNT cell inhibits the growth of pancreatic carcinoma via abnormal expressions of NKG2D and MICA in vivo.

    Science.gov (United States)

    Xu, Hong; Zhu, Xing-Xing; Chen, Jiong

    2016-01-01

    This research aimed to investigate the effects of natural killer group 2 member D (NKG2D) and its ligands major histocompatibility complex class I chain-related molecules A(MICA) in DNT cell killing pancreatic carcinoma. Antibodies adsorption was used to separate DNT cell from human peripheral blood. Human pancreatic tumor models were established via implanting BXPC-3 cells into nude mice. Then randomly divided mice into blank group, gemcitabine group and DNT group. Mice weights and mice tumor volumes were measured every 5 days. 50 days later mice were euthanized at cervical dislocation method. Tumor weights were measured. Relative tumor volume and tumor inhibition rate were calculated. Western blot and qPCR were used to detect the expressions of NKG2D and MICA in the transplanted tumors of the three groups. DNT cell significantly increased over time. The blank group tumor volume and weight were significantly larger than the other groups (p  0.05). Gemcitabine and DNT cell tumor inhibition rate were 40.4% and 35.5%. Western blot and qPCR showed that MICA mRNA and protein levels in blank group were significantly higher than DNT group (p = 0.001, p = 0.003). NKG2D mRNA and protein levels in blank group were significantly lower than DNT cells group (p MICA and NKG2D.

  16. Transforming properties of Felis catus papillomavirus type 2 E6 and E7 putative oncogenes in vitro and their transcriptional activity in feline squamous cell carcinoma in vivo.

    Science.gov (United States)

    Altamura, Gennaro; Corteggio, Annunziata; Pacini, Laura; Conte, Andrea; Pierantoni, Giovanna Maria; Tommasino, Massimo; Accardi, Rosita; Borzacchiello, Giuseppe

    2016-09-01

    Felis catus papillomavirus type 2 (FcaPV2) DNA is found in feline cutaneous squamous cell carcinomas (SCCs); however, its biological properties are still uncharacterized. In this study, we successfully expressed FcaPV2 E6 and E7 putative oncogenes in feline epithelial cells and demonstrated that FcaPV2 E6 binds to p53, impairing its protein level. In addition, E6 and E7 inhibited ultraviolet B (UVB)-triggered accumulation of p53, p21 and pro-apoptotic markers such as Cleaved Caspase3, Bax and Bak, suggesting a synergistic action of the virus with UV exposure in tumour pathogenesis. Furthermore, FcaPV2 E7 bound to feline pRb and impaired pRb levels, resulting in upregulation of the downstream pro-proliferative genes Cyclin A and Cdc2. Importantly, we demonstrated mRNA expression of FcaPV2 E2, E6 and E7 in feline SCC samples, strengthening the hypothesis of a causative role in the development of feline SCC. PMID:27236740

  17. BALB/c小鼠结肠癌肝转移模型建立%Establishment of colonic carcinoma liver metastasis model in BALB/c Mice

    Institute of Scientific and Technical Information of China (English)

    王跃; 刘为青; 陈明清; 张楠; 田晰晰

    2012-01-01

    Objective To establish the colonic liver metastases model in BALB/c mice. Methods BALB/c mice were randomly divided into 3 groups with injection of 0. 2ml CT-26 CRC cells (1×107ml) by intra-abdominal spleen transplanting (spleen removal group and spleen reservation group) and rectum transplanting respectively. The conditions of all the mice were observed, and the survival time and liver metastases rate were recorded. Results The colonic carcinoma liver metastasis model was established by all of the three ways. As for spleen removal group, the incidence rates of liver metastases was 100%, survival time was (28±5)days, there were lung, stomach and diaphragm transferation; as for spleen reservation group, the incidence rates of liver metastases was 95% , survival time was (30±5)days, there were lung, stomach and diaphragm transferation; as for rectum transplanting group, the incidence rates of liver metastases was 30%, survival time was (20±5)days, no lung, stomach, diaphragm metastases. Conclusion Spleen reservation group and spleen removal group has higher rates of liver metastases and longer survival time than rectum transplanting group. The modeling is more stable and better to complete the evaluation of the indicators in the observation period.%目的 建立BALB/c小鼠结肠癌肝转移模型.方法 以BALB/c小鼠为对象,随机分为3组,分别经腹腔脾脏内(分为保脾组和切脾组)、直肠粘膜内注射小鼠结肠癌CT-26细胞0.2ml(浓度为1×107 ml),观察小鼠平均生存期、成瘤情况、肝转移率、肝脏转移肿瘤大小和其他脏器的转移情况.结果 这3种方法均能建立大肠癌肝转移模型,切脾组小鼠平均生存期为(28±5)d,肝转移率为100%,均有肺、胃、膈肌转移及腹水形成,保脾组小鼠平均生存期为(30±5)d,肝转移率为95%,均有肺、胃、膈肌转移及腹水形成;直肠黏膜内注射组小鼠平均生存期为(20±5)d,肝转移率为30%,无肺、胃、膈肌

  18. Evaluation of therapy effect of 131I treatment of nasopharyngeal carcinoma xenograft mediated by hNIS gene transfection in vivo using diffusion weighted MR

    International Nuclear Information System (INIS)

    Objective: To investigate the imaging characteristic of DWI, tumor cell apoptosis and proliferation of nasopharyngeal carcinoma (NPC) xenograft transfected hNIS gene after 131I treatment. Methods: The NPC xenograft models were established with CNE-2-hNIS cells(experimental group) and CNE-2 cells(control group) respectively. After i.p. injections 131I in the experimental group and control group, the changes of xenograft tumor volume and ADC value were observed in 3, 6, 12, 18, 24 days by MR scan. The correlations of changes of ADC with pathological TUNEL, Caspase-3 immunohistochemistry of apoptosis, and Ki-67 proliferation detection were further investigated. Independent samples t-test were compared between the two groups and Pearson linear correlation analysis was used. Results: The tumor volume of the experimental group was significantly reduced compared with that of the control group after 131I treatment (t values: 8.27-19.46, P<0.05). DW-MRI showed that in the 3th day after 131I treatment, ADC values increased in the experimental group,and ADC values reached the peak in the 6th and 12th day after 131I treatment, then ADC values were decreased. ADC values after treatment was positively correlated with apoptotic index (r=0.72, P<0.05) and caspase-3 positive rate (r=0.65, P<0.05) and there was a negative correlation with Ki-67 proliferation index (r=-0.71, P<0.05). Conclusion: ADC values can reflect growth inhibition of NPC xenograft transfected hNIS gene after 131I treatment. It is possible that DW-MRI techniques can be used in early non-invasively monitor the therapy effect of 131I treatment of NPC xenografts transfected hNIS gene. (authors)

  19. Rhodamine-RCA in vivo labeling guided laser capture microdissection of cancer functional angiogenic vessels in a murine squamous cell carcinoma mouse model

    Directory of Open Access Journals (Sweden)

    Bur Monica

    2006-02-01

    Full Text Available Abstract Background Cancer growth, invasion and metastasis are highly related to tumor-associated neovasculature. The presence and progression of endothelial cells in cancer is chaotic, unorganized, and angiogenic vessels are less functional. Therefore, not all markers appearing on the chaotic endothelial cells are accessible if a drug is given through the vascular route. Identifying endothelial cell markers from functional cancer angiogenic vessels will indicate the accessibility and potential efficacy of vascular targeted therapies. Results In order to quickly and effectively identify endothelial cell markers on the functional and accessible tumor vessels, we developed a novel technique by which tumor angiogenic vessels are labeled in vivo followed by Laser Capture Microdissection of microscopically isolated endothelial cells for genomic screening. Female C3H mice (N = 5 with established SCCVII tumors were treated with Rhodamine-RCA lectin by tail vein injection, and after fluorescence microscopy showed a successful vasculature staining, LCM was then performed on frozen section tissue using the PixCell II instrument with CapSure HS caps under the Rhodamine filter. By this approach, the fluorescent angiogenic endothelial cells were successfully picked up. As a result, the total RNA concentration increased from an average of 33.4 ng/ul +/- 24.3 (mean +/- S.D. to 1913.4 ng/ul +/- 164. Relatively pure RNA was retrieved from both endothelial and epithelial cells as indicated by the 260/280 ratios (range 2.22–2.47. RT-PCR and gene electrophoresis successfully detected CD31 and Beta-Actin molecules with minimal Keratin 19 expression, which served as the negative control. Conclusion Our present study demonstrates that in vivo Rhodamine RCA angiogenic vessel labeling provided a practical approach to effectively guide functional endothelial cell isolation by laser capture microdissection with fluorescent microscopy, resulting in high quality RNA and

  20. Investigation of Combined Action of Food Supplement's and Ionizing Radiation on the Cytogenetic Damage Induction and Ehrlich Ascite Carcinoma Growth on Mice in Vivo

    Science.gov (United States)

    Sorokina, Svetlana; Zaichkina, Svetlana; Dyukina, Alsu; Rozanova, Olga; Balakin, Vladimir; Peleshko, Vladimir; Romanchenko, Sergey; Smirnova, Helena; Aptikaeva, Gella; Shemyakov, Alexander

    In recent ten years one of the major problems of modern radiobiology is the study of radiation protective mechanisms with the help of different substances as well as activation of internal resources of the organism. Internal resources mean such phenomena as hormesis and adaptive response which represent cell or body reaction on low doses of inducing factors and predetermine their further high dose effect resistance. At present special interest is attracted by studies of biological effects of low-dose-rate high-LET radiation because of searching for new types of radiation for more effective cancer therapy and searching for new methods of radiation protection. Since natural biologically active substances have low toxicity and are capable of affecting physiological processes taking place in human’s organism and increasing organism’s natural defense system, the interest to protective means of vegetal origin and search of special food supplements intensifies every year. The purpose of this study is to investigate the combined influence of food supplement, low dose rate high-LET radiation simulating high-altitude flight conditions and X-ray radiations on radiosensitivity, induction of radiation adaptive response (RAR) and growth of Ehrlich ascite carcinoma as well. Experiments were performed with males of SHK mice at the age of two months. The animals were being irradiated with low-dose-rate high-LET radiation with the dose of 11,6 cGy (0,5 cGy/day) behind the concrete shield of the 70 GeV protons accelerator (Protvino). The X-ray irradiation was carried out on the RTH device with a voltage of 200 kV (1 Gy/min; Pushchino). The diet composition included products containing big amount of biologically active substances, such as: soybeam meat, buckwheat, lettuce leaves and drug of cod-liver oil. Four groups of mice were fed with selected products mentioned above during the whole irradiation period of 22 days. The control groups received the same food without irradiation

  1. Pegylated derivatives of recombinant human arginase (rhArg1 for sustained in vivo activity in cancer therapy: preparation, characterization and analysis of their pharmacodynamics in vivo and in vitro and action upon hepatocellular carcinoma cell (HCC

    Directory of Open Access Journals (Sweden)

    Wheatley Denys N

    2009-04-01

    Full Text Available Abstract Background Protein used in medicine, e.g. interferon, are immunogenic and quickly broken down by the body. Pegylation is a recognized way of preserving their integrity and reducing immune reactions, and works well with enzymes used to degrade amino acids, a recent focus of attention in controlling cancer growth. Of the two arginine-degrading enzymes being explored clinically, arginine deiminase is a decidedly foreign mycoplasm-derived enzyme, whereas human arginase 1 is a native liver enzyme. Both have been pegylated, the former with adjuncts of 20 kD, the latter with 5 kD PEG. Pegylation is done by several different methods, not all of which are satisfactory or desirable. Methods The preparation of novel polyethylene glycol (PEG derivatives for modifying proteins is described, but directed specifically at pegylation of recombinant human arginase 1 (rhArg1. rhArg1 expressed in Escherichia coli was purified and coupled in various ways with 5 different PEG molecules to compare their protective properties and the residual enzyme activity, using hepatocellular cell lines both in vitro and in vivo. Results Methoxypolyethylene glycol-succinimidyl propionate (mPEG-SPA 5,000 coupled with very high affinity under mild conditions. The resulting pegylated enzyme (rhArg1-peg5,000 mw had up to 6 PEG chains of 5K length which not only protected it from degradation and any residual immunogenicity, but most importantly let it retain >90% of its native catalytic activity. It remained efficacious in depleting arginine in rats after a single ip injection of 1,500 U of the conjugate as the native enzyme, plasma arginine falling to >0.05 μM from ~170 μM within 20 min and lasting 6 days. The conjugate had almost the same efficacy as unpegylated rhArg1 on 2 cultured human liver cancer (HCC cell lines. It was considerably more effective than 4 other pegylated conjugates prepared. Conclusion Valuable data on the optimization of the pegylation procedure and

  2. Basisquamous Carcinoma

    Directory of Open Access Journals (Sweden)

    Yesudian Devakar P

    1997-01-01

    Full Text Available A 50 year old woman presented with an ulceroproliferative mass in the value of 4 month duration. Biopsy of the lesion showed features of a basisquamous cell carcinoma. This is a rare tumour showing histopathological features of both basal cell and squamous cell carcinomas. The clinical, histopathological and histogenetic status of this tumour are discussed.

  3. Development of a gene therapy strategy to target hepatocellular carcinoma based inhibition of protein phosphatase 2A using the α-fetoprotein promoter enhancer and pgk promoter: an in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Li Wei

    2012-11-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related deaths worldwide. Current therapies are insufficient, making HCC an intractable disease. Our previous studies confirmed that inhibition of protein phosphatase 2A (PP2A may provide a promising therapeutic strategy for cancer. Unfortunately, constitutive expression of PP2A in normal tissues limits the application of PP2A inhibition. Thus, a HCC-specific gene delivery system should be developed. The α-fetoprotein (AFP promoter is commonly used in HCC-specific gene therapy strategies; however, the utility of this approach is limited due to the weak activity of the AFP promoter. It has been shown that linking the AFP enhancer with the promoter of the non-tissue-specific, human housekeeping phosphoglycerate kinase (pgk gene can generate a strong and HCC-selective promoter. Methods We constructed a HCC-specific gene therapy system to target PP2A using the AFP enhancer/pgk promoter, and evaluated the efficiency and specificity of this system both in vitro and in vivo. Results AFP enhancer/pgk promoter-driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα exerted cytotoxic effects against an AFP-positive human hepatoma cell lines (HepG2 and Hep3B, but did not affect AFP-negative human hepatoma cells (SK-HEP-1 or normal human liver cells (L-02. Moreover, AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did not affect AFP-negative SK-HEP-1 tumors. Conclusions The novel approach of AFP enhancer/pgk promoter-driven expression of DN-PP2Acα may provide a useful cancer gene therapy strategy to selectively target HCC.

  4. Development of a gene therapy strategy to target hepatocellular carcinoma based inhibition of protein phosphatase 2A using the α-fetoprotein promoter enhancer and pgk promoter: an in vitro and in vivo study

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Current therapies are insufficient, making HCC an intractable disease. Our previous studies confirmed that inhibition of protein phosphatase 2A (PP2A) may provide a promising therapeutic strategy for cancer. Unfortunately, constitutive expression of PP2A in normal tissues limits the application of PP2A inhibition. Thus, a HCC-specific gene delivery system should be developed. The α-fetoprotein (AFP) promoter is commonly used in HCC-specific gene therapy strategies; however, the utility of this approach is limited due to the weak activity of the AFP promoter. It has been shown that linking the AFP enhancer with the promoter of the non-tissue-specific, human housekeeping phosphoglycerate kinase (pgk) gene can generate a strong and HCC-selective promoter. We constructed a HCC-specific gene therapy system to target PP2A using the AFP enhancer/pgk promoter, and evaluated the efficiency and specificity of this system both in vitro and in vivo. AFP enhancer/pgk promoter-driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα) exerted cytotoxic effects against an AFP-positive human hepatoma cell lines (HepG2 and Hep3B), but did not affect AFP-negative human hepatoma cells (SK-HEP-1) or normal human liver cells (L-02). Moreover, AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts, but did not affect AFP-negative SK-HEP-1 tumors. The novel approach of AFP enhancer/pgk promoter-driven expression of DN-PP2Acα may provide a useful cancer gene therapy strategy to selectively target HCC

  5. Targeting PCDH20 gene by microRNA-122 confers 5-FU resistance in hepatic carcinoma.

    Science.gov (United States)

    Wang, Wei; Liu, Wen Bin; Huang, Da Bing; Jia, Wei; Ji, Chu Shu; Hu, Bing

    2016-01-01

    Drug resistance is one of the main hurdles for the successful treatment of hepatic carcinoma. However, the detailed mechanisms underlying resistance remain largely unknown and therapeutic approaches are limited. In the present study, we show that miR-122 confers resistance to 5-fluorouracil induced hepatocellular carcinoma cell apoptosis in vitro and reduces the potency of 5-fluorouracil in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-122 modulates drug resistance through down-regulation of expression of PCDH20, which belongs to the protocadherin gene family and negatively regulates Akt activation. Knockdown of PCDH20 expression increases Akt phosphorylation, which leads to elevated mTOR activity and enhanced 5-fluorouracil resistance; whereas rescue of PCDH20 expression in miR-122-expressing cells decreases Akt and mTOR phosphorylation, re-sensitizing hepatocellular carcinoma cell to 5-fluorouracil induced apoptosis. Moreover, a specific and potent Akt inhibitor reverses miR-122-conferred 5-fluorouracil resistance. These findings indicate that the miR-122/PCDH20/Akt/mTOR signaling axis has an important role in mediating response to chemotherapy in human hepatocellular carcinoma. A major implication of our study is that inhibition of miR-122 or restoration of PCDH20 expression may have significant therapeutic potential to overcome drug resistance in hepatocellular carcinoma and that the combined use of an Akt inhibitor with 5-fluorouracil may increase efficacy in liver cancer treatment. PMID:27648358

  6. Sebaceous Carcinoma

    Science.gov (United States)

    ... of the Year Award Arnold P. Gold Foundation Humanism in Medicine Award Diversity Mentorship Program Eugene Van ... What causes sebaceous carcinoma? SC is rare, so scientists still have much to learn, including what causes ...

  7. [The antiviral activity of the adamantane derivatives against the influenza virus A (H1N1) pdm2009 model in vivo].

    Science.gov (United States)

    Shchelkanov, M Iu; Shibnev, V A; Finogenova, I T; Fediakina, T M; Garaev, T M; Markova, N V; Kirillov, I M

    2014-01-01

    For the first time in vivo, the model of the viral pneumonia in mice was used to study the antiviral activity against influenza A virus (H1N1) pdm09 synthetic derivatives of adamantane series including the amino acid residues and lipoid acid. It was found that the adamantane derivatives with histidine, serine, and lipoid acid could inhibit the rimantadine-resistant strain of the influenza A (H1N1) pdm09. As a result, the lifespan of the mice infected with the virus has increased by 1.6 times with respect to viral control. Thus, the possibility of restoration of antiviral properties of rimantadine both in vitro and in vivo by introducing into its molecular structure new functionally active groups was tested. PMID:25069284

  8. An ex vivo continuous passive motion model in a porcine knee for assessing primary stability of cell-free collagen gel plugs

    Directory of Open Access Journals (Sweden)

    El-Zayat Bilal

    2010-12-01

    Full Text Available Abstract Background Primary stability of cartilage repair constructs is of the utmost importance in the clinical setting but few continuous passive motion (CPM models are available. Our study aimed to establish a novel ex vivo CPM animal model and to evaluate the required motion cycles for testing the mechanical properties of a new cell-free collagen type I gel plug (CaReS®-1S. Methods A novel ex vivo CPM device was developed. Full-thickness cartilage defects (11 mm diameter by 6 mm deep were created on the medial femoral condyle of porcine knee specimens. CaReS®-1S was implanted in 16 animals and each knee underwent continuous passive motion. After 0, 2000, 4000, 6000, and 8000 motions, standardized digital pictures of the grafts were taken, focusing on the worn surfaces. The percentage of worn surface on the total CaReS®-1S surface was evaluated with image processing software. Results Significant differences in the worn surface were recorded between 0 and 2000 motion cycles (p ®-1S with an empty defect site was recorded. Conclusion The ex vivo CPM animal model is appropriate in investigating CaReS®-1S durability under continuous passive motion. 2000 motion cycles appear adequate to assess the primary stability of type I collagen gels used to repair focal chondral defects.

  9. 口腔鳞状细胞癌体内生长的昼夜生物节律特征%Circadian rhythm of oral squamous cell carcinoma in vivo

    Institute of Scientific and Technical Information of China (English)

    杨凯; 赵宁波; 陈丹; 赵丹; 唐洪; 赵春蓉

    2013-01-01

    目的:探讨口腔鳞状细胞癌体内生长的昼夜生物节律改变特征.方法:32只裸鼠置于12h光照、12h黑暗交替的环境中,将人颊鳞状细胞癌BcaCD885细胞接种于裸鼠颊部,建立颊鳞状细胞癌模型,3周后在24h内,按灯亮后4、10、16、22h4个时间点分别处死8只裸鼠时间以开灯后的小时数为参考(hours after light onset,HALO),即4HALO、10HALO、16HALO、22HALO.取出肿瘤测量体积,用流式细胞仪测定肿瘤细胞的增殖指数(proliferation index,PI)和凋亡指数(apoptosis index,AI).用余弦分析法检验肿瘤体积、肿瘤细胞PI和AI是否具有昼夜节律性,用方差分析各指标在4个时间点差异的显著性.结果:肿瘤体积和肿瘤细胞PI具有明显的昼夜节律变化特征,肿瘤体积在不同时间点的差异具有统计学意义,肿瘤体积的峰值和谷值分别出现在3.23HALO、15.23HALO,肿瘤细胞PI的峰值和谷值分别出现在6.60HALO、18.1 6HALO.肿瘤细胞的AI无昼夜节律性,但在不同时间点差异具有统计学意义.结论:体内生长的口腔鳞状细胞癌的细胞增殖活性和肿瘤体积具有昼夜节律变化特点,肿瘤体积和细胞AI在昼夜不同时间点差异变化较大.%Objective:To investigate the change of circadian rhythm in oral squamous cell carcinoma(OSCC)in vivo.Methods:Totally 32 nude mice were maintained in 12 h light alternating with 12 h dark.Human oral squamous cell carcinoma cell line BcaCD885 was transplanted subcutaneously into nude mice cheeks to develop an OSCC animal model.Mice were sacrificed at 4 different time points 4,10,16,22 h(4 hours after light onset(HALO),10HALO,16HALO,22HALO) of 24 h 3 weeks after transplantation,with 8 mice of each group.Tumors were dissected away and tumor sizes were measured.Tumor cell proliferation index(PI) and apoptosis index(AI) were determined by flow cytometry.Cosine analysis was used to detect circadian rhythm of tumor size,tumor cell PI and AI.Variance of

  10. The development of an OxyHb animal model in mice and the study on OxyHb-induced apoptosis of mouse brain cells in vivo

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective On the basis of developing a new animal model for oxyhemoglobin(OxyHb)injection into subarachnoid space in mice,this research was to explore the temporal dependence and spatial distribution of OxyHb-induced apoptosis in the mouse brain cells in vivo and the mechanism of neurocyte injury induced by OxyHb.Methods The animal model for OxyHb injection into subarachnoid space in mice was developed.Mice were divided randomly into the experimental group(n=40)and the control group(n=35).The control group ...

  11. Adenovirus mediated homozygous endometrial epithelial Pten deletion results in aggressive endometrial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Ayesha; Ellenson, Lora Hedrick, E-mail: lora.ellenson@med.cornell.edu

    2011-07-01

    Pten is the most frequently mutated gene in uterine endometriod carcinoma (UEC) and its precursor complex atypical hyperplasia (CAH). Because the mutation frequency is similar in CAH and UEC, Pten mutations are thought to occur relatively early in endometrial tumorigenesis. Previous work from our laboratory using the Pten{sup +/-} mouse model has demonstrated somatic inactivation of the wild type allele of Pten in both CAH and UEC. In the present study, we injected adenoviruses expressing Cre into the uterine lumen of adult Pten floxed mice in an attempt to somatically delete both alleles of Pten specifically in the endometrium. Our results demonstrate that biallelic inactivation of Pten results in an increased incidence of carcinoma as compared to the Pten{sup +/-} mouse model. In addition, the carcinomas were more aggressive with extension beyond the uterus into adjacent tissues and were associated with decreased expression of nuclear ER{alpha} as compared to associated CAH. Primary cultures of epithelial and stromal cells were prepared from uteri of Pten floxed mice and Pten was deleted in vitro using Cre expressing adenovirus. Pten deletion was evident in both the epithelial and stromal cells and the treatment of the primary cultures with estrogen had different effects on Akt activation as well as Cyclin D3 expression in the two purified components. This study demonstrates that somatic biallelic inactivation of Pten in endometrial epithelium in vivo results in an increased incidence and aggressiveness of endometrial carcinoma compared to mice carrying a germline deletion of one allele and provides an important in vivo and in vitro model system for understanding the genetic underpinnings of endometrial carcinoma.

  12. Adenovirus mediated homozygous endometrial epithelial Pten deletion results in aggressive endometrial carcinoma

    International Nuclear Information System (INIS)

    Pten is the most frequently mutated gene in uterine endometriod carcinoma (UEC) and its precursor complex atypical hyperplasia (CAH). Because the mutation frequency is similar in CAH and UEC, Pten mutations are thought to occur relatively early in endometrial tumorigenesis. Previous work from our laboratory using the Pten+/- mouse model has demonstrated somatic inactivation of the wild type allele of Pten in both CAH and UEC. In the present study, we injected adenoviruses expressing Cre into the uterine lumen of adult Pten floxed mice in an attempt to somatically delete both alleles of Pten specifically in the endometrium. Our results demonstrate that biallelic inactivation of Pten results in an increased incidence of carcinoma as compared to the Pten+/- mouse model. In addition, the carcinomas were more aggressive with extension beyond the uterus into adjacent tissues and were associated with decreased expression of nuclear ERα as compared to associated CAH. Primary cultures of epithelial and stromal cells were prepared from uteri of Pten floxed mice and Pten was deleted in vitro using Cre expressing adenovirus. Pten deletion was evident in both the epithelial and stromal cells and the treatment of the primary cultures with estrogen had different effects on Akt activation as well as Cyclin D3 expression in the two purified components. This study demonstrates that somatic biallelic inactivation of Pten in endometrial epithelium in vivo results in an increased incidence and aggressiveness of endometrial carcinoma compared to mice carrying a germline deletion of one allele and provides an important in vivo and in vitro model system for understanding the genetic underpinnings of endometrial carcinoma.

  13. Carcinoma vulvar

    Directory of Open Access Journals (Sweden)

    Yamit Peñas Zayas

    2015-11-01

    Full Text Available El carcinoma de la vulva tiene una incidencia de aproximadamente un 3-5% dentro de todas las enfermedades ginecológicas malignas. El 90% de los tumores malignos de la vulva está constituido por carcinoma epidermoide, el resto son adenocarcinomas, carcinomas de células basales y melanomas. Se realiza la presentación de un caso de una paciente femenina de 25 años de edad con antecedentes  de Diabetes Mellitus tipo II y trombopatia, que ingresa en el servicio de ginecología con un cuadro cutáneo polimorfo, localizado en labios mayores y menores, dado por lesiones eritematoerosivas y vegetante, sospechándose clínicamente el diagnóstico  de un carcinoma epidermoide, corroborándose el mismo histológicamente al realizarse biopsia de piel. Se indicó tratamiento con quimioterapia. Por la edad de la paciente y ser menos frecuente en mucosa que en la piel,  motivo la presentación del caso.

  14. Parathyroid carcinoma

    DEFF Research Database (Denmark)

    Qvist, N; Krøll, L; Ladefoged, C;

    1986-01-01

    Parathyroid carcinoma is a slow growing tumor, and the patients most often die from complications to the hypercalcemia. Therefore, any attempt should be made to remove local recurrence and metastasis surgically, as medical treatment is disappointing. A case treated with extensive vascular surgery...

  15. In vivo models of brain tumors: roles of genetically engineered mouse models in understanding tumor biology and use in preclinical studies.

    Science.gov (United States)

    Simeonova, Iva; Huillard, Emmanuelle

    2014-10-01

    Although our knowledge of the biology of brain tumors has increased tremendously over the past decade, progress in treatment of these deadly diseases remains modest. Developing in vivo models that faithfully mirror human diseases is essential for the validation of new therapeutic approaches. Genetically engineered mouse models (GEMMs) provide elaborate temporally and genetically controlled systems to investigate the cellular origins of brain tumors and gene function in tumorigenesis. Furthermore, they can prove to be valuable tools for testing targeted therapies. In this review, we discuss GEMMs of brain tumors, focusing on gliomas and medulloblastomas. We describe how they provide critical insights into the molecular and cellular events involved in the initiation and maintenance of brain tumors, and illustrate their use in preclinical drug testing.

  16. Arterially transplanted mesenchymal stem cells in a mouse reversible unilateral ureteral obstruction model: in vivo bioluminescence imaging and effects on renal fibrosis

    Institute of Scientific and Technical Information of China (English)

    BAI Zhi-ming; DENG Xiang-dong; LI Jin-dong; LI Dong-hui; CAO Hui; LIU Zhen-xiang; ZHANG Jie

    2013-01-01

    Background Chronic kidney disease (CDK) is a worldwide health problem,but there is currently no effective treatment that can completely cure this disease.Recently,studies with mesenchymal stem cells (MSCs) on treating various renal diseases have shown breakthroughs.This study is to observe the homing features of MSCs transplanted via kidney artery and effects on renal fibrosis in a reversible unilateral ureteral obstruction (R-UUO) model.Methods Thirty-six Balb/c mice were divided into UUO group,UUO-MSC group,and sham group randomly,with 12 mice in each group.The MSCs had been infected by a lentiviral vector to express stably the luciferase reporter gene and green fluorescence protein genes (Luc-GFP-MSC).Homing of MSCs was tracked using in vivo imaging system (IVIS) 1,3,14,and 28 days after transplantation.Imaging results were verified by detecting GFP expression in frozen section under a fluorescence microscope.E-cadherin,α-SMA,TGF-β1,and TNF-α mRNA expression in all groups at 1 and 4 weeks after transplantation were analyzed by quantitative PCR.Results Transplanted Luc-GFP-MSCs showed increased Luciferase expression 3 days after transplantation.The expression decreased from 7 days,weakened thereafter and could not be detected 14 days after transplantation.Quantitative PCR results showed that all gene expressions in UUO group and UUO-MSC group at 1 week had no statistical difference,while at 4 weeks,except TGF-β expression (P>0.05),the expression of E-cadherin,α-SMA,and TNF-α in the above two groups have statistical difference (P<0.01).Conclusion IVIS enables fast,noninvasive,and intuitive tracking of MSC homing in vivo.MSCs can be taken home to kidney tissues of the diseased side in R-UUO model,and renal interstitial fibrosis can be improved as well.

  17. In vivo degradation of magnesium plate/screw osteosynthesis implant systems: Soft and hard tissue response in a calvarial model in miniature pigs.

    Science.gov (United States)

    Schaller, Benoit; Saulacic, Nikola; Imwinkelried, Thomas; Beck, Stefan; Liu, Edwin Wei Yang; Gralla, Jan; Nakahara, Ken; Hofstetter, Willy; Iizuka, Tateyuki

    2016-03-01

    Biodegradable magnesium plate/screw osteosynthesis systems were implanted on the frontal bone of adult miniature pigs. The chosen implant geometries were based on existing titanium systems used for the treatment of facial fractures. The aim of this study was to evaluate the in vivo degradation and tissue response of the magnesium alloy WE43 with and without a plasma electrolytic surface coating. Of 14 animals, 6 received magnesium implants with surface modification (coated), 6 without surface modification (uncoated), and 2 titanium implants. Radiological examination of the skull was performed at 1, 4, and 8 weeks post-implantation. After euthanasia at 12 and 24 weeks, X-ray, computed tomography, and microfocus computed tomography analyses and histological and histomorphological examinations of the bone/implant blocks were performed. The results showed a good tolerance of the plate/screw system without wound healing disturbance. In the radiological examination, gas pocket formation was found mainly around the uncoated plates 4 weeks after surgery. The micro-CT and histological analyses showed significantly lower corrosion rates and increased bone density and bone implant contact area around the coated screws compared to the uncoated screws at both endpoints. This study shows promising results for the further development of coated magnesium implants for the osteosynthesis of the facial skeleton. PMID:26805919

  18. Thyroid cancer - medullary carcinoma

    Science.gov (United States)

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. MTC is very rare. It can occur in children and adults. Unlike other types ...

  19. Basal Cell Carcinoma (BCC)

    Science.gov (United States)

    ... epithelioma, is the most common form of skin cancer. Basal cell carcinoma usually occurs on sun-damaged skin, especially ... other health issues. Infiltrating or morpheaform basal cell carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive ...

  20. Inhibitory effect of N-isoquinoline-3-carbonyl-L-Glycine-benzylester on human esophageal carcinoma cells in vitro and in vivo%IQ-G-OBzl 对人食管癌细胞体内外抑制作用的研究

    Institute of Scientific and Technical Information of China (English)

    杨国栋; 张晓英; 冯志松; 任权; 江毅敏

    2014-01-01

    目的:探讨N-异喹啉-3-羧酸-L-甘氨酸苄酯( IQ-G-OBzl)对人食管癌细胞的体内外抑制作用。`方法①体外实验:人食管癌细胞分为5-FU组、L-甘氨酸苄酯组、3-羧酸异喹啉组及IQ-G-OBzl组,分别采用相应药物干预;MTT法检测药物对细胞的IC50值;流式细胞仪检测细胞内活性氧( ROS)水平。②体内实验:制作115只小鼠食管癌移植瘤模型,分为生理盐水组、IQ-G-OBzl组、L-甘氨酸苄酯组、3-羧酸异喹组及5-FU组,分别给予相应药物干预后计算抑瘤率。结果在体外实验中IQ-G-OBzl 组的IC50高于5-FU组,但低于L-甘氨酸苄酯组、3-羧酸异喹啉组(P<0.05);IQ-G-OBzl组细胞内ROS水平明显高于L-甘氨酸苄酯组、3-羧酸异喹组及生理盐水组(P<0.05)。体内实验中IQ-G-OBzl组抑瘤率高于L-甘氨酸苄酯组及3-羧酸异喹组(P<0.05)。结论 IQ-G-OBzl体内、外均有抗食管癌作用;其作用机制可能为升高细胞内ROS水平。%Objective To investigate antitumor ability of N-isoquinoline-3-carbonyl-L-Glycine-benzylester ( IQ-G-OB-zl)on the human esophageal carcinoma cells in vitro and in vivo .Methods ①In vitro test:there were four groups in vitro test and esophageal carcinoma cells were treated with 5-FU, (L-Gly-OBzl), IQ and IQ-G-OBzl, respectively;MTT assays were performed to assess the IC 50;Intracellular reactive oxygen species ( ROS) were detected by flow cytometry .②In vivo test:the model of esophageal carcinoma in 115 nude mice was established;there were five groups in vivo test ( NS, IQ-G-OBzl, L-G-OBzl, IQ and IQ-G-OBzl) and were treated with each compound respectively .then weight of tumor was meas-ured, the inhibition rate of tumor was calculated .Results In vitro test, the IC50 of IQ-G-OBzl group was higher than that of 5-FU group, but less than that of L-Gly-OBzl and IQ groups(P<0.05).In vivo test, the inhibition rate of IQ-G-OBzl group was higher than that

  1. Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

    Energy Technology Data Exchange (ETDEWEB)

    Galanzha, Ekaterina I. [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Zharov, Vladimir P., E-mail: zharovvladimirp@uams.edu [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2013-12-10

    Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1–10 CTC/mL) due to the small volume of blood samples (5–10 mL). Consequently, they can miss up to 10{sup 3}–10{sup 4} CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 10{sup 2}–10{sup 3} times) by the examination of the entire blood volume in vivo (5 L in adults). We focus on in vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL) and throughput (up to 10 mL/min) than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-resolution PAFC beyond the diffraction and spectral limits.

  2. Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

    Directory of Open Access Journals (Sweden)

    Ekaterina I. Galanzha

    2013-12-01

    Full Text Available Despite progress in detecting circulating tumor cells (CTCs, existing assays still have low sensitivity (1–10 CTC/mL due to the small volume of blood samples (5–10 mL. Consequently, they can miss up to 103–104 CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 102–103 times by the examination of the entire blood volume in vivo (5 L in adults. We focus on in vivo photoacoustic (PA flow cytometry (PAFC of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL and throughput (up to 10 mL/min than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-rsesolution PAFC beyond the diffraction and spectral limits.

  3. Carcinoma verrugoso

    Directory of Open Access Journals (Sweden)

    Esteban Quesada Jiménez

    2004-09-01

    Full Text Available Se presenta el caso de un paciente masculino de 76 años, vecino de Turrialba, agricultor, que consultó por una lesión de 3 años de evolución, localizada en la palma de la mano derecha a nivel palmar y compromiso de los dedos de la misma mano, caracterizada como una neoformación exofítica verrugosa de 5 por 11 cm. aproximadamente, con material caseoso entre sus crestas. La lesión ha estado creciendo de forma acelerada en los últimos 3 meses, causándole dolor y que le imposibilita ellaborar. Se le realizaron exámenes y se descartaron varias causas infecciosas, y concluyendo luego de varias biopsias con el diagnóstico de un carcinoma verrugoso. El paciente fue tratado mediante una amputación parcial de la mano. Este tumor es una variante del carcinoma epidermoide y presentamos su clasificación, patogénesis, histopatología, manifestaciones clínicas más frecuentes y diagnóstico diferencial.A 76 year old farmer from Turrialba (Cartago, presented with a 3 year old lesion of his right pal and proximal fingers. It was exophitic, wart like, and it measured 5x11 cm, draining caseous material from its crests. The lesion had grows quickly for the last 3 months and it became tender to the point of making impossible for him to work. A series of tests were done to rule out other possible infections causes, after several biopsies the diagnosis of verrocous carcinoma was made. The patient underwent a partial amputation of his hand. This tumor is considered a from of squamous cell carcinoma, we present here its classification, pathogenesis, histopathology, clinical manifestations and diferential diagnosis.

  4. The development of an OxyHb animal model in mice and the study on OxyHb-induced apoptosis of mouse brain cells in vivo

    Institute of Scientific and Technical Information of China (English)

    Shi Wei; Wang Ruizhi; Huang Liyong; Sun Jianjun; Wang Fangru; Liu Chongxiao; Zhou Le; Guo Zhenyu; John H Zhang

    2008-01-01

    Objective On the basis of developing a new animal model for oxyhemoglobin (OxyHb) injection into subarachnoid space in mice, this research was to explore the temporal dependence and spatial distribution of OxyHb- induced apoptosis in the mouse brain cells in vivo and the mechanism of neurocyte injury induced by OxyHb. Methods The animal model for OxyHb injection into subarachnoid space in mice was developed. Mice were divided randomly into the experimental group (n=40) and the control group (n= 35). The control group received saline injection (50 μL ) and the experimental group received OxyHb injection (50 μL ), both into the subarachnoid space. The mice of the two groups were subdivided according to different postoperative time (3 h, 6 h, 12 h, 24 h and 48 h). The apoptosis or necrosis of cells was distinguished with microscopy (HE staining), transmission electron microscopy and TUNEL method. Results The distribution of apoptosis was mainly in the ipsilateral neocortex and bilateral hippocampal gyrus. The apoptotic mouse brain cells showed morphological changes in the experimental group by HE staining and transmission electron microscopy. The count of TUNEL-positive cells showed substantial increase in the experimental group, and there was a significant difference between the control and experimental groups, and the number of OxyHb- induced apoptotic cells decreased with time. Conclusion OxyHb in subarachnoid space in mice can induce apoptasis, but not necrosis of mouse brain cells in viro. The apoptotic brain cells show the pattern of temporal dependence and spatial distribution. It is suggested that the early treatment should be the method of first choice for treating the hemorrhagic brain injury.

  5. Effects of acetylsalicylic acid and acetic acid solutions on VX2 liver carcinoma in rabbits: in vivo analysis Efeitos das soluções de aspirina e de ácido acético em fígado de coelhos portadores de tumor hepático VX2: análise in vivo

    Directory of Open Access Journals (Sweden)

    Rogério Saad-Hossne

    2007-08-01

    Full Text Available PURPOSE: To analyze, in vitro, the effects of acetylsalicylic acid (aspirin and acetic acid solutions on VX2 carcinoma cells in the liver of rabbits with VX2 hepatic tumors; to determine the histolytic and anatomopathological characteristics of the solutions; and to evaluate the eventual biochemical and hepatic changes. METHODS: A total of 48 rabbits were evaluated. The animals were randomized into two groups, protocol 3 (study group and protocol 4 (controls, and each group was then subdivided into 3 subgroups. Four days after implantation of the tumor in the liver, median laparotomy was performed with a 0.4-ml injection of a solution of either aspirin (5.0%, acetic acid (5.0% or saline. The animals were sacrificed after 24 hours (protocol 3 or after 11 days (protocol 4. Body weight, clinical evolution and biochemical levels, as well as the abdominal and thoracic cavities, were evaluated, and liver microscopy was performed. RESULTS: No changes in clinical evolution, body weight or biochemical levels were reported. However, an increase in alkaline phosphatase was observed in protocol 4 (controls. The tumor was eliminated in both protocols. CONCLUSION: Acetylsalicylic acid and acetic acid solutions cause the destruction of experimental hepatic tumors.OBJETIVO: Analisar os efeitos das soluções de aspirina e de ácido acético, in vivo, em fígado de coelhos portadores de tumor hepático VX2, verificando o efeito histolítico e anatomo-patológico das soluções e eventuais alterações bioquímicas hepáticas. MÉTODOS: Utilizou-se 48 coelhos, divididos em 2 protocolos experimentais(3 e 4, subdivididos em 3 grupos cada. Após 4 dias da implantação do tumor no fígado, procedeu-se a laparotomia mediana, com injeção de 0,4 ml da solução de aspirina (5,0%, de ácido acético (5,0% e solução salina; o sacrifício ocorreu apos 24 horas (protocolo 3 e 11 dias (protocolo 4; avaliou-se o peso, evolução clinica, dosagens bioquímicas, cavidade

  6. Carcinoma verrugoso

    Directory of Open Access Journals (Sweden)

    Esteban Quesada Jiménez

    2004-09-01

    Full Text Available Se presenta el caso de un paciente masculino de 76 años, vecino de Turrialba, agricultor, que consultó por una lesión de 3 años de evolución, localizada en la palma de la mano derecha a nivel palmar y compromiso de los dedos de la misma mano, caracterizada como una neoformación exofítica verrugosa de 5 por 11 cm. aproximadamente, con material caseoso entre sus crestas. La lesión ha estado creciendo de forma acelerada en los últimos 3 meses, causándole dolor y que le imposibilita ellaborar. Se le realizaron exámenes y se descartaron varias causas infecciosas, y concluyendo luego de varias biopsias con el diagnóstico de un carcinoma verrugoso. El paciente fue tratado mediante una amputación parcial de la mano. Este tumor es una variante del carcinoma epidermoide y presentamos su clasificación, patogénesis, histopatología, manifestaciones clínicas más frecuentes y diagnóstico diferencial.

  7. Vulvar carcinoma

    International Nuclear Information System (INIS)

    Purpose: Controversies exist regarding the use of radiation therapy in the treatment of vulvar carcinoma. A retrospective review was performed to evaluate our institution's experience with surgery and radiation for this disease. Methods and Materials: The medical records of 47 patients treated for squamous cell carcinoma of the vulva at our institution (1974-1992) were reviewed for TNM stage (AJCC criteria), treatment modality, and associated 5-year local control and survival based on Kaplan-Meier analysis. Results: Twenty-eight patients (60%) presented with Stage I and II disease and their 5-year survival was 69%. Stage III patients accounted for 12 (25%) of the patients and their 5-year survival was 73%. Seven patients presented with Stage IV disease and five died within 13 months of diagnosis after predominantly palliative therapy. The 40 patients with Stages I, II, and III disease were treated aggressively and were further evaluated for treatment-modality-associated survival and local control. Radiation therapy was used as primary treatment in nine patients, of whom seven were treated with radiation alone and two were treated postoperatively after wide excision. Surgery alone was performed in 31 patients consisting of either radical vulvectomy (20 patients) or wide excision (11 patients). When comparing outcomes of radical vulvectomy vs. radiation therapy, we noted that the 5-year actuarial survivals were comparable (74% for either modality), despite the presence of more favorable prognostic factors in the group treated with radical vulvectomy. Patients treated with wide excision alone had a trend for a poorer 5-year actuarial survival (51%) and local control (50%). Conclusions: Radical vulvectomy offers good locoregional control and survival. This retrospective review further supports the use of radiation therapy with conservative surgery as an alternative treatment option for patients with vulvar carcinoma treated with curative intent. In contrast, the use of

  8. Identification of HRAS as cancer-promoting gene in gastric carcinoma cell aggressiveness

    Science.gov (United States)

    Wu, Xiao Yu; Liu, Wen Tao; Wu, Zhen Feng; Chen, Che; Liu, Jia Yun; Wu, Guan Nan; Yao, Xue Quan; Liu, Fu Kun; Li, Gang

    2016-01-01

    Gastric carcinoma is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that HRAS is markedly up-regulated in gastric carcinoma. Prognostic analysis indicated that HRAS expression might be a prognostic indicator for the survival of patients with gastric carcinoma. Ectopic expression of HRAS in gastric carcinoma cells accelerated proliferation, migration, invasion, angiogenesis, and clone formation ability of gastric carcinoma cells in vitro. Furthermore, HRAS over-expressing significantly promoted the tumorigenicity of gastric carcinoma cells in vivo whereas silencing endogenous HRAS caused opposite outcomes. Moreover, we demonstrated that HRAS enhanced gastric carcinoma aggressiveness by activating VEGFA/PI3K/AKT pathway and Raf-1 signaling. Together, our results provide new evidence that HRAS overexpression promotes the progression of gastric carcinoma and might represent a novel therapeutic target for its treatment. PMID:27725900

  9. Discovery of a novel anticancer agent with both anti-topoisomerase I and II activities in hepatocellular carcinoma SK-Hep-1 cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.

    Science.gov (United States)

    Perng, Daw-Shyong; Tsai, Yu-Hsin; Cherng, Jonathan; Wang, Jeng-Shing; Chou, Kuo-Shen; Shih, Chia-Wen; Cherng, Jaw-Ming

    2016-01-01

    Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine for various applications. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human hepatocellular carcinoma SK-Hep-1 cell line. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by mitochondrial membrane potential loss, activation of caspase-3 and caspase-9, increase in the DNA content in sub-G1, and morphological characteristics of apoptosis, including blebbing of plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments, suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2, prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against SK-Hep-1 cells is accompanied by downregulations of NF-κB-binding activity, inflammatory responses involving cyclooxygenase-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and volume of acidic compartments. Similar effects (including all of the above-mentioned effects) were found in other tested cell lines, including human hepatocellular carcinoma Hep 3B, lung adenocarcinoma A549, squamous cell carcinoma NCI-H520, colorectal adenocarcinoma COLO 205, and T-lymphoblastic MOLT-3 (results not shown). Our data suggest that 2-MCA could be a potential agent for anticancer therapy. PMID:26792981

  10. Prostata carcinomas

    International Nuclear Information System (INIS)

    Pre-operative staging, using transrectal prostatic sonography and CT, was carried out in 30 patients with cytologically confirmed carcinomas of the prostate and the results compared with the clinical findings. All patients underwent radical prostatectomy and the pre-operative findings could be verified histologically. Transrectal prostatic sonography is better than CT or clinical examination for determining local tumour spread or penetration of the capsule. A high proportion of enlarged pelvic lymphnodes shown by CT had non-specific changes; failure to demonstrate enlarged nodes excludes lymph node metastases with considerable certainty. Transrectal prostatic sonography provides a higher degree of information regarding local tumour spread, whereas CT indicates the presence or absence of lymph node metastases. (orig.)

  11. Nevoid Basal Cell Carcinoma Syndrome

    Science.gov (United States)

    ... Nevoid Basal Cell Carcinoma Syndrome Request Permissions Nevoid Basal Cell Carcinoma Syndrome Approved by the Cancer.Net Editorial Board , 04/2016 What is Nevoid Basal Cell Carcinoma Syndrome? Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is ...

  12. Biodistribution of BPA in a thyroid undifferentiated carcinoma model

    Energy Technology Data Exchange (ETDEWEB)

    Dagrosa, M.A.; Viaggi, M.; Kreimann, E.; Garavaglia, R.; Farias, S.; Juvenal, G.J.; Pisarev, M.A. [Argentine Atomic Energy Commission (CNEA), Buenos Aires (Argentina)

    2000-10-01

    BPA uptake was studied both in vitro and in vivo. A significant greater uptake by a thyroid undifferentiated human carcinoma cell line (ARO) was found when compared to normal bovine and human adenoma cells. When the ARO cells were transplanted into nude mice BPA uptake by the tumor was 4 times greater than normal thyroid and 8 times greater than blood. These results open the possibility of applying BNCT to the treatment of thyroid undifferentiated carcinoma. (author)

  13. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. ...

  14. Thyroid cancer - papillary carcinoma

    Science.gov (United States)

    Papillary carcinoma of the thyroid ... About 80% of all thyroid cancers diagnosed in the United States are the papillary carcinoma type. It is more common in women than in men. It may occur in childhood, but is most often seen ...

  15. Undifferentiated salivary gland carcinomas

    DEFF Research Database (Denmark)

    Herbst, H.; Hamilton-Dutoit, S.; Jakel, K.T.;

    2004-01-01

    Undifferentiated salivary gland carcinomas may be divided into small cell and large cell types. Among large cell undifferentiated carcinomas, lymphoepithelial carcinomas have to be distinguished, the latter of which are endemic in the Arctic regions and southern China where virtually all cases...... of these tumors are associated with the Epstein-Barr virus (EBV). Association with EBV may also be observed in sporadic cases, and detection of EBV gene products may aid their diagnosis. Immunohistology may be employed to resolve the differential diagnosis of undifferentiated salivary gland carcinomas, comprising...... malignant lymphomas, amelanotic melanomas, Merkel cell carcinomas, and adenoid cystic carcinomas, in particular in small biopsy materials. Because of the rarity of undifferentiated salivary gland carcinomas, the differential diagnosis should always include metastases of undifferentiated carcinomas arising...

  16. Antitumor Properties of Modified Detonation Nanodiamonds and Sorbed Doxorubicin on the Model of Ehrlich Ascites Carcinoma.

    Science.gov (United States)

    Medvedeva, N N; Zhukov, E L; Inzhevatkin, E V; Bezzabotnov, V E

    2016-01-01

    We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds. PMID:26742746

  17. The use of the CELLection kit in the isolation of carcinoma cells from mononuclear cell suspensions

    DEFF Research Database (Denmark)

    Werther, K; Normark, M; Hansen, B F;

    2000-01-01

    antibody Ber-EP4 was used as the primary capture antibody. In order to permit phenotyping of the isolated carcinoma cells the magnetic beads were removed from the carcinoma cells by DN'ase digestion of the DNA linker between the magnetic bead and the secondary antibody. In an ex vivo model system...

  18. Hepatocellular carcinoma.

    Science.gov (United States)

    Edwards, J T; Macdonald, G A

    2000-05-01

    The incidence of hepatocellular carcinoma (HCC) appears to be declining in Taiwan and potentially in other high-prevalence areas as a consequence of vaccination for hepatitis B virus (HBV). However, there is evidence that the incidence of HCC is increasing in North America and Europe. This appears to be related to the increasing prevalence and duration of hepatitis C virus (HCV) infection in these countries. There is also growing evidence to support an increase in the risk of HCC in patients with HCV who are coinfected with occult HBV (patients who have lost HBV surface antigen but still have detectable HBV DNA either in blood or liver). Occult HBV infection in patients with HCV may be more common than previously thought, and HCC that occurs in this setting appears to have a worse prognosis. There is continuing interest in the effect of interferon therapy on the incidence of HCC in patients with HCV. Several studies from Japan have shown a benefit in patients without cirrhosis, although there are a number of potentially confounding variables that may partly explain these results. Prospective randomized studies are needed to investigate this important question. The molecular biology of HCC and the events of malignant transformation in the liver continue to be areas of intense study. Recently, there has been considerable interest in telomeres, the repeat units on the ends of chromosomes, and the enzyme that maintains these, telomerase. Telomeres shorten with each cell division and can be used to determine the number of divisions a cell has undergone. Eventually they reach a critical length, with further loss resulting in cellular senescence. Telomerase restores telomere length and may help malignant cells escape senescence. Nearly all HCCs have telomerase activity and assessments of telomeres and telomerase may be clinically useful. PMID:17023886

  19. Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Somi

    2005-09-01

    Full Text Available IntroductionHepatocellular carcinoma (HCC is one of the most common malignant tumors worldwide(1, with over four hundred thousand new cases and almost as many deaths each year(2. The incidence ranges from <10 cases per 100,000 population in North America and Western Europe to 50-150 cases per 100,000 population in parts of Africa and Asia where HCC is responsible for a large proportion of cancer deaths. Studies from the USA, UK, mainland Europe and Australia have shown a rising incidence of HCC(3-6, which probably relates to the increasing prevalence of hepatitis B and C due to immigration(7. Improved care for individuals with cirrhosis has resulted in prolonged and a relatively greater opportunity for malignant changes to develop. HCC is a disease of multifactorial etiology; the development of a carcinoma in a given individual is a multi-step process and the result of an accumulation of risks. It is estimated that persistent infection with hepatotrophic viruses account for well over 80% of the world's liver cancer(8. Hepatocellular carcinoma is the major cause of death in cirrhotic patients in Europe(9,10,11. Once cirrhosis is present, up to 20% of patients will develop HCC over 10 years(12. Genetic alterations are fundamental to the development of HCC by resulting in uncontrolled cellular proliferation and de-differentiation. Without treatment, the prognosis is dismal, with only a few months survival(13. Several surgical and non-surgical therapeutic modalities have been used for the treatment of HCC. Surgical resection, liver transplantation and local ablation therapies demonstrate potentially curative treatment options that should always be considered when the tumor is restricted to liver.EpidemiologyThe incidence of HCC varies widely by geographic location. The distribution of HCC also differs among ethnic groups and regions within the same country(14. High incidence regions (more than 15 cases per 100,000 populations per year include sub

  20. Cryotherapy for hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Awad, Tahany; Thorlund, Kristian; Gluud, Christian

    2009-01-01

    BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy for...... the treatment of hepatocellular carcinoma. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by...... hepatocellular carcinoma. Randomised clinical trials with low-risk of bias may help in defining the role of cryotherapy in the treatment of hepatocellular carcinoma....

  1. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

    OpenAIRE

    Faria, J.

    1985-01-01

    The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

  2. In-vivo fluorescence detection and imaging of porphyrin-producing bacteria in the human skin and in the oral cavity for diagnosis of acne vulgaris, caries, and squamous cell carcinoma

    Science.gov (United States)

    Koenig, Karsten; Schneckenburger, Herbert; Hemmer, Joerg; Tromberg, Bruce J.; Steiner, Rudolf W.

    1994-05-01

    Certain bacteria are able to synthesize metal-free fluorescent porphyrins and can therefore be detected by sensitive autofluorescence measurements in the red spectral region. The porphyrin-producing bacterium Propionibacterium acnes, which is involved in the pathogenesis of acne vulgaris, was localized in human skin. Spectrally resolved fluorescence images of bacteria distribution in the face were obtained by a slow-scan CCD camera combined with a tunable liquid crystal filter. The structured autofluorescence of dental caries and dental plaque in the red is caused by oral bacteria, like Bacteroides or Actinomyces odontolyticus. `Caries images' were created by time-gated imaging in the ns-region after ultrashort laser excitation. Time-gated measurements allow the suppression of backscattered light and non-porphyrin autofluorescence. Biopsies of oral squamous cell carcinoma exhibited red autofluorescence in necrotic regions and high concentrations of the porphyrin-producing bacterium Pseudomonas aerigunosa. These studies suggest that the temporal and spectral characteristics of bacterial autofluorescence can be used in the diagnosis and treatment of a variety of diseases.

  3. Discovery of a novel anti-cancer agent targeting both topoisomerase I and II in hepatocellular carcinoma Hep 3B cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.

    Science.gov (United States)

    Perng, Daw-Shyong; Tsai, Yu-Hsin; Cherng, Jonathan; Kuo, Chih-Wei; Shiao, Chih-Chung; Cherng, Jaw-Ming

    2016-08-01

    Cinnamomum verum has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, in hepatocellular carcinoma Hep 3B cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, increase in the DNA content in sub G1, and morphological characteristics of apoptosis. 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against Hep 3B cells is accompanied by downregulations of NF-κB binding activity, inflammatory responses involving COX-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy. PMID:26707867

  4. Hepatocellular carcinoma.

    Science.gov (United States)

    Okuda, K

    2000-01-01

    Hepatocellular carcinoma (HCC) is increasing in many countries as a result of an increase in hepatitis C virus (HCV) infection since World War II. The epidemiology of HCC varies with the global region. There have been conflicting observations from different parts of the world concerning the frequency of HCC in patients who in the distant past had post-transfusion non-A, non-B hepatitis. The genetic basis of hepatocarcinogenesis is still poorly understood. In hepatitis B virus (HVB) associated HCC, codon 249 mutation in the p 53 gene seems more related to exposure to aflatoxin B1 than to hepatocarcinogenesis itself. HCC that occurs in children in high HBV endemic regions could be associated with germ-line mutations, but little information is available; not much is known about chemical hepatocarcinogens in the environment other than aflatoxins. The X gene of HBV seems to play an important role in HBV-associated hepatocarcinogenesis. There are preliminary observations on the molecular mechanism of HCV-associated HCC, such as HCV core protein inducing HCC in transgenic mice and the NS3 genome transforming NIH 3T3 cells. Pathological distinction between preneoplastic and very early transformed lesions still depends on classical morphology, and a more genetically oriented differential diagnosis is required. Clinical diagnosis based on modern imaging has improved greatly, but is still unsatisfactory in the differential diagnosis of preneoplastic and early transformed nodules, because the vasculature changes that occur within the nodule are not accurately discerned with the current imaging. Use of sensitive des-gamma-carboxy prothrombin (PIVKA II) assay, and lectin affinity chromatography separating HCC specific subspecies of AFP molecules with a more practical biochemical technique will further improve diagnosis. Early diagnosis and transplantation are the best treatment at the moment, but transplantation is not widely available because of the donor shortage. Despite

  5. miR-1 suppresses the growth of esophageal squamous cell carcinoma in vivo and in vitro through the downregulation of MET, cyclin D1 and CDK4 expression

    Science.gov (United States)

    JIANG, SEN; ZHAO, CHAO; YANG, XIAODI; LI, XIANGYANG; PAN, QING; HUANG, HAIJIN; WEN, XUYANG; SHAN, HUSHENG; LI, QIANWEN; DU, YUNXIANG; ZHAO, YAPING

    2016-01-01

    Several aberrant microRNAs (miRNAs or miRs) have been implicated in esophageal cancer (EC), which is widely prevalent in China. However, their role in EC tumorigenesis has not yet been fully elucidated. In the present study, we determined that miR-1 was downregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent non-neoplastic tissues using RT-qPCR, and confirmed this using an ESCC cell line. Using a nude mouse xenograft model, we confirmed that the re-expression of miR-1 significantly inhibited ESCC tumor growth. A tetrazolium assay and a trypan blue exclusion assay revealed that miR-1 suppressed ESCC cell proliferation and increased apoptosis, whereas the silencing of miR-1 promoted cell proliferation and decreased apoptosis, suggesting that miR-1 is a novel tumor suppressor. To elucidate the molecular mechanisms of action of miR-1 in ESCC, we investigated putative targets using bioinformatics tools. MET, cyclin D1 and cyclin-dependent kinase 4 (CDK4), which are involved in the hepatocyte growth factor (HGF)/MET signaling pathway, were found to be targets of miR-1. miR-1 expression inversely correlated with MET, cyclin D1 and CDK4 expression in ESCC cells. miR-1 directly targeted MET, cyclin D1 and CDK4, suppressing ESCC cell growth. The newly identified miR-1/MET/cyclin D1/CDK4 axis provides new insight into the molecular mechanisms of ESCC pathogenesis and indicates a novel strategy for the diagnosis and treatment of ESCC. PMID:27247259

  6. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs;

    2009-01-01

    UNLABELLED: Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case...... of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

  7. Metachronous colorectal carcinoma

    DEFF Research Database (Denmark)

    Bülow, Steffen; Svendsen, L B; Mellemgaard, A

    1990-01-01

    During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous...... colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation....... We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals....

  8. URACHAL CARCINOMA IN BLADDER

    Institute of Scientific and Technical Information of China (English)

    薛丽燕; 吕宁; 何祖根; 林冬梅; 刘秀云

    2004-01-01

    Objective: To investigate the clinicopathologic features and diagnostic criteria of urachal carcinoma in the bladder.Methods: Seven cases of urachal carcinoma in the bladder were analyzed retrospectively. Results: All the tumors were found locating in the dome of bladder. Of them, 4 were mucinous adenocarcinoma, one was well differentiated papillary enteric adenocarcinoma, one was well differentiated squamous carcinoma, and one was neuroendocrine carcinoma. Cystomorphous urachal remnants were found in 4 cases. The main complaint was hematuria and all patients underwent partial excision of bladder and urachus. Conclusion: Mucinous adenocarcinoma is the main histo-pathological type, and cystomorphous urachal remnants are often accompanied with urachal carcinoma in the bladder. The key diagnostic criteria of urachal carcinoma in bladder are site and histopathology. And to examine the specimens carefully to find the urachal remnants is important.

  9. Molecular Mechanism of Cinnamomum verum Component Cuminaldehyde Inhibits Cell Growth and Induces Cell Death in Human Lung Squamous Cell Carcinoma NCI-H520 Cells In Vitro and In Vivo.

    Science.gov (United States)

    Yang, Shu-Mei; Tsai, Kuen-Daw; Wong, Ho-Yiu; Liu, Yi-Heng; Chen, Ta-Wei; Cherng, Jonathan; Hsu, Kwang-Ching; Ang, Yao-Uh; Cherng, Jaw-Ming

    2016-01-01

    Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the effects and the molecular mechanisms of cuminaldehyde (CuA), a constituent of the bark of Cinnamomum verum, on human lung squamous cell carcinoma NCI-H520 cells. Specifically, cell viability was evaluated by colorimetric assay; cytotoxicity by LDH release; apoptosis was determined by Western blotting, and morphological analysis with, acridine orange and neutral red stainings and comet assay; topoisomerase I activity was assessed using assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VAC) were evaluated with neutral red staining. The results show that CuA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and a down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, and morphological characteristics of apoptosis, including blebbing of the plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. In addition, CuA also induced lysosomal vacuolation with increased VAC, cytotoxicity, as well as suppressions of both topoisomerase I and II activities in a dose-dependent manner. Further study revealed the growth-inhibitory effect of CuA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of CuA against NCI-H520 cells is accompanied by downregulations of proliferative control involving apoptosis and both topoisomerase I and II activities, and upregulation of lysosomal with increased VAC and cytotoxicity. Similar effects were found in other cell lines, including human lung adenocarcinoma A549 cells and colorectal adenocarcinoma COLO 205 (results not

  10. Alpha-tomatine attenuation of in vivo growth of subcutaneous and orthotopic xenograft tumors of human prostate carcinoma PC-3 cells is accompanied by inactivation of nuclear factor-kappa B signaling.

    Directory of Open Access Journals (Sweden)

    Sui-Ting Lee

    Full Text Available BACKGROUND: Nuclear factor-kappa B (NF-κB plays a role in prostate cancer and agents that suppress its activation may inhibit development or progression of this malignancy. Alpha (α-tomatine is the major saponin present in tomato (Lycopersicon esculentum and we have previously reported that it suppresses tumor necrosis factor-alpha (TNF-α-induced nuclear translocation of nuclear factor-kappa B (NF-κB in androgen-independent prostate cancer PC-3 cells and also potently induces apoptosis of these cells. However, the precise mechanism by which α-tomatine suppresses NF-κB nuclear translocation is yet to be elucidated and the anti-tumor activity of this agent in vivo has not been examined. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we show that suppression of NF-κB activation by α-tomatine occurs through inhibition of I kappa B alpha (IκBα kinase activity, leading to sequential suppression of IκBα phosphorylation, IκBα degradation, NF-κB/p65 phosphorylation, and NF-κB p50/p65 nuclear translocation. Consistent with its ability to induce apoptosis, α-tomatine reduced TNF-α induced activation of the pro-survival mediator Akt and its inhibition of NF-κB activation was accompanied by significant reduction in the expression of NF-κB-dependent anti-apoptotic (c-IAP1, c-IAP2, Bcl-2, Bcl-xL, XIAP and survivin proteins. We also evaluated the antitumor activity of α-tomatine against PC-3 cell tumors grown subcutaneously and orthotopically in mice. Our data indicate that intraperitoneal administration of α-tomatine significantly attenuates the growth of PC-3 cell tumors grown at both sites. Analysis of tumor material indicates that the tumor suppressing effects of α-tomatine were accompanied by increased apoptosis and lower proliferation of tumor cells as well as reduced nuclear translocation of the p50 and p65 components of NF-κB. CONCLUSION/SIGNIFICANCE: Our study provides first evidence for in vivo antitumor efficacy of

  11. Porcine Ex Vivo intestinal segment model

    OpenAIRE

    Ripken, D.; Hendriks, H.F.J.

    2015-01-01

    This chapter describes the use of the porcine ex vivo intestinal segment model. This includes the advantages and disadvantages of the segment model and a detailed description of the isolation and culture as well as the applications of the porcine ex vivo intestinal segment model in practice. Compared to the Ussing chamber (Chap. 24) the porcine ex vivo small intestinal segment model is a relatively simple to use intestinal tissue model. The main difference being that the tissue segment is not...

  12. Porcine Ex Vivo intestinal segment model

    NARCIS (Netherlands)

    Ripken, D.; Hendriks, H. F J

    2015-01-01

    This chapter describes the use of the porcine ex vivo intestinal segment model. This includes the advantages and disadvantages of the segment model and a detailed description of the isolation and culture as well as the applications of the porcine ex vivo intestinal segment model in practice. Compare

  13. Porcine Ex Vivo intestinal segment model

    NARCIS (Netherlands)

    Ripken, D.; Hendriks, H.F.J.

    2015-01-01

    This chapter describes the use of the porcine ex vivo intestinal segment model. This includes the advantages and disadvantages of the segment model and a detailed description of the isolation and culture as well as the applications of the porcine ex vivo intestinal segment model in practice. Comp

  14. Inhibition effects of Somatostatin on hepatocellular carcinoma in vitro and in vivo%生长抑素作用Cmet抑制肝细胞癌生长的研究

    Institute of Scientific and Technical Information of China (English)

    华贇鹏; 梁力健; 黄洁夫

    2003-01-01

    Objective:To observe the effects of Somatostatin on the proliferation,invasion and adhesion of Bel7402 hepatocellular carcinoma(HCC) cell line and on the growth of HCC xenografts in nude mice.Methods:Nude mice bearing xenografts of cell line were treated with Somatostatin or saline control for 7 weeks after tumor implantation. The effect of Somatostatin on proliferative ability of Bel7402 cells was observed by MTT chromometry.The cell morphologic change was observed by light microscope, the adhesive and invasive ability of 7402 cells by cell adhesion and migration experiments, the Cmet (hepatocyte growth factor repceptor) expression, the cell cycle of 7402 cells and the expression of SSTR2 (somatostatin receptor 2) in 7402 cells by immunofluorescence flow cytometry.Results:The mean tumor weight in mice given Somatostatin was significantly lower than that of the control group. After the treatment with Somatostatin, the proliferative ability and cell form of 7402 cells didn't change significantly, the adhesive and invasive ability decreased significantly; the ratio of cells in resting state (G0/G1) increased, but no apoptosis peak was observed. The Cmet expression in 7402 cells decreased significantly and SSTR2 was detected in 44.3% of 7402 cells.Conclusions: Somatostatin could inhibit the growth of HCC by combining with SSTR. It may be an important mechanism for Somatostatin to inhibit tumor by decreasing the Cmet expression in HCC cells, rather than by killing the liver cancer cells or inducing apoptosis directly.%目的观察生长抑素(Somatostatin,SST)对Bel7402肝癌细胞株以及裸鼠种植瘤生长的影响,同时探索SST的抑瘤机制.方法以裸鼠人肝癌转移模型为材料,观察SST对种植瘤生长的影响.以MTT法测量SST对Bel7402细胞增殖的影响,光镜下观察细胞形态的变化.以细胞迁移实验和粘附实验观察细胞侵袭和粘附能力的影响.以流式细胞仪测量细胞周期及细胞表面肝细胞生长因子

  15. Multiple primary bronchogenic carcinomas.

    Science.gov (United States)

    Yang, X; Ji, H; Paljarvi, L; Soimakallio, S

    1996-07-01

    Multiple primary bronchogenic carcinomas (MPBCa) are extremely rare. The differentiation of a MPBCa from a pulmonary metastasis due to an extrathoracic neoplasm is sometimes difficult. We reviewed 324 pathologically proved primary pulmonary carcinomas and found six cases of MPBCa (1.9%). We herewith present the series and discuss the diagnosis of MPBCa. PMID:21594435

  16. Primary cutaneous myoepithelial carcinoma

    DEFF Research Database (Denmark)

    Frost, Markus Winther; Steiniche, Torben; Damsgaard, Tine Engberg;

    2013-01-01

    This study describes a case of primary myoepithelial carcinoma of the skin and reviews the available literature on this topic. Myoepitheliomas and carcinomas arise most frequently from myoepithelial cells within the salivary glands but are found in many anatomical locations. We documented a case...

  17. Salivary gland carcinomas

    DEFF Research Database (Denmark)

    Therkildsen, M H; Andersen, L J; Christensen, M;

    1998-01-01

    The prognosis of salivary gland carcinomas is difficult to assess. Simple mucin-type carbohydrates (T and sialosyl-T antigens, Tn and sialosyl-Tn antigens) have been shown to be of value in predicting prognosis for carcinomas in other locations. We studied the prognostic significance...... of the expression of these structures in a retrospective study of 133 patients with salivary gland carcinomas, using immunohistochemistry and a panel of well-defined monoclonal antibodies (MAbs) on formalin-fixed paraffin-embedded tissues. Sialosyl-Tn, T and sialosyl-T antigens were not correlated with prognosis...

  18. Derived vascular endothelial cells induced by mucoepidermoid carcinoma cells: 3-dimensional collagen matrix model*

    OpenAIRE

    Yang, Sen; Guo, Li-Juan; Gao, Qing-hong; Xuan, Ming; Tan, Ke; Zhang, Qiang; Wen, Yu-ming; Wang, Chang-mei; Tang, Xiu-fa; Wang, Xiao-yi

    2010-01-01

    Mucoepidermoid carcinoma undergoes uniquely vigorous angiogenic and neovascularization processes, possibly due to proliferation of vascular endothelial cells (ECs) induced by mucoepidermoid carcinoma cells (MCCs) in their three-dimensional (3D) microenvironment. To date, no studies have dealt with tumor cells and vascular ECs from the same origin of mucoepidermoid carcinoma using the in vitro 3D microenvironment model. In this context, the current research aims to observe neovascularization w...

  19. Cyclooxygenases in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Melchiorre Cervello; Giuseppe Montalto

    2006-01-01

    Many epidemiological studies demonstrate that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) reduce the incidence and mortality of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase (COX) enzymes are well-known targets of NSAIDs. However, conventional NSAIDs nonselectively inhibit both the constitutive form COX-1, and the inducible form COX-2. Recent evidence indicates that COX-2 is an important molecular target for anticancer therapies. Its expression is undetectable in most normal tissues, and is highly induced by proinflammatory cytokines, mitogens, tumor promoters and growth factors. It is now well-established that COX-2 is chronically overexpressed in many premalignant, malignant, and metastastic cancers, including hepatocellular carcinoma (HCC). Overexpression of COX-2 in patients with HCC is generally higher in welldifferentiated HCCs compared with less-differentiated HCCs or histologically normal liver, suggesting that COX-2 may be involved in the early stages of hepatocarcinogenesis, and increased expression of COX-2 in noncancerous liver tissue has been significantly associated with shorter disease-free survival in patients with HCC.In tumors, overexpression of COX-2 leads to an increase in prostaglandin (PG) levels, which affect many mechanisms involved in carcinogenesis, such as angiogenesis, inhibition of apoptosis, stimulation of cell growth as well as the invasiveness and metastatic potential of tumor ceils. The availability of novel agents that selectively inhibit COX-2 (COXIB), has contributed to shedding light on the role of this molecule. Experimental studies on animal models of liver cancer have shown that NSAIDs, including both selective and non-selective COX-2 inhibitors, exert chemopreventive as well as therapeutic effects. However, the key mechanism by which COX-2 inhibitors affect HCC cell growth is as yet not fully understood. Increasing evidence suggests the involvement of molecular targets other

  20. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids.

    Directory of Open Access Journals (Sweden)

    Cynthia A Batchelder

    Full Text Available Renal cell carcinomas arise from the nephron but are heterogeneous in disease biology, clinical behavior, prognosis, and response to systemic therapy. Development of patient-specific in vitro models that efficiently and faithfully reproduce the in vivo phenotype may provide a means to develop personalized therapies for this diverse carcinoma. Studies to maintain and model tumor phenotypes in vitro were conducted with emerging three-dimensional culture techniques and natural scaffolding materials. Human renal cell carcinomas were individually characterized by histology, immunohistochemistry, and quantitative PCR to establish the characteristics of each tumor. Isolated cells were cultured on renal extracellular matrix and compared to a novel polysaccharide scaffold to assess cell-scaffold interactions, development of organoids, and maintenance of gene expression signatures over time in culture. Renal cell carcinomas cultured on renal extracellular matrix repopulated tubules or vessel lumens in renal pyramids and medullary rays, but cells were not observed in glomeruli or outer cortical regions of the scaffold. In the polysaccharide scaffold, renal cell carcinomas formed aggregates that were loosely attached to the scaffold or free-floating within the matrix. Molecular analysis of cell-scaffold constructs including immunohistochemistry and quantitative PCR demonstrated that individual tumor phenotypes could be sustained for up to 21 days in culture on both scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures. The use of three-dimensional scaffolds to engineer a personalized in vitro renal cell carcinoma model provides opportunities to advance understanding of this disease.

  1. Functional Role and Therapeutic Potential of the Pim-1 Kinase in Colon Carcinoma

    Directory of Open Access Journals (Sweden)

    Ulrike Weirauch

    2013-07-01

    Full Text Available PURPOSE: The provirus integration site for Moloney murine leukemia virus 1 (Pim-1 kinase is overexpressed in various tumors and has been linked to poor prognosis. Its role as proto-oncogene is based on several Pim-1 target proteins involved in pivotal cellular processes. Here, we explore the functional relevance of Pim-1 in colon carcinoma. EXPERIMENTAL DESIGN: RNAi-based knockdown approaches, as well as a specific small molecule inhibitor, were used to inhibit Pim-1 in colon carcinoma cells. The effects were analyzed regarding proliferation, apoptosis, sensitization toward cytostatic treatment, and overall antitumor effect in vitro and in mouse tumor models in vivo. RESULTS: We demonstrate antiproliferative, proapoptotic, and overall antitumor effects of Pim-1 inhibition. The sensitization to 5-fluorouracil (5-FU treatment upon Pim-1 knockdown offers new possibilities for combinatorial treatment approaches. Importantly, this also antagonizes a 5-FU-triggered Pim-1 up-regulation, which is mediated by decreased levels of miR-15b, a microRNA we newly identify to regulate Pim-1. The analysis of the molecular effects of Pim-1 inhibition reveals a complex regulatory network, with therapeutic Pim-1 repression leading to major changes in oncogenic signal transduction with regard to p21Cip1/WAF1, STAT3, c-jun-N-terminal kinase (JNK, c-Myc, and survivin and in the levels of apoptosis-related proteins Puma, Bax, and Bcl-xL. CONCLUSIONS: We demonstrate that Pim-1 plays a pivotal role in several tumor-relevant signaling pathways and establish the functional relevance of Pim-1 in colon carcinoma. Our results also substantiate the RNAi-mediated Pim-1 knockdown based on polymeric polyethylenimine/ small interfering RNA nanoparticles as a promising therapeutic approach.

  2. MEDULLARY THYROID CARCINOMA

    OpenAIRE

    V S Medvedev; P. A. Isayev; Ilyin, A. A.; D. Yu. Semin; V. V. Polkin; D. N. Derbugov; S. V. Vasilkov

    2013-01-01

    Medullary thyroid carcinoma belongs to orphan diseases affecting a small part of the population. Multicenter trials are required to elaborate a diagnostic algorithm, to define treatment policy, and to predict an outcome.

  3. MEDULLARY THYROID CARCINOMA

    Directory of Open Access Journals (Sweden)

    V. S. Medvedev

    2013-01-01

    Full Text Available Medullary thyroid carcinoma belongs to orphan diseases affecting a small part of the population. Multicenter trials are required to elaborate a diagnostic algorithm, to define treatment policy, and to predict an outcome.

  4. Merkel Cell Carcinoma

    Science.gov (United States)

    ... of the Year Award Arnold P. Gold Foundation Humanism in Medicine Award Diversity Mentorship Program Eugene Van ... 300 PUVA treatments. What causes Merkel cell carcinoma? Scientists are still studying what causes this skin cancer. ...

  5. Pathobiology of ovarian carcinomas

    Institute of Scientific and Technical Information of China (English)

    Mojgan Devouassoux-Shisheboran; Catherine Genestie

    2015-01-01

    Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.

  6. Papillary thyroid carcinoma

    DEFF Research Database (Denmark)

    Godballe, C; Asschenfeldt, P; Sørensen, J A;

    1994-01-01

    The age influence on the prognosis of papillary thyroid carcinoma was analyzed in a group of 67 patients. A marked decline in cause-specific survival was found for patients older than 60 years of age at the time of diagnosis. In order to find a tumor-biological explanation of the prognostic...... invasion and distant metastases. The results indicate that 60 years of age the time of diagnosis may be the "prognostic break-point" for papillary thyroid carcinoma....

  7. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

    Directory of Open Access Journals (Sweden)

    Kucuk Omer

    2007-01-01

    Full Text Available Abstract Background We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC model established in our laboratory. Methods The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. Results In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Conclusion Our studies in both RCC and prostate tumor models demonstrate that the

  8. Concurrent versus sequential sorafenib therapy in combination with radiation for hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Aaron T Wild

    Full Text Available Sorafenib (SOR is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC. However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design.

  9. Dynamic Observation on In vivo Bioluminescence Imaging of Experimental Metastatic Animal Models in Nude Mice%实验性肿瘤细胞转移动物模型的活体成像观察

    Institute of Scientific and Technical Information of China (English)

    闫明霞; 朱淼鑫; 刘蕾; 李静; 林河春; 赵方瑜; 姚明

    2012-01-01

    Objective To observe the tumor metastasis in deep organisms of the nude mice by in vivo bioluminescence imaging system. Methods The SMMC-7721-GFP/Luc cells with different concentrations were intravenously inoculated into the tail vein and spleen of the BALB/c-nu/nu mice, the distribution and expression of luciferase in nude mice were monitored by in vivo bioluminescence imaging system. Results The experimental metastatic animal models had been successfully established. The distribution and expression of luciferase ascended with cell concentration increased and decreased with the passage of time. Conclusion The in vivo bioluminescence imaging system may monitor the in vivo growth and metastasis of tumors and provide for studying the mechanisms of tumor metastasis and development of anticancer drug.%目的 利用小动物活体成像系统观察肿瘤细胞在动物体内的转移情况.方法 分别将不同浓度的绿色荧光蛋白(GPF)和荧光素酶(luciferase,Luc)双标的SMMC-7721细胞接种入裸小鼠尾静脉和脾,建立实验性转移动物模型,采用活体成像技术监测不同浓度的细胞在小鼠体内的转移情况,动态观察同一细胞于不同时间点在小鼠体内的转移情况.结果 成功建立了尾静脉接种肺转移及脾内接种肝转移的实验性转移动物模型,经小动物活体成像系统检测发现,随着接种细胞浓度的增加,荧光素的表达面积和强度逐渐增加,二者呈正比关系;随着接种时间的延长,荧光素的表达面积和强度逐渐减弱,二者呈成反比关系.结论 活体荧光成像系统可较好地观测肿瘤在动物体内深部脏器的转移情况,它将为肿瘤转移机制、抗转移治疗等研究提供有益的帮助.

  10. Enhanced thymidine kinase gene vector and its killing effect on nasopharyngeal carcinoma in vitro and in vivo%增强型胸苷激酶基因表达载体的构建及其杀伤鼻咽癌细胞的实验研究

    Institute of Scientific and Technical Information of China (English)

    申聪香; 文忠; 钱宇虹; 关小芳; 牟少凤

    2010-01-01

    .01).⑤体内实验结果显示,增强型靶向表达载体对裸鼠鼻咽癌移植瘤生长具有明显抑制作用,抑瘤率达56.3%,与对照组比较,差异有统计学意义(P<0.01),而裸鼠肝肾病理检查未发现明显损害.结论 以hTERT/CMV双调控机制介导TK基因的增强型表达载体能够高效、靶向杀伤鼻咽癌细胞及移植瘤,实验动物体内应用无明显毒副作用.%Objective To construct a modified and enhanced thymidine kinase (TK) vector regulated by human telemerase catalytic subunit promoter (hTERT) promoter and cytomegaiovirus (CMV) enhancer and its killing effect on nasopharyngeal carcinoma in vitro and in vivo and its safety in vivo. Methods The pGL3-basic,as basic vector template,was linked and constructed into TK vector regulated by hTKRT promoter and CMV enhancer with mono-promoter vector as control. Enhanced TK expression was confirmed by fluorescent microscopy and real time fluorescent quantitative PCR. Telomerase activity was measured by stretch PCR. Tumour killing effects were examined by MTT and Boyden areole. The effects of enhanced TK on the invasiveness of tumor cell NPC 5-8F and the growth of xenograft implanted in nude mice were investigated. Results Compared with non-enhanced vector, TK expressed by the enhanced vector significantly increased in NPC 5-8F and MCF-7 cells,telomerase activity was positive in human in NPC 5-8F cells and breast cancer MCF-7 cells and negative in control human blood vessel endothelium ECV-304 cells. After ganciclovir (GCV) treatment, NPC 5-8F cell survival rate and invasiveness decreased and tumor progress of NPC xenograft implanted in nude mice was inhibited, without obvious toxicity effects on mouse liver and kidney. Conclusions The enhanced TK vector regulated by hTERT promoter and CMV enhancer can obviously and specifically inhibit and kill nasopharyngeal carcinoma cells in culture and nasopharyngeal carcinoma xenograft in nude mice in vivo, without obviously toxic side

  11. Plumbagin induces the apoptosis of human tongue carcinoma cells through the mitochondria-mediated pathway

    OpenAIRE

    Qiu, Jia-Xuan; He, Yuan-qiao; Wang, Yong; Xu, Ru-liang; Qin, You; Shen, Xiang; Zhou, Shu-Feng; Mao, Zong-Fu

    2013-01-01

    Background Plumbagin, a quinonoid constituent isolated from the root of Plumbago zeylanica L., has been proven to possess anti-tumor activity both in vitro and in vivo. However, its anti-tumor properties for human tongue carcinoma have not been reported. This study aimed to investigate the inhibitory effect and the underlying mechanism of plumbagin on the growth of human tongue carcinoma cells. Material/Methods Cell proliferation ability was detected by EdU incorporation assay and colony form...

  12. Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma

    OpenAIRE

    Han, Xiangkun; Li, Fuming; Fang, Zhaoyuan; Gao, Yijun; Li, Fei; Fang, Rong; Yao, Shun; Sun, Yihua; Li, Li; Zhang, Wenjing; Ma, Huimin; Xiao, Qian; Ge, Gaoxiang; Fang, Jing; Wang, Hongda

    2014-01-01

    Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that redu...

  13. Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1–RAGE and AKT pathways

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Ping; Dai, Weiqi; Wang, Fan; Lu, Jie; Shen, Miao; Chen, Kan; Li, Jingjing; Zhang, Yan; Wang, Chengfen; Yang, Jing; Zhu, Rong; Zhang, Huawei; Zheng, Yuanyuan; Guo, Chuan-Yong, E-mail: guochuanyong@hotmail.com; Xu, Ling, E-mail: xuling606@sina.com

    2014-01-24

    Highlights: • Ethyl pyruvate inhibits liver cancer. • Promotes apoptosis. • Decreased the expression of HMGB1, p-Akt. - Abstract: Ethyl pyruvate (EP) was recently identified as a stable lipophilic derivative of pyruvic acid with significant antineoplastic activities. The high mobility group box-B1 (HMGB1)–receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. We tried to observe the effects of ethyl pyruvate on liver cancer growth and explored its effects in hepatocellular carcinoma model. In this study, three hepatocellular carcinoma cell lines were treated with ethyl pyruvate. An MTT colorimetric assay was used to assess the effects of EP on cell proliferation. Flow cytometry and TUNEL assays were used to analyze apoptosis. Real-time PCR, Western blotting and immunofluorescence demonstrated ethyl pyruvate reduced the HMGB1–RAGE and AKT pathways. The results of hepatoma orthotopic tumor model verified the antitumor effects of ethyl pyruvate in vivo. EP could induce apoptosis and slow the growth of liver cancer. Moreover, EP decreased the expression of HMGB1, RAGE, p-AKT and matrix metallopeptidase-9 (MMP9) and increased the Bax/Bcl-2 ratio. In conclusion, this study demonstrates that ethyl pyruvate induces apoptosis and cell-cycle arrest in G phase in hepatocellular carcinoma cells, plays a critical role in the treatment of cancer.

  14. Synchronous thyroid carcinoma and squamous cell carcinoma. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Seo [Chonnam National Univ. School of Dentistry, Kwangju (Korea, Republic of)

    2006-12-15

    Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (SCC) is unusual. This report presents a synchronous thyroid carcinoma and squamous cell carcinoma in the anterior palate region of a 41-year-old man. The clinical, radiologic, and histologic features are described. At 10-month follow-up after operation, no evidence of recurrence ana metastasis was present.

  15. [Merkel cell skin carcinoma].

    Science.gov (United States)

    Krejcí, K; Zadrazil, J; Tichý, T; Horák, P; Ciferská, H; Hodulová, M; Zezulová, M; Zlevorová, M

    2010-01-01

    Merkel cell carcinoma is a rare tumour of the skin. It affects predominantly elderly Caucasian males on sun-exposed areas of the skin. Distinctively more frequent and at significantly lower age, its incidence is higher in immunocompromised patients. In these patients we often observe the highly aggressive course of Merkel cell carcinoma and a fatal outcome. The incidence of Merkel cell carcinoma has been rising in recent years and is more dramatic than the increased incidence of cutaneous melanoma. More than one-third of Merkel cell carcinoma patients will die from this cancer, making it twice as lethal as melanoma. The malignant transformation of Merkel cells is currently thought to be related to an infection with Merkel cell polyomavirus. In the early stage the discreet clinical picture may be contrary to extensive microscopic invasion and this seemingly benign appearance can delay diagnosis or increase the risk of insufficient tumour excision. The diagnosis is definitely confirmed by histological evaluation and immunohistochemical tests. A typical feature is the tendency of Merkel cell carcinoma to frequent local recurrence and early metastasizing into regional lymph nodes with subsequent tumour generalization. The mainstay of therapy is radical excision of the tumour and adjuvant radiotherapy targeted at the site of primary incidence and local draining lymph nodes. The efficacy of different chemotherapy protocols in Merkel cell carcinoma is limited and the median survival rate is measured in months. In the future, prophylaxis with vaccination against Merkel cell polyomavirus will hopefully be possible in high-risk patients, as well as therapeutic usage of antisense oligonucleotides or microRNAs, eventually complete Merkel cell carcinoma elimination by affecting the tumour suppressor gene Atonal homolog 1 expression. The staging of the tumour at time of diagnosis is the most important prognostic factor. In this respect, the importance of preventative skin

  16. Early onset sebaceous carcinoma

    Directory of Open Access Journals (Sweden)

    Kaltreider Sara A

    2011-09-01

    Full Text Available Abstract Background Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression. Findings A detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided. A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues. Discussion This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.

  17. Optical diagnosis of mammary ductal carcinoma using advanced optical technology

    Science.gov (United States)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-02-01

    Clinical imaging techniques for diagnosing breast cancer mainly include X-ray mammography, ultrasound, and magnetic resonance imaging (MRI), which have respective drawbacks. Multiphoton microscopy (MPM) has become a potentially attractive optical technique to bridge the current gap in clinical utility. In this paper, MPM was used to image normal and ductal cancerous breast tissues, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our results showed that MPM has the ability to exhibit the microstructure of normal breast tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions at the molecular level comparable to histopathology. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time histological diagnosis of mammary ductal carcinoma in vivo.

  18. Effects and mechanism of the circadian clock gene Per1 on the proliferation, apoptosis, cycle, and tumorigenicityin vivo of human oral squamous cell carcinoma%生物钟基因Per1对人口腔鳞状细胞癌细胞增殖、凋亡、细胞周期和体内成瘤的影响及机理

    Institute of Scientific and Technical Information of China (English)

    付小娟; 杨凯; 李晗雪; 赵钦; 陈丹

    2016-01-01

    Objective To determine the regulatory effects of the circadian clock gene Per1 on cell cycle-related genes and its influence on the proliferation, apoptosis, cycle, and tumorigenicity in vivo of human oral squamous cell carcinoma SCC15 cells. Methods Three groups of the short hairpin RNA (shRNA) of lentivirus recombinant plasmids were designed against the RNA of Per1 and then transfected to the SCC15 cells. The optimum interference group was screened through Western blot and quantitative real-time PCR (qRT-PCR) and assigned as the experimental group. The transfected lentivirus plasmid without an interference effect on any gene was set as the control group (Control-shRNA). Untreated SCC15 cells were set as the blank group. The mRNA expressions of cell cycle-related genes, namely, Per1, p53, Cyclin D1, Cyclin E, Cyclin A2, Cyclin B1, CDK1, CDK2, CDK4, CDK6, p16, p21, Wee1, cdc25, E2F, and Rb1, in each group were detected through qRT-PCR. The cell proliferation, apoptosis, and cell cycle distribution in each group were evaluated through flow cytometry. The cells of the experimental group and the blank group were subcutaneously inoculated in nude mice to observe tumorigenesis. Results Three groups of Per1-shRNA lentivirus plasmids were constructed successfully. Among the groups, the Per1-shRNA-Ⅰgroup exhibited the highest interference effect, as indicated by qRT-PCR and Western blot analysis. As such, this group was set as the experimental group. The mRNA expression levels of CyclinD1, CyclinE, CyclinB1, CDK1, and Wee1 gene in the Per1-shRNA-Ⅰgroup were significantly higher than those in the Control-shRNA group and the SCC15 group (P0.05). The mRNA expression levels of CDK2, CDK4, CDK6, E2F, and Rb1 did not significantly differed in the three groups (P>0.05). The proliferation index of the Per1-shRNA-Ⅰgroup was significantly higher than those of the Control-shRNA group and the SCC15 group (P0.05). The tumorigenic ability in vivo was significantly enhanced in the

  19. JAK Kinase Inhibition Abrogates STAT3 Activation and Head and Neck Squamous Cell Carcinoma Tumor Growth

    Directory of Open Access Journals (Sweden)

    Malabika Sen

    2015-03-01

    Full Text Available Aberrant activation of the Janus kinase (JAK/signal transducer and activator of transcription (STAT 3 has been implicated in cell proliferation and survival of many cancers including head and neck squamous cell carcinoma (HNSCC. AZD1480, an orally active pharmacologic inhibitor of JAK1/JAK2, has been tested in several cancer models. In the present study, the in vitro and in vivo effects of AZD1480 were evaluated in HNSCC preclinical models to test the potential use of JAK kinase inhibition for HNSCC therapy. AZD1480 treatment decreased HNSCC proliferation in HNSCC cell lines with half maximal effective concentration (EC50 values ranging from 0.9 to 4 μM in conjunction with reduction of pSTAT3Tyr705 expression. In vivo antitumor efficacy of AZD1480 was demonstrated in patient-derived xenograft (PDX models derived from two independent HNSCC tumors. Oral administration of AZD1480 reduced tumor growth in conjunction with decreased pSTAT3Tyr705 expression that was observed in both PDX models. These findings suggest that the JAK1/2 inhibitors abrogate STAT3 signaling and may be effective in HNSCC treatment approaches.

  20. Correlation between high-resolution CT and pathologic findings of tumor in pulmonary carcinoma

    International Nuclear Information System (INIS)

    To determine the value of high-resolution CT (HRCT) in the diagnosis of pulmonary carcinoma, HRCT was performed in vivo before operation and radiographic and pathologic findings of inflated and fixed lungs were examined after operation (22 primary cases). Only three of 14 adenocarcinomas and three of six squamous cell carcinomas showed ill-defined margins and adjacent subtle high-attenuation areas, representing the alveoli on the lining by neoplastic cells or infiltration of lymphatic cells surrounding the tumor. In the other 16 cases, including two cases of small cell carcinoma, well-defined margins represented mucus secretion or filling entirely with neoplastic cells within alveoli

  1. 胃肠道肿瘤细胞生物标志物的7.0 T磁共振波谱分析%Ex vivo H1-MRS for evaluation of human gastrointestinal carcinoma with 7.0 T NMR spectrometer

    Institute of Scientific and Technical Information of China (English)

    欧阳庆; 黄冉冉; 谢磊; 马树华; 张炯; 肖毅锋

    2014-01-01

    目的:采用7.0 T 高频MRI设备尝试发现胃肠道肿瘤细胞(胃癌)代谢物的脂肪酸相关代谢物在磁共振波谱(MRS)上所呈现的生物学标识特征,分子水平综合分析胃肠道肿瘤脂肪酸波谱特异性表现,为临床在体胃癌MRS 诊断提供依据。方法培养收集正常胃黏膜上皮细胞系GES-1和胃癌细胞系低分化胃癌细胞BGC-823,采用7.0 T MRI检测完整细胞的氢质子波谱,并定量计算谱线中主要脂肪酸代谢物的浓度,采用两独立样本t检验对浓度进行比较。结果 GES-1细胞株与BGC-823细胞株具有不同的波谱特征, GES-1细胞的脂肪酸相关代谢物浓度明显高于BGC-823细胞,其中脂质甲基为2.796±0.975∶0.943±0.629(P<0.001),脂质亚甲基为14.660±5.106∶4.473±2.296(P<0.001),N-乙酰神经氨酸为2.638±1.080∶0.528±0.734(P<0.001)。结论离体细胞株MRS研究可以提供肿瘤细胞分子水平更多相关信息,能反映细胞的生理状态,综合分析两类细胞株波谱特征能更全面地获取胃癌演变过程中代谢物变化信息,为MRS在胃肠道肿瘤的相关研究及临床应用提供一定的理论依据。%Objective The aim of the present study was to examine the metabolic profile of normal and tumoral gastric cell with ex vivo high resolution magnetic resonance spectrometer (7.0 T NMR) to get information on the molecular steps involved in gastric carcinogenesis and the identification of biochemical markers useful for the development of in vivo MRS methodologies to diagnose gastric carcinoma in clinical situation. Methods The Normal gastric mucosa epithelial cell (GES-1) and gastric cancer cell (BGC-823) line were collected and analyzed with NMR, then the concentrations of fatty acids were calculated. Results The spectrums of the GES-1 and BGC-823 showed that presences of differently distributed fatty acids were the markers of a physiological condition. The GES-1 cells had

  2. Cell-mediated immunity in patients with carcinoma under immunotheraphy

    International Nuclear Information System (INIS)

    'In vivo' and 'in vitro' cellular immunity is evaluated in 32 patients with carcinoma under immunotheraphy with subcutaneous or endovenous glucan, transfer factor and levamisole. The immunotheraphy is done relatively by intradermal tests with common antigens, by sensitization with dinitrochlorinebenzene and lymphocytes culture from whole blood. The levels of blood serum of human T lymphotocyte soluble receptor for sheep erythrocytes are detected. (M.A.C.)

  3. Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera

    Science.gov (United States)

    Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

    2015-12-01

    The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

  4. Simultaneous Laryngeal Squamous Cell Carcinoma and Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Bighan Khademi

    2011-04-01

    Full Text Available The association of squamous cell carcinoma of the larynx with thyroid papillary carcinoma is an unusual finding. From 2004 to 2011, approximately 250 patients underwent laryngectomies due to squamous cell carcinoma of the larynx at the Otolaryngology Department of Khalili Hospital, affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. In three patients, synchronous occurrence of squamous cell carcinoma and thyroid papillary carcinoma was found. Histopathologic study of the lymph nodes revealed metastatic papillary thyroid carcinoma in one case. We report three cases of thyroid papillary carcinoma incidentally found on histological examinations of resected thyroid lobes, as a procedure required for treatment of head and neck squamous cell carcinoma. In comparison, laryngeal squamous cell carcinoma needs more aggressive treatment than well-differentiated thyroid carcinoma. The prevalence of thyroid papillary carcinoma, as an incidental finding in our study was 0.01%. Therefore, preoperative evaluation of the thyroid gland by ultrasonography and fine needle aspiration biopsy of suspicious lesions is recommended in patients who are candidates for open laryngectomy.

  5. Primary fallopian tube carcinoma

    Directory of Open Access Journals (Sweden)

    Mladenović-Segedi Ljiljana

    2009-01-01

    Full Text Available Introduction. Primary fallopian tube carcinoma is extremely rare, making 0.3-1.6% of all female genital tract malignancies. Although the etymology of this tumor is unknown, it is suggested to be associated with chronic tubal inflammation, infertility, tuberculous salpingitis and tubal endometriosis. High parity is considered to be protective. Cytogenetic studies show the disease to be associated with over expression of p53, HER2/neu and c-myb. There is also some evidence that BRCA1 and BRCA2 mutations have a role in umorogeneis. Clinical features. The most prevailing symptoms with fallopian tube carcinoma are abdominal pain, abnormal vaginal discharge/bleeding and the most common finding is an adnexal mass. In many patients, fallopian tube carcinoma is asymptomatic. Diagnosis. Due to its rarity, preoperative diagnosis of primary fallopian tube carcinoma is rarely made. It is usually misdiagnosed as ovarian carcinoma, tuboovarian abscess or ectopic pregnancy. Sonographic features of the tumor are non-specific and include the presence of a fluid-filled adnexal structure with a significant solid component, a sausage-shaped mass, a cystic mass with papillary projections within, a cystic mass with cog wheel appearance and an ovoid-shaped structure containing an incomplete separation and a highly vascular solid nodule. More than 80% of patients have elevated pretreatment serum CA-125 levels, which is useful in follow-up after the definite treatment. Treatment. The treatment approach is similar to that of ovarian carcinoma, and includes total abdominal hysterectomy and bilateral salpingo-oophorectomy. Staging is followed with chemotherapy.

  6. Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

    Directory of Open Access Journals (Sweden)

    Kwon JY

    2014-12-01

    Full Text Available Jee Young Kwon,1,* Preeyaporn Koedrith,2,* Young Rok Seo1 1Department of Life Science, Institute of Environmental Medicine, Dongguk University, Seoul, Republic of Korea; 2Faculty of Environment and Resource Studies, Mahidol University, Phuttamonthon District, NakhonPathom, Thailand *These authors contributed equally to this work and should be considered as co-first authors Abstract: Engineered nanoparticles (NPs are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. Keywords: carcinogenicity, exposure assessment, genotoxicity, nanoparticles, risk evaluation

  7. Basal Cell Carcinoma

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... cell carcinoma public SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

  8. Squamous Cell Carcinoma

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... cell carcinoma public SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

  9. Bronchogenic Carcinoma in Khartoum

    International Nuclear Information System (INIS)

    The prospective study was conducted in the period between April 1996 and April 1997, and included 26 with bronchogenic carcinoma. The diagnosis was proved histologically in 24 patients, and it was based on the clinico-radiological picture in the remainder two patients. The mean age was 49 years,SD ±16.5. The male:female ratio was 2.2:1.0. All five patients under thirty years were females. 13 patients(50%) were smokers. The mean duration of smoking was 28 years, SD±8. The mean number of cigarettes per day was 24, SD±11.8. Chest symptoms and signs were observed in 92% and 48% of patients respectively, and 10 patients(38%) showed evidence of metastases at diagnosis. Bronchioscopic was done in 11 patients and transthorasic needle biopsy in 6. The diagnosis in the remainder of patients was confirmed by operative biopsy, or pleural cytology, or pleural biopsy or by biopsy from secondaries. The histology revealed squamous cell carcinoma in 14 patients, small cell carcinoma in 5, adenocarcinoma in 3, large cell carcinoma in 2, and the histology was not obtained in two patients. Radiotherapy alone was given to 9 patients. Ten patients underwent surgery followed by radiotherapy in 5 patients and chemotherapy in 4. Only 10 patients survived for more than 3 months. One patient survived for more than one year after diagnosis.(Author)

  10. Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography

    Directory of Open Access Journals (Sweden)

    Wu Wei-Zhong

    2011-01-01

    Full Text Available Abstract Background Antiangiogenesis is a promising therapy for advanced hepatocellular carcinoma (HCC, but the effects are difficult to be evaluated. Pazopanib (GW786034B is a pan-vascular endothelial growth factor receptor inhibitor, the antitumor effects or antiangiogenic effects haven't been investigated in HCC. Methods In vitro direct effects of pazopanib on human HCC cell lines and endothelial cells were evaluated. In vivo antitumor effects were evaluated in three xenograft nude mice models. In the subcutaneous HCCLM3 model, intratumoral blood perfusion was detected by contrast-enhanced ultrasonography (CEUS, and serial quantitative parameters were profiled from the time-intensity curves of ultrasonograms. Results In vitro proliferation of various HCC cell lines were not inhibited by pazopanib. Pazopanib inhibited migration and invasion and induced apoptosis significantly in two HCC cell lines, HCCLM3 and PLC/PRF/5. Proliferation, migration, and tubule formation of human umbilical vein endothelial cells were inhibited by pazopanib in a dose-dependent manner. In vivo tumor growth was significantly inhibited by pazopanib in HCCLM3, HepG2, and PLC/PRF/5 xenograft models. Various intratumoral perfusion parameters changed over time, and the signal intensity was significantly impaired in the treated tumors before the treatment efficacy on tumor size could be observed. Mean transit time of the contrast media in hotspot areas of the tumors was reversely correlated with intratumoral microvessel density. Conclusions Antitumor effects of pazopanib in HCC xenografts may owe to its antiangiogenic effects, and the in vivo antiangiogenic effects could be evaluated by quantitative CEUS.

  11. An Intraductal Human-in-mouse Transplantation Model Mimics the Subtypes of Ductal Carcinoma In Situ

    OpenAIRE

    Behbod, Fariba; Kittrell, Frances S; LaMarca, Heather; Kerbawy, Sofia; Heestand, Jessica C; Young, Evelin; Mukhopadhyay, Purna; Yeh, Hung-Wen; Allred, D. Craig; Medina, Daniel; Edwards, David; Hu, Min; Polyak, Kornelia; Rosen, Jeffrey M.

    2009-01-01

    Introduction: Human models of noninvasive breast tumors are limited, and the existing in vivo models do not mimic inter- and intratumoral heterogeneity. Ductal carcinoma in situ (DCIS) is the most common type (80%) of noninvasive breast lesions. The aim of this study was to develop an in vivo model whereby the natural progression of human DCIS might be reproduced and studied. To accomplish this goal, the intraductal human-in-mouse (HIM) transplantation model was developed. The resulting model...

  12. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P

    2016-01-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  13. Establishment and dynamic in vivo imaging of a radioresistant,GFP-labelled xenograft tumor model of human nasopharyngeal carcinoma in mouse%绿色荧光蛋白标记的鼻咽癌放射抗拒性裸鼠移植瘤模型的建立及其活体成像观察

    Institute of Scientific and Technical Information of China (English)

    黄小鹏; 马慧; 朱小东; 葛莲英; 曲颂; 李龄; 郭亚; 赵伟; 黎丹戎

    2013-01-01

    Objective To establish a GFP-labelled radioresistant xenograft tumor model of human nasopharyngeal carcinoma(NPC) and build the foundation for further study. Methods Lentivirus was used to establish a stable,radioresistant human NPC cell line expressing GFP(GFP-CNE-2R)and a corresponding non-radioresistant cell line(GFP-CNE-2).Both lines were subcutaneously implanted into BALB/c-nu nude mice;when the tumors had reached 1 cm in size,the animals were irradiated with 10 Gy in 1 fraction.Tumor proliferation and metastasis were analyzed in vivo using dynamic imaging technology. Results GFP-CNE-2R and GFP-CNE-2 lines were successfully established,and clone formation assays showed GFP-CNE-2R cells to be radioresistant.Xenograft tumors were grown from GFP-CNE-2R and GFP-CNE-2 cells,and growth of GFP-CNE-2R tumors was not significantly inhibited by radiation. Conclusion GFP-CNE-2R xenograft tumors are more radioresistant than GFP-CNE-2 xenograft tumors.%目的:建立绿色荧光蛋白(green fluorescent protein,GFP)标记的鼻咽癌放射抗拒性裸鼠移植瘤模型,为后续研究奠定基础。方法将以慢病毒转染的方法建立稳定表达GFP标记的人鼻咽低分化鳞癌细胞株GFP-CNE-2和放射抗拒性细胞株GFP-CNE-2R接种至裸鼠体内,建立皮下移植的肿瘤模型。待肿瘤直径约为1 cm时给予相同剂量10 Gy的X射线一次性照射,通过小动物活体成像仪观察移植瘤的生长和转移情况。结果成功建立了稳定表达GFP标记的放射抗拒性及放射敏感的人鼻咽低分化鳞癌细胞株GFP-CNE-2R和GFP-CNE-2。克隆形成实验显示GFP-CNE-2R细胞株具有放射抗拒性。GFP-CNE-2R和GFP-CNE-2细胞的皮下成瘤率均为100%,证实建模成功。相对于GFP-CNE-2裸鼠移植瘤, GFP-CNE-2R移植瘤的生长受照射抑制不明显。结论相对于GFP-CNE-2裸鼠移植瘤,GFP-CNE-2R裸鼠移植瘤具有更强的放射抗拒性。

  14. Fish oil-derived long-chain n-3 polyunsaturated fatty acids reduce expression of M1-associated macrophage markers in an ex vivo adipose tissue culture model, in part through adiponectin

    Directory of Open Access Journals (Sweden)

    Anna A. De Boer

    2015-10-01

    Full Text Available Adipose tissue (AT macrophages (ATM play a key role in obesity-associated pathologies, and their phenotype can be influenced by the local tissue microenvironment. Interestingly, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA and the LC n-3 PUFA-upregulated adipokine, adiponectin (Ad, may mitigate excessive ATM inflammatory M1-polarization responses. However, to what extent LC n-3 PUFA and Ad work in concert to affect macrophage phenotype has not been examined. Thus, we used an established ex vivo AT organ culture model using visceral AT from mice fed a control (CON; 10% w/w safflower oil n-6 PUFA-rich diet or an isocaloric fish-oil (FO; 3% w/w menhaden oil + 7% w/w safflower oil-derived LC n-3 PUFA-rich diet to generate AT conditioned media (ACM. We then evaluated if CON or FO ACM affected macrophage polarization markers in a model designed to mimic acute (18 h ACM plus LPS for the last 6 h or chronic (macrophages treated with LPS-challenged CON or FO ACM for 24 h inflammation ± Ad-neutralizing antibody and the LPS-neutralizing agent, polymyxin B. In the acute inflammation model, macrophages treated with FO ACM had decreased lipid uptake and mRNA expression of M1 markers (Nos2, Nfκb, Il6, Il18, Ccl2 and Ccl5 compared with CON ACM (p≤0.05; however, these effects were largely attenuated when Ad was neutralized (p>0.05. Further, in the chronic inflammation model, macrophages treated with FO ACM had decreased mRNA expression of M1 markers (Nos2, Tnfα, Ccl2 and Il1β and IL-6 and CCL2 secretion (p≤0.05; however, some of these effects were lost when Ad was neutralized, and were further exacerbated when both Ad and LPS were neutralized. Taken together, this work shows that LC n-3 PUFA and Ad work in concert to suppress certain M1 macrophage responses. Thus, future strategies to modulate the ATM phenotype should consider the role of both LC n-3 PUFA and Ad in mitigating obese AT inflammation.

  15. A rare case report: Carcinoma pancreas with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Vikas Yadav

    2014-01-01

    Full Text Available Synchronous double malignancies involving different organs are relatively rare and uncommon finding. We report an interesting case of double malignancy in which a patient exhibited synchronous two separate carcinomas, pancreatic and hepatocellular carcinoma (HCC. Patient was a 64-year-old male who presented primarily with symptoms pertaining to the biliary obstruction and ultrasound of abdomen revealing pancreatic head mass. HCC was detected incidentally during the investigations for carcinoma pancreas.

  16. Team practice for laryngeal carcinoma. Glottic carcinoma

    International Nuclear Information System (INIS)

    To compare the results of treatment performed with and without team practice in glottic laryngeal cancer patients, including local control rate and preservation of voice. Since April 1991, radiation oncologists, radiologists and otolaryngologists have worked in close collaboration to treat head and neck cancer patients in the Kurume University Hospital. Treatment results of a total of 419 patients with glottic cancer were compared with or without team practice. In group A (period, Jan 1978 to Mar 1991), 237 glottic laryngeal cancer patients were treated before team practice. In group B (period, Apr 1991 to Mar 1997), 182 patients were treated with team practice. All patients had histologically proven invasive squamous cell carcinoma. Follow-up period was at least 2 years. In group A, a laser was preferentially used for T1 lesions (T1a: 41 lesions, 52.6%, T1b: 7 lesions, 15.6%), and partial laryngectomy or total laryngectomy was preferentially used for T2 lesions (partial laryngectomy: 21 lesions, 30.9% and total laryngectomy: 10 lesions, 14.7%). On the other hand, in group B, 126 (81.8%) T1 and T2 lesions were treated with radical radiation with or without laser. Local control rate of T1 and T2 cancer improved significantly from 78.3% for group A patients to 91.2% for group B patients (p<0.01). Larynx preservation rate improved slightly from 88.6% to 95.0%. Five year cause-specific survival rate for all stage I to IV patients improved from 94.8% to 96.5%, but was not significant. Relapse-free survival rate improved significantly from group A to group B: from 75.1% to 87.4% (p<0.01). Team practice has effective results in improved local control and preservation of natural voice for patients with glottic carcinoma. (author)

  17. Lidamycin inhibits tumor initiating cells of hepatocellular carcinoma Huh7 through GSK3β/β-catenin pathway.

    Science.gov (United States)

    Chen, Yi; Yu, Dongke; Zhang, Caixia; Shang, Boyang; He, Hongwei; Chen, Jinjing; Zhang, Hao; Zhao, Wuli; Wang, Zhen; Xu, Xiaoyu; Zhen, Yongsu; Shao, Rong-guang

    2015-01-01

    Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating cells of hepatocellular carcinoma Huh7 and identified the potential mechanism. Flow cytometry analysis and sorting assay, surface marker assay, sphere formation assay, and aldefluor assay were used to evaluate the effect of lidamycin on Huh7 tumor initiating cells in vitro. To investigate the potential mechanism, the activity of GSK3β/β-catenin pathway was detected by Western blot and T cell factors transcriptional activity assay. Subcutaneous tumor model in nude mice was used to observe in vivo effect of lidamycin on Huh7 cells. Lidamycin decreased the proportion of EpCAM+ cells and the expression of EpCAM protein. Lidamycin inhibited sphere formation of sorted EpCAM+ cells in 7 d, and of parental cells in three serial passages. The population of aldehyde dehydrogenase-positive cells was reduced by lidamycin. In addition, lidamycin restrained tumor volume and incidence in vivo. Lidamycin activated GSK3β, and degraded the activity of β-catenin. Consequently, transcriptional activity of β-catenin/T cell factors was decreased. In brief, these results suggest that lidamycin suppressed Huh7 tumor initiating cells via GSK3β/β-catenin pathway. These findings reveal the potential mechanism of lidamycin on tumor initiating cells and the benefit for further clinical evaluation. PMID:23857500

  18. Tumor suppressor and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Juliette Martin; Jean-Frangois Dufour

    2008-01-01

    A few signaling pathways are driving the growth of hepatocellular carcinoma. Each of these pathways possesses negative regulators. These enzymes, which normally suppress unchecked cell proliferation, are circumvented in the oncogenic process, either the over-activity of oncogenes is sufficient to annihilate the activity of tumor suppressors or tumor suppressors have been rendered ineffective. The loss of several key tumor suppressors has been described in hepatocellular carcinoma. Here, we systematically review the evidence implicating tumor suppressors in the development of hepatocellular carcinoma.

  19. Soft tissue myoepithelial carcinoma

    OpenAIRE

    Stojšić Zorica; Brašanac Dimitrije; Bacetić Dragoljub; Janković Radmila; Drndarević Neda

    2006-01-01

    Background. Myoepitheliomas are tumors composed predominantly or exclusively of myoepithelial cells, usually arising in salivary glands. Cutaneous/soft tissue localization is very rare, especially for the malignant myoepitheliomas. Case report. We presented a case of myoepithelial carcinoma involving subcutaneous adipose tissue of the left forearm in a woman aged 62 years. The tumor was composed of epithelioid and hyaline cell types, arranged in diffuse sheets, nests and loose clusters within...

  20. Immunology of hepatocellular carcinoma

    OpenAIRE

    Sachdeva, Meenakshi; Chawla, Yogesh K.; Arora, Sunil K

    2015-01-01

    Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can ...

  1. Differentiated nasosinusal epidermoid carcinoma

    International Nuclear Information System (INIS)

    Two case reports of young patients, who were treated in the Otolaryngology Department from 'Dr. Joaquin Castillo Duany' Teaching Clinical Surgical Hospital in Santiago de Cuba are presented. One of the cases presented nasal obstruction, rhinorrhoea and facial pain, for 7 months; the other one presented an increase of volume in the right ocular globe. In both, the results of the biopsy confirmed the diagnosis of differentiated nasosinusal epidermoid carcinoma

  2. Pathobiology of ovarian carcinomas

    OpenAIRE

    Mojgan Devouassoux-Shisheboran; Catherine Genestie

    2015-01-01

    Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular bas...

  3. Thermoradiotherapy for colorectal carcinoma

    International Nuclear Information System (INIS)

    The Japanese Society for Therapeutic Radiology and Oncology conducted a survey of the present state of thermoradiotherapy for colorectal carcinomas in Japan. In this survey, 105 cases at the 9 institutions were registered which had been treated from January 1981 to December 1992. From this data, we analyzed the trend of hyperthermia for the colorectal carcinoma and the treatment parameters which might have an influence on the treatment results. Ninety-four of 105 cases were recurrent or metastatic lesions. Mainly, the RF capacitive heating equipment was applied for the colorectal carcinoma. The number of cases in which hyperthermia were given once or twice a week were almost equal, and there was no significant difference in the treatment response rate. The mean duration of hyperthermia at therapeutic temperature was 42 min. Measurements of temperature in lesions were performed in 86% of sessions, and the mean tumor temperature was 43.1degC. Higher maximum tumor temperature and longer treatment time have brought significantly better response. Responder groups have shown better survival than non-responder groups. Acute reactions associated with hyperthermia were as follows: pain in 35 cases, burn and/or skin erosion in 12 cases, abscess formation in 3 cases and others in 3 cases. Late effects of treatment were ileus in 9 cases, ulcer of intestinal tract in 5 cases, subcutaneous fibrosis in 3 and others in 6. In conclusion, the application of thermoradiotherapy for reflactory colorectal carcinoma may contribute to the improvement of prognosis and quality of life of patients. (author)

  4. Prevention of hepatocellular carcinoma.

    Science.gov (United States)

    Kew, Michael C

    2010-01-01

    Because of its frequency and grave prognosis, preventing hepatocellular carcinoma is an urgent priority. Prevention should be possible because environmental carcinogens-chronic hepatitis B and C virus infections, dietary exposure to aflatoxins, and iron overload-cause the great majority of these tumors. Chronic hepatitis B virus infection accounts for 55% of global hepatocellular carcinomas and 80% of those in the high-incidence Asia Pacific and sub-Saharan African regions. In these regions the infection that becomes chronic is predominantly acquired very early in life. A safe and effective vaccine against this virus is available and its universal inclusion in the immunization of infants has already resulted in a marked reduction of chronic infection and a 70% decrease in the occurrence of hepatocellular carcinoma in those immunized. Chronic hepatitis C virus infection is the major cause of hepatocellular carcinoma in industrialized countries. The infection is mainly acquired in adulthood and, until a vaccine becomes available, prevention will consist mainly of identifying, counselling, and treating chronically infected individuals, preventing spread of the virus by the use of safe injection practices (particularly in intravenous drug abusers), and screening all donated blood for the presence of the virus. 4.5 billion of the world.s population are exposed to dietary aflatoxins. Prevention involves treating susceptible crops to prevent fungal contamination, and handling the foodstuffs in such a way as to prevent contamination during storage. Iron overload in hereditary hemochromatosis can be prevented by repeated venesection and in African dietary iron overload by fermenting the home-brewed beer in iron-free containers. PMID:20526004

  5. Penis squamous cell carcinoma

    OpenAIRE

    Leonor Hernández Piñero; José Luis Rodríguez López; María de Lourdes Menéndez Villa

    2015-01-01

    Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagn...

  6. Uterine papillary serous carcinoma.

    Science.gov (United States)

    Moore, Kathleen N; Fader, Amanda Nickles

    2011-06-01

    Uterine papillary serous carcinoma (UPSC) is a histologic variant of endometrial cancer that accounts for only 10% of new cases of uterine cancer but is responsible for 40% of deaths from the disease. UPSC is an aggressive tumor with a predilection for early spread beyond the uterus. Treatment for UPSC typically entails surgery and in most women is followed by multimodality adjuvant therapy. In this review, we describe the epidemiology, natural history, treatment, and outcome of UPSC. PMID:21508697

  7. Emerging therapies for thyroid carcinoma.

    LENUS (Irish Health Repository)

    Walsh, S

    2012-02-01

    Thyroid carcinoma is the most commonly diagnosed endocrine malignancy. Its incidence is currently rising worldwide. The discovery of genetic mutations associated with the development of thyroid cancer, such as BRAF and RET, has lead to the development of new drugs which target the pathways which they influence. Despite recent advances, the prognosis of anaplastic thyroid carcinoma is still unfavourable. In this review we look at emerging novel therapies for the treatment of well-differentiated and medullary thyroid carcinoma, and advances and future directions in the management of anaplastic thyroid carcinoma.

  8. Epidemiological investigation of esophageal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hong Zhang; Shao-Hua Chen; You-Ming Li

    2004-01-01

    AIM: To review the characteristics of esophageal carcinoma in recent 30 years in the epidemiological investigation.METHODS: A total of 1 520 cases of esophageal carcinoma in the First Affiliated Hospital of Zhejiang University Medical College admitted from 1970 until now were reviewed. Their age, gender, position of carcinoma and histological type were analyzed.RESULTS: The morbidity of esophageal carcinoma was increasing during the observation period. Compared with the 1970s (9.5%), the ratio of adenocarcinoma significantly increased after the 1980s (19.1%). The difference was significant (P≤0.05).CONCLUSION: The morbidity of esophageal adenocarcinoma was increasing and advanced clinical study should be strengthened.

  9. Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma

    International Nuclear Information System (INIS)

    To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal in any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.

  10. MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2

    Directory of Open Access Journals (Sweden)

    Qin X

    2015-12-01

    Full Text Available Xian Qin,1 Yajun Wan,1 Saiying Wang,2 Min Xue1 1Department of Obstetrics and Gynecology, 2Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China Background: In this study, we intended to understand the regulatory mechanisms of microRNA-125a-5p (miR-125a-5p in human cervical carcinoma.Methods: The gene expressions of miR-125a-5p in seven cervical carcinoma cell lines and 12 human cervical carcinoma samples were evaluated by quantitative real-time reverse transcription polymerase chain reaction. Ca-Ski and HeLa cells were transduced with lentivirus carrying miR-125a-5p mimics, and the effects of lentivirus-induced miR-125a-5p upregulation on cervical carcinoma proliferation and migration were examined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and transwell assays, respectively. In additional, HeLa cells were inoculated into null mice to evaluate the effect of miR-125a-5p upregulation on in vivo cervical carcinoma growth. The direct regulation of miR-125a-5p on its target gene, ABL proto-oncogene 2 (ABL2, in cervical carcinoma was evaluated by quantitative real-time reverse transcription polymerase chain reaction, Western blotting and luciferase reporter assays, respectively. ABL2 was then downregulated by small interfering RNA to examine its effect on cervical carcinoma proliferation and migration.Results: miR-125a-5p was downregulated in both cervical carcinoma cell lines and human cervical carcinomas. In Ca-Ski and HeLa cells, lentivirus-mediated miR-125a-5p upregulation inhibited cancer proliferation and migration in vitro and cervical carcinoma transplantation in vivo. ABL2 was shown to be directly targeted by miR-125a-5p. In cervical carcinoma, ABL2 gene and protein levels were both downregulated by miR-125a-5p. Small interfering RNA-mediated ABL2 downregulation also had tumor-suppressive effects on cervical carcinoma proliferation and migration

  11. Luminescent probes for optical in vivo imaging

    Science.gov (United States)

    Texier, Isabelle; Josserand, Veronique; Garanger, Elisabeth; Razkin, Jesus; Jin, Zhaohui; Dumy, Pascal; Favrot, Marie; Boturyn, Didier; Coll, Jean-Luc

    2005-04-01

    Going along with instrumental development for small animal fluorescence in vivo imaging, we are developing molecular fluorescent probes, especially for tumor targeting. Several criteria have to be taken into account for the optimization of the luminescent label. It should be adapted to the in vivo imaging optical conditions : red-shifted absorption and emission, limited overlap between absorption and emission for a good signal filtering, optimized luminescence quantum yield, limited photo-bleaching. Moreover, the whole probe should fulfill the biological requirements for in vivo labeling : adapted blood-time circulation, biological conditions compatibility, low toxicity. We here demonstrate the ability of the imaging fluorescence set-up developed in LETI to image the bio-distribution of molecular probes on short times after injection. Targeting with Cy5 labeled holo-transferrin of subcutaneous TS/Apc (angiogenic murine breast carcinoma model) or IGROV1 (human ovarian cancer) tumors was achieved. Differences in the kinetics of the protein uptake by the tumors were evidenced. IGROV1 internal metastatic nodes implanted in the peritoneal cavity could be detected in nude mice. However, targeted metastatic nodes in lung cancer could only be imaged after dissection of the mouse. These results validate our fluorescence imaging set-up and the use of Cy5 as a luminescent label. New fluorescent probes based on this dye and a molecular delivery template (the RAFT molecule) can thus be envisioned.

  12. In vivo reflectance confocal microscopy features of a large cell acanthoma: report of a case.

    Science.gov (United States)

    Shahriari, Neda; Grant-Kels, Jane M; Rabinovitz, Harold S; Oliviero, Margaret; Scope, Alon

    2016-07-01

    Reflectance confocal microscopy (RCM) is an FDA approved noninvasive optical imaging technique that acquires cellular level-resolution skin images in vivo. Herein, we report a case of histopathologically proven large cell acanthoma (LCA) whose RCM features simulate those of squamous cell carcinoma in situ. PMID:27648388

  13. In vivo reflectance confocal microscopy features of a large cell acanthoma: report of a case.

    Science.gov (United States)

    Shahriari, Neda; Grant-Kels, Jane M; Rabinovitz, Harold S; Oliviero, Margaret; Scope, Alon

    2016-07-01

    Reflectance confocal microscopy (RCM) is an FDA approved noninvasive optical imaging technique that acquires cellular level-resolution skin images in vivo. Herein, we report a case of histopathologically proven large cell acanthoma (LCA) whose RCM features simulate those of squamous cell carcinoma in situ.

  14. Tubulocystic carcinoma of the kidney

    OpenAIRE

    Podduturi, Varsha; Adair, Carol F.; Zhang, Haiying

    2015-01-01

    Tubulocystic carcinoma (TCC) of the kidney is a unique, rare, and recently recognized neoplasm. Although originally considered a low-grade collecting duct carcinoma, TCC is now considered to be a distinct entity. TCC should be considered in the differential diagnosis of cystic renal neoplasms. We report a case of TCC arising in the left kidney.

  15. Evaluation of drug penetration into the brain: a double study by in vivo imaging with positron emission tomography and using an in vitro model of the human blood-brain barrier; Evaluation de la penetration cerebrale: une double etude utilisant un modele in vitro de barriere hemato-encephalique humaine et l'imagerie par tomographie d'emission de positons in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Josserand, V.; Jego, B.; Duconge, F.; Tavitian, B. [CEA Service Hospitalier Frederic Joliot (DSV/DRM/SHFJ), INSERM ERM 0103, 91 - Orsay (France); Pelerin, H.; Ezan, E.; Mabondzo, A. [CEA Saclay (DSV/DRM), Service de Pharmacologie et d' Immunologie, 91 - Gif-sur-Yvette (France); Bruin, B. de; Kuhnast, B.; Dolle, F. [CEA Service Hospitalier Frederic Joliot (DSV/DRM/SHFJ), Groupe de Radiochimie, 91 - Orsay (France)

    2004-08-01

    The blood brain barrier (BBB) passage of a set of radiopharmaceuticals candidates was measured both in vitro using a newly developed co-culture based model of human BBB and in vivo by positron emission tomography (PET). MATERIAL and METHODS: As an in vitro BBB model, a co-culture of primary human brain endothelial cells and primary human astrocytes was used. Dynamic PET studies were performed simultaneously on 4 anesthetized rats with the EXACT HR+ camera. Volumes of interest (VOI) were manually defined on the tomographic images in order to determine the pharmacokinetics of the compounds in various organs, including brain. The in vivo input function was measured by radioactivity counting of arterial blood samples. A two-compartment model analysis was used to compute the exchanging rate constants between blood and brain and to calculate the in vivo permeability coefficient. RESULTS: There was an excellent correlation between the in vitro and in vivo permeability coefficients (r = 0.99; p < 0.001) as well as between the in vivo distribution volume and the in vitro efflux /influx permeability coefficients ratio (r = 0.76). CONCLUSION: This double study evidenced a close relationship between the in vitro and the in vivo approaches for the assessment of the BBB passage. Hence, small animal PET imaging appeared suitable to screen drugs or radiopharmaceuticals candidates aimed at cerebral targets directly in the real-life situation in vivo. (author)

  16. Adeno-associated virus type 2 (AAV2) capsid-specific cytotoxic T lymphocytes eliminate only vector-transduced cells coexpressing the AAV2 capsid in vivo.

    Science.gov (United States)

    Li, Chengwen; Hirsch, Matthew; Asokan, Aravind; Zeithaml, Brian; Ma, Hong; Kafri, Tal; Samulski, R Jude

    2007-07-01

    A recent clinical trial has suggested that recombinant adeno-associated virus (rAAV) vector transduction in humans induces a cytotoxic T-lymphocyte (CTL) response against the AAV2 capsid. To directly address the ability of AAV capsid-specific CTLs to eliminate rAAV-transduced cells in vitro and in vivo in mice, we first demonstrated that AAV2 capsid-specific CTLs could be induced by dendritic cells with endogenous AAV2 capsid expression or pulsed with AAV2 vectors. These CTLs were able to kill a cell line stable for capsid expression in vitro and also in a mouse tumor xenograft model in vivo. Parent colon carcinoma (CT26) cells transduced with a large amount of AAV2 vectors in vitro were also destroyed by these CTLs. To determine the effect of CTLs on the elimination of target cells transduced by AAV2 vectors in vivo, we carried out adoptive transfer experiments. CTLs eliminated liver cells with endogenous AAV2 capsid expression but not liver cells transduced by AAV2 vectors, regardless of the reporter genes. Similar results were obtained for rAAV2 transduction in muscle. Our data strongly suggest that AAV vector-transduced cells are rarely eliminated by AAV2 capsid-specific CTLs in vivo, even though the AAV capsid can induce a CTL response. In conclusion, AAV capsid-specific CTLs do not appear to play a role in elimination of rAAV-transduced cells in a mouse model. In addition, our data suggest that the mouse model may not mimic the immune response noted in humans and additional modification to AAV vectors may be required for further study in order to elicit a similar cellular immune response.

  17. PROGNOSTIC FACTORS IN CERVICAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    路平; 梁秋冬; 魏磊; 郑全庆

    2002-01-01

    Objective: To evaluate factors for prognosis of cervical carcinoma. Methods: Expressions of mn23- HI, erbB3 and erbB4 were examined by immunohistochemical staining. The apoptosis was detected in situ by the TdT mediated duip-biotin nick end-labeling (TUNEL) technique. Mitotic cell were counted by HE dyeing. Results: FIGO stage and lymph node metastasis were the most important factors for evaluating prognosis in adenocarcinoma or squamous cell carcinoma. AI/MI was positively correlated with 5-year survival of cervical carcinoma. Positive expression of nm23-H1 combed with negative expression of erbB4 [nm23-H1(+)/erbB4(-)] predicted good prognosis for adeno-carcinoma. In multivariable Cox regression analysis, only FIGO stage and AI/MI were into equation. Conclusion: FIGO stage and AI/MI were independent evaluating parameter for adenocarcinoma or squamous cell carcinoma.

  18. Octreotide scintigraphy localizes somatostatin receptor-positive islet cell carcinomas

    International Nuclear Information System (INIS)

    Tyr-3-octreotide is a synthetic derivative of somatostatin and a somatostatin-receptor analogue. The iodine-123-labelled compound localizes somatostatin-receptor-positive tumours. In this paper two patients are reported in whom somatostatin receptors were demonstrated in vitro. In a 60-year-old female with an islet cell carcinoma of the pancreas, multiple liver metastases and previously uncrecognized bone metastases in the right acetabulum could be diagnosed as the reason for a persistent hypoglycaemia. In a 60-year-old male an islet cell carcinoma of the pancreas was localized with 123I-Tyr-3-octreotide. The somatostatin receptors were demonstrated in vitro and the tumour was successfully treated with somatostatin. These studies demonstrate that 123I-Tyr-3-octreotide offers the possibility of localizing somatostatin-receptor-positive tumours and their metastases. Moreover the method makes it possible to determine the receptor status of a tumour in vivo. (orig.)

  19. Analysis of RNA interference expression in vitro and in vivo inhibitory of HIF-1αon esophageal squa-mous carcinoma cell line Eca-109%RNA干扰HIF-1α对食管鳞癌细胞Eca-109抑制效应的体内体外表达分析

    Institute of Scientific and Technical Information of China (English)

    郭爱平; 杭兆康; 李苏宜

    2014-01-01

    目的:探讨分析RNA干扰缺氧诱导因子-1α(HIF-1α)对食管鳞癌细胞Eca-109抑制效应的体外及体内的表达情况。方法选取研究用Eca-109细胞,设计RNA干扰片断h-EGFR构建重组质粒pGensil-1-EGFR转染目的基因片段。测定EGFR蛋白/mRNA表达,挑选转染成功的基因修饰细胞株分别植入裸鼠体内,构建移植瘤模型,且随机分为未转染组与实验组。运用免疫组化技术检测各组裸鼠HIF-1α蛋白表达,逆转录聚合酶链反应(RT-PCR)技术检测各组HIF-1αmRNA表达,最后测量裸鼠移植瘤的重量及体积。结果 Eca-109中HIF-1α蛋白伴随氯化钴浓度的升高而升高。并且HIF-1α蛋白水平在缺氧后12小时升高,24小时后降低,且持续减少。转染后EGFR mRNA的阳性表达率为26.55%、9.48%、4.60%,依次降低,P<0.01。其中EGFR siRNA水平最低。转染后EGFR mRNA阳性表达率为24.30%、34.11%、34.05%,与未转染组(78.27%)相比显著降低(P<0.01)。经RT-PCR分析,实验组裸鼠EIF-1αmRNA表达较少,与未转染组相比差异无显著性(P>0.05)。实验组裸鼠HIF-1α蛋白表达的灰度值显著低于未转染组(P<0.01)。接种1周后裸鼠均出现肿瘤,实验组裸鼠移植瘤体积为(0.20±0.13)cm3,重量为(0.21±0.05)g,均显著少于未转染组。结论 HIF-1α蛋白的表达与氯化钴浓度及缺氧有关,RNA干扰缺氧诱导的HIF-1α只发生在蛋白水平,而非基因水平, RNA干扰技术可以成功抑制食管鳞癌细胞HIF-1α基因,阻碍肿瘤细胞生长、增殖,降低肿瘤恶性程度,值得临床应用与推广。%Objective To study the interference of RNA hypoxia inducible factor-1α(HIF-1α) expression inhibition in vitro and in vivo effect of esophageal squamous cell carcinoma cell line Eca-109. Method Selected in esophageal squamous cancer cells (ESCC) to study the Eca-109, the design of RNA interference fragment h

  20. Circadian rhythm variations of clock gene PER1 expression in oral squamous cell carcinoma and their relations with tumor growth in vivo%生物钟PER1基因在口腔鳞癌中的昼夜节律变化及与体内肿瘤生长的关系

    Institute of Scientific and Technical Information of China (English)

    赵宁波; 杨凯; 陈丹; 唐洪; 赵丹; 赵春蓉

    2013-01-01

    目的 探讨生物钟PER1基因在口腔鳞癌中的昼夜节律变化情况和与肿瘤体内生长的关系.方法 60只裸鼠置于12 h光照和12 h黑暗交替环境中饲养3周后,将人颊鳞癌BcaCD885细胞接种于裸鼠颊部,建立口腔颊鳞癌模型.3周成瘤后,在24 h内按灯亮后4、10、16、22 h(4 HALO、10 HALO、16 HALO、22 HALO)的4个时间点分别处死15只裸鼠,取出肿瘤,称量,常规切片在HE染色下计算各时间点肿瘤的有丝分裂指数(MI);分别用S-P免疫组化、Western blot和Real-time RT-PCR检测各时间点癌细胞中PER1蛋白和mRNA的表达;分别用方差分析和余弦分析检验各指标在4个时间点的差异性和是否具有昼夜节律性.结果 颊鳞癌细胞PER1蛋白、PER1 mRNA、肿瘤MI和肿瘤质量在昼夜不同时间点具有显著性差异(P<0.01),其变化波动具有昼夜节律性特征(P<0.05);肿瘤MI和肿瘤质量与PER1的表达水平呈反比关系,PER1 mRNA表达的峰值与肿瘤MI和质量的谷值均位于活动相的中期,而PER1 mRNA表达的谷值与肿瘤MI和质量的峰值均位于休息相中期.结论 口腔鳞癌中PER1的表达、肿瘤MI和质量在昼夜不同时间点的波动具有24 h昼夜节律性规律,PER1在口腔鳞癌中为抑癌基因.%Objective To determine the circadian rhythm variations of the expression of clock gene PER1 in oral squamous cell carcinoma (OSCC) and their relations with tumor growth in vivo.Methods Sixty nude mice were raised under 12 h light/12 h dark cycles for 3 weeks.Human OSCC cell line BcaCD885 was inoculated in the cheek of nude mice to establish a nude mice model of OSCC.In 3 weeks after the implantation,15 mice were sacrificed at 4 time points,including 4 h after light onset (HALO),10 HALO,16 HALO and 22 HALO,respectively,during a period of 24 h.Tumor tissues were excised and weighed.HE stained sections were prepared and mitotic index (MI) was calculated.The protein and mRNA expression of PER1 in the tumor

  1. Experimental rat bladder urothelial cell carcinoma models

    OpenAIRE

    Arentsen, Harm C.; Hendricksen, Kees; Oosterwijk, Egbert; Witjes, J Alfred

    2009-01-01

    Bladder cancer is a major public health problem. Currently available therapeutic options seem to be unable to prevent bladder cancer recurrence and progression. To enable preclinical testing of new intravesical therapeutic agents, a suitable bladder tumor model that resembles human disease is highly desirable. The aim of this topic paper was to discuss the problems associated with current in vivo animal bladder tumor models, focusing on the orthotopic syngeneic rat bladder tumor model. In the...

  2. Laryngeal carcinoma. I

    International Nuclear Information System (INIS)

    A series of 359 patients with carcinoma of the larynx was found to be very close to being representative of the northern part of Jutland, Denmark (north of Kongeaen). No unequivocal change in the disease as regards sex, age, histology, symptoms and signs, and stage of disease could be observed during the period 1963 to 1972. A not statistically significant improvement in the corrected mortality appeared. The level of complications after irradiation and secondary surgery was found to be low. A statistically significant, better prognosis was found for females than for males in the glottic group. (Auth.)

  3. Metastatic paediatric colorectal carcinoma.

    LENUS (Irish Health Repository)

    Woods, R

    2012-03-01

    A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

  4. Radiotherapy of corpus carcinoma

    International Nuclear Information System (INIS)

    96 women with primary carcinoma corporis uteri and 79 women after surgery were treated between 1965 - 1970 with different radiotherapeutic methods, in some cases in combination with cytostatics and gestagens. In the group of primary radiation best results were obtained with combination of intracavitary brachytherapy and external radiation (55% 5-years-survival), and in the postoperative group with external radiation alone (67% 5-years-survival). Late complications with 17% fibrosis in the parametrial tissue and 12% persistant diarrhea in the postoperative group needs strict individualization in therapy and requires exact knowledge on extention and biological behavior of the tumor. (author)

  5. Chemoradiotherapy in pancreatic carcinoma

    Directory of Open Access Journals (Sweden)

    Pathy Sushmita

    2009-01-01

    Full Text Available Pancreatic cancer patients present late in their course and surgical resection as a modality of treatment is of limited value. Majority develop loco-regional failure and distant metastasis, therefore, adjuvant therapy comprising of radiotherapy and chemotherapy are useful treatment options to achieve higher loco-regional control. Specialized irradiation techniques like intra-operative radiotherapy that help to increase the total tumor dose have been used, however, controvertible survival benefit was observed. Various studies have shown improved median and overall survival with chemoradiotherapy for advanced unresectable pancreatic carcinoma. The role of new agents such as topoisomerase I inhibitors also needs further clinical investigations.

  6. Penis squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Leonor Hernández Piñero

    2015-09-01

    Full Text Available Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagnosed belatedly. Partial amputation of the penis was considered to be performed, but there was no consent on behalf of his family. The patient’s general condition was getting worse until he died.

  7. Hepaticportalvenousgasinpancreaticsolitary metastasisfromanesophagealsquamouscell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Takeshi Sawada; Yasushi Adachi; Manabu Noda; Kimishige Akino; Takefumi Kikuchi; Hiroaki Mita; Yoshifumi Ishii and Takao Endo

    2013-01-01

    BACKGROUND: Hepatic portal venous gas (HPVG) is a rare entity commonly associated with intestinal necrosis and fatal outcome, and various underlying diseases have been reported. Pancreatic solitary metastasis without local extension is also rare in esophageal squamous cell carcinoma. METHODS: This report describes an interesting and unusual case of HPVG arising from pancreatic tumor. Autopsy revealed pathogenesis  of  HPVG  and  synchronous  tumors  of  the esophagus and pancreas. RESULTS: A 73-year-old man developed synchronous double tumor in the esophagus and pancreas several months before acute  abdomen  and  his  death,  which  were  generated  by HPVG. Autopsy revealed that HPVG was caused by gastric wall infarction owing to expansion of an isolated pancreatic metastasis from esophageal squamous cell carcinoma. CONCLUSIONS: This is the ifrst case of HPVG that was derived from pancreatic tumor inifltration. If he had been diagnosed with solitary pancreatic metastasis from esophageal squamous cell carcinoma in the ifrst time, he might have an option for chemotherapy, which could let him live longer.

  8. Human medullary thyroid carcinoma: cell cultures and xenotransplants in nude mice. Immunocytochemistry and calcitonin secretion.

    Science.gov (United States)

    Andry, G; Lothaire, P; Vico, P; Dumont, P; Libert, A; Degeyter, M; Larsimont, D; Saigo, P E; Body, J J; Atassi, G

    1989-12-01

    Occult primary and recurrent medullary thyroid carcinomas (MTC) detected only by elevated calcitonin levels in the peripheral blood, generally after pentagastrin-test stimulation, are difficult to localize. Some new imaging procedures with radionuclide tracers or radiolabelled monoclonal antibodies against carcinoembryonic antigen seem to bring some potentially therapeutic benefits. We report our results with cell cultures and xenotransplants of human MTC with the intention of establishing reproducible models in vitro and in vivo. Cell cultures secrete calcitonin at up to 1200 pg/ml for periods ranging from 3 to 13 weeks. Immunocytochemistry detects cytoplasmic granules positive for calcitonin in polygonal epithelioid cells with dendritic processes. Xenotransplants in nude mice fare better in the subcutaneous axilla than in the subrenal capsule assay. In the former location the tumor-take is good and calcitonin is detected in the blood of the tumor-bearing animals, at levels ranging from 286 to more than 20,000 pg/ml. These models would be potentially usable as targets for radionuclide tracers and/or radiolabelled monoclonal antibodies. PMID:2689238

  9. Downregulation and pro-apoptotic effect of hypoxia-inducible factor 2 alpha in hepatocellular carcinoma

    Science.gov (United States)

    Niu, Leilei; Sun, Yun-fan; Yang, Xing-rong; Fan, Jia; Ren, Jian-wei; Chen, George G.; Lai, Paul B.S.

    2016-01-01

    The role of HIF-2α in hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the expression pattern and role of HIF-2α in HCC patients. Immunohistochemical staining and western blotting analyses were applied to detect the protein level of HIF-2α in 206 paired HCC and peritumoral tissues. Kaplan-Meier survival and Cox proportional hazard regression analyses were performed to identify risk factors for overall survival and recurrence-free survival in these patients. The function of HIF-2α was studied in HCC cells and in vivo models. We found that the protein levels of HIF-2α in HCC tissues were lower than in peritumoral tissues, and were negatively correlated with tumor size (P < 0.05). Kaplan-Meier survival and univariate analysis revealed that HCC patients with high HIF-2α protein levels had longer overall survival (P < 0.05). Over-expression of HIF-2α induced apoptosis in HCC cells and increased the levels of pro-apoptotic proteins, Bak, ZBP-89 and PDCD4, whereas the inhibition of HIF-2α expression achieved opposite results. The findings were confirmed in a mouse HCC xenograft model. In conclusion, our study revealed that HIF-2α was decreased and played an anti-tumorigenic role in HCC. PMID:27119229

  10. Simultaneous fingerprint and high-wavenumber fiber-optic Raman endoscopy for in vivo diagnosis of laryngeal cancer

    Science.gov (United States)

    Lin, Kan; Zheng, Wei; Wang, Jianfeng; Lim, Chwee Ming; Huang, Zhiwei

    2016-02-01

    We report a unique simultaneous fingerprint (FP) and high-wavenumber (HW) fiber-optic confocal Raman spectroscopy for in vivo diagnosis of laryngeal cancer in the head and neck under wide-field endoscopic imaging. The simultaneous FP and HW Raman endoscopy technique was performed on 21 patients and differentiated laryngeal carcinoma from normal tissues with both sensitivity and specificity of ~85%. This study shows the great potential of the FP/HW Raman endoscopic technique developed for in vivo diagnosis of laryngeal carcinoma during routine endoscopic examination.

  11. Pulmonary Metastasis of Basal Cell Carcinoma

    OpenAIRE

    Seo, Sang-Hee; Shim, Woo-Haing; SHIN, DONG-HOON; Kim, Yun-Seong; Sung, Hyun-Woo

    2011-01-01

    Although basal cell carcinoma is the most common skin cancer, it rarely metastasizes. Metastatic basal cell carcinoma may, therefore, initially elude diagnosis and management. We describe the case of a patient with a metastatic basal cell carcinoma present in the lungs. The differential diagnosis of suspected metastatic lesions should include metastases from a cutaneous basal cell carcinoma, in addition to those from more commonly metastasizing carcinomas, especially in patients with a histor...

  12. LANTCET: laser nanotechnology for screening and treating tumors ex vivo and in vivo

    Science.gov (United States)

    Lapotko, Dmitri O.; Lukianova-Hleb, Ekaterina Y.; Zhdanok, Sergei A.; Hafner, Jason H.; Rostro, Betty C.; Scully, Peter; Konopleva, Marina; Andreeff, Michael; Li, Chun; Hanna, Ehab Y.; Myers, Jeffrey N.; Oraevsky, Alexander A.

    2007-06-01

    LANTCET (laser-activated nano-thermolysis as cell elimination technology) was developed for selective detection and destruction of individual tumor cells through generation of photothermal bubbles around clusters of light absorbing gold nanoparticles (nanorods and nanoshells) that are selectively formed in target tumor cells. We have applied bare nanoparticles and their conjugates with cell-specific vectors such as monoclonal antibodies CD33 (specific for Acute Myeloid Leukemia) and C225 (specific for carcinoma cells that express epidermal growth factor -EGF). Clusters were formed by using vector-receptor interactions with further clusterization of nanoparticles due to endocytosis. Formation of clusters was verified directly with optical resonance scattering microscopy and microspectroscopy. LANTCET method was tested in vitro for living cell samples with: (1) model myeloid K562 cells (CD33 positive), (2) primary human bone marrow CD33-positive blast cells from patients with the diagnosis of acute myeloid leukemia, (3) monolayers of living EGF-positive carcinoma cells (Hep-2C), (4) human lymphocytes and red blood cells as normal cells. The LANTCET method was also tested in vivo using rats with experimental polymorphic sarcoma. Photothermal bubbles were generated and detected in vitro with a photothermal microscope equipped with a tunable Ti-Sa pulsed laser. We have found that cluster formation caused an almost 100-fold decrease in the bubble generation threshold of laser pulse fluence in tumor cells compared to the bubble generation threshold for normal cells. The animal tumor that was treated with a single laser pulse showed a necrotic area of diameter close to the pump laser beam diameter and a depth of 1-2 mm. Cell level selectivity of tumor damage with single laser pulse was demonstrated. Combining lightscattering imaging with bubble imaging, we introduced a new image-guided mode of the LANTCET operation for screening and treatment of tumors ex vivo and in vivo.

  13. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni;

    2003-01-01

    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were...... determined and found to be indistinguishable. Comparison of the vitronectin and the hemoglobin concentrations of the extracts showed that their vitronectin content was not derived from blood contamination. Vitronectin mRNA was undetectable in both carcinomas and normal tissue. We conclude that vitronectin...

  14. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review.

    Science.gov (United States)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P

    2016-06-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis. PMID:27398205

  15. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne – case report and literature review

    OpenAIRE

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P.

    2016-01-01

    Key Clinical Message Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment‐resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.

  16. The in vivo biofilm

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Maria; Alhede, Morten;

    2013-01-01

    Bacteria can grow and proliferate either as single, independent cells or organized in aggregates commonly referred to as biofilms. When bacteria succeed in forming a biofilm within the human host, the infection often becomes very resistant to treatment and can develop into a chronic state. Biofilms...... have been studied for decades using various in vitro models, but it remains debatable whether such in vitro biofilms actually resemble in vivo biofilms in chronic infections. In vivo biofilms share several structural characteristics that differ from most in vitro biofilms. Additionally, the in vivo...... experimental time span and presence of host defenses differ from chronic infections and the chemical microenvironment of both in vivo and in vitro biofilms is seldom taken into account. In this review, we discuss why the current in vitro models of biofilms might be limited for describing infectious biofilms...

  17. The Effects of GLUT1 on the Survival of Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Shengjiao Li

    2013-09-01

    Full Text Available Background/Aims: Cancer cells require increased nutrient uptake to support a high rate of proliferation, and the overexpression of glucose transporters, in particular GLUT1, is a common characteristic of human malignancies. Here, we investigated the relationship between the expression of GLUT1 and cell viability, colony forming ability and apoptosis of head and neck squamous cell carcinoma (HNSCC in vitro and in a xenograft mouse model in vivo. Methods: Lentiviral mediated overexpression and knock-down of GLUT1 was performed in two oral cancer cell lines (CAL27 and SCC25. QRT-PCR and Western blot analysis were used to detect the mRNA and protein expression of GLUT1 and nuclear factor-kappa B (NFκB p65 subunit. Cell viability and apoptosis were assessed by MTT and flow cytometry analyses, respectively. Colony formation assays were performed by staining with 0.5% crystal violet. The role of GLUT1 in HNSCC was examined in vivo through the generation of a CAL27 (or CAL27 with different transfections nude mice xenograft model of HNSCC. Results: GLUT1 overexpression promoted cell viability and colony formation whereas GLUT1 silencing had the opposite effect. GLUT1 knock-down significantly increased the number of Annexin V positive cells in both cell lines and GLUT1 overexpression had the opposite effect, indicating that GLUT1 modulates apoptosis. Xenograft mouse models of GLUT1 knockdown and overexpression showed that GLUT1 expression was associated with poor survival and increased tumor growth. GLUT1 overexpression significantly upregulated the expression of NFκB-p65, and this effect was reversed by inhibition of GLUT1 expression. Conclusions: GLUT1 expression plays an important role in the survival of HNSCC, and its effects may be associated with the activation of the NFκB pathway.

  18. In vivo cell tracking with bioluminescence imaging.

    Science.gov (United States)

    Kim, Jung Eun; Kalimuthu, Senthilkumar; Ahn, Byeong-Cheol

    2015-03-01

    Molecular imaging is a fast growing biomedical research that allows the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In vivo tracking of cells is an indispensable technology for development and optimization of cell therapy for replacement or renewal of damaged or diseased tissue using transplanted cells, often autologous cells. With outstanding advantages of bioluminescence imaging, the imaging approach is most commonly applied for in vivo monitoring of transplanted stem cells or immune cells in order to assess viability of administered cells with therapeutic efficacy in preclinical small animal models. In this review, a general overview of bioluminescence is provided and recent updates of in vivo cell tracking using the bioluminescence signal are discussed.

  19. In vivo cell tracking with bioluminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Eun; Kalimuthu, Senthilkumar; Ahn, Byeong Cheol [Dept. of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu (Korea, Republic of)

    2015-03-15

    Molecular imaging is a fast growing biomedical research that allows the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In vivo tracking of cells is an indispensable technology for development and optimization of cell therapy for replacement or renewal of damaged or diseased tissue using transplanted cells, often autologous cells. With outstanding advantages of bioluminescence imaging, the imaging approach is most commonly applied for in vivo monitoring of transplanted stem cells or immune cells in order to assess viability of administered cells with therapeutic efficacy in preclinical small animal models. In this review, a general overview of bioluminescence is provided and recent updates of in vivo cell tracking using the bioluminescence signal are discussed.

  20. In vivo cell tracking with bioluminescence imaging

    International Nuclear Information System (INIS)

    Molecular imaging is a fast growing biomedical research that allows the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In vivo tracking of cells is an indispensable technology for development and optimization of cell therapy for replacement or renewal of damaged or diseased tissue using transplanted cells, often autologous cells. With outstanding advantages of bioluminescence imaging, the imaging approach is most commonly applied for in vivo monitoring of transplanted stem cells or immune cells in order to assess viability of administered cells with therapeutic efficacy in preclinical small animal models. In this review, a general overview of bioluminescence is provided and recent updates of in vivo cell tracking using the bioluminescence signal are discussed

  1. Malaria modeling: In vitro stem cells vs in vivo models.

    Science.gov (United States)

    Noulin, Florian

    2016-03-26

    The recent development of stem cell research and the possibility of generating cells that can be stably and permanently modified in their genome open a broad horizon in the world of in vitro modeling. The malaria field is gaining new opportunities from this important breakthrough and novel tools were adapted and opened new frontiers for malaria research. In addition to the new in vitro systems, in recent years there were also significant advances in the development of new animal models that allows studying the entire cell cycle of human malaria. In this paper, we review the different protocols available to study human Plasmodium species either by using stem cell or alternative animal models.

  2. Irradiation Of Prostatic Carcinoma By Neodymium-YAG-Laser

    Science.gov (United States)

    Bowering, R.; Hofstetter, A.; Keiditsch, E.; Frank, F.

    1980-05-01

    Human Cadaver prostate tumors and canine prostate glands in vivo were irradiated by Nd:YAG laser with different power levels and pulse durations. Temperature measurements were carried out by an arrangement of micro thermo couple, digital volt meter and computer in different layers of the prostate and the rectum. The temporal and spatial temperature measurements showed a good correlation with the histological findings. Endoscopic laser irradiation of prostatic carcinoma in man was performed after TUR. There was a large penetration depth resulting a deep necrosis, but no perforation and no changes in the rectum were to be found also after high power laser irradiation.

  3. Carcinoma triquilemal: relato de caso Trichilemmal carcinoma: case report

    Directory of Open Access Journals (Sweden)

    Miguel Roismann

    2011-10-01

    Full Text Available O carcinoma triquilemal é um tumor raro, que ocorre, geralmente, na pele exposta ao sol, principalmente face, couro cabeludo, pescoço e dorso das mãos, em indivíduos idosos, entre a 4ª e 9ª décadas de vida, sem predilação por sexo. O presente estudo mostra um caso de carcinoma triquilemal, recidivado, de difícil tratamento, em mesma topografia de um carcinoma basocelular tratado previamente com cirurgia e radioterapia.The trichilemmal carcinoma is a rare tumor that usually occurs on sun-exposed skin, especially on the face, scalp, neck and back of hands, mainly in elderly subjects but commonly between the 4th and 9th decades of life. It is not a gender-based illness. This study shows a difficult to treat case of recurrent trichilemmal carcinoma on the same location of a basal-cell carcinoma previously treated with surgery and radiotherapy.

  4. Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma.

    Science.gov (United States)

    Warszawik-Hendzel, Olga; Olszewska, Małgorzata; Maj, Małgorzata; Rakowska, Adriana; Czuwara, Joanna; Rudnicka, Lidia

    2015-12-31

    Squamous cell carcinoma is the second most common cutaneous malignancy after basal cell carcinoma. Although the gold standard of diagnosis for squamous cell carcinoma is biopsy followed by histopathology evaluation, optical non-invasive diagnostic tools have obtained increased attention. Dermoscopy has become one of the basic diagnostic methods in clinical practice. The most common dermoscopic features of squamous cell carcinoma include clustered vascular pattern, glomerular vessels and hyperkeratosis. Under reflectance confocal microscopy, squamous cell carcinoma shows an atypical honeycomb or disarranged pattern of the spinous-granular layer of the epidermis, round nucleated bright cells in the epidermis and round vessels in the dermis. High frequency ultrasound and optical coherence tomography may be helpful in predominantly in pre-surgical evaluation of tumor size. Emerging non-invasive or minimal invasive techniques with possible application in the diagnosis of squamous cell carcinoma of the skin, lip, oral mucosa, vulva or other tissues include high-definition optical coherence tomography, in vivo multiphoton tomography, direct oral microscopy, electrical impedance spectroscopy, fluorescence spectroscopy, Raman spectroscopy, elastic scattering spectroscopy, differential path-length spectroscopy, nuclear magnetic resonance spectroscopy, and angle-resolved low coherence interferometry.

  5. Salivary gland myoepithelial carcinoma.

    Science.gov (United States)

    Vilar-González, S; Bradley, K; Rico-Pérez, J; Vogiatzis, P; Golka, D; Nigam, A; Sivaramalingam, M; Kazmi, S

    2015-11-01

    Salivary gland myoepithelial carcinoma (MC) or malignant myoepithelioma is a rare entity. MC usually presents as a slow-growing painless mass arising in the parotid gland, but may involve other salivary glands. This tumour may be particularly locally aggressive, but its clinical and biological features are not yet fully understood. MC may arise from pre-existing benign lesions, such as pleomorphic adenomas or benign myoepitheliomas, or may arise de novo. It usually affects patients over 50 years old, with no gender preference. Because it is often asymptomatic, the presentation and diagnosis can be delayed by months, even years. The current WHO classification considers MC to be an intermediate- to high-grade malignancy. Other published data suggest it is likely to be a high-grade neoplasm, consistent with its aggressive behaviour. Its epidemiology, histopathological features, immunohistochemical profile, clinical behaviour and optimal management are not well understood. Following review of the current literature we aim to address these.

  6. Carcinoma of the vulva

    International Nuclear Information System (INIS)

    The accepted primary treatment modality in carcinoma of the vulva is a surgical resection. The standard approach is a radical vulvectomy with superficial nodal dissections if the superficial ignuinal nodes are involved. Surgical treatment is associated with a substantial incidence of local recurrence and significant morbidity predominantly associated with nodal dissection. Definitive radiation therapy is a viable alternative to surgery; with it, an overall 5-year survival of 40% to 50% can be expected. The incidence of sequelae with definitive radiation therapy appears acceptable, and is conceivable that it might be reduced substantially if modern techniques and time-dose schemes are applied. A promising area for radiation therapy is in combination with surgery

  7. Merkel cell carcinoma.

    Science.gov (United States)

    Minokadeh, Ardalan; Wulkan, Adam J; Beer, Kenneth; Waibel, Jill S

    2014-01-01

    A 92-year-old man presented for evaluation with a 1-month history of a rapidly growing asymptomatic pink nodule on his forearm. Biopsy results of the lesion demonstrated pathology consistent with Merkel cell carcinoma (MCC). Immunohistochemical studies displayed positive cytoplasmic staining for cytokeratin AE1/AE3, positive dot-like perinuclear staining for cytokeratin-20, diffuse cytoplasmic staining for neuron specific enolase, and no significant staining for S-100. Subsequent positron emission tomography did not reveal evidence of metastatic disease. Wide excision of the lesion was performed along with a sentinel node biopsy of his left axilla. The sentinel nodes were negative for MCC. Adjuvant radiation treatment of the tumor site was provided because the pathologist noted MCC within 2 mm of the deep margin. PMID:24933855

  8. Hepatocellular Carcinoma (HCC)

    Science.gov (United States)

    Helmberger, Thomas K.

    Hepatocellular carcinoma (HCC) is considered to be one of the most common malignancies worldwide, and the most common one in Africa and Asia. Over the last decade, a rising incidence of up to 10-15/100,000 per population has been seen in the Western world, with an estimate of 250,000 deaths and more than a million worldwide per year. By the year 2010, the World Health Organization expects that HCC will be the leading cause of cancer mortality surpassing lung cancer. This increasing incidence is most likely related to an increasing prevalence of chronic hepatitis C (HC) and B (HB) virus infections and other diseases inducing chronic inflammation (Befeler and Di Bisceglie 2002; Llovet et al. 2003).

  9. Genetics of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Frank Staib; Stephan Kanzler; Arndt Weinmann; Henning Schulze-Bergkamen; Peter R Galle

    2007-01-01

    The completely assembled human genome has made it possible for modern medicine to step into an era rich in genetic information and high-throughput genomic analysis. These novel and readily available genetic resources and analytical tools may be the key to unravel the molecular basis of hepatocellular carcinoma (HCC). Moreover, since an efficient treatment for this disease is lacking, further understanding of the genetic background of HCC will be crucial in order to develop new therapies aimed at selected targets. We report on the current status and recent developments in HCC genetics. Special emphasis is given to the genetics and regulation of major signalling pathways involved in HCC such as p53, Wntsignalling, TGFβ, Ras, and Rb pathways. Furthermore, we describe the influence of chromosomal aberrations as well as of DNA methylation. Finally, we report on the rapidly developing field of genomic expression profiling in HCC, mainly by microarray analysis.

  10. Radiotherapic procedures in vulvar carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cintra e Oliveira, V. (Hospital dos Servidores Publicos de Sao Paulo (Brazil); Instituto de Radioterapia de Sao Paulo (Brazil)); Lima, G.R. de (Escola Paulista de Medicina, Sao Paulo (Brazil); Hospital dos Servidores Publicos de Sao Paulo (Brazil)); Peres, O. (Instituto de Radioterapia de Sao Paulo (Brazil))

    The cases of six patients with vulvar squamous carcinoma are discussed. The radiotherapic procedure employed in the treatment is presented and compared to other methods. The small morbidity of the therapeutic procedure followed is commented.

  11. Cutaneous metastases of hepatocellular carcinoma.

    Science.gov (United States)

    Lazaro, M; Serrano, M L; Allende, I; Ratón, J A; Acebo, E; Diaz-Perez, J L

    2009-12-01

    Cutaneous metastases are an unusual finding that may present as the first sign of an internal neoplasia. A case of cutaneous metastases of hepatocellular carcinoma, which may often involve other organs but very rarely metastases to the skin, is reported.

  12. Oncofetal fibronectins in oral carcinomas

    DEFF Research Database (Denmark)

    Mandel, U; Gaggero, B; Reibel, J;

    1994-01-01

    -B-containing isoform and the oncofetal FN isoform derived by O-glycosylation, in oral squamous cell carcinomas, premalignant lesions, and normal oral mucosa. A selective expression of the ED-B-containing isoform was demonstrated in close relation to the invading carcinoma (38/38), whereas there was virtually...... no staining in submucosa underlying premalignant lesions (1/11) and normal epithelium (0/5). The ED-B-containing FN showed close co-distribution and staining pattern with the oncofetal isoform derived by O-glycosylation. These results demonstrate that accumulation of FN adjacent to oral carcinomas includes...... both the ED-B-containing isoform and the isoform derived by O-glycosylation. Although both the change in primary structure and glycosylation of FN create conformational and immunologically detectable changes, the functional consequences in association with invasive carcinoma are poorly understood...

  13. [Bronchial mucoepidermoid carcinoma].

    Science.gov (United States)

    Bregante, J I; Rituerto, B; Font de Mora, F; Alonso, F; Andreu, M J; Figuerola, J; Mulet, J F

    1998-07-01

    We submit the case of a child afflicted with a mucoepidermoid bronchial tumor. The patient is a boy, aged seven, who after undergoing antibiotic treatment for six weeks because of a fever and atelectasia-condensation in the right lower lobe showed no signs of clinical improvement and was sent to our department to undergo further study and treatment. A bronchoscopy performed shows a polypoid mass that partially blocks the main bronchial tube a few milimiters under the access to the right upper lobe. A biopsy is carried out and the anatomopathological test shows there is a low degree epidermoid carcinoma. We decide to perform a lobectomy which for the tumor location and the lung condition has to be medium and lower right. We proceed to remove the adenopaty of hilium not affected by the tumor. The postoperative period develops without incidents. A check-up bronchoscopy performed three months later shows two polypoid masses in the right bronchial tube which, once a biopsy is performed, proved to be granulation tissue. Twelve months after undergoing surgery, the patient's condition is good, there is no evidence of tumor relapse and the breathing capacity is adequate, though there is an obstructive restrictive pattern in the espirometry. Even taking into consideration that lung tumors are extremely unusual, the epidermoid carcinoma is the one which most frequently occurs. The tumor's low malignancy is a sign that points to a good prognosis. Performing conservative surgery by means of bronchoplasty should be taken into account so as to keep the sequelae on the lung condition to a minimum, even though in this case the tumor location made it impossible. PMID:12602035

  14. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  15. Molecular pathology of breast apocrine carcinomas

    DEFF Research Database (Denmark)

    Celis, J.E.; Gromova, I.; Gromov, P.;

    2006-01-01

    Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0...... benign apocrine changes and breast carcinoma is unclear and has been a matter of discussion for many years. Recent proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine biomarkers [15-hydroxyprostaglandin...... dehydrogenase (15-PGDH) and hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early and advanced apocrine lesions. These biomarkers in combination with proteins found to be characteristically upregulated in pure apocrine carcinomas (psoriasin, S100A9, and p53) provide a protein...

  16. The frequency of Helicobacter pylor infection and cagA expression in the Korean patients with gastric carcinoma

    International Nuclear Information System (INIS)

    Helicobacter pylori infection had been approved as a group 1 carcinogen by the international agency for research on cancer. However the association between H.pylori infection and gastric carcinoma was not so definite in South Asia including Korea, and the role of cagA gene of H.pylori in gastric carcinogenesis was a controversial issue. The aims of this study were firstly to study in vivo expression frequency of 16S rRNA and cagA gene of H.pylori, secondly to study the association between H.pylori infection and gastric cancer, the association between cagA expression and gastric cancer in Korean patients. In vivo expression rate of 16S rRNA was 74 % of gastric carcinoma patients and cagA expression rate was 51 % of gastric carcinoma patients with H.pylori infection. Although 90 % of gastric carcinoma patients had H.pylori infection, the association between H.pylori infection and gastric carcinoma was not significant. And there was no significant association between cagA expression and gastric carcinoma. (author). 37 refs., 2 tabs., 1 fig

  17. The frequency of Helicobacter pylor infection and cagA expression in the Korean patients with gastric carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Sook Hyang; Kim, Yoo Chul [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1997-12-01

    Helicobacter pylori infection had been approved as a group 1 carcinogen by the international agency for research on cancer. However the association between H.pylori infection and gastric carcinoma was not so definite in South Asia including Korea, and the role of cagA gene of H.pylori in gastric carcinogenesis was a controversial issue. The aims of this study were firstly to study in vivo expression frequency of 16S rRNA and cagA gene of H.pylori, secondly to study the association between H.pylori infection and gastric cancer, the association between cagA expression and gastric cancer in Korean patients. In vivo expression rate of 16S rRNA was 74 % of gastric carcinoma patients and cagA expression rate was 51 % of gastric carcinoma patients with H.pylori infection. Although 90 % of gastric carcinoma patients had H.pylori infection, the association between H.pylori infection and gastric carcinoma was not significant. And there was no significant association between cagA expression and gastric carcinoma. (author). 37 refs., 2 tabs., 1 fig.

  18. Evaluation of vaginal antifungal formulations in vivo.

    Science.gov (United States)

    McRipley, R. J.; Erhard, P. J.; Schwind, R. A.; Whitney, R. R.

    1979-01-01

    Relatively simple and rapid procedures have been developed for evaluating the local efficacy of vaginal antifungal agents in vivo in a vaginal candidiasis model in ovariectomized rats. The results of this investigation indicate that the model and methods described are quite suitable for screening potential antifungal substances and for assessing the chemotherapeutic effectiveness of new antifungal agents and formulations before carrying out clinical studies. PMID:392480

  19. New treatments for renal carcinoma

    OpenAIRE

    Perez-Gracia, J L; Lopez-Picazo, J M; Olier, C. (Clara); ALFARO, C.; Garcia-Foncillas, J; Melero, I; Gurpide, A

    2007-01-01

    Renal cell carcinoma presents several unique features, which distinguish it from other tumours. The increase in survival that has been described in patients with renal cell carcinoma following nephrectomy breaks a classical rule of oncology, which states that surgery of the primary tumour has no role in the treatment of patients with advanced disease. Together with melanoma, it is the only tumour in which immunomodulatory treatments with drugs such as interleukin-2 produces a clinical benefit...

  20. Genomic profile of ovarian carcinomas

    OpenAIRE

    Micci, Francesca; Haugom, Lisbeth; Vera M. Abeler; Davidson, Ben; Tropé, Claes G; Heim, Sverre

    2014-01-01

    Background It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory. Methods We cytogenetically analyzed 110 new cases of ovarian carcinoma of different histologic...

  1. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

    Directory of Open Access Journals (Sweden)

    Divvya

    2014-05-01

    Full Text Available Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differentiation is practically very rare.

  2. BASAL CELL CARCINOMA WITH ECCRINE DIFFERENTIATION: A RARE ENTITY

    OpenAIRE

    Divvya; Rehana; Viswanathan; Krishnaswamy; Anvar Ali

    2014-01-01

    Basal cell carcinoma preferentially occurs in the face where the surgical excision with adequate margin is curative. Sometimes basal cell carcinoma is also reported rarely in other sites especially associated with basal cell carcinoma syndrome. The histological variants are Nodular basal cell carcinoma, Keratotic basal cell carcinoma, Adenoid basal cell carcinoma, Basal cell carcinoma with sebaceous differentiation. Of these variants, Basal cell carcinoma with eccrine differen...

  3. Ex vivo lung perfusion.

    Science.gov (United States)

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation. PMID:26700566

  4. Inflammatory Breast Carcinoma Presenting with Two Different Patterns of Cutaneous Metastases: Carcinoma Telangiectaticum and Carcinoma Erysipeloides

    OpenAIRE

    Yaghoobi, Reza; Talaizade, Abdolhasan; Lal, Karan; Ranjbari, Nastaran; Sohrabiaan, Nasibe; Feily, Amir

    2015-01-01

    Cutaneous metastases can have many different clinical presentations. They are seen in patients with advanced malignant disease; however, they can be the initial manifestation of undetected malignancies. Inflammatory breast carcinoma is a rare and aggressive form of breast cancer that has a nonspecific appearance mimicking many benign conditions including mastitis, breast abscesses, and/or dermatitis. The authors report the case of a 40-year-old woman with inflammatory breast carcinoma present...

  5. Models of Hepatocellular Carcinoma and Biomarker Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Bagi, Cedo M., E-mail: cedo.bagi@pfizer.com; Andresen, Catharine J. [Global Science & Technology, PGRD, Pfizer Inc, Groton, CT 06340 (United States)

    2010-07-07

    The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients.

  6. Models of Hepatocellular Carcinoma and Biomarker Strategy

    International Nuclear Information System (INIS)

    The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients

  7. Somatostatin receptors and somatostatin content in medullary thyroid carcinomas

    International Nuclear Information System (INIS)

    Human medullary thyroid carcinomas from 19 patients were analyzed for their content in somatostatin (SRIF) receptors using receptor autoradiography with a SRIF-28 analogue and the SRIF octapeptide [Tyr3]-SMS 201-995 as iodinated radioligands. Four out of 19 cases were SRIF receptor positive with the SRIF octapeptide radioligand. These cases as well as four additional tumors were also positive with the SRIF-28 radioligand 125I-[Leu8, D-Trp22, Tyr25]-SRIF-28. High affinity binding sites pharmacologically specific for bioactive SRIF analogues, specifically located on tumor tissue, were identified. In some cases the SRIF receptors were distributed in a non-homogeneous pattern, with labelling occurring preferentially in highly differentiated tumor regions. Numerous cases were shown to have a high tumoral SRIF content measured by radioimmunoassay or immunohistochemical technique. However, there was no correlation between SRIF receptor status and tumor levels of endogenous SRIF. No correlation was seen between the clinical outcome or the survival of the patients and their tumoral SRIF receptor content. Whereas some medullary thyroid carcinomas seem to be a target for SRIF, the SRIF function in these tumors remains unclear. SRIF receptors in a group of medullary thyroid carcinomas may be useful morphological marker of these tumors and of potential interest for their in vivo localization

  8. ESD Hands-on Course Using Ex Vivo and In Vivo Models in South Korea

    OpenAIRE

    Bok, Gene Hyun; Cho, Joo Young

    2012-01-01

    Endoscopic submucosal dissection (ESD) is an established treatment for gastric neoplasias especially in regions with a high volume of gastric cancer. Although ESD has many advantages over endoscopic mucosal resection, ESD is technically more difficult and can result in severe complications. Therefore establishment of an effective training system is required to help endoscopists climb the ESD learning curve. Although a standard training system for ESD remains to be established, some centers ar...

  9. Coculture System with an Organotypic Brain Slice and 3D Spheroid of Carcinoma Cells

    Science.gov (United States)

    Chuang, Han-Ning; Lohaus, Raphaela; Hanisch, Uwe-Karsten; Binder, Claudia

    2013-01-01

    Patients with cerebral metastasis of carcinomas have a poor prognosis. However, the process at the metastatic site has barely been investigated, in particular the role of the resident (stromal) cells. Studies in primary carcinomas demonstrate the influence of the microenvironment on metastasis, even on prognosis1,2. Especially the tumor associated macrophages (TAM) support migration, invasion and proliferation3. Interestingly, the major target sites of metastasis possess tissue-specific macrophages, such as Kupffer cells in the liver or microglia in the CNS. Moreover, the metastatic sites also possess other tissue-specific cells, like astrocytes. Recently, astrocytes were demonstrated to foster proliferation and persistence of cancer cells4,5. Therefore, functions of these tissue-specific cell types seem to be very important in the process of brain metastasis6,7. Despite these observations, however, up to now there is no suitable in vivo/in vitro model available to directly visualize glial reactions during cerebral metastasis formation, in particular by bright field microscopy. Recent in vivo live imaging of carcinoma cells demonstrated their cerebral colonization behavior8. However, this method is very laborious, costly and technically complex. In addition, these kinds of animal experiments are restricted to small series and come with a substantial stress for the animals (by implantation of the glass plate, injection of tumor cells, repetitive anaesthesia and long-term fixation). Furthermore, in vivo imaging is thus far limited to the visualization of the carcinoma cells, whereas interactions with resident cells have not yet been illustrated. Finally, investigations of human carcinoma cells within immunocompetent animals are impossible8. For these reasons, we established a coculture system consisting of an organotypic mouse brain slice and epithelial cells embedded in matrigel (3D cell sphere). The 3D carcinoma cell spheres were placed directly next to the brain

  10. Hepatocellular carcinoma (Letter to the editor)

    DEFF Research Database (Denmark)

    Békássy, Albert N.; Garwicz, Stanislaw; Jensen, O.A.

    1994-01-01

    Øjenpatologi, Alagill's syndrome, hepatic carcinoma, biliary atresia, histopathology, liver, child, liver cirrhosis, autopsy, eyes, AFP......Øjenpatologi, Alagill's syndrome, hepatic carcinoma, biliary atresia, histopathology, liver, child, liver cirrhosis, autopsy, eyes, AFP...

  11. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  12. The many faces of basal cell carcinoma

    OpenAIRE

    Jackson, Robert

    1982-01-01

    Basal cell carcinoma is the most easily cured carcinoma, but because of the many forms it can take, and because it grows so slowly, it can be misdiagnosed or neglected. The author discusses its more common forms and etiologic considerations.

  13. Basal cell carcinoma of penis: case report.

    OpenAIRE

    Sulaiman, M Z; Polacarz, S V; Partington, P E

    1988-01-01

    Basal cell carcinoma of the penis is rare. A patient who presented with a penile and scrotal ulcer due to basal cell carcinoma is reported. Wide local excision and split skin grafting were performed to excise the lesion completely.

  14. ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas.

    Science.gov (United States)

    Adams, April; Warner, Kristy; Pearson, Alexander T; Zhang, Zhaocheng; Kim, Hong Sun; Mochizuki, Daiki; Basura, Gregory; Helman, Joseph; Mantesso, Andrea; Castilho, Rogério M; Wicha, Max S; Nör, Jacques E

    2015-09-29

    A small sub-population of cells characterized by increased tumorigenic potential, ability to self-renew and to differentiate into cells that make up the tumor bulk, has been characterized in some (but not all) tumor types. These unique cells, namedcancer stem cells, are considered drivers of tumor progression in these tumors. The purpose of this work is to understand if cancer stem cells play a functional role in the tumorigenesis of salivary gland mucoepidermoid carcinomas. Here, we investigated the expression of putative cancer stem cell markers (ALDH, CD10, CD24, CD44) in primary human mucoepidermoid carcinomas by immunofluorescence, in vitro salisphere assays, and in vivo tumorigenicity assays in immunodeficient mice. Human mucoepidermoid carcinoma cells (UM-HMC-1, UM-HMC-3A, UM-HMC-3B) sorted for high levels of ALDH activity and CD44 expression (ALDHhighCD44high) consistently formed primary and secondary salispheres in vitro, and showed enhanced tumorigenic potential in vivo (defined as time to tumor palpability, tumor growth after palpability), when compared to ALDHlowCD44low cells. Cells sorted for CD10/CD24, and CD10/CD44 showed varying trends of salisphere formation, but consistently low in vivo tumorigenic potential. And finally, cells sorted for CD44/CD24 showed inconsistent results in salisphere formation and tumorigenic potential assays when different cell lines were evaluated. Collectively, these data demonstrate that salivary gland mucoepidermoid carcinomas contain a small population of cancer stem cells with enhanced tumorigenic potential and that are characterized by high ALDH activity and CD44 expression. These results suggest that patients with mucoepidermoid carcinoma might benefit from therapies that ablate these highly tumorigenic cells.

  15. Insular carcinoma: a distinct de novo entity among follicular carcinomas of the thyroid gland.

    Science.gov (United States)

    Pilotti, S; Collini, P; Mariani, L; Placucci, M; Bongarzone, I; Vigneri, P; Cipriani, S; Falcetta, F; Miceli, R; Pierotti, M A; Rilke, F

    1997-12-01

    We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteria of insular carcinoma and 29 cases those of widely invasive follicular carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival showed a significant association between histotype and pT and pN categories. In particular, pT4 (p AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that insular carcinoma represents a de novo entity distinct from widely invasive follicular carcinoma, that widely invasive follicular carcinoma has biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alterations.

  16. Endometrial carcinoma stage I.

    Science.gov (United States)

    Baram, A; Ron, I; Kupferminc, M; Inbar, M

    1997-01-01

    Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately. PMID:21590195

  17. Immunology of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is primarily a malignancyof the liver, advancing from a damaged, cirrhoticliver to HCC. Globally, HCC is the sixth most prevalentcancer and the third-most prevalent reason for neoplasticdisease-related deaths. A diverse array ofinfiltrating immunocytes regulates the developmentand progression of HCC, as is the case in many othercancers. An understanding of the various immunecomponents during HCC becomes necessary so thatnovel therapeutic strategies can be designed to combatthe disease. A dysregulated immune system (includingchanges in the number and/or function of immunecells, cytokine levels, and the expression of inhibitoryreceptors or their ligands) plays a key role in thedevelopment of HCC. Alterations in either the innateor adaptive arm of the immune system and cross-talkbetween them make the immune system tolerant totumors, leading to disease progression. In this review,we have discussed the status and roles of variousimmune effector cells (e.g. , dendritic cells, natural killercells, macrophages, and T cells), their cytokine profile,and the chemokine-receptor axis in promoting orimpeding HCC.

  18. Eyelid Carcinoma in Patients with Systemic Lymphoma

    OpenAIRE

    Debraj Shome; Diana Bell; Bita Esmaeli

    2010-01-01

    Purpose: To describe a series of patients with Non-Hodgkin′s lymphoma (NHL) and concomitant eyelid carcinoma. Methods: In this non-comparative interventional case series, we retrospectively reviewed the medical records of 5 patients with NHL who developed eyelid carcinoma. Results: The patients included one female and four male subjects. Systemic lymphoma had been diagnosed 1 to 72 months prior to development of the eyelid carcinoma. The lesions were basal cell carcinoma in three, and...

  19. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  20. GENETIC INSTABILITY IN CERVICAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    赵旻; 伍欣星; 邱小萍; 李晖; 戴天力; 谭云

    2002-01-01

    Objective: The role of human papillomavirus (HPV) in the development of cervical carcinoma has been clearly established but other factors could be involved in cervical tumorigenesis such as loss of heterozygosity (LOH) and microsatellite instability (MI). The aim of the present study was to investigate the genetic instability in cervical carcinoma tissues and provide evidence for discoveringnew tumor suppressor genes and screening diagnostic molecular marker of cervical carcinoma. Methods: Fifty primary cervical carcinoma samples from high-incidence area were analyzed by PCR for HPV16 infection, LOH and microsatellite instability. Results: HPV16 was detected in 88% of the cases. Sixty-six percent of total cases showed LOH with no more than 3 different loci per case. The highest frequency of the allelic loss was found in D18S474 (18q21, 40.5%). MI was detected in 4 cases (8%) only. Conclusion: Different percentages of LOH on specific chromosomal regions were found and MI was very infrequent in cervical carcinoma. The putative suppressor gene(s) could be located on specific chromosome regions such as 18q, and genetic instability could be involved in cervical tumorigenesis.

  1. Effects of Antihepatocarcinoma with Apatite Nanoparticles in vivo

    Institute of Scientific and Technical Information of China (English)

    YIN Meizhen; HAN Yingchao; DAI Honglian; LI Shipu

    2006-01-01

    The inhibition effect of hydroxyapatite (HAP) nanoparticles on hepatocarcinoma was investigated in vivo. The human hepatocarcinoma cell line Bel-7402 was transplanted subcutaneously into nude mice. Hydroxyapatite nanoparticles suspension at a dose of 0.2 mL was injected into the transplanted tumors every day for 2 weeks, and saline was used as control. The efficacy of hydroxyapatite nanoparticles on this carcinoma was surveyed and morphological changes of tissue and cells were observed by light microscopy and transmission electron microscopy (TEM). Experimental results show that hydroxyapatite nanoparticles have a visible destructive effect on the structures of hepatocarcinoma cells and tissue. The inhibition rates of tumor growth were 77.21% and 51. 32% after intra- tumor injection of hydroxyapatite nanoparticles for 1 week and 2 weeks, respectively. Compared with the control group, hydroxyapatite nanoparticles can also prolong the survival time of the nude mice bearing this cancer significantly. This indicates that hydroxyapatite nanoparticles have the therapeutic potential on hepatoma in vivo.

  2. Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma

    Science.gov (United States)

    2016-06-14

    Recurrent Oral Cavity Adenoid Cystic Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Oral Cavity Adenoid Cystic Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Oral Cavity Adenoid Cystic Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Oral Cavity Adenoid Cystic Carcinoma

  3. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

    Directory of Open Access Journals (Sweden)

    Brown J.W.

    2000-01-01

    Full Text Available Over a 15-year period, our university-based laboratory obtained 125 adrenal tumors, of which 15 (12% were adrenal cortical carcinomas. Of these, 6 (40% of the carcinomas occurred in patients with clear clinical manifestations of steroid hormone excess. Adrenal cortical carcinoma cells derived from the surgically resected tumors in 4 of these patients were isolated and established in primary culture. Radiotracer steroid interconversion studies were carried out with these cultures and also on mitochondria isolated from homogenized tissues. Large tumors had the lowest steroidogenic activities per weight, whereas small tumors had more moderately depressed enzyme activities relative to cells from normal glands. In incubations with pregnenolone as substrate, 1 mM metyrapone blocked the synthesis of corticosterone and cortisol and also the formation of aldosterone. Metyrapone inhibition was associated with a concomitant increase in the formation of androgens (androstenedione and testosterone from pregnenolone. Administration of metyrapone in vivo before surgery in one patient resulted in a similar increase in plasma androstenedione, though plasma testosterone levels were not significantly affected. In cultures of two of four tumors examined, dibutyryl cAMP stimulated 11ß-hydroxylase activity modestly; ACTH also had a significant stimulatory effect in one of these tumors. Unlike results obtained with normal or adenomatous adrenal cortical tissues, mitochondria from carcinomatous cells showed a lack of support of either cholesterol side-chain cleavage enzyme complex or steroid 11ß-hydroxylase activity by Krebs cycle intermediates (10 mM isocitrate, succinate or malate. This finding is consistent with the concept that these carcinomas may tend to function predominantly in an anaerobic manner, rather than through the oxidation of Krebs cycle intermediates.

  4. [The Dutch guideline 'Renal cell carcinoma'].

    NARCIS (Netherlands)

    Osanto, S.; Bex, A.; Hulsbergen- van de Kaa, C.A.; Soetekouw, P.M.M.B.; Stemkens, D.

    2012-01-01

    The Dutch guideline 'Renal Cell Carcinoma' has been revised on the basis of new literature. With the assistance of the Netherlands Cancer Registry an assessment was made of the current care for patients with renal cell carcinoma. Renal cell carcinoma is a type of cancer for which knowledge of the ge

  5. Small cell undifferentiated carcinoma in the epididymis

    Institute of Scientific and Technical Information of China (English)

    CHEN Jia-wei; YUAN Lin; Hu Hong-hui

    2005-01-01

    @@ Small cell undifferentiated carcinoma is a special type of tumor which is usually found in the lungs. However, it is very rare in extra pulmonary tissues, especially in epididymis. One case of small cell undifferentiated carcinoma in the right epididymis, with partial differentiation to adenocarcinoma and neuroendocrine carcinoma is reported as follows.

  6. Basal cell carcinoma-treatment with cryosurgery

    Directory of Open Access Journals (Sweden)

    Kaur S

    2003-03-01

    Full Text Available Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  7. Basal cell carcinoma-treatment with cryosurgery

    OpenAIRE

    Kaur S; Thami G; Kanwar A

    2003-01-01

    Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  8. The GPR 55 agonist, L-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis

    OpenAIRE

    Nicole A. Hofmann; Yang, Jiang; Trauger, Sunia A.; Nakayama, Hironao; Huang, Lan; Strunk, Dirk; Moses, Marsha A.; Klagsbrun, Michael; Bischoff, Joyce; Graier, Wolfgang F

    2015-01-01

    Background and Purpose Highly vascularized ovarian carcinoma secretes the putative endocannabinoid and GPR55 agonist, L-α-lysophosphatidylinositol (LPI), into the circulation. We aimed to assess the involvement of this agonist and its receptor in ovarian cancer angiogenesis. Experimental Approach Secretion of LPI by three ovarian cancer cell lines (OVCAR-3, OVCAR-5 and COV-362) was tested by mass spectrometry. Involvement of cancer cell-derived LPI on angiogenesis was tested in the in vivo ch...

  9. (-)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma

    OpenAIRE

    Luo, Ting; Wang, Jiao; Yin, Yancun; Hua, Hui; Jing, Jing; Sun, Xiangming; Li, Minjing; Zhang, You; Jiang, Yangfu

    2010-01-01

    Introduction Paclitaxel (Taxol®) is a microtubule-targeted agent that is widely used for cancer treatment. However, resistance to paclitaxel is frequently encountered in the clinic. There is increasing interest in identifying compounds that may increase the sensitivity to conventional chemotherapeutic agents. In this study, we investigated whether green tea polyphenol (-)-epigallocatechin gallate (EGCG) could sensitize breast carcinoma to paclitaxel in vivo. Methods Breast cancer cells were t...

  10. Carcinoma folicular de tireóide: estudo retrospectivo Follicular thyroid carcinoma: retrospective study

    Directory of Open Access Journals (Sweden)

    Vergilius J. F. Araújo Filho

    2001-10-01

    Full Text Available OBJETIVOS: Abordar o diagnóstico, tratamento e evolução do carcinoma folicular da tireóide. MÉTODOS: Análise retrospectiva dos dados de 38 pacientes submetidos à tireoidectomia por carcinoma folicular puro, num período de 10 anos no HC-FMUSP. O tempo médio de seguimento foi de três anos e três meses. Nove pacientes eram do sexo masculino (23,7% e 29 do sexo feminino (76,3%, com idades entre 19 e 87 anos (média=49,5. RESULTADOS: Em 17 (58,6% dos doentes, observou-se nódulo único à ultra-sonografia, e 23 (79,3% tinham nódulos frios à cintilografia. Sintomatologia esteve presente em 33 pacientes (86,8%. A punção aspirativa por agulha fina (PAAF, realizada em 27 pacientes, revelou padrão folicular em 24 (88,9%, carcinoma papilífero em 2 (7,4% e bócio em 1 (3,7%. Tireoidectomia total foi o tratamento final em 34 pacientes e esvaziamento cervical foi realizado em três casos. Apenas 5 (13,1% obtiveram confirmação diagnóstica ao exame de congelação intra-operatória. Houve 2 (5,2% óbitos pela doença e 5 (13,1% pacientes apresentam-se vivos com doença. O aumento da tireoglobulina (TG correlacionou-se com o aparecimento de metástase em 100% dos casos. CONCLUSÕES: Concluímos que pacientes com carcinoma folicular de tireóide geralmente apresentam-se com nódulo único ou predominante ao primeiro exame, cuja PAAF é de padrão folicular. O exame de congelação raramente confirma o diagnóstico. Em nosso serviço, o tratamento de escolha é a tireoidectomia total, permitindo um seguimento mais adequado e confiável do paciente e prevenindo o crescimento de lesões subclínicas no lobo contralateral. A evolução geralmente é favorável.BACKGROUND: Unlike papillary carcinoma, there are limited data regarding diagnosis, treatment and follow-up of patients with follicular thyroid carcinoma. METHODS: We retrospectively analyzed data on 38 patients submitted to thyroidectomy for exclusive follicular carcinoma over a 10 years

  11. A Model to Predict the Risk of Keratinocyte Carcinomas.

    Science.gov (United States)

    Whiteman, David C; Thompson, Bridie S; Thrift, Aaron P; Hughes, Maria-Celia; Muranushi, Chiho; Neale, Rachel E; Green, Adele C; Olsen, Catherine M

    2016-06-01

    Basal cell and squamous cell carcinomas of the skin are the commonest cancers in humans, yet no validated tools exist to estimate future risks of developing keratinocyte carcinomas. To develop a prediction tool, we used baseline data from a prospective cohort study (n = 38,726) in Queensland, Australia, and used data linkage to capture all surgically excised keratinocyte carcinomas arising within the cohort. Predictive factors were identified through stepwise logistic regression models. In secondary analyses, we derived separate models within strata of prior skin cancer history, age, and sex. The primary model included terms for 10 items. Factors with the strongest effects were >20 prior skin cancers excised (odds ratio 8.57, 95% confidence interval [95% CI] 6.73-10.91), >50 skin lesions destroyed (odds ratio 3.37, 95% CI 2.85-3.99), age ≥ 70 years (odds ratio 3.47, 95% CI 2.53-4.77), and fair skin color (odds ratio 1.75, 95% CI 1.42-2.15). Discrimination in the validation dataset was high (area under the receiver operator characteristic curve 0.80, 95% CI 0.79-0.81) and the model appeared well calibrated. Among those reporting no prior history of skin cancer, a similar model with 10 factors predicted keratinocyte carcinoma events with reasonable discrimination (area under the receiver operator characteristic curve 0.72, 95% CI 0.70-0.75). Algorithms using self-reported patient data have high accuracy for predicting risks of keratinocyte carcinomas.

  12. Treatment of thyroid follicular carcinoma.

    Science.gov (United States)

    Ríos, Antonio; Rodríguez, José M; Parrilla, Pascual

    2015-12-01

    Differentiated thyroid carcinoma includes 2 different tumor types, papillary (PC) and follicular carcinoma (FC), and although similar, their prognosis is different. FC is uncommon, and this has led to it often being analyzed together with PC, and therefore the true reality of this tumor is difficult to know. As a result, the diagnostic and therapeutic management and the prognostic factors in differentiated carcinoma are more predictive of PC than FC. In this review we analyze the current state of many of the therapeutic aspects of this pathology. The best surgical technique and the usefulness of associated lymphadenectomy is also analyzed. Regarding post-surgical ablation with 131I, the indications, doses and usefulness are discussed. For the remaining therapies we analyze the few indications for radiotherapy and chemotherapy, and of new drugs such as tyrosine kinase inhibitors.

  13. Genetic heterogeneity of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Unsal, H.; Isselbacher, K.J. (Massachusetts General Hospital Cancer Center, Charlestown, MA (United States)); Yakicier, C.; Marcais, C.; Ozturk, M. (Institut National de la Sante et de la Recherche Medicale, Lyon (France)); Kew, M. (Univ. of Witwatersrand, Johannesburg (South Africa)); Volkmann, M. (Univ. of Heidelberg (Germany)); Zentgraf, H. (Deutsches Krebsforschungszentrum, Heidelberg (Germany))

    1994-01-18

    The authors studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 35% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-types of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.

  14. Radioimmune localization of occult carcinoma

    International Nuclear Information System (INIS)

    Patients with a rising serum carcinoembryonic antigen level and no clinical or roentgenographic evidence of recurrent or metastatic cancer present a treatment dilemma. Eleven such patients, 10 with a previously treated colorectal carcinoma and 1 with a previously treated breast carcinoma, received an injection of the anticarcinoembryonic antigen monoclonal antibody ZCE-025 labeled with the radioisotope indium 111. Nuclear scintigraphy was performed on days 3 and 5 through 7 to detect potential sites of tumor recurrence. The monoclonal antibody scan accurately predicted the presence or absence of occult malignancy in 7 (64%) patients. Second-look laparotomy confirmed the monoclonal antibody scan results in the patients with colorectal cancer, and magnetic resonance imaging confirmed metastatic breast cancer. This study demonstrates that In-ZCE-025 can localize occult carcinoma and may assist the surgeon in facilitating the operative exploration. In-ZCE-025 assisted in the initiation of adjuvant therapy for the patient with breast cancer

  15. Telomerase Activity in Human Ovarian Carcinoma

    Science.gov (United States)

    Counter, Christopher M.; Hirte, Hal W.; Bacchetti, Silvia; Harley, Calvin B.

    1994-04-01

    Telomeres fulfill the dual function of protecting eukaryotic chromosomes from illegitimate recombination and degradation and may aid in chromosome attachment to the nuclear membrane. We have previously shown that telomerase, the enzyme which synthesizes telomeric DNA, is not detected in normal somatic cells and that telomeres shorten with replicative age. In cells immortalized in vitro, activation of telomerase apparently stabilizes telomere length, preventing a critical destabilization of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomeres of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the development and progression of tumors, we have measured enzyme activity and telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintained in these cells and that tumor cells, but not isogenic nonmalignant cells, express telomerase. Our findings suggest that progression of malignancy is ultimately dependent upon activation of telomerase and that telomerase inhibitors may be effective antitumor drugs.

  16. Regulation of human hepatocellular carcinoma cells by Spred2 and correlative studies on its mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Xiao-Ni [Lanzhou University of Technology, Lanzhou 730050 (China); Liu, Xiao-Yun [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Center for Disease Control and Prevention, Lanzhou Military Command, Lanzhou 730020 (China); Yang, Yue-Feng [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Xiao, Feng-Jun [Lanzhou University of Technology, Lanzhou 730050 (China); Li, Qing-Fang [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Yan, Jun [Lanzhou University of Technology, Lanzhou 730050 (China); Zhang, Qun-Wei; Wang, Li-Sheng [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China); Li, Xue-Yan, E-mail: llglixueyan@163.com [Lanzhou University of Technology, Lanzhou 730050 (China); Wang, Hua, E-mail: wanghua@bmi.ac.cn [Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)

    2011-07-15

    Highlights: {yields} Hepatocellular carcinoma is inhibited by Spred2 through as yet unclear mechanisms. {yields} We studied the overexpression of Spred2 in cell line and murine tumor models of HCC. {yields} Spred2 inhibited cell proliferation and migration via attenuating ERK signaling. {yields} Spred2 overexpression induced apoptosis via caspase-3 and downregulated Mcl-1. {yields} A Spred2 knockdown markedly induced tumor growth in vivo. -- Abstract: Members of the Spred gene family are negative regulators of the Ras/Raf-1/ERK pathway, which has been associated with several features of the tumor malignancy. However, the effect of Spred genes on hepatocellular carcinoma (HCC) remains uninvestigated. In the present work, we analyzed the in vitro and in vivo effects of Spred2 expression on the hepatic carcinoma cell line, SMMC-7721. In addition to attenuated ERK activation, which inhibited the proliferation and migration of unstimulated and HGF-stimulated SMMC-7721 cells. Adenovirus-mediated Spred2 overexpression induced the activation of caspase-3 and apoptosis, as well as reduced the expression level of Mcl-1. Most importantly, the knockdown of Spred2 markedly enhanced tumor growth in vivo. In conclusion, these results suggest that Spred2 could qualify as a potential therapeutic target in HCC.

  17. Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice

    Science.gov (United States)

    Wu, Tao; Heuillard, Emilie; Lindner, Véronique; Bou About, Ghina; Ignat, Mihaela; Dillenseger, Jean-Philippe; Anton, Nicolas; Dalimier, Eugénie; Gossé, Francine; Fouré, Gael; Blindauer, Franck; Giraudeau, Céline; El-Saghire, Hussein; Bouhadjar, Mourad; Calligaro, Cynthia; Sorg, Tania; Choquet, Philippe; Vandamme, Thierry; Ferrand, Christophe; Marescaux, Jacques; Baumert, Thomas F.; Diana, Michele; Pessaux, Patrick; Robinet, Eric

    2016-01-01

    The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging. PMID:27739457

  18. Medullary carcinoma of the colon

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Grauslund, Morten; Glenthøj, Anders;

    2015-01-01

    Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic...... differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether...

  19. Radiation therapy in bronchogenic carcinoma

    International Nuclear Information System (INIS)

    Response of intrathoracic symptoms to thoracic irradiation was evaluated in 330 patients. Superior vena caval syndrome and hemoptysis showed the best response, with rates of 86% and 83%, respectively, compared to 73% for pain in the shoulder and arm and 60% for dyspnea and chest pain. Atelectasis showed re-expansion in only 23% of cases, but this figure increased to 57% for patients with oat-cell carcinoma. Vocal cord paralysis improved in only 6% of cases. Radiation therapy has a definite positive role in providing symptomatic relief for patients with carcinoma of the lung

  20. Experimentelle Schlaganfallforschung in vivo

    OpenAIRE

    Prass, Konstantin

    2010-01-01

    The results of animal experimental stroke research could significantly contribute to our understanding of the pathophysiology of the important social disease over the last years. Furthermore they lead to formulations of Treatment recommendations. Since the research in vivo is made in an organic whole it is not restricted to the brain as in cell culture experiments or brain – slice – models but allow a study of the whole organism, its physiology and throughout all potenti...

  1. Ex vivo lung perfusion

    OpenAIRE

    Machuca, Tiago N; Cypel, Marcelo

    2014-01-01

    Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. I...

  2. Epstein-Barr virus and gastric carcinoma

    OpenAIRE

    Takada, K

    2000-01-01

    The Epstein-Barr virus (EBV) is detected in the tissue of about 10% of gastric carcinoma cases throughout the world. In each case, 100% of carcinoma cells are infected with EBV. Analysis of EBV in carcinoma biopsies indicates that carcinoma is formed by the proliferation of a single EBV infected cell. These findings suggest that EBV plays an important role in the development of EBV positive gastric carcinomas. The EBV genes expressed are EBV determined nuclear antigen 1 (EBNA1), two small non...

  3. Papillary thyroid carcinoma in children and adolescents.

    Science.gov (United States)

    Chung, Bo Mi; Park, Sung Hee; Kim, Soo Jin; Seo, Jae Seung; Kim, Yang Soo; Shim, Hyung Jin; Lee, Jong Beum

    2014-09-01

    Differentiated thyroid carcinoma is uncommon in children and constitutes 0.5% to 3% of all pediatric malignancies. Few studies have reported imaging findings of childhood papillary thyroid carcinomas. We report 3 cases of papillary thyroid carcinomas in children. Among the 3 patients, the youngest was a 7-year-old girl. In the current report, we describe 2 cases of classic papillary thyroid carcinoma and 1 case of pediatric diffuse sclerosing variant of papillary thyroid carcinoma. The ultrasonographic features and diagnostic procedures in these pediatric patients are similar to those in adults.

  4. [Lactobacilli and colon carcinoma--A review].

    Science.gov (United States)

    Wang, Shumei; Zhang, Lanwei; Shan, Yujuan

    2015-06-01

    Epidemiological studies showed that incidence of colon carcinoma is increased in the world. There are many difficulties to inhibit colon carcinoma because the causes of inducing colon carcinoma were various and interactive each other. Previous evidence supported the balance of the colonic microflora was critical in inhibiting colon carcinoma and the protection by colonic microflora could be improved by ingesting lactobacilli. Therefore, the biological functions and anticancer effects of lactobacilli attract attention of researchers. In this review we discussed the causes of colon carcinoma; the anticancer mechanisms of lactobacilli on the basis of our own studies. Eventually, we summarized the effects of anticancer of different components and metabolic products extracted from lactobacilli.

  5. Tubulocystic carcinoma of kidney associated with papillary renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Mahesh Deshmukh

    2011-01-01

    Full Text Available Tubulocystic renal cell carcinoma (TCRCC is a rare variant of renal cell carcinoma, which has distinct histology but there is some controversy about its association with papillary renal cell carcinoma (PRCC and cell of origin in literature. We report an 18-year-old girl with the rare TCRCC of kidney associated with PRCC with metastases to the para-aortic nodes. The patient presented with hematuria and a right renal mass with enlarged regional nodes for which a radical nephrectomy with retroperitoneal lymph node dissection was done. On gross examination, a solid cystic lesion involving the lower pole and middle pole of the kidney measuring 12x9x9 cm was seen along with an additional cystic lesion in upper pole of kidney. Microscopically the main tumor showed the typical histology of a tubulocystic carcinoma with multiple cysts filled with secretions lined by variably flattened epithelium with hobnailing of cells. The mass in the upper pole was a high-grade PRCC and the nodal metastases had morphology similar to this component. To conclude, at least a small but definite subset of TCRCC is associated with PRCC, and cases associated with PRCC do seem to have a higher propensity for nodal metastasis as in the case we report.

  6. Thyroid Metastasis from Breast Carcinoma Accompanied by Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Song-I Yang

    2014-07-01

    Full Text Available Metastasis to the thyroid gland is very rare. Recently, we experienced a case of thyroid metastasis from breast cancer accompanying a papillary thyroid. A 51-year-old female patient presented with a palpated lymph node on her left lateral neck. The patient had undergone a left modified radical mastectomy followed by chemotherapy and hormonal therapy 12 years prior. Ultrasonography of the neck revealed a malignant looking nodule at the left thyroid lobe, measuring 0.9 × 0.9 cm, and several cystic nodules at the right thyroid lobe. Ultrasonography of the neck additionally revealed a malignant looking lymph node at the right level VI. Fine-needle aspiration of the left thyroid lobe resulted in a diagnosis of papillary thyroid carcinoma and that of the right level VI in Hurthle cell lesion. The patient had a total thyroidectomy with selective dissection of the left neck node. Pathologic assessment of the specimen revealed metastatic carcinoma from the breast carcinoma and papillary thyroid carcinoma. Although the thyroid gland is highly vascularized, metastasis of malignant tumors to the thyroid is relatively rare and detection of metastasis shows a low frequency. So a careful evaluation of thyroid tumor should be considered in a patient with a history of other malignancy.

  7. Mast cells dysregulate apoptotic and cell cycle genes in mucosal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Davis Paul

    2006-12-01

    Full Text Available Abstract Background Mucosal squamous cell carcinoma of the head and neck is a disease of high mortality and morbidity. Interactions between the squamous cell carcinoma and the host's local immunity, and how the latter contributes to the biological behavior of the tumor are unclear. In vivo studies have demonstrated sequential mast cell infiltration and degranulation during squamous cell carcinogenesis. The degree of mast cell activation correlates closely with distinct phases of hyperkeratosis, dysplasia, carcinoma in-situ and invasive carcinoma. However, the role of mast cells in carcinogenesis is unclear. Aim This study explores the effects of mast cells on the proliferation and gene expression profile of mucosal squamous cell carcinoma using human mast cell line (HMC-1 and human glossal squamous cell carcinoma cell line (SCC25. Methods HMC-1 and SCC25 were co-cultured in a two-compartment chamber, separated by a polycarbonate membrane. HMC-1 was stimulated to degranulate with calcium ionophore A23187. The experiments were done in quadruplicate. Negative controls were established where SCC25 were cultured alone without HMC-1. At 12, 24, 48 and 72 hours, proliferation and viability of SCC25 were assessed with MTT colorimetric assay. cDNA microarray was employed to study differential gene expression between co-cultured and control SCC25. Results HMC-1/SCC25 co-culture resulted in suppression of growth rate for SCC-25 (34% compared with 110% for the control by 72 hours, p Conclusion We show that mast cells have a direct inhibitory effect on the proliferation of mucosal squamous cell carcinoma in vitro by dysregulating key genes in apoptosis and cell cycle control.

  8. In vivo study of human skin using pulsed terahertz radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pickwell, E [Semiconductor Physics Group, Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge CB3 0HE (United Kingdom); Cole, B E [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom); Fitzgerald, A J [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom); Pepper, M [Semiconductor Physics Group, Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge CB3 0HE (United Kingdom); Wallace, V P [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom)

    2004-05-07

    Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumours tend to have different water content from normal tissue, a likely contrast mechanism is variation in water content. Thus, we have previously devised a finite difference time-domain (FDTD) model which is able to closely simulate the interaction of THz radiation with water. In this work we investigate the interaction of THz radiation with normal human skin on the forearm and palm of the hand in vivo. We conduct the first ever systematic in vivo study of the response of THz radiation to normal skin. We take in vivo reflection measurements of normal skin on the forearm and palm of the hand of 20 volunteers. We compare individual examples of THz responses with the mean response for the areas of skin under investigation. Using the in vivo data, we demonstrate that the FDTD model can be applied to biological tissue. In particular, we successfully simulate the interaction of THz radiation with the volar forearm. Understanding the interaction of THz radiation with normal skin will form a step towards developing improved imaging algorithms for diagnostic detection of skin cancer and other tissue disorders using THz radiation.

  9. In vivo bioreactors for mandibular reconstruction.

    Science.gov (United States)

    Tatara, A M; Wong, M E; Mikos, A G

    2014-12-01

    Large mandibular defects are difficult to reconstruct with good functional and aesthetic outcomes because of the complex geometry of craniofacial bone. While the current gold standard is free tissue flap transfer, this treatment is limited in fidelity by the shape of the harvested tissue and can result in significant donor site morbidity. To address these problems, in vivo bioreactors have been explored as an approach to generate autologous prefabricated tissue flaps. These bioreactors are implanted in an ectopic site in the body, where ossified tissue grows into the bioreactor in predefined geometries and local vessels are recruited to vascularize the developing construct. The prefabricated flap can then be harvested with vessels and transferred to a mandibular defect for optimal reconstruction. The objective of this review article is to introduce the concept of the in vivo bioreactor, describe important preclinical models in the field, summarize the human cases that have been reported through this strategy, and offer future directions for this exciting approach.

  10. Therapeutic effects of trehalose liposomes against lymphoblastic leukemia leading to apoptosis in vitro and in vivo.

    Science.gov (United States)

    Matsumoto, Yoko; Kuwabara, Keiji; Ichihara, Hideaki; Kuwano, Masataka

    2016-01-15

    Inhibitory effects of trehalose liposomes (DMTre) composed of 30mol% l-α-dimyristoylphosphatidylcholine (DMPC) and 70mol% trehalose surfactants on the growth of lymphoblastic leukemia (MOLT-4) cells in vitro and therapeutic effects of DMTre for xenograft mice model of carcinoma in vivo were examined. DMTre inhibited the growth of MOLT-4 cells in a dose-dependent manner due to apoptosis. The activation of caspase-3, -8, and 9 was obtained for MOLT-4 cells after the treatment with DMTre. The clustering of lipid rafts in plasma membranes of MOLT-4 cells was examined with a marker Cholera toxin subunit B conjugates Alexa Fluor (CTB), which binds to the pentasaccharide chains of ganglioside GM1 on the cellular surfaces. The clustering of lipid rafts in plasma membranes of MOLT-4 cells was observed after the treatment with DMTre. Therapeutic effects of DMTre were obtained for xenograft mice model of carcinoma in vivo. PMID:26711146

  11. Isolated Uterine Metastasis of Invasive Ductal Carcinoma

    Directory of Open Access Journals (Sweden)

    Deniz Arslan

    2013-01-01

    Full Text Available Introduction. Most common metastasis sites of breast cancer are the lungs, bones, liver, and brain, whereas uterine involvement by metastatic breast disease is rare. Metastatic carcinoma of the uterus usually originates from other genital sites, most commonly being from the ovaries. Invasive lobular carcinoma spreads to gynecologic organs more frequently than invasive ductal carcinoma. Case Report. A 57-year-old postmenopausal woman was diagnosed with breast carcinoma 2 years ago and modified radical mastectomy was performed. Pathological examination of tumor revealed invasive ductal carcinoma, stage IIIc. She presented with abdominal pain and distension. Diagnostic workup and gynecologic examination revealed lesions that caused diffuse thickening of the uterus wall. Endometrial sampling was performed for confirmation of the diagnosis. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically. Conclusion. We herein report the first case of isolated uterine patient who had invasive ductal carcinoma of breast.

  12. Osteopontin expression in salivary gland carcinomas

    DEFF Research Database (Denmark)

    Bjørndal, Kristine; Larsen, Stine R; Godballe, Christian;

    2011-01-01

    J Oral Pathol Med (2010) Background:  In several cancer types, osteopontin (OPN) expression has been correlated with tumor progression and prognosis. Two earlier studies have examined OPN expression in salivary gland carcinomas with contradictory results. Methods:  One hundred and seventy......-five patients with a primary salivary gland carcinoma diagnosed from January 1, 1990 to December 31, 2005 were identified in the local pathology register, Odense University Hospital. Criteria as documented by Allred et al. were used to assess OPN immunostaining that was performed on surgical specimens. Results......:  Osteopontin was expressed in all salivary gland carcinomas. Adenoid cystic carcinomas had the highest mean sum score (7.3) and a significantly higher proportion of carcinomas with high OPN sum score than both mucoepidermoid carcinoma and acinic cell carcinoma. Correlation of OPN expression with known...

  13. DETECTION OF TELOMERASE ACTIVITY IN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    Yang Wentao; Xu Liangzhong; Zhang Taiming; Zhu weiping; Li Xiaomei; Jin Aiping

    1998-01-01

    Objective:To investigate the significance of telomerase activity in breast carcinoma with its respect to axillary lymph node status. Methods: Telomerase activity was analyzed in 88 breast carcinomas and 16benign breast lesions, using polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay. Results: Telomerase activity was detected in 75 (85%) of 88 breast carcinomas (including three breast carcinomas in situ which were all positive for telomerase activity), whereas in benign breast lesions analyzed only 2(12.5%) of 16 cases were positive for telomerase activity. The difference between the two groups was statistically significant (P<0.001). Besides,telomerase activity was expressed significantly higher in node-positive breast carcinoma (93%) than in nodenegative ones (77%) (P<0.05). Conclusion: Our results suggest that telomerase activation plays an important role during breast carcinoma development. It is possible that this enzyme may serve as an early indication of breast carcinoma.

  14. Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma.

    Science.gov (United States)

    Schmithals, Christian; Köberle, Verena; Korkusuz, Hüdayi; Pleli, Thomas; Kakoschky, Bianca; Augusto, Eduardo Alonso; Ibrahim, Ahmed Atef; Arencibia, Jose M; Vafaizadeh, Vida; Groner, Bernd; Korf, Horst-Werner; Kronenberger, Bernd; Zeuzem, Stefan; Vogl, Thomas J; Waidmann, Oliver; Piiper, Albrecht

    2015-08-01

    iRGD is a derivative of the integrin-binding peptide RGD, which selectively increases the penetrability of tumor tissue to various coadministered substances in several preclinical models. In this study, we investigated the ability of iRGD to improve the delivery of sorafenib and doxorubicin therapy in hepatocellular carcinoma (HCC) using established mouse models of the disease. A contrast-enhanced MRI method was developed in parallel to assess the in vivo effects of iRGD in this setting. We found that iRGD improved the delivery of marker substances to the tumors of HCC-bearing mice about three-fold without a parallel increase in normal tissues. Control peptides lacking the critical CendR motif had no effect. Similarly, iRGD also selectively increased the signal intensity from tumors in Gd-DTPA-enhanced MRI. In terms of antitumor efficacy, iRGD coadministration significantly augmented the individual inhibitory effects of sorafenib and doxorubicin without increasing systemic toxicity. Overall, our results offered a preclinical proof of concept for the use of iRGD coadministration as a strategy to widen the therapeutic window for HCC chemotherapy, as monitored by Gd-DTPA-enhanced MRI as a noninvasive, clinically applicable method to identify iRGD-reactive tumors. PMID:26239478

  15. miR-592/WSB1/HIF-1α axis inhibits glycolytic metabolism to decrease hepatocellular carcinoma growth

    Science.gov (United States)

    Song, Ying; Liu, Mei-You; Yang, Xiao-Juan; Xue, Yan; Wen, Ai-Dong; Shi, Lei

    2016-01-01

    Hepatocellular carcinoma (HCC) cells rapidly switch their energy source from oxidative phosphorylation to glycolytic metabolism in order to efficiently proliferate. However, the molecular mechanisms responsible for this switch remain unclear. In this study, we found that miR-592 was frequently downregulated in human HCC tissues and cell lines, and its downregulation was closely correlated with aggressive clinicopathological features and poor prognosis of HCC patients. Overexpression of miR-592 inhibited aerobic glycolysis and proliferation in HCC cells in vitro. Conversely, knockdown of miR-592 promoted HCC growth in both subcutaneous injection and orthotopic liver tumor implantation models in vivo. Mechanistically, miR-592 downregulation in human HCCs was correlated with an upregulation of WD repeat and SOCS box containing 1 (WSB1). We further showed that miR-592 directly binds to the 3′-UTR of the WSB1 gene, thus disrupting hypoxia inducible factor-1α (HIF-1α) protein stabilization. In turn, overexpression of WSB1 in HCC cells rescued decreased HIF-1α expression, glucose uptake, and HCC growth induced by miR-592. Collectively, our clinical data and functional studies suggest that miR-592 is a new robust inhibitor of the Warburg effect and a promising therapeutic target for HCC treatment. PMID:27153552

  16. Xenotransplanted human prostate carcinoma (DU145) cells develop into carcinomas and cribriform carcinomas: ultrastructural aspects.

    Science.gov (United States)

    Gilloteaux, Jacques; Jamison, James M; Neal, Deborah R; Summers, Jack L; Taper, Henryk S

    2012-10-01

    Androgen-independent, human prostate carcinoma cells (DU145) develop into solid, carcinomatous xenotransplants on the diaphragm of nu/nu mice. Tumors encompass at least two poorly differentiated cell types: a rapidly dividing, eosinophilic cell comprises the main cell population and a few, but large basophilic cells able to invade the peritoneal stroma, the muscular tissue, lymph vessels. Poor cell contacts, intracytoplasmic lumina, and signet cells are noted. Lysosomal activities are reflected by entoses and programmed cell deaths forming cribriform carcinomas. In large tumors, degraded cells may align with others to facilitate formation of blood supply routes. Malignant cells would spread via ascites and through lymphatics.

  17. Breast metastases from rectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    LI Jia; FANG Yu; LI Ang; LI Fei

    2011-01-01

    Metastases to the breast from extramammary neoplasms are very rare, constituting 2.7% of all malignant breast tumours. The most common primary tumor metastatic to the breast is primary breast cancer. Rectal cancer metastasizing to the breast is extremely rare. We report a case of aggressive rectal carcinoma with metastasis to the breast.

  18. Genomic profile of ovarian carcinomas

    OpenAIRE

    Micci, Francesca; Haugom, Lisbeth; Vera M. Abeler; Davidson, Ben; Tropé, Claes G; Heim, Sverre

    2014-01-01

    Background It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory. Methods ...

  19. Tumor Budding in Colorectal Carcinomas

    Directory of Open Access Journals (Sweden)

    Sevda SERT BEKTAŞ

    2012-01-01

    Full Text Available Objective: In colorectal carcinomas, tumor budding has been defined as the presence of isolated single tumor cells or small cell clusters in the stroma at the invasive tumor margin. In this study, the relationship between tumor budding density at the invasive tumor margin and pathological parameters is investigated.Material and Method: Haematoxylin and eosin stained slides of 73 cases with colorectal carcinoma were retrospectively evaluated for the presence and intensity of tumor budding by 2 observers. After the specimens were assessed, the highest density of tumor budding area was counted in a microscopic field of x200. Cases were separated into 2 groups according to tumor budding density as low grade (<10 and high grade (≥10. The relationship of these groups with depth of tumor invasion, histological grade, vascular invasion and lymph node involvement was investigated.Results: Of the 73 colorectal carcinoma cases, 33 (45.2% had low and 40 (54.8% had high grade tumor budding density, respectively. There was a statistically significant relationship between high grade tumor budding density and histological grade (p=0.042, lymph node involvement (p=0.0001 and vascular invasion (p=0.0034.Conclusion: High grade tumor budding density is associated with aggressive phenotypical features in colorectal carcinoma.

  20. New Insights in Hepatocellular Carcinoma

    NARCIS (Netherlands)

    C.D.M. Witjes (Carlijn)

    2012-01-01

    textabstractHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality. HCC is one of the few cancers with well-defined major risk factors. Worldwide, in 80% of the cases HCC develops in cirrhotic livers, and cirrhosis is the stronges

  1. Reinforcing endothelial junctions prevents microvessel permeability increase and tumor cell adhesion in microvessels in vivo

    OpenAIRE

    Bingmei M Fu; Jinlin Yang; Bin Cai; Jie Fan; Lin Zhang; Min Zeng

    2015-01-01

    Tumor cell adhesion to the microvessel wall is a critical step during tumor metastasis. Vascular endothelial growth factor (VEGF), a secretion of tumor cells, can increase microvessel permeability and tumor cell adhesion in the microvessel. To test the hypothesis that inhibiting permeability increase can reduce tumor cell adhesion, we used in vivo fluorescence microscopy to measure both microvessel permeability and adhesion rates of human mammary carcinoma MDA-MB-231 cells in post-capillary v...

  2. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    OpenAIRE

    Mirco Galiè; Paolo Farace; Cristina Nanni; Antonello Spinelli; Elena Nicolato; Federico Boschi; Paolo Magnani; Silvia Trespidi; Valentina Ambrosini; Stefano Fanti; Flavia Merigo; Francesco Osculati; Pasquina Marzola; Andrea Sbarbati

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular ...

  3. Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice

    Institute of Scientific and Technical Information of China (English)

    Volker Schmitz; Miroslaw Kornek; Tobias Hilbert; Christian Dzienisowicz; Esther Raskopf; Christian Rabe; Tilman Sauerbruch; Cheng Qian; Wolfgang H Caselmann

    2005-01-01

    AIM: Tumor angiogenesis has been shown to be promoted by vascular endothelial growth factor (VEGF) via stimulating endothelial cell proliferation, migration, and survival.Blockade of VEGF signaling by different means has been demonstrated to result in reduced tumor growth and suppression of tumor angiogenesis in distinct tumor entities.Here, we tested a recombinant adenovirus, AdsFlt1-3,that encodes an antagonistically acting fragment of the VEGF receptor 1 (Flt-1), for systemic antitumor effects in pre-established subcutaneous CRC tumors in mice.METHODS: Murine colorectal carcinoma cells (CT26) were inoculated subcutaneously into Balb/c mice forin vivo studies. Tumor size and survival were determined. 293cell line was used for propagation of the adenoviral vectors.Human lung cancer line 4549 and human umbilical vein endothelial cells were transfected forin vitro experiments.RESULTS: Infection of tumor cells with AdsFlt1-3 resulted in protein secretion into cell supernatant, demonstrating correct vector function. As expected, the secreted sFlt1-3 protein had no direct effect on CT26 tumor cell proliferation in vitro, but endothelial cell function was inhibited by about 46% as compared to the AdLacZ control in a tube formation assay. When AdsFlt1-3 (5×109 PFU/animal) was applied to tumor bearing mice, we found a tumor inhibition by 72% at d 12 after treatment initiation. In spite of these antitumoral effects, the survival time was not improved.According to reduced intratumoral microvessel density in AdsFlt1-3-treated mice, the antitumor mechanism can be attributed to angiostatic vector effects. We did not detect increased systemic VEGF levels after AdsFlt1-3 treatment and liver toxicity was low as judged by serum alanine aminotransferase determination.CONCLUSION: In this study we confirmed the value of a systemic administration of AdsFlt1-3 to block VEGF signaling as antitumor therapy in an experimental metastatic colorectal carcinoma model in mice.

  4. FBX8 Acts as an Invasion and Metastasis Suppressor and Correlates with Poor Survival in Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Feifei Wang

    Full Text Available F-box only protein 8 (FBX8, a novel component of F-box proteins, is lost in several cancers and has been associated with invasiveness of cancer cells. However, its expression pattern and role in the progression of hepatocellular carcinoma remain unclear. This study investigated the prognostic significance of FBX8 in hepatocellular carcinoma samples and analyzed FBX8 function in hepatocellular carcinoma cells by gene manipulation.The expression of FBX8 was detected in 120 cases of clinical paraffin-embedded hepatocellular carcinoma tissues, 20 matched pairs of fresh tissues and five hepatocellular carcinoma cell lines by immunohistochemistry with clinicopathological analyses, real-time RT-PCR or Western blot. The correlation of FBX8 expression with cell proliferation and invasion in five HCC cell lines was analyzed. Moreover, loss of function and gain of function assays were performed to evaluate the effect of FBX8 on cell proliferation, motility, invasion in vitro and metastasis in vivo.We found that FBX8 was obviously down-regulated in HCC tissues and cell lines (P<0.05. The FBX8 down-regulation correlated significantly with poor prognosis, and FBX8 status was identified as an independent significant prognostic factor. Over-expression of FBX8 decreased proliferation, migration and invasion in HepG2 and 97H cells, while knock-down of FBX8 in 7721 cells showed the opposite effect. FBX8 negatively correlated with cell proliferation and invasion in 7701, M3, HepG2 and 97H cell lines. In vivo functional assays showed FBX8 suppressed tumor growth and pulmonary metastatic potential in mice. Our results indicate that down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma treatment.

  5. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  6. Time-resolved multiphoton imaging of basal cell carcinoma

    Science.gov (United States)

    Cicchi, R.; Sestini, S.; De Giorgi, V.; Stambouli, D.; Carli, P.; Massi, D.; Pavone, F. S.

    2007-02-01

    We investigated human cutaneous basal cell carcinoma ex-vivo samples by combined time resolved two photon intrinsic fluorescence and second harmonic generation microscopy. Morphological and spectroscopic differences were found between malignant skin and corresponding healthy skin tissues. In comparison with normal healthy skin, cancer tissue showed a different morphology and a mean fluorescence lifetime distribution slightly shifted towards higher values. Topical application of delta-aminolevulinic acid to the lesion four hours before excision resulted in an enhancement of the fluorescence signal arising from malignant tissue, due to the accumulation of protoporphyrines inside tumor cells. Contrast enhancement was prevalent at tumor borders by both two photon fluorescence microscopy and fluorescence lifetime imaging. Fluorescence-based images showed a good correlation with conventional histopathological analysis, thereby supporting the diagnostic accuracy of this novel method. Combined morphological and lifetime analysis in the study of ex-vivo skin samples discriminated benign from malignant tissues, thus offering a reliable, non-invasive tool for the in-vivo analysis of inflammatory and neoplastic skin lesions.

  7. Expression of ATP7B in human gastric cardiac carcinomas in comparison with distal gastric carcinomas

    Institute of Scientific and Technical Information of China (English)

    Da-Long Wu; Hui-Xing Yi; Feng-Ying Sui; Xiao-Hong Jiang; Xiao-Ming Jiang; Ying-Ying Zhao

    2006-01-01

    AIM: To analyze expression of ATP7B in gastric cardiac adenocarcinomas, its clinicopathologic significance, in comparison with distal gastric adenocarcinomas.METHODS: Immunohistochemical avidin-biotin peroxidase complex method was applied to detect the expression of ATP7B in 49 cases of cardiac carcinomas,the corresponding adjacent non-neoplastic epithelium and 55 cases of distal gastric carcinomas.RESULTS: The proportion of ATP7B positive samples in gastric cardiac carcinomas (51.0%, 25 of 49) was significantly higher than that in the corresponding adjacent non-neoplastic epithelium (22.4%, 11 of 49)(P = 0.003). ATP7B expression in poorly differentiated gastric cardiac carcinomas was significantly higher than that in well/moderately differentiated gastric cardiac carcinomas (P = 0.030). ATP7B expression in gastric cardiac carcinomas was independent of age, tumor size, nodal stage and metastasis status. ATP7B protein was detected in 30.9% (17/55 cases) of distal gastric carcinomas, markedly lower than that in gastric cardiac carcinomas (P = 0.037).CONCLUSION: ATP7B protein is frequently overexpressed in gastric cardiac carcinomas, and correlated with the differentiation of cardiac carcinoma. ATP7B expression in gastric cardiac carcinomas is significantly higher than that in distal gastric carcinomas, which might partially explain the difference of chemotherapy response and prognosis between these two gastric carcinomas.

  8. Bifunctional phage-based pretargeted imaging of human prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Newton-Northup, Jessica R. [Department of Biochemistry, University of Missouri, Columbia, MO 65211 (United States)], E-mail: newtonj@missouri.edu; Figueroa, Said D. [Department of Radiology, University of Missouri, Columbia, MO 65211 (United States); Quinn, Thomas P.; Deutscher, Susan L. [Department of Biochemistry, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S. Truman Veterans Memorial Hospital, Columbia, MO 65201 (United States)

    2009-10-15

    Introduction: Two-step and three-step pretargeting systems utilizing biotinylated prostate tumor-homing bacteriophage (phage) and {sup 111}In-radiolabeled streptavidin or biotin were developed for use in cancer radioimaging. The in vivo selected prostate carcinoma-specific phage (G1) displaying up to five copies of the peptide IAGLATPGWSHWLAL was the focus of the present study. Methods: The ability of G1 phage to extravasate and target prostate tumor cells was investigated using immunohistochemistry. G1 phages were biotinylated, streptavidin was conjugated to diethylenetriaminepentaacetic acid (DTPA) and biotin was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Biodistribution studies and single-photon emission computed tomography (SPECT)/CT imaging of xenografted PC-3 tumors via two-step pretargeted {sup 111}In-labeled streptavidin and three-step pretargeted {sup 111}In-labeled biotin were performed in SCID mice to determine the optimal pretargeting method. Results: The ability of G1 phage to extravasate the vasculature and bind directly to human PC-3 prostate carcinoma tumor cells in vivo was demonstrated via immunocytochemical analysis. Comparative biodistribution studies of the two-step and three-step pretargeting strategies indicated increased PC-3 human prostate carcinoma tumor uptake in SCID mice of 4.34{+-}0.26 %ID g{sup -1} at 0.5 h postinjection of {sup 111}In-radiolabeled biotin (utilized in a three-step protocol) compared to 0.67{+-}0.06 %ID g{sup -1} at 24 h postinjection of {sup 111}In radiolabeled streptavidin (employed in a two-step protocol). In vivo SPECT/CT imaging of xenografted PC-3 tumors in SCID mice with the three-step pretargeting method was superior to that of the two-step pretargeting method, and, importantly, blocking studies demonstrated specificity of tumor uptake of {sup 111}In-labeled biotin in the three-step pretargeting scheme. Conclusion: This study demonstrates the use of multivalent bifunctional

  9. EDITORIAL: Nanotechnology in vivo Nanotechnology in vivo

    Science.gov (United States)

    Demming, Anna

    2010-04-01

    -imaging labels [4]. A surface hydroxyl group renders silicon quantum dots soluble in water and the photoluminescence can be made stable with oxygen-passivation. In addition, researchers in Japan have demonstrated how the initially modest yield in the preparation of silicon quantum dots can be improved to tens of milligrams per batch, thus further promoting their application in bio-imaging [5]. In the search for non-toxic quantum dots, researchers at the Amrita Centre for Nanoscience in India have prepared heavy metal-free quantum dot bio-probes based on single phase ZnS [6]. The quantum dots are selectively doped with metals, transition metals and halides to provide tuneable luminescence properties, and they are surface conjugated with folic acid for cancer targeting. The quantum dots were demonstrated to be water-soluble, non-toxic in normal and cancer cell lines, and have bright, tuneable luminescence. So far most of the quantum dots developed for bio-imaging have had excitation and emission wavelengths in the visible spectrum, which is highly absorbed by tissue. This limits imaging with these quantum dots to superficial tissues. This week, researchers in China and the US reported work developing functionalized dots for in vivo tumour vasculature in the infrared part of the spectrum [7]. In addition the quantum dots were functionalised with glycine-aspartic acid (RGD) peptides, which target the vasculature of almost all types of growing tumours, unlike antibody- or aptamer-mediated targeting strategies that are specific to a particular cancer type. In this issue, researchers in China and the US demonstrate a novel type of contrast agent for ultrasonic tumour imaging [8]. Contrast-enhanced ultrasonic tumour imaging extends the diagnostic and imaging capabilities of traditional techniques. The use of nanoparticles as ultrasound contrast agents exploits the presence of open pores in the range of 380 to 780 nm in tumour blood vessels, which enhance the permeability and retention

  10. The antiprogestins mifepristone and onapristone reduce cell proliferation in the canine mammary carcinoma cell line CMT-U27.

    Science.gov (United States)

    Guil-Luna, Silvia; Hellmén, Eva; Sánchez-Céspedes, Raquel; Millán, Yolanda; Martín de las Mulas, Juana

    2014-07-01

    Canine mammary tumours (CMTs) represent nearly half of all tumours in female dogs and some 50% have malignant behaviour. Simple epithelial carcinomas have shorter disease free periods after surgery and a higher reduction of the proliferation index reduction after antiprogestin aglepristone treatment in vivo related to the expression of progesterone receptors (PR). These findings make simple carcinomas good candidates for endocrine therapy. To further explore this possibility, the effects of the antiprogestins mifepristone (RU486) and onapristone (ZK299) on cell viability and PR expression of the canine mammary carcinoma cell line isolated from a simple epithelial carcinoma CMT-U27 were studied. Twenty five percent of CMT-U27 control cells expressed PR. RU486 (ptest) at 24h but only the latter treatment reduced significantly PR expression in viable tumour cells at 24h of incubation. The results suggest that both RU486 and ZK299 induce a decrease in the number of viable CMT-U27 tumour cells with different effects on PR expression. The canine mammary carcinoma cell line CMT-U27 is sensitive to the effects of antiprogestins and may serve to further explore the role of these drugs in canine mammary carcinomas. PMID:24500783

  11. Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi-mian; YANG Xiao-yun; DENG Shu-hai; XU Wei; GAO Hai-qing

    2007-01-01

    exhibited a markedly higher apoptotic index compared with control tumors. Western blot analysis of tumor tissue revealed that the down-regulated expression of proliferation cell nuclear antigen (PCNA) and Bcl-2 proteins in DATS-PBCA-NP group, and there were no significant differences in the expression of Fas, FasL and Bax proteins among the four groups (P>0.05).Conclusions DATS-PBCA-NP has good prolonged release effect in vivo and hepatic-targeted activity, and significant anti-tumor effect on the orthotopic transplantation HCC model in mice in association with the suppression of proliferation and the induction of apoptosis of tumor cells. These advantages are probably due to their liver targeting characteristics and consequently bring a higher anti-tumor activity.

  12. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism1

    Science.gov (United States)

    Galie, Mirco; Farace, Paolo; Nanni, Cristina; Spinelli, Antonello; Nicolato, Elena; Boschi, Federico; Magnani, Paolo; Trespidi, Silvia; Ambrosini, Valentina; Fanti, Stefano; Merigo, Flavia; Osculati, Francesco; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET), we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition. PMID:18030358

  13. Inhibitory effects of tanshinone Ⅱ-A on invasion and metastasis of human colon carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Yun-feng SHAN; Xian SHEN; Yuan-kang XIE; Ji-cai CHEN; Hong-qi SHI; Zheng-ping YU; Qi-tong SONG; Men-tao ZHOU; Qi-yu ZHANG

    2009-01-01

    Aim: To investigate the effects and possible mechanisms of tanshinone Ⅱ-A, an alcohol extract of the root of Salvia miltiorrhiza Bunge, on tumor invasion and metastasis of human colon carcinoma (CRC) cells.Methods: The effects of tanshinone Ⅱ-A on invasion and metastasis of CRC cell lines HT29 and SW480 were evaluated by in vitro and in vivo assays. Western blotting was used to investigate possible molecular mechanisms of tanshinone Ⅱ-A anti-cancer actions. Results: Tanshinone Ⅱ-A inhibited migration and invasion of CRC cells in a dose-dependent manner. The inhibitory effect also depended on time, with the most significant effects observed at 72 h. Tanshinone Ⅱ-A also significantly inhibited in vivo metastasis of colon carcinoma SW480 cells. It inhibited in vitro and in vivo invasion and metastasis of CRC cells by reducing levels of urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMP)-2 and MMP-9, and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-1 and TIMP-2. Tanshinone Ⅱ-A was also shown to suppress the nuclear factor-kappaB (NF-kB) signal. Conclusion: Tanshinone Ⅱ-A inhibited in vitro and in vivo invasion and metastasis of CRC cells. The effect resulted from changes in the levels of uPA, MMP-2, MMP-9, TIMP-1, and TIMP-2, and apparent inhibition of the NF-kB signal transduction pathway.

  14. Cold atmospheric plasma treatment selectively targets head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Guerrero-Preston, Rafael; Ogawa, Takenori; Uemura, Mamoru; Shumulinsky, Gary; Valle, Blanca L; Pirini, Francesca; Ravi, Rajani; Sidransky, David; Keidar, Michael; Trink, Barry

    2014-10-01

    The treatment of locoregional recurrence (LRR) of head and neck squamous cell carcinoma (HNSCC) often requires a combination of surgery, radiation therapy and/or chemotherapy. Survival outcomes are poor and the treatment outcomes are morbid. Cold atmospheric plasma (CAP) is an ionized gas produced at room temperature under laboratory conditions. We have previously demonstrated that treatment with a CAP jet device selectively targets cancer cells using in vitro melanoma and in vivo bladder cancer models. In the present study, we wished to examine CAP selectivity in HNSCC in vitro models, and to explore its potential for use as a minimally invasive surgical approach that allows for specific cancer cell or tumor tissue ablation without affecting the surrounding healthy cells and tissues. Four HNSCC cell lines (JHU-022, JHU-028, JHU-029, SCC25) and 2 normal oral cavity epithelial cell lines (OKF6 and NOKsi) were subjected to cold plasma treatment for durations of 10, 30 and 45 sec, and a helium flow of 20 l/min-1 for 10 sec was used as a positive treatment control. We showed that cold plasma selectively diminished HNSCC cell viability in a dose-response manner, as evidenced by MTT assays; the viability of the OKF6 cells was not affected by the cold plasma. The results of colony formation assays also revealed a cell-specific response to cold plasma application. Western blot analysis did not provide evidence that the cleavage of PARP occurred following cold plasma treatment. In conclusion, our results suggest that cold plasma application selectively impairs HNSCC cell lines through non-apoptotic mechanisms, while having a minimal effect on normal oral cavity epithelial cell lines.

  15. Epidemiologia do carcinoma basocelular Epidemiology of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Valquiria Pessoa Chinem

    2011-04-01

    Full Text Available O carcinoma basocelular é a neoplasia maligna mais comum em humanos e sua incidência vem aumentando nas últimas décadas. Sua grande frequência gera significativo ônus ao sistema de saúde, configurando problema de saúde pública. Apesar das baixas taxas de mortalidade e de rara ocorrência de metástases, o tumor pode apresentar comportamento invasivo local e recidivas após o tratamento, provocando importante morbidade. Exposição à radiação ultravioleta representa o principal fator de risco ambiental associado a sua gênese. Entretanto, descrevem-se outros elementos de risco: fotótipos claros, idade avançada, história familiar de carcinomas de pele, olhos e cabelos claros, sardas na infância e imunossupressão, além de aspectos comportamentais, como exercício profissional exposto ao sol, atividade rural e queimaduras solares na juventude. Entre 30% e 75% dos casos esporádicos estão associados à mutação do gene patched hedgehog, mas outras alterações genéticas são ainda descritas. A neoplasia é comumente encontrada concomitantemente com lesões cutâneas relacionadas à exposição solar crônica, tais como: queratoses actínicas, lentigos solares e telangiectasias faciais. A prevenção do carcinoma basocelular se baseia no conhecimento de fatores de risco, no diagnóstico e tratamento precoces e na adoção de medidas específicas, principalmente, nas populações susceptíveis. Os autores apresentam uma revisão da epidemiologia do carcinoma basocelular.Basal cell carcinoma is the most common malignant neoplasm in humans and its incidence has increased over the last decades. Its high frequency significantly burdens the health system, making the disease a public health issue. Despite the low mortality rates and the rare occurrence of metastases, the tumor may be locally invasive and relapse after treatment, causing significant morbidity. Exposure to ultraviolet radiation is the main environmental risk factor

  16. Carcinoma verrugoso en paciente joven Verrucous carcinoma in young patient

    Directory of Open Access Journals (Sweden)

    LN Rosa

    2003-06-01

    Full Text Available El carcinoma verrucoso es una variación de bajo grado de malignidad del carcinoma de células escamosas oral, y la mayoría surge en la mucosa oral de individuos que mascan tabaco de forma crónica (6, 8, 10. Estas lesiones encontradas predominantemente en hombres, con más de 55 años de edad (edad promedio de 65 a 70 anos y las regiones de mayor frecuencia en mucosa bucal incluyen vestíbulo mandibular, mucosa yugal y palato duro (6, 8. La lesión aparece como una placa espesa, difusa, bien demarcada e indolora, con proyecciones superficiales papilares o verruciformes. Microscópicamente, se observa la presencia de crestas interpapilares anchas y alargadas y producción abundante de ceratina (2. La metástasis es un evento raro en los carcinomas verrucosos (6, 8, 9. El tratamiento de elección es la excisión quirúrgica, asociada o no a la radioterapia. Los autores relatan un caso clínico de una paciente de 13 años de edad con lesión comprometiendo todo lo vermellion del labio inferior. El tratamiento inicial propuesto fue la radioterapia asociado a la quimioterapia, decido a la edad de la paciente, localización y extensión de la lesión. Después de una dosis total de 70Gy, hubo la regresión total de la lesión. Siendo así, el tratamiento del carcinoma verrucoso asociando a la radioterapia y quimioterapia se mostró adecuado en este caso.The verrucous carcinoma is a low grade variant of oral squamous cell carcinoma, and it mostly appears in the oral mucosa of individuals who chew tobacco chronically 6, 8, 10. The lesions are mainly found in men over 55 years old (average age 65 to 70 years and the most common regions in the oral mucosa include the mandibular vestibule, jugal mucosa and hard palate 6, 8. The lesion appears as a well-defined painless diffuse thick plaque with superficial papillary or verruciform projections. Under the microscope the presence of wide elongated interpapilIary ridges and copious keratin production are

  17. In vivo dosimetry for IMRT

    Science.gov (United States)

    Vial, Philip

    2011-05-01

    In vivo dosimetry has a well established role in the quality assurance of 2D radiotherapy and 3D conformal radiotherapy. The role of in vivo dosimetry for IMRT is not as well established. IMRT introduces a range of technical issues that complicate in vivo dosimetry. The first decade or so of IMRT implementation has largely relied upon pre-treatment phantom based dose verification. During that time, several new devices and techniques for in vivo dosimetry have emerged with the promise of providing the ultimate form of IMRT dose verification. Solid state dosimeters continue to dominate the field of in vivo dosimetry in the IMRT era. In this report we review the literature on in vivo dosimetry for IMRT, with an emphasis on clinical evidence for different detector types. We describe the pros and cons of different detectors and techniques in the IMRT setting and the roles that they are likely to play in the future.

  18. Chaiqiyigan granula enhances Taxol-induced growth inhibition of hepatocellular carcinoma xenografts in nude mice: an in vivo fluorescence imaging study%柴芪益肝颗粒联合紫杉醇抑制裸鼠肝癌生长的在体成像研究

    Institute of Scientific and Technical Information of China (English)

    游敏玲; 罗满芳; 廖蔚茜; 胡世平; 许文学; 靖林林

    2012-01-01

    Objective To study the effects of Chaiqiyigan Granula (CG) and Taxol on the growth of hepatocellular carcinoma (HCC) xenografts and expression of Bax, p53 and VEGF in nude mice. Methods Whole-body fluorescence imaging was used to visualize the growth of HCC in nude mice bearing hepG2/EGFP cell xenograft. Irnmunohistochemistry was used to determine the content of Bax, p53 and vascular endothelial growth factor (VEGF) in the tumor tissues. Results Compared with normal saline, Taxol alone and in combination with CG significantly inhibited the growth of HCC xenografts in the nude mice. The combined treatment with CG and Taxol produced a stronger inhibitory effect on the tumor growth than Taxol alone in the third and fourth weeks. The volume and weight of the xenografts were decreased in the combined treatment group compared with those in saline treatment group. CG combined with Taxol increased the expression of Bax and reduced the expression of p53 and VEGF in the tumor xenografts. Conclusion CG can enhance the inhibitory effects of Taxol on the growth of HCC xenografts, and this effect is related to the up-regulation of Bax and down-regulation of p53 and VEGF expression in the tumor.%目的 探讨柴芪益肝颗粒(CG)和紫杉醇(taxol)对裸鼠异位肝癌的作用及对Bax、p53和VEGF表达的影响.方法 应用转染及G418筛选构建单克隆Hep G2/EGFP细胞系,细胞注射至裸鼠形成异位肝癌模型,应用荧光成像技术在体观察在柴芪益肝颗粒合Taxol作用下肿瘤的生长,用免疫组化法检测肿瘤组织中Bax、p53、VEGF的表达.结果 与对照组相比,Taxol组和Taxol+CG组在3周和4周时降低肝癌增殖速度,Taxol+CG组抑制作用显著优于Taxol组比.Taxol+CG组增加Bax表达,降低p53表达和VEGF表达.结论 柴芪益肝颗粒明显增强Taxol对裸鼠异位肝癌生长的抑制作用,其作用与增加Bax表达、抑制p53、VEGF表达相关.

  19. Pure compared with mixed serous endometrial carcinoma: two different entities?

    NARCIS (Netherlands)

    Roelofsen, T.; Ham, M.A. van; Wiersma van Tilburg, J.M.; Zomer, S.F.; Bol, M.; Massuger, L.F.A.G.; Bulten, J.

    2012-01-01

    OBJECTIVE: : To analyze whether mixed compared with pure uterine papillary serous carcinoma histology affects clinical outcome, and to assess uterine papillary serous carcinoma for its association with the precursor lesion endometrial intraepithelial carcinoma. METHODS: : A multi-institution observa

  20. Axillary node metastasis from primary ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Trupti S Patel

    2014-01-01

    Full Text Available Metastasization and distinction from mammary carcinoma is of great clinical importance because of different treatment modalities. Here, we discuss a case of stage IIIC ovarian serous carcinoma, presenting with bilateral axillary nodes metastasis after 25 months interval of its initial presentation. Increased serum CA-125 level caused clinical suspicion. Computed tomography scan of abdomen and pelvis showed no residual disease or any abdominal lymphadenopathy. Mammography of both breast were normal. Bilateral axillary nodes were noted. Guided fine needle aspiration cytology (FNAC and biopsy of ovarian carcinoma to axillary node is a rare event. Its recogn done. Cytomorphology revealed poorly differentiated carcinoma, compatible to that of primary ovarian tumor. Thus, metastatic carcinoma to axillary node from ovary was confirmed. This case illustrates a rare metastatic presentation of ovarian carcinoma and unequivocal role of FNAC to provide rapid diagnosis and preferred to be first line diagnostic procedure.

  1. Local excision for selected colorectal carcinomas.

    Science.gov (United States)

    Lawrence, M A; Goldberg, S M

    1989-07-01

    In summary, local excision is a useful tool in the management of selected colorectal carcinomas. The advent of the fibreoptic colonoscope has revised the concept of local excision when dealing with carcinoma-containing polyps of the colon. The clinician now has the means of locally excising certain carcinomas which would have required laparotomy in the not so distant past. In dealing with carcinoma of the rectum, local excision is not advocated for all rectal carcinomas. In fact, when the previously discussed tumour related factors are considered, local excision should be the ultimate procedure in less than 5% of operations performed for rectal carcinomas. However, when appropriately used, local excision provides a less morbid alternative to more radical procedures without compromising patient survival rates or local recurrence rates. PMID:2692739

  2. Proteomics in Discovery of Hepatocellular Carcinoma Biomarkers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To discover new proteomic biomarkers of hepatocellular carcinoma. Methods: Surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry was used to discover biomarkers for differentiating hepatocellular carcinoma and chronic liver disease. A population of 50 patients with hepatocellular carcinoma and 33 patients with chronic liver disease was studied. Results: Twelve proteomic biomarkers of hepatocellular carcinoma were detected in this study. Three proteomic biomarkers were highly expressed in hepatocellular carcinoma and nine proteomic biomarkers were highly expressed in chronic liver disease. The most valuable proteomic biomarker with m/z=11498 had no similar diagnostic value as α-fetoprotein. Conclusion:Some of the twelve proteomic biomarkers may become new biomarkers of hepatocellular carcinoma.

  3. EBV-associated gastric carcinoma in high- and low-incidence areas for nasopharyngeal carcinoma

    DEFF Research Database (Denmark)

    Boysen, T.; Mohammadi, M.; Melbye, M.;

    2009-01-01

    BACKGROUND: Approximately 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV). The Inuit in Greenland have a high incidence of EBV-associated nasopharyngeal carcinoma. METHODS: We conducted a population-based case-control study comparing gastric carcinomas in Greenland and in D...

  4. Topical MMP beacon enabled fluorescence-guided resection of oral carcinoma.

    Science.gov (United States)

    Burgess, Laura; Chen, Juan; Wolter, Nikolaus E; Wilson, Brian; Zheng, Gang

    2016-03-01

    Each year almost 300,000 individuals worldwide are diagnosed with oral cancer, more than 90% of these being oral carcinoma [N. Engl. J. Med.328, 1841993]. Surgical resection is the standard of care, but accurate delineation of the tumor boundaries is challenging, resulting in either under-resection with risk of local recurrence or over-resection with increased functional loss and negative impact on quality of life. This study evaluates, in two pre-clinical in vivo tumor models, the potential of fluorescence-guided resection using molecular beacons activated by metalloproteinases, which are frequently upregulated in human oral cancer. In both models there was rapid (beacon activation upon local application, allowing clear fluoresecence imaging in vivo and confirmed by ex vivo fluorescence microscopy and HPLC, with minimal activation in normal oral tissues. Although the tissue penetration was limited using topical application, these findings support further development of this approach towards translation to first-in-human trials. PMID:27231609

  5. Topical MMP beacon enabled fluorescence-guided resection of oral carcinoma.

    Science.gov (United States)

    Burgess, Laura; Chen, Juan; Wolter, Nikolaus E; Wilson, Brian; Zheng, Gang

    2016-03-01

    Each year almost 300,000 individuals worldwide are diagnosed with oral cancer, more than 90% of these being oral carcinoma [N. Engl. J. Med.328, 1841993]. Surgical resection is the standard of care, but accurate delineation of the tumor boundaries is challenging, resulting in either under-resection with risk of local recurrence or over-resection with increased functional loss and negative impact on quality of life. This study evaluates, in two pre-clinical in vivo tumor models, the potential of fluorescence-guided resection using molecular beacons activated by metalloproteinases, which are frequently upregulated in human oral cancer. In both models there was rapid (beacon activation upon local application, allowing clear fluoresecence imaging in vivo and confirmed by ex vivo fluorescence microscopy and HPLC, with minimal activation in normal oral tissues. Although the tissue penetration was limited using topical application, these findings support further development of this approach towards translation to first-in-human trials.

  6. Scalp squamous cell carcinoma in xeroderma pigmentosum

    OpenAIRE

    Awan, Basim A; Hanadi Alzanbagi; Osama A Samargandi; Hossam Ammar

    2014-01-01

    Context: Xeroderma pigmentosum is a rare autosomal-recessive disorder that appears in early childhood. Squamous cell carcinoma is not uncommon in patients with xeroderma pigmentosum and mostly involving the face, head, neck, and scalp. However, squamous cell carcinoma of the scalp may exhibit an aggressive course. Case Report: Here, we present a huge squamous cell carcinoma of the scalp in a three-years-old child with xeroderma pigmentosum. In addition, we illustrate the challenges of a child...

  7. Synchronous Squamous Cell Carcinoma in Multiple Digits

    OpenAIRE

    Abner, Sabra; Redstone, Jeremiah; Chowdhry, Saeed; Kasdan, Morton L.; Wilhelmi, Bradon J.

    2011-01-01

    Cancers of the perionychium are relatively rare occurrences and are often related to chronic inflammation associated with trauma, infection, exposure to ultraviolet radiation, or other carcinogens. Squamous cell carcinoma is the most common tumor reported of the nail bed. Synchronous squamous cell carcinomas of the perionychium have been rarely reported. We present a case of a 46-year-old woman with synchronous squamous cell carcinomas involving both hands and multiple digits. Treatment modal...

  8. Unusual Presentation of Cystic Papillary Thyroid Carcinoma

    OpenAIRE

    Patil, Vijayraj S.; Abhishek Vijayakumar; Neelamma Natikar

    2012-01-01

    Papillary thyroid carcinoma is the most common thyroid malignancy, accounting for 80% of all thyroid cancers. The most common presentation of thyroid cancer is an asymptomatic thyroid mass or a nodule. Usually as thyroid enlarges, it extends in to mediastinum. Papillary thyroid carcinoma presentation as multiple true cystic swelling extending from neck to anterior chest wall in subcutaneous plane is not present in the literature. We present a rare case of cystic papillary thyroid carcinoma wh...

  9. Merkel Cell Carcinoma Concurrent with Bowen's Disease

    OpenAIRE

    Park, Hyun Chul; Kang, Ho Song; Park, Kyoung Tae; Oh, Young Ha; Yu, Hee Joon; Kim, Joung Soo

    2012-01-01

    Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy of the elderly and immunocompromised patients. It is occasionally found coexisting with other diseases, such as squamous cell carcinoma, basal cell carcinoma, actinic keratosis, miscellaneous adnexal tumors, and rarely Bowen disease. A 75-year-old woman presented with a 6-month history of an irregularly shaped erythematous patch on the left mandibular angle. Three months later, a 1.5×1.0 cm sized painless and rapidly growi...

  10. Sinonasal verrucous carcinoma with oral invasion

    Directory of Open Access Journals (Sweden)

    Karthikeya P

    2006-01-01

    Full Text Available Verrucous carcinoma is a rare warty variant of squamous cell carcinoma, most often seen in the oral cavity and larynx. Its occurrence in the sinonasal tract is rare. This tumor constitutes approximately 1% of all sinonasal neoplasms. The clinical presentation and the histopathological features of verrucous carcinoma are a subject of continuous discussion amongst diagnosticians and pathologists. A case with oral and nasal presentation of this tumor is reported here.

  11. Neglected Giant Scalp Basal Cell Carcinoma

    OpenAIRE

    Anne Kristine Larsen, MD; Waseem-Asim Ghulam El-Charnoubi, MD; Julie Gehl, MD, PhD; Christen Krag, MD, PhD

    2014-01-01

    Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstruct...

  12. DNA methylation in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Iris Tischoff; Andrea Tannapfel

    2008-01-01

    As for many other tumors, development of hepatocellular carcinoma (HCC) must be understood as a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes (TSG). In the last decades, in addition to genetic alterations, epigenetic inactivation of (tumor suppressor) genes by promoter hypermethylation has been recognized as an important and alternative mechanism in tumorigenesis. In HCC, aberrant methylation of promoter sequences occurs not only in advanced tumors, it has been also observed in premalignant conditions just as chronic viral hepatitis B or C and cirrhotic liver. This review discusses the epigenetic alterations in hepatocellular carcinoma focusing DNA methylation.

  13. Gastric Large Cell Neuroendocrine Carcinoma

    Science.gov (United States)

    Rustagi, Tarun; Alekshun, Todd J.

    2010-01-01

    Case: A 63-year-old male presented with unintentional weight loss of 20 pounds over a 4-month duration. He reported loss of appetite, intermittent post-prandial nausea, bloating and early satiety. He also complained of dyspepsia and had been treated for reflux during the previous 2 years. He denied vomiting, dysphagia, odynophagia, abdominal pain, melena, hematochezia, or alterations in bowel habits. Additionally, he denied fevers, night sweats, cough, or dyspnea. He quit smoking 25 years ago, and denied alcohol use. His past medical history was significant for basal cell carcinoma treated with local curative therapy and he was without recurrence on surveillance. Pertinent family history included a paternal uncle with lung cancer at the age of 74. Physical examination was unremarkable except for occult heme-positive stools. Laboratory evaluation revealed elevated liver enzymes (ALT-112, AST-81, AlkPhos-364). CT scan of the chest, abdomen and pelvis showed diffuse heterogeneous liver with extensive nodularity, raising the concern for metastases. Serum tumor-markers: PSA, CEA, CA 19-9, and AFP were all within normal limits. Screening colonoscopy was normal, but esophagogastroduodenoscopy revealed a malignant-appearing ulcerative lesion involving the gastro-esophageal junction and gastric cardia. Pathology confirmed an invasive gastric large cell neuroendocrine carcinoma. Ultrasound-guided fine needle aspiration of a hepatic lesion revealed malignant cells with cytologic features consistent with large-cell type carcinoma and positive immunostaining for synaptophysin favoring neuroendocrine differentiation. A PET-CT demonstrated intense diffuse FDG uptake of the liver, suggesting diffuse hepatic parenchymal infiltration by tumor. There were multiple foci of intense osseous FDG uptake with corresponding osteolytic lesions seen on CT scan. The remaining intra-abdominal and intra-thoracic structures were unremarkable. The patient will receive palliative systemic therapy

  14. Thyroid carcinomas of Belarussian children

    International Nuclear Information System (INIS)

    The incidence of thyroid carcinoma increases significantly following exposure to ionizing irradiation. However, the mechanisms of radiation-induced tumorigenesis at the molecular and chromosomal levels have not been identified. In order to gain some indication of the processes affecting the thyroid epithelium, cytogenetic and molecular genetic investigations were performed on childhood thyroid carcinomas that developed after the Chernobyl nuclear accident in Belarussia, and on secondary thyroid tumours that developed after radiotherapy. At the cytogenetic level, the radiation-induced tumours were shown to have an increased frequency of translocations, multiple and complex chromosome aberrations, and novel breakpoints for structural chromosome aberrations. At the molecular level, different alterations of the RET protooncogene were detected in 65% of the Belarussian tumours. (orig.)

  15. [Tumor markers for hepatocellular carcinoma].

    Science.gov (United States)

    Tateishi, Ryosuke; Enooku, Kenichiro; Shiina, Shuichiro; Koike, Kazuhiko

    2012-05-01

    Three tumor markers for hepatocellular carcinoma (HCC) are available in Japan: alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonists-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). Although AFP has drawbacks in its specificity, it is widely utilized in treatment evaluation and prognosis prediction. PIVKA-II is a unique marker that does not correlate with AFP value and can predict microvascular invasion. AFP-L3 is a highly specific marker and strong predictor of poor prognosis. These three markers are indispensable in every aspect of clinical practice of hepatocellular carcinoma including surveillance, diagnosis, treatment evaluation, and prognosis prediction.

  16. PANCREATIC CARCINOMA: REVIEW OF LITERATURE

    Directory of Open Access Journals (Sweden)

    Veena Kumari

    2015-05-01

    Full Text Available It is well known that the prognosis of pancreatic cancer is extremely poor, even when treated with radical surgery. The overall 5 year survival rate following surgical intervention is around 10%.With the increasing use of CT scans for other reasons not related to pancreas, a variety of neoplastic and non - neoplastic lesions are increasingly encountered in clinical practice. The distinction of these lesions has significant therapeutic and prognostic implications. Regarding ductal carcinoma, key distinguishing features from chronic pancreatitis and a discussion of the concept of pancreatic intraepithelial neoplasia ( PanIN are included. Precursors, mo lecular carcinogenesis, risk factors and different morphological patterns of tumors arising from exocrine pancreas are discussed. Research on early detection is ongoing. Screening of people with a family history of hereditary pancreatitis plays an importan t role in the early detection of ductal carcinoma of pancreas.

  17. [Cytostatic treatment of ovarian carcinoma].

    Science.gov (United States)

    Neijt, J P

    1999-10-30

    Shortly after treatment with the cytostatic combination of cisplatin and paclitaxel was generally accepted as the standard therapy for patients with epithelial ovarian carcinoma, many have come to regard the combination of carboplatin and paclitaxel as a better choice. The latter combination causes fewer side effects and may be used in the outpatient clinic. Conceivably, the carboplatin-paclitaxel scheme will shortly have to be adjusted again owing to results of current research. The intensive basic research of recent years, namely, is beginning to yield benefits for the therapeutic arsenal against ovarian carcinoma. Possibilities are inhibitors of the breakdown of extracellular matrix (such as marimastat) and inhibitors of signal transduction (such as trastuzumab). PMID:10578409

  18. Sebaceous carcinoma. Presenting a case

    International Nuclear Information System (INIS)

    Patient of feminine sex of 65 years of age with tumor of approximately 1.5 cm of diameter, located in the right palpebral region, being put under ample exeresis of a tumor more pastia, whose anatomopathology result revealed sebaceous carcinoma with free edges. This is a rare malignant carcinoma that originates in perioculars sebaceous glands like the glands of Meibomio that affects the superior flicker. Clinically it appears like a small nodule, of small growth and its diagnose is based on a high degree of suspicion in any chronic process of the flicker. The selection processing is the surgery, the x-ray, radiotherapy is useful in the postoperating attention and like palliative therapy. (The author)

  19. Management of Recurrent Endometrial Carcinoma.

    OpenAIRE

    Ming-Shian Kao

    2004-01-01

    Management of recurrent endometrial carcinoma has traditionally focused on providingtargeted adjuvant therapy in select groups of patients based on their risk factors. Majorprogress has been made over the last two decades in identifying these clinical-pathologicalrisk factors, which has led to the classification of patients into different risk groups. Patientswith high-risk factors are generally treated with adjunctive radiation therapy immediatelyfollowing surgery to minimize the incidence o...

  20. Inflammatory carcinomas of the breast.

    OpenAIRE

    Anderson, J. M.

    1980-01-01

    Only 4.4% of patients with inflammatory carcinomas of the breast survive 5 years. The incidence of the disease is fortunately low at less than 2% of all mammary malignancies, and there is no relationship to pregnancy or lactation. Clinical diagnosis should be supplemented by searches for microscopic metastases in dermal lymphatics and for distant metastases before a therapeutic programme is planned. Combinations of local and systemic treatments best suited to each individual should be devised...

  1. Herbal Medicine and Hepatocellular Carcinoma: Applications and Challenges

    Directory of Open Access Journals (Sweden)

    Yan Li

    2011-01-01

    Full Text Available Use of herbal medicine in the treatment of liver cancer has a long tradition. The compounds derived from the herb and herbal composites are of considerable interest among oncologists. In the past, certain herbal compounds and herbal composite formulas have been studied through in vitro and in vivo as an anti-hepatocellular carcinoma (HCC agent, enhancing our knowledge about their biologic functions and targets. However there is a significant distinction between the herbal medicine and the herbal production even though both are the plant-based remedies used in the practice. In this article, for the sake of clarity, the effective herbal compounds and herbal composite formulas against HCC are discussed, with emphasizing the basic conceptions of herbal medicine in order to have a better understanding of the prevention and treatment of HCC by herbal active compounds and herbal composite formulas.

  2. Larynx carcinoma regulates tumor-associated macrophages through PLGF signaling.

    Science.gov (United States)

    Zhou, Xu; Qi, Ying

    2015-01-01

    Cancer neovascularization plays an essential role in the metastasis of larynx carcinoma (LC). However, the underlying molecular mechanisms are not completely understood. Recently, we reported that placental growth factor (PLGF) regulates expression of matrix metalloproteinase 3 (MMP3) through ERK/MAPK signaling pathway in LC. Here, we show that MMP9 upregulated in LC, and appeared to be mainly produced by M2 macrophages (tumor-associated macrophages (TAM)). In a transwell co-culture system, PLGF secreted by LC cells triggered macrophage polarization to a TAM subtype that releases MMP9. Moreover, MMP9 was found to be activated in the PLGF-polarized TAM via transforming growth factor β (TGFβ) receptor signaling activation. Furthermore, PLGF in LC cells induced macrophage polarization in vivo, and significantly promoted the growth of LC. Thus, together with our previous work, our study highlights a pivotal role of cross-talk between TAM and LC in regulating the metastasis of LC. PMID:25961789

  3. Intrathyroidal parathyroid carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    You, Woo Young; Han, You Mie; Choi, Young Hee [Hallym University College of Medicine, Dongtan Sacred Heart Hospital, Hwaseong (Korea, Republic of)

    2015-05-15

    Parathyroid carcinoma is an uncommon malignancy and a rare cause of primary hyperparathyroidism. Intrathyroidal parathyroid carcinoma is even rarer and only few cases have been reported previously. A 33-year-old woman presented with hypercalcemia. CT scan revealed a 5-cm sized intrathyroid nodule with a positive beak sign on the surface in contact with the thyroid gland. The patient underwent total thyroidectomy, and the histopathologic examination confirmed the diagnosis of parathyroid carcinoma. We report a case of intrathyroidal parathyroid carcinoma with brief literature review.

  4. Squamous Cell Carcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Andre Luiz De Souza

    2014-11-01

    Full Text Available We previously published our and Johns Hopkins data titled: "Platinum-based therapy in adenosquamous pancreatic cancer: experience at two institutions” [1]. We will here like to submit a related case report as a letter to the editor to JOP in reference to the above paper. Squamous cell carcinoma of the pancreas has various reported incidence rates, ranging from 0.5% to as high as 5% of pancreatic ductal carcinomas [2, 3]. Of the 1300 cases of pancreatic cancers observed at autopsy in a survey in Japan in 1992, 0.7% were squamous cell carcinoma [4]. A Mayo clinic review of very rare exocrine tumors showed an even rarer incidence of squamous cell carcinoma when compared to acinar and small cell carcinoma of the pancreas [5]. This discrepancy in the reported incidence rates related to the fact that some of the cases represent adenosquamous carcinoma rather than pure squamous cell carcinoma of pancreas. In an analysis of 25 patients, mean age at diagnosis of pancreatic squamous cell carcinoma was 62 years (range: 33–80 years and there was no gender difference [6]. There is no study about the molecular profile of squamous carcinoma of the pancreas. There are no retrospective or prospective studies about the best therapy for these tumors

  5. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  6. Immunotherapy in renal cell carcinoma.

    Science.gov (United States)

    Bukowski, R M

    1999-06-01

    Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy include the observations of spontaneous tumor regression, the presence of a T-cell-mediated immune response, and the tumor responses observed in patients receiving cytokine therapy. Analysis of prognostic factors in these patients demonstrates that clinical responses occur most frequently in individuals with good performance status. The cytokines interleukin-2 (IL-2, aldesleukin [Proleukin], interferon-alfa (Intron A, Roferon-A), or the combination produce responses in 15% to 20% of patients. Randomized trials suggest that administration of interferon-alfa may result in a modest improvement in median survival. Investigation of the molecular genetics of renal cell carcinoma and the presence of T-lymphocyte immune dysregulation have suggested new therapeutic strategies. Further preclinical and clinical studies investigating inhibitors of angiogenesis or pharmacologic methods to reverse immune dysregulation are ongoing. Therapeutic results in patients with renal cell carcinoma remain limited, and investigational approaches are warranted. PMID:10378218

  7. Calcitriol-copper interaction leads to non enzymatic, reactive oxygen species mediated DNA breakage and modulation of cellular redox scavengers in hepatocellular carcinoma.

    Science.gov (United States)

    Rizvi, Asim; Farhan, Mohd; Naseem, Imrana; Hadi, S M

    2016-09-01

    Calcitriol is the metabolically active form of Vitamin D and is known to kill cancer cells. Using the rat model of DEN induced hepatocellular carcinoma we show that there is a marked increase in cellular levels of copper in hepatocellular carcinoma and that calcitriol-copper interaction leads to reactive oxygen species mediated DNA breakage selectively in hepatocellular carcinoma cells. In vivo studies show that calcitriol selectively induces severe fluctuations in cellular enzymatic and non enzymatic scavengers of reactive oxygen species in the malignant tissue. Lipid peroxidation, a well established marker of oxidative stress, was found to increase, and substantial cellular DNA breakage was observed. We propose that calcitriol is a proxidant in the cellular milieu of hepatocellular carcinoma cells, and this copper mediated prooxidant action of calcitriol causes selective DNA breakage in malignant cells, while sparing normal (non malignant) cells. PMID:27343126

  8. Oncolytic vaccinia therapy of squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Yong A

    2009-07-01

    Full Text Available Abstract Background Novel therapies are necessary to improve outcomes for patients with squamous cell carcinomas (SCC of the head and neck. Historically, vaccinia virus was administered widely to humans as a vaccine and led to the eradication of smallpox. We examined the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68 as an oncolytic agent against a panel of six human head and neck SCC cell lines. Results All six cell lines supported viral transgene expression (β-galactosidase, green fluorescent protein, and luciferase as early as 6 hours after viral exposure. Efficient transgene expression and viral replication (>150-fold titer increase over 72 hrs were observed in four of the cell lines. At a multiplicity of infection (MOI of 1, GLV-1h68 was highly cytotoxic to the four cell lines, resulting in ≥ 90% cytotoxicity over 6 days, and the remaining two cell lines exhibited >45% cytotoxicity. Even at a very low MOI of 0.01, three cell lines still demonstrated >60% cell death over 6 days. A single injection of GLV-1h68 (5 × 106 pfu intratumorally into MSKQLL2 xenografts in mice exhibited localized intratumoral luciferase activity peaking at days 2–4, with gradual resolution over 10 days and no evidence of spread to normal organs. Treated animals exhibited near-complete tumor regression over a 24-day period without any observed toxicity, while control animals demonstrated rapid tumor progression. Conclusion These results demonstrate significant oncolytic efficacy by an attenuated vaccinia virus for infecting and lysing head and neck SCC both in vitro and in vivo, and support its continued investigation in future clinical trials.

  9. Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma

    International Nuclear Information System (INIS)

    Pancreatic cancer ranks among the tumors most resistant to chemotherapy. Such chemoresistance of tumors can be mediated by various cellular mechanisms including dysregulated apoptosis or ineffective drug concentration at the intracellular target sites. In this review, we highlight recent advances in experimental chemotherapy underlining the role of cellular transporters in drug resistance. Such contribution to the chemoresistant phenotype of tumor cells or tissues can be conferred both by uptake and export transporters, as demonstrated by in vivo and in vitro data. Our studies used human pancreatic carcinoma cells, cells stably transfected with human transporter cDNAs, or cells in which a specific transporter was knocked down by RNA interference. We have previously shown that 5-fluorouracil treatment affects the expression profile of relevant cellular transporters including multidrug resistance proteins (MRPs), and that MRP5 (ABCC5) influences chemoresistance of these tumor cells. Similarly, cell treatment with the nucleoside drug gemcitabine or a combination of chemotherapeutic drugs can variably influence the expression pattern and relative amount of uptake and export transporters in pancreatic carcinoma cells or select for pre-existing subpopulations. In addition, cytotoxicity studies with MRP5-overexpressing or MRP5-silenced cells demonstrate a contribution of MRP5 also to gemcitabine resistance. These data may lead to improved strategies of future chemotherapy regimens using gemcitabine and/or 5-fluorouracil

  10. Molecular backgrounds of ERAP1 downregulation in cervical carcinoma.

    Science.gov (United States)

    Mehta, Akash M; Osse, Michelle; Kolkman-Uljee, Sandra; Fleuren, Gert Jan; Jordanova, Ekaterina S

    2015-01-01

    The antigen processing machinery (APM) plays an important role in immune recognition of virally infected and transformed cells. Defective expression of the APM component ERAP1 is associated with progression and poor clinical outcome in cervical carcinoma. However, the underlying mechanisms of ERAP1 protein downregulation remain to be established. We investigated ERAP1 mRNA expression levels in 14 patients with established ERAP1 protein downregulation. To further examine the possible pretranscriptional mechanisms of ERAP1 downregulation, ERAP1 DNA mutation status was analyzed alongside existing data on various single nucleotide polymorphisms. Moreover, loss of heterozygosity at various loci in the ERAP1 gene was investigated. In cases with ERAP1 protein downregulation, ERAP1 mRNA quantities were found to be significantly lower than in a cohort with normal ERAP1 protein expression (P = 0.001). Loss of heterozygosity was demonstrated to occur in up to 50% of tumors with ERAP1 downregulation. Our data indicate that ERAP1 downregulation is associated with loss of heterozygosity. These data provide the first insight into in vivo mechanisms of ERAP1 downregulation in cervical carcinoma. PMID:26146606

  11. Molecular Backgrounds of ERAP1 Downregulation in Cervical Carcinoma

    Directory of Open Access Journals (Sweden)

    Akash M. Mehta

    2015-01-01

    Full Text Available The antigen processing machinery (APM plays an important role in immune recognition of virally infected and transformed cells. Defective expression of the APM component ERAP1 is associated with progression and poor clinical outcome in cervical carcinoma. However, the underlying mechanisms of ERAP1 protein downregulation remain to be established. We investigated ERAP1 mRNA expression levels in 14 patients with established ERAP1 protein downregulation. To further examine the possible pretranscriptional mechanisms of ERAP1 downregulation, ERAP1 DNA mutation status was analyzed alongside existing data on various single nucleotide polymorphisms. Moreover, loss of heterozygosity at various loci in the ERAP1 gene was investigated. In cases with ERAP1 protein downregulation, ERAP1 mRNA quantities were found to be significantly lower than in a cohort with normal ERAP1 protein expression P=0.001. Loss of heterozygosity was demonstrated to occur in up to 50% of tumors with ERAP1 downregulation. Our data indicate that ERAP1 downregulation is associated with loss of heterozygosity. These data provide the first insight into in vivo mechanisms of ERAP1 downregulation in cervical carcinoma.

  12. Mechanisms and signiifcance of lipoprotein(a) in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Chang-Ping Wu; Ning Xu; Xue-Guang Zhang

    2009-01-01

    BACKGROUND: The liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. It has been demonstrated that plasma lipid proifles are changed in liver cancer. DATA SOURCES: A MEDLINE database search was performed to identify relevant articles using the keywords "hepatocellular carcinoma" and "lipoprotein(a)". The search was conducted and research articles were reviewed from 1960 to 2008. RESULTS: Production and homeostasis of lipids, apo-lipoproteins and lipoproteins depend on the integrity of hepatocellular functions, which ensures normal lipid and lipoprotein metabolismin vivo. When hepatocellular injury or liver cancer occurs these processes can be impaired. It has been suggested that plasma levels of apolipoprotein(a) (apo(a)) and/or lipoprotein(a) (Lp(a)) may be considered as sensitive markers of hepatic impairment. CONCLUSIONS: Plasma levels of apo(a) and Lp(a) display signiifcant correlations with hepatic status. Most studies demonstrated that the plasma levels of apo(a) and Lp(a) can be considered as an additional clinical index of liver function.

  13. 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. PMID:10994367

  14. The Expression of p53 and Cox-2 in Basal Cell Carcinoma, Squamous Cell Carcinoma and Actinic Keratosis Cases

    OpenAIRE

    Ülker KARAGECE YALÇIN; Selda SEÇKİN

    2012-01-01

    Objective: The aim of this study was to investigate p53 and COX-2 expressions in basal cell carcinoma, squamous cell carcinoma and actinic keratoses, and to determine a possible relationship.Material and Method: 50 basal cell carcinoma, 45 squamous cell carcinoma and 45 actinic keratosis cases were evaluated. The type of tumor in basal cell carcinoma and tumor differentiation in squamous cell carcinoma were noted and the paraffin block that best represented the tumor was chosen. Immunostainin...

  15. Circulation times of cancer cells by in vivo flow cytometry

    Science.gov (United States)

    Zhang, Li; Li, Yan; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2012-03-01

    Liver cancer is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every year. Hepatocellular carcinoma may metastasize to lung, bones, kidney, and many other organs. Surgical resection, liver transplantation, chemotherapy and radiation therapy are the foundation of current HCC therapies. However the outcomes are poor: the survival rate is almost zero for metastatic HCC patients. Molecular mechanisms of HCC metastasis need to be understood better and new therapies must be developed. A recently developed "in vivo flow cytometer" combined with real-time confocal fluorescence imaging are used to assess spreading and the circulation kinetics of liver tumor cells. The in vivo flow cytometer has the capability to detect and quantify continuously the number and flow characteristics of fluorescently labeled cells in vivo in real time without extracting blood sample. We have measured the depletion kinetics of two related human HCC cell lines, high-metastatic HCCLM3 cells and low-metastatic HepG2 cells, which were from the same origin and obtained by repetitive screenings in mice. >60% HCCLM3 cells are depleted within the first hour. Interestingly, the low-metastatic HepG2 cells possess noticeably slower depletion kinetics. In comparison, <40% HepG2 cells are depleted within the first hour. The differences in depletion kinetics might provide insights into early metastasis processes.

  16. Targeting increased copper levels in diethylnitrosamine induced hepatocellular carcinoma cells in rats by epigallocatechin-3-gallate.

    Science.gov (United States)

    Farhan, Mohd; Rizvi, Asim; Naseem, Imrana; Hadi, S M; Ahmad, Aamir

    2015-11-01

    We have earlier elucidated a pathway for the anticancer action of plant polyphenolic compounds against malignant cells involving mobilisation of endogenous copper ions and the consequent prooxidant action. To further confirm our hypothesis in vivo, we induced hepatocellular carcinoma (HCC) in rats by diethylnitrosamine (DEN). We show that in such carcinoma cells, there is a progressive elevation in copper levels at various intervals after DEN administration. Concurrently with increasing copper levels, epigallocatechin-3-gallate (EGCG; a potent anticancer plant polyphenol found in green tea) mediated DNA breakage in malignant cells is also increased. The cell membrane permeable copper chelator neocuproine inhibited the EGCG-mediated cellular DNA degradation, whereas the membrane impermeable chelator bathocuproine was ineffective. Iron and zinc specific chelators desferoxamine mesylate and histidine, respectively, were also ineffective in inhibiting EGCG mediated DNA breakage. Through the use of specific scavengers, the mechanism of DNA breakage was determined to be mediated by reactive oxygen species. In summary, we provide an in vivo evidence of accumulating copper in hepatocellular carcinoma that is targeted by EGCG, leading to its anticancer role in a prooxidant manner. Our findings confirm a novel mechanism of anticancer activity of EGCG in particular and plant derived nutraceuticals in general.

  17. Emerging role of microRNAs in the treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Callegari E

    2015-05-01

    Full Text Available Elisa Callegari,1 Marco Domenicali,2 Laura Gramantieri,3 Massimo Negrini,1 Silvia Sabbioni4 1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 2Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 3Center for Applied Biomedical Research, S Orsola-Malpighi University Hospital, Bologna, 4Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy Abstract: Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide. Currently available curative options, such as surgery and transplantation, are not available to patients with advanced stages of disease. Among the potential new treatments being investigated are microRNA (miRNA-based therapies. A number of preclinical studies have reported antitumor activities of miRNA mimics or anti-miRNA molecules. Optimal in vivo delivery of miRNA molecules is crucial to their action. To this end, significant progress has been made in the development of nanoparticles for in vivo delivery of miRNA molecules. Delivery of these molecules, alone or in combination with other drugs, promises to open new possibilities for therapeutic approaches to hepatocellular carcinoma. Keywords: hepatocellular carcinoma, microRNA, nanocarriers, therapy 

  18. Differential Diagnosis of a Follicular Carcinoma and Papillary Carcinoma of the Thyroid Gland Based on Sonographic Findings

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Kyung Sik; Bae, Il Hun; Lee, Seung Young; Jeon, Min Hee [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of)

    2007-12-15

    The purpose of this study was to evaluate and compare the sonographic findings of a conventional papillary carcinoma, follicular carcinoma and a follicular variant of a papillary carcinoma. A total of 308 nodules from 231 patients that were diagnosed with a papillary carcinoma and a follicular carcinoma by surgery after sonography were analyzed. The nodules consisted of a conventional papillary carcinoma (255, 83%), a follicular variant of a papillary carcinoma (25, 8%), and a follicualar carcinoma (28, 9%). We compared and analyzed the sonographic findings of each nodule for content, margin, echotexture, shape, calcification and halo sign. A conventional papillary carcinoma showed significant different sonographic findings than a follicular carcinoma and a follicular variant of a papillary carcinoma for an ill-defined or well-defined spiculated margin (63.1%), marked hypoechogenicity (85.9%) and microcalcification (49%). A follicular carcinoma showed a significant difference than a conventional papillary carcinoma for a well-defined smooth margin (92.9%), iso, hypo- or hyperechogenicity (89.3%), wider than tall shape (100%) and halo sign (82.1%). The follicular variant of a papillary carcinoma showed similar findings to a follicular carcinoma except for marked hypoechogenicity (44%, p = 0.006) and taller than wide shape (16%, p = 0.027). The follicular carcinoma and follicular variant of a papillary carcinoma showed similar sonographic findings, but findings of a conventional papillary carcinoma were different

  19. Cisplatin, Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2016-05-16

    Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma

  20. Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

    Science.gov (United States)

    Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid.

  1. Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

    Science.gov (United States)

    Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid. PMID:26589365

  2. NUT midline carcinomas in the thymic region.

    Science.gov (United States)

    Gökmen-Polar, Yesim; Cano, Oscar D; Kesler, Kenneth A; Loehrer, Patrick J; Badve, Sunil

    2014-12-01

    NUT midline carcinomas (NMCs) are rare tumors described predominantly in the pediatric age group. We recently reported two cases of these tumors occurring in the thymic region. In order to establish the true incidence of these tumors, we examined a large series of thymic carcinomas for morphological features of NUT tumor and further assessed the expression of NUTM1 (also known as NUT) protein by immunohistochemistry. The histological review of slides from 110 cases of thymic carcinoma was undertaken to identify carcinomas with mixed undifferentiated and squamous features that are typically associated with NUT carcinomas. The presenting symptoms, morphological spectrum of tumors and outcome data of patients with these histologies are presented. Immunohistochemistry for NUTM1 was performed on 35 cases of thymic carcinoma with available blocks (3 with these histological features and 32 without these features) to exclude the possibility of midline carcinoma. Tumors from 10 patients had features of mixed small cell undifferentiated squamous cell carcinoma (M:F, 1.5:1; age range, 22-79). These patients predominantly presented with advanced disease and had respiratory-related symptoms or chest pain; four had paraneoplastic syndromes. The squamous component in all cases was well differentiated with little or no atypia. The undifferentiated component varied in cell size and lacked characteristic features of small cell carcinoma. All but one patients developed metastases or died within 3 years of diagnosis. NUTM1 expression was seen in two of three tumors with these histological features and in none of the 32 cases without. Mixed small cell undifferentiated carcinomas share histological and immunohistochemical similarity with NMCs and have aggressive clinical course. These tumors are not uncommon and should be considered in the differential diagnosis of carcinomas in the thymic region as novel therapies might be available.

  3. Role of VEGF in the growth and metastasis of a murine bladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Feng; WU Jihong; TIAN Yuhua; CHEN Xiafang; HU Honghui; WU Wensen; LI Chuanyuan; HUANG Qian

    2003-01-01

    Bladder transitional cell carcinoma is the most common form of carcinoma in the urinary system. Although overexpression of VEGF has been identified in tissue, serum, and urine of patients with bladder cancer, the role of VEGF in transitional cell carcinoma of the bladder has not been clearly elucidated. Here, we dissected the effect of VEGF during bladder tumor growth and progression by modifying a BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine) induced mouse bladder transitional cell carcinoma cell line BTT-T739 by stable transfection of antisense VEGF121 cDNA. The transfection resulted in more than 80% reduction in VEGF production. The growth of the transduced tumor cells in vitro was not affected, however, these cells formed small or no tumors in vivo. Even in the tumors formed, there were mini- mal vascularization, extensive necrosis and longer latency compared to those formed by parental cells. The permeability of tumor vasculature and metastatic tumor growth were also significantly suppressed in antisense VEGF cDNA trans- fected cells. In addition, the transfer of anti-angiogenic gene in a combination of sFlk-1 and ExTek with electroporation can suppress the tumor growth efficiently. Taken together, these results demonstrated that VEGF plays an important role in bladder tumor angiogenesis and angiogenesis plays an important role in bladder tumor growth and metastasis.

  4. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma*

    Science.gov (United States)

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado Filho, Carlos D'Apparecida Santos

    2016-01-01

    Background Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Objectives Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Methods Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). Results The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. Conclusion The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

  5. The diagnostic utility of the minimal carcinoma triple stain in breast carcinomas.

    Science.gov (United States)

    Ross, Dara S; Liu, Yi-Fang; Pipa, Jennifer; Shin, Sandra J

    2013-01-01

    Pathologists are expected to accurately diagnose increasingly smaller breast carcinomas. Correct classification (ie, lobular vs ductal or in situ vs invasive) directly affects subsequent management, especially when the focus is near a surgical margin or present in a needle core biopsy and is further challenging if the lesion is morphologically ambiguous. We assessed the diagnostic utility of a multiplex, trichromogen immunostain of 3 commonly employed antibodies (CK7, p63, and E-cadherin) developed in our laboratory to evaluate these small lesions. Of the 147 specimens containing minimal (defined as ≤3 mm in size) invasive carcinoma, 81 also contained in situ carcinoma. In each case, the Minimal Carcinoma Triple Stain was prepared with a parallel H&E-stained slide. Observations of staining characteristics in the focus of interest were recorded. The Minimal Carcinoma Triple Stain was diagnostically useful in all but 1 case. In a case of invasive lobular carcinoma in an excisional biopsy, the Minimal Carcinoma Triple Stain stained only the surrounding breast tissue (appropriately) and not the focus of interest. Also, a subset of 29 of 81 excisional biopsies had minimal invasive carcinoma located 2 mm or less from the inked surgical margin, in which in all cases the Minimal Carcinoma Triple Stain was fully interpretable despite morphologic distortion due to concomitant cautery artifact and tissue disruption in some cases. The Minimal Carcinoma Triple Stain offers an accurate and tissue-conserving method to diagnose small, morphologically problematic foci of breast carcinoma while ideally leaving more tissue for additional adjunctive studies.

  6. Carcinoma hepatocelular: parte 2. Tratamento Hepatocelular carcinoma: part 2. Therapy

    Directory of Open Access Journals (Sweden)

    Vinício Paride CONTE

    2000-04-01

    Full Text Available São revisadas as formas de tratamento, particularmente as ressecções cirúrgicas, a quimioembolização arterial e as injeções percutâneas de etanol e de ácido acético. Alguns aspectos relativos à dieta, com particular atenção à aflatoxina B1 e aos retinóides, são abordados quanto ao seu desempenho na etiopatogenia e no tratamento da afecção mais comumente encontrada nos países em desenvolvimento. Em relação ao tratamento, fazem-se considerações também referentes ao uso de octreotide, nitrosaminas e outras drogas. A coagulação intersticial a laser e as drogas de ação antivascular também mereceram abordagem sucinta. O problema do carcinoma hepatocelular precoce e a sua destruição é sinalizado de modo sumário. A quimioprevenção com o uso do interferon alfa recombinante considerado e o transplante de fígado encerram a revisão, antes dos comentários finais.Recent improvements on the therapeutical management of hepatocellular carcinoma are revised with special attention to evaluate the role of surgery for the disease. Considering that definitive surgical intervention is not feasible in most cases because of extreme tumor extension, multiplicity of tumor foci, and associated advanced liver cirrhosis at the time of diagnosis, others forms of treatment are listed, such as transcatheterarterial chemoembolization, percutaneous ethanol and acetic acid injections, and chemotherapy only to a small portion of patients with no indication for standard treatments The emerging role of retinoic acid metabolism blocking agents, was examined and may offer a significant new potential treatment for cancer, inclusive the possibility of combining other anticancer drugs with exogenous retinoids or modulation of endogenous retinoids as a real opportunity to advance our ability to treat or prevent human cancer effectively. Octreotide, nitrosamine and other drugs are analyzed and is concluded that improves survival and is a valuable

  7. Focus of tricholemmal differentiation (tricholemmal carcinoma) within Bowen's disease/carcinoma.

    Science.gov (United States)

    Misago, Noriyuki; Toda, Shuji; Nakao, Tomokazu

    2016-04-01

    Bowen's disease (BD)/carcinoma is a type of squamous cell carcinoma of the skin, however, the possibility of adnexal differentiation (the development of sebaceous carcinoma or porocarcinoma) occurring in BD/carcinoma has been suggested. We herein describe a case of BD with superficial invasive carcinoma, which showed a clear cell focus, demonstrating tricholemmal differentiation. This clear cell focus showed the following findings: primarily composed of clear cells, somewhat columnar clear cells aligned in a palisade along a discernible basement membrane, tricholemmal keratinization and glycogen contained within the cells. In addition, the immunohistochemical profile in this clear cell focus, namely, negative staining for cytokeratin (CK)1 and positive staining for CK17 and calretinin in the inner cells of the neoplastic lobule, corresponded to that of the outer root sheath cells. This case suggested that adnexal differentiation can rarely occur within true BD/carcinoma, although adnexal carcinomas are commonly associated with a simple bowenoid change.

  8. Focus of tricholemmal differentiation (tricholemmal carcinoma) within Bowen's disease/carcinoma.

    Science.gov (United States)

    Misago, Noriyuki; Toda, Shuji; Nakao, Tomokazu

    2016-04-01

    Bowen's disease (BD)/carcinoma is a type of squamous cell carcinoma of the skin, however, the possibility of adnexal differentiation (the development of sebaceous carcinoma or porocarcinoma) occurring in BD/carcinoma has been suggested. We herein describe a case of BD with superficial invasive carcinoma, which showed a clear cell focus, demonstrating tricholemmal differentiation. This clear cell focus showed the following findings: primarily composed of clear cells, somewhat columnar clear cells aligned in a palisade along a discernible basement membrane, tricholemmal keratinization and glycogen contained within the cells. In addition, the immunohistochemical profile in this clear cell focus, namely, negative staining for cytokeratin (CK)1 and positive staining for CK17 and calretinin in the inner cells of the neoplastic lobule, corresponded to that of the outer root sheath cells. This case suggested that adnexal differentiation can rarely occur within true BD/carcinoma, although adnexal carcinomas are commonly associated with a simple bowenoid change. PMID:26365015

  9. Raf-1 kinase inhibitory protein expression in thyroid carcinomas.

    Science.gov (United States)

    Kim, Hyun-Soo; Kim, Gou Young; Lim, Sung-Jig; Kim, Youn Wha

    2010-12-01

    Raf-1 kinase inhibitory protein (RKIP) has been implicated in several fundamental signal transduction pathways that control cellular growth, differentiation, apoptosis and migration. RKIP is reduced in a variety of human carcinomas, but RKIP expression in thyroid carcinomas has not been analyzed at the protein level. In this study, we examined the immunohistochemical expression of RKIP in various subtypes of thyroid carcinoma. Immunostaining for RKIP was performed on 104 cases of primary thyroid carcinoma (40 papillary, 29 follicular, 11 medullary, 11 poorly differentiated, and 13 anaplastic carcinomas) and 26 cases of nodal metastatic tumor (17 papillary, 4 medullary, and 5 anaplastic carcinomas). Normal thyroid tissue and all cases of follicular, papillary, and medullary carcinomas showed uniform, strong cytoplasmic immunoreactivity for RKIP. With the exception of one case, poorly differentiated carcinomas also revealed strong RKIP expression. In contrast, RKIP expression was completely absent in all anaplastic carcinomas. The transition zone from the differentiated carcinoma component (strong RKIP expression) to the anaplastic carcinoma component (no RKIP expression) demonstrated a completely opposite pattern of RKIP immunoreactivity. This reduction of RKIP expression in anaplastic carcinoma was statistically significant (P carcinomas showed uniform, strong cytoplasmic RKIP immunoreactivity, in contrast, in metastatic anaplastic carcinomas, RKIP expression was completely absent. RKIP expression is significantly reduced in anaplastic thyroid carcinoma as compared to other subtypes of thyroid carcinoma. Further studies are necessary to elucidate the precise mechanism of RKIP action in anaplastic thyroid carcinoma.

  10. Epidemiologia do carcinoma basocelular Epidemiology of basal cell carcinoma

    OpenAIRE

    Valquiria Pessoa Chinem; Hélio Amante Miot

    2011-01-01

    O carcinoma basocelular é a neoplasia maligna mais comum em humanos e sua incidência vem aumentando nas últimas décadas. Sua grande frequência gera significativo ônus ao sistema de saúde, configurando problema de saúde pública. Apesar das baixas taxas de mortalidade e de rara ocorrência de metástases, o tumor pode apresentar comportamento invasivo local e recidivas após o tratamento, provocando importante morbidade. Exposição à radiação ultravioleta representa o principal fator de risco ambie...

  11. Chronic inflammatory demyelinating polyneuropathy associated with carcinoma.

    OpenAIRE

    Antoine, J C; Mosnier, J. F.; Lapras, J; Convers, P.; Absi, L; Laurent, B.; Michel, D

    1996-01-01

    The association of chronic inflammatory demyelinating polyneuropathy (CIDP) and carcinoma has rarely been reported and its relevance is debated. Thirty three consecutive patients with probable or definite CIDP (idiopathic or associated with M protein) were investigated. Three patients with definite CIDP had a concomitant carcinoma. One had an IgM paraprotein. Steroids and intravenous immunoglobulins were effective.

  12. Adenosquamous Carcinoma of Colon and Rectum

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ In colon and rectum, adenosquamous carcinoma is extremely rare. 6 patients with adenosquamous carcinoma of colon and rectum were identified by Tianjin Medical University Cancer Hospital from Jan. 1967 to Dec. 1997. 2 male and 4 female had a median age of 48 (range, 40- 60) years. All patients were treated surgically.

  13. Acinar Cell Carcinoma of the Pancreas

    Institute of Scientific and Technical Information of China (English)

    Hua Li; Qiang Li

    2008-01-01

    Acinar cell carcinoma of the pancreas is a rare tumor which is defined as a carcinoma that exhibits pancreatic enzyme production by neoplastic cells. This review includes re-cent developments in our understanding of the epidemiology and pathogenesis of ACC, imaging and pathological diagnosis and ap-proaches to treatment with reference to the literature.

  14. Overexpression of vimentin in canine prostatic carcinoma

    DEFF Research Database (Denmark)

    Rodrigues, M M P; Rema, A; Gärtner, F;

    2011-01-01

    is associated with the invasive phenotype of human prostate cancer cells. The aim of the present study was to characterize immunohistochemically the expression of vimentin by canine prostatic carcinomas. Primary carcinomas and metastatic tumour foci both showed vimentin expression. This finding suggests...

  15. Prostatic Adenosquamous Carcinoma Metastasizing to Testis

    Directory of Open Access Journals (Sweden)

    Dilek Ertoy Baydar

    2006-01-01

    Full Text Available Adenosquamous carcinoma of the prostate is an unusual tumor with poor prognosis. Most arise after hormonal or radiotherapy of conventional prostatic adenocarcinoma. Sarcomatous transformation in them has been reported in only a few cases. Here, we present a unique case of “de novo prostatic adenosquamous carcinoma with focal sarcomatoid areas” that showed testicular metastasis, detected after scrotal orchiectomy.

  16. Eyelid Carcinoma in Patients with Systemic Lymphoma

    Directory of Open Access Journals (Sweden)

    Debraj Shome

    2010-01-01

    Full Text Available Purpose: To describe a series of patients with Non-Hodgkin′s lymphoma (NHL and concomitant eyelid carcinoma. Methods: In this non-comparative interventional case series, we retrospectively reviewed the medical records of 5 patients with NHL who developed eyelid carcinoma. Results: The patients included one female and four male subjects. Systemic lymphoma had been diagnosed 1 to 72 months prior to development of the eyelid carcinoma. The lesions were basal cell carcinoma in three, and squamous cell carcinoma in two cases. The lymphoma was advanced (stage III or IV in all patients. Four patients underwent surgical excision of the carcinoma and one patient was awaiting surgical treatment after completing systemic chemotherapy. Three subjects had high-grade carcinomas. Two patients had perineural invasion; one received adjuvant radiotherapy postoperatively but the other did not due to receiving systemic chemotherapy for recurrent NHL. Conclusions: Systemic lymphoma may be associated with aggressive eyelid carcinomas. Perineural invasion is frequently encountered in this situation and should be treated with adjuvant radiation therapy to decrease the likelihood of local recurrence.

  17. Primary papillary serous carcinoma of the peritoneum

    OpenAIRE

    Madan Mohan Gupta; Bahri, Nandini U.

    2014-01-01

    Primary papillary serous carcinoma of the peritoneum (PSCP) is a rare malignant neoplasm of epithelial origin seen only in women, and closely mimics serous ovarian papillary carcinoma except for the absence of ovarian involvement in PSCP on imaging. It is primarily a peritoneal disease with imaging findings simulated by other conditions that have a predominant peritoneal involvement.

  18. Examestane in advanced or recurrent endometrial carcinoma

    DEFF Research Database (Denmark)

    Lindemann, Kristina; Malander, Susanne; Christensen, René dePont;

    2014-01-01

    We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma.......We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma....

  19. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)

    2012-01-01

    textabstractThere are many different cutaneous malignancies, but malignant melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent approximately 98% of all skin cancers.In literature, these three skin cancers are often divided into melanoma and nonmelanoma skin cancers (NMSC

  20. Cytotoxic and antiproliferative activity of Securidaca longepedunculata aqueous extract on Ehrlich ascites carcinoma cells in Swiss albino mice.

    OpenAIRE

    R A Lawal; M D Ozaslan; O S Odesanmi; I D Karagoz; I H Kilic; O AT Ebuehi

    2012-01-01

    Summary: Securidaca longepedunculata is a savannah shrub found growing in tropical Africa. It is reputed to have more than a hundred medicinal uses and is a major component of anticancer decoctions in Nigeria. An attempt was made in this study to determine the in vitro and in vivo cytotoxic activity and possible pro-apoptotic effect of Securidaca longepedunculata aqueous root bark extract on Ehrlich ascites carcinoma cells. In vitro cytotoxic activity was determined using the Trypan blue assa...