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Sample records for human larynx carcinoma

  1. CARCINOMA OF THE LARYNX AND HUMAN PAPILLOMA VIRUS INFECTION

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    Georgi N. Nikolov

    2016-03-01

    Full Text Available Background: Laryngeal carcinoma is one of the most common form of head and neck cancer. During the last two decades, it has been recognized that this cancer is causally related to human papillomavirus (HPV. Objective: We presented a study on prevalence of human papilloma viruses (HPV in patients with laryngeal carcinoma. Methods: This study consists of 43 patients with laryngeal carcinoma who were diagnosed and treated with surgical techniques in Department of Otorhinolaryngology, University Hospital, Pleven, Bulgaria. Immunohistochemistry of p16INK4a and Ki-67 were used to prove the relationship between high-risk-HPV (HR-HPV and carcinogenesis. Results: Papilloma virus infection with high-risk oncogenic types of HPV was determined in more than 39.5% of surgically treated patients with histologically proven laryngeal cancer. HPV-induced carcinogenesis was assumed in 17 (13.9% of all patients whose spouses were operated from cervical cancer. The patients with HPV-positive laryngeal carcinoma were younger than the others in the group (8 years on average. Risk factors for development of HPV-associated laryngeal carcinoma were related to higher number of sexual partners and the practice of oral sex. Frequently, in patients with HPV-associated laryngeal carcinoma we find data for so-called “family’s carcinogenesis”. The possibility of appearance (either preceding or following the treatment of a second carcinoma and/or tumour recurrence is higher in HPV-positive laryngeal carcinomas. Conclusion: It is recommended to extend the diagnostic methods for laryngeal and hypo pharyngeal cancer with a routine search for high-risk oncogenic HPV strains.

  2. [Prevalence of human papillomavirus infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx].

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    Villagómez-Ortíz, Vicente José; Paz-Delgadillo, Diana Estela; Marino-Martínez, Iván; Ceseñas-Falcón, Luis Ángel; Sandoval-de la Fuente, Anabel; Reyes-Escobedo, Alfonso

    2016-01-01

    Cancer of the head and neck comprises a group of neoplasms that share a similar anatomical origin. Most originate from the epithelium of the aerodigestive tract and 90% correspond to squamous cell carcinoma. In the last 15 years, an increase in the incidence of squamous cell carcinoma induced by human papillomavirus (HPV) has been seen, mainly types 16 and 18, which are the most frequent found in cancers of the oral cavity and oropharynx, and types 6 and 11 in laryngeal cancer. There are reports in the literature that show HPV as the leading cause of oropharyngeal squamous cell carcinoma. Determine the prevalence of infection with high-risk HPV in patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx and larynx. An observational, cross-sectional, descriptive, unblinded study was performed. Prevalence of HPV infection was determined by polymerase chain reaction (PCR) in DNA samples from tumour tissue of patients with squamous cell carcinoma of the oral cavity, oropharynx and larynx. Typing was subsequently performed in HPV positive samples in order to detect types 18, 16, 11 and 6, using custom primers. A total of 45 patients were included. The association between laryngeal squamous cell carcinoma and HPV was established in two patients, which represented an overall prevalence of 4.4% in our population, and 10% for laringeal tumours. There is a low prevalence of HPV infection in squamous cell carcinoma of the oral cavity, oropharynx and larynx, in our population. Prospective studies on younger patients could provide more information. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  3. 4-Methoxycinnamaldehyde inhibited human respiratory syncytial virus in a human larynx carcinoma cell line.

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    Wang, Kuo Chih; Chang, Jung San; Chiang, Lien Chai; Lin, Chun Ching

    2009-09-01

    4-Methoxycinnamaldehyde, an active constituent of Agastache rugosa, was examined for its cytoprotective activity against RSV by XTT method in human larynx carcinoma cell line. 4-Methoxycinnamaldehyde could effectively inhibit cytopathic effect of RSV (p<0.0001) with an estimated IC(50) of 0.055microg/ml and a selectivity index (SI) of 898.2. 4-Methoxycinnamaldehyde (0.03microg/ml) could inhibit viral entrance by interfering viral attachment (IC(50) of 0.06microg/ml; p<0.0001) and internalization (IC(50) of 0.01microg/ml; p<0.0001). 4-Methoxycinnamaldehyde significantly increased the basal production of IFN (p=0.0015), but not the virus-induced IFN production. Therefore, its cytoprotective activity against RSV was not mediated by interferon. In conclusion, 4-methoxycinnamaldehyde might be helpful to manage the disease induced by RSV infection.

  4. Cytotoxicity and radiosensitization effect of TRA-8 on radioresistant human larynx squamous carcinoma cells.

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    Wu, F; Hu, Y; Long, J; Zhou, Y J; Zhong, Y H; Liao, Z K; Liu, S Q; Zhou, F X; Zhou, Y F; Xie, C H

    2009-02-01

    TRAIL induces apoptosis in a variety of tumorigenic and transformed cell lines, but not in many normal cells. Recent studies have demonstrated that death receptor 5 (DR5), one of the two death receptors bound by TRAIL, showed expression in most malignantly transformed cells. This study evaluated effects of a monoclonal antibody (TRA-8) to human death receptor 5, combined with ionizing radiation, on radioresistant human larynx squamous carcinoma cell line (Hep-2R). Cells were treated with TRA-8 alone or in combination with radiation, cell viability inhibition was measured by MTT assay, and the induction of apoptosis was determined by Annexin V staining. Radionsensitivity of Hep-2R cells treated with TRA-8 were investigated with long-term clonogenic assays. Regulation of DR5 expression in cells after radiation was analyzed by indirect immunofluorescence using murine TRA-8 in combination with flow cytometry. The results suggested that TRA-8 enhanced radionsensitivity of Hep-2R cells, and that TRA-8 regulated Hep-2R cell cycle arrest at G2/M phase. Irradiation up-regulated the expression of DR5, and when combined with TRA-8 yielded optimal survival benefit. Therefore, TRA-8 can be used in combination with irradiation in radioresistant human larynx squamous carcinoma cells. Monoclonal antibodies such as TRA-8 may play an important role in the development of an effective treatment strategy for patients with radioresistant cancers.

  5. Investigating the Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of the Larynx and Its Correlation with Disease Prognosis.

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    Atighechi, Saeid; Meybodian, Mojtaba; Dadgarnia, Mohammad Hossein; Baradaranfar, Mohammad Hossein; Behniafard, Nasim

    2016-05-01

    The human papilloma virus (HPV) can play a role in the development of head and neck squamous cell carcinoma (SCC). Our aim was to assess the prevalence of HPV DNA in SCC of the larynx. The impact of HPV infection on patient survival was also evaluated. This case-control study was performed in 44 patients with SCC of the larynx (case group), while the control group comprised samples obtained from cadavers with no previous history of malignancy. A preliminary pathologic evaluation was performed on all samples in the control group (36 samples) to ensure the absence of dysplasia or malignancy. Polymerase chain reaction (PCR) was used to detect HPV DNA. After completing the treatment protocol, patients were followed to assess the impact of HPV infection on overall survival (OS). PCR evaluation in the case group showed that HPV DNA was successfully isolated from 11 (25%) samples, while only two (5.6%) HPV DNA-positive were obtained from cadavers. According to these results, a significant difference was obtained in the prevalence of HPV DNA and laryngeal SCC between cases and controls (P=0.031). No statistically significant difference was observed in the OS of patients with or without HPV infection in the case group (P=0.235). Based on these results, we suggest that the prevalence of HPV infection is higher in laryngeal SCC subjects compared with healthy individuals. Although a longer OS was seen in HPV-positive patients, survival analysis did not show a significant difference in the comparison of HPV-positive and negative findings in SCC patients.

  6. Investigating the Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of the Larynx and Its Correlation with Disease Prognosis

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    Saeid Atighechi

    2016-05-01

    Full Text Available Introduction: The human papilloma virus (HPV can play a role in the development of head and neck squamous cell carcinoma (SCC. Our aim was to assess the prevalence of HPV DNA in SCC of the larynx. The impact of HPV infection on patient survival was also evaluated.  Materials and Methods: This case-control study was performed in 44 patients with SCC of the larynx (case group, while the control group comprised samples obtained from cadavers with no previous history of malignancy. A preliminary pathologic evaluation was performed on all samples in the control group (36 samples to ensure the absence of dysplasia or malignancy. Polymerase chain reaction (PCR was used to detect HPV DNA. After completing the treatment protocol, patients were followed to assess the impact of HPV infection on overall survival (OS.  Results: PCR evaluation in the case group showed that HPV DNA was successfully isolated from 11 (25% samples, while only two (5.6% HPV DNA-positive were obtained from cadavers. According to these results, a significant difference was obtained in the prevalence of HPV DNA and laryngeal SCC between cases and controls (P=0.031. No statistically significant difference was observed in the OS of patients with or without HPV infection in the case group (P=0.235.  Conclusion: Based on these results, we suggest that the prevalence of HPV infection is higher in laryngeal SCC subjects compared with healthy individuals. Although a longer OS was seen in HPV-positive patients, survival analysis did not show a significant difference in the comparison of HPV-positive and negative findings in SCC patients.

  7. The presence and prognostic significance of human papillomavirus in squamous cell carcinoma of the larynx.

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    Erkul, Evren; Yilmaz, Ismail; Narli, Gizem; Babayigit, Mustafa Alparslan; Gungor, Atila; Demirel, Dilaver

    2017-07-01

    The aim of the present study was to evaluate the role of HPV in laryngeal squamous cell carcinoma and correlate it with patients' clinicopathological data. In total, 78 laryngeal squamous cell carcinoma patients enrolled in this study. The presence of genotype-specific HPV DNA was evaluated using Genotyping Assay in formalin-fixed paraffin-embedded tissue which was diagnosed between 2005 and 2015. All samples were also evaluated for p16 immunohistochemical staining. HPV DNA and p16 status were assessed in terms of location, smoking, alcohol consumption, lymph node status, tumor stage, overall survival, disease-free survival, perineural invasion, and vascular invasion retrospectively. Five test samples were excluded from the study due to inadequate deoxyribonucleic acid purity. HPV DNA was detected in 19 of 73 (26.02%) in patients with laryngeal squamous cell carcinoma. Human papilloma virus genotyping revealed double human papilloma virus in one case (types 16 and 59) and HPV 16 in the remaining cases. Although HPV-positive cases showed slightly better 3 years survival than HPV-negative ones, this finding was not statistically significant (overall survival p = 0.417, HPV positive: 92.3%, HPV negative: 81.4%, and disease-free survival p = 0.526, HPV positive: 93.8%, HPV negative: 80.9%). The presence of HPV DNA was not significantly associated with any clinicopathological features (p > 0.05). Among 73 patients, only 4 had an immunohistochemical staining of p16 and these patients were also HPV DNA 16 positive. Although our study results revealed a slightly better survival in patients with HPV DNA positivity for HPV 16 compared to the negative ones, the difference was not statistically significant. However, an increasing rate in especially high-risk-type HPV-16 prevalence in laryngeal squamous cell carcinoma by RT-PCR method was observed compared to our previous study. Although the presence of HPV in laryngeal SCCs seems to be associated with slightly better

  8. Salivary gland carcinomas of the larynx

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    Nielsen, Troels Krogh; Bjørndal, Kristine; Krogdahl, Annelise

    2012-01-01

    OBJECTIVE: Salivary gland carcinomas of the larynx are rare. The purpose of this study is to present a national series of laryngeal salivary gland carcinoma patients and to bring a review of recent literature. METHODS: By merging The Danish Cancer Registry, The National Pathology Registry...... and The National Patient Registry all registered patients with laryngeal salivary carcinomas diagnosed from 1990 to 2007 were identified. The histological slides were reviewed and data concerning age, sex, symptoms, topography, histology, treatment and outcome were registered. Based on a supplemented PubMed search....... female ratio was 2:1, the most common location was the supraglottic region (52%) and the most predominant histological subtypes were adenoid cystic carcinoma (46%), mucoepidermoid carcinoma (35%) and adenocarcinoma NOS (12%). CONCLUSION: Laryngeal salivary gland carcinoma is a rare disease with a male...

  9. [Detection of human papillomavirus DNA in formalin fixed invasive squamous cell carcinoma of the larynx with polymerase chain reaction (PCR)].

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    Arndt, O; Brock, J; Kundt, G; Müllender, A

    1994-10-01

    Approximately 67 different subtypes of HPVs have now been described. Regularly most of the cervical cancers are positive for HPV 16/18. Current research also indicates that HPVs may be involved in the development of benign tumours and also squamous cell cancers of head and neck. Studies establishing the presence of different HPV subtypes in oral cancers and precancers suggest the possibility of the virus as etiological factor in oral carcinogenesis too. In this study the prevalence of HPV 6/11, 16 and 18 infection and other exogenous risk factors like nicotine and alcohol in laryngeal cancers were studied. A total of 100 formalin-fixed and paraffin-embedded cancers, 41 glottic and 59 supraglottic, in patients aged 58 years, were detected by use of the E6 specific PCR for HPV DNA. Significantly more glottic cancers, 26 of 41 (63.4%), were positive for the investigated HPV's. HPV 16 was found in all positive cancers. This predominance of HPV 16 was also present in the supraglottic carcinomas, but only 10.2% (6 of 59) of the these groups were HPV positive. In both groups the patients with HPV 16 and/or 18 positive cancers, the exogenous risk factor was higher than with in HPV 16/18 negative tumours. Following infection, the virus either remains dormant or else undergoes active replication resulting in the synthesis of infectious virus. The integration of virus DNA into the host cell DNA may be the result of action of nicotine and/or alcohol. The integration event is the key of the carcinogenesis. The level of the risk factor in the patients with supraglottic tumours was significantly higher.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Squamous cell carcinoma of the larynx with subglottic extension: is larynx preservation possible

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    Levy, A.; Blanchard, P.; Lusinchi, A.; Daly-Schveitzer, N.; Tao, Y. [Gustave Roussy, Department of Radiotherapy, Villejuif (France); Temam, S.; Maison, M.M.; Janot, F.; Mirghani, H. [Gustave Roussy, Department of Otorhinolaryngology - Head and Neck Surgery, Villejuif (France); Bidault, F. [Gustave Roussy, Department of Diagnostic Radiology, Villejuif (France); Guigay, J. [Gustave Roussy, Department of Medical Oncology, Villejuif (France); Bourhis, J. [Gustave Roussy, Department of Radiotherapy, Villejuif (France); University Hospital Lausanne, Department of Radiation Oncology, Lausanne (Switzerland)

    2014-07-15

    Squamous cell carcinoma of larynx with subglottic extension (sSCC) is a rare location described to carry a poor prognosis. The aim of this study was to analyze outcomes and feasibility of larynx preservation in sSCC patients. Between 1996 and 2012, 197 patients with sSCC were treated at our institution and included in the analysis. Stage III-IV tumors accounted for 76 %. Patients received surgery (62 %), radiotherapy (RT) (18 %), or induction chemotherapy (CT) (20 %) as front-line therapy. The 5-year actuarial overall survival (OS), locoregional control (LRC), and distant control rate were 59 % (95 % CI 51-68), 83 % (95 % CI 77-89), and 88 % (95 % CI 83-93), respectively, with a median follow-up of 54.4 months. There was no difference in OS and LRC according to front-line treatments or between primary subglottic cancer and glottosupraglottic cancers with subglottic extension. In the multivariate analysis, age > 60 years and positive N stage were the only predictors for OS (HR 2, 95 % CI 1.2-3.6; HR1.9, 95 % CI 1-3.5, respectively). A lower LRC was observed for T3 patients receiving a larynx preservation protocol as compared with those receiving a front-line surgery (HR 14.1, 95 % CI 2.5-136.7; p = 0.02); however, no difference of ultimate LRC was observed according to the first therapy when including T3 patients who underwent salvage laryngectomy (p = 0.6). In patients receiving a larynx preservation protocol, the 5-year larynx-preservation rate was 55 % (95 % CI 43-68), with 36 % in T3 patients. The 5-year larynx preservation rate was 81 % (95 % CI 65-96) and 35 % (95 % CI 20-51) for patients who received RT or induction CT as a front-line treatment, respectively. Outcomes of sSCC are comparable with other laryngeal cancers when managed with modern therapeutic options. Larynx-preservation protocols could be a suitable option in T1-T2 (RT or chemo-RT) and selected T3 sSCC patients (induction CT). (orig.) [German] Plattenepithelkarzinome des Larynx mit

  11. Euphorbia tirucalli modulates gene expression in larynx squamous cell carcinoma.

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    Franco-Salla, Gabriela Bueno; Prates, Janesly; Cardin, Laila Toniol; Dos Santos, Anemari Ramos Dinarte; Silva, Wilson Araújo da; da Cunha, Bianca Rodrigues; Tajara, Eloiza Helena; Oliani, Sonia Maria; Rodrigues-Lisoni, Flávia Cristina

    2016-05-21

    Some plants had been used in the treatment of cancer and one of these has attracted scientific interest, the Euphorbia tirucalli (E. tirucalli), used in the treatment of asthma, ulcers, warts has active components with activities scientifically proven as antimutagenic, anti-inflammatory and anticancer. We evaluate the influence of the antitumoral fraction of the E. tirucalli latex in the larynx squamous cell carcinoma (Hep-2), on the morphology, cell proliferation and gene expression. The Hep-2 cells were cultivated in complete medium (MEM 10 %) and treated with E. tirucalli latex for 1, 3, 5 and 7 days. After statistically analyzing the proliferation of the tested cells, the cells were cultivated again for RNA extraction and the Rapid Subtractive Hybridization (RaSH) technique was used to identify genes with altered expression. The genes found using the RaSH technique were analyzed by Gene Ontology (GO) using Ingenuity Systems. The five genes found to have differential expression were validated by real-time quantitative PCR. Though treatment with E. tirucalli latex did not change the cell morphology in comparison to control samples, but the cell growth was significantly decreased. The RaSH showed change in the expression of some genes, including ANXA1, TCEA1, NGFRAP1, ITPR1 and CD55, which are associated with inflammatory response, transcriptional regulation, apoptosis, calcium ion transport regulation and complement system, respectively. The E. tirucalli latex treatment down-regulated ITPR1 and up-regulated ANXA1 and CD55 genes, and was validated by real-time quantitative PCR. The data indicate the involvement of E. tirucalli latex in the altered expression of genes involved in tumorigenic processes, which could potentially be applied as a therapeutic indicator of larynx cancer.

  12. A vibroacoustic model of selected human larynx diseases.

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    Engel, Zbigniew Witold; Kłaczyński, Maciej; Wszołek, Wiesław

    2007-01-01

    With the present development of digital registration and methods for processing speech it is possible to make effective objective acoustic diagnostics for medical purposes. These methods are useful as all pathologies and diseases of the human vocal tract influence the quality of a patient's speech signal. Diagnostics of the voice organ can be defined as an unambiguous recognition of the current condition of a specific voice source. Such recognition is based on an evaluation of essential acoustic parameters of the speech signal. This requires creating a vibroacoustic model of selected deformations of Polish speech in relation to specific human larynx diseases. An analysis of speech and parameter mapping in 29-dimensional space is reviewed in this study. Speech parameters were extracted in time, frequency and cepstral (quefrency) domains resulting in diagrams that qualified symptoms and conditions of selected human larynx diseases. The paper presents graphically selected human larynx diseases.

  13. Carcinoma of the larynx: the Dutch national guideline for diagnostics, treatment, supportive care and rehabilitation.

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    Kaanders, J.H.A.M.; Hordijk, G.J.

    2002-01-01

    PURPOSE: This evidence based guideline aims to facilitate proper management and to prevent diverging views concerning diagnosis, treatment and follow-up of carcinoma of the larynx between the major referral centers for head and neck cancer in The Netherlands. METHOD: A multidisciplinary committee

  14. Effect of radiotherapy on serum mucoprotein level in carcinoma Larynx and Pharynx

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    Mali, H. R.; Bhatt, M. L. B.; S.M. Natu; Bhatia, N.

    2001-01-01

    Serum mucoprotein level was determined in 61 individuals including 36 untreated patients of carcinoma Larynx & Pharynx and 25 healthy adults. Patients were treated by standard doses of radiation. Serum mucoprotein was again estimated following therapy. Patients showed a highly significant elevation in serum mucoprotein level as compared to controls (P

  15. Efficacy of radical radiotherapy alone for functional preservation of larynx in laryngeal carcinoma: a retrospective analysis.

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    Bhattacharyya, T; Ghoshal, S; Dhanireddy, B; Kumar, R; Sharma, S C

    2014-01-01

    Concurrent chemoradiation is the current standard of care in locally advanced head and neck cancer. But, in our setup, many patients of carcinoma larynx are treated with only radical radiotherapy because of poor general condition of the patients. This study was performed to assess the influence radical radiotherapy alone on functional preservation of larynx. 110 previously untreated patients with invasive squamous cell carcinoma of larynx were treated with radical radiotherapy alone between January 2006 and June 2009. Conventional one daily fraction of 2 Gy with total doses of 60-66 Gy was used. Voice preservation and local control at median follow-up period of 2 years were analyzed. Several host, tumor, and treatment parameters were also analyzed. Among 110 patients, preservation of larynx was possible in 78 patients (71%). With radical radiotherapy alone, excellent preservation of larynx was achieved in stage I (88.9%) and stage II (75%) disease, while in advanced stages, results were not so encouraging. In stage III and stage IVA, larynx preservation was only 72.4% and 65.3%, respectively. Patients without any cartilage invasion had significantly better laryngeal preservation rate as compared to patients with cartilage invasion. (78.9% vs. 35.3%; P = 0.008). Though concurrent chemoradiation is the standard of care in preservation of voice in laryngeal cancer, definitive radiotherapy alone may also be a good option in terms of preservation of larynx in patients of laryngeal cancer in community practice in the developing world where most of the patients cannot tolerate concurrent chemoradiation.

  16. Clinical Significance of Langerhans Cells in Squamous Cell Carcinoma of the Larynx

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    Francisco Esteban

    2012-01-01

    Full Text Available Langerhans cells (LCs may be involved in the immunosurveillance against tumors as antigen-presenting cells. Our objective has been to determine the relevance of LC in progression of larynx squamous cell carcinomas and their relationship with different subpopulations of tumor-infiltrating cells. LCs were investigated by immunohistochemical methods using anti-CD1 antibody. LCs were detected in most of the primary tumors studied (44 out of 50 and also in metastases (6 out of 10 and recurrences (2 out of 3, but we did not find any statistical association between number of LCs and clinical-pathological parameters or survival. However, the number of LCs was increased in patients with evident infiltration of lymphocytes, mainly cytotoxic T cells. We can conclude that although LCs did not show clinical utility as prognostic marker, they may play a role in releasing an active immune response in larynx carcinomas, according to their ability to present antigens to sensitized T cells.

  17. The Composition of Microbiome in Larynx and the Throat Biodiversity between Laryngeal Squamous Cell Carcinoma Patients and Control Population.

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    Hong-Li Gong

    Full Text Available The throat is an ecological assemblage involved human cells and microbiota, and the colonizing bacteria are important factors in balancing this environment. However, this bacterial community profile has thus been poorly investigated. The purpose of this study was to investigate the microbial biology of the larynx and to analyze the throat biodiversity in laryngeal carcinoma patients compared to a control population in a case-control study. Barcoded pyrosequencing analysis of the 16S rRNA gene was used. We collected tissue samples from 29 patients with laryngeal carcinoma and 31 control patients with vocal cord polyps. The findings of high-quality sequence datasets revealed 218 genera from 13 phyla in the laryngeal mucosa. The predominant communities of phyla in the larynx were Firmicutes (54%, Fusobacteria (17%, Bacteroidetes (15%, Proteobacteria (11%, and Actinobacteria (3%. The leading genera were Streptococcus (36%, Fusobacterium (15%, Prevotella (12%, Neisseria (6%, and Gemella (4%. The throat bacterial compositions were highly different between laryngeal carcinoma subjects and control population (p = 0.006. The abundance of the 26 genera was significantly different between the laryngeal cancer and control groups by metastats analysis (p<0.05. Fifteen genera may be associated with laryngeal carcinoma by partial least squares discriminant analysis (p<0.001. In summary, this study revealed the microbiota profiles in laryngeal mucosa from tissue specimens. The compositions of bacteria community in throat were different between laryngeal cancer patients and controls, and probably were related with this carcinoma. The disruption of this bio-ecological niche might be a risk factor for laryngeal carcinoma.

  18. A case of desmoid tumor co-existing with recurrent squamous cell carcinoma in the larynx.

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    Shinohara, Shogo; Suehiro, Atsushi; Kikuchi, Masahiro; Harada, Hiroyuki; Kishimoto, Ippei; Imai, Yukihiro

    2017-06-01

    Extra-abdominal desmoid tumor, also known as aggressive fibromatosis, has aggressive behavior with local infiltration and tendency for recurrence. Though head and neck is reported to be one of the most common sites, a desmoid tumor in the larynx is extremely rare. A 67-year-old male visited our hospital with prolonged hoarseness and received laryngo-microsurgery with the diagnosis of laryngeal polyp. After the operation, he eventually developed a laryngeal squamous cell carcinoma with papilloma, confirmed by second laryngo-microsurgery and received radiation therapy. After the third laryngo-microsurgery to remove residual papilloma, white irregular mass appeared on the right vocal cord and grew rapidly beneath the glottis, causing dyspnea. After 2 additional laryngo-microsurgeries, he was diagnosed having the dermoid tumor co-existing with recurrent squamous cell carcinoma. He underwent near-total laryngectomy and is currently alive without disease, speaking using a vocal shunt. Only five cases of the desmoid tumors arising in the adult larynx have been reported in the English literature. In this case, repeated surgery and radiation were suspected as the causes. Also, the present report is the first to describe desmoid tumor co-existing with recurrent squamous cell carcinoma in the larynx. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Effect of heavy metals and benzene on porphyrin synthesis of human epithelial larynx carcinoma cells (HEp-2); Wirkung von Schwermetallen und Benzol auf die Porphyrinsynthese von Humanen epithelialen Larynxkarzinomzellen (HEp-2)

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    Tumat, C.; Kath, H.G.; Perlewitz, J.; Manuwald, O. [Institut fuer Umweltmedizin, Erfurt (Germany); Herbarth, O. [UFZ - Umweltforschungszentrum Leipzig-Halle GmbH, Leipzig (Germany). Sektion Expositionsforschung und Epidemiologie

    2001-07-01

    Aim of the investigation was to prepare an environmental epidemiological test to detect the effects of pollutants by a pattern of porphyrin excretion in the urine. The task was to test whether lead, mercury, copper, zinc and benzene in environmentally relevant concentrations influence porphyrin synthesis of cells. The model used was the permanent epithelial larynx carcinoma cell line HEp-2, which was stimulated to synthesize porphyrins by adding {delta}-amino-levulinic acid ({delta}-ALA) in excess. 8- to 4-carboxyporphyrins and protoporphyrin IX were measured both in the cells and in the culture medium by means of high performance liqid cromatography (HPLC). The following pollutant effects were found: lead: extracellular increase of hexacarboxyporphyrin and intracellular decrease of heptacarboxy- and copro-porphyrin; mercury: extracellular decrease of heptacarboxyporphyrin and intracellular increase of coproporphyrin; copper: extracellular decrease of uro-, coproporphyrin and protoporphyrin IX, extracellular increase of heptacarboxyporphyrin and intracellular decrease of uro-, heptacarboxy- and coproporphyrin; zinc: extracellular increase of coproporphyrin; benzene: a tendency to extracellular increase of hexacarboxyporphyrin. The main result is the decrease in the concentrations of porphyrins caused by copper. This result is possibly linked to gastro-intestinal diseases among children due to drinking water from copper water pipes. (orig.) [German] Ziel der Untersuchungen war es, Vorarbeit zu leisten fuer die Entwicklung eines umwelt-epidemiologischen Tests, der es ermoeglicht, geringe Schadstoffwirkungen durch ein Porphyrin-Ausscheidungsmuster im Urin nachzuweisen. In diesem Zusammenhang bestand die Aufgabe zu pruefen, ob Blei, Quecksilber, Kupfer, Zink und Benzol in umweltmedizinisch relevanten Konzentrationen die Porphyrinsythese von Zellen beeinflussen. Als Untersuchungsmodell wurde die permanente humane epitheliale Larynxkarzinomzelllinie HEp-2 genutzt, die

  20. BASALOID SQUAMOUS CELL CARCINOMA OF THE LARYNX: A CASE REPORT

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    Mileta Golubović

    2013-03-01

    Full Text Available Basaloid squamous cell carcinoma is a highly aggressive tumor. The aim of this study was to present a case of a 60 year-old man having progressive hoarseness that lasted for six months. Indirect laryngoscopy and histopathologic examination detected an exophytic growth that involved the left false vocal fold. The patient underwent a left-sided, vertical partial hemilaryngectomy. Patient had no signs of tumor recurrence or metastases eighteen months later.

  1. Complications in CO2 Laser Transoral Microsurgery for Larynx Carcinomas

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    Estomba, Carlos Miguel Chiesa

    2016-01-01

    Full Text Available Introduction Transoral laser microsurgery (TLM has established itself as an effective option in the management of malignant tumors of the glottis, supraglottis, and hypopharynx. Nonetheless, TLM is not a harmless technique. Complications such as bleeding, dyspnea, or ignition of the air may appear in this type of surgery. Objective The aim of this study is to describe the complications that occurred in a group of patients treated for glottic and supraglottic carcinomas in all stages by TLM. Methods This study is a retrospective analysis of patients diagnosed with squamous cell carcinoma of the glottis and supraglottis for all stages (T1, T2, T3, T4, N -/ + , M -/+ treated with TLM between January 2009 and March 2012 in a tertiary hospital. Results Ninety-eight patients met the inclusion criteria, which had undergone a total of 131 interventions. Ninety-four (95.9% patients were male and 4 (4.1% were female. The mean age was 64.2 years (± 10.7 years = min 45; max 88. The presence of intraoperative complications was low, affecting only 2% of patients. Immediate postoperative complications occurred in 6.1%, whereas delayed complications affected 13.2% of patients, without any of them being fatal. Conclusion TLM has shown good oncologic results and low complication rate compared with traditional open surgery during intervention, in the immediate and delayed postoperative period and in the long-term with respect to radiotherapy.

  2. Hybrid Carcinoma of the Larynx: A Case Report (Adenoid Cystic and Adenocarcinoma and Review of the Literature

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    Ilias Karasmanis

    2013-01-01

    Full Text Available Introduction. The nonsquamous carcinomas of the larynx are considered rare with the majority of malignant tumors in this area, reaching the rate of 95%, to be squamous cell neoplasms. Case Report. The case refers to a 53-year-old man that presented with symptomatology of motor nerve disease. During the evaluation of the neurologic disease, a subglottic mass of the larynx was revealed accidentally in the imaging examination. Under general anesthesia, we performed direct laryngoscopy and biopsy of the mass. The histopathologic examination revealed a hybrid carcinoma coexistence of two different carcinomas, an adenoid cystic carcinoma and an adenocarcinoma, not otherwise specified with poor differentiation. Regarding the therapeutic plan, the mass was considered inoperable due to its expansion to trachea and the patient received radiotherapy. Conclusions. Both the adenocarcinoma and adenoid cystic carcinoma are extremely rare types of malignant tumors in the larynx. The special interest of the present case is the coexistence of these two rare tumors in the same region of the larynx, being a hybrid tumor of the salivary glands in the larynx, which is the second reported case, based on our systematic literature review.

  3. Thyroid Gland Involvement in Carcinoma Larynx and Hypopharynx-Predictive Factors and Prognostic Significance.

    Science.gov (United States)

    Iype, Elizabeth Mathew; Jagad, Vijay; Nochikattil, Santhosh Kumar; Varghese, Bipin T; Sebastian, Paul

    2016-02-01

    Intraoperative management of thyroid gland in laryngeal and hypopharyngeal cancer is controversial. The objectives of this study were to determine the incidence of thyroid gland invasion in patients undergoing surgery for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to assess the prognosis in patients with and without thyroid gland invasion. One hundred and thirty-three patients who underwent surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed retrospectively. Surgical specimens were examined to determine the incidence of thyroid gland invasion and predictive factors were analysed. The recurrence rate and the survival in patients with and without thyroid gland invasion were also analysed. Out of the 133 patients with carcinoma larynx and hypopharynx who underwent surgery, histological thyroid gland invasion was observed in 28/133 (21%) patients. Significant relationship was found between histological thyroid gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan and also when gross thyroid gland involvement observed during surgery. There is significant association between thyroid gland invasion when there is upper oesophageal or subglottic involvement. After analysing the retrospective data from our study, we would like to suggest that thyroid gland need not be removed routinely in all laryngectomies, unless there is advanced disease with thyroid cartilage erosion and gross thyroid gland involvement or disease with significant subglottic or oesophageal involvement.

  4. Verrucous Carcinoma of the Larynx Presenting as a Hairy Whitish Tumor

    Directory of Open Access Journals (Sweden)

    Masahiro Kawaida

    1997-01-01

    Full Text Available A patient was encountered with verrucous carcinoma of the larynx that presented as a hairy whitish tumor. There was a recurrence because simple excision with forceps by endolaryngeal microsurgery was performed in the first operation. However, in the second operation endolaryngeal microscopic laser surgery using a direct laryngoscope was performed and followed by adjuvant chemotherapy with oral UFT, a combination of uracil and tegafur in a molar ratio of 4:1. The patient’s course has been favorable to date. The case is reported in this paper and discussed from the viewpoint of diagnosis and treatment of this neoplasm.

  5. Effect of radiotherapy on serum mucoprotein level in carcinoma Larynx and Pharynx.

    Science.gov (United States)

    Mali, H R; Bhatt, M L; Natu, S M; Bhatia, N

    2001-01-01

    Serum mucoprotein level was determined in 61 individuals including 36 untreated patients of carcinoma Larynx & Pharynx and 25 healthy adults. Patients were treated by standard doses of radiation. Serum mucoprotein was again estimated following therapy. Patients showed a highly significant elevation in serum mucoprotein level as compared to controls (Pmucoprotein. The dose of the radiation also had no relation with the decline in serum mucoprotein after irradiation. The fall in serum mucoprotein level was significantly higher in patients having complete response as compared to partial response (P<0.001), however there was no difference between the patients having partial response or no response.

  6. [Analysis on expression of survivin and PTEN in vocal cords polyps, papilloma of larynx and laryngeal squamous cell carcinoma].

    Science.gov (United States)

    Guo, Qiangzhong; Li, Yunying

    2012-08-01

    Through exploring the differentiation on positive expressing rates between oncogene survivin and tumor-suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome ten) on vocal cord polyps (VCP), adult type laryngeal papilloma (ALP), and laryngeal squamous cell carcinoma (LSCC), to reveal the mechanism in cancellation of human laryngeal squamous cells, from benign proliferative lesion, benign tumor to malignant tumor in larynx. After picking out 18 cases of VCP, 10 cases of ALP, and 18 cases of LSCC for immunohistochemical process of Survivin and PTEN with two continuous section preparations, the differentiations of positive expression rates of Survivin and PTEN in the same human laryngeal squamous cells areas among three diseases were compared. The positive expressing rates of survivin and PTEN in VCP were obviously more lower than in ALP and LSCC (P 0.05). The positive expressing rates of survivin were always higher than PTEN in VCP, ALP and LSCC evidently (P laryngeal squamous cells take place or not, Survivin is always playing the leading role and making predominant impact on development of benign proliferative lesion, benign and malignant tumor in larynx.

  7. Thyroid gland invasion in advanced squamous cell carcinoma of the larynx and hypopharynx.

    Science.gov (United States)

    Mangussi-Gomes, João; Danelon-Leonhardt, Fernando; Moussalem, Guilherme Figner; Ahumada, Nicolas Galat; Oliveira, Cleydson Lucena; Hojaij, Flávio Carneiro

    Squamous cell carcinoma of the larynx and hypopharynx has the potential to invade the thyroid gland. Despite this risk, the proposition of either partial or total thyroidectomy as part of the surgical treatment of all such cases remains controversial. To evaluate the frequency of invasion of the thyroid gland in patients with advanced laryngeal or hypopharyngeal squamous cell carcinoma submitted to total laryngectomy or pharyngolaryngectomy and thyroidectomy; to determine whether clinic-pathological characteristics can predict glandular involvement. A retrospective case series with chart review, from January 1998 to July 2013, was undertaken in a tertiary care university medical center. An inception cohort of 83 patients with larynx/hypopharynx squamous cell carcinoma was considered. All patients had advanced stage disease (clinically T3-T4) and underwent total laryngectomy or total pharyngolaryngectomy in association with thyroidectomy. Adjuvant therapy was indicated when tumor or neck conditions required. Frequency of thyroid cartilage invasion was calculated; univariate and multivariate analysis of demographic, clinical and pathological characteristics associated with cartilage invasion were performed. The overall frequency of invasion of the thyroid gland was 18.1%. Glandular involvement was associated with invasion of the following structures: anterior commissure (odds ratio=5.13; 95% confidence interval 1.07-24.5), subglottis (odds ratio=12.44; 95% confidence interval 1.55-100.00) and cricoid cartilage (odds ratio=15.95; 95% confidence interval 4.23-60.11). Invasion of the thyroid gland is uncommon in the context of laryngopharyngeal squamous cell carcinoma. Clinical and pathological features such as invasion of the anterior commissure, subglottis and cricoid cartilage are more associated with glandular invasion. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights

  8. The preepiglottic space in relation to spread of carcinoma of the larynx; Szerzenie sie raka krtani a przestrzen przednaglosniowa

    Energy Technology Data Exchange (ETDEWEB)

    Osuch-Wojcikiewicz, E.; Skarzynski, H.; Janczewski, G.; Zawadowski, J. [Klinika Otolaryngologii, Akademia Medyczna, Warsaw (Poland)

    1994-12-31

    The preepiglottic space significance in relation to spread of carcinoma of the larynx was discussed. Controversy surrounds the status of the preepiglottic space in the two TNM classifications. The authors suggest that preepiglottic space invasion should be assigned a T4 grading. (author) 5 refs, 1 fig

  9. SCC antigen in patients with carcinoma of the larynx; Antygen SCC u chorych na raka krtani

    Energy Technology Data Exchange (ETDEWEB)

    Lachowicz, M.; Hassmann-Poznanska, E. [Akademia Medyczna, Bialystok (Poland)

    1994-12-31

    Squamous Cell Carcinoma Antigen (SCC Ag) was measured in 71 succeeding patients at age 39-80 sufferings from cancer of the larynx. Samples were taken before and after treatment (surgery and/or radiotherapy - {sup 60}Co) and every 3 months during follow up. In control group the mean SCC Ag level was 1.0 ng/ml. The SCC Ag levels more than 2.0 ng/ml were considered as abnormal. At diagnosis the sensitivity of the marker was 17%. Most patients (63.4%) had lower levels of SCC Ag after treatment. Recurrence of cancer was associated with elevation of SCC levels in 81.3% of the 16 patients. An increase in SCC Ag was 3-10 months before clinical recurrence. The marker is of no prognostic value at the time of diagnosis, but is useful in follow-up as an early sign of recurrence. (author) 5 refs, 1 tab

  10. Larynx preservation protocols: long-term functional outcomes in good responders to induction chemotherapy for pyriform sinus carcinoma.

    Science.gov (United States)

    Vourexakis, Zacharias; Janot, François; Dulguerov, Pavel; Le Ridant, Anne-Marie

    2014-01-01

    Larynx preservation for laryngopharyngeal carcinomas aims to avoid the mutilation of a total laryngectomy without compromising survival or functionality. The aim of the present study on pyriform sinus squamous cell carcinoma (SCC) is to evaluate the long-term functional outcomes of larynx preservation in good responders to induction chemotherapy (ICT). The study was carried out in a tertiary referral cancer center in France. The subjects were good responders to ICT for pyriform sinus SCC, subsequently treated with adjuvant radiation therapy (RT) - with or without concomitant chemotherapy - between 1999 and 2008. Only patients without recurrence at 3 years were included. The evaluated pharyngolaryngeal functions were airway patency, oral communication and oral feeding, based on a self-administered questionnaire and the patients' medical records. Twenty-eight patients were retained. Two (7%) patients needed a tracheotomy during or after the treatment and 2 (7%) had total laryngectomy for a late local recurrence. At least 3 years after the end of treatment, all patients were exclusively fed by mouth. All the evaluated patients judged their voice performance as 'adequate for everyday oral communication'. In the long run, patients with pyriform sinus SCC who are candidates for larynx preservation and respond favorably to ICT present a satisfactory functional outcome when treated with adjuvant RT. © 2014 S. Karger AG, Basel.

  11. Metastase i larynx fra colonadenokarcinom

    DEFF Research Database (Denmark)

    Dadkhah, Naser; Hahn, Christoffer

    2015-01-01

    Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, followed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx are extremely...... rare. Tumours spreading to the larynx may be asymptomatic or may result in hoarseness, stridor or airway obstruction. Patients with metastasis of colonic adenocarcinoma to the larynx usually present with disseminated disease. We present a case of an isolated laryngeal metastasis from a colonic...

  12. Gene and miRNA expression changes in squamous cell carcinoma of larynx and hypopharynx

    Science.gov (United States)

    Nair, Jayalakshmi; Jain, Prachi; Chandola, Udita; Palve, Vinayak; Vardhan, N R. Harsha; Reddy, Ram Bhupal; Kekatpure, Vikram D.; Suresh, Amritha; Kuriakose, Moni Abraham; Panda, Binay

    2015-01-01

    Laryngo-pharyngeal squamous cell carcinomas are one of the most common head and neck cancers. Despite the presence of a large body of information, molecular biomarkers are not currently used in the diagnosis, treatment and management of patients for this group of cancer. Here, we have profiled expression of genes and microRNAs of larynx and hypopharynx tumors using high-throughput sequencing experiments. We found that matrix metalloproteinases along with SCEL, CRNN, KRT4, SPINK5, and TGM3 among others have significantly altered expression in these tumors. Alongside gene expression, the microRNAs hsa-miR-139, hsa-miR-203 and the hsa-miR-424/503 cluster have aberrant expression in these cancers. Using target genes for these microRNAs, we found the involvement of pathways linked to cell cycle, p53 signaling, and viral carcinogenesis significant (P-values 10−13, 10−9 and 10−7 respectively). Finally, using an ensemble machine-learning tool, we discovered a unique 8-gene signature for this group of cancers that differentiates the group from the other tumor subsites of head and neck region. We investigated the role of promoter methylation in one of these genes, WIF1, and found no correlation between DNA methylation and down-regulation of WIF1. We validated our findings of gene expression, 8-gene signature and promoter methylation using q-PCR, data from TCGA and q-MSP respectively. Data presented in this manuscript has been submitted to the NCBI Geo database with the accession number GSE67994. PMID:26413216

  13. Larynx Anatomy

    Science.gov (United States)

    ... e.g. -historical Searches are case-insensitive Larynx Anatomy Add to My Pictures View /Download : Small: 648x576 ... View Download Large: 2700x2400 View Download Title: Larynx Anatomy Description: Anatomy of the larynx; drawing shows the ...

  14. Survival Outcomes in Patients with T2N0M0 (Stage II) Squamous Cell Carcinoma of the Larynx.

    Science.gov (United States)

    Gainor, Danielle L; Marchiano, Emily; Bellile, Emily; Spector, Matthew E; Taylor, Jeremy M G; Wolf, Gregory T; Hogikyan, Norman D; Prince, Mark E; Bradford, Carol R; Eisbruch, Avraham; Worden, Francis; Shuman, Andrew G

    2017-10-01

    Objective Emerging data have demonstrated suboptimal outcomes among patients with stage II larynx cancer. Our objective is to report survival outcomes for T2N0M0 larynx cancer and to determine the cause-specific survival. Study Design Case series with planned data collection. Setting Tertiary academic center. Subjects Adults with T2N0M0 squamous cell carcinoma of the larynx treated with curative intent. Methods A head and neck cancer epidemiology database was queried for eligible subjects from 2003 to 2014. Data were extracted from the electronic medical record and research database, and survival analyses were performed. Results Thirty-four patients with previously untreated stage II larynx cancer were identified (median follow-up 48 months). Patients included 27 males and 7 females with a mean age of 59 years. The majority of tumors arose from the glottis (59%). Of the cohort, 12% were treated with surgery, 65% radiation therapy, and 24% chemoradiation therapy. The estimated 2-year overall survival was 81%, (95% confidence interval [CI], 59%-92%), disease-specific survival was 91% (95% CI, 69%-98%), and recurrence-free survival was 84% (95% CI, 65%-93%). Four of 5 patients with persistent or recurrent disease posttreatment were successfully salvaged with total laryngectomy with 100% locoregional control. There were 11 mortalities (2 disease related, 2 due to metachronous primaries, 3 treatment related, and 4 from other/unknown causes). Conclusion Stage II laryngeal cancer has suboptimal survival outcomes. This appears to be a reflection of medical comorbidities, propensity for metachronous primaries, and the sequelae of late treatment effects rather than poor locoregional control.

  15. Alterations of microbiota structure in the larynx relevant to laryngeal carcinoma

    OpenAIRE

    Gong, Hongli; Shi, Yi; Xiao, Xiyan; Cao, Pengyu; Wu, Chunping; Tao, Lei; Hou, Dongsheng; Wang, Yuezhu; Zhou, Liang

    2017-01-01

    The microbial communities that inhabit the laryngeal mucosa build stable microenvironments and have the potential to influence the health of the human throat. However, the associations between the microbiota structure and laryngeal carcinoma remain uncertain. Here, we explored this question by comparing the laryngeal microbiota structure in laryngeal cancer patients with that in control subjects with vocal cord polyps through high-throughput pyrosequencing. Overall, the genera Streptococcus, ...

  16. Longterm results of curative laser microsurgery for carcinoma of the larynx and hypopharynx

    Energy Technology Data Exchange (ETDEWEB)

    Steiner, W. [Univ. of Goettingen, Goettingen (Germany)

    1994-12-31

    This report is based on 282 patients without prior treatment, treated with curative intention for cancer of the larynx and hypopharynx at the ENT Dept. of the Univ. of Erlangen/Nurnberg. Patients were treated with laser microsurgery plus/minus neck dissection, plus/minus postoperative radiotherapy. Low locoregional recurrences, a high adjusted survival rate, a low rate of complications and side effects, and the fact of avoiding total laryngectomy(with partial pharyngectomy) in many cases favor function preserving surgery of the primary and of the neck. Accounting for certain conditions and respecting certain limitations this concept of minimally invasive therapy represents a real progress in the treatment of cancer of the larynx and hypopharynx with respect to oncology, function and economy

  17. p16 (INK4a has clinicopathological and prognostic impact on oropharynx and larynx squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    S.D. Silva

    2012-12-01

    Full Text Available CDKN2A encodes proteins such as p16 (INK4a, which negatively regulate the cell-cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur frequently in cancer. Although p16 (INK4a may be involved in tumor progression, the clinical impact and prognostic implications in head and neck squamous cell carcinoma (HNSCC are controversial. The objective of this study was to evaluate the frequency of the immunohistochemical expression of p16 (INK4a in 40 oropharynx and 35 larynx from HNSCC patients treated in a single institution and followed-up at least for 10 years in order to explore potential associations with clinicopathological outcomes and prognostic implications. Forty cases (53.3% were positive for p16 (INK4a and this expression was more intense in non-smoking patients (P = 0.050, whose tumors showed negative vascular embolization (P = 0.018, negative lymphatic permeation (P = 0.002, and clear surgical margins (P = 0.050. Importantly, on the basis of negative p16 (INK4a expression, it was possible to predict a probability of lower survival (P = 0.055 as well as tumors presenting lymph node metastasis (P = 0.050 and capsular rupture (P = 0.0010. Furthermore, increased risk of recurrence was observed in tumors presenting capsular rupture (P = 0.0083. Taken together, the alteration in p16 (INK4a appears to be a common event in patients with oropharynx and larynx squamous cell carcinoma and the negative expression of this protein correlated with poor prognosis.

  18. p16 (INK4a) has clinicopathological and prognostic impact on oropharynx and larynx squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Silva, S.D. [Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia, Hospital A.C. Camargo, São Paulo, SP (Brazil); Department of Oncology, Lady Davis Institute for Medical Research and Segal Cancer Centre, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Department of Otolaryngology-Head and Neck Surgery, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Nonogaki, S. [Departamento de Anatomia Patológica, Hospital A.C. Camargo, São Paulo, SP (Brazil); Soares, F.A. [Departamento de Anatomia Patológica, Hospital A.C. Camargo, São Paulo, SP (Brazil); Departamento de Estomatologia, Faculdade de Odontologia, Universidade de São Paulo, São Paulo, SP (Brazil); Kowalski, L.P. [Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia, Hospital A.C. Camargo, São Paulo, SP (Brazil)

    2012-09-07

    CDKN2A encodes proteins such as p16 (INK4a), which negatively regulate the cell-cycle. Molecular genetic studies have revealed that deletions in CDKN2A occur frequently in cancer. Although p16 (INK4a) may be involved in tumor progression, the clinical impact and prognostic implications in head and neck squamous cell carcinoma (HNSCC) are controversial. The objective of this study was to evaluate the frequency of the immunohistochemical expression of p16 (INK4a) in 40 oropharynx and 35 larynx from HNSCC patients treated in a single institution and followed-up at least for 10 years in order to explore potential associations with clinicopathological outcomes and prognostic implications. Forty cases (53.3%) were positive for p16 (INK4a) and this expression was more intense in non-smoking patients (P = 0.050), whose tumors showed negative vascular embolization (P = 0.018), negative lymphatic permeation (P = 0.002), and clear surgical margins (P = 0.050). Importantly, on the basis of negative p16 (INK4a) expression, it was possible to predict a probability of lower survival (P = 0.055) as well as tumors presenting lymph node metastasis (P = 0.050) and capsular rupture (P = 0.0010). Furthermore, increased risk of recurrence was observed in tumors presenting capsular rupture (P = 0.0083). Taken together, the alteration in p16 (INK4a) appears to be a common event in patients with oropharynx and larynx squamous cell carcinoma and the negative expression of this protein correlated with poor prognosis.

  19. A Case Report of Spindle Cell (Sarcomatoid Carcinoma of the Larynx

    Directory of Open Access Journals (Sweden)

    Harry Boamah

    2012-01-01

    Full Text Available Spindle cell carcinoma (SpCC or sarcomatoid carcinoma is a highly malignant variant of squamous cell carcinoma which comprises 2% to 3% of all laryngeal cancers. It is considered to be a biphasic tumor that is composed of a squamous cell carcinoma (in situ or invasive and spindle cell carcinoma with sarcomatous appearance. Most spindle cell tumors are polypoid and pedunculated; they are often detected at an early stage, removed by polypectomy during diagnosis, and tend to have a very good prognosis. We present a case of spindle cell carcinoma in a 67-year-old Caucasian male who presented with progressive hoarseness of his voice, dysphagia, odynophagia and a 20-pound weight loss. The patient underwent direct laryngoscopy with excision of the malignant mass and received radiation therapy. His symptoms gradually improved, and he regained good control of his voice.

  20. [Usefulness of postoperative support by enteral nutrition of patients with epidermoid carcinoma of the larynx].

    Science.gov (United States)

    de Luis, D A; Cabezas, G; Aller, R; Izaola, O

    2000-01-01

    At the present time, artificial nutrition has made great strides and enteral nutrition has become the first choice delivery method. The purpose of our paper is to analyze the usefulness of this type of nutrition in the post-operative care of patients with larynx tumours. A total of 38 patients were studied, with an average age of 63.2 +/- 10.2 years. On average, in the post-operative period until oral nutrition was restored enteral nutrition lasted for 10.6 +/- 4.9 days. A biochemical and anthropometric assessment of the nutritional condition was effected at the time of admission and 7-10 days into the nutritional treatment. During the post-operative period, no anthropometric changes were detected; the analytical variation, however, showed an improvement on the first review of pre-albumen (12.5 +/- 5.1 mg/dl versus 18.7 +/- 7.9 mg/dl; p enteral nutrition was 4,723 +/- 1,600 pesetas per day. Enteral nutrition is effective in the post-operative care of patients with tumour of the larynx, improving their nutritional biochemistry parameters and allowing easy transition to oral nutrition, with presentation of few side effects and all for low cost.

  1. A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85

    DEFF Research Database (Denmark)

    Overgaard, J; Hansen, H S; Overgaard, M

    1998-01-01

    A multicenter randomized and balanced double-blind trial with the objective of assessing the efficacy and tolerance of nimorazole given as a hypoxic radiosensitizer in conjunction with primary radiotherapy of invasive carcinoma of the supraglottic larynx and pharynx....

  2. Pyriform sinus squamous cell carcinoma: oncological outcomes in good responders of induction chemotherapy-based larynx preservation protocols.

    Science.gov (United States)

    Vourexakis, Zacharias; Le Ridant, Anne-Marie; Dulguerov, Pavel; Janot, François

    2015-07-01

    Induction chemotherapy-based larynx preservation protocols use chemotherapy to select exclusively patients with 'chemosensitive' tumors for a nonsurgical treatment with radiation therapy. This study on pyriform sinus squamous cell carcinoma (SCC) is interested in the oncological outcome of treatment based on radiation therapy when offered to patients with tumors responding to induction chemotherapy. This was a retrospective cohort study. The cohort included good responders to induction chemotherapy, subsequently treated with definite radiation therapy (with or without concomitant chemotherapy) for pyriform sinus SCC, in a tertiary referral cancer center. The primary endpoints were overall, laryngectomy-free and disease-free survival and the secondary endpoints were analysis of treatment failures and possibilities of salvage treatment. Forty-two patients fulfilled the inclusion criteria and were retained for analysis; 7% were stage II (3/42), 48% stage III (20/42) and 45% stage IV (19/42). At 1, 3 and 5 years, the overall survival was 95% (40/42), 74% (31/42), and 60% (SE ≈ 0.08), respectively. For the same intervals, the laryngectomy-free survival was 90% (38/42), 69% (29/42) and 50% (SE ≈ 0.08), respectively. The estimated 5-year disease-free survival was also 50%. Disease-free survival was significantly better for N0 patients. There was a 28% recurrence rate, mainly in the primary tumor site (9/11), with or without simultaneous nodal recurrence. Interestingly, more than one-third of all oncologic failures occurred beyond the first 3 years of follow-up. Salvage treatment was not possible or definitely inefficient in at least 2/3 of all recurrences. In candidates for larynx preservation for a pyriform sinus SCC, good response to induction chemotherapy followed by definite radiation therapy seems to be associated with a more favorable prognosis. Nevertheless, in case of locoregional recurrence the possibilities for efficient salvage treatment are limited.

  3. Primary candidiasis and squamous cell carcinoma of the larynx: report of a case.

    Science.gov (United States)

    Lee, Dong Hoon; Cho, Hyong Ho

    2013-02-01

    Primary candidiasis is rare and often confused with a pre-cancerous lesion, squamous cell carcinoma, or verrucous carcinoma. We report an extremely rare case of squamous cell carcinoma of the vocal cord following primary candidiasis. A 62-year-old man presented to our department reporting a 1-month history of hoarseness. He underwent laryngeal microscopic surgery for a presumptive diagnosis of glottic carcinoma. Histopathologic examination revealed candidiasis and scattered moderate dysplasia. He was treated with itraconazole for 4 weeks, and followed up without any recurrence of candidiasis. However, the 42-month follow-up examination revealed a focal whitish lesion on the right true vocal cord, and a repeat biopsy of this area revealed squamous cell carcinoma without evidence of candidiasis. The patient was treated with radiotherapy and remains well with no signs of tumor recurrence or candidiasis.

  4. Secondary neoplasms of the larynx from a colonic adenocarcinoma

    DEFF Research Database (Denmark)

    Dadkhah, Naser; Hahn, Christoffer

    2015-01-01

    Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, fol-lowed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx are extrem......Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, fol-lowed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx...

  5. Alterations of microbiota structure in the larynx relevant to laryngeal carcinoma.

    Science.gov (United States)

    Gong, Hongli; Shi, Yi; Xiao, Xiyan; Cao, Pengyu; Wu, Chunping; Tao, Lei; Hou, Dongsheng; Wang, Yuezhu; Zhou, Liang

    2017-07-14

    The microbial communities that inhabit the laryngeal mucosa build stable microenvironments and have the potential to influence the health of the human throat. However, the associations between the microbiota structure and laryngeal carcinoma remain uncertain. Here, we explored this question by comparing the laryngeal microbiota structure in laryngeal cancer patients with that in control subjects with vocal cord polyps through high-throughput pyrosequencing. Overall, the genera Streptococcus, Fusobacterium, and Prevotella were prevalent bacterial populations in the laryngeal niche. Tumor tissue samples and normal tissues adjacent to the tumor sites (NATs) were collected from 31 laryngeal cancer patients, and the bacterial communities in laryngeal cancer patients were compared with control samples from 32 subjects. A comparison of the laryngeal communities in the tumor tissues and the NATs showed higher α-diversity in cancer patients than in control subjects, and the relative abundances of seven bacterial genera differed among the three groups of samples. Furthermore, the relative abundances of ten bacterial genera in laryngeal cancer patients differed substantially from those in control subjects. These findings indicate that the laryngeal microbiota profiles are altered in laryngeal cancer patients, suggesting that a disturbance of the microbiota structure might be relevant to laryngeal cancer.

  6. "MUCOEPIDERMOID CARCINOMA OF THE LARYNX: REPORT OF A RARE LARYNGEAL TUMOR"

    Directory of Open Access Journals (Sweden)

    S. Z. Madani-Kermani

    2004-06-01

    Full Text Available Mucoepidermoid carcinoma is a neoplasm of salivary gland origin, and its laryngeal occurrence is extremely rare. This malignant tumor is composed of two distinct cell types, the epidermoid and mucus cells. Prognosis is largely dependent on the histologic pattern. In this report, an extremely rare laryngeal cancer and its clinicopathologic features are described.

  7. The pars interna/media anatomy and histology in the human larynx.

    Science.gov (United States)

    Charpied, George L

    2007-01-01

    The pars interna/media (PIM) is a small muscle found in the human larynx that has not been successfully described in contemporary literature on laryngeal structure. The objective of this study was to describe the PIM's anatomy in detail. Thirteen human larynges obtained from postmortem examination were cleaned and preserved. Exposure of the PIM was through a lateral disarticulation of the cricothyroid joint and reflection of the cricothyroid muscle and the thyroid lamina. In the human, the PIM was found to be strap-like in form and to have two bellies with attachments to the medial surface of the thyroid cartilage at the root of the inferior horn and anteriosuperior cricoid arch. It appears to be innervated by a middle division, vestibular branch, of the internal superior laryngeal nerve. The average fiber diameter is 40 mum. Its type 1-to-type 2 fiber ratio places it within the range of other intrinsic laryngeal muscles. A muscle spindle was identified in medial bundle at the PIM's thyroid attachment. Thyroid medial surface attachment is within few millimeters of the muscular process of the arytenoid cartilage. These data show that the PIM is a robust muscle and deserves attention anatomically. Its orientation within the thyroid and nonrecurrent laryngeal nerve innervations of the human PIM may place it in the vocal fold tensor group rather than the laryngeal sphincter group. It is possible the PIM reports on cricothyroid distance and right versus left cricothyroid joint stresses. Electromyographic examination of the PIM in the Rhesus larynx may help elucidate its physiology to elaborate its human physiology. Copyright 2007 S. Karger AG, Basel.

  8. NUT midline carcinoma of the larynx: an international series and review of the literature.

    Science.gov (United States)

    Hellquist, Henrik; French, Christopher A; Bishop, Justin A; Coca-Pelaz, Andrés; Propst, Evan J; Paiva Correia, António; Ngan, Bo-Yee; Grant, Ronald; Cipriani, Nicole A; Vokes, David; Henrique, Rui; Pardal, Fernando; Vizcaino, Jose Ramon; Rinaldo, Alessandra; Ferlito, Alfio

    2017-05-01

    NUT midline carcinoma (NMC) is a rare undifferentiated and aggressive carcinoma that locates characteristically to the midline of the head and neck, and mediastinum. NMC is characterized by chromosomal rearrangements of the gene NUT, at 15q14. The BRD4 gene on 19q13 is the most common translocation partner forming a fusion oncogene, BRD4-NUT. By the end of 2014, the International NUT Midline Carcinoma Registry had 48 patients treated for NMC. Laryngeal NMC are exceedingly rare, and we report a case series of seven cases. We searched for cases in files of different hospitals as well as a thorough search of the English language literature. The diagnosis of NMC is made by demonstration of NUT rearrangement either by immunohistochemistry, fluorescence in-situ hybridization (FISH) or reverse transcription-polymerase chain reaction (RT-PCR). We found three previously published cases, and in this series add four cases of our own. NMC consists of monomorphic, often discohesive, cells with an epithelioid appearance and distinct nucleoli. The tumours typically show abrupt squamous differentiation. The mean age of the patients was 34 years, hence significantly lower than that for conventional laryngeal carcinoma. All tumours were located in the supraglottis and five patients died of the disease after 3, 7, 8, 9 and 11 months. Laryngeal NMC may be underdiagnosed, and an increased awareness among pathologists is warranted. NMC has characteristic morphological features, and positive immunostaining with the NUT antibody is diagnostic. Its aggressive behaviour demands a very intense treatment strategy and the need for its recognition is emphasized further by new promising treatment strategies. © 2016 John Wiley & Sons Ltd.

  9. Leiomyosarcoma of Larynx as a Metachronous Tumor of Squamous Cell Carcinoma: An Unusual Case.

    Science.gov (United States)

    Ismi, Onur; Arpaci, Rabia Bozdogan; Puturgeli, Tugce; Ozcan, Cengiz; Gorur, Kemal

    2016-03-01

    Leiomyosarcomas (LMSs) are malignant tumors of smooth muscles accounting for 5-6% of all soft tissue sarcomas. They are mostly seen in the gastrointestinal tractus, the uterus, and the retroperitoneum. Soft tissue sarcomas comprise <1% of all laryngeal malignancies, most of which are chondrosarcomas. Laryngeal LMSs are rarely seen malignancies, which are published as case reports. We presented a case of laryngeal LMS, which was seen 4 years later in a laryngeal squamous cell carcinoma patient who underwent laryngeal laser microsurgery. We discussed the diagnosis and treatment algorithm in the light of the present literature. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  10. 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...... of the role of vitronectin in tumour biology in interaction with the plasminogen activation system and integrins....

  11. Influence of the vocal cord mobility in salvage surgery after radiotherapy for early-stage squamous cell carcinoma of the glottic larynx.

    Science.gov (United States)

    Gorphe, Philippe; Blanchard, Pierre; Temam, Stephane; Janot, François

    2015-10-01

    Disease relapses occur in up to 40% of cases after radiotherapy (RT) for early-stage glottic laryngeal neoplasms, and the foremost remaining treatment option is salvage total laryngectomy (STL). Our objectives were to review the outcomes of patients treated with salvage surgery after RT for early-stage carcinoma of the glottic larynx and to assess prognostic factors. We retrospectively analyzed 43 patients who underwent surgery. Overall and disease-free survival rates among subgroups were calculated and compared, stratified by preoperative stage, vocal cord mobility and postoperative histopathologic data. Recurrences occurred 22.7 months after the end of RT. Surgery was STL in 33 cases (76.8%). The main prognostic factors associated with survival rates were initial vocal cord mobility, vocal cord mobility at the diagnosis of recurrence, and changes in mobility. Vocal cord mobility is an important clinical criterion in treatment decision making for early-stage glottis carcinoma and remains important during follow-up.

  12. Neck nodes metastases in carcinoma of the larynx - results of treatment; Wyniki leczenia przerzutow do wezlow chlonnych szyi w raku krtani

    Energy Technology Data Exchange (ETDEWEB)

    Hassmann-Poznanska, E.; Bucko, M.E. [Klinika Otolaryngologii, Akademia Medyczna, Bialystok (Poland)

    1994-12-31

    584 patients with carcinoma of the larynx treated with surgery of the larynx and bilateral functional neck dissection, between 1980 and 1989, were reviewed. 127 of them had histopathologically proven metastases to the lymph nodes. Pathologic stating of cervical metastases was as followed: pN1 - 24.5%, pN2a - 10.2%, pN2b - 26%, pN2c - 29.1%, pN3 - 10.2%. Of the 127 patients 89% were treated by surgery and postoperative radiation, 20% had surgery alone, that means radical or conservative neck dissection. In the group with combined treatment the results were much better than in cases of surgery alone, in advanced cases (pN2c, pN3) - 43.2% and 10% 5-year survival rate respectively. In the group of less advanced changes in the neck the difference in survival rate in the group with and without radiotherapy was very small. The results indicate that postoperative radiotherapy has great effect on survival rate in advanced cases of cervical metastases. (author)

  13. Molecular profiles as predictive marker for the effect of overall treatment time of radiotherapy in supraglottic larynx squamous cell carcinomas

    DEFF Research Database (Denmark)

    Eriksen, Jesper Grau; Buffa, F.M.; Alsner, Jan

    2004-01-01

    BACKGROUND AND PURPOSE: Reduction of the overall treatment time of radiotherapy increases the probability of local tumour control, but it does not benefit all patients. Identification of molecular marker profiles may aid in the selection of patients likely to benefit from accelerated radiotherapy....... PATIENTS AND METHODS: Two hundred and nine patients with SCC of the supraglottic larynx received primary radiotherapy in the randomised DAHANCA trials to 66-68 Gy, 2 Gy/fx but with different overall treatment times of 9.5 week, 6.5 week and 5.5 week. Formalin-fixed paraffin embedded tumour slides were...... as the endpoint. CONCLUSIONS: Molecular marker profiling may aid in the selection of patients that will benefit of a reduction in overall treatment time of radiotherapy in SCC of the supraglottic larynx....

  14. Vocal handicap and quality of life after treatment of advanced squamous carcinoma of the larynx and/or hypopharynx.

    Science.gov (United States)

    Azevedo, Elma Heitmann Mares; Montoni, Neyller; Gonçalves Filho, João; Kowalski, Luiz Paulo; Carrara-de Angelis, Elisabete

    2012-03-01

    To evaluate and correlate voice-specific quality of life (QOL) and health-related QOL (HR-QOL) after treatment for advanced cancer of the larynx and/or hypopharynx. Cross-sectional study. Patients submitted to partial laryngectomy (PL), salvage PL (sPL), concomitant radiotherapy and chemotherapy (RT+Chemo), total laryngectomy (TL), salvage TL (sTL), total pharyngolaryngectomy (TP) and salvage total pharyngolaryngectomy (sTP). The following questionnaires were used: (1) Voice Handicap Index (VHI) and (2) University of Washington Quality of Life Questionnaire (UW-QOL; version 4). Eighty-four patients participated in the study. All the patients PL (10), sPL (1), and RT+Chemo (24) communicated by laryngeal voice. Of the 49 patients submitted to total removal of the larynx, 30 communicated with alaryngeal phonation, the major part being tracheoesophageal prosthesis (17). The worst subscale of VHI for the total patient group was functional (mean=13.15), and the value of the total score was 31. Patients submitted to PL, RT+Chemo, and TL presented slight handicap (medians of 27, 14, and 21.5, respectively). Patients treated with sTL, TP, and sTP presented moderate handicap (medians of 45, 37.5, and 31.5, respectively). HR-QOL was considered between good and excellent for 78.6% of the patients, and poor for 21.4%. The correlation between voice-specific QOL and HR-QOL was significant (P=0.0001). Patients treated for advanced cancer of the larynx/hypopharynx present slight to moderate voice handicap and good/excellent HR-QOL. Stricter analysis of both the VHI and UW-QOL data suggests that more attention be given to the vocal handicap of the individual patient. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  15. Asbestos and cancer of the larynx

    Energy Technology Data Exchange (ETDEWEB)

    Viallat, J.R.; Farisse, P.; Rey, F.; Boutin, C.; Henin, Y.; Jausseran, M.; D' Istria, J.C.

    1986-01-01

    Two hundred subjects were evaluated using a standardized questionnaire in order to determine possible exposure to asbestos: 50 patients with a carcinoma of the larynx (mean age: 59.2 +/- 1.6 years), 50 patients with a carcinoma of the bronchus (mean age 61.2 +/- 1.5 years) and 100 controls. Rates concerning exposure to asbestos were 27.8%, 23.4% and 4% respectively. The difference between the carcinoma patients and the controls was significant (p less than 0.001). The mean time lapse between the first exposure to asbestos and the development of malignant disease was shorter for the larynx (28.5 +/- 4 years) than for the lung (46.2 +/- 4.2): p less than 0.01. This study confirms the etiological role of asbestos in the pathogenesis of carcinoma of the larynx as well as carcinoma of the lung, and raises the problem of their medicolegal compensation.

  16. Middle frontal horizontal partial laryngectomy (MFHPL: a treatment for stage T1b squamous cell carcinoma of the glottic larynx involving anterior vocal commissure.

    Directory of Open Access Journals (Sweden)

    Wen-bin Lei

    Full Text Available OBJECTIVE: The therapeutic effect of middle frontal horizontal partial laryngectomy (MFHPL in treating stage T1b squamous cell carcinoma of the glottic larynx involving anterior vocal commissure (AVC was compared with that of the anterior frontolateral vertical partial laryngectomy (AFVPL. The feasibility and practical significance of MFHPL in clinical application was discussed in the present study. METHODS: From January 1996 to January 2010, a total of 65 patients diagnosed with stage T1bN0M0 glottic laryngeal cancer were treated with MFHPL or AFVPL. The postoperative complications, glottic reconstruction, recurrence rate, voice quality and survival rates were evaluated and compared between two treatments. RESULTS: AFVPL and MFHPL were performed in 34 and 31 patients, respectively. Flexible fiberoptic laryngoscopy revealed that in the MFHPL-treated patients the reconstructed glottis was spacious and symmetric. In contrast, AFVPL treatment resulted in irregular glottic area with poor symmetry and tubular glottis. The incidence of postoperative laryngeal stenosis significantly differed between the MFHPL- and AFVPL-treated groups (P = 0.025. No significant difference was detected in the 3- and 5-year overall- or tumor-free survival rates between two treatments. The Voice Handicap Index (VHI and maximum phonation time (MPT after surgery were 51.0±12.99 and 12.42±3.44 sec in the AFVPL-treated group; while in the MFHPL-treated patients they were 31.81±7.48 and 7.65±1.98 sec, respectively. Both differences in VHI (P = 0.012 and MPT (P = 0.024 were significant between two treatments. CONCLUSIONS: MFHPL was comparable to AFVPL with respect to postoperative complications, recurrence rate and survival rates, but possessed advantages over AFVPL in terms of the incidence of laryngeal stenosis and voice quality. Our study indicated that MFHPL has a potential value in clinical practice of treating stage T1b squamous cell carcinoma of the

  17. Fatores prognósticos no tratamento do carcinoma epidermóide da laringe: cirurgia conservadora x radical Prognostic factors in the treatment of squamous cell carcinoma of the larynx: partial surgery x radical surgery

    Directory of Open Access Journals (Sweden)

    Maria da Graça Caminha Vidal

    2007-12-01

    Full Text Available O tratamento do carcinoma da laringe tem como desafio a cura do paciente e a preservação do órgão. OBJETIVO: A avaliação dos subsítios na disseminação do carcinoma e a sua influência no tratamento cirúrgico da laringe, no controle local e na sobrevida. MATERIAL E MÉTODO: Cento e sessenta pacientes tratados na Escola Paulista de Medicina - Hospital São Paulo, no período de janeiro de 1998 a dezembro de 2004, foram compilados para análise da disseminação do carcinoma dos subsítios da laringe. Foram incluídos pacientes com seguimento mínimo de 2 anos, após diagnóstico e tratamento. A avaliação estatística foi: Teste X2, Teste de Fisher e a Curva de Kaplan-Meier. Forma de Estudo: Estudo de Coorte Histórica Longitudinal (Trabalho Clínico Retrospectivo. RESULTADOS: A comissura posterior e a infraglote, respectivamente, foram significantes para a laringectomia total: tumores glóticos AC: (p=0,03 AP: (p=0,0001; AC: (p=0,0007 AP: (pThe present study aimed at assessing the other sites as the carcinoma spreads, as well as therapeutic results, in larynx preservation and patient survival. STUDY TYPE: It is a Longitudinal Historical Cohort Study, a retrospective clinical study. MATERIALS AND METHODS: A hundred and sixty (160 patients treated at ‘Escola Paulista de Medicina’ (‘Paulista’ Medical School - São Paulo Hospital, from January 1988 to December 2004 were examined as for the spreading of their larynx carcinoma. Those patients whose evaluations were at least two years old after treatment were the only ones accepted. The parametric tests used were: Test X2, Fisher’s test, and Kaplan-Meier’s curve. RESULTS: The posterior commissure and the infraglottis were significant in terms of the laryngectomy: glottal tumors AC: (p=0.03 AP: (p=0.0001; AC: (p=0.0007 AP: (p<0.0001, respectively. The infraglottis was significant in G+SG tumors in AP: (p=0.04 and in death rate AP: (p=0.03. CONCLUSION: total laryngectomy is the

  18. Treatment of local and nodal recurrences in carcinoma of the larynx; Leczenie nowotworow miejscowych i wezlowych raka krtani

    Energy Technology Data Exchange (ETDEWEB)

    Kowalska, B.; Bulinska, H.; Debniak, E. [Akademia Medyczna, Gdansk (Poland)

    1994-12-31

    Methods of treatment in 93 cases of post surgery recurrences of laryngeal carcinoma have been presented. Treatment prospects and results in 80 patients with local and/or nodal recurrence have been discussed. Among those patients, 12 (15%) displayed a long-term survival rate with no symptoms. (author)

  19. The examination of the lymphatic glands from the patients with larynx carcinoma; Badania wezlow chlonnych u chorych z rakiem krtani

    Energy Technology Data Exchange (ETDEWEB)

    Murlewska, A.; Gryczynski, M.; Grabicka-Grochal, M.; Jaskiewicz, D. [Katedra i Klinika Otolaryngologii, Akademia Medyczna, Lodz (Poland)]|[Zaklad Medycyny Nuklearnej, Instytut Radiologii, Akademia Medyczna, Lodz (Poland)

    1994-12-31

    45 patients with carcinoma laryngis were studied. The ultrasonographic examination of the cervix was performed using a Aloka Hellige instrument Typ SSD 280LS with the presentation in the relative time. The evaluation of the enlargement cervical lymphatic nodes is available with this method. You can determinate their size, the status of their bursa and also the relation of the lymphatic glands to the big cervical vessels and surrounding tissues. 169 YbPtC12Meth was used for the scintigraphy of the cervix and the thorax. 15 patients with carcinoma laryngis were studied. This method is useful to the detection and the evaluation of the extensivity of the pathological process the lungs and the mediastinum. (author) 7 refs, 3 tabs

  20. 21 CFR 874.3375 - Battery-powered artificial larynx.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Battery-powered artificial larynx. 874.3375 Section 874.3375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... artificial larynx. (a) Identification. A battery-powered artificial larynx is an externally applied device...

  1. Human papillomavirus DNA in aerodigestive squamous carcinomas ...

    African Journals Online (AJOL)

    A series of 10 oesophageal and 10 laryngeal squamous carcinomas was examined by means of immuno cytochemistry and in situ DNA hybridisation to demonstrate human papillomavirus (HPV) infection. Changes in the epithelium adjacent to the carcinoma were found in 5 of 10 oesophageal and 7 of 10 laryngeal ...

  2. An unusual human papillomavirus type 82 detection in laryngeal squamous cell carcinoma: case report and review of literature.

    Science.gov (United States)

    Si-Mohamed, Ali; Badoual, Cécile; Hans, Stéphane; Péré, Hélène; Tartour, Eric; Brasnu, Daniel

    2012-06-01

    Squamous cell carcinoma (SCC) of the larynx is extremely rare in adolescent or younger adult and typically has an aggressive nature. The mechanism of laryngeal oncogenesis is complex and little is known about the role of human papillomaviruses (HPVs) in SCC in young age. HPV infection may occur during birth or latter by oro-genital contact. Most HPV genotypes detected were HPV 6, 11, 16, 18, 33 and 51. Herein, we report a case of invasive laryngeal SCC expressing an HPV 82 in an 18 year-old man with a history of unexplored severe acute dysphonia that started in early childhood. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. fibrosarcome du larynx

    African Journals Online (AJOL)

    glionnaire et la radiothérapie. Le pronostic est généralement sévère, dépend essentiellement de degré de différenciation histologique. Mots clés : fibrosarcome ; larynx ; chirurgie ; radiothérapie. SUMMARY. Fibrosarcoma of the larynx is a rare histological entity. It represents less than 10% of all soft tissue sarcomas and less.

  4. Molecular Genetic Study of Human Esophageal Carcinoma

    Science.gov (United States)

    1991-07-16

    virus have been shown to be the causative agent for human cancer, as human papilloma - virus ( HPV ) was associated with...F.J., Syrjanen, S., Shen, Q., J.I, H., & Kyrjanen, K. Human papilloma virus ( HPV ) DNA in esophageal precursor lesions and squamous cell carcinomas...genital tumors. Gene products, such as SV40 tumor antigen, Ela and Elb in adenovirus, E6 and E7 protein of human papilloma virus type 16 and type

  5. Esvaziamento cervical no carcinoma epidermoide de laringe: indicação de esvaziamento eletivo contralateral Neck dissection in squamous cell carcinoma of the larynx: indication of elective contralateral neck dissection

    Directory of Open Access Journals (Sweden)

    Ali Amar

    2012-04-01

    Full Text Available O planejamento terapêutico dos tumores da laringe inclui a possibilidade de esvaziamento cervical uni ou bilateral. OBJETIVO: Avaliar a prevalência e localização de metástases linfonodais bilaterais ou contralaterais nos tumores de laringe. CASUÍSTICA E MÉTODO: Estudo longitudinal retrospectivo de 272 prontuários de pacientes com carcinoma epidermoide de laringe tratados entre 1996 e 2004, selecionados 104 submetidos à cirurgia com esvaziamento cervical. Avaliada a incidência de metástases bilaterais ou contralaterais, de acordo com a localização e extensão do tumor primário, considerando os subsítios anatômicos e a linha mediana. RESULTADOS: A prevalência de metástases contralaterais nos tumores lateralizados foi de 3,5% nas lesões glóticas e 26% nas lesões supraglóticas. As metástases contralaterais foram infrequentes nos casos N0. Tanto no esvaziamento eletivo como no terapêutico, os níveis linfonodais IIa e III foram os mais acometidos. CONCLUSÃO: Nas lesões glóticas lateralizadas, mesmo nos tumores transglóticos, não há necessidade de esvaziamento contralateral eletivo. Nas lesões da supraglote sem metástases ipsilaterais, a incidência de metástases ocultas não justifica o esvaziamento eletivo contralateral. A linha mediana não é um indicador fidedigno do risco de metástases contralaterais nos tumores da laringe.Unilateral or bilateral neck dissection must be considered in the treatment of laryngeal cancer AIM: To evaluate the prevalence of contralateral metastases in larynx cancer and distribution of these metastases according to lymph node levels in the neck. METHOD: Retrospective longitudinal study of 272 charts from patients with squamous cell cancer of the larynx treated between 1996 and 2004; and we selected 104 surgical cases submitted to neck dissection. We evaluated the incidence of bilateral or contralateral metastases, according to the location and extension of the primary tumor

  6. Detection of C-MYC oncogene translocation and copy number change in the normal-dysplasia-carcinoma sequence of the larynx by fluorescence in situ hybridization.

    Science.gov (United States)

    Liu, Yu; Gong, Li-Ping; Dong, Xiao-Li; Liu, Hong-Gang

    2013-06-01

    The aim of this study was to determine the translocation and copy number change of the C-MYC gene in patients with laryngeal dysplasia and laryngeal squamous cell carcinoma (LSCC), and to evaluate the prevalence of such expression in relation to the normal-dysplasia-carcinoma sequence. Fluorescent in situ hybridization (FISH) was applied on formalin-fixed paraffin-embedded blocks of 93 laryngeal lesion specimens (14 normal epithelium, 15 mild dysplasia, 18 moderate dysplasia, 16 severe dysplasia, 9 carcinoma in situ, and 21 invasive carcinoma). C-MYC translocation was not observed in all laryngeal tissue. The high frequency for C-MYC copy-number increased (100%) in invasive carcinoma: 57.14% amplifications and 42.86% gains, and the positive rate of C-MYC amplification and copy-number change increased with the increasing severity of laryngeal lesions (P < 0.0001). The results suggest that C-MYC may be activated by gain/amplification in LSCC and precancerous lesions. Thus, C-MYC may play an important role in promoting LSCC progression, and early FISH detection of C-MYC may be exploited to set a screening test for laryngeal dysplasia. Copyright © 2012 Wiley Periodicals, Inc.

  7. Granular cell tumour of the larynx - A case report | Appiah ...

    African Journals Online (AJOL)

    We present the case due to the rarity of the laryngeal granular cell tumour and the need to highlight the importance of taking deep biopsies. If biopsies are superficial, an inexperienced pathologist would mistake it for well differentiated carcinoma. Keywords: Granular cell tumour, larynx, cordectomy, laryngofissure ...

  8. Changes from 1992 to 2002 in the pretreatment delay for patients with squamous cell carcinoma of larynx or pharynx: a Danish nationwide survey from DAHANCA

    DEFF Research Database (Denmark)

    Primdahl, Hanne; Nielsen, Anni Linnet; Larsen, Susanne

    2006-01-01

    In Denmark, a general impression of prolonged pretreatment delay for patients with head and neck cancer led to a nationwide study of time spans from symptom debut over first health care contact to start of treatment. Charts of consecutive new patients with squamous cell carcinoma of the pharynx...

  9. Cervical metastases in hypopharynx and larynx carcinoma: analyse of treatment failures; Przerzuty do wezlow chlonnych szyi w raku gardla dolnego i krtani: analiza niepowodzen leczenia

    Energy Technology Data Exchange (ETDEWEB)

    Zietek, E.; Sieczka, J.; Jaworowska, E.; Wasilewska, M.; Malec, M. [Pomorska Akademia Medyczna, Szczecin (Poland)

    1994-12-31

    986 patients treated surgically from 1970 to 1991 because of laryngeal and pharyngeal carcinoma were presented. There were 341 cases with radical neck dissection 969 with modified neck dissection and 292 with selective neck dissection. Three of five year survival rate without evidence of the cancer was evaluated. Authors mainly discussed 83 cases of nodal recurrences; the time, location and treatment of all recurrences was analyzed. (author) 3 figs, 2 tabs

  10. [Uterine cervical carcinoma and human papillomaviruses].

    Science.gov (United States)

    Sugase, M

    1992-06-01

    For many years it has been thought that a significant proportion of cervical cancer could be attributed to sexually transmitted agents, such as sperm, smegma, Treponema pallidum, Gonococcus and herpes simplexvirus type 2. Recent advances of molecular biology, however, have revealed that human papillomavirus (HPV) might be the most causative virus of the disease. Since HPV type 16 DNA was found in a patient with cervical cancer in 1983, many HPV types have been cloned from cervical cancers, also from premalignant lesions (intraepithelial neoplasias). In Japan, we have found 6 new types of HPV (HPV 58, 59, 61, 62, 64, 67) in the female genital tract so far. Especially, HPV 58, which was cloned from a patient with cervical squamous cell carcinoma and was already fully sequenced, is thought to be an important agent for the development of cervical cancer as well as HPV 16. Now we are investigating extensively to clarify the real relationship between genital HPV infection and cervical cancer.

  11. Metástasis inusual a distancia de carcinoma epidermoide de laringe: acrometástasis hacia las partes blandas de la muñeca Unusual distant metastasis from epidermoid carcinoma of the larynx: acrometastasis to the soft parts of the wrist

    Directory of Open Access Journals (Sweden)

    José Manuel Ramírez Milanés

    2008-03-01

    Full Text Available Se presenta un caso de metástasis hacia partes blandas de la muñeca (acrometástasis de un carcinoma epidermoide de la laringe. Se trata de un paciente de 65 años de edad, a quien se realizó una laringectomía total con disección radical de cuello derecho y funcional del otro lado. La operación se practicó hace 12 meses a causa de una lesión glótica supraglótica. A los 30 días de la intervención el paciente fue irradiado con cobaltoterapia en ambos cuellos. En la actualidad presenta aumento de volumen de las partes blandas de la región anterior de la muñeca izquierda, por lo que se le realizó una biopsia aspirativa con aguja fina. La biopsia arrojó un informe positivo de metástasis de carcinoma epidermoide y de múltiples metástasis en ambos campos pulmonaresA case of metastasis to soft parts of the wrist (acrometastasis from an epidermoid carcinoma of the larynx was presented. The case of a 65-year-old male patient, who underwent total laryngectomy with radical dissection of the right neck and functional dissection of the other side was presented. The operation was performed 12 months ago due to a supraglotic and glotic lesion. 30 days after surgery, the patient was irradiated with cobalt therapy in both necks. At present, he presents increase of the volume of the soft parts of the anterior region of the left wrist, so a fine needle aspiration biopsy was performed. The biopsy yielded a positive report of metastasis from epidermoid carcinoma and of multiple metastases in both lung fields

  12. [Contact granuloma of the larynx].

    Science.gov (United States)

    Vasilenko, Iu S; Kittel, G

    2006-01-01

    The authors analyse the results of clinical examination of patients with contact granuloma of the larynx treated in Moscow and Erlangen (Germany) clinics. Etiology, pathogenesis of this disease and treatment policy are discussed.

  13. Laser excision of a typical carcinoid tumor of the larynx: a case report.

    Science.gov (United States)

    Cevizci, Raşit; Karakullukçu, Barış; van den Brekel, Michiel W M; Balm, Alfons J

    2010-01-01

    Neuroendocrine carcinomas of the larynx include a range of rare tumors which have variable biologic behavior, affecting treatment and prognosis. Among these, typical carcinoid tumors are the least common type. Prognosis of typical carcinoid tumor is better than atypical carcinoid tumor and small cell carcinoma of the larynx. Conservation surgery is the preferred treatment modality. Transoral CO2 laser surgery can be a good alternative for appropriate cases because of the functional results and less morbidity. In this article, a 71-year-old female presented with complaints of feeling a mass during swallowing. Fiberoptic examination of the larynx revealed a mass located on the right aryepiglottic fold and biopsy revealed the tumor as a typical carcinoid tumor. We describe CO2 laser excision of a typical carcinoid tumor of the larynx in this case report.

  14. Imaging of human urothelial carcinoma samples using multimodal multiphoton microscopy

    Science.gov (United States)

    Baria, E.; Barone, A.; Nesi, G.; Pavone, F. S.; Cicchi, R.

    2017-07-01

    We combined Second Harmonic Generation and Two-Photon Fluorescence for imaging ex vivo tissue sections of human bladder affected by urothelial carcinoma. We studied different grades of the tumor, and compared them to healthy bladder mucosa.

  15. Imaging of the larynx and hypopharynx

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Minerva [Department of Radiology, Geneva University Hospital, 24 Rue Micheli-du Crest, CH-1211 Geneva 14 (Switzerland)], E-mail: Minerva.Becker@hcuge.ch; Burkhardt, Karim [Department of Clinical Pathology, Geneva University Hospital, 24 Rue Micheli-du Crest, CH-1211 Geneva 14 (Switzerland); Dulguerov, Pavel [Department of Otorhinolaryngology, Geneva University Hospital, 24 Rue Micheli-du Crest, CH-1211 Geneva 14 (Switzerland); Allal, Abdelkarim [Department of Radiation Oncology, Geneva University Hospital, 24 Rue Micheli-du Crest, CH-1211 Geneva 14 (Switzerland)

    2008-06-15

    The purpose of this article is to review currently used imaging protocols for the evaluation of pathologic conditions of the larynx and hypopharynx, to describe key anatomic structures in the larynx and hypopharynx that are relevant to tumor spread and to discuss the clinical role of Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and PET CT in the pretherapeutic workup and posttherapeutic follow-up of patients with squamous cell carcinoma of this region. A detailed discussion of the characteristic neoplastic submucosal invasion patterns, including extension to the preepiglottic space, paraglottic space and laryngeal cartilages and the implications of imaging for tumor staging and treatment planning is provided. The present article also reviews less common tumors of this region, such as chondrosarcoma, lymphoma, minor salivary gland tumors and lipoma. As the majority of non-neoplastic conditions do not require imaging the role of CT and MRI is discussed in some particular situations, such as to delineate cysts and laryngoceles, abscess formation in inflammatory conditions, to evaluate laryngeal and hypopharyngeal involvement in granulomatous and autoimmune diseases, and to evaluate the extent of laryngeal fractures due to severe blunt trauma.

  16. The matrix metalloproteinase in larynx cancer

    Directory of Open Access Journals (Sweden)

    Weronika Lucas Grzelczyk

    2016-12-01

    Full Text Available One of the most common carcinoma occurring in the head and neck is laryngeal cancer. Despite the rapid scientific advances in medicine the prognosis for patients with such type of disease is not satisfying. In the last few years matrix metalloproteinases ‑ MMPs and their tissue inhibitors – TIMPs, mostly MMP‑2 and MMP‑9, arouses a great interest, especially in the process of carcinogenesis. It seems that their impact in the formation and development of laryngeal cancer is significant. MMPs a group of zinc‑ and calcium‑ dependent endopeptidases play crucial role extracellular matrix collagen degradation. That are enzymes, that degrade and the basement membrane by facilitating tumor growth, cell migration and tumor invasion. They are implicated in metastasis and angiogenesis potentiate within the tumor. Clear tendency was observed towards the higher MMPs and TIMPs expression in larynx cancer than in the stroma. Recent studies show correlations between increased MMP‑2 gene expression in the tumor tissue and clinical status, histopathological grading and metastases occurrence. The similar MMP2 over expression dependence were found on tumor recurrence and survival. Many authors pointed out, significant higher MMP‑2 expression as a potential marker of tumor invasiveness and worse prognosis in patients with larynx cancer. However, association of MMP 9 gene expression with laryngeal cancer clinicopathological features and survival of patients are ambiguous. Although, numerous researches show that this relationship does exists. Similar correlations could be found in TIMPs, but further studies are necessary because of small amount of literature.

  17. Comparative cytotoxicity of dolomite nanoparticles in human larynx HEp2 and liver HepG2 cells.

    Science.gov (United States)

    Ahamed, Maqusood; Alhadlaq, Hisham A; Ahmad, Javed; Siddiqui, Maqsood A; Khan, Shams T; Musarrat, Javed; Al-Khedhairy, Abdulaziz A

    2015-06-01

    Dolomite is a natural mineral of great industrial and commercial importance. With the advent of nanotechnology, natural minerals including dolomite in the form of nanoparticles (NPs) are being utilized in various applications to improve the quality of products. However, safety or toxicity information of dolomite NPs is largely lacking. This study evaluated the cytotoxicity of dolomite NPs in two widely used in vitro cell culture models: human airway epithelial (HEp2) and human liver (HepG2) cells. Concentration-dependent decreased cell viability and damaged cell membrane integrity revealed the cytotoxicity of dolomite NPs. We further observed that dolomite NPs induce oxidative stress in a concentration-dependent manner, as indicated by depletion of glutathione and induction of reactive oxygen species (ROS) and lipid peroxidation. Quantitative real-time PCR data demonstrated that the mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were up-regulated whereas the anti-apoptotic gene bcl-2 was down-regulated in HEp2 and HepG2 cells exposed to dolomite NPs. Moreover, the activity of apoptotic enzymes (caspase-3 and caspase-9) was also higher in both kinds of cells treated with dolomite NPs. It is also worth mentioning that HEp2 cells seem to be marginally more susceptible to dolomite NPs exposure than HepG2 cells. Cytotoxicity induced by dolomite NPs was efficiently prevented by N-acetyl cysteine treatment, which suggests that oxidative stress is primarily responsible for the cytotoxicity of dolomite NPs in both HEp2 and HepG2 cells. Toxicity mechanisms of dolomite NPs warrant further investigations at the in vivo level. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Human papilloma virus prevalence in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E

    2007-08-01

    To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

  19. Prevalence of human papillomavirus in laryngeal and hypopharyngeal squamous cell carcinomas in northern Spain.

    Science.gov (United States)

    Rodrigo, Juan P; Hermsen, Mario A; Fresno, Manuel F; Brakenhoff, Ruud H; García-Velasco, Fabian; Snijders, Peter J F; Heideman, Daniëlle A M; García-Pedrero, Juana M

    2015-02-01

    Recent studies support a role for human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (SCCs); however, the significance of HPV in non-oropharyngeal head and neck cancers is uncertain. The aim of this study was to determine the prevalence of HPV in a large cohort of laryngeal and hypopharyngeal SCCs in northern Spain. Clinical records and paraffin-embedded tumor specimens of 124 consecutive patients surgically treated for laryngeal (62 cases) and hypopharyngeal (62 cases) SCCs between 2002 and 2007 were retrieved. All cases were histologically evaluated, and presence of HPV was assessed by p16-immunohistochemistry followed by GP5+/6+-PCR-based DNA detection. Samples positive in both assays were subjected to HPV genotyping and HPV E6 transcript analysis. Seventeen cases (14%) were positive for p16 immunostaining, of which 2 (1 larynx, 1 hypopharynx, 1.6% of total series) were found positive for HPV DNA by subsequent GP5+6+-PCR. Both SCCs contained HPV type 16 and showed HPV16 E6 mRNA expression. HPV is only occasionally involved in laryngeal and hypopharyngeal SCC patients in northern Spain. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    Science.gov (United States)

    2015-04-29

    Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx

  1. Laryngeal carcinoma

    African Journals Online (AJOL)

    Biological pharyngo-cutaneous fistula could not. One patient died markers of alcohol abuse in patients with from a ruptured carotid following radiotherapy three carcinoma of the larynx. Acta months after surgery, while the remaining eight are still. Otorrinolaringol Esp 1998 Aug- doing well with an average duration of follow ...

  2. Adult Rhabdomyoma of the Larynx

    Directory of Open Access Journals (Sweden)

    Pinho, Márcia Monteiro

    2013-09-01

    Full Text Available Introduction: Rhabdomyoma is a rare benign tumor derived from skeletal muscles. Laryngeal rhabdomyomas are even rarer, with only approximately 40 reported cases in world literature. Laryngeal rhabdomyomas usually are seen as masses covered by mucosa. They are often solitary asymptomatic tumors, but symptoms such as hoarseness can occur. The radiologic features are usually those typical of benign neoplasms, showing well-delineated borders. The differential diagnoses for laryngeal masses include cysts, laryngoceles, and benign and malignant neoplasms. The diagnosis is usually made using histopathologic findings, but in some cases some difficulties can be found. Immunohistochemical staining is of great value in the differentiation of similar tumors. Treatment of rhabdomyoma is surgical excision. Objective: To describe a case of rhabdomyoma of the larynx attended at Santa Casa de Misericórdia do Rio de Janeiro. Case Report: A 35-year-old man presented with progressive hoarseness in the preceding year. Laryngoscopy showed a large submucosal tumor at the supraglottic region of the larynx. The neck computed tomography scan confirmed the submucosal mass, with distinct borders. The patient was taken to the operating suite, where endoscopic extirpation of the mass was performed. Initial histologic diagnosis was suggestive of paraganglioma, which was not confirmed by studies with immunohistochemical markers, and diagnosis was changed to adult-type rhabdomyoma. The patient recovered well. His voice returned to normal after 3 months. Discussion: Although muscle tumors of the larynx are very rare, rhabdomyoma should be considered when there is a submucosal mass in the larynx.

  3. Proteomic analysis of human oral verrucous carcinoma

    African Journals Online (AJOL)

    Jane

    2011-10-05

    Oct 5, 2011 ... from tumour and adjacent normal oral mucosa of patients with OVC and oral squamous cell carcinoma. (OSCC) were separated with two ... node and implant metastasis can be found in infiltrative type and cystoid type ..... according to circadian rhythms in mouse liver (Wei et al.,. 2006). In the latter study, ...

  4. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell...... carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils....... The association is geographically consistent throughout the economically developed world. The presence and integration of high-risk human papillomavirus genome in tonsillar tumours, and expression of viral oncogenes, are specific and plausible. Analogous to human papillomavirus in cervical cancer, the rising...

  5. Usage of piezoelectric instruments in larynx surgery.

    Science.gov (United States)

    Jurek, Olga; Wójtowicz, Piotr; Krzeski, Antoni

    2017-10-30

    The aim of the study was to estimate usability of the piezoelectric knife in larynx surgery. Prove that the piezoelectric staff can be used to do any different shape incision within the larynx cartilages. 35 patients hospitalized in our Department in 2014-2016 were enrolled in our study. 24 patients went vertical partial laryngectomy and 1 patient went horizontal partial laryngectomy because of larynx cancer. 5 patients went partial laryngectomy because of low stage of piriformis recess cancer. Piezoelectric staff was used to do thyroidectomy and resection of thyroid cartilage suspected of carcinomatosis infiltration. The rest 4 patients had done widening of larynx lumen due to larynx stenosis or slenderness. The piezoelectric tool was used to do different incision or resection within the larynx cartilages in case of widening lumen of the larynx. The larynx cartilages, especially thyroid cartilage could be cut in different shapes using piezoelectric tools. The usage of this equipment causes the minimal loss and small destruction of local healthy tissues. The Piezoelectric instrument is useful instrument suit to operate within larynx cartilages. Exchangeable tip available in different shapes enables different resections of cartilages. Using the piezoelectric staff we can remove pathological tissue with minimal local destruction. Our observation shows that larynx operation with a usage of the piezoelectric knife is safe and effective. Current English literature does not describe usage piezoelectric tools in larynx surgery. It is essential to do more observation about that type of operations.

  6. Quantitative diffusion-weighted MRI parameters and human papillomavirus status in oropharyngeal squamous cell carcinoma

    NARCIS (Netherlands)

    Schouten, C.S.; Graaf, P. de; Bloemena, E.; Witte, B.I.; Braakhuis, B.J.; Brakenhoff, R.H.; Leemans, C.R.; Castelijns, J.A.; Bree, R. de

    2015-01-01

    BACKGROUND AND PURPOSE: Patients with human papillomavirus-positive oropharyngeal squamous cell carcinomas have a better survival rate than those with human papillomavirus-negative oropharyngeal squamous cell carcinomas. DWI characterizes biologically relevant tumor features, and the generated ADC

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...

  8. Is human papillomavirus involved in laryngeal neuroendocrine carcinoma?

    NARCIS (Netherlands)

    Halmos, Gyorgy B; van der Laan, Tom P; van Hemel, Bettien M; Dikkers, Frederik G; Slagter-Menkema, Lorian; van der Laan, Bernard F A M; Schuuring, Ed

    The purpose of this study was to detect human papillomavirus (HPV) infection in laryngeal neuroendocrine carcinoma (LNEC) and to explore the possible relationship between HPV-induced malignant transformation and prognosis in LNEC. Ten cases of LNEC from a tertiary referral hospital were

  9. Sorafenib Tosylate, Cisplatin, and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    Science.gov (United States)

    2017-03-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  10. Rapid induction of senescence in human cervical carcinoma cells

    Science.gov (United States)

    Goodwin, Edward C.; Yang, Eva; Lee, Chan-Jae; Lee, Han-Woong; Dimaio, Daniel; Hwang, Eun-Seong

    2000-09-01

    Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence. This process was accompanied by marked but in some cases transient alterations in the expression of cell cycle regulatory proteins and by decreased telomerase activity. We propose that the human papillomavirus E6 and E7 proteins actively prevent senescence from occurring in cervical carcinoma cells, and that once viral oncogene expression is extinguished, the senescence program is rapidly executed. Activation of endogenous senescence pathways in cancer cells may represent an alternative approach to treat human cancers.

  11. 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.

  12. Dedifferentiated Chondrosarcoma of the Larynx.

    Science.gov (United States)

    Fidai, Shiraz S; Ginat, Daniel T; Langerman, Alexander J; Cipriani, Nicole A

    2016-09-01

    Primary dedifferentiated chondrosarcoma occurring in the larynx is a rare head and neck malignancy. The cases reported in the literature suggest male gender predilection and variable clinical outcomes ranging from disease-free survival to disease-related death. Although a calcified matrix is suggestive of chondrosarcoma, the dedifferentiated component is not readily appreciated on conventional imaging modalities and thorough tissue sampling is necessary for confirming the diagnosis. Histologically, there is an abrupt transition from a well-differentiated chondrosarcoma to a high-grade spindle cell component, which can show focal heterologous differentiation. These features are exemplified in this sine qua non radiology-pathology correlation article.

  13. Selective assembly of laminin variants by human carcinoma cells

    DEFF Research Database (Denmark)

    Wewer, U M; Wayner, E A; Hoffstrom, B G

    1994-01-01

    BACKGROUND: The laminins are heterotrimeric basement membrane glycoproteins. Eight subunits that can be assembled into laminins have been characterized and are known as: A, B1, B2, S, M, K, B2t, B1k laminin chains. Although many neoplastic cells secrete laminins and some of them even assemble...... basement membranes, the pattern of production of various laminin subunits remains to be explored. EXPERIMENTAL DESIGN: The expression of laminin was examined in several human carcinoma cells using a panel of specific cDNA probes as well as polyclonal and chain specific monoclonal antibodies....... For this purpose a human laminin S chain 2 kb cDNA was isolated and characterized and used together with existing probes for laminin chains. RESULTS: All carcinoma cell lines had a high level of expression of three light chains (B1, S and B2) mRNA. In contrast, the heavy chains of laminin, A and M, were expressed...

  14. Leiomyosarcoma of the larynx: emergency tracheostomy.

    Science.gov (United States)

    Kainuma, K; Kikukawa, M; Itoh, T; Osawa, M; Watanabe, M

    2001-07-01

    Leiomyosarcoma of the larynx is extremely rare. Histological diagnosis for excluding other tumours remains extremely difficult. A rare case of leiomyosarcoma of the larynx, treated by surgery and radiotherapy, is reported. We discuss the clinical presentation, diagnosis, and treatment of leiomysarcoma with a review of the literature.

  15. Primary Aspergillosis of the Larynx

    Directory of Open Access Journals (Sweden)

    Richard H. Law

    2016-01-01

    Full Text Available Laryngeal aspergillosis is most commonly seen as a result of secondary invasion from the lungs and tracheobronchial tree in immunocompromised hosts. Primary aspergillosis of the larynx is, however, rare with few cases documented over the past fifty years. We report a case of a 73-year-old woman who presented with persistent hoarseness. She is a nonsmoker with a history of asthma and chronic bronchiectasis treated with bronchodilators, inhaled and oral corticosteroids, and nebulized tobramycin. Direct laryngoscopy with vocal cord stripping confirmed the diagnosis of invasive aspergillosis with no manifestations elsewhere. The patient was successfully treated with oral voriconazole with no signs of recurrence. Although several major risk factors contributing to the development of primary aspergillosis of the larynx have been discussed in the literature, there has been no mention of inhaled antibiotics causing this rare presentation to the best of our knowledge. We, therefore, highlight the use of inhaled tobramycin as a unique catalyst leading to the rapid onset of this rare presentation.

  16. The use of TiNi-based endografts in larynx cancer patients

    Directory of Open Access Journals (Sweden)

    Kulbakin Denis

    2015-12-01

    Full Text Available Purpose: Laryngeal cancer constitutes 26-30% of all head and neck malignant tumors. It is remarkably common in men and it is primarily distributed between ages 40 and 70 years old, but the frequency rate is the highest between ages 50 and 60. Well-known etiologic factors of laryngeal cancer include smoking, alcohol, human papilloma virus and radiation. It has been reported that the occurrence rate is up to 20 times higher in smokers compared to non-smokers, but the exact pathogenesis of the disease is still unknown.Despite an increasing role of non-adjuvant radiotherapy and/or chemotherapy in treatment of larynx cancer, the surgical technique is still a basic one both in combined treatment of patients with locally advanced stages of primary larynx cancer and in the cases when recurrence is treated after radiotherapy or chemoradiotherapy. Leading position in the combined treatment of locally advanced carcinoma of the larynx belongs to surgical treatment. Published reports of salvage treatment for larynx reconstruction after partial laryngectomy are available, some of them using structures of the larynx itself, but few aimed on a search of new materials and techniques for sparing laryngeal surgery.Possibility to perform a sparing surgery depends on several factors, including, the possibility of adequate laryngeal replacement after an extensive resection. Meanwhile, surgery improvement goes along with differentiated choice of an adequate degree of surgical intervention. However, the functional results of such surgeries do not always satisfy both patients and professionals, if we consider that large fragments of the organ have to be resected in locally advanced larynx cancers.The larynx reconstruction is a complex goal, it can be explained by several factors. First of all, this is topographic and anatomical feature of the larynx since it is located next to the digestive tract. Fixation and immobilization of the larynx is hard to perform as it is a

  17. Biomarkers in Advanced Larynx Cancer

    Science.gov (United States)

    Bradford, Carol R.; Kumar, Bhavna; Bellile, Emily; Lee, Julia; Taylor, Jeremy; D’Silva, Nisha; Cordell, Kitrina; Kleer, Celina; Kupfer, Robbi; Kumar, Pawan; Urba, Susan; Worden, Francis; Eisbruch, Avraham; Wolf, Gregory T.; Teknos, Theodoros N.; Prince, Mark E.P.; Chepeha, Douglas B.; Hogikyan, Norman D.; Moyer, Jeffrey S.; Carey, Thomas E.

    2014-01-01

    Objectives/Hypothesis To determine if tumor biomarkers were predictive of outcome in a prospective cohort of patients with advanced larynx cancer treated in a phase II clinical trial. Study Design Prospectively collected biopsy specimens from 58 patients entered into a Phase II trial of organ preservation in advanced laryngeal cancer were evaluated for expression of a large panel of biomarkers and correlations with outcome were determined. Methods Tissue microarrays were constructed from pretreatment biopsies and stained for cyclin D1, CD24, EGFR, MDM2, PCNA, p53, survivin, Bcl-xL, Bcl-2, BAK, rhoC, and NFκB. Pattern of invasion and p53 mutations were assessed. Correlations with overall survival (OS), disease-specific survival (DSS), time free from indication of surgery, induction chemotherapy response, and chemoradiation response were determined. Cox models were used to assess combinations of these biomarkers. Results Low expression of BAK was associated with response to induction chemotherapy. Low expression of BAK and cytoplasmic NFκB was associated with chemoradiation response. Aggressive histologic growth pattern was associated with response induction chemotherapy. Expression of cyclin D1 was predictive of overall and disease-specific survival. Overexpression of EGFR was also associated with an increased risk of death from disease. Bcl-xL expression increased significantly in persistent/recurrent tumors specimens when compared to pretreatment specimens derived from the same patient (p = 0.0003). Conclusions Evaluation of biomarker expression in pretreatment biopsy specimens can lend important predictive and prognostic information for patients with advanced larynx cancer. PMID:23775802

  18. [The difference of larynx cancer stage evaluation between clinical and pathological examinations].

    Science.gov (United States)

    Wolny, Edyta; Idasiak, Adam; Wydmański, Jerzy; Miszczyk, Leszek

    2006-01-01

    Comparison of stage larynx carcinoma and estimation of hazard dissemination lymph nodes in preoperative clinical and postoperative histological examination according to the TNM staging system. The group of 100 patients with previously untreated squamous cell carcinoma of larynx was analysed. The material consisted of: 89 man and 11 women of age 39 to 78 year old (average 56). There were 51 patients with supraglottic carcinoma, 39 with glottic carcinoma, 4 with subglottic carcinoma and 6 patients had all larynx occupied. The anaplastic degree checks out brought following results: G1--17 cases, G2--54, G3--13 and 16 cases were not estimated. The diseases stage was defined preoperatively and postoperatively. The number and risk lymph nodes metastases were correlated with the diameter and topographical distribution. The following of clinical examination were estimated: T2--49 patients, T3--40, T4--11. On the case of postoperative histological examination following stages were found: pT2--29, pT3--34, pT4--37. According to clinical nodal staging we found: N0--70, N1--13, N2a--4, N2b--6, N2c--6, N3--1. The postoperative nodal stage verification showed: N0--64, N1--11, N2a--4, N2b--17, N2c--4, N3--0. The harmony of clinical and pathological tumor stage was found in 62 cases and 38 patients were more advanced in pathological examination. In 62 cases the agreement between clinical and pathological N stage was found. In other 38 cases we found different N stage. In group with clinical enlarge lymph nodes 91% cases were metastases. The topographical distribution of the nodal metastases is determined. The most occupied group of lymph nodal are: upper cervical nodes--44%, the mid jugular nodes--31%, submaxillary nodes--14%, low jugular nodes--6%, perilaryngeal--5%. The risk of nodal metastases with diameter to 1 cm is 9% (659 lymph nodal), to 2 cm 15% (48 nodal), above 3 cm (8 nodal) 100%. The agreement of larynx carcinoma T stage in clinical examination is considerably

  19. Phase 1b Food Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer.

    Science.gov (United States)

    2017-10-04

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage 0 Hypopharyngeal Cancer; Stage 0 Laryngeal Cancer; Stage 0 Lip and Oral Cavity Cancer; Stage 0 Nasopharyngeal Cancer; Stage 0 Oropharyngeal Cancer; Stage 0 Paranasal Sinus and Nasal Cavity Cancer; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Nasal Cavity and Paranasal Sinus Cancer; Stage IVA

  20. Micronuclei with kinetochores in human melanoma cells and rectal carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Weissenborn, U.; Streffer, C. (Essen Univ. (Gesamthochschule) (Germany, F.R.). Inst. fuer Medizinische Strahlenbiologie)

    1991-02-01

    Micronucleus frequencies were analysed in an X-irradiated human melanoma cell line and in untreated rectal carcinoma cells. As a special aspect of the micronucleus formation, micronuclei-containing kinetochores were analysed by the method of indirect immunofluorescence. The incidence of kinetochore-positive micronuclei was taken as a measure of chromosome loss. The authors have attempted to summarize the data by means of a numerical expression which takes into account the relation between lost chromosomes, visible as kinetochore-positive micronuclei, and the total sum of micronuclei. (author).

  1. Elevated expression of squamous cell carcinoma antigen (SCCA is associated with human breast carcinoma.

    Directory of Open Access Journals (Sweden)

    Joseph M Catanzaro

    Full Text Available Squamous cell carcinoma antigen (SCCA belongs to the serine protease inhibitor (Serpin family of proteins. Elevated expression of SCCA has been used as a biomarker for aggressive squamous cell carcinoma (SCC in cancers of the cervix, lung, head and neck, and liver. However, SCCA expression in breast cancer has not been investigated. Immunohistochemical analysis of SCCA expression was performed on tissue microarrays containing breast tumor tissues (n = 1,360 and normal breast epithelium (n = 124. SCCA expression was scored on a tiered scale (0-3 independently by two evaluators blind to the patient's clinical status. SCCA expression was observed in Grade I (0.3%, Grade II (2.5%, and Grade III (9.4% breast cancers (p<0.0001. Comparing tissues categorized into the three non-metastatic TNM stages, I-III, SCCA positivity was seen in 2.4% of Stage I cancers, 3.1% of Stage II cancers, and 8.6% of Stage III breast cancers (p = 0.0005. No positive staining was observed in normal/non-neoplastic breast tissue (0 out of 124. SCCA expression also correlated to estrogen receptor/progesterone receptor (ER/PR double-negative tumors (p = 0.0009. Compared to SCCA-negative patients, SCCA-positive patients had both a worse overall survival and recurrence-free survival (p<0.0001 and p<0.0001, respectively. This study shows that SCCA is associated with both advanced stage and high grade human breast carcinoma, and suggests the necessity to further explore the role of SCCA in breast cancer development and treatment.

  2. Carcinome verruqueux du larynx : Diagnostic et traitement ...

    African Journals Online (AJOL)

    Introduction : Les carcinomes verruqueux du larynx sont des tumeurs rares. Ils posent des problèmes diagnostics et thérapeutiques. Le but de notre travail est de détailler les difficultés diagnostiques et thérapeutiques du carcinome verruqueux du larynx. Patients et méthodes : Treize malades ont été traité d'un carcinomes ...

  3. Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hagmann, Wolfgang, E-mail: w.hagmann@dkfz.de; Faissner, Ralf [Clinical Cooperation Unit of Molecular Gastroenterology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Schnolzer, Martina [Functional Proteome Analysis, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Lohr, Matthias [Clinical Cooperation Unit of Molecular Gastroenterology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Department of Surgical Gastroenterology, CLINTEC, K53, Karolinska Institute, SE-14186 Stockholm (Sweden); Jesnowski, Ralf [Clinical Cooperation Unit of Molecular Gastroenterology, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Department of Medicine II, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany)

    2010-12-30

    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.

  4. Carcinogenic effect of X-rays on the pharynx and larynx

    Energy Technology Data Exchange (ETDEWEB)

    Sekula, J.; Olszewski, E.; Wlodyka, J. (Akademia Medyczna, Krakow (Poland))

    1980-01-01

    In 19 patients receiving X-ray therapy carcinoma of the larynx or pharynx developed after years. Radiotherapy was applied in 2 cases for non-malignant diseases of the neck, in 1 case for infantile laryngeal papilloma, in 7 cases for precancerous laryngeal conditions in adults (6 papillomas, 1 leucoplakia), and in 9 cases of malignant laryngeal and pharyngeal neoplasms cured by this primary radiotherapy or combined treatment. In the latter group late secondary laryngeal or pharyngeal carcinoma developed 6-22 years after regression of the primary tumour (mean 15 years). This analysis is an attempt at demonstration in which cases the tumour was a consequence of past X-ray therapy, and in which the carcinogenic effect of X-rays on the pharynx and larynx was highly feasible.

  5. Low prevalence of human papillomavirus in head and neck squamous cell carcinoma in the northwest region of the Philippines.

    Science.gov (United States)

    Albano, Pia Marie; Holzinger, Dana; Salvador, Christianne; Orosa, Jose; Racelis, Sheryl; Leaño, Modesty; Sanchez, Danilo; Angeles, Lara Mae; Halec, Gordana; Schmitt, Markus; Ramos, John Donnie; Pawlita, Michael

    2017-01-01

    Geographic heterogeneity of human papillomavirus (HPV) involvement in head and neck squamous cell carcinoma (HNSCC) has been observed over the last few years. This trend has not been evaluated in the Philippines. Hence, this study aims to provide for the first time a data on the prevalence of HPV in HNSCC in the northwestern region of the Philippines. Two hundred one (201) biopsy samples (179 formalin fixed paraffin embedded and 22 fresh frozen) from 163 Filipino HNSCC cases (oral cavity = 88; larynx = 60; oropharynx = 15) diagnosed between 2003 to 2013 were initially included in this study. HPV DNA was detected by two methods: (1) BSGP5+/6+-PCR/ multiplex human papillomavirus genotyping and (2) TaqMan probes-based real-time qPCR. Presence of HPV type-specific transcripts were also analyzed by reverse transcription-PCR with subsequent hybridization to oligonucleotide probes coupled to Luminex beads. Co-amplification of the β-globin and ubiquitin C genes served as internal positive controls for DNA and RNA analyses, respectively. Of the 163, 82 (50.3%) cases had at least one tissue sample that was valid for molecular analysis. Only two of the DNA valid cases (2.4%) were HPV DNA-positive (HPV11 and HPV33). All HPV mRNA assays rendered negative results except for HPV11 transcripts. Results of this study may indicate that there is probably very low prevalence of HPV-associated HNSCC among Filipino adults living in a rural region of the Philippines. This study could serve as a benchmark for designing follow-up studies that would assess possible changes in trends of HNSCC among Filipinos in different ethnic regions of the country, especially urban areas in which the population is expected to adapt Western style sexual behavior. A prospective sampling of fresh frozen tissue is also highly recommended to ensure better molecular analyses.

  6. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

    Science.gov (United States)

    Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

    2012-11-01

    Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

  7. Histopathology of candidal hyperplastic lesions of the larynx.

    Science.gov (United States)

    Pabuççuoğlu, Ugur; Tuncer, Canten; Sengiz, Selma

    2002-01-01

    Candidiasis of the larynx is rare, and candidal involvement of the larynx mostly occurs after pulmonary, pharyngeal and esophageal candidiasis, or as part of disseminated disease. We here report our morphologic observations made in five cases of laryngeal candidiasis. These cases had the following morphologic features in common: 1. pronounced epithelial hyperplasia, which may show a verrucous pattern, 2. prominent ortho-parakeratosis, and 3. predominantly neutrophilic infiltration located in the upper layers of the mucosal epithelium. Our morphologic observations were similar to the morphologic changes encountered in chronic hyperplastic candidosis of the oral mucosa. As this type of candidal lesions contains fewer hyphae than the usual thrush, fungal infection may be easily overlooked. Pronounced epithelial hyperplasia and prominent ortho-parakeratosis may mimic squamous cell and verrucous carcinomas. In conclusion, we suggest performing special stains for fungi of laryngeal biopsies that have the morphologic features mentioned above. In that way, it is possible to detect a candidal infection, keeping in mind that the fungal organisms may be very few in number and morphologically distorted.

  8. Human Papillomavirus in Oral Leukoplakia, Verrucous Carcinoma, Squamous Cell Carcinoma, and Normal Mucous Membrane.

    Science.gov (United States)

    Saghravanian, Nasrollah; Ghazi, Narges; Meshkat, Zahra; Mohtasham, Nooshin

    2015-11-01

    Squamous cell carcinoma (SCC) is the most common oral malignancy, and verrucous carcinoma (VC) is a less invasive type of SCC. Leukoplakia (LP) is the most frequent premalignant lesion in the oral cavity. The human papillomavirus (HPV) has been recognized as one of the etiologic factors of these conditions. The association of anogenital and cervical cancers with HPV particularly its high-risk subtypes (HPV HR) has been demonstrated. The purpose of our study was to investigate the hypothetical association between HPV and the mentioned oral cavity lesions. One hundred and seventy-three samples (114 SCCs, 21 VCs, 20 LPs) and 18 normal mucosa samples (as a control group) were retrieved from the Department of Oral and Maxillofacial Pathology of Mashhad Dental School, Iran. The association of HPV genotypes in LP, VC, and SCC was compared to normal oral mucosa using the polymerase chain reaction. The results showed the absence of HPV in normal mucosa and LP lesions. In three samples of VC (14.3%), we observed the presence of HPV HR (types 16 and 18). All VCs were present in the mandibular ridge of females aged over 65 years old. No statistically significant correlation between HPV and VC was observed (p=0.230). Additionally, 15 (13.1%) SCCs showed HPV positivity, but this was not significant (p=0.830). The prevalence of SCC was higher on the tongue with the dominant presence of less carcinogenic species of HPV (types 6 and 11). A statistically significant association was not observed between HPV and SCC or VC in the oral cavity. More studies are necessary to better understand the relationship between HPV and malignant/premalignant oral cavity lesions.

  9. Human Papillomavirus in Oral Leukoplakia, Verrucous Carcinoma, Squamous Cell Carcinoma, and Normal Mucous Membrane

    Directory of Open Access Journals (Sweden)

    Nasrollah Saghravanian

    2015-11-01

    Full Text Available Objectives: Squamous cell carcinoma (SCC is the most common oral malignancy, and verrucous carcinoma (VC is a less invasive type of SCC. Leukoplakia (LP is the most frequent premalignant lesion in the oral cavity. The human papillomavirus (HPV has been recognized as one of the etiologic factors of these conditions. The association of anogenital and cervical cancers with HPV particularly its high-risk subtypes (HPV HR has been demonstrated. The purpose of our study was to investigate the hypothetical association between HPV and the mentioned oral cavity lesions.  Methods: One hundred and seventy-three samples (114 SCCs, 21 VCs, 20 LPs and 18 normal mucosa samples (as a control group were retrieved from the Department of Oral and Maxillofacial Pathology of Mashhad Dental School, Iran. The association of HPV genotypes in LP, VC, and SCC was compared to normal oral mucosa using the polymerase chain reaction.  Results: The results showed the absence of HPV in normal mucosa and LP lesions. In three samples of VC (14.3%, we observed the presence of HPV HR (types 16 and 18. All VCs were present in the mandibular ridge of females aged over 65 years old. No statistically significant correlation between HPV and VC was observed (p=0.230. Additionally, 15 (13.1% SCCs showed HPV positivity, but this was not significant (p=0.830. The prevalence of SCC was higher on the tongue with the dominant presence of less carcinogenic species of HPV (types 6 and 11. A statistically significant association was not observed between HPV and SCC or VC in the oral cavity.  Conclusions: More studies are necessary to better understand the relationship between HPV and malignant/premalignant oral cavity lesions.

  10. Role of Krüppel-like factor 4 and heat shock protein 27 in cancer of the larynx.

    Science.gov (United States)

    Karam, Jihad; Fadous-Khalifé, Marie Claude; Tannous, Rita; Fakhreddine, Sally; Massoud, Marcel; Hadchity, Joseph; Aftimos, Georges; Hadchity, Elie

    2017-11-01

    Late detection and lack of standard treatment strategies in larynx cancer patients result in high levels of mortality and poor prognosis. Prognostic stratification of larynx cancer patients based on molecular prognostic tumor biomarkers may lead to more efficient clinical management. Krüppel-like factor 4 (KLF4) and Heat Shock Protein 27 (HSP27) have an important role in tumorigenesis and are considered promising candidate biomarkers for various types of cancer. However, their role in larynx carcinoma remains to be elucidated. The present study aimed to determine KLF4 and HSP27 expression profiles in laryngeal tumors. The protein and mRNA expression levels of KLF4 and HSP27 were evaluated by immunohistochemical and reverse transcription-polymerase chain reaction analyses in 44 larynx carcinoma samples and 21 normal tissue samples, and then correlated with clinical characteristics. A differential expression of KLF4 and HSP27 was observed between normal and tumor tissues. The protein and mRNA expression levels of KLF4 were significantly decreased in larynx squamous cell carcinoma (LSCC) compared with normal tissue, whereas HSP27 was significantly overexpressed in tumor tissues compared with normal tissues, at the protein and mRNA levels. KLF4 expression decreased gradually with tumor progression whereas HSP27 expression increased. A significant difference was observed between stages I and IV. KLF4 and HSP27 exhibit opposite functions and roles in the carcinogenic process of LSCC. Their role in laryngeal cancer initiation and progression emphasizes their use as potential future targets for prognosis and treatment. KLF4 and HSP27 expression levels may act as potential biomarkers in patients with cancer of the larynx.

  11. Involvement of the larynx motor area in singing-voice perception: a TMS study†

    Science.gov (United States)

    Lévêque, Yohana; Muggleton, Neil; Stewart, Lauren; Schön, Daniele

    2013-01-01

    Recent evidence has reported that the motor system has a role in speech or emotional vocalization discrimination. In the present study we investigated the involvement of the larynx motor representation in singing perception. Twenty-one non-musicians listened to short tones sung by a human voice or played by a machine and performed a categorization task. Thereafter continuous theta-burst transcranial magnetic stimulation was applied over the right larynx premotor area or on the vertex and the test administered again. Overall, reaction times (RTs) were shorter after stimulation over both sites. Nonetheless and most importantly, RTs became longer for sung than for “machine” sounds after stimulation on the larynx area. This effect suggests that the right premotor region is functionally involved in singing perception and that sound humanness modulates motor resonance. PMID:23874314

  12. Involvement of the larynx motor area in singing-voice perception: a TMS study

    Directory of Open Access Journals (Sweden)

    Yohana eLévêque

    2013-07-01

    Full Text Available Recent evidence has reported that the motor system has a role in speech or emotional vocalization discrimination. In the present study we investigated the involvement of the larynx motor representation in singing perception. Twenty-one non-musicians listened to short tones sung by a human voice or played by a machine and performed a categorization task. Thereafter continuous theta-burst transcranial magnetic stimulation was applied over the right larynx pre-motor area or on the vertex and the test administered again. Overall, reaction times were shorter after stimulation over both sites. Nonetheless and most importantly, reaction times became longer for sung than for machine sounds after stimulation on the larynx area. This effect suggests that the right premotor region is functionally involved in singing perception and that sound humanness modulates motor resonance.

  13. Inflammation and cancer: role of annexin A1 and FPR2/ALX in proliferation and metastasis in human laryngeal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Thaís Santana Gastardelo

    Full Text Available The anti-inflammatory protein annexin A1 (ANXA1 has been associated with cancer progression and metastasis, suggesting its role in regulating tumor cell proliferation. We investigated the mechanism of ANXA1 interaction with formylated peptide receptor 2 (FPR2/ALX in control, peritumoral and tumor larynx tissue samples from 20 patients, to quantitate the neutrophils and mast cells, and to evaluate the protein expression and co-localization of ANXA1/FPR2 in these inflammatory cells and laryngeal squamous cells by immunocytochemistry. In addition, we performed in vitro experiments to further investigate the functional role of ANXA1/FPR2 in the proliferation and metastasis of Hep-2 cells, a cell line from larynx epidermoid carcinoma, after treatment with ANXA1(2-26 (annexin A1 N-terminal-derived peptide, Boc2 (antagonist of FPR and/or dexamethasone. Under these treatments, the level of Hep-2 cell proliferation, pro-inflammatory cytokines, ANXA1/FPR2 co-localization, and the prostaglandin signalling were analyzed using ELISA, immunocytochemistry and real-time PCR. An influx of neutrophils and degranulated mast cells was detected in tumor samples. In these inflammatory cells of peritumoral and tumor samples, ANXA1/FPR2 expression was markedly exacerbated, however, in laryngeal carcinoma cells, this expression was down-regulated. ANXA1(2-26 treatment reduced the proliferation of the Hep-2 cells, an effect that was blocked by Boc2, and up-regulated ANXA1/FPR2 expression. ANXA1(2-26 treatment also reduced the levels of pro-inflammatory cytokines and affected the expression of metalloproteinases and EP receptors, which are involved in the prostaglandin signalling. Overall, this study identified potential roles for the molecular mechanism of the ANXA1/FPR2 interaction in laryngeal cancer, including its relationship with the prostaglandin pathway, providing promising starting points for future research. ANXA1 may contribute to the regulation of tumor growth

  14. Inflammation and Cancer: Role of Annexin A1 and FPR2/ALX in Proliferation and Metastasis in Human Laryngeal Squamous Cell Carcinoma

    Science.gov (United States)

    Gastardelo, Thaís Santana; Cunha, Bianca Rodrigues; Raposo, Luís Sérgio; Maniglia, José Victor; Cury, Patrícia Maluf; Lisoni, Flávia Cristina Rodrigues; Tajara, Eloiza Helena; Oliani, Sonia Maria

    2014-01-01

    The anti-inflammatory protein annexin A1 (ANXA1) has been associated with cancer progression and metastasis, suggesting its role in regulating tumor cell proliferation. We investigated the mechanism of ANXA1 interaction with formylated peptide receptor 2 (FPR2/ALX) in control, peritumoral and tumor larynx tissue samples from 20 patients, to quantitate the neutrophils and mast cells, and to evaluate the protein expression and co-localization of ANXA1/FPR2 in these inflammatory cells and laryngeal squamous cells by immunocytochemistry. In addition, we performed in vitro experiments to further investigate the functional role of ANXA1/FPR2 in the proliferation and metastasis of Hep-2 cells, a cell line from larynx epidermoid carcinoma, after treatment with ANXA12–26 (annexin A1 N-terminal-derived peptide), Boc2 (antagonist of FPR) and/or dexamethasone. Under these treatments, the level of Hep-2 cell proliferation, pro-inflammatory cytokines, ANXA1/FPR2 co-localization, and the prostaglandin signalling were analyzed using ELISA, immunocytochemistry and real-time PCR. An influx of neutrophils and degranulated mast cells was detected in tumor samples. In these inflammatory cells of peritumoral and tumor samples, ANXA1/FPR2 expression was markedly exacerbated, however, in laryngeal carcinoma cells, this expression was down-regulated. ANXA12–26 treatment reduced the proliferation of the Hep-2 cells, an effect that was blocked by Boc2, and up-regulated ANXA1/FPR2 expression. ANXA12–26 treatment also reduced the levels of pro-inflammatory cytokines and affected the expression of metalloproteinases and EP receptors, which are involved in the prostaglandin signalling. Overall, this study identified potential roles for the molecular mechanism of the ANXA1/FPR2 interaction in laryngeal cancer, including its relationship with the prostaglandin pathway, providing promising starting points for future research. ANXA1 may contribute to the regulation of tumor growth and

  15. Human papillomavirus detection in moroccan patients with nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Belghmi Khalid

    2011-02-01

    Full Text Available Abstract Background Nasopharyngeal carcinoma (NPC is a malignant tumor which arises in surface epithelium of the posterior wall of the nasopharynx. There's is evidence that Epstein Barr virus (EBV is associated to NPC development. However, many epidemiologic studies point to a connection between viral infections by the human papillomavirus (HPV and NPC. Method Seventy Moroccan patients with NPC were screened for EBV and HPV. EBV detection was performed by PCR amplification of BZLF1 gene, encoding the ZEBRA (Z Epstein-Barr Virus Replication Activator protein, and HPV infection was screened by PCR amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 35, 45 and 59. Results The age distribution of our patients revealed a bimodal pattern. Sixty two cases (88.9% were classified as type 3 (undifferentiated carcinoma, 6 (8.6% as type 2 (non keratinizing NPC and only 2 (2.9% cases were classified as type 1 (keratinizing NPC. EBV was detected in all NPC tumors, whereas HPV DNA was revealed in 34% of cases (24/70. Molecular analysis showed that 20.8% (5/24 were infected with HPV31, and the remaining were infected with other oncogenic types (i.e., HPV59, 16, 18, 33, 35 and 45. In addition, statistical analysis showed that there's no association between sex or age and HPV infection (P > 0.1. Conclusion Our data indicated that EBV is commonly associated with NPC in Moroccan patients and show for the first time that NPC tumours from Moroccan patients harbour high risk HPV genotypes.

  16. Immunohistochemical localization of glutathione s-transferase isoenzymes (gsta, Gstp, Gstm4, And Gstt1) and tumour marker p53 in matched tissue from normal larynx and laryngeal carcinoma: correlations with prognostic factors.

    Science.gov (United States)

    Sedat, Aydin; Serpil, Oguztuzun; Nurdan, Gurbuz; Aylin, Gul; Arif, Sanli; Muzeyyen, Ozhavzali; Bulent, Satar; Sezen, Ozan; Nimet, Karadayi

    2010-10-01

    The immunohistochemical staining characteristics of glutathione S-transferase (GST) alpha (GSTA), pi (GSTP), mu (GSTM4), and theta (GSTT1) and P53 were investigated in laryngeal squamous cell carcinoma (LSCC) cases and normal laryngeal tissue from 46 patients. The relationships between expression of the GST isoenzymes and some clinicopathologic features were also examined. For immunohistochemical studies, tissues from 46 patients with LSCC at the Dr. Lütfi Kirdar Kartal Education and Research Hospital were used. The relationship between expression of the GST isoenzymes and P53 in normal and tumour tissue was analyzed using the Wilcoxon signed rank test. The correlation between GST isoenzymes and P53 and clinicopathologic data was also examined using the Spearman rank test. When the normal and tumour tissues of these cases were compared according to their staining intensity and percentage of positive staining, GSTA expression in normal cells was significantly higher than in tumour cells, and GSTP and P53 expression was higher in tumour cells (p .05). There was no correlation between P53 and GST expression in patients with LSCC. When the immunohistochemical results of GST isoenzymes and P53 were correlated with the clinical parameters, GSTA expression was increased in poorly differentiated laryngeal tumour, but GSTM4 and GSTT1 expression was decreased (p < .05). According to these results, GST-A, -P, and T1 and P53 were important in the diagnosis of LSCC.

  17. Sports Injury to the Larynx and Trachea.

    Science.gov (United States)

    Fabian, Richard L.

    1989-01-01

    Team physicians and coaches need a working knowledge of the pathophysiology of sports injuries to the larynx and trachea, carefully examining any such injuries because they could develop slowly and without symptoms into a compromised airway. Laryngeal and tracheal anatomy are discussed along with diagnosis and treatment. (SM)

  18. Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection.

    Science.gov (United States)

    Qing, Song; Tulake, Wuniqiemu; Ru, Mingfang; Li, Xiaohong; Yuemaier, Reziwanguli; Lidifu, Dilare; Rouzibilali, Aierken; Hasimu, Axiangu; Yang, Yun; Rouziahong, Reziya; Upur, Halmurat; Abudula, Abulizi

    2017-04-01

    It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix ( p potentially associated with human papillomavirus infection. Further validation studies of the profile will contribute to establishing auxiliary diagnostic markers for human papillomavirus-based cancer prognosis.

  19. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    National Research Council Canada - National Science Library

    Skipper, Anthony; Sims, Jennifer N; Yedjou, Clement G; Tchounwou, Paul B

    2016-01-01

    ... mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG₂) cells...

  20. Endolaryngeal laser resection of larynx

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    A. M. Mudunov

    2016-01-01

    Full Text Available Laryngeal cancer takes the leading position among malignant tumors of head and neck. Currently, endolaryngeal laser resection is the leading treatment option for localized processes (T1-T2. In the period from December 2014 to January 2016 such surgeries were performed in 76 patients in our clinic. Carcinoma in situ was detected in 19 (25 %, T1a in 27 (35 %, T1b in 24 (31 %, T2 in 6 (8 % patients. As result of the planned histological examination, in all cases surgical procedures had microscopically radical character. Endolaryngeal CO2 -laser resections allow to perform enough large radical surgical interventions with satisfactory functional and cosmetic results, without compromising long-term outcomes. 

  1. Human papillomavirus (HPV) in vulvar dysplasia and carcinoma in situ

    DEFF Research Database (Denmark)

    Junge, Jette; Poulsen, H; Horn, T

    1995-01-01

    Surgical specimens from 62 patients with vulvar dysplasia and carcinoma in situ were morphologically investigated. Lesions were classified according to WHO (mild, moderate, severe dysplasia and carcinoma in situ) and according to Toki et al. (1991) (warty, basaloid, combined warty/basaloid or bas...

  2. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

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    Chen Chang-Jie

    2010-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

  3. Expression and clinical significance of annexin A2 and human epididymis protein 4 in endometrial carcinoma.

    Science.gov (United States)

    Deng, Lu; Gao, Yiping; Li, Xiao; Cai, Mingbo; Wang, Huimin; Zhuang, Huiyu; Tan, Mingzi; Liu, Shuice; Hao, Yingying; Lin, Bei

    2015-09-11

    It is well-known that the treatment and monitoring methods are limited for advanced stage of endometrial carcinoma. Biological molecules with expression changes during tumor progression become potential therapeutic targets for advanced stage endometrial carcinoma. Annexin A2 (ANXA2) has been reported to be overexpressed in recurrent endometrial carcinoma, and the expression of human epididymis protein 4 (HE4) is upregulated in endometrial carcinoma. What's more, ANXA2 and HE4 interacted in ovarian cancer and promoted the malignant biological behavior. We speculated that their interaction may exist in endometrial carcinoma as well. We evaluated the expression and the correlation relationship of ANXA2 and HE4 in endometrial carcinoma. The expression of ANXA2 and HE4 protein in 84 endometrial carcinoma, 30 endometrial atypical hyperplasia, and 18 normal endometrial tissue samples were then measured using an immunohistochemical assay in paraffin embedded endometrial tissues. The structural relationship between ANXA2 and HE4 was explored by immunoprecipitation and double immunofluorescent staining. ANXA2 and HE4 co-localized in both endometrial tissues and endometrial carcinoma cells. ANXA2 and HE4 were expressed in 95.2 % and 85.7 % of the the endometrial carcinoma, respectively, which were significantly higher than normal endometrium (55.6 % and 16.7 %, both p endometrial carcinoma (p endometrial carcinoma. Expression levels of ANXA2 and HE4 were closely related to the malignant biological behavior of endometrial carcinoma, and ANXA2 was an independent risk factor for poor prognosis. The expression of ANXA2 and HE4 can affect each other.

  4. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    OpenAIRE

    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

    2012-01-01

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repre...

  5. Chondroradionecrosis of the Larynx in a Patient with Laryngeal: A Case Report

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    Aslan Ahmadi

    2017-05-01

    Full Text Available Introduction: Actinomycosis of the larynx has been rarely reported in the literature and usually occurs in patients with a history of laryngeal carcinoma and radiation therapy. However, its co-existence with chondroradionecrosis due to radiotherapy is even rarer. The most common site of infection is the cervicofacial region, especially in the submandibular area.   Case Report: Here we report a 63-year-old male with a history of chemoradiotherapy because of laryngeal cancer 1 year earlier who presented with laryngeal actinomycosis. After prolonged penicillin-based treatment, the patient underwent thyroid cartilage defect reconstructive surgery because of a laryngocutaneous fistula due to chondroradionecrosis. The diagnosis, work-up, and management of the case are discussed, as well as a review of the literature.   Conclusion: Although actinomycotic infection of the larynx is rare, it should be considered in the differential diagnosis of laryngeal complaints, especially in immunocompromised patients.

  6. Chondroradionecrosis of the Larynx in a Patient with Laryngeal: A Case Report.

    Science.gov (United States)

    Ahmadi, Aslan; Salem, Mohammad Mahdi; Safdarian, Mahdi; Ilkhani, Shahriar; Hamidian, Roghaieh; Cheraghipour, Mostafa; Daneshvar, Ali; Izadi, Farzad

    2017-05-01

    Actinomycosis of the larynx has been rarely reported in the literature and usually occurs in patients with a history of laryngeal carcinoma and radiation therapy. However, its co-existence with chondroradionecrosis due to radiotherapy is even rarer. The most common site of infection is the cervicofacial region, especially in the submandibular area. Here we report a 63-year-old male with a history of chemoradiotherapy because of laryngeal cancer 1 year earlier who presented with laryngeal actinomycosis. After prolonged penicillin-based treatment, the patient underwent thyroid cartilage defect reconstructive surgery because of a laryngocutaneous fistula due to chondroradionecrosis. The diagnosis, work-up, and management of the case are discussed, as well as a review of the literature. Although actinomycotic infection of the larynx is rare, it should be considered in the differential diagnosis of laryngeal complaints, especially in immunocompromised patients.

  7. Local Anesthetics Inhibit the Growth of Human Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Le Gac, Grégoire; Angenard, Gaëlle; Clément, Bruno; Laviolle, Bruno; Coulouarn, Cédric; Beloeil, Hélène

    2017-11-01

    Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapeutic options. Retrospective studies have shown that the administration of local anesthetics (LAs) during cancer surgery could reduce cancer recurrence. Besides, experimental studies reported that LAs could inhibit the growth of cancer cells. Thus, the purpose of this study was to investigate the effects of LAs on human HCC cells. The effects of 2 LAs (lidocaine and ropivacaine) (10 to 10 M) were studied after an incubation of 48 hours on 2 HCC cell lines, namely HuH7 and HepaRG. Cell viability, cell cycle analysis, and apoptosis and senescence tests were performed together with unsupervised genome-wide expression profiling and quantitative real-time polymerase chain reaction for relevant genes. We showed that LAs decreased viability and proliferation of HuH7 cells (from 92% [P lidocaine) and HepaRG progenitor cells (from 58% at 5 × 10 M [P lidocaine and 59% [P Lidocaine had no specific effect on cell cycle but increased by 10× the mRNA level of adenomatous polyposis coli (P < .01), which acts as an antagonist of the Wnt/β-catenin pathway. Both LAs increased apoptosis in Huh7 and HepaRG progenitor cells (P < .01). The data demonstrate that LAs induced profound modifications in gene expression profiles of tumor cells, including modulations in the expression of cell cycle-related genes that result in a cytostatic effect and induction of apoptosis.

  8. The influence of human papillomavirus on nasopharyngeal carcinoma in Japan.

    Science.gov (United States)

    Kano, Makoto; Kondo, Satoru; Wakisaka, Naohiro; Moriyama-Kita, Makiko; Nakanishi, Yosuke; Endo, Kazuhira; Murono, Shigeyuki; Nakamura, Hiroyuki; Yoshizaki, Tomokazu

    2017-06-01

    Although Japan is a non-endemic area with nasopharyngeal carcinoma (NPC), the proportion of WHO type I NPC in Japan are different from that in non-endemic areas such as North America and Europe. Recently, it is said that not only Epstein-Barr virus (EBV) but also human papillomavirus (HPV) has an influence on NPC in non-endemic areas. The aim of this study is to clarify the influence of HPV on NPC in Japan. Paraffin-embedded tumor specimens were available for 59 patients with NPC diagnosed between 1996 and 2015. We detected the virus status by p16 immunohistochemistry, HPV PCR, and in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA. Kaplan-Meier curves were used to compare the overall survival by viral status. Among the 59 patients, 49 (83%) were EBV-positive/HPV-negative, 2 (3%) were EBV-positive/HPV-positive, and 8 (16%) were EBV-negative/HPV-negative. All HPV-positive NPCs were co-infected with EBV. There were no significant differences between the overall survival in the three groups (p=0.111). In Japan, HPV was detected in a few patients with NPC, and we suggest that HPV has no influence on NPC carcinogenesis in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. GAGE12 mediates human gastric carcinoma growth and metastasis.

    Science.gov (United States)

    Lee, Eun Kyung; Song, Kyung-A; Chae, Ji-Hye; Kim, Kyoung-Mee; Kim, Seok-Hyung; Kang, Myung-Soo

    2015-05-15

    The spontaneous metastasis from human gastric carcinoma (GC) remains poorly reproduced in animal models. Here, we established an experimental mouse model in which GC progressively developed in the orthotopic stomach wall and metastasized to multiple organs; the tumors colonized in the ovary exhibited typical characteristics of Krukenberg tumor. The expression of mesenchymal markers was low in primary tumors and high in those in intravasating and extravasating veins. However, the expression of epithelial markers did not differ, indicating that the acquisition of mesenchymal markers without a concordant loss of typical epithelial markers was associated with metastasis. We identified 35 differentially expressed genes (DEGs) in GC cells metastasized to ovary, among which overexpression of GAGE12 family genes, the top-ranked DEGs, were validated. In addition, knockdown of the GAGE12 gene family affected transcription of many of the aforementioned 35 DEGs and inhibited trans-well migration, tumor sphere formation in vitro and tumor growth in vivo. In accordance, GAGE12 overexpression augmented migration, tumor sphere formation and sustained in vivo tumor growth. Taken together, the GAGE12 gene family promotes GC growth and metastasis by modulating the expression of GC metastasis-related genes. © 2014 UICC.

  10. Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.

    Science.gov (United States)

    Ahmad, Usama; Akhtar, Juber; Singh, Satya Prakash; Ahmad, Farhan Jalees; Siddiqui, Sahabjada

    2018-03-01

    Nanoemulsion of silymarin was developed and optimized. Nanoemulsion was made by aqueous titration method. Sefsol 218 (5.8% v/v), Kolliphor RH40 and polyethylene glycol 400 (Smix; 2:1; 28.99% v/v) were used as oil phase, surfactant and co-surfactant while distilled water (65.22% v/v) acted as an aqueous phase. Nanoemulsion was characterized on the basis of particle size, viscosity, electrical conductivity and refractive index. Further, in vitro release, in vivo pharmacokinetic study, stability study and cancer cell line studies were also performed. The optimized formulation (NE9) with mean particle size of 21.24 nm showed a minimum viscosity of 9.59 cps, maximum drug release (97.75%) in 24 h. The NE9 formulation also showed higher AUC (p  .05). The cancer cell line studies also confirmed that silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation (p nanoemulsion may be an efficient carrier for oral delivery of silymarin against human hepatocellular carcinoma without damaging normal cells.

  11. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas.

    Science.gov (United States)

    Nault, Jean-Charles; Datta, Shalini; Imbeaud, Sandrine; Franconi, Andrea; Mallet, Maxime; Couchy, Gabrielle; Letouzé, Eric; Pilati, Camilla; Verret, Benjamin; Blanc, Jean-Frédéric; Balabaud, Charles; Calderaro, Julien; Laurent, Alexis; Letexier, Mélanie; Bioulac-Sage, Paulette; Calvo, Fabien; Zucman-Rossi, Jessica

    2015-10-01

    Hepatocellular carcinomas (HCCs) are liver tumors related to various etiologies, including alcohol intake and infection with hepatitis B (HBV) or C (HCV) virus. Additional risk factors remain to be identified, particularly in patients who develop HCC without cirrhosis. We found clonal integration of adeno-associated virus type 2 (AAV2) in 11 of 193 HCCs. These AAV2 integrations occurred in known cancer driver genes, namely CCNA2 (cyclin A2; four cases), TERT (telomerase reverse transcriptase; one case), CCNE1 (cyclin E1; three cases), TNFSF10 (tumor necrosis factor superfamily member 10; two cases) and KMT2B (lysine-specific methyltransferase 2B; one case), leading to overexpression of the target genes. Tumors with viral integration mainly developed in non-cirrhotic liver (9 of 11 cases) and without known risk factors (6 of 11 cases), suggesting a pathogenic role for AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated with oncogenic insertional mutagenesis in human HCC.

  12. Induction of retinoic acid receptor β mediates growth inhibition in retinoid resistant human colon carcinoma cells

    OpenAIRE

    Nicke, B; Riecken, E; Rosewicz, S

    1999-01-01

    BACKGROUND—The molecular mechanisms underlying the differential sensitivity of human colon carcinoma cells to retinoid mediated growth inhibition are poorly understood.
AIM—To identify the intracellular mechanisms responsible for resistance against retinoid mediated growth inhibition in human colon carcinoma cells.
METHODS—Anchorage independent growth of the human colon carcinoma cell lines HT29 and LoVo was determined by a human tumour clonogenic assay. Retinoid receptor expression was evalu...

  13. Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Alarifi, Saud; Ali, Daoud; Alkahtani, Saad; Siddiqui, Maqsood A; Ali, Bahy A

    2013-01-01

    Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells. A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P hepatocellular carcinoma cells exposed to arsenic trioxide. The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

  14. High-risk human papillomavirus in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Antonsson, Annika; Nancarrow, Derek J; Brown, Ian S; Green, Adele C; Drew, Paul A; Watson, David I; Hayward, Nicholas K; Whiteman, David C

    2010-08-01

    Although most cases of esophageal squamous cell carcinoma (ESCC) in western populations have been attributed to high levels of exposure to tobacco and alcohol, infectious agents have been postulated as possible causes, particularly human papillomavirus (HPV). To explore this issue, we analyzed HPV DNA prevalence and HPV types together with lifestyle factors, in relation to tumor stage and survival in a low-incidence population. Archived tumor samples from a nationwide cohort of 222 ESCC patients were tested for the presence of HPV DNA by PCR; positive samples were sequenced to determine HPV type, and p16(INK4a) status was assessed by immunohistochemistry. Of 222 ESCC patients, 8 tested HPV positive (prevalence, 3.6%; 95% confidence interval, 1.1-6.1%), of which 6 were HPV-16 positive and 2 were HPV-35 positive. Four of the eight HPV-positive tumors overexpressed p16(INK4a). None of 55 normal esophageal tissue samples from healthy participants had any detectable HPV. Although the numbers were low, it seemed that patients with HPV-positive ESCC tumors were younger than those with HPV-negative tumors (mean age, 60.8 versus 65.3 years, P = 0.18) and had higher body mass index (BMI) throughout life (mean current BMI of 25.1 for HPV positive, 22.2 for HPV negative, P = 0.08; mean BMI at 20 years of 25.8 for HPV positive, 22.1 for HPV negative, P = 0.003). We found no difference between patients with HPV-positive and HPV-negative tumors with respect to other lifestyle factors. These findings suggest a very low prevalence of HPV DNA in human ESCC. HPV is very unlikely to be a common cause of ESCC in Australia. (c)2010 AACR.

  15. Human papillomavirus-related basaloid squamous cell carcinoma of the bladder associated with genital tract human papillomavirus infection.

    Science.gov (United States)

    Ginori, Alessandro; Barone, Aurora; Santopietro, Rosa; Barbanti, Gabriele; Cecconi, Filippo; Tripodi, Sergio Antonio

    2015-02-01

    Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection. © 2014 The Japanese Urological Association.

  16. Dynamic protein interaction modules in human hepatocellular carcinoma progression.

    Science.gov (United States)

    Yu, Hui; Lin, Chen-Ching; Li, Yuan-Yuan; Zhao, Zhongming

    2013-01-01

    Gene expression profiles have been frequently integrated with the human protein interactome to uncover functional modules under specific conditions like disease state. Beyond traditional differential expression analysis, differential co-expression analysis has emerged as a robust approach to reveal condition-specific network modules, with successful applications in a few human disease studies. Hepatocellular carcinoma (HCC), which is often interrelated with the Hepatitis C virus, typically develops through multiple stages. A comprehensive investigation of HCC progression-specific differential co-expression modules may advance our understanding of HCC's pathophysiological mechanisms. Compared with differentially expressed genes, differentially co-expressed genes were found more likely enriched with Hepatitis C virus binding proteins and cancer-mutated genes, and they were clustered more densely in the human reference protein interaction network. These observations indicated that a differential co-expression approach could outperform the standard differential expression network analysis in searching for disease-related modules. We then proposed a differential co-expression network approach to uncover network modules involved in HCC development. Specifically, we discovered subnetworks that enriched differentially co-expressed gene pairs in each HCC transition stage, and further resolved modules with coherent co-expression change patterns over all HCC developmental stages. Our identified network modules were enriched with HCC-related genes and implicated in cancer-related biological functions. In particular, APC and YWHAZ were highlighted as two most remarkable genes in the network modules, and their dynamic interaction partnership was resolved in HCC development. We demonstrated that integration of differential co-expression with the protein interactome could outperform the traditional differential expression approach in discovering network modules of human diseases

  17. Chondrosarcoma of the larynx: treatment with radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dailiana, T.; Thanos, L.; Papathanasiou, M.; Alexopoulou, E.; Papaioannou, G.; Kelekis, D.A. [2. Department of Radiology, Evgenidion Hospital, Medical School, University of Athens, 20, Papadiamantopoulou St., Athens 15452 (Greece); Nomikos, P. [Department of ENT, Ippokrateion Hospital, Medical School, University of Athens, Athens (Greece); Kapranos, N. [Department of Pathology, Division of Molecular Pathology, Amalia Fleming Hospital, Athens (Greece)

    2002-09-01

    The case of a 50-year-old man with chondrosarcoma of the larynx treated with radiotherapy is reported. The patient presented with hoarseness and dyspnea. He underwent computed tomography (CT), which demonstrated a soft tissue mass of the larynx. Direct laryngoscopy with biopsy established the diagnosis of chondrosarcoma. Although experience with radiotherapy in these cases has been lacking in the literature, it was considered and eventually used, as radical surgery would result in severe cosmetic and functional impairment. Radiation therapy alone resulted in long-term remission of the tumour for more than 3 years. The patient has been followed up using CT and direct laryngoscopy for early detection of recurrence or metastases. (orig.)

  18. 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.

  19. RHINOSCLEROMA OF LARYNX : A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Kusuma Jeevan

    2015-06-01

    Full Text Available Rhinoscleroma is a chronic granulomatous disease of the respiratory mucosa caused by klebsiella rhinoscleromatis. It commonly involves the nose followed by nasopharynx, oropharynx, larynx, trachea and bronchi. Middle aged females are most prone for this disease. Isolated lar yngeal involvement is a rare condition. It should be differentiated from other chronic granulomatous conditions and should be managed early to decrease the morbidity caused by the disease.

  20. Automated quantification of aligned collagen for human breast carcinoma prognosis

    Directory of Open Access Journals (Sweden)

    Jeremy S Bredfeldt

    2014-01-01

    Full Text Available Background: Mortality in cancer patients is directly attributable to the ability of cancer cells to metastasize to distant sites from the primary tumor. This migration of tumor cells begins with a remodeling of the local tumor microenvironment, including changes to the extracellular matrix and the recruitment of stromal cells, both of which facilitate invasion of tumor cells into the bloodstream. In breast cancer, it has been proposed that the alignment of collagen fibers surrounding tumor epithelial cells can serve as a quantitative image-based biomarker for survival of invasive ductal carcinoma patients. Specific types of collagen alignment have been identified for their prognostic value and now these tumor associated collagen signatures (TACS are central to several clinical specimen imaging trials. Here, we implement the semi-automated acquisition and analysis of this TACS candidate biomarker and demonstrate a protocol that will allow consistent scoring to be performed throughout large patient cohorts. Methods: Using large field of view high resolution microscopy techniques, image processing and supervised learning methods, we are able to quantify and score features of collagen fiber alignment with respect to adjacent tumor-stromal boundaries. Results: Our semi-automated technique produced scores that have statistically significant correlation with scores generated by a panel of three human observers. In addition, our system generated classification scores that accurately predicted survival in a cohort of 196 breast cancer patients. Feature rank analysis reveals that TACS positive fibers are more well-aligned with each other, are of generally lower density, and terminate within or near groups of epithelial cells at larger angles of interaction. Conclusion: These results demonstrate the utility of a supervised learning protocol for streamlining the analysis of collagen alignment with respect to tumor stromal boundaries.

  1. ADAMTS8 and ADAMTS15 expression predicts survival in human breast carcinoma

    DEFF Research Database (Denmark)

    Porter, Sarah; Span, Paul N; Sweep, Fred C G J

    2006-01-01

    We recently undertook expression profiling of all 19 human ADAMTS metalloproteinases (a disintegrin and metalloproteinase with thrombospondin motifs) in malignant and non-neoplastic breast tissue and showed that 11 of the ADAMTS genes are dysregulated in breast carcinoma. We identified a subgroup...... of ADAMTSs, based on functional and amino acid sequence similarity (ADAMTS1, 4, 5, 8 and 15), to be the focus of further study in breast carcinoma. Further RNA expression analysis by real-time PCR on a different cohort of 229 patients with breast cancer has identified ADAMTS8 as a predictor of poor overall...... breast carcinoma, fitted the expectation that relatively high expression levels of ADAMTS8 together with low expression levels of ADAMTS15 seen in human breast carcinoma are associated with a poor clinical outcome. In summary, ADAMTS8 and ADAMTS15 have emerged as novel predictors of survival in patients...

  2. Griffonia simplicifolia agglutinin-2-binding glycoprotein as a novel carbohydrate antigen of human colonic carcinoma.

    Science.gov (United States)

    Nakayama, J; Okano, A; Maeda, H; Miyachi, M; Ota, H; Katsuyama, T; Kanai, M

    1990-04-01

    Griffonia simplicifolia agglutinin-2-binding glycoprotein (GBG) in human colonic carcinoma was examined immunochemically and histochemically, GBG was extracted from colonic carcinoma as a serum-type glycoprotein of 160 kilodaltons. GBG was not identical with carcinoembryonic antigen (CEA), since its molecular weight and localization in tissue sections were different from those of CEA. The non-reducing terminals of GBG probably carry N-acetylglucosamine, but not blood group determinants. Furthermore, GBG was released by phosphatidylinositol-specific phospholipase C from cell membrane. GBG was suggested to be anchored to the membrane via linkage to a glycosyl-phosphatidylinositol molecule. Among colonic carcinoma-associated antigens, serum-type glycoproteins having N-acetylglucosamine at non-reducing terminals have not previously been reported. GBG is a novel carbohydrate antigen of human colonic carcinoma.

  3. Aromatase in human endometrial carcinoma and hyperplasia. Immunohistochemical, in situ hybridization, and biochemical studies.

    OpenAIRE

    Watanabe, K.; Sasano, H.; Harada, N.; Ozaki, M.; Niikura, H.; Sato, S.; Yajima, A.

    1995-01-01

    The expression of P450 aromatase and other steroidogenic enzymes were evaluated in 42 endometrioid endometrial carcinomas, 23 endometrial hyperplasias, and 7 normal endometrial specimens. These findings were correlated with clinicopathological findings to elucidate the possible biological significance of in situ estrogen production in the development of human endometrial carcinoma. Only weak aromatase immunoreactivity was observed in vascular walls and myometrial cells. In contrast, strong ar...

  4. Human papillomavirus-driven neck lymph node metastases from oropharyngeal or unknown primary squamous cell carcinoma

    OpenAIRE

    Schroeder, Lea

    2017-01-01

    Patients with neck squamous cell carcinoma from unknown primary tumor (NSCCUP) present with lymph node metastases without evidence for a primary tumor. Most patients undergo an aggressive multimodal treatment, which induces severe toxicity. Primary tumors of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers f...

  5. Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Shunsuke Nojiri

    2014-03-01

    Full Text Available Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP, p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD with appropriate software (ModFit LT; BD. The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore. The mRNA levels of AFP relative to Alb(−: Alb(−, Alb(+, and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−, and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(− and p = 0.004 for Prionex, and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(− and Prionex, and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+. More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+ than in Alb(− (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−, Alb

  6. Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States.

    Science.gov (United States)

    Stenmark, Matthew H; Shumway, Dean; Guo, Cui; Vainshtein, Jeffrey; Mierzwa, Michelle; Jagsi, Reshma; Griggs, Jennifer J; Banerjee, Mousumi

    2017-10-01

    Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single-institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing. Retrospective, cross-sectional study. We identified a comprehensive national sample of 8,359 patients with oropharyngeal carcinoma and known HPV status diagnosed between 2010 and 2011 within the National Cancer Database. Multivariable logistic regression was used to assess correlates of patient and tumor characteristics on HPV status. Among patients with oropharyngeal carcinoma, the frequency of HPV-related squamous cell carcinoma in the United States was 65.4%. HPV-related oropharyngeal carcinoma was associated with younger age, male sex, and white race (P carcinoma in the United States and is associated with a distinct clinical profile, supporting efforts to re-evaluate the staging and treatment paradigm for HPV-associated oropharyngeal cancer. 4. Laryngoscope, 127:2270-2278, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  7. Organotypic in vitro models of human cutaneous squamous cell carcinoma

    NARCIS (Netherlands)

    Commandeur, Suzan

    2013-01-01

    Skin cancer is the most common type of cancer in fair-skinned populations. Cutaneous squamous cell carcinoma (SCC) comprises about 15% of all skin cancer diagnoses. Treatment associated with the high and rising prevalence of cutaneous SCC puts an increasingly high financial burden on society,

  8. Epac inhibits migration and proliferation of human prostate carcinoma cells

    NARCIS (Netherlands)

    Grandoch, M.; Rose, A.; ter Braak, M.; Jendrossek, V.; Ruebben, H.; Fischer, J. W.; Schmidt, M.; Weber, A. A.

    2009-01-01

    BACKGROUND: It was recently found that cAMP mediates protein kinase A-independent effects through Epac proteins. The aim of this study was to investigate the role of Epac in migration and proliferation of prostate carcinoma cells. METHODS: The effect of Epac activation was determined by [(3)H

  9. Molecular typing for detection of high-risk human papillomavirus is a useful tool for distinguishing primary bladder carcinoma from secondary involvement of uterine cervical carcinoma in the urinary bladder.

    Science.gov (United States)

    Kao, Hua-Lin; Lai, Chiung-Ru; Ho, Hsiang-Ling; Pan, Chin-Chen

    2016-03-01

    For patients with carcinoma of the urinary bladder and uterine cervix, distinguishing between metastasis and a second primary carcinoma has significant prognostic and therapeutic implications. The aim of this study was to investigate the prevalence of high-risk human papillomavirus (HR-HPV) in cervical carcinoma with secondary involvement of the bladder and primary bladder carcinoma, in order to explore whether the detection of HR-HPV could help to differentiate between the two. Paired bladder and cervix carcinoma specimens from 37 patients with cervical carcinoma with bladder involvement, four patients with bladder carcinoma with uterine cervical involvement and two patients with double primaries were studied with quantitative multiplex polymerase chain reaction and chromogenic in-situ hybridization. Three hundred and seventy-five bladder carcinomas and 220 cervical carcinomas were analysed as controls. All cases of cervical carcinoma with bladder involvement showed concordant HR-HPV-positive patterns. The four cases of bladder carcinoma with uterine involvement were negative for HR-HPV. HR-HPV was detected in the cervical carcinoma but not in the bladder carcinoma of the patients with double primaries. HR-HPV was detected in 91.9% of cervical carcinomas but in none of the bladder carcinomas in the control group. Molecular typing for HR-HPV detection is useful to distinguish bladder carcinoma from secondary involvement of cervical carcinoma. © 2015 John Wiley & Sons Ltd.

  10. Woodchuck hepatitis virus-induced carcinoma as a relevant natural model for therapy of human hepatoma.

    Science.gov (United States)

    Gouillat, C; Manganas, D; Zoulim, F; Vitrey, D; Saguier, G; Guillaud, M; Ain, J F; Duque-Campos, R; Jamard, C; Praves, M; Trepo, C

    1997-06-01

    Eastern American woodchuck (Marmota monax), naturally infected with woodchuck hepatitis virus, a virus similar to human hepatitis B virus, develops liver cancer with a high prevalence. The aim of this work was to assess Marmota monax as a model of human hepatocellular carcinoma, especially to assess new potential adjuvant therapies after surgical resection. Forty-four woodchuck hepatitis virus-infected animals were regularly screened by ultrasound examination from the age of 18 months and for a 30-month period. One or more liver tumors were diagnosed in 31 animals (70%). Five of them with multifocal tumor or poor general status were considered unsuitable for surgery. The other 26 were operated on. At laparotomy no tumor was found in three. The 18 liver tumors studied were hepatocellular carcinomas, grossly and microscopically similar to human hepatocellular carcinoma. Peritumoral parenchyma studied in 13 specimens was always non-cirrhotic but adequate staining demonstrated patterns of fibrosis in four cases. Clear evidence of chronic active hepatitis, periportal hepatitis and steatosis were demonstrated in five, seven and one of the 13 specimens, respectively. Tumors were treated by tumorectomy in eight animals, by alcoholization in seven and by laser photocoagulation in one. A simple tumor biopsy was performed in the other seven. Ten animals died postoperatively. All the survivors in the tumorectomy group died from tumor recurrence within 10-18 months after surgery. It is concluded that woodchuck hepatitis virus-induced liver carcinoma is a natural model of human hepatocellular carcinoma with similar pathology and natural history, including early ultrasonic detection and tumor recurrence after resection. Tumor excision is feasible in this animal model, which now provides the basis for assessment of new potential adjuvant therapies for human hepatocellular carcinoma in an attempt to reduce the high recurrence rate after surgical resection in humans.

  11. Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models.

    Directory of Open Access Journals (Sweden)

    Fang Peng

    Full Text Available BACKGROUND: Hypoxic tumor cells can reduce the efficacy of radiation. Antiangiogenic therapy may transiently "normalize" the tumor vasculature to make it more efficient for oxygen delivery. The aim of this study is to investigate whether the recombinant human endostatin (endostar can create a "vascular normalization window" to alleviate hypoxia and enhance the inhibitory effects of radiation therapy in human nasopharyngeal carcinoma (NPC in mice. METHODOLOGY/PRINCIPAL FINDINGS: Transient changes in morphology of tumor vasculature and hypoxic tumor cell fraction in response to endostar were detected in mice bearing CNE-2 and 5-8F human NPC xenografts. Various treatment schedules were tested to assess the influence of endostar on the effect of radiation therapy. Several important factors relevant to the angiogenesis were identified through immunohistochemical staining. During endostar treatment, tumor vascularity decreased, while the basement membrane and pericyte coverage associated with endothelial cells increased, which supported the idea of vessel normalization. Hypoxic tumor cell fraction also decreased after the treatment. The transient modulation of tumor physiology caused by endostar improved the effect of radiation treatment compared with other treatment schedules. The expressions of vascular endothelial growth factor (VEGF, matrix metalloproteinase-2 (MMP-2, MMP-9, and MMP-14 decreased, while the level of pigment epithelium-derived factor (PEDF increased. CONCLUSIONS: Endostar normalized tumor vasculature, which alleviated hypoxia and significantly sensitized the function of radiation in anti-tumor in human NPC. The results provide an important experimental basis for combining endostar with radiation therapy in human NPC.

  12. Hericium erinaceus enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Lee, Jong Seok; Hong, Eock Kee

    2010-11-28

    It has been demonstrated that the Hericium erinaceus (HE) mushroom, which primarily consists of polysaccharides, possesses anti-tumor activities. However, the mechanisms by which HE inhibits human hepatocellular carcinoma growth remain unknown. Our study demonstrates that HE acts as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this sensitization can be achieved by reducing c-FLIP expression via JNK activation and enhancing intracellular Dox accumulation via the inhibition of NF-κB activity. These findings suggest that HE in combination with Dox serves as an effective tool for treating drug-resistant human hepatocellular carcinoma. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. TRAP1 protein signature predicts outcome in human metastatic colorectal carcinoma.

    Science.gov (United States)

    Maddalena, Francesca; Simeon, Vittorio; Vita, Giulia; Bochicchio, Annamaria; Possidente, Luciana; Sisinni, Lorenza; Lettini, Giacomo; Condelli, Valentina; Matassa, Danilo Swann; Li Bergolis, Valeria; Fersini, Alberto; Romito, Sante; Aieta, Michele; Ambrosi, Antonio; Esposito, Franca; Landriscina, Matteo

    2017-03-28

    TRAP1 is a HSP90 molecular chaperone upregulated in colorectal carcinomas and involved in control of intracellular signaling, cell cycle, apoptosis and drug resistance, stemness and bioenergetics through co-traslational regulation of a network of client proteins. Thus, the clinical significance of TRAP1 protein network was analyzed in human colorectal cancers. TRAP1 and/or its client proteins were quantified, by immunoblot analysis, in 60 surgical specimens of colorectal carcinomas at different stages and, by immunohistochemistry, in 9 colorectal adenomatous polyps, 11 in situ carcinomas and 55 metastatic colorectal tumors. TRAP1 is upregulated at the transition between low- and high-grade adenomas, in in situ carcinomas and in about 60% of human colorectal carcinomas, being downregulated only in a small cohort of tumors. The analysis of TCGA database showed that a subgroup of colorectal tumors is characterized by gain/loss of TRAP1 copy number, this correlating with its mRNA and protein expression. Interestingly, TRAP1 is co-expressed with the majority of its client proteins and hierarchical cluster analysis showed that the upregulation of TRAP1 and associated 6-protein signature (i.e., IF2α, eF1A, TBP7, MAD2, CDK1 and βCatenin) identifies a cohort of metastatic colorectal carcinomas with a significantly shorter overall survival (HR 5.4; 95% C.I. 1.1-26.6; p=0.037). Consistently, the prognostic relevance of TRAP1 was confirmed in a cohort of 55 metastatic colorectal tumors. Finally, TRAP1 positive expression and its prognostic value are more evident in left colon cancers. These data suggest that TRAP1 protein network may provide a prognostic signature in human metastatic colorectal carcinomas.

  14. Biosynthesis and metabolism of steroid hormones by human adrenal carcinomas

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    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.

  15. [Human papilloma viruses: other risk factor of head and neck carcinoma].

    Science.gov (United States)

    Woto-Gaye, G; M'Farrej, M K; Doh, K; Thiam, I; Touré, S; Diop, R; Dial, C

    2016-08-01

    Head and neck carcinoma (HNC) occupy the sixth place as the most frequent type of cancer worldwide. Next to alcohol and tobacco intoxication, other risk factors (RF) are suspected, including the human papilloma viruses (HPVs). The aim of this study was to highlight the prevalence of HPVs and histo-epidemiological characteristics of HNC HPV+ in Senegal. This is a prospective, multicenter preliminary study of 18 months (January 1, 2012-June 30, 2014). The cases of HNC histologically confirmed in Senegal were then sent to the bio-pathology department of the Curie Institute in Paris to search HPVs. In the 90 included cases, the PCR technique was successful in 54 cases (60%). HPVs were found in seven cases, that is, a prevalence of 13%. HPVs were associated with 5 cases of hypopharyngeal carcinoma and 2 cases of carcinoma of the oral cavity. Patients with HNC HPV+ had a median age of 42 years against 49 years for HPV-patients. Three patients (42.8%) with HPV+ carcinomas were smokers. Of the 47 HPV-patients, 40 patients (87.1%) had alcohol intoxication and/or smoking. The concept of oral sex was refuted by all our patients. Squamous cell carcinoma was the only histological type found. HPV+ cell carcinoma showed no specific histological appearance. HPVs are another certain RF of HNC in Senegal. The major therapeutic and prognostic impact of HPVinduced cancers requires the systematic search of the viruses by the PCR technique.

  16. Cellular binding proteins for vitamin A in human carcinomas and in normal tissues.

    Science.gov (United States)

    Palan, P R; Romney, S L

    1980-11-01

    Blinded analyses of the concentrations of binding proteins for retinol and retinoic acid (CRABP) in homogenates of cancer and normal tissue aliquots obtained from human cervix, endometrium, ovary, breast, and lung were carried out by the sucrose gradient ultracentrifugation technique. In carcinomas of the cervix and endometrium, CRABP mean values of 50.4 and 123.2 pmol/g tissue, respectively were detected. Such concentrations represent a 3- and 4-fold increase over the mean values of CRABP in the normal cervix (16.9 pmol/g) and normal endometrium (30.8 pmol/g), respectively. In carcinomas of the ovary, the mean CRABP level was 128.6 pmol/g compared to the maximal mean value of less than or equal to 0.46 pmol/g in the normal ovary. Elevated levels of CRABP were also found in breast and lung carcinomas compared to the amounts detected in the same patient in normal tissue aliquots of the same organ. The differences between CRABP concentrations in cervical, endometrial, ovarian, and breast carcinomas and those in normal tissue are statistically significant. In contrast, cellular retinol-binding protein concentrations were reduced in the endometrial, ovarian, breast, and lung carcinomas compared to normal tissues. There were no significant differences between the log-mean concentrations of cellular retinol-binding proteins in the cytosols from tissue aliquots of carcinoma of the cervix and those in the cytosols from tissue aliquots of normal cervix.

  17. Determination of strain field on the superior surface of excised larynx vocal folds using DIC.

    Science.gov (United States)

    Bakhshaee, Hani; Young, Jonathan; Yang, Justin C W; Mongeau, Luc; Miri, Amir K

    2013-11-01

    The objective of the present study was to quantify the mechanical strain and stress in excised porcine larynges during self-oscillation using digital image correlation (DIC) method. The use of DIC in the excised larynx setup may yield accurate measurements of the vocal fold displacement field. Ex vivo animal larynx. Measurements were performed using excised porcine larynges on a humidified flow bench, equipped with two high-speed cameras and a commercially available DIC software. Surface deformations were calculated from digital images recorded at 3000 frames per second during continuous self-oscillation for four excised porcine larynges. Larynx preparation consisted of removing the supraglottal wall and the false folds. DIC yielded the deformation field on the superior visible surface of the vocal folds. Measurement data for adducted and freely suspended vocal folds were also used to estimate the distribution of the initial prephonatory strain field. An isotropic constitutive law, the polymer eight-chain model, was used to estimate the surface distributions of planar stresses from the strain data. The Lagrangian normal strain values were between ∼16% and ∼29% along the anterior-posterior direction. The motion of material points on the vocal fold surface described an elliptical trajectory during oscillation. A phase difference was observed between the anterior-posterior and the medial-lateral component of the displacement. The strain data and eight-chain model yielded a maximum stress of ∼4 kPa along the medial-lateral direction on the superior surface. DIC allowed the strain field over the superior surface of an excised porcine larynx to be quantified during self-oscillation. The approach allowed the determination of the trajectory of specific points on the vocal fold surface. The results for the excised larynx were found to be significantly different than previous results obtained using synthetic replicas. The present study provides suggestions for future

  18. Adult obstructive sleep apnoea and the larynx.

    Science.gov (United States)

    Novakovic, Daniel; MacKay, Stuart

    2015-12-01

    The review examines current evidence and thinking regarding the relationship between the larynx and obstructive sleep apnoea (OSA) in adults. Drug-induced sleep endoscopy has an emerging role in the identification of laryngeal obstruction associated with sleep apnoea and may be adjunctive to awake dynamic assessment in specific cases. Nocturnal stridor and OSA is a common and treatable finding in patients with multiple system atrophy. Acromegaly can cause OSA by obstruction at the laryngeal level via supraglottic soft tissue hypertrophy or decreased vocal fold mobility. Emerging evidence suggests a relationship between OSA, laryngopharyngeal reflux, and laryngeal sensory dysfunction including chronic cough. The mechanisms remain unclear and warrant further investigation. The larynx plays an important role in assessment and treatment of adult sleep apnoea. Laryngeal afferent sensory pathways play a critical role in reflexes controlling airway patency during sleep. Airway obstruction at the laryngeal level should be considered and assessed especially in OSA patients nonresponsive to standard therapies. Isolated laryngeal airway obstruction is rare but identification of specific conditions is important as they are amenable to appropriate treatments. OSA can also affect normal laryngeal function. People with OSA exhibit higher levels of laryngeal inflammation, laryngopharyngeal reflux, and chronic cough. Treatment with continuous positive airway pressure has a potential role in improving laryngeal symptomatology in these cases.

  19. Liposomal daunorubicin overcomes drug resistance in human breast, ovarian and lung carcinoma cells.

    Science.gov (United States)

    Sadava, David; Coleman, Aaron; Kane, Susan E

    2002-11-01

    Multi-drug resistance due in part to membrane pumps such as P-glycoprotein (Pgp) is a major clinical problem in human cancers. We tested the ability of liposomally-encapsulated daunorubicin (DR) to overcome resistance to this drug. A widely used breast carcinoma cell line originally selected for resistance in doxorubicin (MCF7ADR) was 4-fold resistant to DR compared to the parent MCF7 cells (IC50 79 nM vs. 20 nM). Ovarian carcinoma cells (SKOV3) were made resistant by retroviral transduction of MDR1 cDNA and selection in vinblastine. The resulting SKOV3MGP1 cells were 130-fold resistant to DR compared to parent cells (IC50 5700 nM vs. 44 nM). Small-cell lung carcinoma cells (H69VP) originally selected for resistance to etoposide were 6-fold resistant to DR compared to H69 parent cells (IC50 180 nM vs. 30 nM). In all three cases, encapsulation of DR in liposomes as Daunoxome (Gilead) did not change the IC50 of parent cells relative to free DR. However, liposomal DR overcame resistance in MCF7ADR breast carcinoma cells (IC50 20 nM), SKOV3MGP1 ovarian carcinoma cells (IC50 237 nM) and H69VP small-cell lung carcinoma cells (IC50 27 nM). Empty liposomes did not affect the IC50 for free DR in the three resistant cell lines, nor did empty liposomes affect the IC50 for other drugs that are part of the multi-drug resistance phenotype (etoposide, vincristine) in lung carcinoma cells. These data indicate the possible value of liposomal DR in overcoming Pgp-mediated drug resistance in human cancer.

  20. Recommendations for the diagnosis of human papilloma virus (HPV) high and low risk in the prevention and treatment of diseases of the oral cavity, pharynx and larynx. Guide of experts PTORL and KIDL.

    Science.gov (United States)

    Wierzbicka, Małgorzata; Józefiak, Agata; Szydłowski, Jarosław; Marszałek, Andrzej; Stankiewicz, Czesław; Hassman-Poznańska, Elżbieta; Osuch-Wójcikiewicz, Ewa; Składzień, Jacek; Klatka, Janusz; Pietruszewska, Wioletta; Puacz, Elżbieta; Szyfter, Krzysztof; Szyfter, Witold

    2013-01-01

    The role of human papilloma viruses (HPV) in malignant and nonmalignant ENT diseases and the corresponding epidemiological burden has been widely described. International head and neck oncology community discussed growing evidence that oral HPV infection contributes to the risk of oro-pharyngeal carcinoma (OPC) and recommended HPV testing as a part of the work up for patients with OPC. Polish Society of ENT Head Neck Surgery and National Chamber of Laboratory Diagnosticians have worked together to define the minimum requirements for assigning a diagnosis of HPV-related conditions and testing strategy that include HPV specific tests in our country. This paper briefly frames the literature information concerning low risk (LR) and high risk (HR) HPV, reviews the epidemiology, general guidance on the most appropriate biomarkers for clinical assessment of HPV. The definition of HPV-related cancer was presented. The article is aiming to highlight some of major issues for the clinician dealing with patients with HPV-related morbidities and to introduce the diagnostic algorithm in Poland. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

  1. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

    Science.gov (United States)

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

    2012-01-01

    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  2. Amplification and over-expression of the neu oncogene in human breast carcinomas

    NARCIS (Netherlands)

    van de Vijver, M. J.; Mooi, W. J.; Peterse, J. L.; Nusse, R.

    1988-01-01

    Amplification of the neu (or c-erbB-2 or HER) oncogene is found to be present in 15-30% of human breast carcinomas and has been reported to correlate with poor prognosis. We briefly review the literature on this subject with emphasis on our own results on immunohistochemical detection of neu

  3. The sinonasal tract: another potential "hot spot" for carcinomas with transcriptionally-active human papillomavirus

    NARCIS (Netherlands)

    Lewis, J.S., Jr.; Westra, W.H.; Thompson, L.D.; Barnes, L.; Cardesa, A.; Hunt, J.L.; Williams, M.D.; Slootweg, P.J.; Triantafyllou, A.; Woolgar, J.A.; Devaney, K.O.; Rinaldo, A.; Ferlito, A.

    2014-01-01

    While high risk human papillomavirus (HPV) is well established as causative and clinically important for squamous cell carcinoma (SCC) of the oropharynx, its role in non-oropharyngeal head and neck SCC is much less clearly elucidated. In the sinonasal region, in particular, although it is a

  4. Cryopreservation of human colorectal carcinomas prior to xenografting

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    Krohn Mathias

    2010-07-01

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

  5. Galectin-3 expression in human papillary thyroid carcinoma.

    Science.gov (United States)

    Sawangareetrakul, Phannee; Srisomsap, Chantragan; Chokchaichamnankit, Daranee; Svasti, Jisnuson

    2008-01-01

    Previous studies have suggested that galectin-3 expression was markedly elevated in papillary thyroid carcinoma compared to other thyroid diseases. In order to better understand this protein, galectin-3 from papillary thyroid carcinoma was partially purified by affinity chromatography on lactose-agarose. Proteins eluted from the column were separated by SDS-PAGE, and galectin-3 was detected with antibodies against the N-terminus and C-terminus of galectin-3. Some protein bands from the lactose binding fraction were also selected for identification by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Seven protein bands, with molecular weights ranging from 16 kDa to 31 kDa, were identified as galectin-3. The antibody raised against the C-terminus of galectin-3 gave a strong band for one of the bands detected by the N-terminal antibody and weak bands for the other three. One additional dark immunoreactive band with an approximate molecular weight of 20 kDa, was also detected by the C-terminal galectin-3 antibody. To determine the structural differences of each protein band, N-terminal amino acid sequencing of the seven protein bands was conducted. The three upper bands were N-terminally blocked, while the other bands had N-terminal amino acid sequences starting at positions Gly35, Gly65 (2 bands) and Ala100, respectively. Further studies are necessary to determine whether these are due to nonspecific proteolysis or post-translation modification.

  6. Squamous cell carcinoma antigen in human liver carcinogenesis.

    Science.gov (United States)

    Guido, M; Roskams, T; Pontisso, P; Fassan, M; Thung, S N; Giacomelli, L; Sergio, A; Farinati, F; Cillo, U; Rugge, M

    2008-04-01

    Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor that can be overexpressed in hepatocellular carcinoma (HCC) at both molecular and protein level, but no data are available on its expression in pre-malignant stages. To assess SCCA expression by immunohistochemistry in HCC and its nodular precursors in cirrhotic livers. 55 nodules from 42 explanted livers were evaluated: 7 large regenerative nodules (LRNs), 7 low-grade dysplastic nodules (LG-DNs), 10 high-grade DNs (HG-DNs), and 31 HCC. SCCA expression was semiquantitatively scored on a four-tiered scale. SCCA hepatocyte immunostaining was always restricted to the cytoplasm, mainly exhibiting a granular pattern. Stain intensity varied, ranging from weak to very strong. Within the nodules, positive cells were unevenly distributed, either scattered or in irregular clusters. The prevalence of SCCA expression was 29% in LRNs, 100% in DNs and 93% in HCC. A significant difference emerged in both prevalence and score for LRNs versus LG-DNs (pHCC (p = 0.000). A barely significant difference (p = 0.49) was observed between LG-DNs and HG-DNs, while no difference in SCCA expression was detected between HG-DNs and HCC. Cirrhotic tissue adjacent to the nodules was positive in 96% of cases, with a significant difference in the score (p = 0.000) between hepatocytes adjacent to HCC and those surrounding LRNs. This study provides the first evidence that aberrant SCCA expression is an early event in liver cell carcinomatous transformation.

  7. Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Yingjian Liang

    Full Text Available Diphenyl difluoroketone (EF24, a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G(2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB pathway and the NF-κB-regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma.

  8. Endoplasmic reticulum stress mediates the arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Zhang, Xin-Yu; Yang, Shu-Meng; Zhang, Hao-Peng; Yang, Yue; Sun, Shi-Bo; Chang, Jian-Ping; Tao, Xuan-Chen; Yang, Tuo-Yun; Liu, Chun; Yang, Yan-Mei

    2015-11-01

    Arsenic trioxide has been proven to trigger apoptosis in human hepatocellular carcinoma cells. Endoplasmic reticulum stress has been known to be involved in apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein. However, it is unknown whether endoplasmic reticulum stress mediates arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Our data showed that arsenic trioxide significantly induced apoptosis in human hepatocellular carcinoma cells. Furthermore, arsenic trioxide triggered endoplasmic reticulum stress, as indicated by endoplasmic reticulum dilation, upregulation of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein. We further found that 4-phenylbutyric acid, an inhibitor of endoplasmic reticulum stress, alleviated arsenic trioxide-induced expression of CCAAT/enhancer-binding protein homologous protein. More important, knockdown of CCAAT/enhancer-binding protein homologous protein by siRNA or inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid alleviated apoptosis induced by arsenic trioxide. Consequently, our results suggested that arsenic trioxide could induce endoplasmic reticulum stress-mediated apoptosis in hepatocellular carcinoma cells, and that CCAAT/enhancer-binding protein homologous protein might play an important role in this process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Synergistic anti-tumor effect of KLF4 and curcumin in human gastric carcinoma cell line.

    Science.gov (United States)

    Ji, Jun; Wang, He-Shuang; Gao, Yan-Yan; Sang, Li-Min; Zhang, Li

    2014-01-01

    Kruppel-like factor 4 is a transcription factor which plays an important role in development and progression of various carcinomas. Curcumin characterized by excellent anti-cancer properties is regarded as a serviceable natural compound used in carcinoma therapy. This study aimed at exploring the impact of KLF4 overexpression in cooperation with curcumin on the proliferation, apoptosis and invasion of human gastric carcinoma BGC- 823 cells. Flow cytometry analysis, CCK-8 assays, transwell assays and Western blot results showed that KLF4 overexpression combined with curcumin had significant anti-proliferation, pro-apoptosis and anti-invasion effects on BGC-823 cells. We also found that KLF4 had synergistic effects with curcumin, better promoting apoptosis and inhibiting proliferation and invasion of gastric carcinona cells. These results indicate that KLF4 could be used as a potential therapeutic target; curcumin could act as an auxiliary and provide a promising therapeutic strategy in stomach cancer.

  10. The Prevalence of Human Papilloma Virus in Esophageal Squamous Cell Carcinoma

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    Sadat Noori

    2012-06-01

    Full Text Available Background: Carcinomas of esophagus, mostly squamous cell carcinomas, occur throughout the world. There are a number of suspected genetic or environmental etiologies. Human papilloma virus (HPV is said to be a major etiology in areas with high incidence of esophageal carcinoma, while it is hardly detectable in low incidence regions. This study was designed to evaluate the prevalence of HPV in esophageal squamous cell carcinoma (ESCC cases diagnosed in Pathology Department, Medical School, Shiraz University of Medical Sciences.Methods: DNA material for PCR amplification of HPV genome was extracted from formalin-fixed paraffin-embedded tissue blocks of 92 cases of ESCC, diagnosed during 20 years from 1982 to 2002. Polymerase chain reaction was performed for amplification and detection of common HPV and type specific HPV-16 and HPV-18 genomic sequences in the presence of positive control (HPV-18 and HPV positive biopsies of uterine exocervix and additional internal controls i.e. beta-globin and cytotoxic T lymphocyte antigen 4 (CTLA4.Result: Good amplification of positive control and internal controls was observed. However, no amplification of HPV genome was observed.Conclusion: There is no association between HPV infection and the development of esophageal squamous cell carcinoma in the cases evaluated.

  11. Plaque assay for human coronavirus NL63 using human colon carcinoma cells

    Directory of Open Access Journals (Sweden)

    Drosten Christian

    2008-11-01

    Full Text Available Abstract Background Coronaviruses cause a broad range of diseases in animals and humans. Human coronavirus (hCoV NL63 is associated with up to 10% of common colds. Viral plaque assays enable the characterization of virus infectivity and allow for purifying virus stock solutions. They are essential for drug screening. Hitherto used cell cultures for hCoV-NL63 show low levels of virus replication and weak and diffuse cytopathogenic effects. It has not yet been possible to establish practicable plaque assays for this important human pathogen. Results 12 different cell cultures were tested for susceptibility to hCoV-NL63 infection. Human colon carcinoma cells (CaCo-2 replicated virus more than 100 fold more efficiently than commonly used African green monkey kidney cells (LLC-MK2. CaCo-2 cells showed cytopathogenic effects 4 days post infection. Avicel, agarose and carboxymethyl-cellulose overlays proved suitable for plaque assays. Best results were achieved with Avicel, which produced large and clear plaques from the 4th day of infection. The utility of plaque assays with agrose overlay was demonstrated for purifying virus, thereby increasing viral infectivity by 1 log 10 PFU/mL. Conclusion CaCo-2 cells support hCoV-NL63 better than LLC-MK2 cells and enable cytopathogenic plaque assays. Avicel overlay is favourable for plaque quantification, and agarose overlay is preferred for plaque purification. HCoV-NL63 virus stock of increased infectivity will be beneficial in antiviral screening, animal modelling of disease, and other experimental tasks.

  12. Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

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    Cheng-Yuan Wang

    2010-02-01

    Full Text Available Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1 to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.

  13. Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells

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    Alarifi S

    2013-02-01

    Full Text Available Saud Alarifi,1 Daoud Ali,1 Saad Alkahtani,1 Maqsood A Siddiqui,2 Bahy A Ali2,31Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 2DNA Research Chair, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 3Genetic Engineering & Biotechnology Research Institute City for Scientific Research and Technology Applications, Alexandria, EgyptBackground: Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells.Methods and results: A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl-2, 5-diphenyl tetrazolium bromide and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01 reduction in glutathione (15.67% and 26.52%, with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01, superoxide dismutase (76.42% and 81.09%; P < 0.01, catalase (73.33% and 76.47%; P < 0.01, and reactive oxygen species generation (44.04% and 56.14%; P < 0.01 after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01 induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide.Conclusion: The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.Keywords: arsenic trioxide, DNA damage, hepatocellular carcinoma

  14. Human papillomavirus in oral cavity and oropharynx carcinomas in the central region of Brazil.

    Science.gov (United States)

    Petito, Guilherme; Carneiro, Megmar Aparecida Dos Santos; Santos, Sílvia Helena de Rabello; Silva, Antonio Marcio Teodoro Cordeiro; Alencar, Rita de Cassia; Gontijo, Antonio Paulo; Saddi, Vera Aparecida

    Molecular studies about carcinomas of the oral cavity and oropharynx demonstrate the presence of human papilomavirus genome in these tumors, reinforcing the participation of human papilomavirus in oral carcinogenesis. This study aimed to determine the prevalence of human papilomavirus and genotype distribution of HPV16 and HPV18 in oral cavity and oropharynx carcinomas, as well as their association with clinical characteristics of the tumors. This is a retrospective study, with clinical data collected from 82 patients. Human papilomavirus detection was conducted on specimens of oral cavity and oropharynx carcinomas included in paraffin blocks. Patients were assisted in a cancer reference center, in the central region of Brazil, between 2005 and 2007. Polymerase chain reaction was used for the detection and genotyping of human papilomavirus. Among the patients evaluated, 78% were male. The average age of the group was about 58 years. Risk factors, such as smoking (78%) and alcohol consumption (70.8%) were recorded for the group. HPV DNA was detected in 21 cases (25.6%; 95% confidence interval 16.9-36.6) of which 33.3% were HPV16 and 14.3% were HPV18. The presence of lymph node metastases and registered deaths were less frequent in human papilomavirus positive tumors, suggesting a better prognosis for these cases; however, the differences between the groups were not statistically significant. The results obtained in the present study, with respect to the presence of the high-risk HPV16 and HPV18 genotypes, highlight the importance of human papilomavirus vaccination in the control of oral cavity and oropharynx carcinomas. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  15. Human papillomavirus in oral cavity and oropharynx carcinomas in the central region of Brazil

    Directory of Open Access Journals (Sweden)

    Guilherme Petito

    Full Text Available Abstract Introduction Molecular studies about carcinomas of the oral cavity and oropharynx demonstrate the presence of human papilomavirus genome in these tumors, reinforcing the participation of human papilomavirus in oral carcinogenesis. Objectives This study aimed to determine the prevalence of human papilomavirus and genotype distribution of HPV16 and HPV18 in oral cavity and oropharynx carcinomas, as well as their association with clinical characteristics of the tumors. Methods This is a retrospective study, with clinical data collected from 82 patients. Human papilomavirus detection was conducted on specimens of oral cavity and oropharynx carcinomas included in paraffin blocks. Patients were assisted in a cancer reference center, in the central region of Brazil, between 2005 and 2007. Polymerase chain reaction was used for the detection and genotyping of human papilomavirus. Results Among the patients evaluated, 78% were male. The average age of the group was about 58 years. Risk factors, such as smoking (78% and alcohol consumption (70.8% were recorded for the group. HPV DNA was detected in 21 cases (25.6%; 95% confidence interval 16.9–36.6 of which 33.3% were HPV16 and 14.3% were HPV18. The presence of lymph node metastases and registered deaths were less frequent in human papilomavirus positive tumors, suggesting a better prognosis for these cases; however, the differences between the groups were not statistically significant. Conclusion The results obtained in the present study, with respect to the presence of the high-risk HPV16 and HPV18 genotypes, highlight the importance of human papilomavirus vaccination in the control of oral cavity and oropharynx carcinomas.

  16. Cilia-mediated Hedgehog signaling controls form and function in the mammalian larynx.

    Science.gov (United States)

    Tabler, Jacqueline M; Rigney, Maggie M; Berman, Gordon J; Gopalakrishnan, Swetha; Heude, Eglantine; Al-Lami, Hadeel Adel; Yannakoudakis, Basil Z; Fitch, Rebecca D; Carter, Christopher; Vokes, Steven; Liu, Karen J; Tajbakhsh, Shahragim; Egnor, Se Roian; Wallingford, John B

    2017-02-13

    Acoustic communication is fundamental to social interactions among animals, including humans. In fact, deficits in voice impair the quality of life for a large and diverse population of patients. Understanding the molecular genetic mechanisms of development and function in the vocal apparatus is thus an important challenge with relevance both to the basic biology of animal communication and to biomedicine. However, surprisingly little is known about the developmental biology of the mammalian larynx. Here, we used genetic fate mapping to chart the embryological origins of the tissues in the mouse larynx, and we describe the developmental etiology of laryngeal defects in mice with disruptions in cilia-mediated Hedgehog signaling. In addition, we show that mild laryngeal defects correlate with changes in the acoustic structure of vocalizations. Together, these data provide key new insights into the molecular genetics of form and function in the mammalian vocal apparatus.

  17. Surgical anatomy of the supraglottic larynx using the da Vinci robot.

    Science.gov (United States)

    Goyal, Neerav; Yoo, Frederick; Setabutr, Dhave; Goldenberg, David

    2014-08-01

    Transoral robotic surgery (TORS) has facilitated organ-preserving surgery of the larynx. It has also presented a change in the surgical perspective. We performed cadaveric dissections using the robot to highlight the vascular and muscular anatomy of the supraglottic larynx. Cadaveric specimens underwent injection of their vasculature, and after injection a robotic surgical system was used to perform a transoral dissection of the supraglottic region. Care was taken to preserve anatomic landmarks and microvascular structures. Five fresh frozen cadaveric human heads were injected with silicone and used for the dissection. The superior laryngeal neurovascular bundle was identified and an absent superior laryngeal vein (SLV) was noted on 1 specimen. Using the robotic endoscope allowed us to visualize and identify the microvasculature of the head and neck. These dissections revealed anatomic variations in the superior laryngeal neurovascular bundle and also highlighted the differences in view using a surgical robotic system. Copyright © 2013 Wiley Periodicals, Inc.

  18. [Vitamin D metabolism and signaling in human hepatocellular carcinoma and surrounding non-tumorous liver].

    Science.gov (United States)

    Horváth, Evelin; Balla, Bernadett; Kósa, János; Lakatos, Péter András; Lazáry, Áron; Németh, Dániel; Jozilan, Hasan; Somorácz, Áron; Korompay, Anna; Gyöngyösi, Benedek; Borka, Katalin; Kiss, András; Kupcsulik, Péter; Schaff, Zsuzsa; Szalay, Ferenc

    2016-11-01

    1,25-Dihydroxy vitamin D 3 mediates antitumor effects in hepatocellular carcinoma. We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D 3 -inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry. Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (pexpressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis. The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D 3 , providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.

  19. 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

  20. Expression Patterns of Glucose Transporter-1 Gene and Thyroid Specific Genes in Human Papillary Thyroid Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sungeun; Chung, Junekey; Min Haesook and others

    2014-06-15

    The expression of glucose transporter-1 (Glut-1) gene and those of major thyroid-specific genes were examined in papillary carcinoma tissues, and the expressions of these genes were compared with cancer differentiation grades. Twenty-four human papillary carcinoma tissues were included in this study. The expressions of Glut-1- and thyroid-specific genes [sodium/iodide symporter (NIS), thyroid peroxidase, thyroglobulin, TSH receptor and pendrin] were analyzed by RT-PCR. Expression levels were expressed as ratios versus the expression of beta-actin. Pathologic differentiation of papillary carcinoma was classified into a relatively well-differentiated group (n=13) and relatively less differentiated group (n=11). Glut-1 gene expression was significantly higher in the less differentiated group (0.66±0.04) than in the well-differentiated group (0.59±0.07). The expression levels of the NIS, PD and TG genes were significantly higher in the well-differentiated group (NIS: 0.67±0.20, PD: 0.65±0.21, TG: 0.74±0.16) than in the less differentiated group (NIS: 0.36±0.05, PD: 0.49±0.08, TG: 0.60±0.11), respectively. A significant negative correlation was found between Glut-1 and NIS expression, and positive correlations were found between NIS and TG, and between NIS and PD. The NIS, PD and TG genes were highly expressed in well-differentiated thyroid carcinomas, whereas the Glut-1 gene was highly expressed in less differentiated thyroid carcinomas. These findings provide a molecular rationale for the management of papillary carcinoma, especially in the selection of FDG PET or radioiodine whole-body scan and I-131-based therapy.

  1. Automatic segmentation of equine larynx for diagnosis of laryngeal hemiplegia

    Science.gov (United States)

    Salehin, Md. Musfequs; Zheng, Lihong; Gao, Junbin

    2013-10-01

    This paper presents an automatic segmentation method for delineation of the clinically significant contours of the equine larynx from an endoscopic image. These contours are used to diagnose the most common disease of horse larynx laryngeal hemiplegia. In this study, hierarchal structured contour map is obtained by the state-of-the-art segmentation algorithm, gPb-OWT-UCM. The conic-shaped outer boundary of equine larynx is extracted based on Pascal's theorem. Lastly, Hough Transformation method is applied to detect lines related to the edges of vocal folds. The experimental results show that the proposed approach has better performance in extracting the targeted contours of equine larynx than the results of using only the gPb-OWT-UCM method.

  2. Differential Diagnosis in Neuroendocrine Neoplasms of the Larynx

    NARCIS (Netherlands)

    Hunt, Jennifer L; Ferlito, Alfio; Hellquist, Henrik; Rinaldo, Alessandra; Skálová, Alena; Slootweg, Pieter J; Willems, Stefan M; Cardesa, Antonio

    2017-01-01

    The differential diagnosis of neuroendocrine neoplasms of the larynx is broad and includes lesions of epithelial, mesenchymal, and neuroectodermal origin. These lesions have overlapping clinical and pathologic aspects and must be carefully considered in the differential diagnosis of laryngeal

  3. Preservation of the Larynx in Laryngeal and Hypopharyngeal Cancer

    NARCIS (Netherlands)

    A. Sewnaik (Aniel)

    2006-01-01

    textabstractIn the last decade the primary treatment of laryngeal and hypopharyngeal cancer was shifted towards organ preservation, i.e. preservation of the larynx. The treatment of laryngeal cancer was changed from standard radiotherapy towards hyperfractionated radiotherapy. Hypopharyngeal

  4. Cyclic AMP phosphodiesterase activity in human gingival carcinoma.

    Science.gov (United States)

    Spoto, Giuseppe; Fioroni, Massimiliano; Rubini, Corrado; Di Nicola, Maurizio; Di Pietrantonio, Francesco; Di Matteo, Elisabetta; Piattelli, Adriano

    2004-05-01

    The phosphodiesterases (PDEs) are responsible for the hydrolysis of the second messengers, cyclic AMP (cAMP) and cyclic GMP (cGMP), to their corresponding monophosphates with a fundamental role in the transduction of the intracellular signals. At least 11 different enzymatic isoforms have been identified, which are listed according to their specificity or affinity for the substratum, identity of the amino acid sequence, cofactor, and inhibitor sensitivity. Variations in PDE activity have been found in different pathologies, and they have also been correlated to different pathological e/o physiological mechanisms, such as cellular differentiation, apoptosis, and tumor invasivity. In this study, we have evaluated cAMP PDE activity in patients with carcinoma of the gingiva, with the purpose of correlating differences in its development and progression. The same enzymatic activity has been used to evaluate differences between patients with lymph node involvement (group N(+)), and patients without lymph node involvement (N(-)). The analysis of PDE activity and the cAMP assay was performed by reverse-phase HPLC on samples of fresh or frozen gingival tissues. Analysis of cAMP was confirmed with the enzyme-linked immunoabsorption assay (EIA). The differences between control and N(-) groups (P = 0.0433), and between control and N(+) groups (P = 0.0156) were statistically significant. PDE3A was also evaluated immunohistochemically in lymph-node negative and lymph-node positive cases. The differences between the two groups were statistically significant (P = 0.0397).

  5. Characterization of a human ovarian carcinoma cell line: UCI 101.

    Science.gov (United States)

    Fuchtner, C; Emma, D A; Manetta, A; Gamboa, G; Bernstein, R; Liao, S Y

    1993-02-01

    A new epithelial ovarian carcinoma cell line (UCI 101) has been established from the ascitic fluids and solid tumor of a patient with progressive papillary adenocarcinoma of the ovary shown previously to be refractory to combination chemotherapy consisting of cyclophosphamide, Adriamycin, and cisplatin as well as single-agent chemotherapy of taxol and high-dose cisplatin. The UCI 101 cell line grows well with an in vitro doubling time of 24 hr. The cell line expresses the B 72.3 (Tag 72), CA125, MH99 (ESA), and E29 (EMA) cell surface antigens and AE1/AE3 cytokeratins. This cell line overexpresses (as determined by immunocytochemistry) both p-glycoprotein and the epidermal growth factor receptor. The in vitro drug response to single agents including Adriamycin, cisplatin, dequalinium chloride, etoposide, 5-fluorouracil, taxol, and tumor necrosis factor was examined. Intraperitoneal transplantation of the cells into athymic mice resulted in foci of tumor on all peritoneal surfaces including the viscera and diaphragm ultimately leading to solid bulky disease with massive production of ascites. High levels of CA125 (> 500 units/ml) were detected in the serum of tumor-bearing mice. Cytogenetic analysis of cultured cells shows several marker chromosomes containing deletions, duplications, and translocations. Cytologic and histologic evaluation of the xenograft revealed morphological characteristics identical to those of the original tumor.

  6. Human papillomavirus (HPV) in vulvar dysplasia and carcinoma in situ

    DEFF Research Database (Denmark)

    Junge, Jette; Poulsen, H; Horn, T

    1995-01-01

    whereas no case of pure basaloid type was found. Various combinations of warty and basaloid types were shown in 52 cases and mixed forms in 7 cases. The results indicate that pure forms of warty and basaloid types probably do not exist. HPV DNA was detected by PCR in 51/58 cases (88%) (45 with HPV type 16...... and 6 with HPV type 33) evenly distributed in all age groups and in all types of lesions (WHO and Toki et al. 1991). By ISH HPV was detected in 24/62 cases (39%) (21 with HPV type 16/18 and 3 with HPV type 31/33), nearly always in warty areas. All these cases were positive for the same virus type by PCR....... No case revealed more than one type of HPV. HPV type 6, 11, 18, and 31 were not detected by PCR. The results indicate a correlation between HPV type 16 and 33 and dysplasia/carcinoma in situ in the vulva....

  7. Antiproliferative and apoptotic effect of Pleurotus ostreatus on human mammary carcinoma cell line (michigan cancer foundation-7

    Directory of Open Access Journals (Sweden)

    Krishnamoorthy Deepalakshmi

    2016-01-01

    Conclusion: The study demonstrates a potent anticancer property of P. ostreatus against human mammary carcinoma cells which might be of value in nutraceutical industry. Further investigations are essential to establish it as a treatment against breast cancer.

  8. THE RELATIONSHIP BETWEEN HUMAN PAPILLOMA VIRUSES AND CERVICAL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Eduard Crauciuc

    2013-11-01

    Full Text Available Cervical carcinoma with squamous cells has many of the characteristics of avenereal disease: high incidence (over 500.000 cases every year, an increased frequency for the women with multiple sex partners and the presence of one of the papillomavirus genotypes with a high carcinogenic risk (HPV 16, 18, 31 and 45 in 100% of the cases. Material and methods.In the period of time 2001-2012, in the Department of Obstetrics and Gynecology belonging to “Sf. Apostol Andrei” Emergency Hospital in Galaţi, 5047 women were hospitalized under the suspicion of having cervical neoplasia.As part of the screening programme, the women belonging to the high risk group are tested for HPV by using Hybrid Capture 2 (HC2.Results and discussions.The seropositive women’s risk of having a persistent HPV infection is 7 times higher than in the case of the seronegative ones, with the same age. This risk is double for the women with CD4 lymphocytes below 200/mmc.Infection with cancer-causing HPV types is limited to the epithelium of the uterine exocervix and it does not spread to other parts of the body. Conclusions. Cervical cancer is caused by the oncogenic types of HPV, types 16 and 18 being responsible for over 70% of the cases. It represents the second cause of mortality by cancer for the women between 15 and 44 years old. Anti-HPV vaccination comes as a partner of the screening programmes aiming to reduce the incidence and mortality by cervical cancer.

  9. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP.

    OpenAIRE

    Bang, Y J; Pirnia, F; Fang, W G; Kang, W K; Sartor, O; Whitesell, L; Ha, M J; Tsokos, M.; Sheahan, M D; Nguyen, P.

    1994-01-01

    Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analog...

  10. Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular carcinoma cell line.

    Science.gov (United States)

    Ruffa, M J; Ferraro, G; Wagner, M L; Calcagno, M L; Campos, R H; Cavallaro, L

    2002-03-01

    Methanolic extracts from Achyrocline satureioides (Dc.) Lam, Aristolochia macroura Gomez, Lithraea molleoides (Vell.) Engl., Schinus molle L., unlike those from Celtis spinosa Spreng, Chenopodium ambrosioides L., Petiveria alliacea L., and Plantago major L. showed cytotoxic activity against a human hepatocellular carcinoma cell line, Hep G2. Schinus molle L. was the most active (IC50=50+/-7 microg/ml). These results call for further studies of these extracts.

  11. Growth arrest and apoptosis of human hepatocellular carcinoma cells induced by hexamethylene bisacetamide

    Science.gov (United States)

    Ouyang, Gao-Liang; Cai, Qiu-Feng; Liu, Min; Chen, Rui-Chuan; Huang, Zhi; Jiang, Rui-Sheng; Chen, Fu; Hong, Shui-Gen; Bao, Shi-Deng

    2004-01-01

    AIM: To investigate the cellular effects of hybrid polar compound hexamethylene bisacetamide (HMBA) on the growth and apoptosis of human hepatocellular carcinoma cells and to provide the molecular mechanism for potential application of HMBA in the treatment of liver cancer. METHODS: Effects of HMBA on the growth of human hepatocellular carcinoma SMMC-7721 cells were assayed by MTT chronometry. Apoptosis induced by HMBA was detected by phase-contrast microscopy, flow cytometry, propidium iodide staining and immunocytochemical analysis. RESULTS: The growth of SMMC-7721 cells was significantly inhibited by HMBA, and the growth inhibitory rate was 51.1%, 62.6%, 68.7% and 73.9% respectively after treatment with 5.0, 7.5, 10.0 and 12.5 mmol/L of HMBA. In the cells treated with 10 mmol/L of HMBA for 72 h, the population of cells at sub-G1 phase significantly increased, and the apoptotic bodies and condensed nuclei were detected. Moreover, treatment of SMMC-7721 cells with 10 mmol/L of HMBA down-regulated the expression of Bcl-2 anti-apoptotic protein, while slightly up-regulated the level of pro-apoptotic protein Bax. CONCLUSION: Treatment with 10.0 mmol/L of HMBA can significantly inhibit the growth and induce apoptosis of human hepatocellular carcinoma SMMC-7721 cells by decreasing the ratio of Bcl-2 to Bax. PMID:15052673

  12. [Effects of matrine on proliferation and apoptosis of human renal cell carcinoma cell line GRC-1].

    Science.gov (United States)

    Chong, Tie; Niu, Jian-Qiang; Wang, Zi-Ming; She, Jun-Jun; Huang, Chen

    2006-07-01

    To observe the effects of matrine on proliferation and apoptosis of human renal cell carcinoma cell line GRC-1 in vitro, and to explore its mechanism. The human renal cell carcinoma cell line GRC-1 was treated with matrine of different concentrations for 24, 48, 72 and 96 h respectively. The MTT assay was used to evaluate the cytotoxic effects of matrine on GRC-1 cells. The transmission electron microscope and flow cytometry were utilized to observe and detect the apoptosis of GRC-1 cells induced by matrine. The expression levels of Bcl-2 and Bax proteins were evaluated by streptavidin-biotin-peroxidase method. The matrine of different concentrations all have cytotoxic effects on GRC-1 cells, with obvious dose- and time-dependent effects. The apoptosis induced by matrine was confirmed in GRC-1 cells. With intervention of matrine (1.5 g/L) for 12 h, the expression level of Bcl-2 in GRC-1 cells was decreased while the expression level of Bax was increased as compared with those in the untreated group. The proliferation-inhibiting effects of matrine on human renal cell carcinoma cell line GRC-1 may be related to down-regulating the ratio of Bcl-2/Bax protein expression and promoting the apoptosis.

  13. Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients.

    Science.gov (United States)

    Werner-Klein, Melanie; Proske, Judith; Werno, Christian; Schneider, Katharina; Hofmann, Hans-Stefan; Rack, Brigitte; Buchholz, Stefan; Ganzer, Roman; Blana, Andreas; Seelbach-Göbel, Birgit; Nitsche, Ulrich; Männel, Daniela N; Klein, Christoph A

    2014-01-01

    Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.

  14. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Magaldi, Thomas G.; Almstead, Laura L. [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Bellone, Stefania [Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063 (United States); Prevatt, Edward G. [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Santin, Alessandro D. [Department of Obstetrics and Gynecology and Reproductive Sciences, Yale School of Medicine, P.O. Box 208063, New Haven, CT 06520-8063 (United States); Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028 (United States); DiMaio, Daniel, E-mail: daniel.dimaio@yale.edu [Department of Genetics, Yale School of Medicine, P.O. Box 208005, New Haven, CT 06520-8005 (United States); Department of Therapeutic Radiology, Yale School of Medicine, P.O. Box 208040, New Haven, CT 06520-8040 (United States); Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, P.O. Box 208024 (United States); Yale Comprehensive Cancer Center, P.O. Box 208028, New Haven, CT 06520-8028 (United States)

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  15. Leprosy of the Larynx: A Case Report

    Directory of Open Access Journals (Sweden)

    Mansoureh Momen Heravi

    2009-12-01

    Full Text Available Leprosy is an ancient deforming disease caused by Mycobacterium leprae, which is still poorly understood and often feared by the general public and even by some in the health care professions Fortunately, the outlook for patients has dramatically improved over the last three decades with the introduction of multi-drug treatment and management strategies that have somewhat diminished the stigma of this diagnosis. We report a rare case of leprosy of larynx. A 45 year old man presented with complaints cough, dyspnea and hoarseness since many years ago. Because of demonstration of acid fast bacilli in smear of his sputum, the diagnosis of tuberculosis was made and anti tuberculosis treatment was initiated. But he developed fever and his symptoms exacerbated. In examination there was a tender erythematous nodule on right supraclavicular region, loss of eyebrows and lashes and disseminated hyper and hypo pigmented cutaneous lesions on abdomen, thorax, back with normal chest x ray. Laryngoscopy to rule out laryngeal tuberculosis was done and granulomatous lesion was seen. Laryngeal and skin biopsy was performed which numerous acid fast bacilli, macrophages and foamy cells suggestive of lepromatous leprosy were demonstrated in both specimens. Treatment was started on multi bacillary regime of WHO multidrug therapy. In conclusion, this report highlights the importance of systemic involvement in lepromatous leprosy especially when the initial presentation is laryngitis or respiratory symptoms. Laryngeal leprosy may mistaken with tuberculosis laryngitis due to respiratory problems and existence of acid fast bacilli in respiratory secretions.

  16. Magnetic resonance imaging of the larynx; Resonancia magnetica de la laringe

    Energy Technology Data Exchange (ETDEWEB)

    Oleaga, L. [Hospital de Basurto. Bilbao (Spain)

    2001-07-01

    Larynx and hypopharynx represent difficult anatomical structures to evaluate by imaging. Pathological processes inflammatory conditions and neoplasms are frequently found specially neoplasms. The most common tumor originating in this region is squamous cell carcinoma that represents 90%, of malignancies, magnetic Resonance Imaging (MRI) is used for staging of those tumors. In our study we evaluate the technique used for MRI studies as well as the anatomy of the larynx, hypopharynx and nodes and the different classification system used for neck nodes. We also analyze the different types of neoplasm that can be found being and malignant and the use of MRI for staging neoplasms. Clinical and laryngoscope staging of laryngeal tumors is not accurate if fails to demonstrate deep submucosal and laryngeal spaces invasion (pre-epi glottic. para laryngeal, para glottic, anterior commissures posterior commissure and sub glottis) as well as cartilage infiltration and extra laryngeal extension. We need accurate imaging diagnostic methods like MRI to evaluate the extension of tumors. (Author) 38 refs.

  17. CHD1L Protein is overexpressed in human ovarian carcinomas and is a novel predictive biomarker for patients survival

    Directory of Open Access Journals (Sweden)

    He Wei-Peng

    2012-09-01

    Full Text Available Abstract Background Our recent studies suggested that the chromodomain helicase DNA binding protein 1-like (CHD1L gene plays an oncogenic role in human hepatocellular carcinoma. However, the status of CHD1L protein expression in ovarian cancer and its clinical/prognostic significance are obscure. Methods In this study, immunohistochemistry (IHC for CHD1L was performed on a tissue microarray (TMA containing 102 primary ovarian carcinomas and 44 metastatic lesions (omental metastasis. Receiver-operator curve (ROC analysis was used to evaluate patients’ survival status. Results There is an augmented tendency of CHD1L expression in ovarian carcinoma metastasis than in primary lesions (PP PP Conclusions These findings provide evidence that positive expression of CHD1L protein is significantly correlated with the metastasis proceeding of ovarian carcinoma, and CHD1L protein expression, as examined by IHC, may act as a novel prognostic biomarker for patients with ovarian carcinoma.

  18. Hybrid verrucous-squamous cell carcinoma of the ovary with synchronous squamous cell carcinoma of the endometrium.

    Science.gov (United States)

    Fancher, Tiffany T; Hamzi, Munir H; Macaron, Shady H; Magno, Winston B; Dudrick, Stanley J; Palesty, J Alexander

    2008-01-01

    Verrucous carcinoma, a variant of well-differentiated squamous cell carcinoma, is usually described in the literature as arising in the oral cavity, skin, and larynx. The reports on verrucous carcinoma arising in the genital tract, usually originating in the vagina, vulva, or uterine cervix, are few. Verrucous carcinoma arising in the ovary has not been previously reported. In this article, a unique hybrid carcinoma, a large aggressive verrucous carcinoma in combination with squamous carcinoma of the left ovary and synchronously occurring with a squamous cell carcinoma in the endometrium, is presented. This unique case of a hybrid carcinoma includes the first-known case of this type of carcinoma involving the ovary. The negative cervical evaluation findings, together with the histologic patterns of the tumors in the uterus and the ovary, support the conclusion that these 2 carcinomas are synchronous, one arising in the left ovary and the other arising in the uterus.

  19. Morphological changes in the enteric nervous system caused by carcinoma of the human large intestine.

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    Janusz Godlewski

    2010-06-01

    Full Text Available The innervations of the large intestine is responsible for it peristalsis and contractibility. Investigations of the enteric nervous system in many colon diseases have revealed changes in this structure. No study has been carried out on morphological changes of the enteric nervous system in the human large intestine with carcinoma. The aim of this study was to investigate potential changes in the structure of the enteric neurons in patients with sigmoid and rectal cancer. Material for the study was obtained from patients undergoing operations due to carcinoma of the sigmoid colon and rectum. Microscopic observation of the cancerous tumor of the human large intestine revealed changes in the enteric nervous system innervating this part of the gastrointestinal tract. In the region of the enteric plexuses located close to the tumour, disruption of their correct placement and structure was observed. The changes also consisted of the disappearance of neurons and nerve fibers forming these plexuses. In the solid cancerous tumour, elements of the enteric nervous system were not present. Destruction of the enteric nervous system in the course of carcinoma of the large intestine may cause disruption of proper intestinal function and may be responsible for part of symptoms which the patients suffer.

  20. 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.

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

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

    2012-02-03

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

  2. Cytotoxicity of Thymus vulgaris essential oil towards human oral cavity squamous cell carcinoma.

    Science.gov (United States)

    Sertel, Serkan; Eichhorn, Tolga; Plinkert, Peter K; Efferth, Thomas

    2011-01-01

    Oral cavity squamous cell carcinoma (OCSCC) accounts for 2% to 3% of all malignancies and has a high mortality rate. The majority of anticancer drugs are of natural origin. However, it is unknown whether the medicinal plant Thymus vulgaris L. (thyme) is cytotoxic towards head and neck squamous cell carcinoma (HNSCC). Cytotoxicity of thyme essential oil was investigated on the HNSCC cell line, UMSCC1. The IC₅₀ of thyme essential oil extract was 369 μg/ml. Moreover, we performed pharmacogenomics analyses. Genes involved in the cell cycle, cell death and cancer were involved in the cytotoxic activity of thyme essential oil at the transcriptional level. The three most significantly regulated pathways by thyme essential oil were interferon signaling, N-glycan biosynthesis and extracellular signal-regulated kinase 5 (ERK5) signaling. Thyme essential oil inhibits human HNSCC cell growth. Based on pharmacogenomic approaches, novel insights into the molecular mode of anticancer activity of thyme are presented.

  3. [A PTHrP-producing cell line derived from human small cell lung carcinoma].

    Science.gov (United States)

    Iguchi, H

    1996-03-01

    We established a cell line, designated MS-1, from pleural effusion of a 54-yrs-old male patient with small cell lung carcinoma. MS-1 cells grew as a floating in RPMI-1640 medium supplemented with 10% FBS and the population doubling time was 45 hours. The chromosome number ranged from 49 to 52 and structural abnormalities of 1p+, 3q-, 6p-, 14p+ and 17p+ were observed in all the cells examined. MS-1 cells released PTHrP into the conditioned medium and heterogeneity of the PTHrP molecule produced in the cells was found in the gel permeation chromatography. Expression of the PTHrP gene as well as presence of the PTHrP protein in the cells were confirmed by reverse-transcriptase PCR(RT-PCR) and immunohistochemical staining. These findings indicate that MS-1 cells are derived from human small cell lung carcinoma, which produce PTHrP.

  4. Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas.

    Science.gov (United States)

    McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O; Hue, Yue; Ried, Thomas

    2017-03-01

    Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells. During this process, cells progress through stages of pre-immortalization, immortalization and, finally, transformation, and result in tumors when injected into immunocompromised mice. We analyzed our model for genome and transcriptome alterations using ArrayCGH, spectral karyotyping (SKY), and array based gene expression profiling. ArrayCGH revealed a recurrent pattern of genomic imbalances. These results were confirmed by SKY. Comparing these imbalances with orthologous maps of human chromosomes revealed a remarkable overlap. We observed focal deletions of the tumor suppressor genes Trp53 and Cdkn2a/p16. High-level focal genomic amplification included the locus harboring the oncogene Mdm2, which was confirmed by FISH in the form of double minute chromosomes. Array-based global gene expression revealed distinct differences between the sequential steps of spontaneous transformation. Gene expression changes showed significant similarities with human colorectal carcinomas. Pathways most prominently affected included genes involved in chromosomal instability and in epithelial to mesenchymal transition. Our novel mouse model therefore recapitulates the most prominent genome and transcriptome alterations in human colorectal cancer, and might serve as a valuable tool for understanding the dynamic process of tumorigenesis, and for preclinical drug testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Differential responses to x-irradiation of subpopulations of two heterogeneous human carcinomas in vitro

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    Leith, J.T.; Dexter, D.L.; DeWyngaert, J.K.; Zeman, E.M.; Chu, M.Y.; Calabresi, P.; Glicksman, A.S.

    1982-07-01

    The responses of two heterogeneous human cancer cell lines and their derivative clones to graded single doses of X-rays were examined in vitro. One system consisted of the human colon carcinoma line DLD-1 and two subpopulations (clones A and D). The second system consisted of the human lung carcinoma line (LX1) and four subpopulations (LX1-1, LX1-2, LX1-3, and LX1-9). These subpopulations have previously been shown to be markedly heterogeneous in terms of such characteristics as karyotype, morphology, drug sensitivity, tumorigenicity, and expression of membrane glycoproteins (such as carcinoembryonic antigen and tumor colonic mucoprotein antigen). Exponentially growing cultures were irradiated with graded single doses of 100-kVp X-rays. Survival was assessed using colony formation as the end point, and responses from multiple experiments were fitted to the single-hit, multitarget equation of cell survival. Values for the mean lethal dose (D0, grays), quasithreshold dose (Dq, grays), and extrapolation number (n) were obtained. For the human colon adenocarcinoma system, these values for the three tumor lines were: DLD-1, 0.95, 2.34, and 11.7; clone A, 1.06, 2.23 and 8.20; and clone D, 1.08, 1.89, and 5.80. For the human lung carcinoma system, these values for the five sublines were: LX1, 1.14, 0.19, and 1.20; LX1-1, 0.96, 2.06, and 8.54; LX1-2, 0.98, 0.88, and 2.48; LX1-3, 0.68, 2.05, and 20.3; and LX1-9, 1.12, 0.00, and 1.00. These two human tumor systems therefore exhibit variability in their intrinsic sensitivity to X-irradiation. The data indicate that failure of some human carcinomas to respond to physical treatment modalities can be due to preexisting resistant subpopulations.

  6. Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells.

    Science.gov (United States)

    Kang, Seo-Hee; Kim, Yon-Suk; Kim, Eun-Kyung; Hwang, Jin-Woo; Jeong, Jae-Hyun; Dong, Xin; Lee, Jae-Woong; Moon, Sang-Ho; Jeon, Byong-Tae; Park, Pyo-Jam

    2016-01-01

    Numerous plants have been documented to contain phenolic compounds. Thymol is one among these phenolic compounds that possess a repertoire of pharmacological activities, including anti-inflammatory, anticancer, antioxidant, antibacterial, and antimicrobial effects. Despite of the plethora of affects elicited by thymol, its activity profile on gastric cancer cells is not explored. In this study, we discovered that thymol exerts anticancer effects by suppressing cell growth, inducing apoptosis, producing intracellular reactive oxygen species, depolarizing mitochondrial membrane potential, and activating the proapoptotic mitochondrial proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in human gastric AGS cells. The outcomes of this study displayed that thymol, via an intrinsic mitochondrial pathway, was responsible for inducing apoptosis in gastric AGS cells. Hence, thymol might serve as a tentative agent in the future to treat cancer.

  7. Accelerated cellular senescence phenotype of GAPDH-depleted human lung carcinoma cells

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    Phadke, Manali; Krynetskaia, Natalia [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Mishra, Anurag [Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Krynetskiy, Evgeny, E-mail: ekrynets@temple.edu [Temple University School of Pharmacy, Philadelphia, PA 19140 (United States); Jayne Haines Center for Pharmacogenomics, Temple University School of Pharmacy, Philadelphia, PA 19140 (United States)

    2011-07-29

    Highlights: {yields} We examined the effect of glyceraldehyde 3-phosphate (GAPDH) depletion on proliferation of human carcinoma A549 cells. {yields} GAPDH depletion induces accelerated senescence in tumor cells via AMPK network, in the absence of DNA damage. {yields} Metabolic and genetic rescue experiments indicate that GAPDH has regulatory functions linking energy metabolism and cell cycle. {yields} Induction of senescence in LKB1-deficient lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation. -- Abstract: Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a pivotal glycolytic enzyme, and a signaling molecule which acts at the interface between stress factors and the cellular apoptotic machinery. Earlier, we found that knockdown of GAPDH in human carcinoma cell lines resulted in cell proliferation arrest and chemoresistance to S phase-specific cytotoxic agents. To elucidate the mechanism by which GAPDH depletion arrests cell proliferation, we examined the effect of GAPDH knockdown on human carcinoma cells A549. Our results show that GAPDH-depleted cells establish senescence phenotype, as revealed by proliferation arrest, changes in morphology, SA-{beta}-galactosidase staining, and more than 2-fold up-regulation of senescence-associated genes DEC1 and GLB1. Accelerated senescence following GAPDH depletion results from compromised glycolysis and energy crisis leading to the sustained AMPK activation via phosphorylation of {alpha} subunit at Thr172. Our findings demonstrate that GAPDH depletion switches human tumor cells to senescent phenotype via AMPK network, in the absence of DNA damage. Rescue experiments using metabolic and genetic models confirmed that GAPDH has important regulatory functions linking the energy metabolism and the cell cycle networks. Induction of senescence in LKB1-deficient non-small cell lung cancer cells via GAPDH depletion suggests a novel strategy to control tumor cell proliferation.

  8. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence

    Directory of Open Access Journals (Sweden)

    San-Yuan Chen

    2016-04-01

    Full Text Available Oral squamous cell carcinoma (OSCC, an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL, a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.

  9. High-risk human papillomavirus is transcriptionally active in a subset of sinonasal squamous cell carcinomas.

    Science.gov (United States)

    Larque, Ana B; Hakim, Sofia; Ordi, Jaume; Nadal, Alfons; Diaz, Alba; del Pino, Marta; Marimon, Lorena; Alobid, Isam; Cardesa, Antonio; Alos, Llucia

    2014-03-01

    It has been reported that high-risk human papillomavirus (HPV) is a causative agent of a subgroup of oropharyngeal carcinomas. In these tumors, the presence of the transcriptionally active HPV has been proved through the identification of HPV E6 or E7 messenger RNA (mRNA) transcripts. The aim of the study was to assess the HPV-active transcription in a series of sinonasal carcinomas, in correlation with the HPV DNA identification and the p16 immunohistochemistry. Seventy patients with squamous cell carcinomas of the sinonasal tract were included in the survey. The main clinicopathological characteristics were recorded. All tumors were investigated for HPV through the HPV DNA detection by PCR, using the SPF10 primers and by in situ hybridization, using the high-risk GenPoint probe (Dako, Glostrup, Denmark). HPV16 E7 mRNA transcripts detection was performed by RT-PCR in 27 cases. The immunostaining for p16 was performed in all cases. Fourteen carcinomas (20%) were positive for high-risk HPV by PCR: 13 HPV16 and one HPV35. In situ hybridization showed a dotted nuclear positivity in all these cases. HPV16 E7 mRNA was detected in seven tumors harboring HPV16; in the remaining HPV-positive cases, RNA did not reach the quality for analysis. Strong, diffuse positivity for p16 was observed only in the HPV-positive cases. The 14 HPV-positive squamous cell carcinomas were non-keratinizing or scarcely keratinizing tumors. No significant differences were found in terms of gender, age, or staging at diagnosis between HPV-positive and HPV-negative tumors. However, differences in disease-free survival and overall survival between both groups of patients were significant (P=0.004 and P=0.028, respectively). In conclusion, we have shown that HPV is the etiological agent of a subset of sinonasal carcinomas demonstrating the transcriptionally active HPV in these tumors. Immunostaining for p16 can be used as a surrogate marker to identify these tumors.

  10. Role of Human Papillomavirus in Penile Carcinomas Worldwide.

    Science.gov (United States)

    Alemany, Laia; Cubilla, Antonio; Halec, Gordana; Kasamatsu, Elena; Quirós, Beatriz; Masferrer, Emili; Tous, Sara; Lloveras, Belén; Hernández-Suarez, Gustavo; Lonsdale, Ray; Tinoco, Leopoldo; Alejo, Maria; Alvarado-Cabrero, Isabel; Laco, Jan; Guimerà, Nuria; Poblet, Enrique; Lombardi, Luis E; Bergeron, Christine; Clavero, Omar; Shin, Hai-Rim; Ferrera, Annabelle; Felix, Ana; Germar, Julieta; Mandys, Vaclav; Clavel, Christine; Tzardi, Maria; Pons, Luis E; Wain, Vincent; Cruz, Eugenia; Molina, Carla; Mota, Jose D; Jach, Robert; Velasco, Julio; Carrilho, Carla; López-Revilla, Ruben; Goodman, Marc T; Quint, Wim G; Castellsagué, Xavier; Bravo, Ignacio; Pawlita, Michael; Muñoz, Nubia; Bosch, F Xavier; de Sanjosé, Silvia

    2016-05-01

    Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. HPV DNA prevalence and type distributions were estimated. HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV

  11. [Clinic and pathological analysis the larynx leukoplakia in 74 cases].

    Science.gov (United States)

    Yu, He; Li, Xiaotian; Wang, Yan; Yang, Huaian; Guo, Xing; Pan, Zimin; Jiang, Xuejun

    2009-08-01

    To study the clinic and pathological features of leukoplakia of the larynx, and reduce canceration rate. Seventy-four postoperative patients of leukoplakia of the larynx were followed up for four years by telephone or clinic service. None of eighteen cases of pure leukoplakia was recurrence. Fifty-six cases were leukoplakia with epithelial dysplasia histologically. Seven out of fifty-six postoperative cases occurred hoarseness; three out of fifty-six postoperative cases recurred, and accepted twice or more operations successively; three out of fifty-six postoperative cases occurred canceration. Operation is the main means for the treatment of leukoplakia of the larynx, and the effect is comparatively well. The patients with histological epithelial dysplasia should be pay great attention because of their higher canceration rate, and enlarged operation ranges appropriately with the patient consent could effectually prevent recurrence or canceration during the early lesions. Close observation is important for these patients.

  12. 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

    2016-10-14

    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.

  13. Human papillomavirus-16 is integrated in lung carcinomas: a study in Chile

    Science.gov (United States)

    Aguayo, F; Castillo, A; Koriyama, C; Higashi, M; Itoh, T; Capetillo, M; Shuyama, K; Corvalan, A; Eizuru, Y; Akiba, S

    2007-01-01

    The human papillomavirus (HPV) was detected in 20 (29%) out of 69 lung carcinomas (LCs) in Chile, by PCR and Southern blot, and was more frequently detected in squamous cell carcinoma (SQC) than in adenocarcinomas (46 vs 9%, P=0.001). HPV-16, positive in 11 cases, was the most frequently detected HPV genotype determined by DNA sequencing. HPV-16 E2/E6 ratio, estimated from real-time PCR analysis, was much lower than the unity, suggesting that at least a partial HPV-16 genome was integrated in all but one HPV-16-positive SQCs. The remaining one case was suspected to have only episomal HPV-16. Although the viral load was low in most of the LCs, a case showed the HPV-16 copy number as high as 8479 per nanogram DNA, which was even a few times higher than the minimum viral load of seven cervical carcinomas (observed viral load: 3356–609 392 per nanogram DNA). The expression of the HPV-16/18 E6 protein was found in only two HPV-16-positive SQCs (13%) but not in the case with the highest viral load. Although the viral load was in general very low and HPV E6 expression is none or weak, further studies seem warranted to examine aetiological involvement of high-risk HPV in lung carcinogenesis. PMID:17579626

  14. Oncogenic PIK3CA Mutation and Dysregulation in Human Salivary Duct Carcinoma

    Directory of Open Access Journals (Sweden)

    Wanglong Qiu

    2014-01-01

    Full Text Available Salivary duct carcinoma (SDC is an aggressive malignant tumor with a high mortality, which resembles high-grade breast ductal carcinoma in morphology. The parotid gland is the most common location. Its molecular genetic characteristics remain largely unknown. We have previously reported high incidence of PIK3CA somatic mutations in head and neck squamous cell carcinoma, particularly in pharyngeal cancers. Here we examined the PIK3CA gene expression status and hotspot mutations in six cases of SDC by immunohistochemistry and genomic DNA sequencing. Immunohistochemistry showed that PIK3CA expression was elevated in all six patients with SDC. By DNA sequencing, two hotspot mutations of the PIK3CA gene, E545K (exon 9 and H1047R (exon 20, were identified in two of the six cases. Our results support that oncogenic PIK3CA is upregulated and frequently mutated in human SDC, adding evidence that PIK3CA oncogenic pathway is critical in the tumorigenesis of SDC, and may be a plausible drug target for this rare disease.

  15. Concurrent Human Papillomavirus-Positive Squamous Cell Carcinoma of the Oropharynx in a Married Couple

    Directory of Open Access Journals (Sweden)

    Tyler D. Brobst

    2016-01-01

    Full Text Available Background. Although alcohol and tobacco use are known risk factors for development of squamous cell carcinoma in the head and neck, human papillomavirus (HPV has been increasingly associated with this group of cancers. We describe the case of a married couple who presented with HPV-positive oropharynx squamous cell carcinoma within two months of each other. Methods. Tumor biopsies were positive for p16 and high-risk HPV in both patients. Sanger sequencing showed a nearly identical HPV16 strain in both patients. Both patients received chemoradiation, and one patient also underwent transoral robotic tongue base resection with bilateral neck dissection. Results. Both patients showed no evidence of recurrent disease on follow-up PET imaging. Conclusions. New head and neck symptoms should be promptly evaluated in the partner of a patient with known HPV-positive oropharynx cancer. This case expands the limited current literature on concurrent presentation of HPV-positive oropharynx squamous cell carcinoma in couples.

  16. Frequency of Human Papillomavirus (HPV) 16 and 18 Detection in Paraffin- Embedded Laryngeal Carcinoma Tissue

    Science.gov (United States)

    Hosseini, Seyed Zinab; Makvandi, Manoochehr; Samarbafzade, Alireza; Timori, Ali; Ranjbar, Nastaran; Saki, Nader; Nisi, Nilofar; Shahani, Toran; Varnaseri, Mehran; Ahmadi, Kambiz Angali

    2017-01-01

    Background and Objective: Human papilloma virus (HPV) 16 and HPV18 have been detected in head and neck squamous cell carcinomas (HNSCC) and there is evidence that detection of HPVs would have better prognostic value than patients with HNSCC negative for HPVs. Thus, this study was conducted to evaluate frequency of HPV 16 and HPV 18 genotypes in patients with laryngeal carcinoma. Materials and methods: Fifty formalin-fixed, paraffin-embedded (FFPE) tissue blocks of laryngeal cancers were collected. Sections were prepared at 5 µm and DNA was extracted from each sample and subjected to the polymerase chain reaction (PCR) to detect HPV-16/18 DNA s. Results: All samples were squamous cell carcinomas (SCCs). Overall 14/50 (28%) were positive for HPVs, 8 (18%) with HPV-16 and 6 (12%) with HPV-18. Additionally, 2 (4%) mixed infections of HPV 16 and 18 genotypes were observed among these cases. Conclusions: Overall, 28% of HNSCC samples proved positive for HPV16 and HPV18 genotypes, two high-risk HPV types. It is important to further assess whether such viral infection, could be a risk factor in HNSCC progression. PMID:28545184

  17. Applications of monoclonal antibodies and recombinant cytokines for the treatment of human colorectal and other carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Greiner, J.W.; Smalley, R.V.; Borden, E.C.; Martin, E.W.; Guadagni, F.; Roselli, M.; Schlom, J. (Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States))

    1991-01-01

    Monoclonal antibodies (MAbs) which recognize a human tumor antigen, termed tumor-associated glycoprotein-72 (TAG-72), have successfully been used to localize primary as well as metastatic colorectal tumor lesions in patients. The localization of the anti-TAG-72 MAbs has also been exploited intraoperatively using a hand-held gamma probe. That procedure, termed radioimmunoguided surgery (RIGS), has identified occult tumors which were not detected using standard external imaging techniques. In another clinical trial, interferon-gamma (IFN-gamma) was administered intraperitoneally to patients diagnosed with either gastrointestinal or ovarian carcinoma with secondary ascites. Analysis of the tumor cells isolated from the malignant ascites revealed a substantial increase in TAG-72 expression on the surface of tumor cells isolated from seven of eight patients. The results provide evidence that the combination of an anti-carcinoma MAb with the administration of a cytokine, such as IFN-gamma, may be an effective approach for the detection and subsequent treatment, of colorectal carcinoma. 15 references.

  18. Incidence of human papillomavirus positive tonsillar and base of tongue carcinoma: a stabilisation of an epidemic of viral induced carcinoma?

    Science.gov (United States)

    Näsman, Anders; Nordfors, Cecilia; Holzhauser, Stefan; Vlastos, Andrea; Tertipis, Nikolaos; Hammar, Ulf; Hammarstedt-Nordenvall, Lalle; Marklund, Linda; Munck-Wikland, Eva; Ramqvist, Torbjörn; Bottai, Matteo; Dalianis, Tina

    2015-01-01

    To investigate whether the rise during the past decades in the incidence of tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC) and the proportion of human papillomavirus (HPV) positive cancer has continued in Stockholm. Pre-treatment biopsies (n=252) available from 280 patients diagnosed with TSCC and BOTSCC during 2008-2012 in the County of Stockholm were tested for HPV DNA by a multiplex bead-based assay. Incidence records were acquired from the Swedish Cancer Registry. The data obtained were evaluated together with previous figures from 1970 to 2007. HPV DNA was present in 186/252 (74%) of TSCC and BOTSCC biopsies obtained during 2008-2012 in Stockholm. In this region the age-standardised incidence, including the prevalence of HPV-positive and HPV-negative TSCC stabilised 2007-2012 compared to 2000-2006, while for BOTSCC throughout 1998-2012 the same parameters increased moderately (p<0.05, for all). In parallel, from 2000 to 2006 through 2007-2012 in Sweden, the age-standardised incidence of both TSCC and BOTSCC continued to rise (p=0.012 and p=0.001 respectively). During 2000-2012 the age-standardised incidence and the proportion of HPV-positive TSCC have stabilised at a high level, while the proportion of HPV-negative cancer has remained at a low level in Stockholm, whereas for BOTSCC all parameters are increasing moderately. In contrast, in Sweden the incidence of both TSCC and BOTSCC is still increasing. We hypothesise that the HPV epidemic could be stabilising, first for TSCC, but so far not for BOTSCC, in e.g. some urban areas, while previous trends for both tumours persist at other geographic locations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Molecular targets for the protodynamic action of cis-urocanic acid in human bladder carcinoma cells

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    Laihia Jarmo K

    2010-10-01

    Full Text Available Abstract Background cis-urocanic acid (cis-UCA is an endogenous amino acid metabolite capable of transporting protons from the mildly acidic extracellular medium into the cell cytosol. The resulting intracellular acidification suppresses many cellular activities. The current study was aimed at characterizing the molecular mechanisms underlying cis-UCA-mediated cytotoxicity in cultured cancer cells. Methods 5367 bladder carcinoma cells were left untreated or treated with cis-UCA. Cell death was assessed by measuring caspase-3 activity, mitochondrial membrane polarization, formation and release of cytoplasmic histone-associated DNA fragments, and cellular permeabilization. Cell viability and metabolic activity were monitored by colorimetric assays. Nuclear labelling was used to quantify the effects of cis-UCA on cell cycle. The activity of the ERK and JNK signalling pathways was studied by immunoblotting with specific antibodies. Phosphatase activity in cis-UCA-treated cells was determined by assay kits measuring absorbance resulting from the dephosphorylation of an artificial substrate. All statistical analyses were performed using the two-way Student's t-test (p Results Here we report that treatment of the 5637 human bladder carcinoma cells with 2% cis-UCA induces both apoptotic and necrotic cell death. In addition, metabolic activity of the 5637 cells is rapidly impaired, and the cells arrest in cell cycle in response to cis-UCA. Importantly, we show that cis-UCA promotes the ERK and JNK signalling pathways by efficiently inhibiting the activity of serine/threonine and tyrosine phosphatases. Conclusions Our studies elucidate how cis-UCA modulates several cellular processes, thereby inhibiting the proliferation and survival of bladder carcinoma cells. These anti-cancer effects make cis-UCA a potential candidate for the treatment of non-muscle invasive bladder carcinoma.

  20. Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells

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    Li Fan

    2010-04-01

    Full Text Available Abstract Background In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Methods We constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7. Results CXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo

  1. [Cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma].

    Science.gov (United States)

    Fan, Bing-Lin; Zhu, Wu-Ling; Zou, Guo-Lin; Luo, Guo-Sheng; Xu, Chun-Lei; Zhao, Wei-Xing

    2004-03-01

    Abnormal expression of genes is related to development and progression of hepatocellular carcinoma (HCC); however, the detailed mechanism is unclear yet because the known genetic information is not sufficient at present. This study was to explore cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma. The suppression subtractive hybridization was used to obtain subtracted cDNA products of HCC, then the products were cloned by T/A method. The differential expression of gene in HCC was identified by DNA sequencing analysis, Northern blot analysis, rapid amplification of cDNA end (RACE), and reverse transcription polymerase chain reaction (RT-PCR). Firstly, a cDNA fragment of 787 nucleotides was screened from the subtracted cDNA clones, and it was further discovered that the expression of the cDNA fragment was higher significantly in human hepatocellular carcinoma cell strains of SMMC-7721 and HepG2 than in normal hepatocytes by Northern blot analysis. The RACE was carried out and the gene of 1 597 bp containing polyA in 3'end was obtained, which has an entire open reading frame encoding 437 amino acids. Homology analysis showed that this was a gene encoding human FGG. RT-PCR analysis of FGG showed that the amplification of cancerous tissues, especially in metastasis of HCC, was raised as compared to that of adjacent non-cancerous tissues. Overexpression of FGG was discovered in SMMC-7721 and HepG2 cells. The up-regulation of FGG may be associated with the pathogenesis of HCC.

  2. Abnormal number cell division of human thyroid anaplastic carcinoma cell line, SW 1736

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    Keiichi Ikeda

    2015-12-01

    Full Text Available Cell division, during which a mother cell usually divides into two daughter cells during one cell cycle, is the most important physiological event of cell biology. We observed one-to-four cell division during imaging of live SW1736 human thyroid anaplastic carcinoma cells transfected with a plasmid expressing the hybrid protein of green fluorescent protein and histone 2B (plasmid eGFP-H2B. Analysis of the images revealed a mother cell divided into four daughter cells. And one of the abnormally divided daughter cells subsequently formed a dinucleate cell.

  3. Induction of apoptosis by Armillaria mellea constituent armillarikin in human hepatocellular carcinoma

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    Chen YJ

    2016-08-01

    Full Text Available Yu-Jen Chen,1–4 Chien-Chih Chen,5 Huey-Lan Huang6 1Department of Medical Research, 2Department of Radiation Oncology, Mackay Memorial Hospital, 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 4Institute of Pharmacology, Taipei Medical University, Taipei, 5Department of Biotechnology, HungKuang University, Taichung, 6Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan, Taiwan Abstract: Armillaria mellea is a honey mushroom often used in the traditional Chinese medicine “Tianma”. Currently, this medicinal mushroom is also used as a dietary supplement in numerous Western and Eastern countries. Armillarikin was isolated from A. mellea, and we previously discovered that it induced cytotoxicity in human leukemia cells. In this study, we further investigated the cytotoxicity of armillarikin against liver and intrahepatic bile duct cancer cells. Armillarikin was cytotoxic against human hepatocellular carcinoma Huh7, HA22T, and HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium and alamarBlue® assays. Armillarikin treatment also induced the collapse of the mitochondrial transmembrane potential of these cells. Furthermore, armillarikin-induced apoptotic cell death was demonstrated by sub-G1 chromosomal DNA formation by using flow cytometry. In addition, the apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-fmk. Immunoblotting also revealed the armillarikin-induced activation of procaspase-3, -8, and -9 and upregulation of the apoptosis- and cell cycle arrest-related phospho-histones 2 and 3, respectively. Moreover, reactive oxygen species scavengers also inhibited the armillarikin-induced apoptosis in human hepatocellular carcinoma, suggesting that reactive oxygen species formation played an important role in the armillarikin-induced apoptosis of human hepatocellular carcinoma. In

  4. High-risk HPVs and human carcinomas in the Syrian population

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    Ala-Eddin eAl Moustafa

    2014-04-01

    Full Text Available Human papillomavirus (HPV infection is the most common sexually transmitted infection; persistent infection with high-risk types of HPV present a major risk factor for the initiation and progression of a variety of human carcinomas including cervical, colorectal, head and neck as well as breast carcinomas. A huge number of studies investigated and reported the incidence of high-risk HPVs in these cancers worldwide particularly in the developed countries; therefore, two HPV prophylactic vaccines against the two most frequent high-risk HPV types (16 and 18 have been developed and used worldwide. However, there are very limited studies about the prevalence of HPVs in the developing countries especially in Africa and some states of the Middle East (ME. In this mini review, we outline the presence of high-risk HPVs in human cervical, colorectal, head and neck as well as breast cancers in the Syrian population, which was recently explored for the first time by a Canadian/Syrian group.

  5. Chimeric DNA Vaccines against ErbB2{sup +} Carcinomas: From Mice to Humans

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    Quaglino, Elena; Riccardo, Federica; Macagno, Marco; Bandini, Silvio; Cojoca, Rodica; Ercole, Elisabetta [Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin, 10126 Turin (Italy); Amici, Augusto [Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy); Cavallo, Federica, E-mail: federica.cavallo@unito.it [2 Department of Molecular Cellular and Animal Biology, University of Camerino, 62032 Camerino (Italy)

    2011-08-10

    DNA vaccination exploits a relatively simple and flexible technique to generate an immune response against microbial and tumor-associated antigens (TAAs). Its effectiveness is enhanced by the application of an electrical shock in the area of plasmid injection (electroporation). In our studies we exploited a sophisticated electroporation device approved for clinical use (Cliniporator, IGEA, Carpi, Italy). As the target antigen is an additional factor that dramatically modulates the efficacy of a vaccine, we selected ErbB2 receptor as a target since it is an ideal oncoantigen. It is overexpressed on the cell membrane by several carcinomas for which it plays an essential role in driving their progression. Most oncoantigens are self-tolerated molecules. To circumvent immune tolerance we generated two plasmids (RHuT and HuRT) coding for chimeric rat/human ErbB2 proteins. Their immunogenicity was compared in wild type mice naturally tolerant for mouse ErbB2, and in transgenic mice that are also tolerant for rat or human ErbB2. In several of these mice, RHuT and HuRT elicited a stronger anti-tumor response than plasmids coding for fully human or fully rat ErbB2. The ability of heterologous moiety to blunt immune tolerance could be exploited to elicit a significant immune response in patients. A clinical trial to delay the recurrence of ErbB2{sup +} carcinomas of the oral cavity, oropharynx and hypopharynx is awaiting the approval of the Italian authorities.

  6. Establishment and characterization of a human primary prostate carcinoma cell line, HH870.

    Science.gov (United States)

    Selvan, Senthamil R; Cornforth, Andrew N; Rao, Nagesh P; Reid, Yvonne A; Schiltz, Patric M; Liao, Ray P; Price, David T; Heinemann, F Scott; Dillman, Robert O

    2005-04-01

    Development of new therapeutic modalities for human prostate carcinoma has been impeded by a lack of adequate in vitro and in vivo models. Most in vitro studies have been carried out using a limited number of human prostate cancer cell lines that are mostly derived from metastatic tumors sites or are immortalized. Characterization of the prostate cancer cell line, HH870, included description of morphology, determination of doubling time, response to androgens, immunocytochemistry, and immunoblotting of proteins known to be associated with prostate carcinoma, karyotyping, fluorescence in situ hybridization (FISH), DNA profiling, and growth as xenograft in athymic rodents. HH870 expresses various epithelial marker antigens that correlate with known basic immunostaining profiles of prostate adenocarcinoma, although the cell line does not express PSA, PSMA, or PAP. HH870 exhibits complex chromosomal abnormalities and harbors no immortalizing HPV, BKV, JCV, and SV40 DNA. We report the successful establishment and characterization of a new long-term primary human prostate tumor cell line HH870. Copyright (c) 2004 Wiley-Liss, Inc.

  7. SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK: NEW AVENUES OF TREATMENT?

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    T. Braunschweig

    2013-01-01

    Full Text Available Squamous cell carcinoma of the head and neck counts for 3 % of all cancers in men and half of this number less in women with a 5-year survival of 61 %. While the number of laryngeal carcinoma is decreasing, carcinoma of the oral cavity related to an infection by the human papilloma virus (HPV, high-risk subtypes is increasing, especially in younger patients. HPV related squamous cell carcinomas show better survival data, especially in regard to recurrence free rates or secondary carcinoma of adjacent locations. Squamous cell carcinomas related to the presence of HPV DNA material is almost exclusively found in carcinoma of the oral cavity and oropharyngeal mucosa. Much less frequently HPV is present in hypopharyngeal carcinomas and even less number of cases of squamous cell carcinoma with proof for HPV in the nasopharynx and larynx. In case of evidence for HPV DNA; most cases are positively tested for subtype 16, followed by subtype 18. As a surrogate immunhistochemical marker, p16 INK4A is stained positive, cytoplasmic and nuclear. In a small study by ourselves, we found a positive correlation in 100 % of p16 INK4A positivity and positive HPV testing. Oral squamous cell carcinoma is more frequently related to HPV in patients below 50 years of age with a prevalence of ca. 20 %. Whilst HPV high-risk positive carcinomas show very few mutations in single signalling molecules of the downstream receptor tyrosin kinase pathways, HPV negative carcinomas show in many cases a chaotic DNA mutation type with typical mutations in tumor suppressor genes, as p53 and CDKN2A. This pattern is often seen in carcinoma types develop from a summation of accidental mutations often caused by toxins (e.g. inhaled cigarette smoke. However, it is discussed and under investigation whether a subset of head and neck squamous cell carcinomasdevelop from so called driver mutations, as are called mutations in critical members of signalling pathways and receptor tyrosin kinases

  8. Talin-1 correlates with reduced invasion and migration in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Fang, Kun-Peng; Zhang, Jian-Lin; Ren, Yan-Hong; Qian, Ye-Ben

    2014-01-01

    Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines. We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell (LO2 cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation. Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and LO2 cell line (pmigration capabilities of the five cancer cell lines differed significantly (pmigration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma.

  9. Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration.

    Science.gov (United States)

    Takagi, Kiyoshi; Miki, Yasuhiro; Tanaka, Sota; Hashimoto, Chiaki; Watanabe, Mika; Sasano, Hironobu; Ito, Kiyoshi; Suzuki, Takashi

    2016-01-01

    Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains, and associated with wide variety of biological process such as food intake and energy homeostasis. Recently, NUCB2 has been implicated in not only normal human tissues but also some kinds of human malignancies. However, its clinical and/or biological significance has largely remained unknown in endometrial carcinomas. We therefore immunolocalized NUCB2 protein in 87 endometrial carcinoma tissues and examined its clinical significance. NUCB2 immunoreactivity was detected in 19 out of 87 (22%) of endometrial carcinoma cases examined, and positively correlated with Ki67 labeling index, while there was no significant correlation between NUCB2 and stage, histological grade, and progesterone receptor status. Furthermore, NUCB2 immunoreactivity was significantly correlated with increased risk of recurrence and worse clinical outcome regardless of stage or histological grade. Subsequent multivariate analyses did reveal that NUCB2 immunoreactivity was an independent prognostic factor for both disease-free survival and endometrial cancer specific survival. In vitro experiments demonstrated that knockdown of NUCB2 using specific siRNA for NUCB2 significantly impaired cell proliferation and migration of the endometrial carcinoma cell lines, Ishikawa and Sawano cells, and that nesfatin-1 treatment significantly promoted cell proliferation and migration in Ishikawa cells. These findings possibly suggested that NUCB2 and/or nesfatin-1 had pivotal roles in the progression of endometrial carcinomas. Immunohistochemical NUCB2 status may therefore serve as a potent biomarker for endometrial carcinomas.

  10. Establishment and characterization of a new human oestradiol- and progesterone-receptor-positive mammary carcinoma serially transplantable in nude mice.

    Science.gov (United States)

    Naundorf, H; Fichtner, I; Büttner, B; Frege, J

    1992-01-01

    A human mammary carcinoma originating from a postmenopausal patient was successfully transplanted into nude mice. According to the adopted criteria the tumour proved to be oestradiol- and progesterone-receptor-positive. Histological studies of the patient tumour revealed a ductal invasive mammary carcinoma with 80% tubular growth pattern. Following transplantation the adenoid structures decreased to 30%; the mitosis rate and grade of malignancy increased. Treatment of the nude mice with 20 micrograms oestradiol benzoate/mouse caused a loss of the oestradiol receptor of the mammary carcinoma. The mammary carcinoma 3366 can be used for testing of antineoplastic substances, antihormones and for studies in regard to down-regulation or blocking of hormone receptors and possible consequences for therapies.

  11. Parameters Derived from Integrated Nuclear Fluorescence, Syntactic Structure Analysis, and Vascularization in Human Lung Carcinomas

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    Klaus Kayser

    1997-01-01

    Full Text Available Combined measurements of integrated nuclear fluorescence (INF and vascularization were performed on surgical specimens of human lung carcinomas. Histological slides of formalin‐fixed, paraffin‐embedded tissue samples were treated with Texas Red‐labeled antibody to factor VIII and the fluorochrome DAPI. The resulting images were analyzed with an epi‐illumination fluorescence microscope and two different filter blocks. The first image displayed the vessels, and the second the DAPI‐stained nuclei of surrounding cells. The extent of vascularization was assessed by calculating the volume fraction (Vv, the surface fraction (Sv, the area, and the minimum diameter of the vessels. The INF was measured in tumour cells and lymphocytes, and was grouped according to the distance from the nearest vascular boundary into the intervals of 0–20, 21–40, 41–60, 61–80, and >80 μ. The numerical densities (Nv as well as the percentages of S‐phase‐related tumour cell fraction (SPRF and of tumour cells with an INF > 5C were computed. A minimum of 50 vessels and 300 tumour cells were examined. The material included 100 cases with primary lung carcinoma (39 epidermoid carcinomas, 39 adenocarcinomas, 13 large cell carcinomas, three small cell anaplastic carcinomas, and 6 carcinoid tumours. On the average, the volume density of the stroma amounts to 16.7%, and that of the vessels (Vv to 12.8%. The minimum diameter of the intratumoral vessels is 13 μ and the measured circumference 138 μ. The numerical densities of tumour cells (lymphocytes decrease with increasing distance from the vascular boundary from 6.3 (1.7 to 1.0 (0.1. A reduction is also seen in the percentage of the SPRF from 10.7 to 8.1%. The percentage of tumour cells with an INF > 5C, however, is positively correlated to the distance from the vascular surfaces from 34.2 to 38.2%. The measurements reveal that tumour cells are densely positioned and have an increased proportion of

  12. [Prokaryotic expression, purification and antigenicity identification of human renal cell carcinoma-associated antigen G250].

    Science.gov (United States)

    Xiao, Yi; Gao, Jiangping; Gao, Kun; Yan, Jinqi; Zhang, Liang; Wang, Yu; Xu, Yuanji; Wang, Wei; Wang, Xiaoxiong; Yu, Jiyun

    2013-03-01

    To amplify human renal cell carcinoma (RCC)-associated antigen G250 gene and construct a recombinant plasmid pET-42a-hG250, express and purify human G250 protein and identify its antigenicity. The gene of human G250 was amplified from pGEM-T-G250 by PCR. After sequencing, the PCR product (112-1242 bp) was cloned into pET-42a prokaryotic expression vector to construct the recombinant plasmid pET-42a-hG250. The plasmid was transformed into BL21 (DE3) and human G250 protein was expressed under the induction of IPTG. The fusion protein was purified and identified by SDS-PAGE, Western blotting and ELISA sequentially. The human G250 prokaryotic expression vector pET-42a-hG250 was successfully constructed as confirmed by enzyme digestion and DNA sequencing. After transformation into BL21 (DE3), the target protein was successfully induced to express and purified as expected. Western blotting and ELISA demonstrated that the purified human G250 protein had a desirable immunogenicity. The recombinant prokaryotic expression vector pET-42a-hG250 has been constructed successfully. The purified human G250 protein has a good antigenicity.

  13. Effects of Roundabout 5 on adhesion, invasion and potential motility of human tongue carcinoma Tb cells.

    Science.gov (United States)

    Xiao, Rui; Zhao, Yuan; Wang, Li-jing; Li, Wei-ping

    2011-08-01

    Roundabout 5 (R5) is a monoclonal antibody which can neutralize the binding of Roundabout 1 (Robo1) to Slit2. Oral squamous cell carcinoma angiogenesis was significantly inhibited when R5 blocked slit-robo signaling pathway. However, the effect of R5 on the invasion of tongue cancer cells has not been investigated clearly. In this study, we treated human brain metastasis of tongue cancer cell lines (Tb cells) with R5 at different concentrations, and the control Tb cells were treated with 10 mg/ml immunoglobin G 2b (IgG2b). The effect of R5 on the proliferation, adhension, invasion and motility of Tb cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cell attachment assay on fibronectin (FN), wound assay and chemotaxis assay, respectively. And gelatin-incorporated sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to investigate the activity of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9). R5 had no effect on the proliferation of Tb cells. However, R5 could significantly inhibit the motility, attachment and chemotaxis of Tb cells to FN, and it could also significantly inhibit the activity of MMP2 and MMP9 in Tb cells. R5 can inhibit the adhesion, invasion and motility of human tongue carcinoma Tb cells.

  14. Epigallocatechin-3-gallate Sensitizes Human 786-O Renal Cell Carcinoma Cells to TRAIL-Induced Apoptosis.

    Science.gov (United States)

    Wei, Ruojing; Zhu, Guodong; Jia, Ning; Yang, Wenzeng

    2015-05-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent. Epigallocatechin-3-gallate (EGCG) is a polyphenolic constituent of green tea. In this study, potentiating effect of EGCG on TRAIL-induced apoptosis human renal carcinoma cell line 786-O which is relatively resistant to TRAIL was examined, and the possible mechanism was investigated. Here, we show that co-treatment with EGCG and TRAIL induced significantly more profound apoptosis in 786-O cells. Treatment of 786-O cells with EGCG and TRAIL downregulated c-FLIP, Mcl-1, and Bcl-2 proteins in a caspase-dependent pathway. Moreover, we found that pretreatment with NAC markedly inhibited the expression levels of c-FLIP, Mcl-1, and Bcl-2 downregulated by the combinatory treatment, suggesting that the regulating effect of EGCG on these above apoptosis-relevant molecules was partially mediated by generation of ROS. Taken together, the present study demonstrates that EGCG sensitizes human 786-O renal cell carcinoma cells to TRAIL-induced apoptosis by downregulation of c-FLIP, Mcl-1, and Bcl-2.

  15. Chlorella vulgaris Induces Apoptosis of Human Non-Small Cell Lung Carcinoma (NSCLC) Cells.

    Science.gov (United States)

    Zhang, Zhi-Dong; Liang, Kai; Li, Kun; Wang, Guo-Quan; Zhang, Ke-Wei; Cai, Lei; Zhai, Shui-Ting; Chou, Kuo-Chen

    2017-01-01

    Chlorella vulgaris (C. vulgaris), a unicellular green microalga, has been widely used as a food supplement and reported to have antioxidant and anticancer properties. The current study was designed to assess the cytotoxic, apoptotic, and DNA-damaging effects of C. vulgaris growth factor (CGF), hot water C. vulgaris extracts, inlung tumor A549 and NCI-H460 cell lines. A549 cells, NCI-H460 cells, and normal human fibroblasts were treated with CGF at various concentrations (0-300 μg/ml) for 24 hr. The comet assay and γH2AX assay showed DNA damage in A549 and NCI-H460 cells upon CGF exposure. Evaluation of apoptosis by the TUNEL assay and DNA fragmentation analysis by agarose gel electrophoresis showed that CGF induced apoptosis in A549 and NCI-H460 cells. Chlorella vulgaris hot water extract induced apoptosis and DNA damage in human lung carcinoma cells. CGF can thus be considered a potential cytotoxic or genotoxic drug for treatment of lung carcinoma. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Study of the betulin enriched birch bark extracts effects on human carcinoma cells and ear inflammation

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    Dehelean Cristina A

    2012-11-01

    Full Text Available Abstract Background Pentacyclic triterpenes, mainly betulin and betulinic acid, are valuable anticancer agents found in the bark of birch tree. This study evaluates birch bark extracts for the active principles composition. Results New improved extraction methods were applied on the bark of Betula pendula in order to reach the maximum content in active principles. Extracts were analyzed by HPLC-MS, Raman, SERS and 13C NMR spectroscopy which revealed a very high yield of betulin (over 90%. Growth inhibiting effects were measured in vitro on four malignant human cell lines: A431 (skin epidermoid carcinoma, A2780 (ovarian carcinoma, HeLa (cervix adenocarcinoma and MCF7 (breast adenocarcinoma, by means of MTT assay. All of the prepared bark extracts exerted a pronounced antiproliferative effect against human cancer cell lines. In vivo studies involved the anti-inflammatory effect of birch extracts on TPA-induced model of inflammation in mice. Conclusions The research revealed the efficacy of the extraction procedures as well as the antiproliferative and anti-inflammatory effects of birch extracts.

  17. Mechanisms by Which Interleukin-6 Attenuates Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

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    Ke-Hung Tsui

    2013-01-01

    Full Text Available Interleukin-6, a multifunctional cytokine, contributes to tumor cell proliferation and differentiation. However, the biological mechanisms that are affected by the expression of interleukin-6 in bladder cancer cells remain unclear. We evaluated the effects of interleukin-6 expression in human bladder carcinoma cells in vitro and in vivo. The results of interleukin-6-knockdown experiments in T24 cells and interleukin-6-overexpression experiments in HT1376 cells revealed that interleukin-6 reduced cell proliferation, migration, and invasion in vitro. Xenograft animal studies indicated that the overexpression of interleukin-6 downregulated tumorigenesis of bladder cells and that interleukin-6 knockdown reversed this effect. The results of RT-PCR, immunoblotting, and reporter assays indicated that the overexpression of interleukin-6 upregulated the expression of the mammary serine protease inhibitor (MASPIN, N-myc downstream gene 1 (NDRG1, and KAI1 proteins in HT1376 cells and that interleukin-6 knockdown reduced the expression of these proteins in T24 cells. In addition, results of immunoblotting assays revealed that interleukin-6 modulated epithelial-mesenchymal transitions by upregulating the expression of the E-cadherin, while downregulation N-cadherin and vimentin proteins. Our results suggest that the effects of interleukin-6 on the regulation of epithelial-mesenchymal transitions and the expressions of the MASPIN, NDRG1, and KAI1 genes attribute to the modulation of tumorigenesis in human bladder carcinoma cells.

  18. The enamel matrix derivative (Emdogain) enhances human tongue carcinoma cells gelatinase production, migration and metastasis formation.

    Science.gov (United States)

    Laaksonen, Matti; Suojanen, Juho; Nurmenniemi, Sini; Läärä, Esa; Sorsa, Timo; Salo, Tuula

    2008-08-01

    Enamel matrix derivative Emdogain (EMD) is widely used in periodontal treatment to regenerate lost connective tissue and to improve the attachment of the teeth. Gelatinases (MMP-2 and -9) have an essential role in the promotion and progression of oral cancer growth and metastasis formation. We studied the effects of EMD on human tongue squamous cell carcinoma (HSC-3) cells in vitro and in vivo. In vitro, EMD (100 microg/ml and 200 microg/ml) remarkably induced the MMP-2 and -9 production from HSC-3 cells analysed by zymography and enzyme-linked immunosorbent assay. EMD also slightly induced the MMP-2 and -9 production from benign human mucosal keratinocytes (HMK). Furthermore, EMD clearly induced the transmigration of HSC-3 cells but had no effect on the HMK migration in transwell assays. The in vitro wound closure of HSC-3 cells was notably accelerated by EMD, whereas it had only minor effect on the wound closure of HMKs. The migration of both cell lines was inhibited by a selective cyclic anti-gelatinolytic peptide CTT-2. EMD had no effect on HSC-3 cell proliferation or apoptosis and only a limited effect on cell attachment to various extracellular matrix components. The in vivo mice experiment revealed that EMD substantially induced HSC-3 xenograft metastasis formation. Our results suggest that the use of EMD for patients with oral mucosal carcinomas or premalignant lesions should be carefully considered, possibly avoided.

  19. Laryngeal Structure and Function in the Pediatric Larynx: Clinical Applications

    Science.gov (United States)

    Sapienza, Christine M.; Ruddy, Bari Hoffman; Baker, Susan

    2004-01-01

    This article presents an overview of the normal anatomy and physiology of the pediatric larynx, followed by some examples of pediatric voice disorders that were chosen to exemplify the alterations to the laryngeal anatomy and the subsequent modifications to laryngeal function. Vocal fold nodules are primarily reviewed due to their high incidence…

  20. Collision tumors of the larynx: A critical review

    NARCIS (Netherlands)

    Coca-Pelaz, A.; Triantafyllou, A.; Devaney, K.O.; Rinaldo, A.; Takes, R.P.; Ferlito, A.

    2016-01-01

    Problems related to definition of collision tumors are briefly examined in conjunction with etiology and natural history. Examples of genuine collision tumors in larynx are rare in the literature and are herein identified and tabulated. Aspects related to diagnosis and therapeutic strategies are

  1. LYMPHOME T/NK PRIMITIF DU LARYNx : LOCALISATION ...

    African Journals Online (AJOL)

    INTRODUCTION. Les néoplasies hématopoïétiques primitifs du larynx sont rares, elles constituent moins de 1% des tumeurs laryn- gées(1). La plupart d'entre elles sont des plasmocytomes extra médullaires, lymphomes diffus à grandes cellules B, des lymphomes de type MALT de la zone marginale, cependant les ...

  2. A Case of Angiomyolipoma Rarely Located in the Larynx

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    Hulya Eyigor

    2011-01-01

    Full Text Available Angiomyolipoma is a rare benign mesenchymal tumor, which is mostly renal in origin. A sixty-year-old male patient with the diagnosis of angiomyolipoma located in the larynx has been presented here, and the literature is reviewed.

  3. A Rat Excised Larynx Model of Vocal Fold Scar

    Science.gov (United States)

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  4. BENIGN LESIONS OF LARYNX - A CLINICAL STUDY OF 50 CASES

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    Sridhar Reddy

    2016-01-01

    Full Text Available INTRODUCTION Benign Lesions of Larynx (BLL have been defined as “An abnormal mass of tissue in larynx, the growth of which exceeds and is coordinated with that of normal tissue and persists in the same excessive manner after cessation of stimuli which evoked the change.” These lesions have significant influence on vocal, social and emotional adjustments of patients. These patients present with hoarseness of voice. AIM A clinical study was undertaken at Govt. ENT Hospital, Hyderabad, for 1 year from January 2014 to December 2014. Aim of this study was to analyze age and sex distribution, symptomatology, sites of involvement, management and recurrence of benign lesions of larynx. MATERIAL AND METHODS A total of 50 patients were studied who were admitted in the hospital. Inclusion criteria: Patients with Hoarseness of Voice (HOV /change of voice, difficulty in breathing and swallowing, vocal fatigue, Foreign Body (FB sensation in the throat. Exclusion criteria: Malignancy of larynx and acute inflammatory conditions of larynx. RESULTS Benign lesions of larynx show male preponderance with M:F ratio of 2.12:1, with common age group between 31 to 40 years. Chronic vocal misuse was the predominant cause and more in professional voice users. The common lesion was Vocal Cord (VC polyp, followed by VC nodules and papillomas. Common side involved was right side. Majority of the patients had to undergo surgery. Majority of recurrence was seen in laryngeal papillomas (33.33%. CONCLUSION Benign lesions of larynx produce symptoms which vary from mild HOV to life threatening stridor. Early diagnosis leads to effective management. Males were more affected and maximum cases seen between 31 to 40 years. Chronic voice abuse, smoking, alcohol, frequent throat clearing and Laryngopharyngeal Reflux (LPR/Gastroesophageal Reflux Disease (GERD are precipitating factors. Microlaryngeal Surgery (MLS, voice rest and speech therapy offer a cost effective, useful and safe

  5. COX-2 correlates with F-box protein, Skp2 expression and prognosis in human gastric carcinoma.

    Science.gov (United States)

    Honjo, Soichiro; Kase, Satoru; Osaki, Mitsuhiko; Ardyanto, Tonang Dwi; Kaibara, Nobuaki; Ito, Hisao

    2005-02-01

    The expression of cyclooxygenase (COX)-2 is induced by growth factors, tumor promoters and cytokines, and is correlated with carcinogenesis, tumor progression and inhibition of apoptosis. To clarify the pathological significance of COX-2, we examined the effect of a selective COX-2 inhibitor, NS398, on two human gastric carcinoma cell lines, MKN-45 and KATO-III, and the expression of Skp2, P27/Kip1 and COX-2 protein in human gastric carcinomas. NS398 inhibited cell growth in a time- and dose-dependent manner and exerted cell cycle arrest in the G0/G1 phase without induction of apoptosis in MKN-45, but had no effect in KATO-III. In MKN-45, NS398 induced up-regulation of P27/Kip1 and down-regulation of COX-2, cyclin D1 and Skp2. Immunohistochemistry using 63 surgically resected gastric carcinomas disclosed that COX-2 expression was correlated with Skp2 expression and that P27/Kip1 expression was inversely correlated with COX-2 and Skp2 expression. High levels of COX-2 or Skp2 were significantly correlated with poor survival (P=0.02 and P=0.004). Our results suggested that: a) NS398 induced inhibition of cell proliferation through cell cycle arrest and suppressed the expression of Skp2 in COX-2-expressing gastric carcinoma cells, and b) COX-2 contributes to the expression of Skp2 and poor survival in human gastric carcinomas.

  6. Curcumin promotes the apoptosis of human endometrial carcinoma cells by downregulating the expression of androgen receptor through Wnt signal pathway.

    Science.gov (United States)

    Feng, W; Yang, C X; Zhang, L; Fang, Y; Yan, M

    2014-01-01

    The current study aimed to explore the effect ofcurcumin on androgen receptor (AR) expression in endometrial carcinoma cells, as well as the underlying mechanisms. Endometrial carcinoma cells were treated with curcumin (10, 50, and 100 micromol/l) for 12, 24, and 48 hours. Their growth curves were drawn using MTT assays and their apoptotic rates were determined using flow cytometry. The mRNA and protein expression of AR was detected using PCR and that of the Wnt signal related nucleopro- tein beta-cantenin was observed using western blot analysis. The influence of beta-cantenin on the action of curcumin was observed. Curcumin downregulated the proliferation and apoptosis of human endometrial carcinoma cells in concentration and time-dependent manners. It downregulated the expression of AR and beta-cantenin in the cells. rWnt3a partially cancelled the effects of curcumin on the proliferation and apoptosis of human endometrial carcinoma cells as well as the AR expression-downregulating effect of curcumin. Curcumin inhibits the proliferation and apoptosis of human endometrial carcinoma cells by downregulating their AR expression through the Wnt signal pathway.

  7. NF-kappa B signaling pathway is involved in growth inhibition, G2/M arrest and apoptosis induced by Trichostatin A in human tongue carcinoma cells

    NARCIS (Netherlands)

    Yao, Jun; Duan, Li; Fan, Mingwen; Wu, Xinxing

    2006-01-01

    The HDAC inhibitor Trichostatin A (TSA) exhibits antiturnour activity in various tumour cells. However, little is known about the effect of TSA on growth of human tongue carcinoma cells. In this study, we observed that TSA concentration-dependently inhibited growth of human tongue carcinoma Tca8113

  8. Expression of GLUT1 in stratified squamous epithelia and oral carcinoma from humans and rats

    DEFF Research Database (Denmark)

    Voldstedlund, M; Dabelsteen, Erik

    1997-01-01

    Most cells express facilitative glucose transporters. Four isoforms (GLUT1-4) transporting D-glucose across the plasma membrane show a specific tissue distribution, which is the basis for tissue-specific patterns in glucose metabolism. GLUT1 is expressed at high levels in tissue barriers...... such as the blood-brain barrier, and this isoform has been suggested as an indicator of such barriers. GLUT1 has been found in basal layers of human epidermis where no such tissue barrier is present. To further clarify these issues, we examined the distribution of GLUT1 and GLUT4 in skin, different types of oral...... mucosa from rat and man, and a human oral carcinoma by indirect immunofluorescence microscopy. The results showed that GLUT1 was expressed in the basal and parabasal layers of the different stratified squamous epithelia, with some variations between keratinized and non-keratinized subtypes. GLUT1...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-01-01

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

  10. Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Yi-Fan; Ho, Mitchell

    2016-09-26

    Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework. Interestingly, we found that the proline at position 41, a non-CDR residue in heavy chain variable regions (VH), is important for humanization of mouse antibodies. We also showed that two humanized anti-GPC3 antibodies (hYP7 and hYP9.1b) in the IgG format induced antibody-dependent cell-mediated cytotoxicity and complement-dependent-cytotoxicity in GPC3-positive cancer cells. The hYP7 antibody was tested and showed inhibition of HCC xenograft tumor growth in nude mice. This study successfully humanizes and validates high affinity anti-GPC3 antibodies and sets a foundation for future development of these antibodies in various clinical formats in the treatment of liver cancer.

  11. Abnormal expression of HAX-1 is associated with cellular proliferation and migration in human hypopharyngeal squamous cell carcinoma

    Science.gov (United States)

    Wu, Hao; Chen, Jianqiu; Wang, Qiang; Yin, Yong; Da, Peng; Le, Huijun; Zhang, Zhenxin; Qiu, Xiaoxia

    2017-01-01

    HCLS1-associated protein X-1 (HAX-1) is highly expressed or overexpressed in various types of human tumor, and its overexpression is associated with cancer metastasis and cellular proliferation. However, the precise molecular mechanism involved in HAX-1-associated proliferation and metastasis in hypopharyngeal carcinoma is unknown. The present study aimed to investigate the role of HAX-1 in the metastasis and proliferation of hypopharyngeal carcinoma. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting indicated that HAX-1 was overexpressed in hypopharyngeal carcinoma specimens. MTT, clone formation and transwell assays were performed to detect the effects of HAX-1 knockdown or overexpression on the major oncogenic properties of the FaDu hypopharyngeal carcinoma cell line. Downregulation of HAX-1 was observed to significantly suppress cellular proliferation, migration and clonal. By contrast, overexpression of HAX-1 significantly promoted cellular proliferation, migration and clonal formation. Furthermore, HAX-1 knockdown markedly suppressed epithelial-mesenchymal transition. In conclusion, HAX-1 is a potential oncogene, and may promote the tumorigenesis and progression of hypopharyngeal carcinoma, as well as serve as a valuable molecular target for the treatment of hypopharyngeal carcinoma. PMID:28791389

  12. miR-297 modulates multidrug resistance in human colorectal carcinoma by down-regulating MRP-2.

    Science.gov (United States)

    Xu, Ke; Liang, Xin; Shen, Ke; Cui, Daling; Zheng, Yuanhong; Xu, Jianhua; Fan, Zhongze; Qiu, Yanyan; Li, Qi; Ni, Lei; Liu, Jianwen

    2012-09-01

    Colorectal carcinoma is a frequent cause of cancer-related death in men and women. miRNAs (microRNAs) are endogenous small non-coding RNAs that regulate gene expression negatively at the post-transcriptional level. In the present study we investigated the possible role of microRNAs in the development of MDR (multidrug resistance) in colorectal carcinoma cells. We analysed miRNA expression levels between MDR colorectal carcinoma cell line HCT116/L-OHP cells and their parent cell line HCT116 using a miRNA microarray. miR-297 showed lower expression in HCT116/L-OHP cells compared with its parental cells. MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells and is a predicted target of miR-297. Additionally miR-297 was down-regulated in a panel of human colorectal carcinoma tissues and negatively correlated with expression levels of MRP-2. Furthermore, we found that ectopic expression of miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. Taken together, our findings suggest that miR-297 could play a role in the development of MDR in colorectal carcinoma cells, at least in part by modulation of MRP-2.

  13. Human papillomavirus (HPV) status of non-tobacco related squamous cell carcinomas of the lateral tongue

    Science.gov (United States)

    Poling, JS; Ma, X-J; Bui, S; Luo, Y; Li, R; Koch, WM; Westra, WH

    2014-01-01

    Objectives The human papillomavirus (HPV) is an important cause of some head and neck squamous cell carcinomas (HNSCCs), but its role in cancer of the lateral tongue is debatable. Suspicion of HPV causation is heightened when these lateral tongue carcinomas arise in patients that are young and/or have never smoked. The purpose of this study was to determine the incidence of transcriptionally active high risk HPV in these tumors, with a particular emphasis on non-smoking patients who are often presumed to have HPV-positive tumors. Methods We evaluated 78 HNSCCs of the lateral tongue for the presence of HPV using p16 immunohistochemistry and an RNA in situ hybridization assay targeting HPV E6/E7 mRNA. The study population was enriched for patients without traditional risk factors such as smoking and drinking. Results P16 overexpression was detected in 9 (11.5%) of 78 cases, but HPV E6/E7 mRNA transcripts were detected in only 1 (1.3%) case (positive predictive value of p16 staining for the presence of transcriptionally active HPV = 0.12). HPV mRNA transcripts were not detected in any patient under 40 (n = 11), or in patients who had never smoked (n=44), had quit smoking (n=15), and/or were only light consumers of alcohol (n = 57). Conclusions HPV is not detected in the vast majority of lateral tongue carcinomas. In light of the observation that HPV plays little if any role in the development of these cancers, routine HPV testing is unwarranted , even for patients without traditional risk factors. P16 staining is not a reliable marker for the presence of transcriptionally active HPV at this particular anatomic site. PMID:24485566

  14. Interdependence of Gemcitabine Treatment, Transporter Expression, and Resistance in Human Pancreatic Carcinoma Cells

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    Wolfgang Hagmann

    2010-09-01

    Full Text Available Gemcitabine is widely used as first-line chemotherapeutic drug in the treatment of pancreatic cancer. Our previous experimental chemotherapy studies have shown that treatment of human pancreatic carcinoma cells with 5-fluorouracil (5-FU alters the cellular transporter expression profile and that modulation of the expression of multidrug resistance protein 5 (MRP5; ABCC5 influences the chemoresistance of these tumor cells. Here, we studied the influence of acute and chronic gemcitabine treatment on the expression of relevant uptake and export transporters in pancreatic carcinoma cells by reverse transcription-polymerase chain reaction (RT-PCR, quantitative RT-PCR, and immunoblot analyses. The specific role of MRP5 in cellular gemcitabine sensitivity was studied by cytotoxicity assays using MRP5-overexpressing and MRP5-silenced cells. Exposure to gemcitabine (12 nM for 3 days did not alter the messenger RNA (mRNA expression of MRP1, MRP3, MRP5, and equilibrative nucleoside transporter 1 (ENT1, whereas high dosages of the drug (20 µM for 1 hour elicited up-regulation of these transporters in most cell lines studied. In cells with acquired gemcitabine resistance (up to 160 nM gemcitabine, the mRNA or protein expression of the gemcitabine transporters MRP5 and ENT1 was upregulated in several cell lines. Combined treatment with 5-FU and gemcitabine caused a 5- to 40-fold increase in MRP5 and ENT1 expressions. Cytotoxicity assays using either MRP5-overexpressing (HEK and PANC-1 or MRP5-silenced (PANC1/shMRP5 cells indicated that MRP5 contributes to gemcitabine resistance. Thus, our novel data not only on drug-induced alterations of transporter expression relevant for gemcitabine uptake and export but also on the link between gemcitabine sensitivity and MRP5 expression may lead to improved strategies of future chemotherapy regimens using gemcitabine in pancreatic carcinoma patients.

  15. Human papillomavirus and post-transplant cutaneous squamous-cell carcinoma: a multicenter, prospective cohort study.

    Science.gov (United States)

    Bouwes Bavinck, Jan Nico; Feltkamp, Mariet C W; Green, Adele C; Fiocco, Marta; Euvrard, Sylvie; Harwood, Catherine A; Proby, Charlotte M; Naldi, Luigi; Diphoorn, Janouk C D; Venturuzzo, Anna; Tessari, Gianpaolo; Nindl, Ingo; Sampogna, Francesca; Abeni, Damiano; Neale, Rachel E; Goeman, Jelle J; Quint, Koen D; Halk, Anne Berthe; Sneek, Carmen; Genders, Roel E; de Koning, Maurits N C; Quint, Wim G V; Wieland, Ulrike; Weissenborn, Sönke; Waterboer, Tim; Pawlita, Michael; Pfister, Herbert

    2017-10-11

    Organ-transplant recipients (OTR) have a 100-fold increased risk of cutaneous squamous-cell carcinoma (cSCC). We prospectively evaluated the association between beta-genus human-papillomaviruses (betaPV) and keratinocyte carcinoma in OTR. Two OTR cohorts without cSCC were assembled: cohort 1 transplanted in 2003-2006 (n=274) and cohort 2 in 1986-2002 (n=352). Participants were followed until death or cessation of follow-up in 2016. BetaPV infection was assessed in eyebrow hairs using PCR-based methods. BetaPV IgG seroresponses were determined by multiplex serology. A competing risk model with delayed entry was used to estimate cumulative incidence of histologically proven cSCC and the effect of betaPV using a multivariable Cox regression model. Results are reported as adjusted hazard ratios (HR). OTR with ≥5 different betaPV types in eyebrow hairs had 1.7 times the risk of cSCC versus those with 0-4 different types (HR: 1.7 (1.1;2.6)). A similar risk was seen with high betaPV loads (HR: 1.8 (1.2;2.8)). No significant associations were seen between serum antibodies and cSCC or between betaPV and basal-cell carcinoma. The diversity and load of betaPV types in eyebrow hairs are associated with cSCC risk in OTR, providing evidence that betaPV is associated with cSCC carcinogenesis and may present a target for future preventive strategies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Prognostic impact of human papilloma virus (HPV) genotyping and HPV-16 subtyping in vaginal carcinoma.

    Science.gov (United States)

    Larsson, Gabriella Lillsunde; Helenius, Gisela; Andersson, Sören; Sorbe, Bengt; Karlsson, Mats G

    2013-05-01

    The objectives of this study are to investigate the human papilloma virus (HPV) distribution in vaginal cancer and to evaluate HPV-genotype as well as HPV16-variant impact on prognosis. Sixty-nine patients diagnosed with primary vaginal carcinoma (1975-2002) were included in the study. Detection of twelve high-risk HPV (hr HPV) and two low-risk HPV (lr HPV) was performed with realtime-PCR. Samples positive for HPV-16 were analyzed for variants in the E6-gene with PCR and pyrosequencing. 53.6% (37/69) of the tumors were found to be HPV-positive, mostly for HPV-16 (N=26). Other HPV-types were HPV-18 (N=2), HPV-31 (N=2), HPV-33 (N=2), HPV-45 (N=1), HPV-52 (N=2), HPV-56 (N=1) and HPV-58 (N=1). Only European subtypes of HPV-16 were represented and the two most common HPV-16-variants were E-p (N=13) and E-G350 (N=11). Patients with HPV-positive tumors (N=37) had a significantly (log-rank test=3.341; p=0.0008) superior 5-year overall survival rate as well as cancer-specific survival rate and progression-free survival rate (p=0.0002; p=0.0004), compared with patients with HPV-negative tumors (N=32). Interestingly, patients with HPV-16-positive tumors had a superior overall survival compared with patients with tumors containing other HPV-genotypes. In a Cox proportional multivariate analysis age, tumor size, and HPV-status were independent and significant prognostic factors with regard to overall survival rate. HPV-status is of prognostic importance in vaginal carcinoma and varies with viral genotype. In this era of HPV-vaccination, genotypes other than those included in the vaccination program could still lead to vaginal carcinoma with unfavorable prognosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Leptin as a critical regulator of hepatocellular carcinoma development through modulation of human telomerase reverse transcriptase

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    Stefanou Nikolaos

    2010-08-01

    Full Text Available Abstract Background Numerous epidemiological studies have documented that obesity is associated with hepatocellular carcinoma (HCC. The aim of this study was to investigate the biological actions regulated by leptin, the obesity biomarker molecule, and its receptors in HCC and the correlation between leptin and human telomerase reverse transcriptase (hTERT, a known mediator of cellular immortalization. Methods We investigated the relationship between leptin, leptin receptors and hTERT mRNA expression in HCC and healthy liver tissue samples. In HepG2 cells, chromatin immunoprecipitation assay was used to study signal transducer and activator of transcription-3 (STAT3 and myc/mad/max transcription factors downstream of leptin which could be responsible for hTERT regulation. Flow cytometry was used for evaluation of cell cycle modifications and MMP1, 9 and 13 expression after treatment of HepG2 cells with leptin. Blocking of leptin's expression was achieved using siRNA against leptin and transfection with liposomes. Results We showed, for the first time, that leptin's expression is highly correlated with hTERT expression levels in HCC liver tissues. We also demonstrated in HepG2 cells that leptin-induced up-regulation of hTERT and TA was mediated through binding of STAT3 and Myc/Max/Mad network proteins on hTERT promoter. We also found that leptin could affect hepatocellular carcinoma progression and invasion through its interaction with cytokines and matrix mettaloproteinases (MMPs in the tumorigenic microenvironment. Furthermore, we showed that histone modification contributes to leptin's gene regulation in HCC. Conclusions We propose that leptin is a key regulator of the malignant properties of hepatocellular carcinoma cells through modulation of hTERT, a critical player of oncogenesis.

  18. Multiple endocrine neoplasia similar to human subtype 2A in a dog: Medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma

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    E.A. Soler Arias

    2016-10-01

    Full Text Available Human multiple endocrine neoplasia subtype 2A (MEN 2A is characterized by medullary thyroid carcinoma, pheochromocytoma and parathyroid hyperplasia or adenoma in the same individual. In this report, a case of a female Rottweiler with medullary thyroid carcinoma, bilateral pheochromocytoma and parathyroid adenoma was described. Clinical manifestations of muscle weakness, polydipsia, polyuria, diarrhea and weight loss were observed. Two adrenal neoplasms were identified incidentally by ultrasonography, and tumor in the left thyroid lobe was identified by palpation. Primary hyperparathyroidism was diagnosed by biochemical testing. Histopathology report was consistent with diagnosis of bilateral pheochromocytoma and parathyroid adenoma. Immunohistochemical staining was positive for calcitonin and synaptophysin, and negative for thyroglobulin, which confirmed medullary thyroid carcinoma. This case in a dog is presenting neoplastic characteristics similar to human MEN 2A and emphasizing the importance of using immunohistochemistry for confirmation.

  19. Detection of human papillomavirus in laryngeal lesions by in situ hybridization

    DEFF Research Database (Denmark)

    Multhaupt, H A; Fessler, J N; Warhol, M J

    1994-01-01

    Human papillomavirus (HPV) is associated with human neoplasms of squamous epithelium. Squamous papillomas and verrucous carcinomas are two types of squamous neoplasms of the larynx that present difficult problems in differential diagnosis. Using in situ hybridization with biotinylated DNA probes...... Hospital, Philadelphia, PA. Tissue sections were hybridized with an HPV DNA cocktail. The HPV-positive cases then were subtyped further with DNA probes specific for HPV subtypes 6/11, 16/18, and 31/33/35. All benign squamous papillomas (42 of 42) were positive for HPV subtype 6/11. None of the verrucous...

  20. Cytoplasmic Skp2 expression is associated with p-Akt1 and predicts poor prognosis in human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Jing Liu

    Full Text Available BACKGROUND: S-phase kinase protein 2 (Skp2, an oncogenic protein, is a key regulator in different cellular and molecular processes, through ubiquitin-proteasome degradation pathway. Increased levels of Skp2 are observed in various types of cancer and associated with poor prognosis. However, in human breast carcinomas, the underlying mechanism and prognostic significance of cytoplasmic Skp2 is still undefined. METHODS: To investigate the role of cytoplasmic Skp2 expression in human breast carcinomas, we immnohistochemically assessed cytoplasmic Skp2, p-Akt1, and p27 expression in 251 patients with invasive ductal carcinomas of the breast. Association of cytoplasmic Skp2 expression with p-Akt1 and p27 was analyzed as well as correspondence with other clinicopathological parameters. Disease-free survival and overall survival were determined based on the Kaplan-Meier method and Cox regression models. RESULTS: Cytoplasmic of Skp2 was detected in 165 out of 251 (65.7% patients. Cytoplasmic Skp2 expression was associated with larger tumor size, more advanced histological grade, and positive HER2 expression. Increased cytoplasmic Skp2 expression correlated with p-Akt1 expression, with 54.2% (51/94 of low p-Akt1-expressing breast carcinomas, but 72.6% (114/157 of high p-Akt1-expressing breast carcinomas exhibiting cytoplasmic Skp2 expression. Elevated cytoplasmic Skp2 expression with low p-Akt1 expression was associated with poor disease-free and overall survival (DFS and OS, and Cox regression models demonstrated that cytoplasmic Skp2 expression was an independent prognostic marker for invasive breast carcinomas. CONCLUSION: Cytoplasmic Skp2 expression is associated with aggressive prognostic factors, such as larger tumor size, and advanced histological grade of the breast cancers. Results demonstrate that combined cytoplasmic Skp2 and p-Akt1 expression may be prognostic for patients with invasive breast carcinomas, and cytoplasmic Skp2 may serve as a

  1. Adenoid cystic carcinoma of the mandible : Case report | Lawal ...

    African Journals Online (AJOL)

    Adenoid Cystic Carcinoma (ACC) is an uncommon salivary gland malignancy which can also develop in the mucus glands of the larynx, trachea, bronchus, lungs and mammary glands besides the head and neck region (1). The most frequently affected sites are the parotid gland, sub-mandibular gland and palate, whereas ...

  2. Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Dai W

    2016-04-01

    Full Text Available Wei Dai,1,2 Changfu Sun,1,2 Shaohui Huang,1,2 Qing Zhou1,21Department of Oromaxillofacial-Head and Neck Surgery, 2Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaAbstract: Carvacrol, a component of thyme oil, as a novel antitumor agent, has been implicated in several types of cancer cells. However, the mechanisms underlying the effect of carvacrol in human oral squamous cell carcinoma (OSCC remain unclear. Here, we report that carvacrol significantly inhibits tumor cell proliferation, metastasis and invasion, and induces apoptosis in OSCC. Our results demonstrated that the molecular mechanisms of the effect of carvacrol in Tca-8113 induces G1/S cell cycle arrest through downregulation of CDK regulator CCND1 and CDK4, and upregulation of CDK inhibitor P21. Further analysis demonstrated that carvacrol also inhibited Tca-8113 cells’ clone formation in clonogenic cell survival assay. Student’s t-test (two-tailed was used to compare differences between groups, and the significance level was P<0.01. Then, treatment of Tca-8113 cells with carvacrol resulted in downregulation of Bcl-2, Cox2, and upregulation of Bax. Carvacrol significantly inhibited the migration and invasion of human OSCC cells by blocking the phosphorylation of FAK and MMP-9 and MMP-2, transcription factor ZEB1, and β-catenin proteins’ expression. Taken together, these results provide novel insights into the mechanism of carvacrol and suggest potential therapeutic strategies for human OSCC.Keywords: carvacrol, proliferation, metastasis and invasion, oral squamous cell carcinoma

  3. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

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    Anthony Skipper

    2016-01-01

    Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

  4. Marked activity of irofulven toward human carcinoma cells: comparison with cisplatin and ecteinascidin.

    Science.gov (United States)

    Poindessous, Virginie; Koeppel, Florence; Raymond, Eric; Comisso, Martine; Waters, Stephen J; Larsen, Annette K

    2003-07-01

    To characterize the activities of irofulven, a novelanticancer agent derived from the mushroom natural productilludin S toward human cancer cells. We have determined the activity spectrum of irofulven toward a human tumor cell panel comprised of 10 different tumor types in comparison with cisplatin and ET-743. We have also evaluated the influence of major resistance mechanisms, such as expression of multidrug resistance-associated drug efflux pumps, cisplatin resistance, loss of p53 function, and absence of mismatch repair on the cytotoxic activity of irofulven. The activity spectrum of irofulven is clearly different from that of ET-743 and cisplatin. Irofulven shows excellent cytotoxicity toward the majority of human carcinoma cell lines tested, but lesser activity toward sarcoma and leukemia cell lines. The cytotoxic activity of irofulven was particularly pronounced toward head and neck, non-small cell lung, colon, and ovary carcinoma cells, as well as toward malignant glioma cell lines. In addition, irofulven displayed good activity toward poorly differentiated, androgen-independent prostate cancer cells and cell lines expressing high levels of the detoxifying enzymes glutathione S-transferase and gamma-glutamyl cysteine synthetase. The cytotoxicity of irofulven was not affected by loss of p53 or mismatch repair function, and the drug was not a substrate for multidrug transporters, such as the P-glycoprotein and multidrug resistance protein 1. Irofulven has an unusual activity spectrum with strong activity toward tumor cells of epithelial origin. Furthermore, irofulven is not or only marginally affected by resistance mechanisms limiting the efficacy of other alkylating agents.

  5. Reduced cilia frequencies in human renal cell carcinomas versus neighboring parenchymal tissue

    Directory of Open Access Journals (Sweden)

    Basten Sander G

    2013-01-01

    Full Text Available Abstract Background Cilia are essential organelles in multiple organ systems, including the kidney where they serve as important regulators of renal homeostasis. Renal nephron cilia emanate from the apical membrane of epithelia, extending into the lumen where they function in flow-sensing and ligand-dependent signaling cascades. Ciliary dysfunction underlies renal cyst formation that is in part caused by deregulation of planar cell polarity and canonical Wnt signaling. Renal cancer pathologies occur sporadically or in heritable syndromes caused by germline mutations in tumor suppressor genes including VHL. Importantly, Von Hippel-Lindau (VHL patients frequently develop complex renal cysts that can be considered a premalignant stage. One of the well-characterized molecular functions of VHL is its requirement for the maintenance of cilia. In this study, tissue from 110 renal cancer patients who underwent nephrectomy was analyzed to determine if lower ciliary frequency is a common hallmark of renal tumorigenesis by comparing cilia frequencies in both tumor and adjacent parenchymal tissue biopsies from the same kidney. Methods We stained sections of human renal material using markers for cilia. Preliminary staining was performed using an immunofluorescent approach and a combination of acetylated-α-tubulin and pericentrin antibodies and DAPI. After validation of an alternative, higher throughput approach using acetylated-α-tubulin immunohistochemistry, we continued to manually quantify cilia in all tissues. Nuclei were separately counted in an automated fashion in order to determine ciliary frequencies. Similar staining and scoring for Ki67 positive cells was performed to exclude that proliferation obscures cilia formation potential. Results Samples from renal cell carcinoma patients deposited in our hospital tissue bank were previously used to compose a tissue microarray containing three cores of both tumor and parenchymal tissue per patient

  6. Macrophages modulate migration and invasion of human tongue squamous cell carcinoma.

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    Pirilä, Emma; Väyrynen, Otto; Sundquist, Elias; Päkkilä, Kaisa; Nyberg, Pia; Nurmenniemi, Sini; Pääkkönen, Virve; Pesonen, Paula; Dayan, Dan; Vered, Marilena; Uhlin-Hansen, Lars; Salo, Tuula

    2015-01-01

    Oral tongue squamous cell carcinoma (OTSCC) has a high mortality rate and the incidence is rising worldwide. Despite advances in treatment, the disease lacks specific prognostic markers and treatment modality. The spreading of OTSCC is dependent on the tumor microenvironment and involves tumor-associated macrophages (TAMs). Although the presence of TAMs is associated with poor prognosis in OTSCC, the specific mechanisms underlying this are still unknown. The aim here was to investigate the effect of macrophages (Mfs) on HSC-3 tongue carcinoma cells and NF-kappaB activity. We polarized THP-1 cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type Mfs. We then investigated the effect of Mfs on HSC-3 cell migration and NF-kappaB activity, cytokine production and invasion using several different in vitro migration models, a human 3D tissue invasion model, antibody arrays, confocal microscopy, immunohistochemistry and a mouse invasion model. We found that in co-culture studies all types of Mfs fused with HSC-3 cells, a process which was partially due to efferocytosis. HSC-3 cells induced expression of epidermal growth factor and transforming growth factor-beta in co-cultures with M2 Mfs. Direct cell-cell contact between M2 Mfs and HSC-3 cells induced migration and invasion of HSC-3 cells while M1 Mfs reduced HSC-3 cell invasion. M2 Mfs had an excess of NF-kappaB p50 subunit and a lack of p65 subunits both in the presence and absence of HSC-3 cells, indicating dysregulation and pro-tumorigenic NF-kappaB activation. TAM-like cells were abundantly present in close vicinity to carcinoma cells in OTSCC patient samples. We conclude that M2 Mfs/TAMs have an important role in OTSCC regulating adhesion, migration, invasion and cytokine production of carcinoma cells favouring tumor growth. These results demonstrate that OTSCC patients could benefit from therapies targeting TAMs, polarizing TAM-like M2 Mfs to inflammatory macrophages and modulating NF

  7. Stromal interaction molecule 1 regulates growth, cell cycle, and apoptosis of human tongue squamous carcinoma cells.

    Science.gov (United States)

    Cui, Xiaobo; Song, Laixiao; Bai, Yunfei; Wang, Yaping; Wang, Boqian; Wang, Wei

    2017-04-30

    Oral tongue squamous cell carcinoma (OTSCC) is the most common type of oral carcinomas. However, the molecular mechanism by which OTSCC developed is not fully identified. Stromal interaction molecule 1 (STIM1) is a transmembrane protein, mainly located in the endoplasmic reticulum (ER). STIM1 is involved in several types of cancers. Here, we report that STIM1 contributes to the development of human OTSCC. We knocked down STIM1 in OTSCC cell line Tca-8113 with lentivirus-mediated shRNA and found that STIM1 knockdown repressed the proliferation of Tca-8113 cells. In addition, we also showed that STIM1 deficiency reduced colony number of Tca-8113 cells. Knockdown of STIM1 repressed cells to enter M phase of cell cycle and induced cellular apoptosis. Furthermore, we performed microarray and bioinformatics analysis and found that STIM1 was associated with p53 and MAPK pathways, which may contribute to the effects of STIM1 on cell growth, cell cycle, and apoptosis. Finally, we confirmed that STIM1 controlled the expression of MDM2, cyclin-dependent kinase 4 (CDK4), and growth arrest and DNA damage inducible α (GADD45A) in OTSCC cells. In conclusion, we provide evidence that STIM1 contributes to the development of OTSCC partially through regulating p53 and MAPK pathways to promote cell cycle and survival. © 2017 The Author(s).

  8. Registered report: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma.

    Science.gov (United States)

    Repass, John; Maherali, Nimet; Owen, Kate

    2016-02-11

    The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from 'Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma' by Castellarin and colleagues published in Genome Research in 2012 (Castellarin et al., 2012). The experiment to be replicated is reported in Figure 2. Here, Castellarin and colleagues performed a metagenomic analysis of colorectal carcinoma (CRC) to identify potential associations between inflammatory microorganisms and gastrointestinal cancers. They conducted quantitative real-time PCR on genomic DNA isolated from tumor and matched normal biopsies from a patient cohort and found that the overall abundance of Fusobacterium was 415 times greater in CRC versus adjacent normal tissue. These results confirmed earlier studies and provide evidence for a link between tissue-associated bacteria and tumorigenesis. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.

  9. Acacia catechu ethanolic bark extract induces apoptosis in human oral squamous carcinoma cells

    Directory of Open Access Journals (Sweden)

    Thangavelu Lakshmi

    2017-01-01

    Full Text Available Oral cancer is in approximately 30% of all cancers in India. This study was conducted to evaluate the cytotoxic activity of ethanolic extract of Acacia catechu bark (ACB against human squamous cell carcinoma cell line-25 (SCC-25. Cytotoxic effect of ACB extract was determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium Bromide assay. A. catechu extract was treated SCC-25 cells with 25 and 50 μg/mL for 24 h. Apoptosis markers such as caspases-8 and 9, bcl-2, bax, and cytochrome c (Cyt-c were done by RT-PCR. Morphological changes of ACB treated cells were evaluated using acridine orange/ethidium bromide (AO/EB dual staining. Nuclear morphology and DNA fragmentation were evaluated using propidium iodide (PI staining. Further, cell cycle analysis was performed using flow cytometry. A. catechu treatment caused cytotoxicity in SCC-25 cells with an IC50 of 52.09 μg/mL. Apoptotic marker gene expressions were significantly increased on ACB treatment. Staining with AO/EB and PI shows membrane blebbing and nuclear membrane distortion, respectively, and it confirms the apoptosis induction in SCC-25 cells. These results suggest that ACB extract can be used as a modulating agent in oral squamous cell carcinoma.

  10. Allicin inhibits human renal clear cell carcinoma progression via suppressing HIF pathway.

    Science.gov (United States)

    Song, Bin; Shu, Ying; Cui, Tianlei; Fu, Ping

    2015-01-01

    Hypoxia-inducible factor 1-alpha (HIF-1α) protects hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. Allicin is characterized by the anti-cancer characteristics. This study aims to explore whether allicin is involved in renal clear cell carcinoma progression through HIF-1α. A total of 40 RCC tissues and 39 normal renal tissues were collected H&E and immunohistochemistry were applied to study morphology changes. MTT assay and flow cytometry (FCM) were used to analyze cell viability and apoptosis. In vitro colony formation assay and wound healing assay were conducted to explore cell migration. The protein levels of Bcl-2, VEGF and HIF-1α were increased in RCC tissues. More importantly, treatment with allicin significantly decreased HIF-1α protein level, thereby reducing Bcl-2 and VEGF expression. In addition, allicin also obviously enhanced apoptotic cells. And colony formation capacity and cell migration rate were reduced in RCC-9863 cells treated with allicin. Further study revealed that overexpression of HIF-1α could partially repress allicin-induced downstream effects. To conclude, allicin inhibits human renal clear cell carcinoma progression partially by suppressing HIF pathway.

  11. Acetaminophen Enhances Cisplatin- and Paclitaxel-mediated Cytotoxicity to SKOV3 Human Ovarian Carcinoma

    Science.gov (United States)

    Wu, Y. Jeffrey; Neuwelt, Alexander J.; Muldoon, Leslie L.; Neuwelt, Edward A.

    2013-01-01

    Background Ovarian cancer is commonly treated with cisplatin/paclitaxel but many tumors become resistant. Acetaminophen reduced glutathione and enhanced chemotherapy efficacy in treating hepatic cancer. The objective of this study was to examine if acetaminophen enhances the cytotoxicity of cisplatin/paclitaxel in ovarian cancer. Materials and Methods SKOV3 human ovarian carcinoma cells in vitro and a subcutaneous tumor nude rat model were used and treated with cisplatin/paclitaxel with or without acetaminophen. Results In vitro, acetaminophen enhanced apoptosis induced by cisplatin and paclitaxel with similar effects on glutathione, reactive oxygen species and mitochondrial membrane potential but different effects on nuclear factor erythroid 2-related factor 2 (NRF2) translocation. In vivo, acetaminophen was uniformly distributed in tissue and significantly reduced hepatic glutathione. Acetaminophen enhanced cisplatin chemotherapeutic effect by reducing tumor recurrence Conclusion Our results suggest that acetaminophen as a chemoenhancing adjuvant could improve the efficacy of cisplatin and paclitaxel in treating patients with ovarian carcinoma and other tumor types. PMID:23749887

  12. Identification of p53 and Its Isoforms in Human Breast Carcinoma Cells

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    Zorka Milićević

    2014-01-01

    Full Text Available In breast carcinoma, disruption of the p53 pathway is one of the most common genetic alterations. The observation that the p53 can express multiple protein isoforms adds a novel level of complexity to the outcome of p53 mutations. p53 expression was analysed by Western immunoblotting and immunohistochemistry using monoclonal antibodies DO-7, Pab240, and polyclonal antiserum CM-1. The more frequently p53-positive nuclear staining has been found in the invasive breast tumors. One of the most intriguing findings is that mutant p53 appears as discrete dot-shaped regions within the nucleus of breast cancer cells. In many malignant cells, the nucleolar sequestration of p53 is evident. These observations support the view that the nucleolus is involved directly in the mediation of p53 function or indirectly by the control of the localization of p53 interplayers. p53 expressed in the nuclear fraction of breast cancer cells revealed a wide spectrum of isoforms. p53 isoforms ΔNp53 (47 kDa and Δ133p53β (35 kDa, known as dominant-negative repressors of p53 function, were detected as the most predominant variants in nuclei of invasive breast carcinoma cells. The isoforms expressed also varied between individual tumors, indicating potential roles of these p53 variants in human breast cancer.

  13. Human papilloma virus in oral squamous cell carcinoma in a Mexican population.

    Science.gov (United States)

    Ibieta, Blanca R; Lizano, Marcela; Fras-Mendivil, Mauricio; Barrera, José L; Carrillo, Adela; Ma Ruz-Godoy, Luz; Mohar, Alejandro

    2005-03-01

    To determine the human papilloma virus (HPV) infection in oral cancer and its association with smoking and drinking habits. A cross-sectional study was performed; samples were collected from 51 patients with histological diagnosis of squamous-cell carcinoma were collected at the Instituto Nacional de Cancerología in Mexico City. HPV infection was detected by polymerase chain reaction, and the clinical characteristics of this population were analyzed. Fifty samples out of 51 were positive for beta-globin; 21 (42%) cases were HPV-positive, and 14/21 were positive for HPV-16. We found more samples positive in men than in women (71% vs 29%). No differences were observed between HPV-positive and -negative patients in relation to smoking and drinking habits (81% vs 79%). HPV infection was present in 42% of patients with oral squamous-cell carcinoma (OSCC); HPV-16 was the most frequent type, identified in 66.6%. Other cofactors participate in the development of OSCC, independent of HPV infection.

  14. First-in-human trial of nanoelectroablation therapy for basal cell carcinoma: proof of method.

    Science.gov (United States)

    Nuccitelli, Richard; Wood, Ryan; Kreis, Mark; Athos, Brian; Huynh, Joanne; Lui, Kaying; Nuccitelli, Pamela; Epstein, Ervin H

    2014-02-01

    This nanoelectroablation therapy effectively treats subdermal murine allograft tumors, autochthonous basal cell carcinoma (BCC) tumors in Ptch1+/-K14-Cre-ER p53 fl/fl mice, and UV-induced melanomas in C57/BL6 HGF/SF mice. Here, we described the first human trial of this modality. We treated 10 BCCs on three subjects with 100-1000 electric pulses 100 ns in duration, 30 kV/cm in amplitude, applied at 2 pulses per second. Seven of the 10 treated lesions were completely free of basaloid cells when biopsied and two partially regressed. Two of the 7 exhibited seborrheic keratosis in the absence of basaloid cells. One of the 10 treated lesions recurred by week 10 and histologically had the appearance of a squamous cell carcinoma. No scars were visible at the healed sites of any of the successfully ablated lesions. One hundred pulses were sufficient for complete ablation of BCCs with a single, 1-min nanoelectroablation treatment. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Mogoltacin enhances vincristine cytotoxicity in human transitional cell carcinoma (TCC) cell line.

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    Behnam Rassouli, F; Matin, M M; Iranshahi, M; Bahrami, A R; Neshati, V; Mollazadeh, S; Neshati, Z

    2009-03-01

    Bladder cancer is the second common cancer of the genitourinary system throughout the world and intravesical chemotherapy is usually used to reduce tumour recurrence and progression. Human transitional cell carcinoma (TCC) is an epithelial-like adherent cell line originally established from primary bladder carcinoma. Here we report the effect of mogoltacin, a sesquiterpene coumarin from Ferula badrakema on TCC cells. Mogoltacin was isolated from the fruits of F. badrakema, using silica gel column chromatography and preparative thin layer chromatography. Mogoltacin did not have any significant cytotoxicity effect on neoplastic TCC cells at 16, 32, 64, 128, 200 and 600 microg ml(-1) concentrations. In order to analyse its combination effect, TCC cells were cultured in the presence of various combining concentrations of mogoltacin and vincristine. Cells were then observed for morphological changes (by light microscopy) and cytotoxicity using MTT assay. The effect of mogoltacin on vincristine toxicity was studied after 24, 48 and 72 h of drug administration. The results of MTT assay showed that mogoltacin can significantly enhance the cytotoxicity of vincristine and confirmed the morphological observations. Results revealed that combination of 40 microg ml(-1) vincristine with 16 microg ml(-1) mogoltacin increased the cytotoxicity of vincristine after 48 h by 32.8%.

  16. Galectin-3 inhibition sensitizes human renal cell carcinoma cells to arsenic trioxide treatment.

    Science.gov (United States)

    Xu, Yangyang; Gu, Xin; Gong, Mancheng; Guo, Guiying; Han, Kaiyu; An, Ruihua

    2013-10-01

    The anti-tumor effects of arsenic trioxide (ATO) were well established in acute promyelocytic leukemia, but not in renal cell carcinoma (RCC). Recent evidences indicate that galectin-3 (Gal-3) plays an anti-apoptotic role in chemotherapy induced tumor cell death. This study was intended to clarify the exact roles of Gal-3 performed in ATO-induced apoptosis in RCC cells. Weak apoptosis was observed in Gal-3-positive RCC cells (Caki-1, Caki-2, 786-0, and ACHN) following ATO treatment. However, ATO treatment upregulated Gal-3 expression concurrently caused a Synexin-cooperated translocation of Gal-3 from the nucleus to the cytoplasm. Gal-3-knockdown cells were more sensitive to ATO treatment as indicated by a strong mitochondria-dependent apoptosis following ATO treatment. Meanwhile, Gal-3 was found to inhibit ATO-induced apoptosis through enhancing Bcl-2 expression and stabilizing mitochondria. To confirm the results obtained from genetic method, we employed a Gal-3 inhibitor, modified citrus prectin (MCP), and co-treated the RCC cells with ATO. The cells showed an increased apoptosis in the syngeneic application of Gal-3 inhibition and ATO compared with ATO application alone. Based on these results, we conclude that Gal-3 inhibition sensitizes human renal cell carcinoma cells to ATO treatment through increasing mitochondria-dependent apoptosis. Our studies implicate synergetic application of ATO and Gal-3 inhibition as a potential strategy for RCC treatment.

  17. c-Fos is involved in inhibition of human bladder carcinoma T24 cells by brazilin.

    Science.gov (United States)

    Zhang, Tingting; Fan, Xinping; Song, Lili; Ren, Lu; Ma, Enbo; Zhang, Shengwan; Ren, Liansheng; Zheng, Yaowu; Zhang, Jianzhen

    2015-03-01

    Crude brazilin extract from Sappan wood has demonstrated strong anti tumor activity in the mouse model of human bladder carcinoma and clinical trial for intravesical therapy. Purified brazilin was confirmed the most active molecule in inhibition of bladder carcinoma T24 cells. Brazilin decreased proliferation and viability of T24 cells in a dose- and time-dependent manner, with a calculated LC50 of 32 µg/mL. More than 1,000 of genes were found upregulated and down regulated by brazilin treatment in digital gene expression profiling. Gene ontology analysis indicated that stress response, apoptosis, and cell cycle regulatory pathways were highly enriched. Among the regulated genes, c-Fos was the most and specifically upregulated. Overexpression of c-Fos in T24 cells resulted in tumor cell specific changes in cell morphology and viability. Over expression of stress-responsive gene, HSP70, and other highly upregulated genes did not have any effect on cell growth. Brazilin may inhibit T24 cell growth and trigger cell death through a c-Fos-mediated and tumor cell specific signaling pathway. Further studies of its down stream mediators may help to identify better tumor cell type specific drug targets. © 2015 International Union of Biochemistry and Molecular Biology.

  18. Gene methylation of human ovarian carcinoma stromal progenitor cells promotes tumorigenesis.

    Science.gov (United States)

    Ho, Chih-Ming; Shih, Daniel Tzu-Bi; Hsiao, Chih-Chiang; Huang, Shih-Hung; Chang, Shwu-Fen; Cheng, Wen-Fang

    2015-11-23

    This study aimed to investigate whether the DNA methylation of human ovarian carcinoma stromal progenitor cells (OCSPCs) could promote the tumorigenesis of ovarian carcinoma. OCSPCs were first isolated from fresh tumor tissues and ascites of ovarian cancer patients. In vivo and in vitro experiments on the effect of the OCSPCs on tumorigenesis and the effects of DNA demethylation on the OCSPCs were then performed. The OCSPCs possessed self-renewal and multipotent differentiation capacity with elevated expressions of OCT4, NANOG, BMP2, BMP4, Rex-1, AC133 and TGF-β. The OCSPCs, when combined with tumor cells in vivo could promote tumor growth. The methylation profiles of tumor suppressor genes (TSGs) were significantly higher in the OCSPCs than in ovarian cancer cells (p cells. The expression levels of TSGs were re-expressed by 5-aza-2-dC to inhibit the self-renewal and growth of OCSPCs. OCSPCs with decreased TSG expressions in the ovarian tumor microenvironment were able to promote tumorigenesis which could be reversed by DNA demethylation. DNA demethylation reversing the expression of TSGs in OCSPCs may represent a potential therapeutic target for ovarian cancer.

  19. Growth of human prostate carcinomas with and without hormone alpha- dehydrotestosterone in nude mice.

    Science.gov (United States)

    Baisch, H; Otto, U; Fack, H

    1998-12-01

    The dependence of human prostate carcinoma growth on hormone was studied in xenotransplants in nude mice. The objective was to determine differences in cell kinetic parameters and volume growth of tumors growing with alpha-dehydrotestosterone (alphaDHT) and without alphaDHT. These differences could be used as arguments pro and contra the adaptation versus the clonal selection hypothesis. Human prostate carcinomas were xenotransplanted into nude mice. Growth of tumors was observed in castrated male mice without and with implanted osmotic pumps secreting alphaDHT. In a further series of experiments the alphaDHT tubes were removed when the tumors had reached a volume of 0.3 cm3. Tumor volume was measured to determine tumor doubling time with and without alphaDHT. Detailed cell kinetics were analyzed using the bromodeoxyuridine (BrdUrd) method with flow cytometry. Applying the relative movement (RM) and a simulation analysis to parallel single and multiple BrdUrd labelling experimental data we determined transit times through the phases of cell cycle, potential doubling time Tpot, growth fraction (GF) and cell loss. Five human prostate carcinomas were xenotransplanted into nude mice. Tumor take was only achieved when androgen hormone was present. However, when alphaDHT was removed when the tumors had grown to a volume of 0.3 cm3, they continued to grow at nearly the same Td as those tumors with continued alphaDHT application. The BrdUrd experiments, on the other hand, showed considerable increase of Tc and Tpot upon withdrawal of alphaDHT in 4 out of 5 tumors. The GF and labelling index (LI) were maintained at about the same level as alphaDHT consuming tumors. While small transplanted tumor pieces do not grow without alphaDHT, larger tumors grow with the same Td after removal of alphaDHT. The slower proliferation shown by the increased Tc and Tpot is balanced by less cell loss. Since GF and LI were maintained at about the same level, we conclude that in our tumors the

  20. Papilomavírus humano e sua associação com o carcinoma colorretal Human papillomavirus and its association with colorectal carcinoma

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    Carmen Ruth Manzione

    2010-12-01

    Full Text Available Atualmente, sabe-se que 15% dos tumores malignos humanos têm associação com infecções virais. Destes, 80% correspondem aos carcinomas da cérvix uterina, associados ao papilomavírus humano (HPV, e aos hepatocarcinomas. Nos últimos anos, entretanto, artigos da literatura especializada vêm mostrando a presença do DNA do HPV em amostras de tecido de carcinomas do esôfago, estômago, pulmão, da mama e do cólon e reto, o que foi negado por outros autores. O HPV vem sendo encontrado entre 41,7 e 82,1% dos adenocarcinomas e entre 28 e 56% dos adenomas do cólon. Embora o DNA viral esteja integrado ao tumoral, a maneira de contaminação não é evidente. As vias linfáticas e hematogênicas não são reconhecidas. Fica a dúvida quanto à especificidade dos exames de detecção viral e quanto às formas de disseminação viral para os segmentos mais proximais do cólon. De qualquer forma, a literatura não é categórica em afirmar se esse vírus pode ser agente causal da doença, sendo necessários mais estudos para definir esse assunto.Nowadays, we know that 15% of all malignancies have association with viral infections; 80% of them are cervical carcinomas, provoked by human papillomavirus (HPV, and liver carcinomas. However, in the last years, many articles are revealing HPV types occurrence in specimens of carcinomas from esophagus, stomach, lung, breast and colon and rectum, which was denied by other authors. HPV DNA was found in 41.7 to 82.1% of colon carcinomas and in 28 to 56% of colon adenomas. Although viral DNA is integrated with tumoral DNA, the way of contamination is not evident. Hematogenic and lymphatic routes are not well defined. There is doubt concerning the specificity of the exams of viral detection and the ways of viral dissemination in proximal colonic segments. Anyway, literature is not sure to affirm if this virus could be causal agent of this kind of cancer, and more studies are necessary.

  1. Decreased helenalin-induced cytotoxicity by flavonoids from Arnica as studied in a human lung carcinoma cell line

    NARCIS (Netherlands)

    Woerdenbag, HJ; Merfort, [No Value; Schmidt, TJ; Passreiter, CM; Willuhn, G; vanUden, W; Pras, N; Konings, AWT

    1995-01-01

    The effect of the flavones apigenin, luteolin, hispidulin and eupafolin, and of the flavonols kaempferol, quercetin, 6-methoxykaempferol and patuletin from Amica spp, on the cytotoxicity of the sesquiterpene lactone helenalin was studied in the human lung carcinoma cell line GLC(4) using the

  2. Polarimetry based partial least square classification of ex vivo healthy and basal cell carcinoma human skin tissues.

    Science.gov (United States)

    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ikram, Masroor

    2016-06-01

    Optical polarimetry was employed for assessment of ex vivo healthy and basal cell carcinoma (BCC) tissue samples from human skin. Polarimetric analyses revealed that depolarization and retardance for healthy tissue group were significantly higher (ppolarimetry together with PLS statistics hold promise for automated pathology classification. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients

    NARCIS (Netherlands)

    Braakhuis, B.J.M.; Rietbergen, M.M.; Buijze, M.; Snijders, P.J.F.; Bloemena, E.; Brakenhoff, R.H.; Leemans, C.R.

    2014-01-01

    Objective Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. Methods TP53 mutations

  4. Laryngeal carcinoma in a non-smoker female patient with thyroid carcinoma: report of a case.

    Science.gov (United States)

    Shimizu, Naoki; Okamoto, Hideyuki; Koyama, Shinji; Yane, Katsunari; Hosoi, Hiroshi; Okamura, Ryuji

    2008-12-01

    Laryngeal carcinoma is usually encountered in smoker men, and thyroid carcinoma is sometimes discovered incidentally during treatment for these patients. However, this coexistence of malignancies could occur in non-smoker female. We report an unusual case of multiple primary malignancies in the larynx and the thyroid gland. The laryngeal carcinoma was suspected to be related to the malignant transformation of the papillomas. The case suggests the importance of meticulous examination in the head and neck region for treatment of cervical metastatic lymph nodes with negative cytology in non-smoker female.

  5. Wnt pathway reprogramming during human embryonal carcinoma differentiation and potential for therapeutic targeting

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    Bee Thomas

    2009-10-01

    Full Text Available Abstract Background Testicular germ cell tumors (TGCTs are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency. Methods Human embryonal carcinoma cells were stably infected with a lentiviral construct carrying a canonical Wnt responsive reporter to assess Wnt signalling activity following induced differentiation. Cells were differentiated with all-trans retinoic acid (RA or by targeted repression of pluripotency factor, POU5F1. A Wnt pathway real-time-PCR array was used to evaluate changes in gene expression as cells differentiated. Highlighted Wnt pathway genes were then specifically repressed using siRNA or stable shRNA and transfected EC cells were assessed for proliferation, differentiation status and levels of core pluripotency genes. Results Canonical Wnt signalling activity was low basally in undifferentiated EC cells, but substantially increased with induced differentiation. Wnt pathway gene expression levels were compared during induced differentiation and many components were altered including ligands (WNT2B, receptors (FZD5, FZD6, FZD10, secreted inhibitors (SFRP4, SFRP1, and other effectors of Wnt signalling (FRAT2, DAAM1, PITX2, Porcupine. Independent repression of FZD5, FZD7 and WNT5A using transient as well as stable methods of RNA interference (RNAi inhibited cell growth of pluripotent NT2/D1 human EC cells, but did not appreciably induce differentiation or repress key pluripotency genes. Silencing of FZD7 gave the greatest growth suppression in all human EC cell lines

  6. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines

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    Scheffner, M.; Muenger, K.; Byrne, J.C.; Howley, P.M. (National Cancer Inst., Bethesda, MD (United States))

    1991-07-01

    Human cervical carcinoma cell lines that were either positive or negative for human papillomavirus (HPV) DNA sequences were analyzed for evidence of mutation of the p53 and retinoblastoma genes. Each of five HPV-positive cervical cancer cell lines expressed normal pRB and low levels of wild-type p53 proteins, which are presumed to be altered in function as a consequence of association with HPV E7 and E6 oncoproteins, respectively. In contrast, mutations were identified in the p53 and RB genes expressed in the C-33A and HT-3 cervical cancer cell lines, which lack HPV DNA sequences. Mutations in the p53 genes mapped to codon 273 and codon 245 in the C33-A and HT-3 cell lines, respectively, located in the highly conserved regions of p53, where mutations appear in a variety of human cancers. Mutations in RB occurred at splice junctions, resulting in in-frame deletions, affecting exons 13 and 20 in the HT-3 and C-33A cell lines, respectively. These mutations resulted in aberrant proteins that were not phosphorylated and were unable to complex with the adenovirus E1A oncoprotein. These results support the hypothesis that the inactivation of the normal functions of the tumor-suppressor proteins pRB and p53 are important steps in human cervical carcinogenesis, either by mutation or from complex formation with the HPV E6 and E7 oncoproteins.

  7. Cell death after high-LET irradiation in orthotopic human hepatocellular carcinoma in vivo.

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    Altmeyer, Anaïs; Ignat, Mihaela; Denis, Jean-Marc; Messaddeq, Nadia; Gueulette, John; Mutter, Didier; Bischoff, Pierre

    2011-01-01

    Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and a major health problem since the choice of treatment is limited due to chemo- and radio-resistance. It was previously reported that high linear energy transfer (LET) radiation induced massive autophagic cell death in the human HCC SK-Hep1 cell line in vitro. This study analyzed the effects of high-LET radiation on the same HCC tumor model, orthotopically transplanted into nude mice. For this purpose, after surgical xenograft in the liver, animals were irradiated with fast neutrons and cell death occurring in the tumors was assessed with various techniques, including electron microscopy and probe-based confocal laser endomicroscopy. Results indicate that considerable autophagy and only limited apoptosis took place in the tumor xenografts after high-LET irradiation. These data confirm the previous in vitro results, suggesting that autophagy may act as a predominant mode of cell death in the efficacy of high-LET radiation.

  8. Celecoxib-induced cytotoxic effect is potentiated by inhibition of autophagy in human urothelial carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kuo-How Huang

    Full Text Available Celecoxib, a cyclooxygenase-2 (COX-2 inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum (ER stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine (3-MA, bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC.

  9. Anticancer activity of Moringa oleifera mediated silver nanoparticles on human cervical carcinoma cells by apoptosis induction.

    Science.gov (United States)

    Vasanth, Karunamoorthy; Ilango, Kaliappan; MohanKumar, Ramasamy; Agrawal, Aruna; Dubey, Govind Prasad

    2014-05-01

    Silver nanomaterial plays a crucial role in the growing field of nanotechnology as there is an increasing commercial demand for silver nanoparticles (AgNPs) owing to their wide biological applications. The present investigation aims at developing anti-cancerous colloidal silver using Moringa olifera stem bark extract. Electron and atomic force microscopic images were taken to analyze the surface morphology of the synthesized AgNPs. The effects of synthesized AgNPs were tested against human cervical carcinoma cells (HeLa) and cell morphology was further evaluated using 4,6-diamidino-2-phenylindole (DAPI) staining. The efficiency of green synthesized AgNPs was studied with the help of fluorescence activated cell sorting (FACS) and was shown to induce apoptosis through reactive oxygen species (ROS) generation in HeLa cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Association of pretreatment body mass index and survival in human papillomavirus positive oropharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Albergotti, William G; Davis, Kara S; Abberbock, Shira; Bauman, Julie E; Ohr, James; Clump, David A; Heron, Dwight E; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T; Ferris, Robert L

    2016-09-01

    Pretreatment body mass index (BMI) >25kg/m(2) is a positive prognostic factor in patients with head and neck cancer. Previous studies have not been adequately stratified by human papilloma virus (HPV) status or subsite. Our objective is to determine prognostic significance of pretreatment BMI on overall survival in HPV+ oropharyngeal squamous cell carcinoma (OPSCC). This is a retrospective review of patients with HPV+ OPSCC treated between 8/1/2006 and 8/31/2014. Patients were stratified by BMI status (>/25kg/m(2) had a longer overall survival (HR=0.49, P=0.01) as well as a longer disease-specific survival (HR=0.43, P=0.02). Overall survival remained significantly associated with high BMI on multivariate analysis (HR=0.54, P=0.04). Pre-treatment normal or underweight BMI status is associated with worse overall survival in HPV+ OPSCC. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Gene expression profile analysis in human hepatocellular carcinoma by cDNA microarray.

    Science.gov (United States)

    Chung, Eun Jung; Sung, Young Kwan; Farooq, Mohammad; Kim, Younghee; Im, Sanguk; Tak, Won Young; Hwang, Yoon Jin; Kim, Yang Il; Han, Hyung Soo; Kim, Jung-Chul; Kim, Moon Kyu

    2002-12-31

    We performed gene expression profiling of normal and hepatocellular carcinoma (HCC) liver tissues using a high-density microarray that contained 3,063 human cDNA. The results of a microarray hybridization experiment from eight different HCC tissues were analyzed and classified by the Cluster program. Among these differentially-expressed genes, the galectin-3, serine/threonine kinase SGK, translation factor eIF-4A, -4B, -3, fibroblast growth factor receptor, and ribosomal protein L35A were up-regulated; the mRNAs of Nip3, decorin, and the insulin-like growth factor binding protein-3 were down-regulated in HCC. The differential expression of these genes was further confirmed by an RT-PCR analysis. In addition, our data suggest that the gene expression profile of HCC varies according to the histological types.

  12. Genetic instability of cell lines derived from a single human small cell carcinoma of the lung

    DEFF Research Database (Denmark)

    Engelholm, S A; Vindeløv, L L; Spang-Thomsen, M

    1985-01-01

    Specimens from a human small cell carcinoma of the lung were established as a cell line in vitro. Flow cytometric DNA analysis demonstrated only one tumor cell population in the parent tumor as well as in the early passages in vitro. After six passages in vitro, two new subpopulations...... content was examined regularly by flow cytometric DNA analysis and instability was found in one of the cloned cell lines. Chromosome analysis showed that the cloned cell lines consisted of more than one population after 17 in vitro passages. Both cloned cell lines produced tumors in nude mice. Genetic...... with different DNA content appeared. By cloning, permanent cell lines were established from the new subpopulations, whereas the original population stopped growing. The cloned cell lines were characterized by morphology, chromosomes analysis, electron microscopy and plating efficiency; the stability of the DNA...

  13. Mapping the stem cell state: eight novel human embryonic stem and embryonal carcinoma cell antibodies

    DEFF Research Database (Denmark)

    Wright, A; Andrews, N; Bardsley, K

    2011-01-01

    The antigenic profile of human embryonic stem (ES) and embryonal carcinoma (EC) cells has served as a key element of their characterization, with a common panel of surface and intracellular markers now widely used. Such markers have been used to identify cells within the 'undifferentiated state...... of reactivity for all antibodies against both ES and EC cells, suggesting that these markers will afford recognition of unique sub-states within the undifferentiated stem cell compartment....... and EC cells, and herein describe their characterization. The reactivity of these antibodies against a range of cell lines is reported, as well as their developmental regulation, basic biochemistry and reactivity in immunohistochemistry of testicular germ cell tumours. Our data reveal a range...

  14. Ancillary Studies in Determining Human Papillomavirus Status of Squamous Cell Carcinoma of the Oropharynx: A Review

    Directory of Open Access Journals (Sweden)

    Richard L. Cantley

    2011-01-01

    Full Text Available Squamous cell carcinoma (SCC of the oral cavity and pharynx represents the sixth most common form of malignancy worldwide. A significant proportion of these cases are related to human papillomavirus (HPV infection. In general, HPV-associated SCC is more commonly nonkeratinizing and poorly differentiated, whereas non-HPV-associated SCC is typically keratinizing and moderately differentiated. Nevertheless, significant overlap in morphology is seen between these two forms of SCC. The purpose of this paper is to highlight the utility of ancillary studies in the establishment of HPV status of oropharyngeal SCC, including p16 immunohistochemistry, high-risk HPV in situ hybridization, polymerase chain reaction, and newer HPV detection modalities.

  15. Co-infection of syphilis and hepatitis B with carcinoma penis in a human immunodeficiency virus male.

    Science.gov (United States)

    Govindan, Balaji; Subramanian, Kalaivani; Karunakaran, Maduravasagam

    2017-01-01

    Human immunodeficiency virus (HIV) infections have a high probability of co-infections with Syphilis and hepatitis B virus since they share the common routes of transmission. We report a 41-year-old HIV male (on antiretroviral therapy for the past 6 years) admitted for a complaint of penile ulcer for 2 months. Serology for syphilis and hepatitis B were positive. Skin biopsy of the penile ulcer confirmed squamous cell carcinoma. Henceforth, the patient was referred to oncology department for further management. We present this rare combination of syphilis and hepatitis B with carcinoma penis in an HIV patient.

  16. Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Mincione, Gabriella, E-mail: g.mincione@unich.it [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Tarantelli, Chiara [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Vianale, Giovina [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy); Di Marcantonio, Maria Carmela [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cotellese, Roberto [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Francomano, Franco [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Di Nicola, Marta; Costantini, Erica [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Cichella, Annadomenica [Unit of General and Laparoscopic Surgery, SS Annunziata Hospital, Chieti (Italy); Muraro, Raffaella [Department of Experimental and Clinical Sciences, University ‘G. d' Annunzio of Chieti-Pescara, Chieti (Italy); Center of Excellence on Aging, Ce.S.I., ‘G. d' Annunzio’ University Foundation, Chieti (Italy)

    2014-09-10

    The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma.

  17. Large Lipoma of the Larynx: A Case Report

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Khorsandi Ashtiani

    2010-10-01

    Full Text Available Fewer than 15% of lipomas occur in the head and neck. Lipomas of the larynx are very rare benign laryngeal tumors (0.6%. To date less than 100 case of laryngeal lipoma have been reported in the literature.Clinical manifestation include progressive horseness, dyspnea, and even dysphagia. In the direct exam smooth or pedunculated mass is seen in the larynx and sometimes if tumor is large enough a mass palpated in the neck. In the computed tomography (CT low attenuation mass is seen. Treatment of laryngeal lipoma consists of endoscopic removal or external surgical approach depending on tumor size. The authors present a case of laryngeal lipoma that involved the true vocal cord. The following is a report of a single case of laryngeal lipoma, Including esteroboscopy, radiologic and intraoperative finding as well as review of the literature.

  18. Tissue-Engineered Larynx: Future Applications in Laryngeal Cancer.

    Science.gov (United States)

    Hamilton, Nick J I; Birchall, Martin A

    2017-01-01

    This article reviews the latest developments in tissue engineering for the larynx with a specific focus on the treatment of laryngeal cancer. Challenges in tissue engineering a total larynx can be divided into scaffold design, methods of re-mucosalization, and how to restore laryngeal function. The literature described a range of methods to deliver a laryngeal scaffold including examples of synthetic, biomimetic, and biological scaffolds. Methods to regenerate laryngeal mucosa can be divided into examples that use a biological dressing and those that engineer a new mucosal layer de novo. Studies aiming to restore laryngeal function have been reported, but to date, the optimum method for achieving this as part of a total laryngeal transplant is yet to be determined. There is great potential for tissue engineering to improve the treatments available for laryngeal cancer within the next 10 years. A number of challenges exist however and advances in restoring function must keep pace with developments in scaffold design.

  19. Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas.

    Science.gov (United States)

    Mincione, Gabriella; Tarantelli, Chiara; Vianale, Giovina; Di Marcantonio, Maria Carmela; Cotellese, Roberto; Francomano, Franco; Di Nicola, Marta; Costantini, Erica; Cichella, Annadomenica; Muraro, Raffaella

    2014-09-10

    The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC and FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. [The clinical analysis and treatment of contact granuloma of larynx].

    Science.gov (United States)

    Zhang, Jianhui; Tang, Siquan; Tang, Yiping

    2014-03-01

    To explore the clinical features and treatments of contact granuloma of larynx. To find the best treatments by analyzing the clinical features, related causes and the treatments of the 13 contact granuloma of larynx cases, which have complete data, of our department from Jan 2005 to Dec 2012, also by comparing the effect of conservative treatment and operation treatment. Contact granuloma of larynx is more common in men (84.6%). The main causes are gastro esophageal reflux, chronic cough, habitual hawk and endotracheal intubation disease. However, a big part (38.4%) gets the disease without any other disease history. The main clinical feature of the disease includes: sensation of foreign matter in throat, easy to get exhausted when talking and voice hoarse, but also 30.7% without any feature in throat. Among the 13 cases, 6 were treated by operation and the first recurrence was 66.6%. The cure rate was 50% after one or two operations. The other 7 were treated in conservative way, including anti- Gastro esophageal reflux, avoiding excessive talking, reducing habitual hawk ,or without any medical treatment. The cure rate was 57.1%. The total cure rate was 53.8%. However, it is nonsense to comparing the two different treatments (Chi2 = 0.066, P > 0.05). There is still no standard treatment for contact granuloma of larynx and the effect is not good enough. The treatment should be depending on individual case. Conservative treatment is the first choice. However, operation should be considered if the patient has obviously hoarse and his granuloma is too large to breathe well.

  1. Ultrasonography of the Tympanic Bullae and Larynx in Cattle.

    Science.gov (United States)

    Gosselin, Véronique Bernier; Babkine, Marie; Francoz, David

    2016-03-01

    Diseases of the middle ear or the larynx are not numerous in cattle but their diagnosis can be challenging for veterinary practitioners in the field. This article presents the ultrasonography of these 2 anatomic structures in order to provide new diagnostic tools to veterinary practitioners in the field. Brief anatomic reminders are first reported. The scanning techniques and normal images are then described. Finally, abnormal images of specific conditions are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. [The molecular mechanisms of curcuma wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells in vitro].

    Science.gov (United States)

    Jing, Zhao; Zou, Hai-Zhou; Xu, Fang

    2012-09-01

    To study the molecular mechanisms of Curcuma Wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells. The Curcuma Wenyujin extract was obtained by supercritical carbon dioxide extraction. TE-1 cells were divided into 4 groups after adherence. 100 microL RMPI-1640 culture medium containing 0.1% DMSO was added in Group 1 as the control group. 100 microL 25, 50, and 100 mg/L Curcuma Wenyujin extract complete culture medium was respectively added in the rest 3 groups as the low, middle, and high dose Curcuma Wenyujin extract groups. The effects of different doses of Curcuma Wenyujin extract (25, 50, and 100 mg/L) on the proliferation of human esophageal carcinoma cell line TE-1 in vitro were analyzed by MTT assay. The gene expression profile was identified by cDNA microarrays in esophageal carcinoma TE-1 cells exposed to Curcuma Wenyujin extract for 48 h. The differential expression genes were further analyzed by Gene Ontology function analysis. Compared with the control group, MTT results showed that Curcuma Wenyujin extract significantly inhibited the proliferation of TE-1 cells in a dose-dependent manner (PCurcuma Wenyujin extract could inhibit the growth of human esophageal carcinoma cell line TE-1 in vitro. The molecular mechanisms might be associated with regulating genes expressions at multi-levels.

  3. Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse.

    Science.gov (United States)

    Kerjaschki, Dontscho; Bago-Horvath, Zsuzsanna; Rudas, Margaretha; Sexl, Veronika; Schneckenleithner, Christine; Wolbank, Susanne; Bartel, Gregor; Krieger, Sigurd; Kalt, Romana; Hantusch, Brigitte; Keller, Thomas; Nagy-Bojarszky, Katalin; Huttary, Nicole; Raab, Ingrid; Lackner, Karin; Krautgasser, Katharina; Schachner, Helga; Kaserer, Klaus; Rezar, Sandra; Madlener, Sybille; Vonach, Caroline; Davidovits, Agnes; Nosaka, Hitonari; Hämmerle, Monika; Viola, Katharina; Dolznig, Helmut; Schreiber, Martin; Nader, Alexander; Mikulits, Wolfgang; Gnant, Michael; Hirakawa, Satoshi; Detmar, Michael; Alitalo, Kari; Nijman, Sebastian; Offner, Felix; Maier, Thorsten J; Steinhilber, Dieter; Krupitza, Georg

    2011-05-01

    In individuals with mammary carcinoma, the most relevant prognostic predictor of distant organ metastasis and clinical outcome is the status of axillary lymph node metastasis. Metastases form initially in axillary sentinel lymph nodes and progress via connecting lymphatic vessels into postsentinel lymph nodes. However, the mechanisms of consecutive lymph node colonization are unknown. Through the analysis of human mammary carcinomas and their matching axillary lymph nodes, we show here that intrametastatic lymphatic vessels and bulk tumor cell invasion into these vessels highly correlate with formation of postsentinel metastasis. In an in vitro model of tumor bulk invasion, human mammary carcinoma cells caused circular defects in lymphatic endothelial monolayers. These circular defects were highly reminiscent of defects of the lymphovascular walls at sites of tumor invasion in vivo and were primarily generated by the tumor-derived arachidonic acid metabolite 12S-HETE following 15-lipoxygenase-1 (ALOX15) catalysis. Accordingly, pharmacological inhibition and shRNA knockdown of ALOX15 each repressed formation of circular defects in vitro. Importantly, ALOX15 knockdown antagonized formation of lymph node metastasis in xenografted tumors. Furthermore, expression of lipoxygenase in human sentinel lymph node metastases correlated inversely with metastasis-free survival. These results provide evidence that lipoxygenase serves as a mediator of tumor cell invasion into lymphatic vessels and formation of lymph node metastasis in ductal mammary carcinomas.

  4. Immunomodulatory Effectiveness of Fish Oil and omega-3 Fatty Acids in Human Non-melanoma Skin Carcinoma Cells.

    Science.gov (United States)

    Rehman, Khurram; Mohd Amin, Mohd Cairul Iqbal; Yuen, Ng Pei; Zulfakar, Mohd Hanif

    2016-01-01

    Fish oil is composed of various fatty acids among which omega-3 fatty acids are considered as most beneficial. The effects of fish oil on the activity of a topical anticancer drug, imiquimod, and the immunomodulatory activity of omega-3 fatty acids was investigated in human basal and squamous cell carcinoma cell lines. Imiquimod-fish oil mixture exhibited higher carcinoma cell growth inhibition and immunomodulatory activity than imiquimod alone, especially against squamous cell carcinoma cells. Omega-3 fatty acids exhibited growth inhibition of both basal cell and squamous cell carcinoma cell lines and modulated the immune response. Omega-3 fatty acids of fish oil serve as inducers of interleukin-10, an anti-inflammatory cytokine, and as suppressors of interleukin-6 and tumor necrosis factor-alpha, which not only depress tumor growth but also adequately control the inflammatory side effects of imiquimod. Thus, imiquimod administration with fish oil could be beneficial for inhibition of non-melanoma skin carcinoma cells but further in vivo studies are needed to understand their role in skin cancer.

  5. High-risk human papilloma virus genotypes in cervical carcinoma of Serbian women: Distribution and association with pathohistological findings.

    Science.gov (United States)

    Stamenković, Miodrag; Knežević, Aleksandra; Knežević, Ivana; Kuzmanović, Igor; Karalić, Danijela; Milenković, Sanja; Jovanović, Tanja

    2016-09-01

    A significant role of high-risk Human papilloma viruses (HR HPV) in the development of cervical carcinoma is well known. HR HPV 16 and 18 account for approximately 70% of all cases of cervical cancer worldwide. The incidence of cervical cancer in Serbia, is one of the highest in Europe. The aim of our study was to investigate the distribution of HR HPV types in cervical carcinoma of Serbian women, as well as association between the HPV types and pathohistological findings. The study included 80 archival cervical cancer tissues from the same number of patients. The presence of HPV DNA was determined using MY09/MY11 primers for L1 gene and GP1/GP2 primers for E1 gene. HPV was detected in 78.75% tissues. HR HPV genotypes found in the decreasing order of frequency were: HPV16 (80.39%), HPV33 (7.84%), HPV58 (5.88%), HPV18 (1.96%), HPV45 (1.96%) and HPV53 (1.96%). The examined tissues were 91.25% squamous cell carcinomas and 8.75% adenocarcinoma. The high frequency of HPV 16 was observed in both types of carcinoma (80.8% and 75%, respectively) while the prevalence of HPV18 was low. These results may contribute to the implementation of cervical carcinoma prevention program in Serbia, including the selection of the most appropriate vaccine and immunization program. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  6. Evaluation of immunohistochemical expression of p16 and presence of human papillomavirus in oral and oropharyngeal carcinoma.

    Science.gov (United States)

    Cantarutti, Ana Luíza Laguardia; Fernandes, Lais Papini; Saldanha, Marina Vaz de Lima Fullin; Marques, Ana Elizia Mascarenhas; Vianna, Leonora Maciel de Souza; de Melo, Nilce Santos; Guerra, Eliete Neves da Silva

    2014-01-01

    Carcinogenesis concerns several changes that eventually result in the inactivation of tumor suppressor genes and activation of protooncogenes, leading to loss of cell cycle control. Inactivation of p16 seems to be an early event in this process and occurs in approximately 80% of squamous cell carcinoma cases. The aims of this study were to evaluate the immunohistochemical expression of p16 protein in oral and oropharyngeal squamous cell carcinoma cases, with both the tumoral area itself and its surgical margin being analyzed (dysplastic areas and histologically normal epithelium adjacent to carcinoma), and to verify the presence of human papillomavirus (HPV) and its relation to p16 expression. Paraffin-embedded biopsy tissues from 26 patients, 13 with oral squamous cell carcinoma and 13 with oropharyngeal squamous cell carcinoma, comprised the analyzed samples. To detect HPV, a nested polymerase chain reaction test using PGMY 09/11 and GP5*/GP6* primers and visualization of the product on a 2% agarose gel was performed. Demographic data were obtained from medical records. The results showed low expression of p16 in the tumor area (38.46%), compared with surgical margins in the histologically normal epithelium (84.6%) and dysplastic areas (57.7%). These findings indicate the inactivation of p16 in the process of malignant transformation. The association described in the literature between expression of p16 and presence of HPV could not be verified in this study, because none of the cases was HPV positive.

  7. Detection of human papillomavirus DNA and p53 codon 72 polymorphism in prostate carcinomas of patients from Argentina

    Directory of Open Access Journals (Sweden)

    Kahn Tomas

    2005-11-01

    Full Text Available Abstract Background Infections with high-risk human papillomaviruses (HPVs, causatively linked to cervical cancer, might also play a role in the development of prostate cancer. Furthermore, the polymorphism at codon 72 (encoding either arginine or proline of the p53 tumor-suppressor gene is discussed as a possible determinant for cancer risk. The HPV E6 oncoprotein induces degradation of the p53 protein. The aim of this study was to analyse prostate carcinomas and hyperplasias of patients from Argentina for the presence of HPV DNA and the p53 codon 72 polymorphism genotype. Methods HPV DNA detection and typing were done by consensus L1 and type-specific PCR assays, respectively, and Southern blot hybridizations. Genotyping of p53 codon 72 polymorphism was performed both by allele specific primer PCRs and PCR-RFLP (Bsh1236I. Fischer's test with Woolf's approximation was used for statistical analysis. Results HPV DNA was detected in 17 out of 41 (41.5 % carcinoma samples, whereas all 30 hyperplasia samples were HPV-negative. Differences in p53 codon 72 allelic frequencies were not observed, neither between carcinomas and hyperplasias nor between HPV-positive and HPV-negative carcinomas. Conclusion These results indicate that the p53 genotype is probably not a risk factor for prostate cancer, and that HPV infections could be associated with at least a subset of prostate carcinomas.

  8. Dynamic study of the larynx with spiral CT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Yeon; Choi, Chang Ho; Yoon, Chi Soon; Kim, Yoon Gyoo; Nam, Sang Hwa; Kim, Kun Il; Kim, Byung Soo; Wang, Soo Guen [College of Medicine, Pusan National University, Busan (Korea, Republic of)

    1994-03-15

    It is essential to know the functional and morphologic changes of the larynx in the evaluation of laryngeal lesions. Conventional CT which has relatively long examination time is not suitable for this aim. The purposes of this study are to evaluate the capability of spiral CT in the dynamic study of the larynx and to know whether this new technique can replace conventional laryngography or not. Five healthy volunteers and 20 patients with laryngeal lesions underwent spiral dynamic CT scans with 3-dimensional reconstruction of the mucosal surface. A series of spiral CT scans were done while the volunteers performed various laryngeal positions to obtain the functional and morphologic information. The maneuvers used were: quite breathing, 'E' phonation, Valsalva maneuver, modified Valsalva maneuver, and a new method of our own, 'modified breath holding' technique. The patients were scanned when in quite breathing. Additional scans were obtained by using the 'modified breath holding' technique. The dynamic study with spiral CT could provide high resolutional images which nicely depicted the mobility of vocal cords and the mucosal changes of the laryngeal cavity in both healthy volunteer and patient groups. In patient group, the new 'modified breath holding' technique was easier and more reproducible than other maneuvers. Spiral CT allows a dynamic study of the larynx and can be a new alternative of laryngography.

  9. Detection of human papilloma virus (HPV and human immunodeficiency virus (HIV in oral squamous cell carcinoma: A polymerized chain reaction (PCR study

    Directory of Open Access Journals (Sweden)

    Suresh Dirasantchu

    2015-01-01

    Full Text Available Aims and Objectives: Certain strains of human papillomavirus (HPV have been shown to be etiologically related to the development of uterine, cervical, and other genital cancers, but their role in the development of malignancies at other sites is less well established. Previous studies have shown HPV in tumors of the head and neck, but its prevalence has varied depending on the detection methods and the types of tumor and/or tissue examined. This study was undertaken for the detection of high-risk HPV types 16 and 18 and human immunodeficiency virus (HIV in oral squamous cell carcinoma. Materials and Methods: Twenty-five patients histologically diagnosed with oral squamous cell carcinoma and 10 apparently normal persons as controls were selected for the present study. Two biopsy specimens were removed surgically by incision biopsy for histopathological examination and polymerized chain reaction (PCR study. Results: Out of 25 oral squamous cell carcinoma subjects, 8 were found to be HPV positive in PCR. Out of these eight subjects, four had HPV 16 and the other four had other genotypes, and one subject was HIV positive. Conclusion: The conclusion drawn from the present study was that well-defined risk factors like HPV may play a prominent role in the development of oral squamous cell carcinomas, in addition to other risk factors. Further studies with a larger sample size are necessary to arrive at conclusions and to explore the relationship of HPV and HIV in oral squamous cell carcinoma.

  10. Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes

    Directory of Open Access Journals (Sweden)

    G. Perrone

    2010-09-01

    Full Text Available The human equilibrative nucleoside transporter 1 (hENT1 is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively. Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036, while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma.

  11. Myofibroblasts are responsible for collagen synthesis in the stroma of human hepatocellular carcinoma: an in vivo and in vitro study.

    Science.gov (United States)

    Faouzi, S; Le Bail, B; Neaud, V; Boussarie, L; Saric, J; Bioulac-Sage, P; Balabaud, C; Rosenbaum, J

    1999-02-01

    Marked changes in extracellular matrix occur in the stroma of hepatocellular carcinoma, as compared to normal or cirrhotic liver. The cell types responsible for extracellular matrix synthesis within hepatocellular carcinoma have not been clearly identified. In vivo collagen synthesis was studied by in situ hybridization and immunohistochemistry for types I, IV, V and VI collagen, together with immunolabeling of alpha-smooth muscle actin, a myofibroblast marker, and CD34, an endothelial cell marker. In vitro, extracellular matrix deposition by cultured myofibroblasts was studied by reticulin staining, immunocytochemistry and RNase protection. All collagens studied were expressed in the stroma of the tumor, with a higher level of type VI and IV collagens than of type I and V. The majority of the cells expressing collagen transcripts in human hepatocellular carcinoma stroma were alpha-actin positive and CD 34 negative. In vitro experiments demonstrated that the hepatocellular carcinoma cell lines HepG2, HuH7 and Hep3B markedly increased extracellular matrix deposition by human liver myofibroblasts. This increase was mediated by a soluble mediator present in tumor cell conditioned medium. It was not explained by an increase in mRNA levels of extracellular matrix components, nor by a decrease in the secretion of matrix-degrading proteinases by myofibroblasts. Myofibroblasts are the main source of collagens in the stroma of hepatocellular carcinoma. Our data also indicate that tumoral hepatocytes increase extracellular matrix deposition by cultured myofibroblasts, probably by post-transcriptional mechanisms. The generation of hepatocellular carcinoma stroma by myofibroblasts could thus be under control of tumoral cells.

  12. Estrogen mediated expression of nucleophosmin 1 in human endometrial carcinoma clinical stages through estrogen receptor-α signaling.

    Science.gov (United States)

    Zhou, Yunxiao; Shen, Jie; Xia, Liqun; Wang, Yanli

    2014-01-01

    Endometrial carcinoma is one of the most common gynecologic malignancies. Estrogen plays a critical role in its pathogenesis, but the underlying mechanism is not clear. Nucleophosmin 1 (NPM1), a multifunctional protein involved in many cellular activities, has been implicated in the tumorigenesis processes. However, the role of NPM1 in endometrial carcinogenesis remains to be elucidated. The present study was aimed to elucidate the role of NPM1 in different clinical stages of human endometrial carcinoma and the underlying mechanism of NPM1 action. The distribution and expression of NPM1 in normal endometrium, FIGO stages I to IV endometrial carcinoma tissues was analyzed using immunohistochemistry, RT-qPCR and Western blotting. The association between NPM1 expression and estrogen and estrogen receptor signaling was investigated in primary-cultured FIGO stage I endometrial adenocarcinoma cells. A strong positive correlation between NPM1 level and the clinical stage and histological grade of endometrial carcinomas was observed. Expression of NPM1 was up-regulated by estrogen in primary-cultured human endometrial adenocarcinoma cells. Furthermore, estrogen increased NPM1 level via estrogen receptor-α (ERα) signaling, nor estrogen receptor-β signaling. Expression of NPM1 was gradually increased with the increase of clinical stages of endometrial carcinomas. Overexpression of NPM1 may play a role in the effects of estrogen on the malignant progression of endometrioid adenocarcinoma via ERα signaling. These findings may extend our understanding of the oncogenesis of steroid hormone-related cancers and have significance for the diagnosis and treatment of this carcinoma.

  13. Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro.

    Science.gov (United States)

    Rao, Quan; Zuo, Bingfeng; Lu, Zhen; Gao, Xianjun; You, Abin; Wu, Chenxuan; Du, Zhi; Yin, HaiFang

    2016-08-01

    Hepatocellular carcinoma (HCC) remains a global challenge due to high morbidity and mortality rates and poor response to treatment. Immunotherapy, based on introduction of dendritic cells (DCs) activated by tumor cell lysates as antigens ex vivo, shows limited response rates in HCC patients. Here, we demonstrate that tumor cell-derived exosomes (TEXs), displaying an array of HCC antigens, can elicit a stronger immune response than cell lysates in vitro and in vivo. Significant tumor growth inhibition was achieved in ectopic and orthotopic HCC mice treated with TEX-pulsed DCs. Importantly, the tumor immune microenvironment was significantly improved in orthotopic HCC mice treated by TEX-pulsed DCs, demonstrated by increased numbers of T lymphocytes, elevated levels of interferon-γ, and decreased levels of interleukin-10 and tumor growth factor-β in tumor sites. As expected, T cells played an essential role in the TEX-pulsed DC-mediated immune response. Notably, exosomes from HCC cells not only promoted HCC-specific cytolysis but also provided cross-protective effects against pancreatic cancer cells. Moreover, HCC-specific cytolysis, elicited by DCs pulsed with human HepG2 cell-derived exosomes, was observed across different human HCC cells irrespective of human leukocyte antigen types. HCC TEXs can potently carry HCC antigens, trigger a strong DC-mediated immune response, and improve the HCC tumor microenvironment. (Hepatology 2016;64:456-472). © 2016 by the American Association for the Study of Liver Diseases.

  14. Integrative Genomic Analysis Identifies the Core Transcriptional Hallmarks of Human Hepatocellular Carcinoma.

    Science.gov (United States)

    Allain, Coralie; Angenard, Gaëlle; Clément, Bruno; Coulouarn, Cédric

    2016-11-01

    Integrative genomics helped characterize molecular heterogeneity in hepatocellular carcinoma (HCC), leading to targeted drug candidates for specific HCC subtypes. However, no consensus was achieved for genes and pathways commonly altered in HCC. Here, we performed a meta-analysis of 15 independent datasets (n = 784 human HCC) and identified a comprehensive signature consisting of 935 genes commonly deregulated in HCC as compared with the surrounding nontumor tissue. In the HCC signature, upregulated genes were linked to early genomic alterations in hepatocarcinogenesis, particularly gains of 1q and 8q. The HCC signature covered well-established cancer hallmarks, such as proliferation, metabolic reprogramming, and microenvironment remodeling, together with specific hallmarks associated with protein turnover and epigenetics. Subsequently, the HCC signature enabled us to assess the efficacy of signature-relevant drug candidates, including histone deacetylase inhibitors that specifically reduced the viability of six human HCC cell lines. Overall, this integrative genomics approach identified cancer hallmarks recurrently altered in human HCC that may be targeted by specific drugs. Combined therapies targeting common and subtype-specific cancer networks may represent a relevant therapeutic strategy in liver cancer. Cancer Res; 76(21); 6374-81. ©2016 AACR. ©2016 American Association for Cancer Research.

  15. A Novel Role of Silibinin as a Putative Epigenetic Modulator in Human Prostate Carcinoma

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    Ioannis Anestopoulos

    2016-12-01

    Full Text Available Silibinin, extracted from milk thistle (Silybum marianum L., has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2 members Enhancer of Zeste Homolog 2 (EZH2, Suppressor of Zeste Homolog 12 (SUZ12, and Embryonic Ectoderm Development (EED in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR. Furthermore immunoblot and immunofluorescence analysis revealed that silibinin-mediated reduction of EZH2 levels was accompanied by an increase in trimethylation of histone H3 on lysine (Κ-27 residue (H3K27me3 levels and that such response was, in part, dependent on decreased expression levels of phosphorylated Akt (ser473 (pAkt and phosphorylated EZH2 (ser21 (pEZH2. Additionally silibinin exerted other epigenetic effects involving an increase in total DNA methyltransferase (DNMT activity while it decreased histone deacetylases 1-2 (HDACs1-2 expression levels. We conclude that silibinin induces epigenetic alterations in human prostate cancer cells, suggesting that subsequent disruptions of central processes in chromatin conformation may account for some of its diverse anticancer effects.

  16. Tissue eosinophilia: a morphological marker for assessing stromal invasion in squamous neoplasms of the larynx

    Directory of Open Access Journals (Sweden)

    RR Bhatta

    2013-03-01

    Full Text Available Background: The assessment of tumour invasion in squamous neoplasms of the larynx poses a diagnostic challenge, especially in small biopsies that are frequently sectioned tangentially. Eosinophilic infi ltration is thought to be an adjunctive criterion in determining tumour invasion. We investigated whether thresholds of eosinophilic infi ltration in laryngeal squamous neoplasms would aid in determining the presence of invasion. Materials and Methods: Fifty cases of invasive squamous carcinoma, preinvasive squamous neoplasms and benign squamous neoplasms were evaluated. The number of eosinophils per high power field and per 10 high power fields in the stroma adjacent to the neoplastic epithelium were counted and tabulated. For statistical purposes, the elevated eosinophils were defi ned and categorized as: focally and moderately elevated (5-9/HPF, focally and markedly elevated (>10/HPF, diffusely and moderately elevated (5- 19/10HPF, and diffusely and markedly increased (>20/10/HPF. Results: Eosinophil counts were elevated focally and/or diffusely more frequently in invasive squamous carcinoma than in noninvasive tumours. The increased eosinophil counts, specifically >10/HPF and >20/10HPF, were statistically significantly associated with stromal invasion. Greater than 10/HPF and >20/10HPF had sensitivity, specifi city and positive predictive values of 23%,100%, 100% and 11%,100% and 100% respectively. Cytology was able to diagnose 33 out of 36 malignant cases. Of 17 cases which were diagnosed as benign on cytology, 3 cases turned out to be malignant on biopsy. The sensitivity and specifi city of touch smear cytology are 91.6% and 100% respectively. Conclusion: The elevated eosinophil count in squamous neoplasms of larynx is a morphologic feature associated with presence of tumour invasion. When the number of infiltrating eosinophils exceeds 10/ HPF and or >20/10HPF in a laryngeal biopsy with squamous neoplasm, it represents an indicator for the

  17. A practical guide for the identification of membrane and plasma membrane proteins in human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Mummery, C.L.; Krijgsveld, J.; Heck, A.

    2008-01-01

    The identification of (plasma) membrane proteins in cells can provide valuable insights into the regulation of their biological processes. Pluripotent cells such as human embryonic stem cells and embryonal carcinoma cells are capable of unlimited self-renewal and share many of the biological

  18. Detection of integrated human papillomavirus by human papillomavirus types 16 and 18 in situ hybridization: a valuable diagnostic tool in diagnosing cervical carcinoma?

    NARCIS (Netherlands)

    Golde, R.J.T. van; Hullu, J.A. de; Bekkers, R.L.M.; Bulten, J.; Grefte, J.M.

    2008-01-01

    Human papillomavirus (HPV) infection is an important factor in cervical carcinogenesis. We describe 3 cases of patients with difficulties in diagnosing either a primary or recurrent cervical carcinoma. These cases illustrate that detection of integrated HPV is helpful in diagnosing cervical

  19. Radiological normal anatomy of the larynx and pharynx and imaging techniques; Radiologische Normalanatomie des Larynx und Pharynx sowie bildgebende Techniken

    Energy Technology Data Exchange (ETDEWEB)

    Nemec, S.F.; Krestan, C.R.; Noebauer-Huhmann, I.M.; Fruehwald, J.; Peloschek, P.; Kainberger, F.; Czerny, C. [Universitaetsklinik fuer Radiodiagnostik, Medizinische Universitaet Wien, Klinische Abteilung fuer Neuroradiologie und muskuloskelettale Radiologie, Wien (Austria); Formanek, M. [Medizinische Universitaet Wien, Universitaetsklinik fuer Hals-, Nasen- und Ohrenkrankheiten, Wien (Austria)

    2009-01-15

    The larynx and the pharynx represent anatomically as well as functionally a very complex organ which serves as an airway and a nutrition channel. Knowledge of anatomy and anatomical topography is therefore a fundamental basis for the evaluation of any pathological process. Beside the clinical examination and endoscopy performed by ear, nose and throat specialists, imaging techniques play a crucial role in pre-therapeutic and post-therapeutic diagnostics. The radiologist employs a conventional x-ray swallow examination, as well as contrast-enhanced multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), positron emission tomography (PET) and positron emission tomography-computed tomography (PET-CT), depending on the medical problem in question. The following article demonstrates the functional and especially the structural anatomy of the larynx and the pharynx. Furthermore, the broad range of imaging techniques in clinical use is discussed. (orig.) [German] Larynx und Pharynx repraesentieren sowohl anatomisch als auch funktionell ein sehr komplexes Organsystem, das als Luft- und Speiseweg dient. Die Kenntnis der Anatomie und anatomischen Topographie ist daher die elementare Grundlage fuer die Beurteilung jeglicher pathologischer Prozesse. Neben der klinischen Untersuchung und der Endoskopie durch den Hals-Nasen-Ohren-Arzt kommt den bildgebenden Verfahren in der prae- und posttherapeutischen Diagnostik eine entscheidende Rolle zu. Der Radiologe bedient sich hierbei - in Abhaengigkeit von der Fragestellung - der konventionellen Roentgenschluckuntersuchung, der kontrastmittelverstaerkten Multidetektorcomputertomographie (MDCT), der Magnetresonanztomographie (MRT), der Positronenemissionstomographie (PET) und der Positronenemissionstomographie-Computertomographie (PET-CT). Der folgende Artikel demonstriert die funktionelle und insbesondere die strukturelle Anatomie des Larynx und Pharynx. Darueber hinaus wird das breite Spektrum der bildgebenden

  20. [Therapeutic effect of flavopiridol, a small molecular cyclin-dependent kinase inhibitor, in human ovarian carcinoma].

    Science.gov (United States)

    Song, Yue; Shen, Keng; Tang, Ping-ping

    2007-11-01

    To investigate the antitumor effect of flavopiridol in ovarian cancer. After the treatment with flavopiridol of AO cells, cell apoptotic rate and cell cycle distribution were detected by flow cytometer and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL). Real time PCR was used to detect the expression of cyclin D and active caspase-3 in AO cells. Subcutaneous tumor models and abdominally spread tumor models of human ovarian carcinoma using AO cells in BALB/c nude mice were established. The mouse survival rates were measured for abdominally spread tumor models and the volume of tumor nodules was determined for subcutaneous tumor models following the treatments of flavopiridol. TUNEL was used to detect cell apoptosis, and immunohistochemistry was used to measure microvessel density (MVD) in tumor tissues. AO cells showed apoptotic rates of 4.1%, 10.7% and 7.6% following the treatments with flavopiridol at 150, 300 and 500 nmol/L respectively, accompanied by an increase in G(1) progression and a decrease in S phase progression. The level of active caspase-3 increased (2.55 vs 2.49) and the level of cyclin D expression decreased significantly (0.25 vs 0.69, P flavopiridol. Flavopiridol prolonged mouse survival [mean survival time of (141 +/- 14) days] and suppressed tumor growth significantly (tumor growth suppression rate of 40%), when compared with treatment using phosphate-buffered saline [(106 +/- 11) days, P flavopiridol. MVD of tumor tissue was 12 +/- 5 following flavopiridol treatment, significantly higher than that of 35 +/- 10 treated with phosphate-buffered saline (P Flavopiridol results in significant suppression of ovarian carcinoma cell growth and prolongs survival of mice.

  1. Epithelial cell adhesion molecule in human hepatocellular carcinoma cell lines: a target of chemoresistence.

    Science.gov (United States)

    Li, Yan; Farmer, Russell W; Yang, Yingbin; Martin, Robert C G

    2016-03-16

    The low survival rate of hepatocellular carcinoma (HCC) is partly attributable to its resistance to existing chemotherapeutic agents. Until now, there have been limited chemotherapeutic agents for liver cancer. Epithelial cell adhesion molecule (EpCAM) has been found to be over-expressed during stages of carcinogenesis and has been associated with poor overall survival in many cancers. The aim of this study was to evaluate EpCAM expression in HCC and evaluate the effects of EpCAM to established chemotherapy. Three human hepatocellular carcinoma cell lines--HepG2, Hep3B and HuH-7--were pre- and post-treated with doxorubicin, 5-fluorouracil (5-FU) and cisplatin. Cell viability and EpCAM protein expression were measured by MTT assay and Western Blotting respectively. EpCAM positive cells were analyzed by flow cytometry. To evaluate the effects of doxorubicin efficacy on EpCAM positive cells, a small interfering RNA (siRNA) specific to EpCAM was transfected into the cells and treated with doxorubicin. EpCAM was significantly down-regulated by doxorubicin treatment in all three HCC cell lines (P cells, however the EpCAM expression was up-regulated by 5-FU and cisplatin in Hep3B cell line. EpCAM expression was down-regulated by 5-FU, and up-regulated by cisplatin in Huh-7 cell line. Flow cytometry assay showed doxorubicin exposure decreased EpCAM positive cell quantities in three HCC cell lines. EpCAM siRNA knock-down attenuated cell mortality after doxorubicin exposure. All of these findings demonstrate that EpCAM is one of targets of chemoresistence.

  2. Differential BCCIP gene expression in primary human ovarian cancer, renal cell carcinoma and colorectal cancer tissues.

    Science.gov (United States)

    Liu, Xiaoxia; Cao, Lingling; Ni, Jinsong; Liu, Ning; Zhao, Xiaoming; Wang, Yanfang; Zhu, Lin; Wang, Lingyao; Wang, Jin; Yue, Ying; Cai, Yong; Jin, Jingji

    2013-12-01

    Human BCCIP, a protein which interacts with BRCA2 and CDKN1A (Cip1, p21), has been implicated in many cellular processes including cell cycle regulation, DNA recombination and damage repair, telomere maintenance, embryonic development and genomic stability. BCCIP gene expression, which is an important BRCA2 cofactor in tumor suppression, has been identified in some primary cancers. Thus, we investigated the role of BCCIP expression in a large sample of clinically diagnosed primary ovarian cancer, renal cell carcinoma (RCC) and colorectal cancer (CRC) tissues. Using clinically diagnosed frozen primary cancer tissues, quantitative PCR (qPCR), western blot analysis (WB) and immunohistochemical staining (IHC) approaches were used to detect and measure gene expression. Reduced BCCIP gene expression in ovarian cancer, RCC and CRC tissues occurred in 74, 89 and 75% of tissue samples, respectively. qPCR analysis of mRNA expression in 54 ovarian cancer, 50 RCC and 44 CRC samples revealed significant (>2-fold decreased) BCCIP downregulation in 56, 70 and 46% of tissue samples, respectively. Although BCCIP expression in three different tumor tissues decreased, the relationship between BCCIP expression and clinicopathological features of each cancer was distinct. Compared to normal tissues, BCCIP expression in ovarian cancers was significantly downregulated in serous, endometrioid and mucinous carcinomas. Downregulation of BCCIP expression was strongly associated with clear cell RCC (ccRCC) and Fuhrman tumor grading, but significant differences in BCCIP expression between CRC and matched normal tissues occurred only in male CRC tissues (povarian cancer and RCC tissue samples (povarian cancer, RCC and CRC tissues, suggesting a role for the gene in the pathogenesis of these cancers.

  3. In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Giuseppe Perrone

    Full Text Available Breast cancer cells with the CD44+/CD24- phenotype have been reported to be tumourigenic due to their enhanced capacity for cancer development and their self-renewal potential. The identification of human tumourigenic breast cancer cells in surgical samples has recently received increased attention due to the implications for prognosis and treatment, although limitations exist in the interpretation of these studies. To better identify the CD44+/CD24- cells in routine surgical specimens, 56 primary breast carcinoma cases were analysed by immunofluorescence and confocal microscopy, and the results were compared using flow cytometry analysis to correlate the amount and distribution of the CD44+/CD24- population with clinicopathological features. Using these methods, we showed that the breast carcinoma cells displayed four distinct sub-populations based on the expression pattern of CD44 and CD24. The CD44+/CD24- cells were found in 91% of breast tumours and constituted an average of 6.12% (range, 0.11%-21.23% of the tumour. A strong correlation was found between the percentage of CD44+/CD24- cells in primary tumours and distant metastasis development (p = 0.0001; in addition, there was an inverse significant association with ER and PGR status (p = 0.002 and p = 0.001, respectively. No relationship was evident with tumour size (T and regional lymph node (N status, differentiation grade, proliferative index or HER2 status. In a multivariate analysis, the percentage of CD44+/CD24- cancer cells was an independent factor related to metastasis development (p = 0.004. Our results indicate that confocal analysis of fluorescence-labelled breast cancer samples obtained at surgery is a reliable method to identify the CD44+/CD24- tumourigenic cell population, allowing for the stratification of breast cancer patients into two groups with substantially different relapse rates on the basis of CD44+/CD24- cell percentage.

  4. Detection of human papillomavirus infection in oral squamous cell carcinoma: a cohort study of Japanese patients.

    Science.gov (United States)

    Kouketsu, Atsumu; Sato, Ikuro; Abe, Satoko; Oikawa, Mariko; Shimizu, Yoshinaka; Takahashi, Tetsu; Kumamoto, Hiroyuki

    2016-09-01

    Recent evidence suggests that human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is a separate HNSCC subgroup with distinct epidemiology, histopathological characteristics, therapeutic response to chemotherapy and radiation, and clinical outcome. This study aimed to investigate the role of HPV infection in oral squamous cell carcinoma (OSCC) and the correlation between HPV infection, tumor suppressor protein p16 expression, and clinicopathological features in Japanese patients. In total, 174 OSCC specimens were examined for p16 levels by immunohistochemistry, and p16-positive OSCCs were analyzed for HPV DNA by in situ hybridization (ISH) and HPV genotypes by real-time PCR. The results were evaluated for the association with clinicopathological characteristics of OSCC patients. Twenty-four OSCC samples were found positive for p16 expression; all of them were well-differentiated tumors. P16 immunoreactivity was significantly associated with the invasion depth and tended to correlate with sex, site in the oral cavity, stromal reaction, TNM stage, and survival. HPV DNA was detected in 13 of 24 (54%) p16-positive OSCC by real-time PCR; HPV 16, 18, and other high-risk genotypes were the most prevalent. However, ISH failed to detect HPV DNA in p16-positive OSCCs. P16 immunoreactivity and HPV genotyping by real-time PCR may be useful markers of HPV infection in OSCC. However, although HPV-related OSCC showed good outcomes, HPV infection may have a minor role in oral oncogenesis in Japanese patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Transcriptionally-active human papillomavirus is consistently retained in the distant metastases of primary oropharyngeal carcinomas.

    Science.gov (United States)

    Mehrad, Mitra; Zhao, Hongwei; Gao, Ge; Wang, Xiaowei; Lewis, James S

    2014-06-01

    High-risk human papillomavirus (HPV) is both causative and prognostic in the majority of oropharyngeal squamous cell carcinomas (OPSCCs). The aim of this study was to evaluate for transcriptionally-active HPV in matched primary OPSCCs and their distant metastases given the implications of HPV status for diagnosis and treatment. Twenty matched pairs of primary OPSCC and their distant metastases were retrieved from departmental files. Two study pathologists reviewed all cases to confirm the diagnoses and to evaluate histologic features. Real-time PCR (RT-PCR) for detection of E6/E7 mRNA for all major high-risk HPV types and p16 immunohistochemistry were performed. Distant metastases were to lung (70 %), bone (20 %), non-regional lymph nodes (5 %) and pericardium (5 %). Histologically, 15 primary tumors were nonkeratinizing, 3 nonkeratinizing with maturation, one basaloid, and one keratinizing. Seventeen (85 %) of the metastases had the same histologic type as the primary tumor. All 20 matched pairs were concordant for HPV status by RT-PCR and for p16 expression with 19 of 20 cases positive for high risk HPV and one negative. HPV types were concordant in all cases. These findings show that the distant metastases from HPV-related primary OPSCCs uniformly retain transcriptionally-active HPV and p16 overexpression. They also retain similar morphology. This argues that HPV status can be utilized to differentiate metastatic OPSCC from separate, new, primary squamous cell carcinomas in other organs, and that therapies specifically targeting HPV or virus-related proteins in patients with distant metastases can be utilized.

  6. Cacospongionolide and scalaradial, two marine sesterterpenoids as potent apoptosis-inducing factors in human carcinoma cell lines.

    Science.gov (United States)

    De Stefano, Daniela; Tommonaro, Giuseppina; Malik, Shoaib Ahmad; Iodice, Carmine; De Rosa, Salvatore; Maiuri, Maria Chiara; Carnuccio, Rosa

    2012-01-01

    Apoptosis, a form of programmed cell death, is a critical defence mechanism against the formation and progression of cancer and acts by eliminating potentially deleterious cells without causing such adverse effects, as inflammatory response and ensuing scar formation. Therefore, targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents. In last decades, marine natural products, such as sesterterpenoids, have played an important role in the discovery and development of new drugs. Interestingly, many of these compounds have a strong potential as anticancer drugs by inhibiting cell proliferation and/or inducing cell death. In the present study, we investigated the effects of scalaradial and cacospongionolide, two sesterterpenoids from Cacospongia scalaris and Fasciospongia cavernosa marine sponges, on the apoptotic signalling pathway in three different human tumoral cells. Results were obtained by using DNA fragmentation, comet and viability assays, quantification of the mitochondrial transmembrane potential and Western blot. The T47D (human breast carcinoma), A431 (human epidermoid carcinoma), HeLa (human cervix carcinoma) and HCT116 (human colon carcinoma) cells were incubated for 24 h with scalaradial or cacospongionolide. Treatment of T47D cells with scalaradial or cacospongionolide for 24 h brought about a significant increase in DNA migration as well as fragmentation. Moreover, incubation of HCT116 and HeLa cells with scalaradial or cacospongionolide for 24 h caused an increased expression of pro-apoptotic proteins. Furthermore, scalaradial or cacospongionolide, added to HCT116 and HeLa cells overnight, induced a significant and concentration-dependent loss of mitochondrial transmembrane potential, an early apoptosis signalling event. These effects paralleled with those achieved with p50 and p65, NF-κB subunits, nuclear level. In conclusion, scalaradial and cacospongionolide, by determining human cancer cell

  7. Expression of leukemia/lymphoma-related factor (LRF/POKEMON) in human breast carcinoma and other cancers.

    Science.gov (United States)

    Aggarwal, Anshu; Hunter, William J; Aggarwal, Himanshu; Silva, Edibaldo D; Davey, Mary S; Murphy, Richard F; Agrawal, Devendra K

    2010-10-01

    The POK family of proteins plays an important role in not only embryonic development and cell differentiation, but also in oncogenesis. Leukemia/lymphoma-related factor (LRF) belongs to the POK family of transcriptional repressors and is also known as POK erythroid myeloid ontogenic factor (POKEMON), which binds to short transcripts of HIV-1 (FBI-1) and TTF-1 interacting peptide (TIP21). Its oncogenic role is known only in lymphoma, non-small cell lung carcinoma, and malignant gliomas. The functional expression of LRF in human breast carcinoma has not yet been confirmed. The aim of this study was to investigate and compare the expression of LRF in human breast cancer tissues and other human tumors. The expression of LRF mRNA transcripts and protein was observed in twenty human benign and malignant breast biopsy tissues. Expression of LRF was observed in several formalin-fixed tissues by immunohistochemistry and immunofluorescence. All malignant breast tissues expressed mRNA transcripts and protein for LRF. However, 40% and 15% benign breast biopsy tissues expressed LRF mRNA transcripts and protein, respectively. The overall expression of LRF mRNA transcripts and total protein was significantly more in malignant breast tissues than the benign breast tissues. LRF expression was also observed in the nuclei of human colon, renal, lung, hepatocellular carcinomas and thymoma tumor cells. In general, a significantly higher expression of LRF was seen in malignant tissues than in the corresponding benign or normal tissue. Further studies are warranted to determine the malignant role of LRF in human breast carcinoma. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Inhibitory effect of iron withdrawal by chelation on the growth of human and murine mammary carcinoma and fibrosarcoma cells.

    Science.gov (United States)

    Power Coombs, Melanie R; Grant, Taryn; Greenshields, Anna L; Arsenault, Daniel J; Holbein, Bruce E; Hoskin, David W

    2015-10-01

    Since iron uptake is essential for cell growth, rapidly dividing cancer cells are sensitive to iron depletion. To explore the effect of iron withdrawal on cancer cell growth, mouse and human mammary carcinoma cells (4T1 and MDA-MB-468, respectively) and mouse and human fibrosarcoma cells (L929 and HT1080, respectively) were cultured in the absence or presence of DIBI, a novel iron-chelating polymer containing hydroxypyridinone iron-ligand functionality. Cell growth was measured by a colorimetric assay for cell metabolic activity. DIBI-treated 4T1, MDA-MB-468, L929 and HT1080 cells, as well as their normal counterparts, showed a dose- and time-dependent reduction in growth that was selective for human cancer cells and mouse fibrosarcoma cells. The inhibitory effect of DIBI on fibrosarcoma and mammary carcinoma cell growth was reversed by addition of exogenous iron in the form of iron (III) citrate, confirming the iron selectivity of DIBI and that its inhibitory activity was iron-related. Fibrosarcoma and mammary carcinoma cell growth inhibition by DIBI was associated with S-phase cell cycle arrest and low to moderate levels of cell death by apoptosis. Consistent with apoptosis induction following DIBI-mediated iron withdrawal, fibrosarcoma and mammary carcinoma cells exhibited mitochondrial membrane permeabilization. A comparison of DIBI to other iron chelators showed that DIBI was superior to deferiprone and similar to or better than deferoxamine for inhibition of fibrosarcoma and mammary carcinoma cell growth. These findings suggest that iron withdrawal from the tumor microenvironment with a selective and potent iron chelator such as DIBI may prevent or inhibit tumor progression. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Analysis of gene expression changes associated with human carcinoma-associated fibroblasts in non-small cell lung carcinoma.

    Science.gov (United States)

    Wu, Xiaofen; Ruan, Lei; Yang, Yi; Mei, Qi

    2017-02-23

    This study aimed to investigate the gene expression changes associated with carcinoma-associated fibroblasts (CAFs) involving in non-small cell lung carcinoma (NSCLC). We downloaded the GEO series GSE22862, which contained matched gene expression values for 15 CAF and normal fibroblasts samples, and series GSE27289 containing SNP genotyping for four matched NSCLC samples. The differentially expressed genes in CAF samples were identified using the limma package in R. Then we performed gene ontology (GO) and pathway enrichment analysis and protein-protein interaction (PPI) network construction using the identified DEGs. Moreover, aberrant cell fraction, ploidy, allele-specific copy number, and loss of heterozygosity (LOH) within CAF cells were analyzed using the allele-specific copy number analysis. We obtained 545 differentially expressed genes between CAF and normal fibroblasts samples. The up-regulated genes are mainly involved in GO terms such as positive regulation of cell migration and extracellular region, while the down-regulated genes participate in the lung development and extracellular region. Multiple genes including bone morphogenetic protein 4 (BMP4) and transforming growth factor, beta 3 (TGFB3) are involved in the TGF-β signaling pathway. Genes including BMP4, TGFBI and matrix Gla protein (MGP) were hub genes. Moreover, no LOH event for BMP4 and MGP was found, that for sphingosine kinase 1 (SPHK1) was 70%, and for TGFBI was 40%. Our data suggested that BMP4, MGP, TGFBI, and SPHK1 may be important in CAFs-associated NSCLC, and the abnormal expression and high LOH frequency of them may be used as the diagnosis targets of CAFs in NSCLC.

  10. Bone morphogenetic protein-7 expression is down-regulated in human clear cell renal carcinoma.

    Science.gov (United States)

    Basic-Jukic, Nikolina; Hudolin, Tvrtko; Radic-Antolic, Margareta; Coric, Marijana; Zadro, Renata; Kastelan, Zeljko; Pasini, Josip; Bandic-Pavlovic, Daniela; Kes, Petar

    2011-01-01

    Recent studies demonstrated that the expression pattern of bone morphogenetic protein-7 (BMP-7) is altered in different tumors. We determined expression of BMP-7 in human clear cell renal carcinoma (CCRC). Samples from cancer and corresponding healthy tissue were obtained from 20 patients who underwent nephrectomy for CCRC. Expression of BMP-7 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR), and protein expression was analyzed by immunohistochemistry. RT-PCR showed strong down-regulation of BMP-7 mRNA in cancer tissue. Immunohistochemistry revealed expression of BMP-7 in normal renal tissue, with almost complete loss of BMP-7 expression in malignant cells of 6 patients (30%). After 3 years of follow-up, 5 out of 6 patients with high BMP-7 mRNA expression were alive and disease-free, compared with 9 out of 14 patients with low BMP-7 mRNA expression. BMP-7 mRNA and protein expression were down-regulated in CCRC. Further prospective studies are needed to characterize the role of BMP-7 in human CCRC.

  11. Effects of guggulsterone on proliferation and apoptosis of HepG2 human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    JIA Xiaoli

    2013-06-01

    Full Text Available ObjectiveTo investigate the potential therapeutic effects of the plant-derived polyphenol, guggulsterone, on cell proliferation and apoptosis of hepatocellular carcinoma (HCC by using an in vitro system with the human hepatoma cell line, HepG2. MethodsHepG2 cells and normal human liver L-02 cells were treated with different concentrations of guggulsterone (5-100 μmol/L for 24-72 hours. Differential effects on cell proliferation were tested by MTT assay and on cell cycle and apoptosis were detected by flow cytometry (FACS. ResultsGuggulsterone significantly inhibited HepG2 cell proliferation in a dose- and time-dependent manner, with the maximal inhibition effect being observed with 100 μmol/L guggulsterone (81.9%±1.92%. FACS analysis indicated that guggulsterone-treated HepG2 cells were arrested in the G0/G1 phase. Guggulsterone also induced apoptosis of HepG2 cells (apoptotic %: 50 μmol/L, 24.91±2.41 and 75 μmol/L, 53.03±2.28. ConclusionGuggulsterone exerts anticancer effects on HepG2 hepatoma cells by inhibiting cell proliferation and inducing apoptosis. The anti-proliferative effect may be related to interference of the cell cycle.

  12. GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma

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    Toshihiko Inowa

    2010-01-01

    Full Text Available Side population (SP cells are an enriched population of stem, and the existence of SP cells has been reported in human cancer cell lines. In this study, we performed an SP analysis using 11 human cancer cell lines and confirmed the presence of SP cells in an embryonic carcinoma cell line, NEC8. NEC8 SP cells showed characteristics of cancer stem cells, such as high growth rate, chemoresistance and high invasiveness. To further characterize the NEC8 SP cells, we used DNA microarrays. Among 38,500 genes, we identified 12 genes that were over-expressed in SP cells and 1 gene that was over-expressed in non-SP cells. Among these 13 genes, we focused on GADD45b. GADD45b was over-expressed in non-SP cells, but the inhibition of GADD45b had no effect on non-SP cells. Paradoxically, the inhibition of GADD45b significantly reduced the viability of NEC8 SP cells. The inhibition of ABCG2, which determines the SP phenotype, had no effect on the invasiveness of NEC8 SP cells, but the inhibition of GADD45b significantly reduced invasiveness. These results suggest that GADD45b, but not ABCG2, might determine the cancer stem cell-like phenotype, such as chemoresistance and the high invasiveness of NEC8 SP cells, and might be a good therapeutic target.

  13. [Effect of monoclonal antibodies against LI-cadherin on the proliferation of human hepatocellular carcinoma cells].

    Science.gov (United States)

    Chen, Xiao-ting; DU, Hong-yan; Yuan, Shao-fei; Wang, Sen-ming; Li, Ming

    2009-05-01

    To obtain monoclonal antibodies (mAb) against LI-cadherin and investigate their effects on the proliferation of human hepatocellular carcinoma cells. Balb/c mice were immunized with recombinant LI-cadherin, and hybridoma cell lines secreting monoclonal antibodies against LI-cadherin were established with routine cell fusion and subcloning approach. The specificity of these mAbs was determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of the mAbs obtained on the growth of HepG2 cells was assessed using inverted microscope and MTT assay. Two hybridoma cell lines (F001 and F002) stably secreting specific mAbs were obtained. Western blot analysis showed that the two antibodies specifically recognized LI-cadherin antigen derived from human eucaryotic cells or tissue. Treatment of the HepG2 cells with the mAbs resulted in reduced viable cell number and changes in the cell morphologies, and the two mAbs inhibited the proliferation of HepG2 cells in a concentration-dependent manner (Pcells in vitro, which facilitates further study of the relationship between LI-cadherin and tumors.

  14. In Vitro Cytotoxic Effect of Brazilian Green Propolis on Human Laryngeal Epidermoid Carcinoma (HEp-2 Cells

    Directory of Open Access Journals (Sweden)

    Michelle C. Búfalo

    2009-01-01

    Full Text Available Propolis is a sticky dark-colored material showing a very complex chemical composition that honeybees collect from plants. It has been used in folk medicine since ancient times, due to several biological properties, such as antimicrobial, anti-inflammatory, antioxidant and immunomodulatory activities, among others. Its antitumor action in vivo and in vitro has also been reported, using propolis extracts or its isolated compounds. The goal of this work was to evaluate propolis's cytotoxic action in vitro on human laryngeal epidermoid carcinoma (Hep-2 cells. These cells were incubated with different concentrations of this bee product for different time periods, and morphology and the number of viable HEp-2 cells analyzed. Data showed that propolis exhibited a cytotoxic effect in vitro against HEp-2 cells, in a dose- and time-dependent way. Propolis solvent had no effects on morphology and number of viable cells, proving that the cytotoxic effects were exclusively due to propolis components. Since humans have been using propolis for a long time, further assays will provide a better comprehension of propolis's antitumor action.

  15. Nicotine induces mitochondrial fission through mitofusin degradation in human multipotent embryonic carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Naoya; Yamada, Shigeru [Division of Pharmacology, National Institute of Health Sciences (Japan); Asanagi, Miki [Division of Pharmacology, National Institute of Health Sciences (Japan); Faculty of Engineering, Department of Materials Science and Engineering, Yokohama National University (Japan); Sekino, Yuko [Division of Pharmacology, National Institute of Health Sciences (Japan); Kanda, Yasunari, E-mail: kanda@nihs.go.jp [Division of Pharmacology, National Institute of Health Sciences (Japan)

    2016-02-05

    Nicotine is considered to contribute to the health risks associated with cigarette smoking. Nicotine exerts its cellular functions by acting on nicotinic acetylcholine receptors (nAChRs), and adversely affects normal embryonic development. However, nicotine toxicity has not been elucidated in human embryonic stage. In the present study, we examined the cytotoxic effects of nicotine in human multipotent embryonal carcinoma cell line NT2/D1. We found that exposure to 10 μM nicotine decreased intracellular ATP levels and inhibited proliferation of NT2/D1 cells. Because nicotine suppressed energy production, which is a critical mitochondrial function, we further assessed the effects of nicotine on mitochondrial dynamics. Staining with MitoTracker revealed that 10 μM nicotine induced mitochondrial fragmentation. The levels of the mitochondrial fusion proteins, mitofusins 1 and 2, were also reduced in cells exposed to nicotine. These nicotine effects were blocked by treatment with mecamylamine, a nonselective nAChR antagonist. These data suggest that nicotine degrades mitofusin in NT2/D1 cells and thus induces mitochondrial dysfunction and cell growth inhibition in a nAChR-dependent manner. Thus, mitochondrial function in embryonic cells could be used to assess the developmental toxicity of chemicals.

  16. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level.

    Directory of Open Access Journals (Sweden)

    Deli Liu

    2015-06-01

    Full Text Available Spontaneous canine head and neck squamous cell carcinoma (HNSCC represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling, and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

  17. Canine spontaneous head and neck squamous cell carcinomas represent their human counterparts at the molecular level.

    Science.gov (United States)

    Liu, Deli; Xiong, Huan; Ellis, Angela E; Northrup, Nicole C; Dobbin, Kevin K; Shin, Dong M; Zhao, Shaying

    2015-06-01

    Spontaneous canine head and neck squamous cell carcinoma (HNSCC) represents an excellent model of human HNSCC but is greatly understudied. To better understand and utilize this valuable resource, we performed a pilot study that represents its first genome-wide characterization by investigating 12 canine HNSCC cases, of which 9 are oral, via high density array comparative genomic hybridization and RNA-seq. The analyses reveal that these canine cancers recapitulate many molecular features of human HNSCC. These include analogous genomic copy number abnormality landscapes and sequence mutation patterns, recurrent alteration of known HNSCC genes and pathways (e.g., cell cycle, PI3K/AKT signaling), and comparably extensive heterogeneity. Amplification or overexpression of protein kinase genes, matrix metalloproteinase genes, and epithelial-mesenchymal transition genes TWIST1 and SNAI1 are also prominent in these canine tumors. This pilot study, along with a rapidly growing body of literature on canine cancer, reemphasizes the potential value of spontaneous canine cancers in HNSCC basic and translational research.

  18. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

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    Rodrigo Ramirez-Tagle

    2016-02-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1 and 3′-bromo-3,4-dimethoxy-chalcone (CH2, over human hepatoma cells (HepG2 and Huh-7 and cultured mouse hepatocytes (HepM. Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i a caspase-dependent intrinsic pathway; and (ii by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  19. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-02-22

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  20. Progesterone receptor structure and protease activity in primary human endometrial carcinoma.

    Science.gov (United States)

    Feil, P D; Clarke, C L; Satyaswaroop, P G

    1988-03-01

    Monoclonal antibodies were used to investigate progesterone receptor structure (isoforms) in 33 primary human endometrial tumors. The monoclonal antibodies recognized on protein blots two progesterone receptor proteins with molecular weights of 116,000 and 81,000. The Mr 116,000 protein appeared as a triplet, while a single band was found for the Mr 81,000 protein. The triplet/singlet structure was found in all progesterone receptor-positive tumors, regardless of the degree of tumor differentiation. Protease activity, which gave rise to a false-negative pattern on protein blots, was found in approximately one-half of the tumors in which it was investigated. Inclusion of a cocktail of protease inhibitors during sample preparation resulted in the maintenance of the triplet/singlet progesterone receptor structure. Mixing experiments using a progesterone receptor-rich human endometrial carcinoma (EnCa 101), which lacks protease activity, and protease-containing primary tumor homogenates indicated that the protease was leupeptin sensitive. Interestingly, while the proteolytic activity reduced or eliminated the triplet/singlet progesterone receptor structure seen on protein blot analysis, it did not affect progesterone receptor concentration measured by Scatchard analysis. Sample preparation in the presence of protease inhibitors is therefore a requisite for structural analysis of the progesterone receptor in endometrial tumors.

  1. Assessment of the Selenoprotein M (SELM over-expression on human hepatocellular carcinoma tissues by immunohistochemistry

    Directory of Open Access Journals (Sweden)

    E. Guerriero

    2014-10-01

    Full Text Available Selenium is an essential trace mineral of fundamental importance to human healthy and exerts its biological function through selenoproteins. In particular, Selenoprotein M (SELM is located in the endoplasmic reticulum and contains the common redox motif of cysteine-X-X-selenocysteine type. It attracts great attention due to its high expression in brain and its potential roles as antioxidant, neuroprotective, and cytosolic calcium regulator. Recently, our group found SELM over-expression  in human hepatocellular carcinoma (HCC cell lines. In this report some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV-related cirrhosis and HCC were immunohistochemically stained and SELM expression scoring was evaluated. Our results evidence for the first time an increase of SELM expression in HCC liver tissues, and its gradual expression raise associated with an increased malignancy grade. Therefore, we propose to use i SELM as putative marker for HCC as well as ii simple immunohistochemistry technique to distinguish between the different grades of malignancy. 

  2. Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma.

    Science.gov (United States)

    Guidolin, Diego; Marinaccio, Christian; Tortorella, Cinzia; Annese, Tiziana; Ruggieri, Simona; Finato, Nicoletta; Crivellato, Enrico; Ribatti, Domenico

    2017-02-01

    Mast cells (MCs) accumulate in the stroma surrounding tumors, where they secrete angiogenic cytokines and proteases, and an increased number of MCs have been demonstrated in angiogenesis associated with solid and hematological tumors. The aim of this study is to contribute to the knowledge of distribution of MCs in tumors, investigating the pattern of distribution of tryptase-positive MCs around the blood vessels in human endometrial carcinoma samples by introducing a quantitative approach to characterize their spatial distribution. The results have shown that in human endometrial cancer bioptic specimens the spatial distribution of MCs shows significant deviation from randomness as compared with control group in which, instead, the spatial distribution of MCs is consistent with a random distribution. These findings confirm that MCs enhance tumor angiogenesis and their preferential localization along blood vessels and sites of new vessel formation sustaining the suggestion for an association between MCs and angiogenesis. However, this spatial association between vessels and MCs might simply reflect migrating MCs from the blood stream at vessel growing sites.

  3. Human embryonic stem cells and embryonal carcinoma cells have overlapping and distinct metabolic signatures.

    Directory of Open Access Journals (Sweden)

    Raed Abu Dawud

    Full Text Available While human embryonic stem cells (hESCs and human embryonal carcinoma cells (hECCs have been studied extensively at the levels of the genome, transcriptome, proteome and epigenome our knowledge of their corresponding metabolomes is limited. Here, we present the metabolic signatures of hESCs and hESCs obtained by untargeted gas chromatography coupled to mass spectrometry (GC-MS. Whilst some metabolites are common to both cell types, representing the self-renewal and house-keeping signatures, others were either higher (e.g., octadecenoic acid, glycerol-3-phosphate, 4-hydroxyproline or lower (e.g., glutamic acid, mannitol, malic acid, GABA in hESCs (H9 compared to hECCs (NTERA2, these represent cell type specific signatures. Further, our combined results of GC-MS and microarray based gene expression profiling of undifferentiated and OCT4-depleted hESCs are consistent with the Warburg effect which is increased glycolysis in embryonic cells and tumor cells in the presence of O(2 while oxidative phosphorylation (OXPHOS is impaired or even shut down. RNAi-based OCT4 knock down mediated differentiation resulted in the activation of the poised OXPHOS machinery by expressing missing key proteins such as NDUFC1, UQCRB and COX, increase in TCA cycle activity and decreased lactate metabolism. These results shed light on the metabolite layer of pluripotent stem cells and could potentially establish novel metabolic markers of self renewal and pluripotency.

  4. Desenvolvimento de protótipo para aplicação do laser de CO2 na laringe humana a curtas distâncias Prototype development for CO2 laser application on human larynx at small distances

    Directory of Open Access Journals (Sweden)

    Plínio F. Morgado

    2002-03-01

    beam waist. The beam waist size can be described as: 2omega0 =lambdaf /pw², where lambda is the CO2 wavelength and 2omega is the beam diameter. We developed an optical system which produces a very small beam waist. This small shaft of laser is delivered precisely on the target resulting in a reduced impact spot size enhancing precision and lessening surrounding tissue trauma on laryngeal surgery. Aim: To present an optical system which delivers the laser beam at a small distance from the human glottis. Study design: Clinical trial. Material and Methods: The manufactured prototype has two metallic cylindrical shafts joined in a 135º angle from the horizontal. A coated mirror positioned in its joint change the ray path in the same angle. Two coated lenses converge the laser to a calculated beam waist. The hand piece was coupled to the laser articulated arm and the system was set to 0.5 - 2.0 W at 0.05 sec. exposure time. Laryngeal exposure was achieved with the angled videolaryngoscopy. Three patients with vocal fold polyp underwent laser surgery with the technique above described. Results: A beam waist ranging from 200 to 250 mum was obtained (lambdaCO2 = 10,6 mum. The technique offered adequate laryngeal exposure and satisfactory image quality for a proper laser application. No technical difficulties nor major bleeding or mucosal charring was observed during the treatment. No excessive scarring was observed in a two-month follow-up laryngoscopy. Conclusion: The developed prototype produced very small laser shafts which are useful in the treatment of vocal fold polyps.

  5. Expression pattern of RAGE and IGF-1 in the human fetal ovary and ovarian serous carcinoma.

    Science.gov (United States)

    Poljicanin, Ana; Filipovic, Natalija; Vukusic Pusic, Tanja; Soljic, Violeta; Caric, Ana; Saraga-Babic, Mirna; Vukojevic, Katarina

    2015-01-01

    The expression pattern of RAGE and IGF-1 proteins in different ovarian cell lineages was histologically analyzed in six fetal, nine adult human ovaries, and nine serous ovarian carcinomas (OSC) using immunohistochemical methods. Mild expression of IGF-1 in ovarian surface epithelium (Ose) and oocytes in the 15-week human ovaries increased to moderate or strong in the stromal cells, oocytes and follicular cells in week 22. Occasional mild RAGE expression was observed in Ose during week 15, while strong expression characterized primordial follicles in week 22. In the reproductive human ovary, IGF-1 was mildly to moderately expressed in all ovarian cell lineages except in theca cells of the tertiary follicle where IGF-1 was negative. RAGE was strongly positive in the granulosa cells and some theca cells of the tertiary follicle, while negative to mildly positive in all cells of the secondary follicle. In the postmenopausal human ovary IGF-1 and RAGE were mildly expressed in Ose and stroma. In OSC, cells were strongly positive to IGF-1 and RAGE, except for some negative stromal cells. Different levels of IGF-1 and RAGE co-expression characterized fetal ovarian cells during development. In reproductive ovaries, IGF-1 and RAGE were co-localized in the granulosa and theca interna cells of tertiary follicles, while in postmenopausal ovaries and OSC, IGF-1 and RAGE were co-localized in Ose and OSC cells respectively. Our results indicate that intracellular levels of IGF-1 and RAGE protein might regulate the final destiny of the ovarian cell populations prior and during folliculogenesis, possibly controlling the metastatic potential of OSC as well. Copyright © 2015. Published by Elsevier GmbH.

  6. Sp1 upregulates expression of TRF2 and TRF2 inhibition reduces tumorigenesis in human colorectal carcinoma cells.

    Science.gov (United States)

    Dong, Wenjie; Shen, Ruizhe; Wang, Qi; Gao, Yabo; Qi, Xiaoguang; Jiang, He; Yao, Jingjing; Lin, Xiaolin; Wu, Yunlin; Wang, Lifu

    2009-11-01

    Telomere repeat binding factor 2 (TRF2) plays a key role in the protective activity of telomere and is overexpression in several kinds of solid cancer cells. However, the role of overexpressed TRF2 in colorectal carcinoma remains unclear. The aim of this study was to determine the expression of TRF2, address the mechanism of TRF2 overexpression in human colorectal carcinoma. In present study, we examined the expression of TRF2 in colorectal cancer tissues from 39 patients, peritumoral normal tissues from 21 patients, and colon carcinoma SW480 cell line by quantitative PCR, immunohistochemistry and western blot. After siRNA silencing TRF2 expression in SW480, tumorigenesis of TRF2 was tested by cell proliferation, soft agar assay, cytofluorimetric analysis and cytogenetic analysis. To discover transcription factor that mediated TRF2 expression, Chromatin Immunoprecipitation (Chip) Assay and Electrophoretic mobility shift assays (EMSA) were employed. Overexpression of TRF2 protein was detected in SW480 cells and 19 of 39 colorectal carcinoma tissues (49%), no overexpression was observed in 21 of 21 adjacent peritumoral normal colorectal tissues. After siRNA silencing TRF2 expression, the proliferation and colony formation of SW480 cells were significantly inhibited. Defective TRF2 induced apoptosis and increased chromosomal instability in SW480 cells, in which there were more end-to-end fusions and ring chromosomes. Chip assay and EMSA showed that transcription factor Sp1 is involved in upregulation of TRF2. These results indicate that TRF2 is overexpressed in colorectal carcinoma, Sp1 upregulates TRF2 expression, TRF2 inhibition reduces tumorigenesis of colorectal cancer, which suggests that TRF2 and SP1 may become new targets for the development of anti-cancer therapy in colorectal carcinoma.

  7. Total Laryngectomy Versus Larynx Preservation for T4a Larynx Cancer: Patterns of Care and Survival Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Grover, Surbhi; Swisher-McClure, Samuel [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mitra, Nandita; Li, Jiaqi [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Cohen, Roger B. [Department of Hematology Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Ahn, Peter H.; Lukens, John N. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Chalian, Ara A.; Weinstein, Gregory S.; O' Malley, Bert W. [Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Lin, Alexander, E-mail: alexander.lin@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2015-07-01

    Purpose: To examine practice patterns and compare survival outcomes between total laryngectomy (TL) and larynx preservation chemoradiation (LP-CRT) in the setting of T4a larynx cancer, using a large national cancer registry. Methods and Materials: Using the National Cancer Database, we identified 969 patients from 2003 to 2006 with T4a squamous cell larynx cancer receiving definitive treatment with either initial TL plus adjuvant therapy or LP-CRT. Univariate and multivariable logistic regression were used to assess predictors of undergoing surgery. Survival outcomes were compared using Kaplan-Meier and propensity score–adjusted and inverse probability of treatment–weighted Cox proportional hazards methods. Sensitivity analyses were performed to account for unmeasured confounders. Results: A total of 616 patients (64%) received LP-CRT, and 353 (36%) received TL. On multivariable logistic regression, patients with advanced nodal disease were less likely to receive TL (N2 vs N0, 26.6% vs 43.4%, odds ratio [OR] 0.52, 95% confidence interval [CI] 0.37-0.73; N3 vs N0, 19.1% vs 43.4%, OR 0.23, 95% CI 0.07-0.77), whereas patients treated in high case-volume facilities were more likely to receive TL (46.1% vs 31.5%, OR 1.78, 95% CI 1.27-2.48). Median survival for TL versus LP was 61 versus 39 months (P<.001). After controlling for potential confounders, LP-CRT had inferior overall survival compared with TL (hazard ratio 1.31, 95% CI 1.10-1.57), and with the inverse probability of treatment–weighted model (hazard ratio 1.25, 95% CI 1.05-1.49). This survival difference was shown to be robust on additional sensitivity analyses. Conclusions: Most patients with T4a larynx cancer receive LP-CRT, despite guidelines suggesting TL as the preferred initial approach. Patients receiving LP-CRT had more advanced nodal disease and worse overall survival. Previous studies of (non-T4a) locally advanced larynx cancer showing no difference in survival between LP-CRT and TL may not

  8. MiR-4282 suppresses proliferation and mobility of human colorectal carcinoma cells by targeting semaphorin 3E.

    Science.gov (United States)

    Kang, Xing; Wang, Meng; Wang, Hao; Shen, Xiaofei; Guan, Wenxian

    2016-09-01

    MicroRNAs play an important role in cancer development. Deregulation of microRNAs can lead to tumorigenesis. Class 3 semaphorin, semaphorin 3E (Sema3E), has been shown to be implicated in tumor growth and metastasis. The role of miR-4282 in regulating colorectal carcinoma and its correlation to Sema3E remain uncertain. Real-time quantitative reverse transcription polymerase chain reaction was used to detect the levels of miR-4282 and Sema3E in colorectal carcinoma cells and colorectal tumor tissues. Sema3E protein level in cell lines and human tissues was analyzed by western blot Transient transfections of miR-4282 inhibitor or mimics were conducted to silence or overexpress miR-4282. Sema3E siRNA was transfected to knockdown Sema3E in tumor cell lines. MTT assay was employed to measure colorectal tumor cell growth. Migration and invasion of the cells were examined by trans-well assays. Luciferase reporter assays were performed to confirm miR-4282 targeted at Sema3E. In the present study, reduced miR-4282 expression was observed in the colorectal carcinoma cell lines and human carcinoma tissues in comparison with normal human colon cells (Phuman colorectal tumor tissues (Pmobility (P<0.05). Sema3E was predicted as a target of miR-4282 in miRDB database. We found that miR-4282 overexpression significantly reduced luciferase activity of pRL-Sema3E-3'-UTR (P<0.05), but failed to alter the activity of pRL-sema3E-3'-UTR-mutation. Also, miR4282 overexpression suppressed Sema3E expression in the colorectal carcinoma cell lines. To further confirm the role of Sema3E suppression in the function of the colorectal carcinoma cells by miR-4282, HT29 and HCT116 cells were transfected with Sema3E siRNA. We found that cell growth, migration and invasion of HT29 and HCT116 cells were dramatically inhibited by Sema3E knockdown (P<0.05). Our findings suggested that miR-4282 is a tumor suppressor in colorectal carcinoma cells and exerted its inhibitory effect on the tumor cells

  9. Expression of the human sodium/iodide symporter (hNIS) in xenotransplanted human thyroid carcinoma

    NARCIS (Netherlands)

    Smit, J.W.A.; Schröder - van der Elst, J.P.; Karperien, M.; Que, I.; Romijn, J.A.; Heide, van der D.

    2001-01-01

    The uptake of iodide in thyroid epithelial cells is mediated by the sodium/iodide symporter (NIS). The uptake of iodide is of vital importance for thyroid physiology and is a prerequisite for radioiodine therapy in thyroid cancer. Loss of iodide uptake due to diminished expression of the human NIS

  10. MicroRNA-328 enhances cellular motility through posttranscriptional regulation of PTPRJ in human hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Luo X

    2015-10-01

    Full Text Available Xiaoling Luo,1 Shiyan Yang,2 Chuanwen Zhou,1 Feng Pan,1 Qianjun Li,1 Shijie Ma1 1Department of Gastroenterology, Huai’an First People’s Hospital, Nanjing Medical University, 2Department of Gastroenterology, Huai’an Hospital Affiliated to Xuzhou Medical College and Huai’an Second People’s Hospital, Huai’an, Jiangsu, People’s Republic of China Objective: Interaction between microRNA (miR-328 and PTPRJ (protein tyrosine phosphatase, receptor type, J has been reported to be responsible for miR-328-dependent increase in epithelial cancer cell proliferation. However, the role of miR-328 and PTPRJ in hepatocellular carcinoma (HCC remains unclear. The aim of this study was to investigate the clinical significance of miR-328 and/or PTPRJ expression in human HCC and determine their precise biological functions in this malignancy. Methods: Expression levels of miR-328 and PTPRJ messenger RNA (mRNA in 100 pairs of HCC and adjacent noncancerous tissues were detected using quantitative real-time reverse transcription polymerase chain reaction. The associations between miR-328 and/or PTPRJ expression and various clinicopathological features of HCC patients were further statistically assessed. Then, the functions of miR-328 and PTPRJ in migration and invasion of two human HCC cell lines were determined by transwell assays. Results: miR-328 and PTPRJ mRNA expression levels were markedly upregulated and downregulated in HCC tissues, respectively, compared to adjacent noncancerous tissues. Notably, the upregulation of miR-328 in HCC tissues was significantly correlated with the downregulation of PTPRJ mRNA in HCC tissues (r=-0.362, P=0.01. In addition, miR-328-high and/or PTPRJ-low expression were found to be closely correlated with high Edmondson–Steiner grading (all P<0.05 and advanced tumor-node-metastasis stage (all P<0.05. Moreover, the restoration of miR-328 dramatically promoted HCC cell migration and invasion by repressing PTPRJ expression

  11. Detection of human papillomavirus in squamous cell carcinoma arising from dermoid cysts.

    Science.gov (United States)

    Chiang, An-Jen; Chen, Di-Rong; Cheng, Jiin-Tsuey; Chang, Tsung-Hsien

    2015-10-01

    Primary squamous cell carcinoma (SCC) of the ovary in humans is rare. Most cases represent a malignant transformation of ovarian teratoma, Brenner tumor, or endometriosis. The etiology of this cancer remains largely unknown. Human papillomavirus (HPV) infection is a critical factor that induces tumor formation, particularly cervical cancer. Therefore, this study aimed to evaluate the association of HPV with malignant transformation of mature cystic teratoma (MCT) into SCC of the ovary. The samples included four formalin-fixed paraffin-embedded SCC-MCT tissues and their adjacent tissues from the cervix to the ovaries, 12 cases of benign teratoma ovarian tissues (dermoid tissues), and 11 cases of benign nonteratoma ovarian tissues (nondermoid tissues). The two squamous carcinoma tissues of the cervix were used as control samples. HPV was detected by immunohistochemistry (IHC) with anti-HPV capsid or E6 (HPV type 16/18) antibodies and in situ hybridization (ISH) with three sets of genotyping probes, HPV types 6/11, 16/18, and 31/33. IHC revealed HPV infection associated with the four cases of SCC-MCT and the two cases of control cervical cancer samples. Importantly, HPV was also detected in adjacent reproductive tissues of the SCC-MCT cases, which suggested that the viral particles might spread in an ascending route through the fallopian tubes, endometrium, endocervix, and cervix to the ovaries. ISH revealed HPV type 16/18 in all SCC-MCT cases and HPV type 31/33 in two, with no HPV type 6/11 in any SCC-MCT cases. However, compared with the SCC-MCT cases, the lower detection rates of HPV in dermoid cysts and nondermoid tissues suggested that HPV might not be associated with normal ovarian tissues or benign ovarian teratomas. Our data suggest that high-risk HPV infection might be a causal factor that induces malignant transformation of MCT into SCC of the ovary, although further investigation is still required. Copyright © 2015. Published by Elsevier B.V.

  12. Cyclic AMP Induces Transforming Growth Factor β2 Gene Expression and Growth Arrest in the Human Androgen-Independent Prostate Carcinoma Cell Line PC-3

    National Research Council Canada - National Science Library

    Yung-Jue Bang; Seong-Jin Kim; David Danielpour; Michael A. O'Reilly; Kyung Young Kim; Charles E. Myers; Jane B. Trepel

    1992-01-01

    .... To develop an additional approach to the treatment of advanced prostate cancer, we have been studying the signal transductions controlling the growth of human androgen-independent prostate carcinoma cell lines...

  13. Cyclic AMP induces transforming growth factor beta 2 gene expression and growth arrest in the human androgen-independent prostate carcinoma cell line PC-3

    National Research Council Canada - National Science Library

    Y J Bang; S J Kim; D Danielpour; M A O'Reilly; K Y Kim; C E Myers; J B Trepel

    1992-01-01

    .... To develop an additional approach to the treatment of advanced prostate cancer, we have been studying the signal transductions controlling the growth of human androgen-independent prostate carcinoma cell lines...

  14. Cyclic AMP-independent secretion of mucin by SW1116 human colon carcinoma cells. Differential control by Ca2+ ionophore A23187 and arachidonic acid

    National Research Council Canada - National Science Library

    Yedgar, S; Eidelman, O; Malden, E; Roberts, D; Etcheberrigaray, R; Goping, G; Fox, C; Pollard, H B

    1992-01-01

    The regulation of mucin secretion by SW1116 human colon carcinoma cells has been studied using monoclonal antibody 19-9, which has previously been used to detect mucin in the serum of cancer and cystic fibrosis patients...

  15. Nano-engineering of biomedical prednisolone liposomes: evaluation of the cytotoxic effect on human colon carcinoma cell lines.

    Science.gov (United States)

    Lorente, Cristina; Arias, José L; Cabeza, Laura; Ortiz, Raúl; Prados, José C; Melguizo, Consolación; Delgado, Ángel V; Clares-Naveros, Beatriz

    2018-01-30

    Liposomes have attracted the attention of researchers due to their potential to act as drug delivery systems for cancer treatment. The present investigation aimed to develop liposomes loaded with prednisolone base and the evaluation of the antiproliferative effect on human colon carcinoma cell lines. Liposomes were elaborated by following a reproducible thin film hydration technique. The physicochemical characterization of liposomes included photon correlation spectroscopy, microscopy analysis, Fourier transform infrared spectroscopy, rheological behaviour and electrophoresis. On the basis of these data and drug loading values, the best formulation was selected. Stability and drug release properties were also tested. Resulting liposomes exhibited optimal physicochemical and stability properties, an excellent haemocompatibility and direct antiproliferative effect on human colon carcinoma T-84 cell lines. This study shows direct antitumour effect of prednisolone liposomal formulation, which opens the door for liposomal glucocorticoids as novel antitumour agents. © 2018 Royal Pharmaceutical Society.

  16. Isolation of a hemidesmosome-rich fraction from a human squamous cell carcinoma cell line

    Energy Technology Data Exchange (ETDEWEB)

    Hirako, Yoshiaki, E-mail: s47526a@cc.nagoya-u.ac.jp [Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan); Yonemoto, Yuki; Yamauchi, Tomoe [Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan); Nishizawa, Yuji; Kawamoto, Yoshiyuki [Department of Biomedical Sciences, Chubu University, 1200 Matsumoto-cho, Kasugai 487-8501 (Japan); Owaribe, Katsushi [Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan)

    2014-06-10

    Hemidesmosomes are cell-to-matrix adhesion complexes anchoring keratinocytes to basement membranes. For the first time, we present a method to prepare a fraction from human cultured cells that are highly enriched in hemidesmosomal proteins. Using DJM-1 cells derived from human squamous cell carcinoma, accumulation of hemidesmosomes was observed when these cells were cultured for more than 10 days in a commercial serum-free medium without supplemental calcium. Electron microscopy demonstrated that numerous electron-dense adhesion structures were present along the basal cell membranes of DJM-1 cells cultured under the aforementioned conditions. After removing cellular materials using an ammonia solution, hemidesmosomal proteins and deposited extracellular matrix were collected and separated by electrophoresis. There were eight major polypeptides, which were determined to be plectin, BP230, BP180, integrin α6 and β4 subunits, and laminin-332 by immunoblotting and mass spectrometry. Therefore, we designated this preparation as a hemidesmosome-rich fraction. This fraction contained laminin-332 exclusively in its unprocessed form, which may account for the promotion of laminin deposition, and minimal amounts of Lutheran blood group protein, a nonhemidesmosomal transmembrane protein. This hemidesmosome-rich fraction would be useful not only for biological research on hemidesmosomes but also for developing a serum test for patients with blistering skin diseases. - Highlights: • A defined condition promoted accumulation of hemidesmosomes in human cultured cells. • A fraction isolated from the cells contained eight major polypeptides. • The polypeptides were the five major hemidesmosome proteins and laminin-332. • The cultured cells deposited laminin-332 in its unprocessed form under the condition. • We report a method to prepare a fraction highly enriched in hemidesmosome proteins.

  17. Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma

    Directory of Open Access Journals (Sweden)

    Kim Il-Han

    2009-06-01

    Full Text Available Abstract Background Peroxiredoxins (Prxs are a novel group of peroxidases containing high antioxidant efficiency. The mammalian Prx family has six distinct members (Prx I-VI in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. The function of Prx I in particular has been implicated in regulating cell proliferation, differentiation, and apoptosis. Since thioredoxin1 (Trx1 as an electron donor is functionally associated with Prx I, we investigated levels of expression of both Prx I and Trx1. Methods We investigated levels of expression of both Prx I and Trx1 in breast cancer by real-time polymerase chain reaction (RT-PCR and Western blot. Results Levels of messenger RNA (mRNA for both Prx I and Trx1 in normal human breast tissue were very low compared to other major human tissues, whereas their levels in breast cancer exceeded that in other solid cancers (colon, kidney, liver, lung, ovary, prostate, and thyroid. Among members of the Prx family (Prx I-VI and Trx family (Trx1, Trx2, Prx I and Trx1 were preferentially induced in breast cancer. Moreover, the expression of each was associated with progress of breast cancer and correlated with each other. Western blot analysis of different and paired breast tissues revealed consistent and preferential expression of Prx I and Trx1 protein in breast cancer tissue. Conclusion Prx I and Trx1 are overexpressed in human breast carcinoma and the expression levels are associated with tumor grade. The striking induction of Prx I and Trx1 in breast cancer may enable their use as breast cancer markers.

  18. Mutational spectra of aflatoxin B1in vivo establish biomarkers of exposure for human hepatocellular carcinoma.

    Science.gov (United States)

    Chawanthayatham, Supawadee; Valentine, Charles C; Fedeles, Bogdan I; Fox, Edward J; Loeb, Lawrence A; Levine, Stuart S; Slocum, Stephen L; Wogan, Gerald N; Croy, Robert G; Essigmann, John M

    2017-04-11

    Aflatoxin B 1 (AFB 1 ) and/or hepatitis B and C viruses are risk factors for human hepatocellular carcinoma (HCC). Available evidence supports the interpretation that formation of AFB 1 -DNA adducts in hepatocytes seeds a population of mutations, mainly G:C→T:A, and viral processes synergize to accelerate tumorigenesis, perhaps via inflammation. Responding to a need for early-onset evidence predicting disease development, highly accurate duplex sequencing was used to monitor acquisition of high-resolution mutational spectra (HRMS) during the process of hepatocarcinogenesis. Four-day-old male mice were treated with AFB 1 using a regimen that induced HCC within 72 wk. For analysis, livers were separated into tumor and adjacent cellular fractions. HRMS of cells surrounding the tumors revealed predominantly G:C→T:A mutations characteristic of AFB 1 exposure. Importantly, 25% of all mutations were G→T in one trinucleotide context (C G C; the underlined G is the position of the mutation), which is also a hotspot mutation in human liver tumors whose incidence correlates with AFB 1 exposure. The technology proved sufficiently sensitive that the same distinctive spectrum was detected as early as 10 wk after dosing, well before evidence of neoplasia. Additionally, analysis of tumor tissue revealed a more complex pattern than observed in surrounding hepatocytes; tumor HRMS were a composite of the 10-wk spectrum and a more heterogeneous set of mutations that emerged during tumor outgrowth. We propose that the 10-wk HRMS reflects a short-term mutational response to AFB 1 , and, as such, is an early detection metric for AFB 1 -induced liver cancer in this mouse model that will be a useful tool to reconstruct the molecular etiology of human hepatocarcinogenesis.

  19. In vitro anti-proliferative activity of clove extract on human gastric carcinoma

    Directory of Open Access Journals (Sweden)

    A. Karimi

    2017-10-01

    Full Text Available Background and objectives: Cancer cell resistance to common chemotherapy agents is on rise. Plants are considered valuable sources of herbal drugs for cancer therapy. The present study was conducted to investigate the in vitro antioxidant, anti-proliferative, and apoptosis-inducing properties of clove (Syzygium aromaticum L. extract in human gastric carcinoma (AGS. Methods: Crude ethanol extract of S. aromaticum dried buds was prepared and  in vitro anti-proliferative effects of the extract on AGS and normal Human dermal fibroblasts (HDF cell lines were studied by MTT assay. To examine apoptosis induction, AGS cells were incubated with IC50 concentrations of the extract, stained with propidium iodide (PI and annexin V-fluorescein isothiocyanate (FITC, and analyzed by flow cytometry. Antioxidant activity and total phenolics and flavonoids contents were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method, respectively. Results: The IC50 of DPPH and total phenolics and flavonoids contents of the extract were 10.05±1.93 μg/mL, 225.6±40 mg GAE/g, and 29.30±2.35 mgRUT/g, respectively. The IC50 of the extract against HDFs was 649 µg/mL, higher than AGS cells, which was 118.7 g/mL at 48 h after treatment. Flow cytometric analysis showed that the extract induced cell apoptosis. Conclusions: Crude ethanol S. aromaticum extract had high total phenolics content, and suppressed the proliferation of human gastric cancer cells, likely due to apoptosis induction. Further studies should be conducted to determine the mechanisms of its anticancer effects.

  20. Molecular basis of arsenite (As+3-induced acute cytotoxicity in human cervical epithelial carcinoma cells

    Directory of Open Access Journals (Sweden)

    Muhammad Nauman Arshad

    2015-04-01

    Full Text Available Background: Rapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As+3 on DNA biosynthesis and cell death. Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry. Results: We show that As+3 ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As+3 (7.5 µg/ml. Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest. Conclusion: Our results indicate that sudden exposure of cells to arsenite (As+3 resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases.

  1. Gene expression and pathway analysis of human hepatocellular carcinoma cells treated with cadmium.

    Science.gov (United States)

    Cartularo, Laura; Laulicht, Freda; Sun, Hong; Kluz, Thomas; Freedman, Jonathan H; Costa, Max

    2015-11-01

    Cadmium (Cd) is a toxic and carcinogenic metal naturally occurring in the Earth's crust. A common route of human exposure is via diet and cadmium accumulates in the liver. The effects of Cd exposure on gene expression in human hepatocellular carcinoma (HepG2) cells were examined in this study. HepG2 cells were acutely-treated with 0.1, 0.5, or 1.0 μM Cd for 24h; or chronically-treated with 0.01, 0.05, or 0.1 μM Cd for three weeks and gene expression analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Acute and chronic exposures significantly altered the expression of 333 and 181 genes, respectively. The genes most upregulated by acute exposure included several metallothioneins. Downregulated genes included the monooxygenase CYP3A7, involved in drug and lipid metabolism. In contrast, CYP3A7 was upregulated by chronic Cd exposure, as was DNAJB9, an anti-apoptotic J protein. Genes downregulated following chronic exposure included the transcriptional regulator early growth response protein 1. Ingenuity Pathway Analysis revealed that the top networks altered by acute exposure were lipid metabolism, small molecule biosynthesis, cell morphology, organization, and development; while top networks altered by chronic exposure were organ morphology, cell cycle, cell signaling, and renal and urological diseases/cancer. Many of the dysregulated genes play important roles in cellular growth, proliferation, and apoptosis, and may be involved in carcinogenesis. In addition to gene expression changes, HepG2 cells treated with cadmium for 24h indicated a reduction in global levels of histone methylation and acetylation that persisted 72 h post-treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Felicia Hosein

    2013-04-01

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

  3. Detection of human papillomavirus DNA and oncoprotein overexpression are associated with distinct morphological patterns of tonsillar squamous cell carcinoma.

    OpenAIRE

    Wilczynski, S P; Lin, B T; Xie, Y; Paz, I.B.

    1998-01-01

    Human papillomavirus (HPV) DNA has been detected in approximately 15% of squamous cell carcinomas (SCCs) of the head and neck. Recent studies have shown a predilection of HPV for certain anatomical sites, especially the tonsillar region, with viral DNA identified in approximately 60% of SCCs of the Waldeyer's tonsillar ring. This study was undertaken to determine whether there are differences in morphology or in oncogene expression in SCC of the tonsil with and without detectable HPV DNA. Twe...

  4. The caspase 3-dependent apoptotic effect of pycnogenol in human oral squamous cell carcinoma HSC-3 cells

    OpenAIRE

    Yang, In-Hyoung; Shin, Ji-Ae; Kim, Lee-Han; Kwon, Ki Han; CHO, SUNG-DAE

    2015-01-01

    In the present study, the apoptotic effect of pycnogenol and its molecular mechanism in human oral squamous cell carcinoma HSC-3 cells were investigated. Pycnogenol significantly inhibited the viability of HSC-3 cells and suppressed neoplastic cell transformation in HSC-3 cells and TPA-treated JB6 cells. It caused caspase-dependent apoptosis evidenced by the increase in cleaved poly (ADP-ribose) polymerase and caspase 3 in a dose-dependent manner. Pycnogenol increased Bak protein by enhancing...

  5. Antiproliferative activity and phenotypic modification induced by selected Peruvian medicinal plants on human hepatocellular carcinoma Hep3B cells

    OpenAIRE

    Carraz, Maëlle; Lavergne, C.; Jullian, Valérie; Wright, M.; Gairin, J E; de la Cruz, M. G.; Bourdy, Geneviève

    2015-01-01

    Ethnopharmacological relevance: The high incidence of human hepatocellular carcinoma (HCC) in Peru and the wide use of medicinal plants in this country led us to study the activity against HCC cells in vitro of somes species used locally against liver and digestive disorders. Materials and methods: Ethnopharmacological survey: Medicinal plant species with a strong convergence of use for liver and digestive diseases were collected fresh in the wild or on markets, in two places of Peru: Chiclay...

  6. Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest.

    Directory of Open Access Journals (Sweden)

    Md Sultan Ahamad

    Full Text Available A natural predominant flavanone naringenin, especially abundant in citrus fruits, has a wide range of pharmacological activities. The search for antiproliferative agents that reduce skin carcinoma is a task of great importance. The objective of this study was to analyze the anti-proliferative and apoptotic mechanism of naringenin using MTT assay, DNA fragmentation, nuclear condensation, change in mitochondrial membrane potential, cell cycle kinetics and caspase-3 as biomarkers and to investigate the ability to induce reactive oxygen species (ROS initiating apoptotic cascade in human epidermoid carcinoma A431 cells. Results showed that naringenin exposure significantly reduced the cell viability of A431 cells (p<0.01 with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed statistically significant (p<0.001 dose-related increment in ROS production for naringenin. It also caused naringenin-mediated epidermoid carcinoma apoptosis by inducing mitochondrial depolarization. Cell cycle study showed that naringenin induced cell cycle arrest in G0/G1 phase of cell cycle and caspase-3 analysis revealed a dose dependent increment in caspase-3 activity which led to cell apoptosis. This study confirms the efficacy of naringenin that lead to cell death in epidermoid carcinoma cells via inducing ROS generation, mitochondrial depolarization, nuclear condensation, DNA fragmentation, cell cycle arrest in G0/G1 phase and caspase-3 activation.

  7. Antiepiligrin cicatricial pemphigoid of the larynx successfully treated with a combination of tetracycline and niacinamide.

    Science.gov (United States)

    Sakamoto, Kikuo; Mori, Kazunori; Hashimoto, Takashi; Yancey, Kim B; Nakashima, Tadashi

    2002-12-01

    A case of antiepiligrin cicatricial pemphigoid that primarily involved the larynx and required a tracheostomy was studied. The diagnosis was based on the direct immunofluorescence findings of a biopsy specimen from the glottis, immunofluorescence using normal and 1M sodium chloride-split normal human skin as substrates, and immunoprecipitation. A dramatic clinical improvement was observed after the combined administration of tetracycline hydrochloride and niacinamide. The tracheal stoma could be shut after the narrow segment was cut by means of carbon dioxide laser therapy. The patient showed no respiratory difficulty during the 2-year follow-up period. The combined therapy of tetracycline and niacinamide is thus considered to be an effective treatment for various types of cicatricial pemphigoid.

  8. Overexpression of stefin A in human esophageal squamous cell carcinoma cells inhibits tumor cell growth, angiogenesis, invasion, and metastasis.

    Science.gov (United States)

    Li, Wendong; Ding, Fang; Zhang, Liyong; Liu, Zhongmin; Wu, Yu; Luo, Aiping; Wu, Min; Wang, Mingrong; Zhan, Qimin; Liu, Zhihua

    2005-12-15

    Evidence is accumulating that an inverse correlation exists between stefin A level and malignant progression. The aim of this study is to investigate the role of stefin A in human esophageal squamous cell carcinoma cells and to evaluate the possibility of stefin A for cancer therapy. We stably transfected stefin A cDNA into human EC9706 or KYSE150 esophageal squamous cell carcinoma cells. Subsequently, we evaluated the effect of stefin A overexpression on cell growth, cathepsin B activity, cell motility and invasion, tumor growth, and metastasis. Immunoanalysis was done to assess the expression of factor VIII and to support the localization of stefin A and cathepsin B. We also evaluated the effect of CA074Me, a selective membrane-permeant cathepsin B inhibitor. Both transfection of stefin A and treatment with 10 micromol/L CA074Me significantly reduced cathepsin B activity and inhibited the Matrigel invasion. Combination of both further reduced cathepsin B activity and inhibited the Matrigel invasion. Overexpression of stefin A delayed the in vitro and in vivo growth of cells and significantly inhibited lung metastasis compared with 50% of lung metastasis in xenograft mice from EC9706 or empty vector cells. Transfection with stefin A showed a dramatic reduction of factor VIII staining in the tumors of xenograft mice. Our data strongly indicate that stefin A plays an important role in the growth, angiogenesis, invasion, and metastasis of human esophageal squamous cell carcinoma cells and suggest that stefin A may be useful in cancer therapy.

  9. Lycopene inhibits the cell proliferation and invasion of human head and neck squamous cell carcinoma.

    Science.gov (United States)

    Ye, Min; Wu, Qundan; Zhang, Min; Huang, Jinbei

    2016-10-01

    Lycopene has been shown to be associated with anticancer effects in numerous tumor types. However, the underlying mechanisms of lycopene in human head and neck squamous cell carcinoma (HNSCC) remain to be determined. The present study aimed to investigate the involvement of lycopene overload and the cytotoxic effects of lycopene on HNSCC cells, and to determine the possible mechanisms involved. Treatment with lycopene at a dose of >10 µM for >24 h inhibited the growth of FaDu and Cal27 cells in a time‑ and dose‑dependent manner. The clearest increase in growth inhibition was due to the apoptotic population being significantly increased. The invasion abilities decreased with 25 µM lycopene exerting significant inhibitory effects (Plycopene induced the upregulation of the pro‑apoptotic protein, B‑cell lymphoma‑associated X protein, and therefore, resulted in the inhibition of the protein kinase B and mitogen‑activated protein kinase signaling pathway. These data provided insights into the antitumor activity of lycopene in HNSCC cells.

  10. Regorafenib Induces Apoptosis and Inhibits Metastatic Potential of Human Bladder Carcinoma Cells.

    Science.gov (United States)

    Hsu, Fei-Ting; Sun, Cho-Chin; Wu, Chia-Hsing; Lee, Yen-Ju; Chiang, Chih-Hung; Wang, Wei-Shu

    2017-09-01

    The aim of the present study was to verify the effects of regorafenib on apoptosis and metastatic potential in TSGH 8301 human bladder carcinoma cells in vitro. Cells were treated with different concentration of regorafenib for different periods of time. Effects of regorafenib on cell viability, apoptosis pathways, metastatic potential, and expression of metastatic and anti-apoptotic proteins were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, flow cytometry, cell migration and invasion assay, and western blotting. We found regorafenib significantly reduced cell viability, cell migration and invasion, and expression of metastatic and anti-apoptotic proteins. In addition, regorafenib significantly induced accumulation of sub-G1 phase cells, loss of mitochondrial membrane potential, and expression of active caspase-3 and caspase-8. These results show that regorafenib not only induces apoptosis, but also inhibits metastatic potential in bladder cancer TSGH 8301 cells in vitro. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.

    Science.gov (United States)

    Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria

    2016-10-01

    Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.

  12. Antiproliferative effect of chitosan-added kimchi in HT-29 human colon carcinoma cells.

    Science.gov (United States)

    Kong, Chang-Suk; Bahn, Young-Eun; Kim, Boh-Kyung; Lee, Kang-Yoon; Park, Kun-Young

    2010-02-01

    The anticancer effects of chitosan-added kimchi were investigated by using an in vitro cellular system with HT-29 human colon carcinoma cells. Two different kinds of chitosan-soluble chitosan with a 90% degree of deacetylation and 3 cps viscosity and nonsoluble chitosan with a 95% degree of deacetylation and 22 cps viscosity-were used as sub-ingredients to increase anticancer effects of kimchi. The soluble chitosan-added kimchi (SK) and nonsoluble chitosan-added kimchi (NK) were stronger growth inhibitors in HT-29 cells than the control kimchi (CK) according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the growth inhibition test. Treatment with SK and NK induced apoptosis, as determined by 4,6-diamidino-2-phenylindole staining, and resulted in the up-regulation of Bax expression and down-regulation of Bcl-2, cIAP-1, cellular inhibitor of apoptosis-2, cyclooxygenase-2, inhibitory nitric oxide synthase, and nuclear factor kappaB (NF-kappaB) expressions when compared to CK. The antiproliferative and anti-apoptotic effects appeared to be more pronounced in the cells treated with NK. The antiproliferative effects of the chitosan-added kimchi appeared to be associated with the induction of apoptosis through NF-kappaB or an NF-kappaB-dependent pathway. These results suggest that chitosan has potential to be a valuable active ingredient in functional kimchi products with anticancer effects.

  13. Inhibition of cell motility by troglitazone in human ovarian carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Chen Show-Li

    2007-11-01

    Full Text Available Abstract Background Troglitazone (TGZ is a potential anticancer agent. Little is known about the effect of this agent on cancer cell migration. Methods Human ovarian carcinoma cell line, ES-2 cells were treated with various concentrations of TGZ. Cell migration was evaluated by wound-healing and Boyden chamber transwell experiments. PPARγ expression was blocked by PPARγ small interfering RNA. The effects of TGZ on phosphorylation of FAK, PTEN, Akt were assessed by immunoblotting using phospho-specific antibodies. The cellular distribution of paxillin, vinculin, stress fiber and PTEN was assessed by immunocytochemistry. Results TGZ dose- and time-dependently impaired cell migration through a PPARγ independent manner. TGZ treatment impaired cell spreading, stress fiber formation, tyrosine phosphorylation of focal adhesion kinase (FAK, and focal adhesion assembly in cells grown on fibronectin substratum. TGZ also dose- and time-dependently suppressed FAK autophosphorylation and phosphorylation of the C-terminal of PTEN (a phosphatase. At concentration higher than 10 μM, TGZ caused accumulation of PTEN in plasma membrane, a sign of PTEN activation. Conclusion These results indicate that TGZ can suppress cultured ES-2 cells migration. Our data suggest that the anti-migration potential of TGZ involves in regulations of FAK and PTEN activity.

  14. The peiminine stimulating autophagy in human colorectal carcinoma cells via AMPK pathway by SQSTM1

    Directory of Open Access Journals (Sweden)

    Zheng Zhi

    2016-01-01

    Full Text Available Autophagy is a conserved catabolic process, which functions in maintenance of cellular homeostasis in eukaryotic cells. The self-eating process engulfs cellular long-lived proteins and organelles with double-membrane vesicles, and forms a so-called autophagosome. Degradation of contents via fusion with lysosome provides recycled building blocks for synthesis of new molecules during stress, e.g. starvation. Peiminine is a steroidal alkaloid extracted from Fritillaria thunbergii which is widely used in Traditional Chinese Medicine. Previously, peiminine has been identified to induce autophagy in human colorectal carcinoma cells. In this study, we further investigated whether peiminine could induce autophagic cell death via activating autophagy-related signaling pathway AMPK-mTOR-ULK by promoting SQSTM1(P62. Xenograft tumor growth in vivo suggested that both peiminine and starvation inhibit the growth of tumor size and weight, which was prominently enhanced when peiminine and starvation combined. The therapeutical effect of peiminine in cancer treatment is to be expected.

  15. Synthetic Isoliquiritigenin Inhibits Human Tongue Squamous Carcinoma Cells through Its Antioxidant Mechanism

    Directory of Open Access Journals (Sweden)

    Cuilan Hou

    2017-01-01

    Full Text Available Isoliquiritigenin (ISL, a natural antioxidant, has antitumor activity in different types of cancer cells. However the antitumor effect of ISL on human tongue squamous carcinoma cells (TSCC is not clear. Here we aimed to investigate the effects of synthetic isoliquiritigenin (S-ISL on TSCC and elucidate the underlying mechanisms. S-ISL was synthesized and elucidated from its nuclear magnetic resonance spectrum and examined using high performance liquid chromatography. The effects of S-ISL on TSCC cells (Tca8113 were evaluated in relation to cell proliferation, apoptosis and adhesion, migration, and invasion using sulforhodamine B assay, fluorescence microscopy technique, flow cytometry (FCM analysis, and Boyden chamber assay. The associated regulatory mechanisms were examined using FCM and fluorescence microscopy for intracellular reactive oxygen species (ROS generation, Gelatin zymography assay for matrix metalloproteinase (MMP activities, and Western blot for apoptosis regulatory proteins (Bcl-2 and Bax. Our data indicated that S-ISL inhibited Tca8113 cell proliferation, adhesion, migration, and invasion while promoting the cell apoptosis. Such effects were accompanied by downregulation of Bcl-2 and upregulation of Bax, reduction of MMP-2 and MMP-9 activities, and decreased ROS production. We conclude that S-ISL is a promising agent targeting TSCC through multiple anticancer effects, regulated by its antioxidant mechanism.

  16. Synthetic Isoliquiritigenin Inhibits Human Tongue Squamous Carcinoma Cells through Its Antioxidant Mechanism

    Science.gov (United States)

    Hou, Cuilan; Li, Wenguang; Li, Zengyou; Gao, Jing; Chen, Zhenjie; Zhao, Xiqiong; Yang, Yaya

    2017-01-01

    Isoliquiritigenin (ISL), a natural antioxidant, has antitumor activity in different types of cancer cells. However the antitumor effect of ISL on human tongue squamous carcinoma cells (TSCC) is not clear. Here we aimed to investigate the effects of synthetic isoliquiritigenin (S-ISL) on TSCC and elucidate the underlying mechanisms. S-ISL was synthesized and elucidated from its nuclear magnetic resonance spectrum and examined using high performance liquid chromatography. The effects of S-ISL on TSCC cells (Tca8113) were evaluated in relation to cell proliferation, apoptosis and adhesion, migration, and invasion using sulforhodamine B assay, fluorescence microscopy technique, flow cytometry (FCM) analysis, and Boyden chamber assay. The associated regulatory mechanisms were examined using FCM and fluorescence microscopy for intracellular reactive oxygen species (ROS) generation, Gelatin zymography assay for matrix metalloproteinase (MMP) activities, and Western blot for apoptosis regulatory proteins (Bcl-2 and Bax). Our data indicated that S-ISL inhibited Tca8113 cell proliferation, adhesion, migration, and invasion while promoting the cell apoptosis. Such effects were accompanied by downregulation of Bcl-2 and upregulation of Bax, reduction of MMP-2 and MMP-9 activities, and decreased ROS production. We conclude that S-ISL is a promising agent targeting TSCC through multiple anticancer effects, regulated by its antioxidant mechanism. PMID:28203317

  17. No evidence of human papilloma virus infection in basal cell carcinoma

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    Yalda Nahidi

    2015-01-01

    Full Text Available Background: Basal cell carcinoma (BCC is the most common skin cancer among whites, and several risk factors have been discussed in itsdevelopment and progress. Detection of human papilloma virus (HPV deoxyribonucleic acid (DNA BCCs in some studies suggests that the virus may play a role in the pathogenesis of this disease. Several molecular studies showed conflicting reports. Aims: The purpose of this study was to investigate the association between HPV and BCC using polymerase chain reaction (PCR. Materials and Methods: HPV DNA detection was done for 42 paraffin-embedded tissue specimens of BCC and 42 normal skin samples around the lesions by PCR using GP5+/GP6+ primers. Results: HPV DNA was not found in any of the 42 samples of BCC, and only one normal skin sample around the lesions was positive for HPV DNA by PCR. Conclusion: In this study, no statistically significant difference was seen between the presence of HPV DNA in BCC and normal skin around the lesion, and HPV is not likely to have an important role in pathogenesis of BCC.

  18. ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

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    Miao Yun

    Full Text Available Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC method in two independent cohorts of nasopharygeal carcinoma (NPC cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS (P<0.05. Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response could significantly stratify risk (low, intermediate and high for DSS in NPC patients (P<0.001. These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

  19. Targeting canine bladder transitional cell carcinoma with a human bladder cancer-specific ligand

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    Li Bin

    2011-01-01

    Full Text Available Abstract Objective To determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells. Experimental Design The binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. In vivo tumor-specific homing/targeting property and biodistribution of PLZ4 was performed in a mouse xenograft model via tail vein injection and was confirmed with ex vivo imaging. Results PLZ4 exhibited high affinity and specific dose-dependent binding to canine bladder TCC cell lines, but not to normal canine urothelial cells. No significant changes in cell viability or proliferation were observed upon incubation with PLZ4. The in vivo and ex vivo optical imaging study showed that, when linked with the near-infrared fluorescent dye Cy5.5, PLZ4 substantially accumulated at the canine bladder cancer foci in the mouse xenograft model as compared to the control. Conclusions and Clinical Relevance PLZ4 can specifically bind to canine bladder cancer cells. This suggests that the preclinical studies of PLZ4 as a potential diagnostic and therapeutic agent can be performed in dogs with naturally occurring bladder cancer, and that PLZ4 can possibly be developed in the management of canine bladder cancer.

  20. Tributyltin induces mitochondrial fission through NAD-IDH dependent mitofusin degradation in human embryonic carcinoma cells.

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    Yamada, Shigeru; Kotake, Yaichiro; Nakano, Mizuho; Sekino, Yuko; Kanda, Yasunari

    2015-08-01

    Organotin compounds, such as tributyltin (TBT), are well-known endocrine disruptors. TBT acts at the nanomolar level through genomic pathways via the peroxisome proliferator activated receptor (PPAR)/retinoid X receptor (RXR). We recently reported that TBT inhibits cell growth and the ATP content in the human embryonic carcinoma cell line NT2/D1 via a non-genomic pathway involving NAD(+)-dependent isocitrate dehydrogenase (NAD-IDH), which metabolizes isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we evaluated the effects of TBT on mitochondrial NAD-IDH and energy production. Staining with MitoTracker revealed that nanomolar TBT levels induced mitochondrial fragmentation. TBT also degraded the mitochondrial fusion proteins, mitofusins 1 and 2. Interestingly, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. Incubation with an α-ketoglutarate analogue partially recovered TBT-induced mitochondrial dysfunction, supporting the involvement of NAD-IDH. Our data suggest that nanomolar TBT levels impair mitochondrial quality control via NAD-IDH in NT2/D1 cells. Thus, mitochondrial function in embryonic cells could be used to assess cytotoxicity associated with metal exposure.

  1. [Study of inhibitory effect of extracts from Actinidia arguta on human carcinoma of esophagus cells].

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    Zhang, Li; Guo, Hong-Li; Tian, Lin; Cao, Shu-Fen; Du, Chang-Hai

    2007-05-01

    To study the inhibitory effect of extracts from Actinidia arguta by n-butyl alcohol on human carcinoma of esophagus cells (Eca-109) and Its mechanism. MTT colonmetric assay was used to examine the growth inhibitory of concentration-effect (1 microg/ml, 10 microg/ml,100 microg/ml) and time-effect (24 h, 48 h, 72 h) of extracts from Actinidia arguta by n-butyl alcohol on Eca-109 cells. TUNEL test were performed to observe the apoptosis induced by the extracts (1 microg/ml, 10 microg/ml, 100 microg/ml) on Eca-109 cells. The inhibitory effect of the extracts on Eca-109 cells increased in a dose-time Manner and the highest rate of inhibition was 87.2%. The extracts could significantly induce apoptosis of Eca-109 cells, but in control group, apoptosis wasn't observed. The extracts from Actinidia arguta by n-butyl alcohol have good inhibitory effect on Eca-109 cells.

  2. Spatial distribution of mast cells and macrophages around tumor glands in human breast ductal carcinoma.

    Science.gov (United States)

    Tamma, Roberto; Guidolin, Diego; Annese, Tiziana; Tortorella, Cinzia; Ruggieri, Simona; Rega, Serena; Zito, Francesco A; Nico, Beatrice; Ribatti, Domenico

    2017-10-01

    Macrophages and mast cells are usually present in the tumor microenvironment and play an important role as regulators of inflammation, immunological response and angiogenesis in the tumor microenvironment. In this study, we have evaluated macrophage, mast cell, and microvessel density in a selected group of different grade of invasive breast carcinoma tumor specimens. Furthermore, we have investigated the pattern of distribution of CD68-positive macrophages and tryptase-positive mast cells around tumor glands. Results have shown that: A) Macrophages are more numerous in G2 and G3 breast cancer stages respect to controls, the per cent of macrophages in G1 samples was comparable to the controls, and the spatial relationship between macrophages and glands (as indicated by the mean cell-to-gland distance) correlated with CD31-positive vessels. B) Mast cells in G2 and G3 tumor specimens show a significant increase in their number as compared to control samples, and their spatial distribution around the glands did not show any significant difference among groups. Overall, the results of this study confirm the important role of macrophages and mast cells in tumor progression and angiogenesis in human ductal breast cancer, and pointed out the spatial relationship between tumor macrophages and glands, and its correlation with microvascular density. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. The Antitumor Activity of the Novel Compound Jesridonin on Human Esophageal Carcinoma Cells.

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    Cong Wang

    Full Text Available Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP, alanine transaminase (ALT, aspartate transaminase (AST, gamma-glutamyl transferase (GGT, total protein (TP and albumin (ALB indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development.

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

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    Edhyana Sahiratmadja

    2015-12-01

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

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

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    Edhyana Sahiratmadja

    2014-04-01

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

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

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

    2012-04-01

    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) in comparison with biopsies from the adjacent normal tissue. Colon cancer biopsies were used to study the cell populations with an upregulated level of expression of API-5 more closely. Using a magnetic bead-based selection for the epithelial cell marker EpCAM, we purified epithelial cells from the tumor and control tissues and analyzed these cells for API-5 expression by western immunoblotting. We observed that EpCAM-positive tumor cells expressed API-5 in all three colorectal cancer cases tested, in contrast to the control EpCAM-positive and EpCAM-negative cells isolated from the control or tumor tissues. These data suggest that the expression of the API-5 protein is upregulated in tumor epithelial cells and may serve as a prognostic marker in colorectal cancer.

  7. CD200-expressing human basal cell carcinoma cells initiate tumor growth.

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    Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

    2013-01-22

    Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

  8. Ganciclovir uptake in human mammary carcinoma cells expressing herpes simplex virus thymidine kinase

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    Haberkorn, Uwe; Khazaie, Khashayarsha; Morr, Iris; Altmann, Annette; Mueller, Markus; Kaick, Gerhard van

    1998-05-01

    Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after transfection with a retroviral vector bearing the herpes simplex virus thymidine kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (r=0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the nucleoside transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk.

  9. Piperine Triggers Apoptosis of Human Oral Squamous Carcinoma Through Cell Cycle Arrest and Mitochondrial Oxidative Stress.

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    Siddiqui, Sahabjada; Ahamad, Md Sultan; Jafri, Asif; Afzal, Mohd; Arshad, Md

    2017-07-01

    Piperine is a nitrogenous pungent substance exhibiting multifunctional pharmacological properties. However, the mechanism underlying its anticancer potential is not well elucidated in human oral squamous carcinoma (KB) cell line. The anticancer potential of piperine was evaluated through potent biomarkers viz. reactive oxygen species (ROS), cellular apoptosis, and loss of mitochondrial membrane potential (MMP). In addition, cell cycle kinetics and caspases-3 activity were also carried out to confirm anticancer activity of piperine. Results showed that various concentrations (25-300 μM) of piperine exposure reduced the cell viability of KB cells significantly (P Piperine induced significant (P piperine stimulated cell death by inducing loss of MMP, and caspase-3 activation. Cell cycle study revealed that piperine arrested the cells in G2/M phase and decreased the DNA content. Findings of this study suggest the efficacy of piperine in inducing cell death via the decrease in MMP and ROS liberation followed by caspase-3 activation and cell cycle arrest. Further assessment of the anticancer potency of piperine is needed for anticancer drug development.

  10. Pheophorbide a mediated photodynamic therapy against human epidermoid carcinoma cells (A431)

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    Chen, Yi-Chun; Li, Wen-Tyng

    2011-02-01

    The objective of this study was to characterize the death mechanism of human epidermoid carcinoma cells (A431) triggered by photodynamic therapy (PDT) with pheophorbide a. First of all, significant inhibition on the survival of A431 cells (cancer cells selectively. Mitochondria were the main target sites where pheophorbide a accumulated. Formation of reactive oxygen species (ROS) was detected after PDT. Addition of antioxidant N-Acetyl cysteine prevented ROS production and increased cell survival thereafter. The decrease in cellular ATP level was also observed at 6 hrs after PDT. Typical apoptotic cellular morphology and a collapse of mitochondrial membrane potential occurred after PDT. The loss of mitochondrial membrane potential led to the release of cytochrome c from the mitochondria to the cytosol, followed by activation of caspase-9 and caspase-3. The activation of caspase-3 resulted in poly(ADP-ribose) polymerase (PARP) cleavage in A431 cells, followed by DNA fragmentation. In conclusion, the results demonstrated that pheophorbide a possessed photodynamic action against A431 cells, mainly through apoptosis mediated by mitochondrial intrinsic pathway triggered by ROS.

  11. Synchronism in mitochondrial ROS flashes, membrane depolarization and calcium sparks in human carcinoma cells.

    Science.gov (United States)

    Kuznetsov, Andrey V; Javadov, Sabzali; Saks, Valdur; Margreiter, Raimund; Grimm, Michael

    2017-06-01

    Mitochondria are major producers of reactive oxygen species (ROS) in many cells including cancer cells. However, complex interrelationships between mitochondrial ROS (mitoROS), mitochondrial membrane potential (ΔΨm) and Ca2+ are not completely understood. Using human carcinoma cells, we further highlight biphasic ROS dynamics: - gradual mitoROS increase followed by mitoROS flash. Also, we demonstrate heterogeneity in rates of mitoROS generation and flash initiation time. Comparing mitochondrial and near-extra-mitochondrial signals, we show that mechanisms of mitoROS flashes in single mitochondria, linked to mitochondrial permeability transition pore opening (ΔΨm collapse) and calcium sparks, may involve flash triggering by certain levels of external ROS released from the same mitochondria. In addition, mitochondria-mitochondria interactions can produce wave propagations of mitoROS flashes and ΔΨm collapses in cancer cells similar to phenomena of ROS-induced ROS release (RIRR). Our data suggest that in cancer cells RIRR, activation of mitoROS flashes and mitochondrial depolarization may involve participation of extramitochondrial-ROS produced either by individual mitochondria and/or by neighboring mitochondria. This could represent general mechanisms in ROS-ROS signaling with suggested role in both mitochondrial and cellular physiology and signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Case report: human papilloma virus type 120-related papillomatosis mimicking laryngeal carcinoma.

    Science.gov (United States)

    Belvisi, Valeria; Martellucci, Salvatore; Garbuglia, Anna Rosa; Del Borgo, Cosmo; Martellucci, Stanislao; Baiocchini, Andrea; Manicone, Anna Maria; Bagni, Oreste; Mastroianni, Claudio Maria; Gallo, Andrea

    2017-10-01

    The relationship between human papilloma virus (HPV) and upper respiratory tract pathology was better understood in recent years and represents now an issue of particular interest in carcinogenesis and in immunocompromised host. We describe a case in which a rare genotype HPV-related papillomatosis mimics laryngeal carcinoma in an immunocompromised host. A 54-year-old woman with a history of HIV-HCV coinfection and anal and laryngeal cancer successfully treated some years before was hospitalized for severe dyspnea, cough and dysphagia. Fiberoptic endoscopic evaluation raised the suspicion of tumor relapse showing the presence of a large glottic-supraglottic ulcerated mass. Several laryngeal biopsies demonstrated koilocytosis and p16 expression, according to a possible HPV infection, and focal figures of mild dysplasia of epithelium. 18 F-FDG PET/CT did not show high glycolytic activity at laryngeal level. An invasive upper respiratory tract papillomatosis in an immunocompromised host was suspected because of the patient's clinical improvement after antiretroviral therapy. Pharyngeal swab and oral rinse harboured the same HPV120 genotype sequence, a betapapillomavirus of recent description and not yet related to any similar clinical presentations.

  13. Ethanolic Extracts of Pluchea indica Induce Apoptosis and Antiproliferation Effects in Human Nasopharyngeal Carcinoma Cells

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    Chiu-Li Kao

    2015-06-01

    Full Text Available Pluchea indica is used in traditional medicine for the treatment of lumbago, ulcer, tuberculosis and inflammation. The anti-cancer activities and the underlying molecular mechanisms of the ethanolic extracts of P. indica root (PIRE were characterized in the present study. PIRE strongly inhibited the viability of the human nasopharyngeal carcinoma cells (NPC-TW 01 and NPC-TW 04 in a time- and dose-dependent manner. Migration of cancer cells was also suppressed by PIRE. In addition, PIRE significantly increased the occurrence of the cells in sub-G1 phase and the extent of DNA fragmentation in a dose-dependent manner, which indicates that PIRE significantly increased apoptosis in NPC cells. The apoptotic process triggered by PIRE involved up-regulation of pro-apoptotic Bax protein and down-regulation of anti-apoptotic Bcl-2 protein, consequently increasing the ratios of Bax/Bcl-2 protein levels. Moreover, the p53 protein was up-regulated by PIRE in a concentration-dependent manner. Therefore, PIRE could induce the apoptosis-signaling pathway in NPC cells by activation of p53 and by regulation of apoptosis-related proteins.

  14. Synergy of Raddeanin A and cisplatin induced therapeutic effect enhancement in human hepatocellular carcinoma.

    Science.gov (United States)

    Li, Jian-Nan; Yu, Ye; Zhang, Yan-Fei; Li, Zhi-Meng; Cai, Guang-Zhi; Gong, Ji-Yu

    2017-04-01

    Cisplatin is a main compound for human hepatocellular carcinoma (HCC) chemotherapies, but it has certain cytotoxicity during applications. To release that, combining with other drugs are being as a regular plan in clinic. In our present study, we are focusing on one of active monomers extracted from Anemone Raddeana Regel, Raddeanin A (RA), which is on behalf of the same character like cisplatin in the tumor remedies. In order to investigate whether combination usage of RA and cisplatin can be priority to the later drug's effect development and its toxicity reduction in HCC, both of two drugs were treated 24 h or 48 h in QGY-7703 cells for estimating their abilities in tumor cell proliferation inhibition. Results show RA makes synergistic functions with cisplatin after measuring and analyzing their combination index (CI) values. Meanwhile it can strengthen cisplatin's effect through arresting the tumor cells in G0/G1 cycle and further promoting their apoptosis. Interestingly, the molecule signals correlated to tumor cell apoptosis containing both of p53 and bax are simultaneously activated, but bcl-2 and survivin are all depressed in mRNA level. Meanwhile, combining usage with RA can even raise the intracellular productions of reactive oxygen species (ROS). All these consequences reflect RA plays an important role in enhancing the therapeutic effect of cisplatin in HCC. This finding may guide for the drug usage of cisplatin in clinic practice. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Euphorbia Species-derived Diterpenes and Coumarins as Multidrug Resistance Modulators in Human Colon Carcinoma Cells.

    Science.gov (United States)

    Wiśniewski, Jerzy; Wesołowska, Olga; Środa-Pomianek, Kamila; Paprocka, Maria; Bielawska-Pohl, Aleksandra; Krawczenko, Agnieszka; Duarte, Noelia; Ferreira, Maria-José U; Duś, Danuta; Michalak, Krystyna

    2016-05-01

    Recently, many new potent multidrug resistance (MDR) reversal agents have been discovered, among them lathyrane and jatrophane diterpenes isolated from various Euphorbia species. In the present study, the cytotoxicity, P-glycoprotein inhibition activity, and MDR reversal potency of six diterpenes and two coumarins from two Euphorbia species were studied in human colon carcinoma LoVo cells, and doxorubicin-resistant, LoVo/Dx cells. Cytotoxicity of the studied compounds (alone and in combination with doxorubicin) was investigated. Inhibition of P-glycoprotein transport activity was monitored by flow cytometry. Changes in intracellular doxorubicin accumulation were observed by means of fluorescence microscopy. Latilagascene B was demonstrated to be an effective P-glycoprotein inhibitor, able to increase doxorubicin accumulation in resistant cells, however not able to restore doxorubicin cytotoxicity in LoVo/Dx cells. The structure of latilagascene B seems to be an interesting candidate for further synthesis of new derivatives of reduced cytotoxicity and high anti-MDR potency. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial).

    Science.gov (United States)

    Dietz, Andreas; Rudat, Volker; Dreyhaupt, Jens; Pritsch, Maria; Hoppe, Florian; Hagen, Rudolph; Pfreundner, Leo; Schröder, Ursula; Eckel, Hans; Hess, Markus; Schröder, Michael; Schneider, Petra; Jens, Bünzel; Zenner, Hans P; Werner, Jochen A; Engenhardt-Cabillic, Rita; Vanselow, Bernhard; Plinkert, Peter; Niewald, Marcus; Kuhnt, Thomas; Budach, Wilfried; Flentje, Michael

    2009-08-01

    A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m(2) paclitaxel, 100 mg/m(2) cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56-70 Gy in 5.5-7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4-72.2%), after 42 months was 56.5% (95% CI, 44.2-68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9-55.0%); after 42 months, 41.3% (95% CI, 29.3-53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good

  17. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space.

    Science.gov (United States)

    Gale, Nina; Poljak, Mario; Zidar, Nina

    2017-03-01

    Chapter 3 "Tumours of the hypopharynx, larynx, trachea, and parapharyngeal space" of the World Health Organization (WHO) Blue Book 2017 "Classification of Head and Neck Tumours" shows a shortened list of entities, especially due to reducing the number of benign and malignant soft tissue tumours, malignant melanoma and some others, which are transferred to more frequently affected regions of the head and neck. The basic concept of the new edition is to assimilate all advances concerning the discussed tumours in a shorter framework, appropriate for daily work. The main emphasis is on the most frequent lesions and tumors originating from the covering squamous epithelium. Laryngeal and hypopharyngeal conventional squamous cell carcinoma (CSCC), its variants and precursor lesions, occupy a major part of the chapter. New data on etiopathogenesis, with the focus on human papillomavirus (HPV) infection, are discussed in relation to the entities of the squamous epithelium. Although only a small fraction of these lesions are HPV-related, further studies are required for evaluation of the potential prognostic and therapeutic benefit of mRNA HPV determination. In contrast to earlier data, laryngeal and hypopharyngeal verrucous SCC, spindle cell SCC and basaloid SCC are not anymore considered as HPV-related tumours. New data on the pathogenesis of spindle cell SCC exhibiting divergent differentiation by epithelial-mesenchymal transition, are also briefly discussed. The most important innovation is brought by the section on precursor lesions, in which a unified two-tier classification, consisting of low- and high-grade dysplasia, is introduced. The proposed two-tier system can also be transformed into a three-tier classification for treatment purposes, with a distinction between carcinoma in situ and high-grade dysplasia. The reviewed morphological criteria of the proposed system are based on the amended Ljubljana classification. The section on laryngeal neuroendocrine

  18. Epigenetic silencing of MAL, a putative tumor suppressor gene, can contribute to human epithelium cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Jun

    2010-11-01

    suppressor gene, can contribute to human epithelial cell carcinoma and may be served as a biomarker in HNSCC.

  19. [Inhibition of human laryngeal carcinoma growth by gene therapy and epigenetic therapy].

    Science.gov (United States)

    Lian, Meng; Jiang, Ling-yan; Wang, Hong; Fan, Er-zhong; Wang, Qi; Fang, Ju-gao

    2012-09-01

    To observe the effects of gene therapy and epigenetic therapy on the tumor growth of laryngeal carcinoma and the underlying mechanisms. The animal model of human laryngeal carcinoma was established by the subcutaneous inoculation of Hep-2 cells at the right armpit of BALB/c nu/nu mice. The tumor-bearing mice were randomized into 4 groups, p53 therapy group(rAd-p53), epigenetic therapy group(5-aza-dC), combination therapy group (rAd-p53+5-aza-dC) and control group. The gene and protein expressions of molecular markers p53 and E-cadherin were detected by FQ-PCR and immunohistochemistry. By the day 20 of the treatments, the mean tumor volumes were(106.09 ± 24.40)mm(3) in p53 therapy group, (166.55 ± 40.11) mm(3) in epigenetic therapy group, (126.11 ± 22.49) mm(3) in combination therapy group,and (252.83 ± 54.09) mm(3) in control group. Both gene therapy (F = 37.30, P epigenetic therapy (F = 4.79, P epigenetic therapy group, 494.76 ± 102.88 in combination therapy group,and 162.60 ± 40.38 in control group respectively, indicating the enhancements of E-cadherin protein expression by gene therapy (F = 45.24, P epigenetic therapy(F = 5.73, P epigenetic therapy. The expression levels of p53 gene were 4.43 ± 0.12 in p53 therapy group, 1.06 ± 0.11 in epigenetic therapy group, 3.51 ± 0.10 in combination therapy group,and 1.09 ± 0.11 in control group, respectively, showing an interaction effect between gene therapy and epigenetic therapy (F = 298.11, P epigenetic therapy group, 2.99 ± 0.12 in combination therapy group, and 1.00 ± 0.11 in control group, respectively. The expression of E-cadherin gene was enhanced by gene therapy (F = 329.12, P epigenetic therapy(F = 88.57, P epigenetic therapy and the combination therapy. The gene therapy was significantly better than the epigenetic therapy or the combination therapy. There might be antagonistic effect between p53 and 5-aza-dC.

  20. Chlorin e6 – polyvinylpyrrolidone mediated photosensitization is effective against human non-small cell lung carcinoma compared to small cell lung carcinoma xenografts

    Science.gov (United States)

    Chin, William WL; Heng, Paul WS; Olivo, Malini

    2007-01-01

    Background Photodynamic therapy (PDT) is an effective local cancer treatment that involves light activation of a photosensitizer, resulting in oxygen-dependent, free radical-mediated cell death. Little is known about the comparative efficacy of PDT in treating non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), despite ongoing clinical trials treating lung cancers. The present study evaluated the potential use of chlorin e6 – polyvinylpyrrolidone (Ce6-PVP) as a multimodality photosensitizer for fluorescence detection and photodynamic therapy (PDT) on NSCLC and SCLC xenografts. Results Human NSCLC (NCI-H460) and SCLC (NCI-H526) tumor cell lines were used to establish tumor xenografts in the chick chorioallantoic membrane (CAM) model as well as in the Balb/c nude mice. In the CAM model, Ce6-PVP was applied topically (1.0 mg/kg) and fluorescence intensity was charted at various time points. Tumor-bearing mice were given intravenous administration of Ce6-PVP (2.0 mg/kg) and laser irradiation at 665 nm (fluence of 150 J/cm2 and fluence rate of 125 mW/cm2). Tumor response was evaluated at 48 h post PDT. Studies of temporal fluorescence pharmacokinetics in CAM tumor xenografts showed that Ce6-PVP has a selective localization and a good accuracy in demarcating NSCLC compared to SCLC from normal surrounding CAM after 3 h post drug administration. Irradiation at 3 h drug-light interval showed greater tumor necrosis against human NSCLC xenografts in nude mice. SCLC xenografts were observed to express resistance to photosensitization with Ce6-PVP. Conclusion The formulation of Ce6-PVP is distinctly advantageous as a diagnostic and therapeutic agent for fluorescence diagnosis and PDT of NSCLC. PMID:18053148

  1. Oxidative stress may enhance the malignant potential of human hepatocellular carcinoma by telomerase activation.

    Science.gov (United States)

    Nishikawa, Taichiro; Nakajima, Tomoki; Katagishi, Tatsuo; Okada, Yoshihisa; Jo, Masayasu; Kagawa, Keizo; Okanoue, Takeshi; Itoh, Yoshito; Yoshikawa, Toshikazu

    2009-07-01

    Continuous oxidative stress (OS) plays an important role in the progression of chronic liver diseases and hepatocarcinogenesis through telomere shortening in hepatocytes. However, it has not been established how the OS influences the progression of human hepatocellular carcinomas (HCCs). We examined the correlations of OS with telomere length of cancer cells, telomerase activity and other clinicopathological factors in 68 HCCs. The level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker of OS was examined immunohistochemically and OS was scored in four grades (0-3). The telomere length of cancer cells was measured by quantitative fluorescence in situ hybridization. Telomerase activity was measured by (i) immunodetection of human telomerase reverse transcriptase (hTERT) and (ii) telomere repeat amplification protocol (TRAP) assay. Telomerase related proteins, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Akt, and other clinicopathological factors were also evaluated. As the OS grade increased, the average telomere length became significantly shorter in HCCs, especially in the hTERT-negative group. In the state of high-grade OS, hTERT-positive HCC cells showed more proliferative and less apoptotic features compared with hTERT-negative HCC cells. Telomerase activity, as measured by the TRAP assay, was strongly correlated with OS grade in HCCs. Furthermore, a high OS grade was correlated with the downexpression of PTEN and the activation of Akt. Oxidative stress enhanced the malignant potential of HCCs through the activation of telomerase, which raises the possibility of using OS as a marker for assessing the clinical state of HCCs.

  2. Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Chih-Jen

    2011-05-01

    Full Text Available Abstract Purpose This work aimed to investigate the effect of costunolide, a sesquiterpene lactone isolated from Michelia compressa, on cell cycle distribution and radiosensitivity of human hepatocellular carcinoma (HCC cells. Methods The assessment used in this study included: cell viability assay, cell cycle analysis by DNA histogram, expression of phosphorylated histone H3 (Ser 10 by flow cytometer, mitotic index by Liu's stain and morphological observation, mitotic spindle alignment by immunofluorescence of alpha-tubulin, expression of cell cycle-related proteins by Western blotting, and radiation survival by clonogenic assay. Results Our results show that costunolide reduced the viability of HA22T/VGH cells. It caused a rapid G2/M arrest at 4 hours shown by DNA histogram. The increase in phosphorylated histone H3 (Ser 10-positive cells and mitotic index indicates costunolide-treated cells are arrested at mitosis, not G2, phase. Immunofluorescence of alpha-tubulin for spindle formation further demonstrated these cells are halted at metaphase. Costunolide up-regulated the expression of phosphorylated Chk2 (Thr 68, phosphorylated Cdc25c (Ser 216, phosphorylated Cdk1 (Tyr 15 and cyclin B1 in HA22T/VGH cells. At optimal condition causing mitotic arrest, costunolide sensitized HA22T/VGH HCC cells to ionizing radiation with sensitizer enhancement ratio up to 1.9. Conclusions Costunolide could reduce the viability and arrest cell cycling at mitosis in hepatoma cells. Logical exploration of this mitosis-arresting activity for cancer therapeutics shows costunolide enhanced the killing effect of radiotherapy against human HCC cells.

  3. Inhibitory Effect of Endostar on Specific Angiogenesis Induced by Human Hepatocellular Carcinoma

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    Qing Ye

    2015-01-01

    Full Text Available To investigate the effect of endostar on specific angiogenesis induced by human hepatocellular carcinoma, this research systematically elucidated the inhibitory effect on HepG2-induced angiogenesis by endostar from 50 ng/mL to 50000 ng/mL. We employed fluorescence quantitative Boyden chamber analysis, wound-healing assay, flow cytometry examination using a coculture system, quantitative analysis of tube formation, and in vivo Matrigel plug assay induced by HCC conditioned media (HCM and HepG2 compared with normal hepatocyte conditioned media (NCM and L02. Then, we found that endostar as a tumor angiogenesis inhibitor could potently inhibit human umbilical vein endothelial cell (HUVEC migration in response to HCM after four- to six-hour action, inhibit HCM-induced HUVEC migration to the lesion part in a dose-dependent manner between 50 ng/mL and 5000 ng/mL at 24 hours, and reduce HUVEC proliferation in a dose-dependent fashion. Endostar inhibited HepG2-induced tube formation of HUVECs which peaked at 50 ng/mL. In vivo Matrigel plug formation was also significantly reduced by endostar in HepG2 inducing system rather than in L02 inducing system. It could be concluded that, at cell level, endostar inhibited the angiogenesis-related biological behaviors of HUVEC in response to HCC, including migration, adhesion proliferation, and tube formation. At animal level, endostar inhibited the angiogenesis in response to HCC in Matrigel matrix.

  4. WISP-1 overexpression upregulates cell proliferation in human salivary gland carcinomas via regulating MMP-2 expression

    Directory of Open Access Journals (Sweden)

    Li FJ

    2016-10-01

    Full Text Available Fu-Jun Li, Xin-Juan Wang, Xiao-Li Zhou Department of Stomatology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, People’s Republic of China Background: WISP-1 is a member of the CCN family of growth factors and has been reported to play an important role in tumorigenesis by triggering downstream events via integrin signaling. However, little is known about the role of WISP-1 in proliferation of salivary gland carcinoma (SGC cells.Methods: In this study, we investigated the WISP-1 expression in SGC tissues via immunohistochemical staining, Western blotting assay, and real-time quantitative polymerase chain reaction method, and then evaluated the regulatory role of WISP-1 in the growth of SGC A-253 cells. In addition, the role of MMP-2 in the WISP-1-mediated growth regulation was also investigated.Results: It was demonstrated that the WISP-1 expression was upregulated at both mRNA and protein levels in 15 of 21 SGC tumor tissues, compared to the non-tumor tissues (five of 21, associated with the lymph node dissection and bone invasion. The in vitro CCK-8 assay and colony-forming assay demonstrated that the exogenous WISP-1 treatment or the WISP-1 overexpression promoted the growth of A-253 cells. In addition, we confirmed that the WISP-1 overexpression upregulated the MMP-2 expression in A-253 cells with the gain-of-function and loss-of-function strategies, and that the MMP-2 knockdown attenuated the WISP-1-mediated growth promotion of A-253 cells.Conclusion: We found that WISP-1 was overexpressed in the human SGCs, and the WISP-1 overexpression promoted the salivary gland cell proliferation via upregulating MMP-2 expression. Our study recognized the oncogenic role of WISP-1 in human SGCs, which could serve as a potential target for anticancer therapy. Keywords: WISP-1, SGCs, proliferation, MMP-2

  5. WISP-1 overexpression upregulates cell proliferation in human salivary gland carcinomas via regulating MMP-2 expression.

    Science.gov (United States)

    Li, Fu-Jun; Wang, Xin-Juan; Zhou, Xiao-Li

    2016-01-01

    WISP-1 is a member of the CCN family of growth factors and has been reported to play an important role in tumorigenesis by triggering downstream events via integrin signaling. However, little is known about the role of WISP-1 in proliferation of salivary gland carcinoma (SGC) cells. In this study, we investigated the WISP-1 expression in SGC tissues via immunohistochemical staining, Western blotting assay, and real-time quantitative polymerase chain reaction method, and then evaluated the regulatory role of WISP-1 in the growth of SGC A-253 cells. In addition, the role of MMP-2 in the WISP-1-mediated growth regulation was also investigated. It was demonstrated that the WISP-1 expression was upregulated at both mRNA and protein levels in 15 of 21 SGC tumor tissues, compared to the non-tumor tissues (five of 21), associated with the lymph node dissection and bone invasion. The in vitro CCK-8 assay and colony-forming assay demonstrated that the exogenous WISP-1 treatment or the WISP-1 overexpression promoted the growth of A-253 cells. In addition, we confirmed that the WISP-1 overexpression upregulated the MMP-2 expression in A-253 cells with the gain-of-function and loss-of-function strategies, and that the MMP-2 knockdown attenuated the WISP-1-mediated growth promotion of A-253 cells. We found that WISP-1 was overexpressed in the human SGCs, and the WISP-1 overexpression promoted the salivary gland cell proliferation via upregulating MMP-2 expression. Our study recognized the oncogenic role of WISP-1 in human SGCs, which could serve as a potential target for anticancer therapy.

  6. Differential requirement for de novo lipogenesis in cholangiocarcinoma and hepatocellular carcinoma of mice and humans.

    Science.gov (United States)

    Li, Lei; Che, Li; Tharp, Kevin M; Park, Hyo-Min; Pilo, Maria G; Cao, Dan; Cigliano, Antonio; Latte, Gavinella; Xu, Zhong; Ribback, Silvia; Dombrowski, Frank; Evert, Matthias; Gores, Gregory J; Stahl, Andreas; Calvisi, Diego F; Chen, Xin

    2016-06-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most prevalent types of primary liver cancer. These malignancies have limited treatment options, resulting in poor patient outcomes. Metabolism reprogramming, including increased de novo lipogenesis, is one of the hallmarks of cancer. Fatty acid synthase (FASN) catalyzes the de novo synthesis of long-chain fatty acids from acetyl-coenzyme A and malonyl-coenzyme A. Increased FASN expression has been reported in multiple tumor types, and inhibition of FASN expression has been shown to have tumor-suppressing activity. Intriguingly, we found that while FASN is up-regulated in human HCC samples, its expression is frequently low in human ICC specimens. Similar results were observed in mouse ICC models induced by different oncogenes. Ablating FASN in the mouse liver did not affect activated AKT and Notch (AKT/Notch intracellular domain 1) induced ICC formation in vivo. Furthermore, while both HCC and ICC lesions develop in mice following hydrodynamic injection of AKT and neuroblastoma Ras viral oncogene homolog oncogenes (AKT/Ras), deletion of FASN in AKT/Ras mice triggered the development almost exclusively of ICCs. In the absence of FASN, ICC cells might receive lipids for membrane synthesis through exogenous fatty acid uptake. In accordance with the latter hypothesis, ICC cells displayed high expression of fatty acid uptake-related proteins and robust long-chain fatty acid uptake. Our data demonstrate that FASN dependence is not a universal feature of liver tumors: while HCC development is highly dependent of FASN and its mediated lipogenesis, ICC tumorigenesis can be insensitive to FASN deprivation; our study supports novel therapeutic approaches to treat this pernicious tumor type with the inhibition of exogenous fatty acid uptake. (Hepatology 2016;63:1900-1913). © 2016 by the American Association for the Study of Liver Diseases.

  7. Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.

    Directory of Open Access Journals (Sweden)

    Mingquan Chen

    Full Text Available FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10 human hepatocellular carcinoma, 66.7% (6/9 liver cancer cell lines and 100% (6/6 colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2'-deoxycytidine (Aza, indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis.

  8. Expression and clinical significance of high risk human papillomavirus and invasive gene in cervical carcinoma.

    Science.gov (United States)

    Lu, Zhai; Chen, Hua; Zheng, Xiao-Mei; Chen, Man-Ling

    2017-02-01

    To study the expression of E6 and E7 mRNA in high-risk human papillomavirus (HPV) HPV-18 and the relationship between the expression of invasive gene and cervical carcinoma. A total of 119 patients with cervical cancer, cervical erosion and cervical HPV infection who were diagnosed in our hospital were selected and randomly divided into two groups: cervical cancer group (n = 58) and non-cancerous group (n = 61). Another 60 patients with uterine leiomyoma were selected as normal control group. Detection of HPV18 E6, E7 mRNA expression and invasion, migration, proliferation inhibition genes, epithelial mesenchymal transition genes and proliferation related protein content. The relative expression of E6 and E7 HPV-18 in cervical cancer group was significant higher than that in non-cancerous group and control group (mRNA) (P mRNA content of CD44v6 and MMP-9 in cervical cancer group was significantly higher than that in non-cancerous group and control group (P mRNA content of beta -catenin and Vimentin in cervical cancer group was significantly lower than that in non cancerous group and control group (P detection of cervical cancer in high-risk human papilloma virus HPV-18 E6 and E7 mRNA, and the invasion, migration, proliferation inhibition gene, epithelial mesenchymal transition and proliferation related gene protein content, HPV expression rate of mRNA increased with the development of cervical cancer, the expression is also enhanced. The expression has a certain correlation between the level and development of cervical cancer. Through the above indicators, the development of cervical cancer monitoring and treatment to provide important clinical guidance. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  9. Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular CarcinomaSummary

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    Zeribe Chike Nwosu

    2017-09-01

    Full Text Available Background & Aims: Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolic gene alterations that repeatedly occur in liver cancer are largely unknown. We aimed to identify metabolic genes that are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC. Methods: We studied the expression of 2,761 metabolic genes in 8 microarray datasets comprising 521 human HCC tissues. Genes exclusively up-regulated or down-regulated in 6 or more datasets were defined as consistently deregulated. The consistent genes that correlated with tumor progression markers (ECM2 and MMP9 (Pearson correlation P < .05 were used for Kaplan-Meier overall survival analysis in a patient cohort. We further compared proteomic expression of metabolic genes in 19 tumors vs adjacent normal liver tissues. Results: We identified 634 consistent metabolic genes, ∼60% of which are not yet described in HCC. The down-regulated genes (n = 350 are mostly involved in physiologic hepatocyte metabolic functions (eg, xenobiotic, fatty acid, and amino acid metabolism. In contrast, among consistently up-regulated metabolic genes (n = 284 are those involved in glycolysis, pentose phosphate pathway, nucleotide biosynthesis, tricarboxylic acid cycle, oxidative phosphorylation, proton transport, membrane lipid, and glycan metabolism. Several metabolic genes (n = 434 correlated with progression markers, and of these, 201 predicted overall survival outcome in the patient cohort analyzed. Over 90% of the metabolic targets significantly altered at the protein level were similarly up- or down-regulated as in genomic profile. Conclusions: We provide the first exposition of the consistently altered metabolic genes in HCC and show that these genes are potentially relevant targets for onward studies in preclinical and clinical contexts. Keywords: Liver Cancer, HCC, Tumor Metabolism

  10. HLA-E expression and its clinical relevance in human renal cell carcinoma

    Science.gov (United States)

    Seliger, Barbara; Jasinski-Bergner, Simon; Quandt, Dagmar; Stoehr, Christine; Bukur, Juergen; Wach, Sven; Legal, Wolfgang; Taubert, Helge; Wullich, Bernd; Hartmann, Arndt

    2016-01-01

    The non-classical human leukocyte antigen E (HLA-E) expression is frequently overexpressed in tumor diseases, transplants and virus-infected cells and represents an immunomodulatory molecule by binding to the receptors CD94/NKG2A, -B and –C on NK and T cells. Due to its immune suppressive features HLA-E expression might represent an important mechanism of tumors to escape immune surveillance. While an aberrant expression of the non-classical HLA-G antigen in human renal cell carcinoma (RCC) has been demonstrated to be associated with a worse outcome of patients and reduced sensitivity to immune effector cell-mediated cytotoxicity, the expression and function of HLA-E has not yet been analyzed in this tumor entity. Higher levels of HLA-E transcripts were detected in all RCC cell lines and tumor lesions, which were tested in comparison to normal kidney epithelium. Immunohistochemical staining of a tissue microarray (TMA) using the HLA-E-specific monoclonal antibody TFL-033 recognizing the cytoplasmic HLA-E α-chain as monomer revealed a heterogeneous HLA-E expression in RCC lesions with the highest frequency in chromophobe RCC when compared to other RCC subtypes. HLA-E expression did not correlate with the frequency of CD3+, CD4+, CD8+ and FoxP3+ immune cell infiltrations, but showed an inverse correlation with infiltrating CD56+ cells. In contrast to HLA-G, HLA-E expression in RCCs was not statistically significant associated with a decreased disease specific survival. These data suggest that HLA-E overexpression frequently occurs in RCC and correlates with reduced immunogenicity. PMID:27589686

  11. Bonnes pratiques en cancerologie du larynx et de l’hypopharynx

    National Research Council Canada - National Science Library

    Dubrulle, F

    2007-01-01

    ... permettent une tres bonne rentabilite de l'examen. Mots cles : ORL - Pharynx - Cavite buccale 16 h 30 Duree : 15 minutes BONNES PRATIQUES EN CANCEROLOGIE DU LARYNX ET DE L'HYPOPHARYNX F Dubrulle Lille - Fronce Objectifs pedagogiques : Elements anatomiques utiles au bilan d'extension des tumeurs du larynx et de l'hypopharynx. Apprendre a...

  12. Investigating the acoustic effect of the descended larynx with articulatory models

    NARCIS (Netherlands)

    de Boer, B.

    2010-01-01

    A strongly simplified articulatory model, as well as three more realistic models are investigated for the effect of larynx height on the extent of vowel signaling space. The models explore a larger range of larynx positions than previous models, and the use of the convex hull for measuring

  13. Repression of hTERT transcription by the introduction of chromosome 3 into human oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishio, Sachiyo [Division of Oral and Maxillofacial Biopathological Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503 (Japan); Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori, 683-8503 (Japan); Ohira, Takahito; Sunamura, Naohiro [Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori, 683-8503 (Japan); Oshimura, Mitsuo [Chromosome Engineering Research Center, Tottori University, Yonago, Tottori, 683-8503 (Japan); Ryoke, Kazuo [Division of Oral and Maxillofacial Biopathological Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori, 683-8503 (Japan); Kugoh, Hiroyuki, E-mail: kugoh@med.tottori-u.ac.jp [Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Yonago, Tottori, 683-8503 (Japan); Chromosome Engineering Research Center, Tottori University, Yonago, Tottori, 683-8503 (Japan)

    2015-10-30

    Telomerase is a ribonucleoprotein enzyme that maintains telomere length. Telomerase activity is primarily attributed to the expression of telomerase reverse transcriptase (TERT). It has been reported that introduction of an intact human chromosome 3 into the human oral squamous cell carcinoma cell line HSC3 suppresses the tumorigenicity of these cells. However, the mechanisms that regulate tumorigenicity have not been elucidated. To determine whether this reduction in tumorigenicity was accompanied by a reduction in telomerase activity, we investigated the transcriptional activation of TERT in HSC3 microcell hybrid clones with an introduced human chromosome 3 (HSC3#3). HSC#3 cells showed inhibition of hTERT transcription compared to that of the parental HSC3 cells. Furthermore, cell fusion experiments showed that hybrids of HSC3 cells and cells of the RCC23 renal carcinoma cell line, which also exhibits suppression of TERT transcription by the introduction of human chromosome 3, also displayed suppressed TERT transcription. These results suggested that human chromosome 3 may carry functionally distinct, additional TERT repressor genes. - Highlights: • hTERT mRNA expression level decreased in the chromosome 3 introduced HSC3 clones. • hTERT mRNA expression level was tend to suppressed in HSC3 and RCC23 hybrid cells. • We provide evidence that human chromosome 3 carries at least two distinct hTERT regulatory factors.

  14. Preliminary report--near total laryngectomy for SCC larynx.

    Science.gov (United States)

    Arain, Asif; Ghaffar, Shehzad

    2011-06-01

    A retrospective analysis was performed on patients subjected to near-total laryngectomy at Aga Khan University Hospital Karachi from September 2006 and May 2010, to evaluate the functional outcome of Near Total Laryngectomy and its effect on disease control. In all of these advanced stage laryngeal-hypopharyngeal squamous cancer patients, the disease was limited to one side of the larynx-hypopharynx. Four patients were staged as T3 and rest were T4; near total laryngectomy was done in all 07 patients. Post operative adjuvant radiotherapy was given to 06 patients. All of these patients are on regular oral diet and maintaining their body weight. Six patients are using their preserved hemi larynx effectively. Mean follow up of these patients was 15 months. Three patients developed regional recurrence whereas the remaining four patients were well till their last follow-up. Near total laryngectomy is a safe surgical option even for advanced laryngeal-hypopharyngeal cancer without compromising oncological clearance. It gives patients their own physiological voice that does not require maintenance but at the expense of permanent tracheostomy.

  15. A Macroanatomic Study on Larynx Cranialis of Turkeys in Thrace Region, Turkey

    Directory of Open Access Journals (Sweden)

    Ozan GUNDEMİR

    2017-07-01

    Full Text Available This study was conducted to determine the differences and similarities between larynx cranialis of turkey and other species of poultry. For this purpose, 8 female and 8 male adult turkeys were used for the anatomical measurements. Furthermore, histological examinations were performed on larynx cranialis of 2 turkeys. Cartilago thyroidea and epiglottis were not observed in the larynx cranialis, in our study. Besides, larynx cranialis were found to constitute from paired cartilago arytneoidea and unpaired cartilago cricoidea and cartilago procricoidea. Crista ventralis was detected on larynx cranialis of turkeys. According to our results, it has been determined that in turkey; the width of glottis in female turkeys were larger than males. Cartilago procricoidea were observed bigger than cartilago arytenoidea and crista ventralis were found to be more prominent than in other birds.

  16. Lentivirus mediated silencing of Ubiquitin Specific Peptidase 39 inhibits cell proliferation of human hepatocellular carcinoma cells in vitro

    OpenAIRE

    PAN, ZEYA; Pan, Hao; Zhang, Jin; Yang, Yun; Liu, Hui; Yang, Yuan; Huang, Gang; Ni, Junsheng; Huang, Jian; Zhou, Weiping

    2015-01-01

    Background Ubiquitin Specific Peptidase 39 (USP39) is a 65?kDa SR-related protein involved in RNA splicing. Previous studies showed that USP39 is related with tumorigenesis of human breast cancer cells. Results In the present study, we investigated the functions of USP39 in human hepatocellular carcinoma (HCC) cell line SMMC-7721. We knocked down the expression of USP39 through lentivirus mediated RNA interference. The results of qRT-PCR and western blotting assay showed that both the mRNA an...

  17. Knockdown of asparagine synthetase by RNAi suppresses cell growth in human melanoma cells and epidermoid carcinoma cells.

    Science.gov (United States)

    Li, Hui; Zhou, Fusheng; Du, Wenhui; Dou, Jinfa; Xu, Yu; Gao, Wanwan; Chen, Gang; Zuo, Xianbo; Sun, Liangdan; Zhang, Xuejun; Yang, Sen

    2016-05-01

    Melanoma, the most aggressive form of skin cancer, causes more than 40,000 deaths each year worldwide. And epidermoid carcinoma is another major form of skin cancer, which could be studied together with melanoma in several aspects. Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine, and its expression is associated with the chemotherapy resistance and prognosis in several human cancers. The present study aims to explore the potential role of ASNS in melanoma cells A375 and human epidermoid carcinoma cell line A431. We applied a lentivirus-mediated RNA interference (RNAi) system to study its function in cell growth of both cells. The results revealed that inhibition of ASNS expression by RNAi significantly suppressed the growth of melanoma cells and epidermoid carcinoma cells, and induced a G0/G1 cell cycle arrest in melanoma cells. Knockdown of ASNS in A375 cells remarkably downregulated the expression levels of CDK4, CDK6, and Cyclin D1, and upregulated the expression of p21. Therefore, our study provides evidence that ASNS may represent a potential therapeutic target for the treatment of melanoma. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

  18. Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells.

    Science.gov (United States)

    Qiao, Li; Xu, Chengshan; Li, Qiang; Mei, Zhusong; Li, Xinji; Cai, Hong; Liu, Wei

    2016-06-01

    5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been used for part of squamous cell carcinoma (premalignant conditions or in situ cutaneous SCC-Bowen disease). However, mechanism of ALA-PDT is not fully understood yet on the cell apoptosis pathway. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on human squamous carcinoma A431cells. Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay. The mRNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Our data showed that 5-ALA-PDT significantly inhibited cell proliferation (pPDT treatment was correlated to more cells being arrested in the G0/G1 phase of the cell cycle (pPDT treatment for the mRNA and protein expression. Our studies confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. Copyright © 2016. Published by Elsevier B.V.

  19. Down-regulated miR-9 and miR-433 in human gastric carcinoma

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    Nie Na

    2009-06-01

    Full Text Available Abstract Background MircoRNAs(miRNAs are short, endogenously non-coding RNAs. The abnormal expression of miRNAs may be valuable for the diagnosis and treatment of tumors. Methods To screening the special miRNAs in gastric carcinoma, expression level of miRNAs in gastric carcinoma and normal gaster samples were detected by miRNA gene chip. Then, the expressions of miR-9 and miR-433 in gastric carcinoma tissue and SGC7901 cell line were validated by qRT-PCR. GRB2 and RAB34, targets of miR-433 and miR-9 respectively, were detected by Western blot. Results We found 19 miRNAs and 7 miRNAs were down-regulated and up-regulated respectively. Compared with normal gaster samples, our data showed that miR-9 and miR-433 were down-regulated in gastric carcinoma. Meanwhile, we also found that miR-433 and miR-9 regulated the expression levels of GRB2 and RAB34 respectively. Conclusion Our data show miR-9 and miR-433 was down-regulated in gastric carcinoma. The targets of miR-433 and miR-9 were tumor-associated proteins GRB2 and RAB34 respectively. This result provided the related information of miRNAs in gastric carcinoma.

  20. Expression of Fra-1 in human hepatocellular carcinoma and its prognostic significance.

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    Gao, Xiao-Qiang; Ge, Yong-Sheng; Shu, Qing-Hua; Ma, Hua-Xing

    2017-06-01

    This study aimed to explore the clinical significance and prognostic value of Fra-1 in hepatocellular carcinoma patients after curative resection. Fra-1 expression was investigated using a combination of techniques: immunohistochemistry for 66 samples of hepatocellular carcinoma and quantitative real-time polymerase chain reaction and western blotting assays for 19 matched hepatocellular carcinoma specimens. Fra-1 was present in 38 of 66 (57.6%) tumor tissues, with intense staining in the nuclei. There was also positive staining in 14 of 66 (21.2%) adjacent peritumoral tissues, with weak staining in the cytoplasm. Quantitative real-time polymerase chain reaction and western blotting assays confirmed higher expression of Fra-1 messenger RNA and Fra-1 protein in tumor tissues than adjacent non-tumor tissues for 19 hepatocellular carcinoma samples (p expression of Fra-1 was significantly related to vascular invasion and serum alpha-fetoprotein. Kaplan-Meier survival analysis found that overexpressed Fra-1 was correlated with poor overall survival and disease-free survival. Multivariate analysis identified Fra-1 as an independent prognostic factor. Fra-1 may be involved in the progress of hepatocellular carcinoma and could be a promising molecular candidate in the diagnosis and treatment of hepatocellular carcinoma.

  1. Cyclooxygenase-2 gene silence induces apoptosis of human hepatocellular carcinoma cells

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    Dan GUO

    2012-07-01

    Full Text Available Objective To specifically silence COX-2 gene expression in cultured human hepatocellular carcinoma cells HepG2 by construction and transfection of COX-2 hairpin RNA (shRNA expression vectors, and investigate the effects of knocking COX-2 down on cell proliferation and apoptosis. Methods The inserted sequences coding shRNA homologous to COX-2 gene were designed and COX-2 shRNA expression vectors were constructed and transfected into HepG2 cells with Lipofectamine 2000. The inhibitory efficiency of COX-2 shRNA was determined by detection of COX-2 mRNA levels in transfected cells using semi-quantitative RT-PCR. Cell viability was analyzed by cell counting kit-8 (CCK-8 assay. Indexes of apoptotic cells and cell cycle distribution were analyzed by flow cytometry. Western blotting was used to detect the changes of protein levels of COX-2 and Bcl-2 in HepG2 cells. Results Plasmid sequencing indicated the successful construction of two shRNA expression vectors. The expressive levels of COX-2 mRNA in HepG2 cells transfected with two COX-2 shRNA expression vectors decreased to 41.66% and 77.79%, respectively, of that in cells transfected with control scrambled shRNA expression vector. The vector which efficiently suppressed the expression of COX-2 mRNA was transfected into HepG2 cells, and G418 was used to select a population of cells which may stably express the shRNA. The expression of COX-2 mRNA decreased by 75.30% and the cell viability decreased by 29.33% in cells which stably expressed COX-2 shRNA. Flow cytometry analysis showed a higher proportion of apoptotic cells in COX-2 shRNA group than in untransfected and scrambled shRNA groups (17.83% vs4.47% and 4.63%. The proportion of cells in G0/G1 phase was 73.93%, 57.63% and 61.2%, while in S phase was 13.43%, 26.90% and 26.03%, respectively, in COX-2 shRNA group, untransfected and scrambled shRNA groups. Western blotting revealed that the protein levels of COX-2 and Bcl-2 in HepG2 cells which

  2. Antiproliferative Effects of Tetrabuthylammonium Chloride Ionic Liquid on HCT 8 Human Colon Carcinoma Cells

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    Gabi Dumitrescu

    2017-05-01

    Full Text Available The ionic liquids have attracted a great of attention in the scientific community due to their potential pharmaceutical such as antimicrobial. In this paper, the main objective was the assessment of the cytotoxic effect of tetrabutylammonium chloride against HCT 8 human colon carcinoma cell line. The cells were cultured in 75 cm2 culture flasks  using RPMI medium supplemented with 10% inactivated fetal bovine serum (FBS, penicillin (100 IU/mL and streptomycin (100 μg/mL and maintained at 37 °C and 5% CO2. Before achieving viability test, the cells were harvested using trypsin solution (0.25%. Then, the cells were seeded in 24 – well plates at a density of 5 x 105 cells/mL in 100 µL medium/well in order to reach confluence. After 24 h, the medium was replaced with fresh medium containing different concentrations of ionic liquid, respectively, 0.085, 0.17, 0.34, 0.68 and 1.36 mg /mL. Control group contained cells without treatment. Cell proliferation kinetics have been studied at 24 and 48 h after IL treatment, following trypsinization and counting total cells per plate by using a Trypan blue dye and a hemocytometer. Data obtained from the growth kinetics assay shows that the tetrabutylammonium chloride (TBAC had an inhibitory effect on the growth of cells in a concentration dependent manner. The maximum inhibitory effect on HCT 8 cells it was obtained at 1.36 mg TBAC/mL.

  3. Sequential combination of flavopiridol with Taxol synergistically suppresses human ovarian carcinoma growth.

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    Song, Yue; Xin, Xing; Zhai, Xingyue; Xia, Zhijun; Shen, Keng

    2015-01-01

    The purpose is to investigate the effects of the sequential combination treatment of Taxol and flavopiridol on human ovarian carcinoma in vitro and in vivo. Cell viabilities were determined using the cell counting kit and by flow cytometry. RT-PCR, TUNEL, and immunoblotting assays were used to detect cellular apoptotic activities following treatments. Tumor growth and microvessel density (MVD) detection of mice bearing SKOV3 cells were studied. Taxol or flavopiridol alone was cytotoxic against SKOV3 cells in vitro with a viability rate of 38.2 ± 1.3 % for 1 µmol/L Taxol and 44.3 ± 5.9 % for 300 nM flavopiridol. Sequential combination treatment with Taxol and flavopiridol resulted in a viability rate of 9.1 ± 0.8 %. The apoptotic rate of SKOV3 cells was 15.7 ± 1.7, 9.4 ± 0.4 and 51.1 ± 2.5 % for Taxol, flavopiridol, and combination of Taxol and flavopiridol, respectively. Significant synergisms were observed in SKOV3 cells in vitro, following the sequential combination of Taxol for 24 h followed by flavopiridol for 24 h, which resulted in the most substantial cell death and the highest apoptotic rate. All treatments showed significant suppression of tumor growth at the end point of the in vivo study. All treatments significantly reduce the value of MVD. Sequential combination treatment with Taxol and flavopiridol exerted synergistic cytotoxic activities against SKOV3 cells in vitro and significantly suppress the tumor growth of mice bearing SKOV3 cells. It should be further explored as a potential clinically useful regimen against ovarian cancer.

  4. Identification and Analysis of P53-Mediated Competing Endogenous RNA Network in Human Hepatocellular Carcinoma.

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    Zhang, Yiming; Kang, Ran; Liu, Wenrong; Yang, Yalan; Ding, Ruofan; Huang, Qingqing; Meng, Junhua; Xiong, Lili; Guo, Zhiyun

    2017-01-01

    Recent studies have indicated that long non-coding RNAs (lncRNAs) and mRNA function as competing endogenous RNAs (ceRNAs) that compete to bind to shared microRNA (miRNA) recognition elements (MREs) to perform specific biological functions during tumorigenesis. The tumor suppressor p53 is a master regulator of cancer-related biological processes by acting as a transcription factor to regulate target genes including miRNA and lncRNA. However, the mechanism in human hepatocellular carcinoma and whether p53-mediated RNA targets could form ceRNA network remain unclear. Here, we identified a series of differential expressed miRNAs, lncRNA and mRNA which were potentially regulated by p53 using RNA sequencing in HepG2. Genomic characteristics comparative analysis showed significant differences between mRNAs and lncRNAs. By integrating experimentally confirmed Ago2 and p53 binding sites, we constructed a highly reliable p53-mediated ceRNA network using hypergeometric test. The KEGG pathway enrichment analysis showed that the ceRNA network highly enriched in the cancer or p53-associated signaling pathways. Finally, using betweenness centrality analysis, we identified five master miRNAs (hsa-miR-3620-5p, hsa-miR-3613-3p, hsa-miR-6881-3p, hsa-miR-6087 and hsa-miR-18a-3p) that regulated most of the target RNAs, suggesting these miRNAs play central roles in the whole p53-mediated ceRNAs network. Taken together, our results provide a new regulatory mechanism of p53 networks for future studies in cancer therapeutics.

  5. Upregulation of KLHDC4 Predicts a Poor Prognosis in Human Nasopharyngeal Carcinoma.

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    Yi-Fan Lian

    Full Text Available Kelch proteins are implicated in the pathogenesis of many human diseases, including cancer. Nasopharyngeal carcinoma (NPC is a rare malignancy in most countries, but prevalent in southern China and certain areas of Southeast Asia. In this study, we identified Kelch Domain Containing 4 (KLHDC4, an orphan member of the kelch repeat superfamily, as a prognosis marker for NPC. We examined the expression of KLHDC4 in 168 NPC cases by immunohistochemical staining and found a substantially higher level of KLHDC4 in NPC biopsies compared to adjacent normal nasopharyngeal mucosa. KLHDC4 expression was significantly related to the T classification (P <0.05, N classification (P <0.05 and total staging (P <0.01 in NPC, and patients with higher KLHDC4 expression had poorer overall (P <0.01 and metastasis-free survival (P <0.05 rates. Knockout (KO of KLHDC4 via CRISPR/Cas9-mediated gene editing in NPC cell line dramatically inhibited cell proliferation, colony formation in soft agar and tumor formation in nude mice. In addition, cell migration and invasion were also impaired by KLHDC4 depletion as revealed by wound healing and Transwell assay. Mechanically, loss of KLHDC4 markedly induced spontaneous apoptosis in NPC cells, as evidenced by increased levels of cleaved caspase-3 and cleaved PARP. Consistently, KLHDC4 knockout cell-derived xenografts also showed elevated cleaved caspase-3 and PARP but reduced Ki-67 staining. In conclusion, our results suggest that KLHDC4 promotes NPC oncogenesis by suppressing cellular apoptosis. Thus, KLHDC4 may serve as a prognosis biomarker and a potential therapeutic target for NPC.

  6. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

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    Song Zhang

    Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

  7. Oncolytic adenoviruses targeted to Human Papilloma Virus-positive head and neck squamous cell carcinomas.

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    LaRocca, Christopher J; Han, Joohee; Salzwedel, Amanda O; Davydova, Julia; Herzberg, Mark C; Gopalakrishnan, Rajaram; Yamamoto, Masato

    2016-05-01

    In recent years, the incidence of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) has markedly increased. Our aim was to design a novel therapeutic agent through the use of conditionally replicative adenoviruses (CRAds) that are targeted to the HPV E6 and E7 oncoproteins. Each adenovirus included small deletion(s) in the E1a region of the genome (Δ24 or CB016) intended to allow for selective replication in HPV-positive cells. In vitro assays were performed to analyze the transduction efficiency of the vectors and the cell viability following viral infection. Then, the UPCI SCC090 cell line (HPV-positive) was used to establish subcutaneous tumors in the flanks of nude mice. The tumors were then treated with either one dose of the virus or four doses (injected every fourth day). The transduction analysis with luciferase-expressing viruses demonstrated that the 5/3 fiber modification maximized virus infectivity. In vitro, both viruses (5/3Δ24 and 5/3CB016) demonstrated profound oncolytic effects. The 5/3CB016 virus was more selective for HPV-positive HNSCC cells, whereas the 5/3Δ24 virus killed HNSCC cells regardless of HPV status. In vivo, single injections of both viruses demonstrated anti-tumor effects for only a few days following viral inoculation. However, after four viral injections, there was statistically significant reductions in tumor growth when compared to the control group (p<0.05). CRAds targeted to HPV-positive HNSCCs demonstrated excellent in vitro and in vivo therapeutic effects, and they have the potential to be clinically translated as a novel treatment modality for this emerging disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Trichomonas vaginalis induces cytopathic effect on human lung alveolar basal carcinoma epithelial cell line A549.

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    Salvador-Membreve, Daile Meek C; Jacinto, Sonia D; Rivera, Windell L

    2014-12-01

    Trichomonas vaginalis, the causative agent of trichomoniasis is generally known to inhabit the genitourinary tract. However, several case reports with supporting molecular and immunological identifications have documented its occurrence in the respiratory tract of neonates and adults. In addition, the reports have documented that its occurrence is associated with respiratory failures. The medical significance or consequence of this association is unclear. Thus, to establish the possible outcome from the interaction of T. vaginalis with lung cells, the cytopathic effects of the parasites were evaluated using monolayer cultures of the human lung alveolar basal carcinoma epithelial cell line A549. The possible effect of association of T. vaginalis with A549 epithelial cells was analyzed using phase-contrast, scanning electron microscopy and fluorescence microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), crystal-violet and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) assays were conducted for cytotoxicity testing. The results demonstrate that T. vaginalis: (1) adheres to A549 epithelial cells, suggesting a density-dependent parasite-cell association; (2) adherence on A549 is through flagella, membrane and axostyle; (3) causes cell detachment and cytotoxicity (50-72.4%) to A549 and this effect is a function of parasite density; and (4) induces apoptosis in A549 about 20% after 6 h of incubation. These observations indicate that T. vaginalis causes cytopathic effects on A549 cell. To date, this is the first report showing a possible interaction of T. vaginalis with the lung cells using A549 monolayer cultures. Further studies are recommended to completely elucidate this association. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Quantitation of Human Papillomavirus DNA in Plasma of Oropharyngeal Carcinoma Patients

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    Cao Hongbin; Banh, Alice [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Kwok, Shirley [Department of Pathology, Stanford University School of Medicine, Stanford, CA (United States); Shi Xiaoli; Wu, Simon; Krakow, Trevor; Khong, Brian; Bavan, Brindha [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Bala, Rajeev; Pinsky, Benjamin A. [Department of Pathology, Stanford University School of Medicine, Stanford, CA (United States); Colevas, Dimitrios [Department of Medicine, Stanford University School of Medicine, Stanford, CA (United States); Pourmand, Nader [Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA (United States); Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Kong, Christina S. [Department of Pathology, Stanford University School of Medicine, Stanford, CA (United States); Le, Quynh-Thu, E-mail: qle@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States)

    2012-03-01

    Purpose: To determine whether human papillomavirus (HPV) DNA can be detected in the plasma of patients with HPV-positive oropharyngeal carcinoma (OPC) and to monitor its temporal change during radiotherapy. Methods and Materials: We used polymerase chain reaction to detect HPV DNA in the culture media of HPV-positive SCC90 and VU147T cells and the plasma of SCC90 and HeLa tumor-bearing mice, non-tumor-bearing controls, and those with HPV-negative tumors. We used real-time quantitative polymerase chain reaction to quantify the plasma HPV DNA in 40 HPV-positive OPC, 24 HPV-negative head-and-neck cancer patients and 10 non-cancer volunteers. The tumor HPV status was confirmed by p16{sup INK4a} staining and HPV16/18 polymerase chain reaction or HPV in situ hybridization. A total of 14 patients had serial plasma samples for HPV DNA quantification during radiotherapy. Results: HPV DNA was detectable in the plasma samples of SCC90- and HeLa-bearing mice but not in the controls. It was detected in 65% of the pretreatment plasma samples from HPV-positive OPC patients using E6/7 quantitative polymerase chain reaction. None of the HPV-negative head-and-neck cancer patients or non-cancer controls had detectable HPV DNA. The pretreatment plasma HPV DNA copy number correlated significantly with the nodal metabolic tumor volume (assessed using {sup 18}F-deoxyglucose positron emission tomography). The serial measurements in 14 patients showed a rapid decline in HPV DNA that had become undetectable at radiotherapy completion. In 3 patients, the HPV DNA level had increased to a discernable level at metastasis. Conclusions: Xenograft studies indicated that plasma HPV DNA is released from HPV-positive tumors. Circulating HPV DNA was detectable in most HPV-positive OPC patients. Thus, plasma HPV DNA might be a valuable tool for identifying relapse.

  10. N-glycan alterations are associated with drug resistance in human hepatocellular carcinoma

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    Nakagawa Takahito

    2007-05-01

    Full Text Available Abstract Background Correlations of disease phenotypes with glycosylation changes have been analysed intensively in the tumor biology field. Glycoforms potentially associated with carcinogenesis, tumor progression and cancer metastasis have been identified. In cancer therapy, drug resistance is a severe problem, reducing therapeutic effect of drugs and adding to patient suffering. Although multiple mechanisms likely underlie resistance of cancer cells to anticancer drugs, including overexpression of transporters, the relationship of glycans to drug resistance is not well understood. Results We established epirubicin (EPI – and mitoxantrone (MIT – resistant cell lines (HLE-EPI and HLE-MIT from the human hepatocellular carcinoma cell line (HLE. HLE-EPI and HLE-MIT overexpressed transporters MDR1/ABCB1 and BCRP/ABCG2, respectively. Here we compared the glycomics of HLE-EPI and HLE-MIT cells with the parental HLE line. Core fucosylated triantennary oligosaccharides were increased in the two resistant lines. We investigated mRNA levels of glycosyltransferases synthesizing this oligosaccharide, namely, N-acetylglucosaminyltransferase (GnT-IVa, GnT-IVb and α1,6-fucosyltransferase (α1,6-FucT, and found that α1,6-FucT was particularly overexpressed in HLE-MIT cells. In HLE-EPI cells, GnT-IVa expression was decreased, while GnT-IVb was increased. Both GnT-IVs were downregulated in HLE-MIT cells. HLE-MIT cells also showed decreases in fucosylated tetraantennary oligosaccharide, the product of GnT-V. GnT-V expression was decreased in both lines, but particularly so in HLE-MIT cells. Thus both N-glycan and glycosyltransferase expression was altered as cells acquired tolerance, suggesting novel mechanisms of drug resistance. Conclusion N-glycan and glycosyltransferase expression in HLE-EPI and HLE-MIT were analysed and presented that glycans altered according with acquired tolerance. These results suggested novel mechanisms of drug resistance.

  11. Autocrine human growth hormone increases sensitivity of mammary carcinoma cell to arsenic trioxide-induced apoptosis.

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    Zekri, Ali; Ghaffari, Seyed H; Yousefi, Meysam; Ghanizadeh-Vesali, Samad; Mojarrad, Majid; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir

    2013-09-05

    Human growth hormone (hGH) has been increasingly implicated in a variety of cancers; its up-regulation is observed in breast cancer and correlates with a poor outcome. Autocrine hGH promotes mammary carcinoma cell survival, proliferation, immortalization; it confers an invasive phenotype as a result of an epithelial-mesenchymal transition and contributes to chemoresistance and radioresistance. Arsenic trioxide (ATO) is being successfully used as a first and second line therapy for the treatment of patients with acute promyelocytic leukemia. It also inhibits tumor cell growth and induces apoptosis in a broad range of solid tumors. In the present study, we investigated the effect of hGH on sensitivity of a mammary adenocarcinoma cell to ATO, using a stable hGH-transfectant MCF-7 cell line, MCF7-hGH. Our results demonstrated for the first time that the overexpression of hGH increased sensitivity of the breast cancer cell line MCF-7 to ATO through apoptotic and anti-proliferative mechanisms. The effect of ATO on the transcriptional level of genes involved in survival (Bcl-2, Bax and Survivin), self-sufficiency in growth signals (c-Myc, ARF, Cdc25A, p53 and Bax), immortalization (hTERT) and invasion and metastasis (MMP-2 and MMP-9, uPA and uPAR and E-cadherin) was more pronounced in MCF7-hGH compared with its parental MCF-7 line. Our study may highlight the potential application of ATO for the treatment of patients with breast cancer, especially in those who have metastatic and chemoresistant tumor phenotype possibly due to the over expression of hGH. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Epigenetic differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas.

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    Biron, Vincent L; Mohamed, Adil; Hendzel, Michael J; Alan Underhill, D; Seikaly, Hadi

    2012-04-01

    Epigenetic modifications are defined as heritable changes in gene expression that are not encoded in deoxyribonucleic acid (DNA). Despite the importance of epigenetics in tumorigenesis, there is a paucity of information regarding the epigenetic profiles of oropharyngeal squamous cell carcinoma (OPSCC). The objective of this study was to identify epigenetic signatures associated with human papillomavirus (HPV)-positive and -negative OPSCC. We collected demographic, pathologic, and survival data from 44 patients with advanced-stage OPSCC treated with surgery and chemoradiation at the University of Alberta between January 2006 and December 2008. Tumour specimen from these patients were retreived and sectioned for immunohistochemical analysis. Double immunofluorescence staining was performed with p16 (HPV surrogate) and a panel of epigenetic markers, namely, histone methyl-lysines 4, 9, and 27 and H4 methyl-lysine 20. Correlation between p16 and epigenetic markers was measured using Metamorph and Image J software. Forty-one percent of patients were p16 positive. No statistically significant differences were found between p16-positive and -negative patients in terms of age at diagnosis, tumour subsite, or smoking history. We found significant differences in histone methylation between p16-positive and -negative tumours. OPSCC tumours positive for p16 had global elevations of histone H4 monomethylated lysine 20 (H4K20me1) and H3 trimethylated lysine 27 (H3K27me3) with depletions of H4 trimethylated lysine 20 (H4K20me3). In contrast, p16-negative tumours had depleted levels of H4K20me1 and H3K27me3 with high levels of H4K20me3. HPV-positive and -negative OPSCCs have distinct epigenetic profiles representing broad gene expression differences between these tumours.

  13. Evidence of Distinct Tumour-Propagating Cell Populations with Different Properties in Primary Human Hepatocellular Carcinoma

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    Colombo, Federico; Baldan, Francesca; Mazzucchelli, Silvia; Martin-Padura, Ines; Marighetti, Paola; Cattaneo, Alessandra; Foglieni, Barbara; Spreafico, Marta; Guerneri, Silvana; Baccarin, Marco; Bertolini, Francesco; Rossi, Giorgio; Mazzaferro, Vincenzo; Cadamuro, Massimiliano; Maggioni, Marco; Agnelli, Luca; Rebulla, Paolo

    2011-01-01

    Background and Aims Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC) compartments within human hepatocellular carcinoma (HCC). Methods After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ−/− mice. Results The primary cell populations (hcc-1, -2 and -3) and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8) differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features. Conclusions Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution. PMID:21731718

  14. Evidence of distinct tumour-propagating cell populations with different properties in primary human hepatocellular carcinoma.

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    Federico Colombo

    Full Text Available Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC compartments within human hepatocellular carcinoma (HCC.After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ/⁻ mice.The primary cell populations (hcc-1, -2 and -3 and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8 differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features.Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution.

  15. Molecular detection of human papillomavirus and viral DNA load after radiotherapy for cervical carcinomas.

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    Kahla, Saloua; Kochbati, Lotfi; Sarraj, Sana; Ben Daya, Imen; Maalej, Mongi; Oueslati, Ridha

    2016-10-13

    Infection with high-risk types of human papillomavirus (HPV) is a necessary cause for cervical carcinoma. Radiation therapy together with surgery is the most effective treatment. The purpose of this study was to investigate the molecular basis of the response to radiotherapy in cervical cancer cells. Tumor cells were obtained from biopsies of 44 cervical cancers, collected before and after radiotherapy. The presence of HPV was analyzed by polymerase chain reaction (PCR) using primers specific for the L1 region. The prevalence of HPV was 70.4%, with HPV16 being the most common (54.5%) and HPV18 the second (15.9%). Our analyses show that ionizing radiation does not influence HPV detection, as the percentage of HPV-positive biopsies was similar in patients before and after radiotherapy (HPV16 60% vs. 51.7% and HPV18 20% vs. 13.7%, respectively). However, the detection of HPV did vary by tumor stage, with the highest proportion observed in late-stage tumors (HPV16 and HPV18 in 80% and 60% of stage III tumors, respectively). We also found that HPV viral load is influenced by radiotherapy and tumor stage, with the highest viral loads in late-stage tumors (stage III) after 1 day since radiotherapy (p<0.05). According to Kaplan-Meier curves, higher HPV viral load was associated with significantly shortened progression-free survival (p = 0.04). Our data provide prospective evidence that ionizing radiation can affect the HPV viral load and this might offer the best strategies for assessment of therapeutic efficacy.

  16. Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.

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    Jablonska, Karolina; Pula, Bartosz; Zemla, Agata; Owczarek, Tomasz; Wojnar, Andrzej; Rys, Janusz; Ambicka, Aleksandra; Podhorska-Okolow, Marzena; Ugorski, Maciej; Dziegiel, Piotr

    2013-04-01

    In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  17. Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Shu-Cheng [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Tao, Ze-Zhang, E-mail: zezhangtao@gmail.com [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China)

    2013-09-13

    Highlights: •We identified that PPP inhibits IGF-1R/Akt pathway in NPC cells. •PPP dose-dependently inhibits NPC cell proliferation in vitro. •PPP suppresses tumor growth of NPC in nude mice. •PPP have little effect on microtubule assembly. -- Abstract: Insulin-like growth factor-1 receptor (IGF-1R) is a cell membrane receptor with tyrosine kinase activity and plays important roles in cell transformation, tumor growth, tumor invasion, and metastasis. Picropodophyllin (PPP) is a selective IGF-1R inhibitor and shows promising antitumor effects for several human cancers. However, its antitumor effects in nasopharyngeal carcinoma (NPC) remain unclear. The purpose of this study is to investigate the antitumor activity of PPP in NPC using in vitro cell culture and in vivo animal model. We found that PPP dose-dependently decreased the IGF-induced phosphorylation and activity of IGF-1R and consequently reduced the phosphorylation of Akt, one downstream target of IGF-1R. In addition, PPP inhibited NPC cell proliferation in vitro. The half maximal inhibitory concentration (IC50) of PPP for NPC cell line CNE-2 was ⩽1 μM at 24 h after treatment and ⩽0.5 μM at 48 h after treatment, respectively. Moreover, administration of PPP by intraperitoneal injection significantly suppressed the tumor growth of xenografted NPC in nude mice. Taken together, these results suggest targeting IGF-1R by PPP may represent a new strategy for treatment of NPCs with positive IGF-1R expression.

  18. Merkel cell carcinoma: The first human cancer shown to be associated with a polyomavirus.

    Science.gov (United States)

    Samimi, Mahtab; Touzé, Antoine

    2014-12-01

    Merkel cell carcinoma (MCC) is a rare, malignant primary neuroendocrine cancer of the skin, usually affecting elderly, white people in sun-exposed areas. This is a highly aggressive tumor with strong propensity to metastasize. Surgery and radiation therapy remain the mainstay of treatment, with no curative treatment in case of disseminated metastases. Until 2008, MCC was thought to be caused by the malignant transformation of resident Merkel cells, but no investigation of a predominant molecular pathway that could be involved in MCC pathogenesis was successful. A real revolution in MCC understanding and management occurred in 2008, when a new human polyomavirus (MCPyV) was found to be the main etiological agent of this skin cancer. Following the discovery of MCPyV, the association of MCPyV with MCC has been confirmed worldwide, with detection of MCPyV in about 80% of MCCs. At the same time it had been shown that MCPyV infection is almost ubiquitous in healthy subjects, and MCPyV is thought to be persistent resident of the skin microbiome although the route of transmission, the host cell, the viral cycle and/or latency remain unknown. Most studies suggest that there may be two subtypes of MCC: MCPyV-positive (80%) and MCPyV-negative (20%) MCCs, and various studies have reported a better prognosis associated with MCPyV infection. The discovery of MCPyV in MCC patients opens up new therapeutic insights. The necessity and persistence of expression of MCPyV oncoproteins during MCC development make these proteins promising therapeutic targets. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. MICA/B expression is inhibited by unfolded protein response and associated with poor prognosis in human hepatocellular carcinoma.

    Science.gov (United States)

    Fang, Liang; Gong, Jiuyu; Wang, Ying; Liu, Rongrong; Li, Zengshan; Wang, Zhe; Zhang, Yun; Zhang, Chunmei; Song, Chaojun; Yang, Angang; Ting, Jenny P-Y; Jin, Boquan; Chen, Lihua

    2014-09-18

    MICA/B are major ligands for NK cell activating receptor NKG2D and previous studies showed that the serum level of soluble MICA (sMICA) is an independent prognostic factor for advanced human hepatocellular carcinoma. However, the correlation between cellular MICA/B expression pattern and human hepatocellular carcinoma progression has not been well explored. The unfolded protein response is one of the main causes of resistance to chemotherapy and radiotherapy in tumor cells. However, whether the UPR in HCC could regulate the expression levels of MICA/B and affect the sensitivity of HCC cells to NK cell cytolysis has not been established yet. MICA/B expression pattern was evaluated by immunohistochemistry and Kaplan-Meier survival analysis was done to explore the relationship between MICA/B expression level and patient survival. The protein and mRNA expression levels of MICA/B in SMMC7721 and HepG2 cells treated by tunicamycin were evaluated by flow cytometry, Western Blot and RT-PCR. The cytotoxicity analysis was performed with the CytoTox 96 Non-Radioactive LDH Cytotoxicity Assay. MICA/B was highly expressed in human hepatocellular carcinoma and the expression level was significantly and negatively associated with tumor-node metastasis (TNM) stages. Patients with low level of MICA/B expression showed a trend of shorter survival time. The unfolded protein response (UPR) downregulated the expression of MICA/B. This decreased protein expression occurred via post-transcriptional regulation and was associated with proteasomal degradation. Moreover, decreased expression level of MICA/B led to the attenuated sensitivity of human HCC to NK cell cytotoxicity. These new findings of the connection of MICA/B, UPR and NK cells may represent a new concrete theory of NK cell regulation in HCC, and suggest that targeting this novel NK cell-associated immune evasion pathway may be meaningful in treating patients with HCC.

  20. Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Mu-Yun [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Shen, Yuh-Chiang [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); National Research Institute of Chinese Medicine, Taipei, Taiwan (China); Lu, Chien-Hsing [Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Yang, Shu-Yi [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Ho, Tsing-Fen [Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan (China); Peng, Yu-Ta [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chang, Chia-Che, E-mail: chia_che@dragon.nchu.edu.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China)

    2012-12-15

    Prodigiosin is a bacterial tripyrrole pigment with potent cytotoxicity against diverse human cancer cell lines. Endoplasmic reticulum (ER) stress is initiated by accumulation of unfolded or misfolded proteins in the ER lumen and may induce cell death when irremediable. In this study, the role of ER stress in prodigiosin-induced cytotoxicity was elucidated for the first time. Comparable to the ER stress inducer thapsigargin, prodigiosin up-regulated signature ER stress markers GRP78 and CHOP in addition to activating the IRE1, PERK and ATF6 branches of the unfolded protein response (UPR) in multiple human breast carcinoma cell lines, confirming prodigiosin as an ER stress inducer. Prodigiosin transcriptionally up-regulated CHOP, as evidenced by its promoting effect on the CHOP promoter activity. Of note, knockdown of CHOP effectively lowered prodigiosin's capacity to evoke PARP cleavage, reduce cell viability and suppress colony formation, highlighting an essential role of CHOP in prodigiosin-induced cytotoxic ER stress response. In addition, prodigiosin down-regulated BCL2 in a CHOP-dependent manner. Importantly, restoration of BCL2 expression blocked prodigiosin-induced PARP cleavage and greatly enhanced the survival of prodigiosin-treated cells, suggesting that CHOP-dependent BCL2 suppression mediates prodigiosin-elicited cell death. Moreover, pharmacological inhibition of JNK by SP600125 or dominant-negative blockade of PERK-mediated eIF2α phosphorylation impaired prodigiosin-induced CHOP up-regulation and PARP cleavage. Collectively, these results identified ER stress-mediated cell death as a mode-of-action of prodigiosin's tumoricidal effect. Mechanistically, prodigiosin engages the IRE1–JNK and PERK–eIF2α branches of the UPR signaling to up-regulate CHOP, which in turn mediates BCL2 suppression to induce cell death. Highlights: ► Prodigiosin is a bacterial tripyrrole pigment with potent anticancer effect. ► Prodigiosin is herein identified

  1. YAP induces cisplatin resistance through activation of autophagy in human ovarian carcinoma cells

    Directory of Open Access Journals (Sweden)

    Xiao L

    2016-03-01

    Full Text Available Lan Xiao,1,* Xiao-Yan Shi,2,* Ying Zhang,1 Ying Zhu,1 Lin Zhu,3 Wang Tian,1 Bing-Kun Zhu,1 Zhao-Lian Wei11Department of Obstetrics and Gynecology, First Affiliated Hospital, Anhui Medical University, Hefei, 2Key Laboratory for Molecular Diagnosis of Hubei Province, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 3Obstetrics and Gynecology Hospital of Fudan University (Shanghai Red House Obstetrics and Gynecology Hospital, Shanghai, People’s Republic of China*These authors contributed equally to this workObjective: To identify the role of YAP in cisplatin resistance in human ovarian cancer cells and in the regulation of autophagy in these cancer cells.Materials and methods: The cisplatin-sensitive OV2008 parental cell line and its cisplatin-resistant variant C13K were cultured. RNA interference was used to knock down the YAP gene. Accumulation of GFP-LC3 puncta was performed by fluorescence microscopy. The formation of autophagosomes was observed by transmission electron microscopy. Drug sensitivity was examined using CCK-8 assay, while apoptosis, the level of intracellular rhodamine 123 and lysosomal acidification were analyzed by fluorescence-activated cell sorting. Acid phosphatase activity was measured using an acid phosphatase-assay kit. Real-time polymerase chain reaction, Western blotting, and immunofluorescence detection were used to detect the protein and messenger RNA expression of YAP, YAP target genes, CCND1, cleaved PARP, and caspase 3, Atg-3 and -5, and the LC3B protein.Results: YAP signaling may regulate cisplatin resistance in ovarian cancer cells by augmenting cellular autophagic flux. After knockdown of YAP-sensitized C13K cells to cisplatin by inducing a decrease in autophagy, YAP led to an increase in autophagy via enhancement of autolysosome degradation.Conclusion: YAP-mediated autophagy may play a protective role in cisplatin-resistant human ovarian cancer cells

  2. AP-2γ Induces p21 Expression, Arrests Cell Cycle, Inhibits the Tumor Growth of Human Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Hualei Li

    2006-07-01

    Full Text Available Activating enhancer-binding protein 2γ (AP-2γ is a member of the developmentally regulated AP-2 transcription factor family that regulates the expression of many downstream genes. Whereas the effects of AP-2α overexpression on cell growth are fairly well established, the cellular effects of AP-2γ overexpression are less well studied. Our new findings show that AP-2γ significantly upregulates p21 mRNA and proteins, inhibits cell growth, decreases clonogenic survival. Cell cycle analysis revealed that forced AP-2γ expression induced G1-phase arrest, decreased DNA synthesis, decreased the fraction of cells in S phase. AP-2γ expression also led to cyclin D1 repression, decreased Rb phosphorylation, decreased E2F activity in breast carcinoma cells. AP-2γ binding to the p21 promoter was observed in vivo, the absence of growth inhibition in response to AP-2γ expression in p21 (-/- cells demonstrated that p21 caused, at least in part, AP-2-induced cell cycle arrest. Finally, the tumor growth of human breast carcinoma cells in vivo was inhibited by the expression of AP-2γ relative to empty vector-infected cells, suggesting that AP-2γ acts as a tumor suppressor. In summary, expression of either AP-2γ or AP-2α inhibited breast carcinoma cell growth; thus, these genes may be therapeutic targets for breast cancer.

  3. PBK/TOPK in the differential diagnosis of cholangiocarcinoma from hepatocellular carcinoma and its involvement in prognosis of human cholangiocarcinoma.

    Science.gov (United States)

    He, Furong; Yan, Qingguo; Fan, Linni; Liu, Yixiong; Cui, Jihong; Wang, Juanhong; Wang, Lu; Wang, Yingmei; Wang, Zhe; Guo, Ying; Huang, Gaosheng

    2010-03-01

    The increased expression of PDZ binding kinase/lymphokine-activated killer T-cell-originated protein kinase (PBK/TOPK) is associated with some human malignant tumors. In this study, we analyzed PBK/TOPK expression in hepatic primary tumor and explored its role in cholangiocarcinoma biology. Seventy-four cholangiocarcinomas, 33 hepatocellular carcinomas, and 10 normal liver tissues were prepared from paraffin-embedded specimens. PBK/TOPK protein was assessed by immunohistochemical staining, and the survival time was analyzed with the Kaplan-Meier method. The protein, mRNA of PBK/TOPK, and cell cycle of cholangiocarcinoma cell line after PBK/TOPK suppression with small interfere RNA were studied by Western blot, semiquantitative reverse transcriptase-polymerase chain reaction, and flow cytometry, respectively. PBK/TOPK was usually expressed in normal bile duct epithelial cells and much more frequently expressed in cholangiocarcinoma (68/74) but never expressed in hepatocytes and hepatocellular carcinomas (0/33). PBK/TOPK down-regulation was related to the poor prognosis of patients with cholangiocarcinoma (P = .013). Epidermal growth factor can enhance PBK/TOPK expression in cholangiocarcinoma QBC 939 cells, but suppression of PBK/TOPK in the cells did not affect their proliferation. PBK/TOPK protein could serve as a useful indicator for histopathologic differentiation between cholangiocarcinoma and hepatocellular carcinomas and the low expression of PBK/TOPK is predicative of poor survival in cholangiocarcinoma patients. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Genotyping, levels of expression and physical status of human papilloma virus in oropharyngeal squamous cell carcinoma among Colombian patients.

    Science.gov (United States)

    Erira, Alveiro; Motta, Leidy Angélica; Chala, Andrés; Moreno, Andrey; Gamboa, Fredy; García, Dabeiba Adriana

    2015-10-23

    One of the risk factors for squamous cell oropharyngeal carcinoma is infection with the human papilloma virus (HPV), with prevalences that vary depending on the geographical region.  To identify the most frequent HPV viral types in oropharyngeal cancer, the levels of expression and the physical condition of the viral genome.  Forty-six patients were included in the study from among those attending head and neck surgical services in the cities of Bogotá, Manizales and Bucaramanga. In the histopathological report all study samples were characterized as oropharyngeal squamous cell carcinoma. DNA extraction was subsequently performed for HPV genotyping and to determine the physical state of the viral genome, as well as RNA to determine viral transcripts using real-time PCR.  HPV prevalence in tumors was 21.74% (n=10) and the most common viral type was HPV-16 (nine cases). Viral expression for HPV-16 was low (one of 11 copies) and the predominant physical state of the virus was mixed (eight cases), with disruption observed at the E1 - E2 binding site (2525 - 3720 nucleotides).  The prevalence of HPV associated with oropharyngeal carcinoma among the Colombian study population was 21.7%, which is relatively low. The most frequent viral type was HPV-16, found in a mixed form and with low expression of E7, possibly indicating a poor prognosis for these patients.

  5. [New surgical method for contact granuloma of larynx].

    Science.gov (United States)

    Huang, De-liang; Zhao, Hui; Liu, Liang-fa; Feng, Bo; Wu, Wen-ming; Wang, Jia-ling; Jiang, Wen; Yuan, Yong-yi

    2009-09-01

    For the purpose of improving the surgical effect of contact granuloma of larynx, a new surgical method was used and its effect observed. Under suspension laryngoscope, a part of cartilage of vocal process of arytenoid cartilage was removed until the cartilage was covered by local soft tissue after the granuloma was excised. Among 8 patients in this group, 7 were male, 1 female. Their ages ranged from 29 to 51(median 45 years old). The courses were 1 to 9 months (median 7 months). All patients experienced 1 to 5 times operations (median 2 times). Using the new operative method, all 8 patients were cured for only 1 time, without recurrence followed- up for 1.5 years. The granuloma were very easily recurred after the operation. The reason might be related to the exposure and inflammation of the local vocal process cartilage. The difficult key of the operation is exposure of granuloma and cartilage of vocal process because of intratracheal anesthetic tube.

  6. The role of the larynx in chronic cough.

    Science.gov (United States)

    Cobeta, Ignacio; Pacheco, Adalberto; Mora, Elena

    2013-01-01

    Cough lasting more than 8 weeks is considered chronic. If the classic causes of chronic cough have been discarded, vagus nerve sensory disturbances are currently considered the most important etiological cause. Patients with chronic cough of laryngeal origin have associated symptoms such as globus, dysphagia, dysphonia, dyspnoea and/or stridor. These patients are more likely to have paradoxical vocal fold movement. There is a higher cough reflex sensibility and neuropathic laryngeal response, mainly caused by viral infection or reflux. The cough associated with reflux has 2 mechanisms: Exposure to acid in the distal oesophagus (gastroesophageal reflux) and microaspiration of oesophageal contents into the larynx and tracheo-bronchial tree (pharyngo-laryngeal reflux). Laryngeal neuropathy hypersensitivity responds well to speech therapy as a treatment for refractory chronic cough. Because chronic cough is a sign of laryngeal sensory, neuropathy can improve with neuroleptic drugs such as amitriptyline and gabapentin. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  7. Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

    Science.gov (United States)

    Chitose, Shun-ichi; Sakazaki, T; Ono, T; Kurita, T; Mihashi, H; Nakashima, T

    2010-06-01

    This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity

  8. Total laryngectomy for a dysfunctional larynx after (chemo)radiotherapy.

    Science.gov (United States)

    Theunissen, Eleonoor A R; Timmermans, Adriana J; Zuur, Charlotte L; Hamming-Vrieze, Olga; Paul de Boer, Jan; Hilgers, Frans J M; van den Brekel, Michiel W M

    2012-06-01

    To evaluate the functional outcomes after total laryngectomy (TLE) for a dysfunctional larynx in patients with head and neck cancer that is in complete remission after (chemo)radiotherapy. Retrospective cohort study. Tertiary comprehensive cancer center. The study included 25 patients from a cohort of 217 consecutive patients with TLE who were treated between January 2000 and July 2010. The inclusion criteria for this subgroup analysis were complete remission and functional problems for which TLE was considered to be the only resolution. Quality of life assessment was carried out using the European Organization for Research and Treatment of Cancer Quality of Life C30 and Head and Neck Module 35 questionnaires and an additional study-specific questionnaire covering functional aspects, such as swallowing and dyspnea, in more detail. Total laryngectomy. Morbidity, mortality, and functional outcomes. RESULTS The indication for TLE was chronic aspiration with or without recurrent pneumonia (n = 15 [60%]), debilitating dyspnea (n = 8 [32%]), and persistent profuse hemorrhage (radiation ulcer) (n = 2 [8%]). After TLE, 14 of the 25 patients (56%) had 20 major postoperative complications, including 11 pharyngocutaneous fistulas, requiring additional treatment. Tube feeding and recurrent pneumonia incidence had decreased from 80% and 28% to 29% and 0%, respectively, 2 years after surgery. Prosthetic voice rehabilitation was possible in 19 patients (76%). Two years after surgery, 10 of 14 patients (71%) still reported TLE-related pulmonary problems despite the consistent use of a heat and moisture exchanger. The 5-year overall survival rate was 35%. Total laryngectomy for a dysfunctional larynx tends to have a high complication rate. However, in this study, the initial functional problems (aspiration, recurrent pneumonia, and dyspnea) did not recur. Tube feeding was significantly reduced, and the quality of life of the surviving patients appeared to be reasonable.

  9. Usefulness of ultrasound examination in larynx traumas in children.

    Science.gov (United States)

    Jakubowska, Anna; Zawadzka-Głos, Lidia; Brzewski, Michał

    2011-04-01

    The aim of the paper was to evaluate the usefulness of ultrasonographic examination in diagnosing laryngeal traumas, and monitoring the progress or complications in its treatment. In the years 2004-2009, 12 children, including 5 girls and 7 boys with laryngeal injuries, aged 5-12 years, were diagnosed and treated. In all the children, US examination of the neck and larynx, using a high-frequency linear transducer, as well as laryngoscopy and radiological examination of the cervical spine and chest were performed. Blunt injury of the larynx was found in 12 children; in 9 children, the injury had been caused by hitting the neck against an obtuse object, 1 child had been kicked in the neck, and in one there had been an attempt of strangling. One of the children had sustained blunt injuries of the neck and chest in a traffic accident. IN US EXAMINATIONS, THE FINDINGS INCLUDED: unilateral lack of vocal cord mobility in 5 children, asymmetry in vocal cord mobility in 1 child, fractured thyroid cartilage with local hematoma in the affected area in 2 children, and thickened vocal cords in 5 children. IN RADIOLOGICAL EXAMINATION, THE FINDINGS INCLUDED: subcutaneous emphysema in the cervical area of the chest in 4 children, and mediastinal emphysema in 2 children with traumatic rupture of the trachea shown in laryngoscopy. US examination is helpful in the assessment of the extensiveness of laryngeal trauma, especially in the evaluation of vocal cord mobility, cervical cartilage and the soft tissues of the neck. A high level of conformity was demonstrated between the results of cervical US and the respective laryngoscopic findings. US examination does not allow to differentiate between vocal cord paralysis and their immobilization.

  10. [The expression and significance of Pin1 and CyclinD1 in adult papilloma of larynx].

    Science.gov (United States)

    Fan, Guoliang; Wang, Dali; Fan, Xinlong; Wang, Tie

    2009-12-01

    To study the expression and relationship of Pin1 and CyclinD1 in adult papilloma of larynx, and the effect of both in laryngeal papilloma's canceration. Ninety-two cases of paraffin section with immunoperoxidase (SP) staining method was used to detect the distribution of Pin1 and CyclinD1 in 10 cases of laryngeal normal epithelial tissue, 39 cases of laryngeal papilloma, 27 cases of laryngeal papilloma with middle, severe atypical hyperplasia and 16 cases of laryngeal carcinoma. The distribution of Pin1 and CyclinD1 increased gradually from laryngeal normal epithelial tissue to laryngeal carcinoma (Plaryngeal papilloma and laryngeal papilloma with middle, severe atypical hyperplasia (P>0.0125), but there had significant difference of the expression of Pin1 and CyclinD1 among the rest groups; There was significantly direct correlation between the expression of Pin1 and CyclinD1 (Plaryngeal papilloma's malignant change. Pin1 up-regulating the expressions of cyclinD1 possibly participate in its malignant change.

  11. CHD1L promotes hepatocellular carcinoma progression and metastasis in mice and is associated with these processes in human patients

    OpenAIRE

    Chen, Leilei; Chan, Tim Hon Man; Yuan, Yun-Fei; Hu, Liang; Huang, Jun; Ma, Stephanie; Wang, Jian; Dong, Sui-sui; Tang, Kwan Ho; Xie, Dan; Li, Yan; Guan, Xin-Yuan

    2010-01-01

    Chromodomain helicase/ATPase DNA binding protein 1–like gene (CHD1L) is a recently identified oncogene localized at 1q21, a frequently amplified region in hepatocellular carcinoma (HCC). To explore its oncogenic mechanisms, we set out to identify CHD1L-regulated genes using a chromatin immunoprecipitation–based (ChIP-based) cloning strategy in a human HCC cell line. We then further characterized 1 identified gene, ARHGEF9, which encodes a specific guanine nucleotide exchange factor (GEF) for ...

  12. Lectins from the Red Marine Algal Species Bryothamnion seaforthii and Bryothamnion triquetrum as Tools to Differentiate Human Colon Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Vicente P. T. Pinto

    2009-01-01

    Full Text Available The carbohydrate-binding activity of the algal lectins from the closely related red marine algal species Bryothamnion triquetrum (BTL and Bryothamnion seaforthii (BSL was used to differentiate human colon carcinoma cell variants with respect to their cell membrane glyco-receptors. These lectins interacted with the cells tested in a dose-dependent manner. Moreover, the fluorescence spectra of both lectins clearly differentiated the cells used as shown by FACS profiles. Furthermore, as observed by confocal microscopy, BTL and BSL bound to cell surface glycoproteins underwent intense internalization, which makes them possible tools in targeting strategies.

  13. T24 human bladder carcinoma cells with activated Ha-ras protooncogene: nontumorigenic cells susceptible to malignant transformation with carcinogen.

    OpenAIRE

    Senger, D. R.; Perruzzi, C A; Ali, I U

    1988-01-01

    A comparative analysis of T24 human bladder carcinoma cells and N-methyl-N'-nitro-N-nitrosoguanidine (MeNNG)-transformed derivatives (MeNNG-T24 cells) revealed the following: (i) The presence of an activated c-Ha-ras gene (in the absence of the normal allele) is insufficient to confer upon T24 cells a tumor-associated phenotype. (ii) MeNNG-transformed T24 cells not only acquire tumor-associated (in vitro) traits (growth in soft agar and rhodamine retention) but, are highly tumorigenic in nude...

  14. Clonal evolution demonstrated by flow cytometric DNA analysis of a human colonic carcinoma grown in nude mice

    DEFF Research Database (Denmark)

    Vindeløv, L L; Spang-Thomsen, M; Visfeldt, J

    1982-01-01

    A spontaneous change in DNA content of a human colonic carcinoma grown in nude mice was observed fortuitously. The tumor initially had a G1 cell DNA content of 1.3 times that of normal cells. Flow cytometric DNA analysis showed in transplant generation 56 the appearance of a new subpopulation whi...... evolution of a tumor would be less pronounced if old subpopulations often become extinct as new ones emerge. Heterogeneity of human tumors is of clinical importance because the individual subpopulations may have different sensitivity patterns to antineoplastic drugs.......A spontaneous change in DNA content of a human colonic carcinoma grown in nude mice was observed fortuitously. The tumor initially had a G1 cell DNA content of 1.3 times that of normal cells. Flow cytometric DNA analysis showed in transplant generation 56 the appearance of a new subpopulation which...... in three passages completely overgrew the original population. The DNA content of the new subpopulation was twice that of the original population. The observation supports the hypothesis of clonal evolution of tumor cell populations. The growth rates of the tumor before and after the change showed...

  15. Lobaplatin induces BGC-823 human gastric carcinoma cell apoptosis via ROS- mitochondrial apoptotic pathway and impairs cell migration and invasion.

    Science.gov (United States)

    Li, Yali; Liu, Bin; Yang, Fangfang; Yu, Yang; Zeng, Anqi; Ye, Tinghong; Yin, Wenya; Xie, Yongmei; Fu, Zhengyan; Zhao, Chengjian

    2016-10-01

    Human gastric cancer is the fifth common cancer with considerable metastasis potential, and its high incidence and mortality rate threaten public health. In this study, we examined the anticancer effects of lobaplatin on the human gastric carcinoma cell line BGC-823 in vitro, and explored its relative mechanisms. The results of MTT assay showed dose- and time-dependent cytotoxicity in BGC-823 cells with lobaplatin. Flow cytometry (FCM) assay indicated that lobaplatin affected BGC-823 cells' survival by inducing apoptosis. Western blot analysis also demonstrated that the occurrence of its apoptosis was associated with activation of Cleaved caspase-3 and Bax, downregulation of Bcl-2. Moreover, lobaplatin could also increase the reactive oxygen species (ROS) slightly and decrease the mitochondrial membrane potential (ΔYm) obviously, elucidating that lobaplatin may induce apoptosis via mitochondria-dependent apoptotic pathway. Furthermore, lobaplatin markedly blocked BGC-823 cells migration and invasion, and the reduction of matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed in vitro. Our findings demonstrated the chemotherapeutic potential of lobaplatin for treatment of human gastric carcinoma cell line BGC-823 by inhibiting proliferation, inducing apoptosis and attenuating cell migration and invasion. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Construction and characterization of a fusion protein of single-chain anti-carcinoma antibody 323/A3 and human beta-glucuronidase

    NARCIS (Netherlands)

    Haisma, HJ; Brakenhoff, RH; Van der Meulen-Muileman, I.H.; Pinedo, HM; Boven, E

    We report the construction and expression of a fusion protein between a single-chain antibody specific for human carcinomas and human beta-glucuronidase by recombinant DNA technology. The sequences encoding the murine monoclonal antibody 323/A3 light- and heavy-chain variable genes were joined by a

  17. Nonuniform Distribution of High-risk Human Papillomavirus in Squamous Cell Carcinomas of the Oropharynx: Rethinking the Anatomic Boundaries of Oral and Oropharyngeal Carcinoma From an Oncologic HPV Perspective.

    Science.gov (United States)

    Gelwan, Elise; Malm, Ian-James; Khararjian, Armen; Fakhry, Carol; Bishop, Justin A; Westra, William H

    2017-12-01

    The oral cavity and oropharynx have historically been viewed as a single anatomic compartment of the head and neck. The practice of combining the oral cavity and oropharynx has recently been revised, largely owing to the observation that human papillomavirus (HPV)-related carcinogenesis has a strong predilection for the oropharynx but not the oral cavity. The purpose of this study was to determine whether HPV is evenly distributed across squamous cell carcinomas of the oropharynx including those sites that do not harbor tonsillar tissues such as the soft palate. A search of the medical records of the Johns Hopkins Hospital identified 32 primary squamous cell carcinomas of the soft palate (n=31) and posterior pharyngeal wall (n=1). All were evaluated with p16 immunohistochemistry and high-risk HPV in situ hybridization (ISH) (29 by RNA ISH and 3 by DNA ISH). For comparison, we also reviewed the medical records to obtain the HPV status of patients who had undergone HPV testing of primary tonsillar carcinomas over the same time interval as part of their clinical care. High-risk HPV as detected by ISH was present in just 1 (3.1%) of the 32 oropharyngeal squamous cell carcinomas, including 1 of 2 p16-positive carcinomas. The difference in HPV detection rates between tonsillar and nontonsillar sites was significant (1/32, 3.1% vs. 917/997, 92%; Pdetected in squamous cell carcinomas arising from nontonsillar regions of the oropharynx. Indeed, squamous cell carcinomas of the soft palate more closely resemble those arising in the oral cavity than those arising in areas of the oropharynx harboring tonsillar tissue. This finding not only further sharpens our understanding of site-specific targeting by HPV, but may have practical implications regarding HPV testing and even the way the oral vault is oncologically compartmentalized to partition HPV-positive from HPV-negative cancers.

  18. Establishment and characterization of two new cell lines derived from human metastatic breast carcinomas.

    Science.gov (United States)

    Zoli, W; Roncuzzi, L; Zini, N; Lenzi, L; Gruppioni, R; Barzanti, F; Sensi, A; Amadori, D; Gasperi-Campani, A

    1997-04-01

    Two human cancer cell lines (MA 2 and MA 3) were established from pleural effusions of infiltrating ductal carcinomas of the breast. The lines were maintained in continuous monolayer culture with doubling times of 70 (MA 2) and 78 (MA 3) hr for more than two years and possessed extensively rearranged abnormal karyo-types with modal chromosome number of 83 (MA 2) and 81 (MA 3) and DNA index values of 1.65 and 1.77, respectively. No amplifications or rearrangements were evident in the c-myc, int-2, c-erb B2, c-Ha-ras, or hst 1 genes in MA 2 and MA 3 cell lines. The clinical histories of the patients from whom the cell lines were derived are reported and compared with the results observed in the cell lines in vitro. The presence of CEA, CA 15-3, and MCA tumor markers observed in the primary tumor tissues was retained by the established cell lines. While the primary tumor tissues were ER+/PgR borderline+ (MA 2) and ER-/PgR+ (MA 3), the MA 2 line was ER+/PgR- and the MA 3 line remained ER-/PgR+. The MDR P-glycoprotein was not expressed either in primary tumor tissues or in the respective cell lines. High expression of cytokeratins 7, 18, and 19 was evident by immunohistochemical analysis in each cell line. whereas cytokeratins 8 and 17 were poorly or not at all expressed. The treatment history of the patients from whom the cell lines were derived involved CMF followed six months later by novantrone and cisplatin plus VP 16 (MA 2) and FEC followed four years later by CMF (MA 3). The chemosensitivity pattern assay of the cell lines indicated that the MA 2 line was sensitive to doxorubicin, cisplatin, and vinblastine, whereas the MA 3 line was sensitive to doxorubicin and cisplatin. The characteristics of these cell lines indicate them to be a good experimental model to investigate breast cancer biology and anticancer drug response.

  19. Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas.

    Science.gov (United States)

    Lingen, Mark W; Xiao, Weihong; Schmitt, Alessandra; Jiang, Bo; Pickard, Robert; Kreinbrink, Paul; Perez-Ordonez, Bayardo; Jordan, Richard C; Gillison, Maura L

    2013-01-01

    Human papillomavirus (HPV) is a cause of oropharyngeal cancer, but a role for HPV in the etiology of oral cavity squamous cell carcinomas (OCSCC) remains uncertain. We sought to estimate the etiologic fraction for HPV among consecutive, incident OCSCC diagnosed from 2005 to 2011 at four North American hospitals. DNA and RNA purified from paraffin-embedded tumors were considered evaluable if positive for DNA and mRNA control genes by quantitative PCR. Fifteen high-risk (HR) HPV types were detected in tumors by consensus PCR followed by type-specific HR-HPV E6/7 oncogene expression by quantitative reverse-transcriptase PCR. P16 expression was evaluated by immunohistochemistry (IHC). A study of 400 cases allowed for precision to estimate an etiologic fraction of as low as 0% (97.5% confidence interval, 0-0.92%). Of 409 evaluable OCSCC, 24 (5.9%, 95%CI 3.6-8.2) were HR-HPV E6/7 expression positive; 3.7% (95%CI 1.8-5.5) for HPV16 and 2.2% (95%CI 0.8-3.6) for other HR-HPV types. HPV-positive tumors arose from throughout the oral cavity (floor of mouth [n=9], anterior tongue [6], alveolar process [4], hard palate [3], gingiva [1] and lip [1]) and were significantly associated with male gender, small tumor stage, poor tumor differentiation, and basaloid histopathology. P16 IHC had very good-to-excellent sensitivity (79.2%, 95%CI 57.9-92.9), specificity (93.0%, 95%CI 90.0-95.3), and negative-predictive value (98.6%, 95%CI 96.8-99.6), but poor positive-predictive value (41.3%, 95%CI 27.0-56.8) for HR-HPV E6/7 expression in OCSCC. The etiologic fraction for HR-HPV in OCSCC was 5.9%. p16 IHC had poor positive predictive value for detection of HPV in these cancers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. The aetiological role of human papillomavirus in oesophageal squamous cell carcinoma: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Surabhi S Liyanage

    Full Text Available BACKGROUND: The aetiological role of human papillomavirus (HPV in oesophageal squamous cell carcinoma (OSCC has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC. METHODS: Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR. RESULTS: From all OSCC specimens included in this meta-analysis, 35% (426/1223 were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20. Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76 than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91. CONCLUSIONS: Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.

  1. Human papillomavirus 16 infection predicts poor outcome in patients with esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Xi R

    2015-03-01

    Full Text Available Ruxing Xi,1 Xiaozhi Zhang,1 Xin Chen,1 Shupei Pan,1 Beina Hui,1 Li Zhang,1 Shenbo Fu,1 Xiaolong Li,2 Xuanwei Zhang,1 Tuotuo Gong,1 Jia Guo,1 Shaomin Che1 1Department of Radiotherapy, The First Affiliated Hospital of Xi’an Jiao Tong University, 2Department of Radiotherapy, The People’s Liberation Army 323 Hospital, Xi’an, People’s Republic of China Background: Previous studies indicate that human papillomavirus 16 (HPV16 infection plays a pivotal role in the etiology of esophageal squamous cell carcinoma (ESCC. We aim to detect the influence of HPV16 infection on ESCC patient prognosis. Patients and methods: Immunohistochemical staining for HPV16 E6 oncoprotein, the low-affinity p75 neurotrophin receptor (p75NTR, and phosphatidylinositol 3-kinase (PI3K was performed on 103 archived surgical specimens from patients with ESCC and 54 control samples from patients with benign esophageal tumor or inflammatory lesions. All patients were from the Shaan Xi Province, People’s Republic of China. Results: HPV16 E6 expression was significantly higher in the ESCC group (P<0.05. HPV16 E6 expression was significantly higher in men than in women (P<0.05. p75NTR expression was higher in those aged >56 years (P<0.05. PI3K expression was higher in those with a more advanced histopathological grade (P<0.05. There was a positive correlation between HPV16 E6 and p75NTR expression (r=0.547, P<0.001 and between p75NTR and PI3K expression (r=0.364, P<0.001. In 100 evaluable patients, the 5-year overall survival (OS rate was 11%. In patients with ESCC, HPV16 E6 and PI3K expression were negatively correlated with the 3-year OS (P<0.05, 5-year OS (P<0.05, and progression-free survival (P<0.05. Conclusion: HPV16 infection likely contributes to the etiology of ESCC patients in Shaan Xi, People’s Republic of China. HPV16 infection status and PI3K expression levels could be useful for predicting prognosis in patients with ESCC. Keywords: low-affinity p75

  2. Characterization of Hepatocellular Carcinoma Related Genes and Metabolites in Human Nonalcoholic Fatty Liver Disease

    Czech Academy of Sciences Publication Activity Database

    Clarke, D. J.; Novák, Petr; Lake, A.D.; Shipkova, P.; Aranibar, N.; Robertson, D.; Severson, P.L.; Reily, M.D.; Futscher, B. W.; Lehman-McKeeman, L.D.; Cherrington, N.J.

    2014-01-01

    Roč. 59, č. 2 (2014), s. 365-374 ISSN 0163-2116 Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : nonalcoholic fatty liver disease * nonalcoholic steatohepatitis * hepatocellular carcinoma * metabolomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.613, year: 2014

  3. Prognostic impact of carbonic anhydrase IX expression in human renal cell carcinoma.

    NARCIS (Netherlands)

    Sandlund, J.; Oosterwijk, E.; Grankvist, K.; Oosterwijk-Wakka, J.C.; Ljungberg, B.; Rasmuson, T.

    2007-01-01

    OBJECTIVE: To evaluate the prognostic information of carbonic anhydrase (CA) IX expression in patients with renal cell carcinoma (RCC), as increased expression of CA IX is correlated with a worse prognosis in several malignancies. PATIENTS AND METHODS: CA IX expression was assessed in RCC tumours

  4. Protein expression profiling of nuclear membrane protein reveals potential biomarker of human hepatocellular carcinoma

    OpenAIRE

    Khan, Rizma; Zahid, Saadia; Wan, Yu-Jui; Forster, Jameson; Karim, A-Bashar; Nawabi, Atta M; Azhar, Abid; Rahman, M; Ahmed, Nikhat

    2013-01-01

    Abstract Background Complex molecular events lead to development and progression of liver cirrhosis to HCC. Differentially expressed nuclear membrane associated proteins are responsible for the functional and structural alteration during the progression from cirrhosis to carcinoma. Although alterations/ post translational modifications in protein expression have been extensively quantified, complementary analysis of nuclear membrane proteome changes h...

  5. Abnormal A-type lamin organization in a human lung carcinoma cell line

    NARCIS (Netherlands)

    Machiels, BM; Broers, JL; Raymond, Y; de Leij, Louis; Kuijpers, HJH; Caberg, NEH; Ramaekers, Frans C. S.

    We have studied the expression of lamins A and C (A-type lamins) in a lung carcinoma cell line using type-specific monoclonal antibodies, Using immunofluorescence and immunoblotting studies it was noted that several irregularities in lamin expression exist in the cell line GLC-A1, derived from an

  6. Structural alterations of transforming growth factor-beta receptor genes in human cervical carcinoma

    NARCIS (Netherlands)

    Chen, TP; De Vries, EGE; Hollema, H; Yegen, HA; Vellucci, VF; Strickler, HD; Hildesheim, A; Reiss, M

    1999-01-01

    The development and progression of invasive uterine cervical carcinomas appear to be associated with the progressive loss of sensitivity to transforming growth factor-beta (TGF beta)-mediated cell cycle arrest. In order to identify possible molecular mechanisms responsible for TGF beta resistance,

  7. Human papillomavirus-related carcinoma with adenoid cystic-like features of the sinonasal tract: clinical and morphological characterization of six new cases.

    Science.gov (United States)

    Andreasen, Simon; Bishop, Justin A; Hansen, Thomas van Overeem; Westra, William H; Bilde, Anders; von Buchwald, Christian; Kiss, Katalin

    2017-05-01

    Human papillomavirus (HPV) is known as causative for squamous cell carcinoma (SCC) of the oropharynx, but is also found not infrequently in carcinomas of the sinonasal tract. Recently, a subset of these carcinomas was recognized to harbour HPV33 and have a significant morphological overlap with adenoid cystic carcinoma (ACC), a rare and aggressive carcinoma originating in the minor salivary glands. Termed 'HPV-related carcinoma with ACC-like features', only nine cases have been reported. To clarify the occurrence of these tumours we screened a large material for the presence of HPV-related ACC-like carcinoma. The identified tumours were characterized immunohistochemically and with fluorescence in-situ hybridization, and clinicopathological information for all cases is presented. Forty-seven candidate cases were screened for presence of HPV. Six cases were identified and genotyped as HPV types 33, 35, and 56. All six cases had areas of dysplastic mucosal lining and showed remarkable heterogeneous morphologies. MYB, MYBL1, and NFIB genes were intact and, interestingly, staining for MYB protein was largely negative in contrast to what was found in ACC. One patient experienced a local recurrence 11 years after initial treatment and the remaining five patients were alive without evidence of disease. We report six new cases of HPV-related ACC-like carcinoma and found that, although in a small material, the prognosis for these patients seems more favourable than for ACC. For the distinction between ACC and HPV-related ACC-like carcinoma, p16, MYB immunohistochemistry or investigation of MYB, MYBL1 and NFIB gene status are valuable. © 2016 John Wiley & Sons Ltd.

  8. The mRNA expression of hTERT in human breast carcinomas correlates with VEGF expression

    Directory of Open Access Journals (Sweden)

    Kirkpatrick Katharine L

    2004-01-01

    Full Text Available Abstract Background Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalisation. hTERT (human telomerase reverse transcriptase is the rate-limiting determinant of telomerase reactivation. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any correlation between hTERT and the negative prognostic indicators VEGF and PCNA by quantitatively measuring the mRNA expression of these genes in human breast cancer and in adjacent non-cancerous tissue (ANCT. Materials and methods RNA was extracted from 38 breast carcinomas and 40 ANCT. hTERT and VEGF165, VEGF189 and PCNA mRNA expressions were estimated by reverse transcriptase-PCR (RT-PCR and Taqman methodology. Results The level of expression of VEGF-165 and PCNA was significantly higher in carcinoma tissue than ANCT (p = 0.02. The ratio of VEGF165/189 expression was significantly higher in breast carcinoma than ANCT (p = 0.025. hTERT mRNA expression correlated with VEGF-189 mRNA (p = 0.008 and VEGF165 (p = 0.07. Conclusions hTERT mRNA expression is associated with the expression of the VEGF189 and 165 isoforms. This could explain the poorer prognosis re