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Sample records for cancer involves short

  1. Involvement of hyaluronidases in colorectal cancer

    International Nuclear Information System (INIS)

    Hyaluronidases belong to a class of enzymes that degrade, predominantly, hyaluronan. These enzymes are known to be involved in physiological and pathological processes, such as tumor growth, infiltration and angiogenesis, but their exact role in tumor promotion or suppression is not clear yet. Advanced colorectal cancer is associated with elevated amounts of hyaluronan of varying size. The aim of the present study was therefore to illuminate the importance of hyaluronidases in colon carcinoma progression. The patients' samples (macroscopically normal and cancerous) were subjected to sequential extraction with PBS, 4 M GdnHCl and 4 M GdnHCl - 1% Triton X-100. The presence of the various hyaluronidases in the extracts was examined by zymography and western blotting. Their expression was also examined by RT-PCR. Among hyaluronidases examined, Hyal-1, -2, -3 and PH-20 were detected. Their activity was higher in cancerous samples. Hyal-1 and Hyal-2 were overexpressed in cancerous samples, especially in advanced stages of cancer. Both isoforms were mainly extracted with PBS. Hyal-3 was observed only in the third extract of advanced stages of cancer. PH-20 was abundant in all three extracts of all stages of cancer. The expression of only Hyal-1 and PH-20 was verified by RT-PCR. A high association of hyaluronidases in colorectal cancer was observed. Each hyaluronidase presented different tissue distribution, which indicated the implication of certain isoforms in certain cancer stages. The results provided new evidence on the mechanisms involved in the progression of colorectal cancer

  2. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: epatsavoudi@pasteur.gr [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)

    2015-01-26

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  3. The epidemiology of long- and short-term cancer survivors

    DEFF Research Database (Denmark)

    Jarlbæk, Lene; Christensen, Linda; Bruera, Eduardo; Hansen, Dorte Gilså

    2014-01-01

    Introduction. In this study, we present data from a population-based cohort of incident cancer patients separated in long- and short-term survivors. Our aim was to procure denominators for use in the planning of rehabilitation and palliative care programs. Material and methods. A registry......' difference in age at TOCD was seen between long- and short-term survivors, with median ages of 60 versus 72 years, respectively. Females comprised 64% of long-term, and 46% of short-term survivors. The proportion of breast and lung cancers differed between the groups: Long-term survivors: 31% breast cancer......, 2.4% lung cancer. Short-term survivors: 21% lung cancer, 7.2% breast cancer. Chemotherapy was provided to 15% of all patients, and to 10% of the 60 + year olds. Discussion. The epidemiology of long- and short-term survivors shows significant differences with regard to age at TOCD, cancer types and...

  4. Parental involvement in paediatric cancer treatment decisions

    OpenAIRE

    McKenna, K; Collier, J; Hewitt, M.; Blake, H

    2010-01-01

    This study investigated parents' information needs and involvement in decision-making processes affecting the care of children diagnosed with cancer. Interviews and questionnaires were used to assess parental satisfaction in 50 mothers and 16 fathers responsible for 58 children in an English Paediatric Oncology Unit. Parents reported that doctors contributed almost twice as much to the decision-making process as they did, but parental satisfaction was positively correlated with the amount of ...

  5. Occupational cancers in leather tanning industries: A short review

    OpenAIRE

    Rastogi S; Kesavachandran C; Mahdi Farzana; Pandey Amit

    2007-01-01

    Work in leather tanning involves exposure to a wide range of chemicals. Some of these are carcinogens or suspected carcinogens. Increased risks for a number of cancers have been reported among the tannery workers. In the present review, a detailed account of lung cancer, testicular cancer, soft tissue sarcoma, pancreatic cancer, bladder cancer among tannery workers is mentioned.

  6. Occupational cancers in leather tanning industries: A short review

    Directory of Open Access Journals (Sweden)

    Rastogi S

    2007-01-01

    Full Text Available Work in leather tanning involves exposure to a wide range of chemicals. Some of these are carcinogens or suspected carcinogens. Increased risks for a number of cancers have been reported among the tannery workers. In the present review, a detailed account of lung cancer, testicular cancer, soft tissue sarcoma, pancreatic cancer, bladder cancer among tannery workers is mentioned.

  7. Stakeholder involvement techniques. A short guide and annotated bibliography

    International Nuclear Information System (INIS)

    The Forum on Stakeholder Confidence (FSC) was created under a mandate from the Radioactive Waste Management Committee (RWMC) of the OECD Nuclear Energy Agency (NEA) to facilitate the sharing of international experience in addressing the societal dimension of radioactive waste management. It explores means of ensuring an effective dialogue amongst all stakeholders, and considers ways to strengthen confidence in decision-making processes. FSC documents may be obtained online at www.nea.fr/html/rwrnifsc.html. OECD countries are increasingly implementing forms of participatory democracy that will require new or enhanced forms of dialogue amongst a broader range of concerned parties. The 4. regular FSC meeting held in Paris in May 2003 included a topical session on Stakeholder involvement tools: Criteria for choice and evaluation. The internal Minutes of the 4. meeting noted, in response to the discussions initiated by this topical session: 'Given that FSC members have one specific issue - radioactive waste management (RWM) - to deal with, a continuing relationship and dialogue among stakeholders seems important. What is desired is a well-informed citizen, because this is - in the end - an issue of democracy. Perhaps we have suffered in our field from a lack of recognition that RWM, like others, is an issue of democracy as well as a technical one'. At the close of the topical session, it was agreed that the FSC would prepare a short guide on stakeholder involvement techniques. The present guide approaches the topic from the point of view of radioactive waste management. However, because dialogue and deliberation techniques can be used in many fields, it will be of interest to a wide readership. It includes an annotated bibliography pointing to easily accessible handbooks and other resources. (author)

  8. The effect of nursing consultation involving cancer survivors on newly diagnosed cancer patients’ quality of life

    Science.gov (United States)

    Bahrami, Masoud; Parnian, Raziyeh; Samimi, Mozhgan Alam

    2012-01-01

    Introduction: Cancer and its treatments have a significant effect on the Quality of Life (QoL) of people who suffer from cancer. Nursing consultation involving cancer survivors might be beneficial for other patients as they successfully managed and lived with cancer. But controversies still exist in the research findings as how nursing consultation involving cancer survivors might influence other cancer patients’ QoL. Therefore, a research study was done to determine the effect of nursing consultation with the presence of cancer survivors on cancer patients’ QoL. Materials and Methods: The study was a quasi-experimental research using a pre-post test design, which was conducted in Sayyed- AL-Shohada Hospital affiliated to Isfahan University of Medical Sciences, Iran, in 2010. Twenty-two adult patients who suffered from acute leukemia who were receiving chemotherapy were selected. They participated in a nursing consultation group in which cancer survivors were actively engaged. The patients’ QoL was assessed before, 1 week, and 1 month after the nursing consultation using the European Organization for Research and Treatment of Cancer Quality of Life Core-30 Version 3 (EORTC QLQ-C30-V3) questionnaire. Results: Comparing QoL mean scores of patients in the symptom, performance, and the general health status scales showed that there was not any significant change in the QoL scores before, 1 week, and 1 month after the consultation. Conclusion: It seems that the nursing consultation with the presence of cancer survivors couldn’t enhance patients’ QoL, although it might prevent worsening the patients’ QoL. Cancer has deleterious impacts on patients’ QoL and nursing consultation may not improve QoL in a short period of time. It is recommended that the study be conducted with a larger sample, in a longer time and with a case-control design. PMID:23853645

  9. Short-Term Prognostic Index for Breast Cancer: NPI or Lpi

    OpenAIRE

    Van Belle, V.; Decock, J; Hendrickx, W.; Brouckaert, O.; Pintens, S.; Moerman, P; Wildiers, H; Paridaens, R.; M. R. Christiaens; Van Huffel, S.; Neven, P.

    2011-01-01

    Axillary lymph node involvement is an important prognostic factor for breast cancer survival but is confounded by the number of nodes examined. We compare the performance of the log odds prognostic index (Lpi), using a ratio of the positive versus negative lymph nodes, with the Nottingham Prognostic Index (NPI) for short-term breast cancer specific disease free survival. A total of 1818 operable breast cancer patients treated in the University Hospital of Leuven between 2000 and 2005 were ...

  10. Short telomere length, cancer survival, and cancer risk in 47102 individuals

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Cawthon, Richard M; Freiberg, Jacob J; Tybjærg-Hansen, Anne; Bojesen, Stig E

    2013-01-01

    Recent meta-analyses have suggested that short telomere length was associated with increased risk of cancer. We therefore tested the hypotheses that short telomere length was associated with increased risk of cancer and with increased risk of early death after cancer.......Recent meta-analyses have suggested that short telomere length was associated with increased risk of cancer. We therefore tested the hypotheses that short telomere length was associated with increased risk of cancer and with increased risk of early death after cancer....

  11. Characterizing genetic syndromes involved in cancer and radiogenic cancer risk

    International Nuclear Information System (INIS)

    The COG project 2806A (1995), reviewed the On-line Mendelian Inheritance in Man (OMIM) database of genetic syndromes to identify those syndromes, genes, and DNA sequences implicated in some way in the cancer process, and especially in radiogenic cancer risk. The current report describes a recent update of the survey in light of two years of further progress in the Human Genome project, and is intended to supply a comprehensive list of those genetic syndromes, genes, DNA sequences and map locations that define genes likely to be involved in cancer risk. Of the 8203 syndromes in OMIM in 1997 June, 814 are associated, even if marginally, with cancer. Of the 814 syndromes so linked, 672 have been mapped to a chromosome, and 476 have been mapped to a chromosome and had a DNA sequence associated with their messenger RNA (or cDNA) sequences. In addition, 35 syndromes have sequences not associated with map locations, and the remaining 107 have neither been mapped nor sequenced. We supply the list of the various genetic syndromes sorted by chromosome location and by OMIM descriptor, together with all the associated but unmapped and unsequenced syndromes. (author)

  12. Short-term outcomes following laparoscopic resection for colon cancer.

    LENUS (Irish Health Repository)

    Kavanagh, Dara O

    2011-03-01

    Laparoscopic resection for colon cancer has been proven to have a similar oncological efficacy compared to open resection. Despite this, it is performed by a minority of colorectal surgeons. The aim of our study was to evaluate the short-term clinical, oncological and survival outcomes in all patients undergoing laparoscopic resection for colon cancer.

  13. The effect of nursing consultation involving cancer survivors on newly diagnosed cancer patients’ quality of life

    OpenAIRE

    Bahrami, Masoud; Parnian, Raziyeh; Samimi, Mozhgan Alam

    2012-01-01

    Introduction: Cancer and its treatments have a significant effect on the Quality of Life (QoL) of people who suffer from cancer. Nursing consultation involving cancer survivors might be beneficial for other patients as they successfully managed and lived with cancer. But controversies still exist in the research findings as how nursing consultation involving cancer survivors might influence other cancer patients’ QoL. Therefore, a research study was done to determine the effect of nursing con...

  14. NK cells, pregnancy, cancer. A short review

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca; Pospíšil, Miloslav; Fišerová, Anna

    2005-01-01

    Roč. 8, č. 4 (2005), s. 147-152. ISSN 1506-4794 R&D Projects: GA AV ČR IAA500200509; GA AV ČR IAA5020403; GA ČR GA524/04/0102; GA AV ČR IAA500200510 Institutional research plan: CEZ:AV0Z50200510 Keywords : natural killer cells * immune tolerance * cancer Subject RIV: EE - Microbiology, Virology

  15. Parathyroid involvement in thyroid cancer: an unforeseen event

    Directory of Open Access Journals (Sweden)

    Chrisoulidou Alexandra

    2012-06-01

    Full Text Available Abstract Background Parathyroid metastatic disease from thyroid cancer has not been studied extensively, mainly due to the need for parathyroid preservation during thyroid surgery. Methods We reviewed files from 1,770 patients with thyroid cancer followed up in our department and 10 patients with parathyroid metastases (0.5% were identified. Patient and tumor characteristics were recorded. Results Six out of ten patients had metastases from papillary thyroid cancer, three from follicular thyroid cancer and one from anaplastic thyroid cancer. In nine patients parathyroid infiltration from thyroid cancer was found in direct contact with the thyroid cancer, and in one patient metastatic foci were observed not in continuity with the thyroid cancer. Conclusions Parathyroid involvement, although infrequent, may occur in thyroid cancer independently of patient age and tumor size. The clinical significance of such event is not clear. The influence on disease outcome remains to be elucidated.

  16. Involvement of Aberrant Glycosylation in Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Eiji Miyoshi

    2010-01-01

    Full Text Available Glycosylation is one of the most common posttranslational modification reactions and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharides structures are associated with many physiological and pathological events, including cell growth, migration and differentiation, and tumor invasion. Therefore, functional glycomics, which is a comprehensive study of the structures and functions of glycans, is attracting the increasing attention of scientists in various fields of life science. In cases of thyroid cancer, the biological characters and prognosis are completely different in each type of histopathology, and their oligosaccharide structures as well as the expression of glycosyltransferases are also different. In this review, we summarized our previous papers on oligosaccharides and thyroid cancers and discussed a possible function of oligosaccharides in the carcinogenesis in thyroid cancer.

  17. Involvement of Relatives in Cancer Rehabilitation

    DEFF Research Database (Denmark)

    Ledderer, Loni; Madsen, Biddy; Mogensen, Ole;

    2010-01-01

    Purpose: The purpose of this study is to analyze the effect of a rehabilitation intervention (supportive conversations and a residential rehabilitation course) offered to cancer patients and their relatives in pairs. The hypothesis is that the intervention can improve the pairs’ health related...... quality of life and that patients and their relatives in the intervention group will show a better capacity for handling the everyday life together. Methods: A randomized, controlled study is designed to assess the effect of the rehabilitation intervention. Patients admitted to the hospital and diagnosed...... with lung cancer or gynecological cancer are included in the study together with a relative by patient’s choice both giving informed consent (N=120 pairs). The intervention group (60 pairs) receives three supportive conversations with a trained nurse initiated from the admission date and completed...

  18. Involvement of free radicals in breast cancer

    OpenAIRE

    Ríos-Arrabal, Sandra; Artacho-Cordón, Francisco; León, Josefa; Román-Marinetto, Elisa; del Mar Salinas-Asensio, María; Calvente, Irene; Núñez, Maria Isabel

    2013-01-01

    Researchers have recently shown an increased interest in free radicals and their role in the tumor microenvironment. Free radicals are molecules with high instability and reactivity due to the presence of an odd number of electrons in the outermost orbit of their atoms. Free radicals include reactive oxygen and nitrogen species, which are key players in the initiation and progression of tumor cells and enhance their metastatic potential. In fact, they are now considered a hallmark of cancer. ...

  19. Pancreatic involvement in small cell lung cancer

    International Nuclear Information System (INIS)

    Few data are available concerning incidence, clinical picture, and prognosis for pancreatic metastases of small cell lung carcinoma. In this paper we review the related literature available in English language. Although pancreatic metastases are generally asymptomatic, they can rarely produce clinical symptoms or functional abnormalities. The widespread use of multi-detector computerised tomography (CT) in contemporary medical practice has led to an increased detection of pancreatic metastases in oncology patients. Tissue diagnosis is imperative because radiological techniques alone are incapable of differentiating them from primary pancreatic tumours. Pancreatic metastases occur in the relative end stage of small cell lung cancer. The main complications of these lesions, although rare, are acute pancreatitis and obstructive jaundice. Early chemotherapy can provide a survival benefit even in patients with mild acute pancreatitis or extrahepatic biliary obstruction

  20. Minimally Invasive Esophagectomy for Cancer -Short Up-to-Date

    Directory of Open Access Journals (Sweden)

    Radu Mircea Neagoe

    2014-07-01

    Full Text Available Surgery remains the main treatment for localized resectable esophageal cancer. Open esophagectomy is still the standard surgical approach for esophageal cancer but it has a lower patient satisfaction when compared with other treatment options. In the era of “key-hole” surgeries, minimally invasive esophagectomy (MIE stands as a solution to improve the results after standard open esophagectomies. The aim of the present paper is to provide a short update regarding the minimally invasive esophagectomy, with special emphasis on its indications, results and current controversies.

  1. Short Inverted Repeats Are Hotspots for Genetic Instability: Relevance to Cancer Genomes

    Directory of Open Access Journals (Sweden)

    Steve Lu

    2015-03-01

    Full Text Available Analyses of chromosomal aberrations in human genetic disorders have revealed that inverted repeat sequences (IRs often co-localize with endogenous chromosomal instability and breakage hotspots. Approximately 80% of all IRs in the human genome are short (<100 bp, yet the mutagenic potential of such short cruciform-forming sequences has not been characterized. Here, we find that short IRs are enriched at translocation breakpoints in human cancer and stimulate the formation of DNA double-strand breaks (DSBs and deletions in mammalian and yeast cells. We provide evidence for replication-related mechanisms of IR-induced genetic instability and a novel XPF cleavage-based mechanism independent of DNA replication. These discoveries implicate short IRs as endogenous sources of DNA breakage involved in disease etiology and suggest that these repeats represent a feature of genome plasticity that may contribute to the evolution of the human genome by providing a means for diversity within the population.

  2. Short-course palliative radiotherapy for uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Hyun; Lee, Ju Hye; Ki, Yong Kan; Kim, Won Taek; Park, Dahl; Kim, Dong Won [Dept. of Radiation Oncology, Biomedical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of); Nam, Ji Ho; Jeon, Sang Ho [Dept. of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2013-12-15

    The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer. Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions. The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity. Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.

  3. Short-Term Prognostic Index for Breast Cancer: NPI or Lpi

    Directory of Open Access Journals (Sweden)

    V. Van Belle

    2011-01-01

    Full Text Available Axillary lymph node involvement is an important prognostic factor for breast cancer survival but is confounded by the number of nodes examined. We compare the performance of the log odds prognostic index (Lpi, using a ratio of the positive versus negative lymph nodes, with the Nottingham Prognostic Index (NPI for short-term breast cancer specific disease free survival. A total of 1818 operable breast cancer patients treated in the University Hospital of Leuven between 2000 and 2005 were included. The performance of the NPI and Lpi were compared on two levels: calibration and discrimination. The latter was evaluated using the concordance index (cindex, the number of patients in the extreme groups, and difference in event rates between these. The NPI had a significant higher cindex, but a significant lower percentage of patients in the extreme risk groups. After updating both indices, no significant differences between NPI and Lpi were noted.

  4. Stakeholder Involvement in Decision Making: A Short Guide to Issues, Approaches and Resources

    International Nuclear Information System (INIS)

    Radioactive waste management is embedded in broader societal issues such as the environment, risk management, energy, health policy and sustainability. In all these fields, there is an increasing demand for public involvement and engagement. This 2015 update of Stakeholder Involvement Techniques: Short Guide and Annotated Bibliography, assists practitioners and non-specialists by outlining the steps and issues associated with stakeholder involvement in decision making and by facilitating access to useful online resources (handbooks, toolboxes and case studies). The updated guide has been considerably enriched with experiences since 2004 and includes extensive references to the literature. It is published alongside the release of an online annotated bibliography that will be updated regularly. (authors)

  5. Associations between successful palliative cancer pathways and community nurse involvement

    DEFF Research Database (Denmark)

    Neergaard, Mette Asbjoern; Vedsted, Peter; Olesen, Frede;

    2009-01-01

    ABSTRACT: BACKGROUND: Most terminally ill cancer patients and their relatives wish that the patient dies at home. Community nurses (CNs) are often frontline workers in the patients' homes and CN involvement may be important in attaining successful palliative pathways at home.The aim of the present...... were used to obtain data on CNs' efforts, GP-questionnaires were used to obtain data on pathway characteristics and relatives answered questionnaires to evaluate the palliative pathway at home. Questionnaires addressed the palliative pathway of a total of 599 deceased cancer patients. Associations...

  6. Nanotoxicology and Metalloestrogens: Possible Involvement in Breast Cancer

    Directory of Open Access Journals (Sweden)

    David R. Wallace

    2015-10-01

    Full Text Available As the use of nanotechnology has expanded, an increased number of metallic oxides have been manufactured, yet toxicology testing has lagged significantly. Metals used in nano-products include titanium, silicon, aluminum, silver, zinc, cadmium, cobalt, antimony, gold, etc. Even the noble metals, platinum and cerium, have been used as a treatment for cancer, but the toxicity of these metals is still unknown. Significant advances have been made in our understanding and treatment of breast cancer, yet millions of women will experience invasive breast cancer in their lifetime. The pathogenesis of breast cancer can involve multiple factors; (1 genetic; (2 environmental; and (3 lifestyle-related factors. This review focuses on exposure to highly toxic metals, (“metalloestrogens” or “endocrine disruptors” that are used as the metallic foundation for nanoparticle production and are found in a variety of consumer products such as cosmetics, household items, and processed foods, etc. The linkage between well-understood metalloestrogens such as cadmium, the use of these metals in the production of nanoparticles, and the relationship between their potential estrogenic effects and the development of breast cancer will be explored. This will underscore the need for additional testing of materials used in nano-products. Clearly, a significant amount of work needs to be done to further our understanding of these metals and their potential role in the pathogenesis of breast cancer.

  7. Involvement of chemokine receptors in breast cancer metastasis

    Science.gov (United States)

    Müller, Anja; Homey, Bernhard; Soto, Hortensia; Ge, Nianfeng; Catron, Daniel; Buchanan, Matthew E.; McClanahan, Terri; Murphy, Erin; Yuan, Wei; Wagner, Stephan N.; Barrera, Jose Luis; Mohar, Alejandro; Verástegui, Emma; Zlotnik, Albert

    2001-03-01

    Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1α and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

  8. Breast cancer with axillary lymph node involvement; Cancer du sein avec atteinte ganglionnaire axillaire

    Energy Technology Data Exchange (ETDEWEB)

    Belaid, A.; Kanoun, S.; Kallel, A.; Ghorbel, I.; Azoury, F.; Heymann, S.; Marsiglia, H.; Bourgier, C. [Departement de radiotherapie, Unite fonctionnelle de Senologie, institut Gustave-Roussy, 94 - Villejuif (France); Belaid, A.; Ghorbel, I. [Service de radiotherapie Carcinologique, institut Salah-Azaiez, Tunis (Tunisia); Kanoun, S. [Service de radiotherapie, hopital Farhat-Hached, Sousse (Tunisia); Kallel, A. [dUnite de radiotherapie, clinique Ennasr (Tunisia); Pichenot, C.; Verstraet, R. [Departement de physique, institut Gustave-Roussy, 94 - Villejuif (France); Marsiglia, H. [Universite de Florence (Italy)

    2010-07-01

    Breast cancer is the most frequent cancer of women in western countries. There are one million new cases per year in the world which represents 22% of all female cancers, and more than 370.000 deaths due to breast cancer per year (14% of cancer mortality). More than half of breast cancers are associated with axillary nodal involvement. Post-operative radiation therapy (XRT) is a crucial part of locoregional treatment in axillary nodal involvement breast cancer owing to a 15-years risk reduction of locoregional recurrence of 70% and to a 5.4% risk reduction of specific mortality. In 3D-conformal irradiation in such breast cancers, target volumes are chest wall when mastectomy was performed or breast and boost of tumor bed in case of breast conservative surgery, and supra-clavicular and/or axillary and/or internal mammary node areas. The main organs at risk are ipsilateral lung, heart and brachial plexus. The aim of this article is to describe epidemiologic, radio anatomic and prognostic features of axillary nodal involvement breast cancer and to propose guidelines for 3D-conformal treatment planning in locally advanced breast cancers. This review is illustrated by a case report. (authors)

  9. Short- and long-term memory: differential involvement of neurotransmitter systems and signal transduction cascades

    Directory of Open Access Journals (Sweden)

    MÔNICA R.M. VIANNA

    2000-09-01

    Full Text Available Since William James (1890 first distinguished primary from secondary memory, equivalent to short- and long-term memory, respectively, it has been assumed that short-term memory processes are in charge of cognition while long-term memory is being consolidated. From those days a major question has been whether short-term memory is merely a initial phase of long-term memory, or a separate phenomena. Recent experiments have shown that many treatments with specific molecular actions given into the hippocampus and related brain areas after one-trial avoidance learning can effectively cancel short-term memory without affecting long-term memory formation. This shows that short-term memory and long-term memory involve separate mechanisms and are independently processed. Other treatments, however, influence both memory types similarly, suggesting links between both at the receptor and at the post-receptor level, which should not be surprising as they both deal with nearly the same sensorimotor representations. This review examines recent advances in short- and long-term memory mechanisms based on the effect of intra-hippocampal infusion of drugs acting upon neurotransmitter and signal transduction systems on both memory types.

  10. Ratios of involved nodes in early breast cancer

    International Nuclear Information System (INIS)

    The number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that the proportion of node-positive lymph nodes (or a function thereof) is a much better predictor of survival than the number of excised and node-positive lymph nodes, alone or together. The data were abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results (SEER) program of women diagnosed with nonmetastatic T1–T2 primary breast carcinoma between 1988 and 1997, in whom axillary node dissection was performed. The end-point was death from breast cancer. Cox models based on different expressions of nodal involvement were compared using the Nagelkerke R2 index (R2N). Ratios were modeled as percentage and as log odds of involved nodes. Log odds were estimated in a way that avoids singularities (zero values) by using the empirical logistic transform. In node-negative cases both the number of nodes excised and the log odds were significant, with hazard ratios of 0.991 (95% confidence interval 0.986–0.997) and 1.150 (1.058–1.249), respectively, but without improving R2N. In node-positive cases the hazard ratios were 1.003–1.088 for the number of involved nodes, 0.966–1.005 for the number of excised nodes, 1.015–1.017 for the percentage, and 1.344–1.381 for the log odds. R2N improved from 0.067 (no nodal covariate) to 0.102 (models based on counts only) and to 0.108 (models based on ratios). Ratios are simple optimal predictors, in that they provide at least the same prognostic value as the more traditional staging based on counting of involved nodes, without replacing them with a needlessly complicated alternative. They can be viewed as a per patient standardization in which the number of involved nodes is standardized to the

  11. Involvement of patients with lung and gynecological cancer and their relatives in psychosocial cancer rehabilitation

    DEFF Research Database (Denmark)

    Hoeck, Bente; Ledderer, Loni; Hansen, Helle Ploug

    2015-01-01

    INTRODUCTION: Getting cancer is stressful for most patients and their relatives, and research has shown that psychosocial support is needed. Still, cancer care fails to appropriately address psychosocial problems associated with cancer. Research on this topic is often seen from the perspective of...... either the patient or the relative, even though it is suggested that psychosocial support is beneficial for the patient and the relative as a pair. Furthermore, research on the need for psychosocial support rarely involves patients with gynecological and lung cancer and their relatives, even though they...... included in the review. The studies were divided into two main categories: (1) studies focusing on needs for psychosocial support; and (2) studies focusing on interventions. The needs studies were analyzed, and three themes emerged: the needs of the patient and the significant other across the cancer...

  12. Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors

    OpenAIRE

    2008-01-01

    Abstract Introduction Prognostic subgroup classification of operable breast cancers using cDNA clustering of breast cancer-related genes resembles the classification based on the combined immunohistochemical (IHC) expression of the hormone and HER-2 receptors. We here report the short-term disease-free interval (DFI) of operable breast cancers by their joint hormone receptor/HER-2 phenotype. Patients and methods Short-term follow-up (FU) of ...

  13. A case of breast cancer involving a ventriculoperitoneal shunt.

    Science.gov (United States)

    Kamei, Mirei; Kikuchi, Nobuyuki; Ichimura, Homare; Chujo, Masao; Takahashi, Yoshiaki; Sugio, Kenji

    2016-12-01

    An 84-year-old woman was examined for an enlargement of an induration in the left breast. A ventriculoperitoneal shunt had been placed for postoperative normal pressure hydrocephalus of a cerebral hemorrhage, and it had penetrated the mass according to the computed tomography findings. Breast cancer was diagnosed after a close examination; however, close observation was selected because her family rejected treatment. She developed somnolence 7 months after the initial examination, and ventricular dilatation and expansion of the low-density region around the ventricle were noted on computed tomography, suggesting that the enlarged tumor had excluded the shunt and caused obstruction. The growth of breast carcinoma involving a shunt tube can be the cause of obstruction of a ventriculoperitoneal shunt. Our findings suggest that a breast lesion should be evaluated at both pre- and postoperation. PMID:26943684

  14. Multi drug resistance to cancer chemotherapy: Genes involved and blockers

    International Nuclear Information System (INIS)

    During the last three decades, important and considerable research efforts had been performed to investigate the mechanism through which cancer cells overcome the cytotoxic effects of a variety of chemotherapeutic drugs. Most of the previously published work has been focused on the resistance of tumor cells to those anticancer drugs of natural source. Multidrug resistance (MDR) is a cellular cross-resistance to a broad spectrum of natural products used in cancer chemotherapy and is believed to be the major cause of the therapeutic failures of the drugs belonging to different naturally obtained or semisynthetic groups including vinca alkaloids, taxans, epipodophyllotoxins and certain antibiotics. This phenomenon results from overexpression of four MDR genes and their corresponding proteins that act as membrane-bound ATP consuming pumps. These proteins mediate the efflux of many structurally and functionally unrelated anticancer drugs of natural source. MDR may be intrinsic or acquired following exposure to chemotherapy. The existence of intrinsically resistant tumor cell clone before and following chemotherapeutic treatment has been associated with a worse final outcome because of increased incidence of distant metasis. In view of irreplaceability of natural product anticancer drugs as effective chemotherapeutic agents, and in view of MDR as a major obstacle to successful chemotherapy, this review is aimed to highlight the genes involved in MDR, classical MDR blockers and gene therapy approaches to overcome MDR. (author)

  15. Lentivirus-Mediated Short-Hairpin RNA Targeting Protein Phosphatase 4 Regulatory Subunit 1 Inhibits Growth in Breast Cancer

    OpenAIRE

    Qi, Yuying; Hu, Tinghui; Li, Kai; Ye, Renqing; Ye, Zuodong

    2015-01-01

    Purpose Protein phosphatase 4 regulatory subunit 1 (PP4R1), as an interaction partner of the catalytic serine/threonine-protein phosphatase 4 catalytic subunit has been shown to involve in cellular processes and nuclear factor κB signaling. However, the functions of PP4R1 in human breast cancers remain unclear. This study is designed to explore the effect of PP4R1 knockdown on the biological characteristics of breast cancer cells. Methods A lentivirus-mediated short hairpin RNA (shRNA) was de...

  16. Upfront systemic chemotherapy and preoperative short-course radiotherapy with delayed surgery for locally advanced rectal cancer with distant metastases

    International Nuclear Information System (INIS)

    Choosing the most effective approach for treating rectal cancer with mesorectal fascia (MRF) involvement or closeness and synchronous distant metastases is a current clinical challenge. The aim of this retrospective study was to determine if upfront systemic chemotherapy and short-course radiotherapy (RT) with delayed surgery enables R0 resection. Between March 2009 and October 2009, six patients were selected for upfront chemotherapy and short-course RT (5 × 5 Gy) with delayed surgery. The patients had locally advanced primary tumors with MRF involvement or closeness, as well as synchronous and potentially resectable distant metastases. Chemotherapy was administered to five patients between the end of the RT and surgery. All patients underwent total mesorectal excision (TME). The median patient age was 54 years (range 39-63). All primary and metastatic lesions were resected simultaneously. The median duration between short-course RT and surgery was 13 weeks (range, 7-18). R0 resection of rectal lesions was achieved in 5 patients. One patient, who had a very low-lying tumor, had an R1 resection. The median follow-up duration for all patients was 16.7 months (range, 15.5-23.5). One patient developed liver metastasis at 15.7 months. There have been no local recurrences or deaths. Upfront chemotherapy and short course RT with delayed surgery is a valuable alternative treatment approach for patients with MRF involvement or closeness of rectal cancer with distant metastases

  17. Syncytin is involved in breast cancer-endothelial cell fusions

    OpenAIRE

    Bjerregaard, Bolette; Holck, S.; Christensen, I. J.; Larsson, Lars-Inge

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to ex...

  18. Three-dimensional in vitro cancer models: a short review

    International Nuclear Information System (INIS)

    The re-creation of the tumor microenvironment including tumor–stromal interactions, cell–cell adhesion and cellular signaling is essential in cancer-related studies. Traditional two-dimensional (2D) cell culture and animal models have been proven to be valid in some areas of explaining cancerous cell behavior and interpreting hypotheses of possible mechanisms. However, a well-defined three-dimensional (3D) in vitro cancer model, which mimics tumor structures found in vivo and allows cell–cell and cell–matrix interactions, has gained strong interest for a wide variety of diagnostic and therapeutic applications. This communication attempts to provide a representative overview of applying 3D in vitro biological model systems for cancer related studies. The review compares and comments on the differences in using 2D models, animal models and 3D in vitro models for cancer research. Recent technologies to construct and develop 3D in vitro cancer models are summarized in aspects of modeling design, fabrication technique and potential application to biology, pathogenesis study and drug testing. With the help of advanced engineering techniques, the development of a novel complex 3D in vitro cancer model system will provide a better opportunity to understand crucial cancer mechanisms and to develop new clinical therapies. (topical review)

  19. Linking Genetic Counseling Content to Short-Term Outcomes in Individuals at Elevated Breast Cancer Risk

    OpenAIRE

    Kelly, Kimberly M.; Ellington, Lee; Schoenberg, Nancy; Agarwal, Parul; Jackson, Thomas; Dickinson, Stephanie; Abraham, Jame; Paskett, Electra D.; Leventhal, Howard; Andrykowski, Michael

    2014-01-01

    Few studies have linked actual genetic counseling content to short-term outcomes. Using the Self-regulation Model, the impact of cognitive and affective content in genetic counseling on short-term outcomes was studied in individuals at elevated risk of familial breast-ovarian cancer. Surveys assessed dependent variables: distress, perceived risk, and 6 knowledge measures (Meaning of Positive Test; Meaning of Negative Test; Personal Behavior; Practitioner Knowledge; Mechanisms of Cancer Inheri...

  20. In Vitro Evaluation of Biofield Treatment on Cancer Biomarkers Involved in Endometrial and Prostate Cancer Cell Lines

    OpenAIRE

    Trivedi, Mahendra Kumar

    2015-01-01

    Increasing cancer rates particularly in the developed world are associated with related lifestyle and environmental exposures. Combined immunotherapy and targeted therapies are the main treatment approaches in advanced and recurrent cancer. An alternate approach, energy medicine is increasingly used in life threatening problems to promote human wellness. This study aimed to investigate the effect of biofield treatment on cancer biomarkers involved in human endometrium and prostate cancer cell...

  1. A Rare Case: Gastric Cancer; Involving Primery Thoracal Vertebral Metastases

    Directory of Open Access Journals (Sweden)

    Harun Arslan

    2013-06-01

    Full Text Available Primery bone metastases rarely occur in gastric cancer. Bone metastases indicate that the prognosis is bad. In that article we present a case that is diagnosed as a gastric cancer with primary bone metasteses that caused pathologic thoracal vertebral fracture seenby computer ised tomography.

  2. A Rare Case: Gastric Cancer; Involving Primery Thoracal Vertebral Metastases

    OpenAIRE

    Harun Arslan

    2013-01-01

    Primery bone metastases rarely occur in gastric cancer. Bone metastases indicate that the prognosis is bad. In that article we present a case that is diagnosed as a gastric cancer with primary bone metasteses that caused pathologic thoracal vertebral fracture seenby computer ised tomography.

  3. Risk factors of circumferential resection margin involvement in the patients with extraperitoneal rectal cancer

    OpenAIRE

    Oh, Sung Jin; Shin, Jin Yong

    2012-01-01

    Purpose Currently, circumferential resection margins (CRM) are used as a clinical endpoint in studies on the prognosis of rectal cancer. Although the concept of a circumferential resection margin in extraperitoneal rectal cancer differs from that in intraperitoneal rectal cancer due to differences in anatomical and biologic behaviors, previous reports have provided information on CRM involvement in all types of rectal cancer including intraperitoneal lesions. Therefore, the aim of this study ...

  4. Therapeutic cancer vaccines and combination immunotherapies involving vaccination

    OpenAIRE

    Nguyen T; Urban J.; Kalinski P

    2014-01-01

    Trang Nguyen,1 Julie Urban,1 Pawel Kalinski1–5 1Department of Surgery, 2Department of Immunology, 3Department of Microbiology and Infectious Disease, 4Department of Bioengineering, University of Pittsburgh, 5University of Pittsburgh Cancer Institute, Pittsburgh, PA, USAAbstract: Recent US Food and Drug Administration approvals of Provenge® (sipuleucel-T) as the first cell-based cancer therapeutic factor and ipilimumab (Yervoy®/anticytotoxic T-lymphocyte antigen-4) as the first &...

  5. Involvement of tumor acidification in brain cancer pathophysiology

    OpenAIRE

    AvinashHonasoge

    2013-01-01

    Gliomas, primary brain cancers, are characterized by remarkable invasiveness and fast growth. While they share many qualities with other solid tumors, gliomas have developed special mechanisms to convert the cramped brain space and other limitations afforded by the privileged central nervous system into pathophysiological advantages. In this review we discuss gliomas and other primary brain cancers in the context of acid-base regulation and interstitial acidification; namely, how the altered ...

  6. Nanotoxicology and Metalloestrogens: Possible Involvement in Breast Cancer

    OpenAIRE

    Wallace, David R.

    2015-01-01

    As the use of nanotechnology has expanded, an increased number of metallic oxides have been manufactured, yet toxicology testing has lagged significantly. Metals used in nano-products include titanium, silicon, aluminum, silver, zinc, cadmium, cobalt, antimony, gold, etc. Even the noble metals, platinum and cerium, have been used as a treatment for cancer, but the toxicity of these metals is still unknown. Significant advances have been made in our understanding and treatment of breast cancer...

  7. The Prognostic Value of Circumferential Resection Margin Involvement in Patients with Extraperitoneal Rectal Cancer.

    Science.gov (United States)

    Shin, Dong Woo; Shin, Jin Yong; Oh, Sung Jin; Park, Jong Kwon; Yu, Hyeon; Ahn, Min Sung; Bae, Ki Beom; Hong, Kwan Hee; Ji, Yong Il

    2016-04-01

    The prognostic influence of circumferential resection margin (CRM) status in extraperitoneal rectal cancer probably differs from that of intraperitoneal rectal cancer because of its different anatomical and biological behaviors. However, previous reports have not provided the data focused on extraperitoneal rectal cancer. Therefore, the aim of this study was to examine the prognostic significance of the CRM status in patients with extraperitoneal rectal cancer. From January 2005 to December 2008, 248 patients were treated for extraperitoneal rectal cancer and enrolled in a prospectively collected database. Extraperitoneal rectal cancer was defined based on tumors located below the anterior peritoneal reflection, as determined intraoperatively by a surgeon. Cox model was used for multivariate analysis to examine risk factors of recurrence and mortality in the 248 patients, and multivariate logistic regression analysis was performed to identify predictors of recurrence and mortality in 135 patients with T3 rectal cancer. CRM involvement for extraperitoneal rectal cancer was present in 29 (11.7%) of the 248 patients, and was the identified predictor of local recurrence, overall recurrence, and death by multivariate Cox analysis. In the 135 patients with T3 cancer, CRM involvement was found to be associated with higher probability of local recurrence and mortality. In extraperitoneal rectal cancer, CRM involvement is an independent risk factor of recurrence and survival. Based on the results of the present study, it seems that CRM involvement in extraperitoneal rectal cancer is considered an indicator for (neo)adjuvant therapy rather than conventional TN status. PMID:27097629

  8. Recent discoveries concerning the involvement of transcription factors from the Grainyhead-like family in cancer.

    Science.gov (United States)

    Mlacki, Michal; Kikulska, Agnieszka; Krzywinska, Ewa; Pawlak, Magdalena; Wilanowski, Tomasz

    2015-11-01

    The Grainyhead-like (GRHL) family of transcription factors has three mammalian members, which are currently termed Grainyhead-like 1 (GRHL1), Grainyhead-like 2 (GRHL2), and Grainyhead-like 3 (GRHL3). These factors adopt a DNA-binding immunoglobulin fold homologous to the DNA-binding domain of key tumor suppressor p53. Their patterns of expression are tissue and developmentally specific. Earlier studies of the GRHL proteins focused on their functions in mammalian development. In recent years, these factors have been linked to many different types of cancer: squamous cell carcinoma of the skin, breast cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, clear cell renal cell carcinoma, neuroblastoma, prostate cancer, and cervical cancer. The roles of GRHL proteins in these various types of cancer are complex, and in some cases appear to be contradictory: they can serve to promote cancer development, or they may act as tumor suppressors, depending on the particular GRHL protein involved and on the cancer type. The reasons for obvious discrepancies in results from different studies remain unclear. At the molecular level, the GRHL transcription factors regulate the expression of genes whose products are involved in cellular proliferation, differentiation, adhesion, and polarity. We herein review the roles of GRHL proteins in cancer development, and we critically examine relevant molecular mechanisms, which were proposed by different authors. We also discuss the significance of recent discoveries implicating the involvement of GRHL transcription factors in cancer and highlight potential future applications of this knowledge in cancer treatment. PMID:26069269

  9. The decalog of long non-coding RNA involvement in cancer diagnosis and monitoring.

    Science.gov (United States)

    Kunej, Tanja; Obsteter, Jana; Pogacar, Ziva; Horvat, Simon; Calin, George Adrian

    2014-12-01

    Long non-coding RNAs (lncRNAs) are transcripts without protein-coding capacity; initially regarded as "transcriptional noise", lately they have emerged as essential factors in both cell biology and mechanisms of disease. In this article, we present basic knowledge of lncRNA molecular mechanisms, associated physiological processes and cancer association, as well as their diagnostic and therapeutic value in the form of a decalog: (1) Non-coding RNAs (ncRNAs) are transcripts without protein-coding capacity divided by size (short and long ncRNAs), function (housekeeping RNA and regulatory RNA) and direction of transcription (sense/antisense, bidirectional, intronic and intergenic), containing a broad range of molecules with diverse properties and functions, such as messenger RNA, transfer RNA, microRNA and long non-coding RNAs. (2) Long non-coding RNAs are implicated in many molecular mechanisms, such as transcriptional regulation, post-transcriptional regulation and processing of other short ncRNAs. (3) Long non-coding RNAs play an important role in many physiological processes such as X-chromosome inactivation, cell differentiation, immune response and apoptosis. (4) Long non-coding RNAs have been linked to hallmarks of cancer: (a) sustaining proliferative signaling; (b) evading growth suppressors; (c) enabling replicative immortality; (d) activating invasion and metastasis; (e) inducing angiogenesis; (f) resisting cell death; and (g) reprogramming energy metabolism. (5) Regarding their impact on cancer cells, lncRNAs are divided into two groups: oncogenic and tumor-suppressor lncRNAs. (6) Studies of lncRNA involvement in cancer usually analyze deregulated expression patterns at the RNA level as well as the effects of single nucleotide polymorphisms and copy number variations at the DNA level. (7) Long non-coding RNAs have potential as novel biomarkers due to tissue-specific expression patterns, efficient detection in body fluids and high stability. (8) LncRNAs serve

  10. Semiquantitative diagnosis of cancer using short-lived radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Tomio; Oriuchi, Noboru; Endo, Keigo [Gunma Univ., Maebashi (Japan). School of Medicine

    1997-03-01

    The accuracy and usefulness of semiquantitative diagnoses of SPECT using radiolabeled monoclonal antibodies in patients with colorectal cancer and PET using FDG in patients with recurrent lung cancer were investigated. The tumor to normal tissue count ratio (T/N ratio) was determined with SPECT and compared with the same index (T/N ratio) obtained by measuring radioactivity in tumor and normal tissue of the resected specimens. Significant correlation between SPECT T/N ratios and tissue T/N ratio was observed (r=0.92, p<0.001, n=8). In PET study, standardized uptake value (SUV) was obtained with PET images and assessed the difference in SUV between recurrent tumors and noncancerous lesions. The relationship between the SUV threshold and diagnostic accuracy in differentiating recurrent tumors from post-treatment changes was also assessed. The maximum SUV in recurrent tumor ranged from 3.0 to 25.8 with a mean {+-} s.d. of 11.2 {+-} 5.7 (n=16) and in the noncancerous lesion ranged from 2.0 to 7.5 with a mean {+-} s.d. of 3.5 {+-} 1.8 (n=9). The SUV was significantly higher in the recurrent cancer (P<0.0001). A threshold SUV of 5.0 provided optimal diagnostic accuracy (sensitivity 93.8%, specificity 88.9%, accuracy 92.0%). It was superior to visual interpretation of FDG PET (sensitivity 100%, specificity 55.6%, accuracy 84%). In conclusion, semiquantitative diagnoses with SPECT using radiolabeled monoclonal antibody and PET using FDG were accurate and useful in detecting malignant tumors. (author)

  11. Polyphenols: Key Issues Involved in Chemoprevention of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Sebastiano Cimino

    2012-01-01

    Full Text Available Prostate cancer is is the most common solid neoplasm and it is now recognized as one of the most important medical problems facing the male population. Due to its long latency and its identifiable preneoplastic lesions, prostate cancer is an ideal target tumor for chemoprevention. Different compounds are available and certainly polyphenols represent those with efficacy against prostate cancer. This review take a look at activity and properties of major polyphenolic substances, such as epigallocatechin-3-gallate, curcumin, resveratrol and the flavonoids quercetin and genistein. Although the current studies are limited, mechanisms of action of polyphenols added with the lack of side effects show a a start for future strategies in prostate chemoprevention.

  12. Measurement properties of PROMIS Sleep Disturbance short forms in a large, ethnically diverse cancer cohort

    OpenAIRE

    Jensen, Roxanne E.; King-Kallimanis, Bellinda L.; Eithne Sexton; Reeve, Bryce B.; Moinpour, Carol M.; Potosky, Arnold L.; Tania Lobo; Teresi, Jeanne A.

    2016-01-01

    AIMS: To evaluate model fit, differential item function (DIF), and construct validity of select short forms from the PROMIS® Sleep Disturbance item bank. METHODS: We recruited cancer survivors who were between 6 - 13 months post diagnosis (n = 4,956), as part of the Measuring Your Health (MY-Health) study. We measured sleep disturbance using 10 items commonly found in PROMIS Sleep Disturbance short forms (Sleep 4a, Sleep 6a, Sleep 8b), and which are frequently administered in computerized ...

  13. Influence of obesity on the short-term outcome of laparoscopic colectomy for colorectal cancer

    Directory of Open Access Journals (Sweden)

    Sakamoto Kazuhiro

    2007-01-01

    Full Text Available Purpose: Obesity has been generally associated with increased surgical risk. However, data on the outcome of laparoscopic colectomy in obese and non-obese patients are controversial. The aim of this study is to assess the short-term outcome of laparoscopic colectomy for colorectal cancer (CRC in obese patients as compared with non-obese patients. Materials and Methods: Sixty-nine patients who underwent laparoscopic anterior resection for CRC during the past six years were retrospectively evaluated. The patients with CRC involving the sigmoid or rectosigmoid colon and subjected to intracorporeal anastomosis were included in this study. They were divided into three groups according to body mass index (BMI: obese (BMI ≥ 28.0 kg/m 2 , pre-obese (BMI: 25.0-27.9 kg/m 2 and non-obese (BMI < 25.0 kg/m 2 . Results: Nine patients (13.0 % were obese, 11 patients (15.9% were pre-obese and 49 patients (71.1% were non-obese. Patient characteristics, such as age, gender, tumor location, previous laparotomy, were similar among the three groups. There were no significant differences in operative time, blood loss, intraoperative complications and conversion rates. Postoperative complications and duration of postoperative hospital stay were also similar among the three groups. However, two of the three patients in the pre-obese group had to be operated on again due to incarceration of the small bowel into a port site. Conclusions: Laparoscopic colectomy can be safely performed in obese patients with short-term results similar to those obtained in non-obese and pre-obese patients.

  14. Involvement of RDR6 in short-range intercellular RNA silencing in Nicotiana benthamiana

    OpenAIRE

    Cheng Qin; Nongnong Shi; Mei Gu; Hang Zhang; Bin Li; Jiajia Shen; Atef Mohammed; Eugene Ryabov; Chunyang Li; Huizhong Wang; Yule Liu; Toba Osman; Manu Vatish; Yiguo Hong

    2012-01-01

    In plants, non-cell autonomous RNA silencing spreads between cells and over long distances. Recent work has revealed insight on the genetic and molecular components essential for cell-to-cell movement of RNA silencing in Arabidopsis. Using a local RNA silencing assay, we report on a distinct mechanism that may govern the short-range (6–10 cell) trafficking of virus-induced RNA silencing from epidermal to neighbouring palisade and spongy parenchyma cells in Nicotiana benthamiana. This process ...

  15. Clinical outcome in 520 consecutive Danish rectal cancer patients treated with short course preoperative radiotherapy

    DEFF Research Database (Denmark)

    Jensen, L H; Altaf, R; Harling, H; Jensen, M; Laurberg, S; Muhic, A; Vestermark, L; Jakobsen, A; Bülow, S; Jess, Danish Colorectal Cancer Group, Per

    2010-01-01

    T3 or T4 and 41% of the local recurrences occurred in patients with a fixed tumour at surgery. CONCLUSION: This study confirms data from randomised studies that the short course 5 x 5 Gy regime is a feasible treatment for locally advanced rectal cancer even when applied in a population outside...

  16. Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

    Science.gov (United States)

    Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

    2016-01-01

    The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

  17. Translating Patient Involvement into Clinical Practice: An Example from Psychosocial Cancer Rehabilitation in Denmark

    DEFF Research Database (Denmark)

    Ledderer, Loni; Nissen, Nina

    We examine meanings and practices of patient involvement, using a psychosocial cancer rehabilitation intervention in Denmark as an example. Drawing on Scandinavian sociological institutionalism and the concepts of translation and editing, we analyse three contexts in which understandings and inte...

  18. Cadherins: The Superfamily Critically Involved in Breast Cancer.

    Science.gov (United States)

    Ashaie, Maeirah Afzal; Chowdhury, Ezharul Hoque

    2016-01-01

    Breast cancer, one of the leading causes of mortality and morbidity among females, is regulated in part by diverse classes of adhesion molecules one of which is known as cadherins. Located at adherens junctions, the members of this superfamily are responsible for upholding proper cell-cell adhesion. Cadherins possess diverse structures and functions and any alteration in their structures or functions causes impeding of normal mammary cells development and maintenance, thus leading to breast malignancy. E-, N-, P-, VE-, Proto-, desmosomal and FAT cadherins have been found to regulate breast cancer in positive as well as negative fashion, whereby both Ecadherin (CDH1) and N-cadherin (CDH2) contribute significantly towards transitioning from epithelial state to mesenchymal state (EMT) and enacting the abnormal cells to invade and metastasize nearby and distant tissues. Aberration in gene expression of cadherins can be either due to somatic or epigenetic silencing or via transcriptional factors. Besides other cadherins, E-cadherin which serves as hallmark of EMT is associated with several regulatory factors such as Snail, Slug, Twist, Zeb, KLF4, NFI, TBX2, SIX, b-Myb, COX-2, Arf6, FOXA2, GATA3 and SMAR1, which modulate E-cadherin gene transcription to promote or represses tumor invasion and colonization. Signaling molecules such as Notch, TGF-β, estrogen receptors, EGF and Wnt initiate numerous signaling cascades via these vital factors of cell programming, controlling expression of E-cadherin at transcriptional (mRNA) and protein level. Thus, interactions of cadherins with their roles in tumor suppression and oncogenic transformation can be beneficial in providing valuable insights for breast cancer diagnosis and therapeutics development. PMID:26825466

  19. Management of prostate cancer patients with lymph node involvement: A rapidly evolving paradigm

    OpenAIRE

    Créhange, Gilles; Chen, Chien Peter; Hsu, Charles C.; Kased, Norbert; Coakley, Fergus V.; Kurhanewicz, John; Roach, Mack

    2012-01-01

    Although widespread PSA screening has inevitably led to increased diagnosis of lower risk prostate cancer, the number of patients with nodal involvement at baseline remains high (nearly 40% of high risk patients initially staged cN0). These rates probably do not reflect the true incidence of prostate cancer with lymph node involvement among patients selected for external beam radiotherapy (EBRT), as patients selected for surgery often have more favorable prognostic features. At many instituti...

  20. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    Directory of Open Access Journals (Sweden)

    Deniz Arslan

    2014-01-01

    Full Text Available Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding identified in BM metastasis of solid organ cancers, and isolated thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2 is positive in gastric cancer at a rate of 7–34%. Here, we have presented our HER-2 positive gastric cancer incident which presented with BM and cutaneous metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG involvement except bone metastases.

  1. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    Science.gov (United States)

    Arslan, Deniz; Tatlı, Ali Murat; Goksu, Sema Sezgin; Başsorgun, Cumhur İbrahim; Coskun, Hasan Senol; Bozcuk, Hakan; Savaş, Burhan

    2014-01-01

    Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM) and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding identified in BM metastasis of solid organ cancers, and isolated thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2) is positive in gastric cancer at a rate of 7–34%. Here, we have presented our HER-2 positive gastric cancer incident which presented with BM and cutaneous metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG) involvement except bone metastases. PMID:25045559

  2. Loss of heterozigosity in the short arm of human chromosome 3 in sporadic lung cancer

    Directory of Open Access Journals (Sweden)

    Lina Marcela Barrera

    2010-12-01

    Full Text Available Introduction: Loss of Heterozygocity (LOH in the short arm of human chromosome 3 (3p is a frequent event in different types of sporadic tumors, including lung cancer (LC.Aim: To determine 3p LOH in LC samples using 17 microsatellite markers.Methodology: In a pilot study on volunteers, thirteen LC biopsies (tumor tissue and 4 ml of blood (normal tissue from the same patient were collected. DNA extraction and Polymerase Chain Reaction (PCR were performed with 17 microsatellite markers to analyze LOH. Amplified fragments were run on 6% denaturalizing polyacrilamide gels and were visualized by using silver stain. Descriptive analysis was performed for each region on the 3p chromosome.Results: All tumors were informative for one or more of the analyzed markers. LOH was found in one or more loci in eleven samples (84.6%. The markers with major LOH were UBE1L (23.1%, D3S1317, D3S1300, D3S1284, D3S1274, D3S3049, and D3S1577 (15.4%. Three samples showed microsatellite instability (changes in the length of the microsatellite in different loci. The percentages of LOH for the regions of 3p were: 17.6 % for 3p24-25, 11.62% for 3p21-22, 20% for 3p13-14, and 18.42% for the 3p12 region.Conclusions: Chromosomal regions with allelic loss were identified where probably other GSTs involved in the development of the LC are localized. It should increases sample size and marker number in order to narrow a minimal region and to identify a unknown gene involved in LC.

  3. Cdc20 and securin overexpression predict short-term breast cancer survival

    Science.gov (United States)

    Karra, H; Repo, H; Ahonen, I; Löyttyniemi, E; Pitkänen, R; Lintunen, M; Kuopio, T; Söderström, M; Kronqvist, P

    2014-01-01

    Background: Cdc20 is an essential component of cell division and responsible for anaphase initiation regulated by securin degradation. Cdc20 function is strongly regulated by the spindle assembly checkpoint to ensure the timely separation of sister chromatids and integrity of the genome. We present the first results on Cdc20 in a large clinical breast cancer material. Methods: The study was based on 445 breast cancer patients with up to 20 years of follow-up (mean 10.0 years). DNA content was determined by image cytometry on cell imprints, and Cdc20 and securin immunohistochemistry on tissue microarrays of breast cancer tissue. Results: In our results, high Cdc20 and securin expression was associated with aneuploid DNA content. In prognostic analyses, high Cdc20 immunoexpression alone and in combination with high securin immunoexpression indicated aggressive course of disease and up to 6.8-fold (P<0.001) risk of breast cancer death. Particularly, high Cdc20 and securin immunoexpression identified a patient subgroup with extremely short, on average 2.4 years, breast cancer survival and triple-negative breast cancer (TNBC) subtype. Conclusions: We report for the first time the association of high Cdc20 and securin immunoexpression with extremely poor outcome of breast cancer patients. Our experience indicates that Cdc20 and securin are promising candidates for clinical applications in breast cancer prognostication, especially in the challenging prognostic decisions of TNBC. PMID:24853182

  4. Identification of genes involved in breast cancer and breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Apostolou P

    2015-07-01

    Full Text Available Panagiotis Apostolou, Maria Toloudi, Ioannis Papasotiriou Research and Development Department, Research Genetic Cancer Centre Ltd, Florina, Greece Abstract: Breast cancer is the most frequent type of cancer in women. Great progress has been made in its treatment but relapse is common. One hypothesis to account for the high recurrence rates is the presence of cancer stem cells (CSCs, which have the ability to self-renew and differentiate into multiple malignant cell types. This study aimed to determine genes that are expressed in breast cancer and breast CSCs and to investigate their correlation with stemness. RNA was extracted from established breast cancer cell lines and from CSCs derived from five different breast cancer patients. DNA microarray analysis was performed and any upregulated genes were also studied in other cancer types, including colorectal and lung cancer. For genes that were expressed only in breast cancer, knockdown-based experiments were performed. Finally, the gene expression levels of stemness transcription factors were measured. The outcome of the analysis indicated a group of genes that were aberrantly expressed mainly in breast cancer cells with stemness properties. Knockdown experiments confirmed the impact of several of these on NANOG, OCT3/4, and SOX2 transcription factors. It seems that several genes that are not directly related with hormone metabolism and basic signal transduction pathways might have an important role in relapse and disease progression and, thus, can be targeted for new treatment approaches for breast cancer. Keywords: breast cancer, cancer stem cells, stemness, DNA microarray

  5. The Involvement of NRF2 in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Alison K. Bauer

    2013-01-01

    Full Text Available Nuclear factor, erythroid-derived 2, like 2 (NRF2 is a key regulator of antioxidants and cellular stress responses. The role of NRF2 in pulmonary neoplasia, a diverse disease for which few biomarkers exist, is complicated and appears to depend on several main factors including the existence of activating mutations in NRF2 and/or loss of function mutations in KEAP1 and the stage of carcinogenesis studied, particularly in the mouse models tested. Therapeutic strategies for lung cancer targeting NRF2 have observed mixed results, both anti- and protumorigenic effects; however, these differences seem to reflect the mutation status of NRF2 or KEAP1. In this paper, we will discuss the studies on human NRF2 and the mechanisms proposed, several mouse models using various mice deficient in NRF2, as well as xenograft models, and the chemotherapeutic strategies using the NRF2 pathway.

  6. Involvement of Toll-like receptors in acute radiation syndrome and radiation therapy for cancer

    International Nuclear Information System (INIS)

    Toll-like receptors (TLR) are one of pattern recognition receptors that are indispensable for antibacterial and antiviral immunity. After TLRs sense pathogen-derived components, they activate intracellular signaling pathways, which results in the induction of proinflammatory cytokines. Although it is well known that radiation therapy is one of effective cancer therapies, radiation affects immune system. Recent evidences show the involvement of TLR in acute radiation syndrome and radiation therapy for cancer. I summarize to date knowledge on the involvement of Toll-like receptors in acute radiation syndromes and radiation therapy for cancer, and discuss the effects of ionizing radiation on TLR of innate immune cells. (author)

  7. Identification of genes involved in breast cancer and breast cancer stem cells

    OpenAIRE

    Apostolou P; Toloudi M; Papasotiriou I

    2015-01-01

    Panagiotis Apostolou, Maria Toloudi, Ioannis Papasotiriou Research and Development Department, Research Genetic Cancer Centre Ltd, Florina, Greece Abstract: Breast cancer is the most frequent type of cancer in women. Great progress has been made in its treatment but relapse is common. One hypothesis to account for the high recurrence rates is the presence of cancer stem cells (CSCs), which have the ability to self-renew and differentiate into multiple malignant cell types. This study aimed t...

  8. A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yanagihara Kazuyoshi

    2009-06-01

    Full Text Available Abstract Background Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS, which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells. Methods DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively. Results DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20 of gastric cancer cell lines (8–18-fold amplification and 4.7% (4/86 of primary gastric tumors (8–50-fold amplification. KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild

  9. A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

    International Nuclear Information System (INIS)

    Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells. DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively. DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification). KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild-type KRAS resulted in the inhibition of cell growth and

  10. Statistical models for predicting number of involved nodes in breast cancer patients

    OpenAIRE

    Dwivedi, Alok Kumar; Dwivedi, Sada Nand; Deo, Suryanarayana; Shukla, Rakesh; Kopras, Elizabeth

    2010-01-01

    Clinicians need to predict the number of involved nodes in breast cancer patients in order to ascertain severity, prognosis, and design subsequent treatment. The distribution of involved nodes often displays over-dispersion—a larger variability than expected. Until now, the negative binomial model has been used to describe this distribution assuming that over-dispersion is only due to unobserved heterogeneity. The distribution of involved nodes contains a large proportion of excess zeros (neg...

  11. Technique and short-term outcomes of single-port surgery for rectal cancer

    DEFF Research Database (Denmark)

    Bulut, O; Aslak, K K; Rosenstock, S

    2013-01-01

    Although conventional laparoscopic surgery is less traumatic than open surgery, it does cause tissue trauma and multiple scar formation. The size and number of ports determine the extent of the trauma. Single-port laparoscopic surgery is assumed to minimize and perhaps eliminate the potential...... adverse effects of conventional laparoscopy. The aim of this study was to examine short-term outcomes of single-port laparoscopic surgery for rectal cancer....

  12. Short-term pulmonary side-effects following radiation therapy in breast cancer

    OpenAIRE

    Lind, Pehr

    1999-01-01

    The purpose of this dissertation was to study the short-term pulmonary sideeffects following adjuvant radiotherapy for breast cancer in terms of clinical pulmonary complications, loss of pulmonary function and radiological abnormalities, and the association to irradiated lung volume and dose. Furthermore, we wanted to estimate the influence of covariates, e.g. age, sequential chemotherapy, concurrent tamoxifen treatment, smoking habits, pretreatment functional level and prem...

  13. Surgical Margins and Short-Term Results of Laparoscopic Total Mesorectal Excision for Low Rectal Cancer

    OpenAIRE

    Yang, Qingqiang; Xiu, Peng; Qi, Xiaolong; Yi, Guoping; Xu, Liang

    2013-01-01

    Background and Objectives: The confines of the narrow bony pelvis make laparoscopic surgery more challenging in the treatment of low rectal cancer. Macroscopic evaluation of the completeness of the mesorectum provides detailed information about the quality of surgery. This study was performed to observe the short-term outcomes and evaluate the macroscopic quality of specimens acquired from laparoscopic total mesorectal excision versus open total mesorectal excision in patients with low rectal...

  14. Short, sharp shock public health campaign had limited impact on raising awareness of laryngeal cancer.

    Science.gov (United States)

    Sethi, Neeraj; Rafferty, Amy; Rawnsley, Trisha; Jose, Jemy

    2016-09-01

    Laryngeal cancer has poorer outcomes if diagnosed at a later stage. Improving awareness could encourage earlier presentation and improve outcomes. This study aimed to evaluate a public engagement campaign targeted at raising awareness of laryngeal cancer. An epidemiological study identified high-risk populations in the region. A target population as well as a matched control population was selected. A cancer awareness survey combined with focus groups guided the design of a 3-month multimedia campaign. The survey was repeated post-campaign to evaluate the campaign effectiveness. The study identified populations with the highest rates of laryngeal cancer and late stage disease at presentation. The surveys performed revealed a limited effect of the multimedia campaign in raising awareness of the signs and symptoms of laryngeal cancer. Recall of the campaign also faded rapidly. This is the first public awareness campaign aimed at laryngeal cancer carried out in the UK. The results suggest that short-term campaigns have a limited effect and a more prolonged approach should be considered. PMID:26573156

  15. Short-course hypofrationated radiochemotherapy for unresectable locally advanced cancer of the base of tongue: Palliation only? A case report and short review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Kalogeridi, Maria-Aggeliki; Zygogianni, Anna; Kyrgias, George [University Hospital of Larissa, Larissa (Greece); Kouloulias, Vassilios [School of Health Sciences, Kapodistrian University of Athens, Athens (Greece)

    2014-06-15

    We present a case of unresectable cancer of the base of tongue treated with hypofractionated 3D conformal radiotherapy and concomitant chemotherapy. Based on the excellent tumour response in this radiotherapy regimen and international experience in short course treatments we shortly reviewed, we propose that this therapeutic approach could be considered in a curative setting for patients unsuitable for the a standard long course radiochemotherapy schedule.

  16. Short-course hypofrationated radiochemotherapy for unresectable locally advanced cancer of the base of tongue: Palliation only? A case report and short review of the literature

    International Nuclear Information System (INIS)

    We present a case of unresectable cancer of the base of tongue treated with hypofractionated 3D conformal radiotherapy and concomitant chemotherapy. Based on the excellent tumour response in this radiotherapy regimen and international experience in short course treatments we shortly reviewed, we propose that this therapeutic approach could be considered in a curative setting for patients unsuitable for the a standard long course radiochemotherapy schedule.

  17. Inhibition of DACH1 activity by short hairpin RNA represses cell proliferation and tumor invasion in pancreatic cancer.

    Science.gov (United States)

    Bu, Xiao-Na; Qiu, Chan; Wang, Chuan; Jiang, Zheng

    2016-08-01

    Cancer of the pancreas is one of the most lethal diseases worldwide. Better understanding of the molecular mechanisms involved in tumorigenesis is of great consequence to elevate the survival rate. Human Dachshund homologue 1 (DACH1) plays a controversial role in human malignancy progression with its expression being altered in a variety of cancers. Nevertheless, its functional roles and molecular mechanisms in pancreatic cancer remain unknown. The expression of DACH1 in pancreatic cancer cell lines and the ductal epithelial cells were evaluated both at mRNA and protein levels. Three pairs of siRNA targeting the DACH1 gene were designed and synthesized, double-stranded short hairpin RNA (shRNA) were annealed and inserted into pGenesil-1 vector, which was confirmed by enzymatic digestion and sequencing analyses. The successfully constructed recombinant plasmids were transfected into Capan-1 cells and our data indicated that knockdown of DACH1 gene expression showed strong correlation with repressing tumorigenesis. The proliferation of Capan-1 cells was significantly repressed as evaluated by CCK-8 and colony formation assays. Flow cymetry revealed that cell apoptosis was promoted in interference plasmid group compared with control groups (P0.05). Transwell assay validated the abilities of migration and invasion as being significantly reduced in pshRNA-DACH1 group. Furthermore, our study suggested that DACH1 expression regulates the pancreatic cancer cell apoptosis through interacting with Bcl-2 signaling axis, whereas it controls cell migration and invasion via epithelial-mesenchymal transition (EMT) process. PMID:27278537

  18. MicroRNAs: short non-coding players in cancer chemoresistance.

    Science.gov (United States)

    Donzelli, Sara; Mori, Federica; Biagioni, Francesca; Bellissimo, Teresa; Pulito, Claudio; Muti, Paola; Strano, Sabrina; Blandino, Giovanni

    2014-01-01

    Chemoresistance is one of the main problems in the therapy of cancer. There are a number of different molecular mechanisms through which a cancer cell acquires resistance to a specific treatment, such as alterations in drug uptake, drug metabolism and drug targets. There are several lines of evidence showing that miRNAs are involved in drug sensitivity of cancer cells in different tumor types and by different treatments. In this review, we provide an overview of the more recent and significant findings on the role of miRNAs in cancer cell drug resistance. In particular, we focus on specific miRNA mechanisms of action that in various steps lead from drug cell sensitivity to drug cell resistance. We also provide evidence on how miRNA profiling may unveil relevant predictive biomarkers for therapy outcomes. PMID:26056584

  19. Involvement of Ghrelin-Growth Hormone Secretagogue Receptor System in Pathoclinical Profiles of Digestive System Cancer

    Institute of Scientific and Technical Information of China (English)

    Zhigang WANG; Weigang WANG; Wencai QIU; Youben FAN; Jun ZHAO; Yu WANG; Qi ZHENG

    2007-01-01

    Ghrelin receptor has been shown to be expressed along the human gastrointestinal tract.Recent studies showed that ghrelin and a synthetic ghrelin receptor agonist improved weight gain and lean body mass retention in a rat model of cancer cachexia by acting on ghrelin receptor, that is, growth hormone secretagogue receptor (GHS-R). This study aims to explore the expression and the distribution of ghrelin receptor in human gastrointestinal tract cancers and to investigate the possible involvement of the ghrelin-GHS-R system in human digestive cancers. Surgical human digestive cancer specimens were obtained from various portions of the gastrointestinal tract from different patients. The expression of ghrelin receptor in these tissues was detected by tissue microarray technique. Our results showed that ghrelin receptor was expressed in cancers throughout the gastrointestinal tract, mainly in the cytoplasm of mucosal layer cells.Its expression level possibly correlated with organ type, histological grade, tumor-nodes-metastases stage,and nutrition status (weight loss) of the patients. For the first time, we identified the distribution of ghrelin receptor in digestive system cancers. Our results implied that the ghrelin-GHS-R system might be involved in the pathoclinical profiles of digestive cancers.

  20. TP53 polymorphisms are involved in inverse colorectal cancer comorbidity in Chinese schizophrenia patients

    Institute of Scientific and Technical Information of China (English)

    Sun Liming; Huang Guoxin; Zhao Leyong; Chen Xiaofen; Chen Wenjiao

    2015-01-01

    The inverse cancer comorbidity in schizophrenia patients may be related to the genetic factors ,involving the regu‐lation of apoptosis .The tumour suppressor gene TP53 ,involved in neural apoptosis ,is one of the potential candidate genes associat‐ed with schizophrenia which might reduce colorectal cancer risk .We recruited 270 schizophrenia patients and 312 colorectal cancer patients without schizophrenia .To examine the genetic association between schizophrenia and colorectal cancer ,we analysed eight SNPs (rs12951053 ,rs1625895 ,rs2909430 ,rs9895829 ,rs1042522 ,rs8079544 ,rs8064946 ,rs17806770) covering 14 .35 kb in the re‐gion of TP53 .We observed that one of the eight genetic polymorphisms showed statistically significant differences between the colo‐rectal cancer subjects and the schizophrenia subjects (rs12951053 ,P=0 .000 1 ,OR 1 .70 ,95% CI 1 .30-2 .23) .In addition ,the hap‐lotype of A‐G (rs12951053‐rs8064946) ,giving a global P=0 .001 8 ,was the most significant .Our data indicate that the polymor‐phisms of rs12951053 in TP53 confer reduced susceptibility to colorectal cancer and suggest a potential protective mechanism a‐gainst colorectal cancer in the schizophrenia patients of Han Chinese origin .

  1. Diameter of involved nerves is a valuable prognostic factor for gastric cancer.

    Science.gov (United States)

    Zhou, Zhi-hua; Zhang, Jian-dong; Zhao, Hai-Bin; Wu, Yao-yi

    2015-09-01

    The prognostic role of perineural invasion (PNI) in gastric cancer remains unclear. We hypothesized that the diameter of the tumor-involved nerves might be a useful indicator for prognosis. By labeling nerves and cancer cells in 204 cases of gastric cancer with single or double immunochemistry, we found that 146 cases were PNI positive and that 58 were PNI negative. For each case with PNI, the maximum diameter of the involved nerve was measured microscopically. Then, we correlated this parameter with the patients' 5-year overall survival, and receiver operating curves were used to determine the cutoff value. We found that the optimal cutoff value for predicting 5-year survival was 65 µm (sensitivity 76.9%, specificity 70.0%). Next, all 204 patients were classified into two groups as follows: Group A, PNI-positive cases in which the largest involved nerves were ≥65 µm in diameter (110 cases); Group B, PNI-positive cases in which the largest involved nerves were P˂65 µm and all PNI-negative cases (94 cases). Compared with Group A, Group B had a better 5-year survival (74.5% vs 27.3%) and a better 5-year disease-free survival (63.8% vs 23.6%). Multivariate analysis suggested that a ≥65 µm maximum diameter of the involved nerves was an independent risk factor for both recurrence (P˂0.001) and gastric cancer-related death (P˂0.001) within 5 years. However, if all patients were classified simply based on whether PNI existed (regardless of the nerve size), this did not provide more information than traditional clinicopathological variables. In conclusion, the presence of cancer-involved nerves with a diameter ≥65 µm was a valuable prognostic factor for gastric cancer. PMID:25791836

  2. Mutant p53 proteins alter cancer cell secretome and tumour microenvironment: Involvement in cancer invasion and metastasis.

    Science.gov (United States)

    Cordani, Marco; Pacchiana, Raffaella; Butera, Giovanna; D'Orazi, Gabriella; Scarpa, Aldo; Donadelli, Massimo

    2016-07-01

    An ever-increasing number of studies highlight the role of mutant p53 proteins in the alteration of cancer cell secretome and in the modification of tumour microenvironment, sustaining an invasive phenotype of cancer cell. The knowledge of the molecular mechanisms underlying the interplay between mutant p53 proteins and the microenvironment is becoming fundamental for the identification of both efficient anticancer therapeutic strategies and novel serum biomarkers. In this review, we summarize the novel findings concerning the regulation of secreted molecules by cancer cells bearing mutant TP53 gene. In particular, we highlight data from available literature, suggesting that mutant p53 proteins are able to (i) alter the secretion of enzymes involved in the modulation of extracellular matrix components; (ii) alter the secretion of inflammatory cytokines; (iii) increase the extracellular acidification; and (iv) regulate the crosstalk between cancer and stromal cells. PMID:27045472

  3. Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer

    Directory of Open Access Journals (Sweden)

    Dong Zhongyun

    2008-06-01

    Full Text Available Abstract Background Our previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor, and stimulates growth in prostate cancer cells. The current study is to determine a potential role of Vav3 oncogene in human breast cancer and impact on estrogen receptor a (ERα-mediated signaling axis. Methods Immunohistochemistry analysis was performed in 43 breast cancer specimens and western blot analysis was used for human breast cancer cell lines to determine the expression level of Vav3 protein. The impact of Vav3 on breast cancer cell growth was determined by siRNA knockdown of Vav3 expression. The role of Vav3 in ERα activation was examined in luciferase reporter assays. Deletion mutation analysis of Vav3 protein was performed to localize the functional domain involved in ERα activation. Finally, the interaction of Vav3 and ERα was assessed by GST pull-down analysis. Results We found that Vav3 was overexpressed in 81% of human breast cancer specimens, particularly in poorly differentiated lesions. Vav3 activated ERα partially via PI3K-Akt signaling and stimulated growth of breast cancer cells. Vav3 also potentiated EGF activity for cell growth and ERα activation in breast cancer cells. More interestingly, we found that Vav3 complexed with ERα. Consistent with its function for AR, the DH domain of Vav3 was essential for ERα activation. Conclusion Vav3 oncogene is overexpressed in human breast cancer. Vav3 complexes with ERα and enhances ERα activity. These findings suggest that Vav3 overexpression may aberrantly enhance ERα-mediated signaling axis and play a role in breast cancer development and/or progression.

  4. Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer

    International Nuclear Information System (INIS)

    Our previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor, and stimulates growth in prostate cancer cells. The current study is to determine a potential role of Vav3 oncogene in human breast cancer and impact on estrogen receptor a (ERα)-mediated signaling axis. Immunohistochemistry analysis was performed in 43 breast cancer specimens and western blot analysis was used for human breast cancer cell lines to determine the expression level of Vav3 protein. The impact of Vav3 on breast cancer cell growth was determined by siRNA knockdown of Vav3 expression. The role of Vav3 in ERα activation was examined in luciferase reporter assays. Deletion mutation analysis of Vav3 protein was performed to localize the functional domain involved in ERα activation. Finally, the interaction of Vav3 and ERα was assessed by GST pull-down analysis. We found that Vav3 was overexpressed in 81% of human breast cancer specimens, particularly in poorly differentiated lesions. Vav3 activated ERα partially via PI3K-Akt signaling and stimulated growth of breast cancer cells. Vav3 also potentiated EGF activity for cell growth and ERα activation in breast cancer cells. More interestingly, we found that Vav3 complexed with ERα. Consistent with its function for AR, the DH domain of Vav3 was essential for ERα activation. Vav3 oncogene is overexpressed in human breast cancer. Vav3 complexes with ERα and enhances ERα activity. These findings suggest that Vav3 overexpression may aberrantly enhance ERα-mediated signaling axis and play a role in breast cancer development and/or progression

  5. Involvement of epigenetic modifiers in the pathogenesis of testicular dysgenesis and germ cell cancer

    DEFF Research Database (Denmark)

    Lawaetz, Andreas C.; Almstrup, Kristian

    2015-01-01

    cell is a fetal germ cell that has been arrested during development due to testicular dysgenesis. CIS cells retain a fetal and open chromatin structure, and recently several epigenetic modifiers have been suggested to be involved in testicular dysgenesis in mice. We here review the possible involvement...... of epigenetic modifiers with a focus on jumonji C enzymes in the development of testicular dysgenesis and germ cell cancer in men....

  6. Efficacy of psychodynamic short-term psychotherapy for depressed breast cancer patients: study protocol for a randomized controlled trial

    OpenAIRE

    Zwerenz Rüdiger; Beutel Manfred E; Imruck Barbara H; Wiltink Jörg; Haselbacher Antje; Ruckes Christian; Schmidberger Heinz; Hoffmann Gerald; Schmidt Marcus; Köhler Uwe; Langanke Dagmar; Kortmann Rolf-Dieter; Kuhnt Susanne; Weißflog Gregor; Barthel Yvette

    2012-01-01

    Abstract Background There is a lack of psychotherapeutic trials of treatments of comorbid depression in cancer patients. Our study determines the efficacy of a manualized short-term psychodynamic psychotherapy and predictors of outcome by personality and quality of the therapeutic relationship. Methods/design Eligible breast cancer patients with comorbid depression are assigned to short-term psychodynamic psychotherapy (up to 20 + 5 sessions) or to treatment as usual (augmented by recommendat...

  7. Whereas Short-Term Facilitation Is Presynaptic, Intermediate-Term Facilitation Involves Both Presynaptic and Postsynaptic Protein Kinases and Protein Synthesis

    Science.gov (United States)

    Jin, Iksung; Kandel, Eric R.; Hawkins, Robert D.

    2011-01-01

    Whereas short-term plasticity involves covalent modifications that are generally restricted to either presynaptic or postsynaptic structures, long-term plasticity involves the growth of new synapses, which by its nature involves both pre- and postsynaptic alterations. In addition, an intermediate-term stage of plasticity has been identified that…

  8. Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shengzhang Lin

    2013-01-01

    Full Text Available Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990 with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153, a marker of the endoplasmic-reticulum-stress- (ERS- mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78, phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK, and phosphoeukaryotic initiation factor-2α (phospho-eIF2α, activating transcription factor 4 (ATF4 and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.

  9. LAMP3 is involved in tamoxifen resistance in breast cancer cells through the modulation of autophagy

    NARCIS (Netherlands)

    Nagelkerke, A.P.; Sieuwerts, A.M.; Bussink, J.; Sweep, F.C.; Look, M.P.; Foekens, J.A.; Martens, J.W.; Span, P.N.

    2014-01-01

    Lysosome-associated membrane protein 3 (LAMP3) is a member of the LAMP-family of proteins, which are involved in the process of autophagy. Autophagy is induced by tamoxifen in breast cancer cells and may contribute to tamoxifen resistance. In this study, the significance of LAMP3 for tamoxifen resis

  10. LAMP3 is involved in tamoxifen resistance in breast cancer cells through the modulation of autophagy

    NARCIS (Netherlands)

    A. Nagelkerke (Anika); A.M. Sieuwerts (Anieta); J. Bussink (Johan); F.C. Sweep (Fred); M.P. Look (Maxime); J.A. Foekens (John); J.W.M. Martens (John); P.N. Span (Paul)

    2014-01-01

    textabstractLysosome-associated membrane protein 3 (LAMP3) is a member of the LAMP-family of proteins, which are involved in the process of autophagy. Autophagy is induced by tamoxifen in breast cancer cells and may contribute to tamoxifen resistance. In this study, the significance of LAMP3 for tam

  11. Analysis of BRCA1 involvement in breast cancer in Indian women

    Indian Academy of Sciences (India)

    P H Pestonjamasp; I Mittra

    2000-03-01

    The involvement of the familial breast-ovarian cancer gene (BRCA1) in the molecular pathogenesis of breast cancer among Indian women is unknown. We have used a set of microsatellite polymorphisms to examine the frequency of allele loss at the BRCA1 region on chromosome 17q21, in a panel of 80 human breast tumours. Tumour and blood leukocyte/normal tissue DNA from a series of 80 patients with primary breast cancer was screened by PCR-amplified microsatellite length polymorphisms to detect deletions at three polymorphic BRCA1 loci. PCR-allelotype was valuable in examining allele losses from archival and small tumour samples. Loss of alleles at BRCA1 in the patient set, confirmed a noteworthy role of this gene in the molecular pathogenesis of breast cancer and was in accordance with its well-documented tumour suppressive function.

  12. Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines: less involvement of metallothionein

    Directory of Open Access Journals (Sweden)

    Moon Sung-Pyo

    2004-10-01

    Full Text Available Abstract Background Heptaplatin is a new platinum derivative with anticancer activity against various cancer cell lines, including cisplatin-resistant cancer cell lines (Cancer Chemother Pharmacol 1995; 35: 441. Methods Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines has been investigated in connection with metallothionein (MT. Cytotoxicity was determined by an MTT assay. MT mRNA, was determined by RT-PCR assay. Transfection study was carried out to examine the function of MT. Results Of various gastric cancer cell lines, SNU-638 and SNU-601 showed the highest and lowest levels of MT mRNA, respectively, showing 80-fold difference. The IC50 values of SNU-638 to cisplatin, carboplatin and heptaplatin were 11.2-fold, 5.1-fold and 2.0-fold greater than those of SNU-601, respectively. Heptaplatin was more effective against cisplatin-resistant and MT-transfected gastric cancer sublines than cisplatin or carboplatin was. In addition, heptaplatin attenuated cadmium, but not zinc, induction of MT. Conclusion These results indicate that molecular mechanisms of heptaplatin effective against cisplatin-resistant gastric cancer sublines is at least in part due to the less involvement of MT in heptaplatin resistance as well as its attenuation of MT induction.

  13. Elevated expression of protein regulator of cytokinesis 1, involved in the growth of breast cancer cells.

    Science.gov (United States)

    Shimo, Arata; Nishidate, Toshihiko; Ohta, Tomohiko; Fukuda, Mamoru; Nakamura, Yusuke; Katagiri, Toyomasa

    2007-02-01

    To elucidate molecular mechanisms of mammary carcinogenesis and discover novel therapeutic targets for breast cancer, we previously carried out a genome-wide expression profile analysis of 81 breast cancer cases by means of a combination of cDNA microarray and laser microbeam microdissection. Among the upregulated genes, we focused on the functional significance of protein regulator of cytokinesis 1 (PRC1) in the development of breast cancer. Western blot analysis using breast cancer cell lines revealed a significant increase in endogenous PRC1 levels in G(2)/M phase. Treatment of breast cancer cells with small interfering RNA against PRC1 effectively suppressed its expression and inhibited the growth of breast cancer cell lines T47D and HBC5. Furthermore, we found an interaction between PRC1 and kinesin family member 2C/mitotic centromere-associated kinesin (KIF2C/MCAK) by coimmunoprecipitation and immunoblotting using COS-7 cells, in which these molecules were introduced exogenously. These findings suggest the involvement of a PRC1-KIF2C/MCAK complex in breast tumorigenesis, and this complex should be a promising target for the development of novel treatments for breast cancer. PMID:17233835

  14. Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer.

    Science.gov (United States)

    zur Hausen, Harald

    2012-06-01

    An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. PMID:22212999

  15. Robotic Versus Laparoscopic Surgery for Rectal Cancer after Preoperative Chemoradiotherapy: Case-Matched Study of Short-Term Outcomes

    OpenAIRE

    Kim, Yong Sok; Kim, Min Jung; Park, Sung Chan; Sohn, Dae Kyung; Kim, Dae Yong; Chang, Hee Jin; Nam, Byung-Ho; Oh, Jae Hwan

    2015-01-01

    Purpose Robotic surgery is expected to have advantages over laparoscopic surgery; however, there are limited data regarding the feasibility of robotic surgery for rectal cancer after preoperative chemoradiotherapy (CRT). Therefore, we evaluated the short-term outcomes of robotic surgery for rectal cancer. Materials and Methods Thirty-three patients with cT3N0-2 rectal cancer after preoperative CRT who underwent robotic low anterior resection (R-LAR) between March 2010 and January 2012 were ma...

  16. Cancer-Specific Stress and Mood Disturbance: Implications for Symptom Perception, Quality of Life, and Immune Response in Women Shortly after Diagnosis of Breast Cancer

    OpenAIRE

    Duck-Hee Kang; Na-Jin Park; Traci McArdle

    2012-01-01

    Purpose. To determine the levels of cancer-specific stress and mood disturbance in women shortly after diagnosis of breast cancer and to assess their associations with symptom perception, quality of life, and immune response. Design. Descriptive and correlational. Sample and Setting. One hundred women with newly diagnosed breast cancer were recruited from interdisciplinary breast clinics. Methods. Baseline data were collected using standardized questionnaires and established bioassay prior to...

  17. The fragile X protein binds mRNAs involved in cancer progression and modulates metastasis formation.

    Science.gov (United States)

    Lucá, Rossella; Averna, Michele; Zalfa, Francesca; Vecchi, Manuela; Bianchi, Fabrizio; La Fata, Giorgio; Del Nonno, Franca; Nardacci, Roberta; Bianchi, Marco; Nuciforo, Paolo; Munck, Sebastian; Parrella, Paola; Moura, Rute; Signori, Emanuela; Alston, Robert; Kuchnio, Anna; Farace, Maria Giulia; Fazio, Vito Michele; Piacentini, Mauro; De Strooper, Bart; Achsel, Tilmann; Neri, Giovanni; Neven, Patrick; Evans, D Gareth; Carmeliet, Peter; Mazzone, Massimiliano; Bagni, Claudia

    2013-10-01

    The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS while a patient-case with FXS showed an unusual decrease of tumour brain invasiveness. However, a role for FMRP in regulating cancer biology, if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate with prognostic indicators of aggressive breast cancer, lung metastases probability and triple negative breast cancer (TNBC). We establish that FMRP overexpression in murine breast primary tumours enhances lung metastasis while its reduction has the opposite effect regulating cell spreading and invasion. FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression. PMID:24092663

  18. Divided care and the Third Way: user involvement in statutory and voluntary sector cancer services.

    Science.gov (United States)

    Tritter, J Q; Barley, V; Daykin, N; Evans, Simon; McNeill, Judith; Rimmer, James; Sanidas, M; Turton, Pat

    2003-07-01

    In health care, as in much of the public sphere, the voluntary sector is playing an increasingly large role in the funding, provision and delivery of services and nowhere is this more apparent than in cancer care. Simultaneously the growth of privatisation, marketisation and consumerism has engendered a rise in the promotion of 'user involvement' in health care. These changes in the organisation and delivery of health care, in part inspired by the 'Third Way' and the promotion of public and citizen participation, are particularly apparent in the British National Health Service. This paper presents initial findings from a three-year study of user involvement in cancer services. Using both case study and survey data, we explore the variation in the definition, aims, usefulness and mechanisms for involving users in the evaluation and development of cancer services across three Health Authorities in South West England. The findings have important implications for understanding shifts in power, autonomy and responsibility between patients, carers, clinicians and health service managers. The absence of any common definition of user involvement or its purpose underlines the limited trust between the different actors in the system and highlights the potentially negative impact of a Third Way health service. PMID:14498919

  19. Clinical impact of radiographic carotid artery involvement in neck metastases from head and neck cancer.

    Science.gov (United States)

    Teymoortash, A; Rassow, S; Bohne, F; Wilhelm, T; Hoch, S

    2016-04-01

    The treatment of lymph node metastases involving the carotid artery is controversial. The aim of the present study was to determine the outcomes of head and neck cancer patients with radiographic carotid artery involvement in neck metastases. A total of 27 patients with head and neck cancer and radiologically diagnosed advanced metastases involving the common carotid artery or internal carotid artery were enrolled. All patients underwent a primary or salvage neck dissection and surgical carotid peeling. The oncological outcome and survival of all patients were analyzed. Loco-regional control was observed in 13 of the 27 patients (48.1%). During follow-up, five patients (18.5%) developed second primaries and 11 (40.7%) developed distant metastases. The survival time was poor independent of regional control. The median overall survival was 1.55 years and disease-free survival was 0.71 year. Radiographic carotid artery involvement in neck metastases in head and neck cancer appears to correlate with a poor long-term prognosis, with a high rate of distant metastases despite loco-regional control. PMID:26723499

  20. A new methodology involving stable isotope tracer to compare short- and long- term selenium mobility in soils

    Science.gov (United States)

    Tolu, Julie; Thiry, Yves; Potin-gautier, Martine; Le hécho, Isabelle; Bueno, Maïté

    2013-04-01

    Selenium is an element of environmental concern given its dual beneficial and toxic character to animal and human health. Its radioactive isotope 79Se, a fission product of 235U, is considered critical in safety assessment of nuclear waste repositories in case of leakage and hypothetical soil contamination. Therefore, Se species transformations and interactions with soil components have to be clearly understood to predict its dispersion in the biosphere (e.g., accumulation in soils, migration to waters, transfer to living organisms). While natural Se interactions with soils run over centuries to millennia time scales, transformations and partitioning are generally studied with short-term experiments (often inferior to 1 month) after Se addition. The influence of slower, long-term processes involved in Se speciation and mobility in soils is thus not properly accounted for. We tested if using ambient Se would be relevant for long-term risk assessment while added Se would be more representative of short-term contamination impact. For that purpose, we developed a new methodology to trace the differential reactivity of ambient and spiked Se at trace level (µg kg-1) in soils. It combined the use of a stable isotopically enriched tracer with our previous published analytical method based on specific extractions and HPLC-ICP-MS to determine trace Se species partition in different soil phases. Given that soil extracts contains very high concentrations of various elements interfering Se (e.g., Fe, Cl, Br), the ICP-MS parameters and mathematical corrections were optimized to cope with such interferences. Following optimization, three correct and accurate (methodology can be further used to simultaneous monitor the reactivity of three different Se forms (e.g., added Se(IV), Se(VI) or Se(0), ambient Se), that will be useful for both soil Se contamination and supplementation contexts.

  1. The Value of Prostate MRI with Endorectal Coil in Detecting Seminal Vesicle Involvement in Patients with Prostate Cancer

    OpenAIRE

    Ghafoori, Mahyar; Alavi, Manijeh; Shakiba, Madjid; Hoseini, Kamal

    2015-01-01

    Background: In prostate cancer, detection of seminal vesicle involvement is important because it influences the treatment planning and prognosis of the patients. Objectives: The objective of this study was to determine the value of prostate MRI with endorectal coil in the detection of seminal vesicle involvement in patients with prostate cancer. Patients and Methods: A total number of 238 biopsy-proven prostate cancer patients were examined by 1.5 Tesla MRI with a combination of pelvic and en...

  2. Lymphoscintigraphy in breast cancer: a short review about the impact on upper limb after surgical treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bergmann, Anke; Resende, Juliana Miranda Dutra de; Bello, Marcelo Adeodato; Oliveira, Juliana Flavia de; Bernardo-Filho, Mario [Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil); Santos-Filho, Sebastiao David [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Lab. de Radiofarmacia Experimental; Palestro, Christopher J. [Yeshiva University, NY (United States). Albert Einstein College of Medicine

    2008-12-15

    Breast cancer is still associated with high mortality rates and one of the most important factors governing long survival is accurate and early diagnosis. In underdeveloped countries, this disease frequently is only detected in advanced stages; however, through mammography, many women have been diagnosed at early stages. In this context, the sentinel lymph node (SLN) technique is associated with less postoperative morbidity compared to axillary lymphadenectomy. Lymphoscintigraphy has emerged as a method for the evaluation of lymphatic drainage chains in various tumours, being both accurate and non invasive. The aim of this work is to present the main aspects which cause controversy about SLN and lymphoscintigraphy and the impact that these procedures have had on lymphedema after surgical treatment for breast cancer. A short review including papers in English, Spanish and Portuguese, available on Lilacs and Medline database, published between January, 2000 and July, 2008 was performed. The key words breast cancer, lymphoscintigraphy, SLN biopsy, lymphedema were used. Various studies have aimed to compare the incidence and prevalence of lymphedema according to the technique used; however, the population subjected to SLN is different from the one with indication for axillary lymphadenectomy regarding staging. Moreover, little is known about long term morbidity since it is a relatively new technique. In conclusion, the development of surgical techniques has permitted to minimize deformities and the current trend is that these techniques be as conservative as possible. Thus, lymphoscintigraphy plays an important role in the identification of SLN, contributing to the prevention and minimization of postoperative complications. (author)

  3. A case of pyoderma gangrenosum involving the prostate gland after radiation therapy for prostate cancer

    International Nuclear Information System (INIS)

    A 76-year-old man complained of difficulty in urination and miction pain with abacterial pyuria after radiation therapy for prostate cancer. Transurethral resection of the prostate was performed and histopathologically widespread necrosis was observed in the prostate. Thereafter retention of urine and fever occurred and computed tomography scan revealed an abscess of the penile corpus. The abscess was drained, but the fever continued. He developed an abacterial lung abscess and abacterial necrotic ulcerating lesions on his back, his left leg and his lower abdomen. Macroscopic findings demonstrated typical features of pyoderma gangrenosum. Steroid treatment was initiated and the response to steroid therapy was dramatic. Finally urinary diversion using an ileal conduit was performed. We found few cases of pyoderma gangrenosum involving lesions other than those of the skin in the literature. This is the first report of pyoderma gangrenosum involving the prostate gland after radiation therapy for prostate cancer. (author)

  4. ER stress and autophagy are involved in the apoptosis induced by cisplatin in human lung cancer cells

    OpenAIRE

    Shi, Shaomin; Tan, Ping; Yan, Bingdi; Gao, Rong; Zhao, Jianjun; Jing WANG; Guo, Jia; Li, Ning; Ma, Zhongsen

    2016-01-01

    Cisplatin [cis-diamminedichloroplatinum II (CDDP)] is one of the most classical and effective chemotherapeutic drugs for the treatment of cancers including lung cancer. However, the presence of cisplatin resistance in cancer lowers its curative effect and limits its usage in the clinic. The aim of the present study was to investigate the underlying mechanisms of cisplatin resistance in lung cancer involving endoplasmic reticulum (ER) stress and autophagy. In the present study, we detected the...

  5. Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis

    International Nuclear Information System (INIS)

    Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response. Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance. Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and α-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified. Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer

  6. Methodology to predict long-term cancer survival from short-term data using Tobacco Cancer Risk and Absolute Cancer Cure models

    International Nuclear Information System (INIS)

    Three parametric statistical models have been fully validated for cancer of the larynx for the prediction of long-term 15, 20 and 25 year cancer-specific survival fractions when short-term follow-up data was available for just 1-2 years after the end of treatment of the last patient. In all groups of cases the treatment period was only 5 years. Three disease stage groups were studied, T1N0, T2N0 and T3N0. The models are the Standard Lognormal (SLN) first proposed by Boag (1949 J. R. Stat. Soc. Series B 11 15-53) but only ever fully validated for cancer of the cervix, Mould and Boag (1975 Br. J. Cancer 32 529-50), and two new models which have been termed Tobacco Cancer Risk (TCR) and Absolute Cancer Cure (ACC). In each, the frequency distribution of survival times of defined groups of cancer deaths is lognormally distributed: larynx only (SLN), larynx and lung (TCR) and all cancers (ACC). All models each have three unknown parameters but it was possible to estimate a value for the lognormal parameter S a priori. By reduction to two unknown parameters the model stability has been improved. The material used to validate the methodology consisted of case histories of 965 patients, all treated during the period 1944-1968 by Dr Manuel Lederman of the Royal Marsden Hospital, London, with follow-up to 1988. This provided a follow-up range of 20- 44 years and enabled predicted long-term survival fractions to be compared with the actual survival fractions, calculated by the Kaplan and Meier (1958 J. Am. Stat. Assoc. 53 457-82) method. The TCR and ACC models are better than the SLN model and for a maximum short-term follow-up of 6 years, the 20 and 25 year survival fractions could be predicted. Therefore the numbers of follow-up years saved are respectively 14 years and 19 years. Clinical trial results using the TCR and ACC models can thus be analysed much earlier than currently possible. Absolute cure from cancer was also studied, using not only the prediction models which

  7. Predicting Pelvic Lymph Node Involvement in Current-Era Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: The Roach formula [2/3 × prostate-specific antigen + (Gleason score – 6) × 10], derived in 1993 during the early prostate specific antigen (PSA) screening era, has been used to predict the risk of pelvic lymph node involvement in patients with prostate cancer. In the current era of widespread PSA screening with a shift to earlier disease stages, there is evidence to suggest that the Roach score overestimates risk of nodal metastasis. This study retrospectively reviews the validity of this formula as a prediction tool. Methods and Materials: We conducted a retrospective institutional review including men with clinical T1c–T3 prostate cancer, with baseline PSA levels and biopsy-obtained Gleason scores who underwent radical prostatectomy with pelvic node dissection from 2001 through 2009 (N = 1,022). The predicted risk of nodal involvement was calculated for each patient using the Roach formula and then compared with actual rates following surgery. Results: The study included 1,022 patients; 99.6% had clinical T1c/T2 disease, with a mean of 10.3 lymph nodes surgically evaluated. Overall, 42 patients (4.1%) had nodal metastasis. For every range of scores, the Roach formula overestimates the risk of nodal involvement. Observed nodal positivity was 1%, 6.3%, 10%, 15.2%, and 16.7% for Roach scores ≤10%, >10%–20%, >20%–30%, >30%–40%, and >40%, respectively. The Roach score overestimates the risk by approximately 4.5-fold in patients with scores ≤10%, by 2.5-fold for all scores between 10% and 40%, and by 4-fold for scores >40%. Conclusion: The Roach formula overpredicts the risk of pelvic nodal involvement in current-era prostate cancer patients undergoing regular PSA screening and with mainly T1c/T2 disease. Contemporary patients are much less likely to have nodal involvement for a given PSA and Gleason score.

  8. CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Oue, Erika [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Lee, Ji-Won; Sakamoto, Kei [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Iimura, Tadahiro [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Aoki, Kazuhiro [Section of Pharmacology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Kayamori, Kou [Section of Diagnostic Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Department of Pathology, Ome Municipal General Hospital, Ome, Tokyo (Japan); Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo [Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Oral cancer cells synthesize CXCL2. Black-Right-Pointing-Pointer CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. Black-Right-Pointing-Pointer CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. Black-Right-Pointing-Pointer We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first

  9. CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

    International Nuclear Information System (INIS)

    Highlights: ► Oral cancer cells synthesize CXCL2. ► CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. ► CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. ► We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction.

  10. Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

    International Nuclear Information System (INIS)

    KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it

  11. Short hairpin RNA library-based functional screening identified ribosomal protein L31 that modulates prostate cancer cell growth via p53 pathway.

    Directory of Open Access Journals (Sweden)

    Yojiro Maruyama

    Full Text Available Androgen receptor is a primary transcription factor involved in the proliferation of prostate cancer cells. Thus, hormone therapy using antiandrogens, such as bicalutamide, is a first-line treatment for the disease. Although hormone therapy initially reduces the tumor burden, many patients eventually relapse, developing tumors with acquired endocrine resistance. Elucidation of the molecular mechanisms underlying endocrine resistance is therefore a fundamental issue for the understanding and development of alternative therapeutics for advanced prostate cancer. In the present study, we performed short hairpin RNA (shRNA-mediated functional screening to identify genes involved in bicalutamide-mediated effects on LNCaP prostate cancer cells. Among such candidate genes selected by screening using volcano plot analysis, ribosomal protein L31 (RPL31 was found to be essential for cell proliferation and cell-cycle progression in bicalutamide-resistant LNCaP (BicR cells, based on small interfering RNA (siRNA-mediated knockdown experiments. Of note, RPL31 mRNA is more abundantly expressed in BicR cells than in parental LNCaP cells, and clinical data from ONCOMINE and The Cancer Genome Altas showed that RPL31 is overexpressed in prostate carcinomas compared with benign prostate tissues. Intriguingly, protein levels of the tumor suppressor p53 and its targets, p21 and MDM2, were increased in LNCaP and BicR cells treated with RPL31 siRNA. We observed decreased degradation of p53 protein after RPL31 knockdown. Moreover, the suppression of growth and cell cycle upon RPL31 knockdown was partially recovered with p53 siRNA treatment. These results suggest that RPL31 is involved in bicalutamide-resistant growth of prostate cancer cells. The shRNA-mediated functional screen in this study provides new insight into the molecular mechanisms and therapeutic targets of advanced prostate cancer.

  12. Nuclear genes involved in mitochondria-to-nucleus communication in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Gabrielson Edward

    2002-11-01

    Full Text Available Abstract Background The interaction of nuclear and mitochondrial genes is an essential feature in maintenance of normal cellular function. Of 82 structural subunits that make up the oxidative phosphorylation system in the mitochondria, mitochondrial DNA (mtDNA encodes 13 subunits and rest of the subunits are encoded by nuclear DNA. Mutations in mitochondrial genes encoding the 13 subunits have been reported in a variety of cancers. However, little is known about the nuclear response to impairment of mitochondrial function in human cells. Results We isolated a Rho0 (devoid of mtDNA derivative of a breast cancer cell line. Our study suggests that depletion of mtDNA results in oxidative stress, causing increased lipid peroxidation in breast cancer cells. Using a cDNA microarray we compared differences in the nuclear gene expression profile between a breast cancer cell line (parental Rho+ and its Rho0 derivative impaired in mitochondrial function. Expression of several nuclear genes involved in cell signaling, cell architecture, energy metabolism, cell growth, apoptosis including general transcription factor TFIIH, v-maf, AML1, was induced in Rho0 cells. Expression of several genes was also down regulated. These include phospholipase C, agouti related protein, PKC gamma, protein tyrosine phosphatase C, phosphodiestarase 1A (cell signaling, PIBF1, cytochrome p450, (metabolism and cyclin dependent kinase inhibitor p19, and GAP43 (cell growth and differentiation. Conclusions Mitochondrial impairment in breast cancer cells results in altered expression of nuclear genes involved in signaling, cellular architecture, metabolism, cell growth and differentiation, and apoptosis. These genes may mediate the cross talk between mitochondria and the nucleus.

  13. Is there evidence of involvement of DNA repair polymorphisms in human cancer?

    Science.gov (United States)

    Ricceri, Fulvio; Matullo, Giuseppe; Vineis, Paolo

    2012-08-01

    DNA suffers from a wide range of damage, both from extracellular agents and via endogenous mechanisms. Damage of DNA can lead to cancer and other diseases. Therefore, it is plausible that sequence variants in DNA repair genes are involved in cancer development. A recent systematic review and meta-analysis, based on the "Venice criteria", showed that out of 241 associations investigated, only three resulted to have a strong grade of cumulative evidence. These associations were: two SNPs rs1799793 and rs13181 in the ERCC2 gene and lung cancer (recessive model) and rs1805794 in the NBN gene and bladder cancer (dominant model). An update of this meta-analysis has been performed in the present paper, and we found partially inconsistent results. Inconsistencies in the literature are thus far not easy to explain. In addition, none of the cancer genome-wide association studies (GWAs) published so far showed highly statistically significant associations for any of the common DNA repair gene variants, in such a way as to place DNA repair genes among the top 10-20 hits identified in GWAs. Though this suggests that it is unlikely that DNA repair gene polymorphisms per se play a major role, a clarification of the discrepancies in the literature is needed. Also, gene/environment and gene/lifestyle interactions for the carcinogenic mechanisms involving DNA repair should be investigated more systematically and with less classification error. Finally, the combined effect of multiple SNPs in several genes in one or more relevant DNA repair pathways could have a greater impact on pathological phenotypes than SNPs in single genes, but this has been investigated only occasionally. PMID:21864546

  14. The Service Pledge for Breast Cancer – Improving services through patient involvement

    International Nuclear Information System (INIS)

    A guiding principle for today’s National Health Service is for services to reflect the needs and choices of patients and carers. There is evidence that meaningful patient involvement and engagement of people in their own care supports relationships with NHS professionals, and improves the quality and experience of healthcare. This paper reviews the Service Pledge for Breast Cancer, developed by the charity Breakthrough Breast Cancer as a tried and tested route to delivering effective patient involvement and examines some implications for radiotherapy services. The Service Pledge, which has benefitted an estimated 19,000 patients across the UK, is a tool that enables healthcare professionals and patients to work in partnership to improve local breast cancer services. Based on the results of a patient survey and in depth interviews to determine to what extent standards of care are being met at each participating hospital, improvement goals are identified helping turn the patient voice into constructive action. Improvement goals resulting from the Service Pledge range from small changes that make a real difference to patients, through to much larger changes to local breast services. To date, there has been limited involvement of radiotherapy staff in the Service Pledge, yet radiographers play an important role in the treatment of breast cancer as most patients will be offered radiotherapy. However, radiotherapy services have been criticised for not being patient -centred and for not providing enough information, psychological and emotional support before, during and after treatment. It is contended that radiographers are ideally placed to address many of these concerns and engage further with patients through projects such as the Service Pledge, empowering their patients to voice what is most important to them and driving the quality improvements that emerge.

  15. Short term morbidity and cosmesis following lumpectomy and radical radiotherapy for operable breast cancer

    International Nuclear Information System (INIS)

    One hundred and eighty-four patients with TO-T2, NO-N1b, MO breast cancer were treated by local excision and radical radiotherapy. Short-term morbidity and cosmetic assessment are reported after a median follow-up of 21 months. At 1 year 80% of women considered the cosmetic result very good or excellent, whereas only 63% of their consultants gave a similar assessment. Mild or moderate arm oedema developed in 22% of patients, radiation pneumonitis in 9% and oesophagitis in 11%. Mild discomfort in the treated breast was reported by 39% and moderate by 17%. Oedema of the breast was noted in 20%. It is too early to comment on long term disease control or final cosmetic result but to date the morbidity has been considered acceptable and measures to reduce it further are being implemented. (author)

  16. Can we predict very short term survival in small cell lung cancer?

    Science.gov (United States)

    Quoix, E; Hedelin, G; Popin, E; Charloux, A; Dietemann, A; Seibert, R; Roeslin, N; Pauli, G

    1993-12-01

    We retrospectively reviewed the charts of 151 consecutive patients diagnosed as small cell lung cancer in our department and who had at least one course of chemotherapy. Nineteen patients died during the first 2 months, of the probability were reported to construct a receiver operating characteristic curve i.e. 13% of the population. The probability of dying within 2 months was investigated through a stepwise logistic regression. A performance status 60, a platelet count equation for the probability of dying within a 2-month period. Sensitivity and specificity for various cutoff points characteristic curve allowing one to determine for a given patient his risk of being a very short term survivor. Such an approach could prevent inclusion of patients with high risk of early death in clinical trials and help to choose appropriate treatments for such poor risk patients. PMID:8075968

  17. Efficacy and safety assessment of short EOF program regional arterial infusion chemotherapy and conventional chemotherapy for advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ming-Cai Shui; Lin Xiong

    2016-01-01

    Objective:To study the efficacy and safety of short EOF program regional arterial infusion chemotherapy and conventional chemotherapy for advanced gastric cancer.Methods: 66 cases of patients diagnosed of advanced gastric cancer in our hospital were enrolled for study, given preoperative short EOF program chemotherapy and randomly divided into two groups. Observation group received short EOF program regional arterial infusion chemotherapy and control group received short EOF program intravenous chemotherapy. Then number of apoptosis cells and contents of apoptosis genes in the tumor tissue, serum liver and kidney function indicators as well as cfDNA methylation degree of two groups were detected. Results:(1) indicators of efficacy: the number of apoptosis cells in gastric cancer tissue of observation group was more than that of control group, mRNA levels of Caspase-3, Caspase-9, Fas and FasL were higher than those of control group, and serum p16, RNF180, SFRP2, SOX17 and RUNX methylation ratios were lower than those of control group; (2) indicators of safety: serum RBP, CysC, ALT and AST contents of observation group were lower than those of control group.Conclusions:Short EOF program regional arterial infusion chemotherapy can more effectively kill cancer cells, reduce methylation degree of tumor-associated genes and decrease liver function and kidney function damage; both efficacy and safety of it are better than conventional chemotherapy.

  18. The effect of tobacco and alcohol and their reduction/cessation on mortality in oral cancer patients: short communication

    OpenAIRE

    Jerjes, W.; Upile, T; Radhi, H.; Petrie, A.; Abiola, J.; Adams, A.; Kafas, P.; Callear, J.; Carbiner, R.; Rajaram, K.; Hopper, C

    2012-01-01

    BACKGROUND: The use of tobacco is known to increase the incidence of developing oral cancer by 6 times, while the additive effect of drinking alcohol further increases the risk leading to higher rate of morbidity and mortality. In this short communication, we prospectively assessed the effect of tobacco smoking and alcohol drinking in oral cancer patients on the overall mortality from the disease, as well as the effect of smoking and drinking reduction/cessation at time of diagnosis on mortal...

  19. A New View of Radiation-Induced Cancer: Integrating Short- and Long-Term Processes. Part II: Second Cancer Risk Estimation

    Science.gov (United States)

    Shuryak, Igor; Brenner, David J.; Hahnfeldt, Philip; Hlatky, Lynn; Sachs, Rainer K.

    2009-01-01

    As the number of cancer survivors grows, prediction of radiotherapy-induced second cancer risks becomes increasingly important. Because the latency period for solid tumors is long, the risks of recently introduced radiotherapy protocols are not yet directly measurable. In the accompanying article, we presented a new biologically based mathematical model, which, in principle, can estimate second cancer risks for any protocol. The novelty of the model is that it integrates, into a single formalism, mechanistic analyses of pre-malignant cell dynamics on two different time scales: short-term during radiotherapy and recovery; long-term during the entire life span. Here, we apply the model to nine solid cancer types (stomach, lung, colon, rectal, pancreatic, bladder, breast, central nervous system, and thyroid) using data on radiotherapy-induced second malignancies, on Japanese atomic bomb survivors, and on background US cancer incidence. Potentially, the model can be incorporated into radiotherapy treatment planning algorithms, adding second cancer risk as an optimization criterion.

  20. Differential involvement of RASSF2 hypermethylation in breast cancer subtypes and their prognosis

    Science.gov (United States)

    Perez-Janices, Noemi; Blanco-Luquin, Idoia; Torrea, Natalia; Liechtenstein, Therese; Escors, David; Cordoba, Alicia; Vicente-Garcia, Francisco; Jauregui, Isabel; De La Cruz, Susana; Illarramendi, José Juan; Coca, Valle; Berdasco, Maria; Kochan, Grazyna; Ibañez, Berta; Lera, José Miguel; Guerrero-Setas, David

    2015-01-01

    Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal A-like, luminal B-like/HER2-negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumorigenesis of each tumor subtype. RASSF2 is a gene that is hypermethylated in breast cancer and whose clinical value has not been previously studied. The hypermethylation of RASSF1 and RASSF2 genes was analyzed in 198 breast tumors of different subtypes. The effect of the demethylating agent 5-aza-2′-deoxycytidine in the re-expression of these genes was examined in triple-negative (BT-549), HER2 (SK-BR-3), and luminal cells (T-47D). Different patterns of RASSF2 expression for distinct tumor subtypes were detected by immunohistochemistry. RASSF2 hypermethylation was much more frequent in luminal subtypes than in non-luminal tumors (p = 0.001). The re-expression of this gene by lentiviral transduction contributed to the differential cell proliferation and response to antineoplastic drugs observed in luminal compared with triple-negative cell lines. RASSF2 hypermethylation is associated with better prognosis in multivariate statistical analysis (P = 0.039). In conclusion, RASSF2 gene is differently methylated in luminal and non-luminal tumors and is a promising suppressor gene with clinical involvement in breast cancer. PMID:26284587

  1. SOX7 is involved in aspirin-mediated growth inhibition of human colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Shu-Yan Huang; Jing-Xin Feng; Yan-Yan Gao; Li Zhao; Jun Lu; Bai-Qu Huang; Yu Zhang

    2011-01-01

    AIM: To confirm the role of sex-determining region Y-box 7 (Sox7) in aspirin-mediated growth inhibition of COX-independent human colorectal cancer cells.METHODS: The cell survival percentage was examined by MTT (Moto-nuclear cell direc cytotoxicity) assay.SOX7 expression was assessed by using reverse transcription-polymerase chain reaction and Western blotting. SB203580 was used to inhibit the p38MAPK signal pathway. SOX7 promoter activity was detected by Luciferase reporter assay.RESULTS: SOX7 was upregulated by aspirin and was involved in aspirin-mediated growth inhibition of SW480 human colorectal cancer cells. The p38MAPK pathway played a role in aspirin-induced SOX7 expression, during which the AP1 transcription factors c-Jun and c-Fos upregulated SOX7 promoter activities.RESULTS: SOX7 is upregulated by aspirin and is involved in aspirin-mediated growth inhibition of human colorectal cancer SW480 cells.

  2. Interlobar fissures involvement by lung cancer. Evaluation with thin-section computed tomography images

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yuji; Yamada, Kouzo; Nomura, Ikuo; Noda, Kazumasa; Ishiwa, Naoki; Maehara, Takamitsu; Kameda, Youichi [Kanagawa Cancer Center (Japan)

    1998-11-01

    Pleural involvement of interlobar fissure by a tumor is one of the most important factors in the clinical diagnosis of lung cancer. A positive finding of incomplete interlobar fissure of the lung influences not only the surgical procedure but also the prognosis. The aim of this retrospective study was to investigate the usefulness of thin-section computed tomography (CT) compared with conventional CT in the detection of pleural invasion of the interlobar fissure by lung cancer or incomplete interlobar fissure, and the results of surgery, according to the involvement of the pleural surface. We reviewed 90 patients whose tumors were adjacent to the interlobar fissure of the lung through conventional CT scans and subsequent thoracotomy. A comparison of diagnoses based on the findings of thin-section CT and pathologic examination showed that thin-section CT was 94% accurate for pleural invasion of the interlobar fissure, and 100% for incomplete interlobar fissure. Conventional CT, however, was only 63% accurate for pleural invasion of the interlobar fissure and 31% for incomplete interlobar fissure. This leads us to conclude that thin-section CT is helpful in the accurate evaluation of pleural invasion of the interlobar fissure and in the findings of incomplete interlobar fissure in lung cancer for patients in whom tumors are adjacent to the interlobar fissure on conventional CT findings. (author)

  3. Involvement of Fatty Acid Binding Protein 5 and PPARβ/δ in Prostate Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Elwin Morgan

    2010-01-01

    Full Text Available Fatty acid binding protein 5 (FABP5 delivers ligands from the cytosol directly to the nuclear receptor PPARβ/δ and thus facilitates the ligation and enhances the transcriptional activity of the receptor. We show here that expression levels of both FABP5 and PPARβ/δ are correlated with the tumorigenic potential of prostate cancer cell lines. We show further that FABP5 comprises a direct target gene for PPARβ/δ and thus the binding protein and its cognate receptor are engaged in a positive feedback loop. The observations demonstrate that, similarly to effects observed in mammary carcinomas, activation of the FABP5/PPARβ/δ pathway induces PPARβ/δ target genes involved in cell survival and growth and enhances cell proliferation and anchorage-independent growth in prostate cancer cells. Furthermore, the data show that downregulation of either FABP5 or PPARβ/δ inhibits the growth of the highly malignant prostate cancer PC3M cells. These studies suggest that the FABP5/PPARβ/δ pathway may play a general role in facilitating tumor progression and that inhibition of the pathway may comprise a novel strategy in treatment of cancer.

  4. An Evaluation Methodology for Longitudinal Studies of Short-Term Cancer Research Training Programs.

    Science.gov (United States)

    Padilla, Luz A; Venkatesh, Raam; Daniel, Casey L; Desmond, Renee A; Brooks, C Michael; Waterbor, John W

    2016-03-01

    The need to familiarize medical students and graduate health professional students with research training opportunities that cultivate the appeal of research careers is vital to the future of research. Comprehensive evaluation of a cancer research training program can be achieved through longitudinal tracking of program alumni to assess the program's impact on each participant's career path and professional achievements. With advances in technology and smarter means of communication, effective ways to track alumni have changed. In order to collect data on the career outcomes and achievements of nearly 500 short-term cancer research training program alumni from 1999-2013, we sought to contact each alumnus to request completion of a survey instrument online, or by means of a telephone interview. The effectiveness of each contact method that we used was quantified according to ease of use and time required. The most reliable source of contact information for tracking alumni from the early years of the program was previous tracking results, and for alumni from the later years, the most important source of contact information was university alumni records that provided email addresses and telephone numbers. Personal contacts with former preceptors were sometimes helpful, as were generic search engines and people search engines. Social networking was of little value for most searches. Using information from two or more sources in combination was most effective in tracking alumni. These results provide insights and tools for other research training programs that wish to track their alumni for long-term program evaluation. PMID:25412722

  5. PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement.

    Directory of Open Access Journals (Sweden)

    Silvia Gärtner

    Full Text Available Protein Tyrosin Kinase 7 (PTK7 is upregulated in several human cancers; however, its clinical implication in breast cancer (BC and lymph node (LN is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033 in BC and nodal involvement (ANOVA, p = 0.007 in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041. Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance.

  6. PTK 7 is a transforming gene and prognostic marker for breast cancer and nodal metastasis involvement.

    Science.gov (United States)

    Gärtner, Silvia; Gunesch, Angela; Knyazeva, Tatiana; Wolf, Petra; Högel, Bernhard; Eiermann, Wolfgang; Ullrich, Axel; Knyazev, Pjotr; Ataseven, Beyhan

    2014-01-01

    Protein Tyrosin Kinase 7 (PTK7) is upregulated in several human cancers; however, its clinical implication in breast cancer (BC) and lymph node (LN) is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC) cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033) in BC and nodal involvement (ANOVA, p = 0.007) in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041). Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance. PMID:24409301

  7. Preoperative Treatment of Locally Advanced Rectal Cancer: Assets and Drawbacks of Short Course and Long Course in Clinical Practice.

    Science.gov (United States)

    Ngan, Samuel Y

    2016-07-01

    Preoperative short-course radiotherapy and preoperative long-course chemoradiotherapy are the standards of care for high-risk rectal cancer in different parts of the world. Both treatments are effective in local control and carry a low morbidity. The advantage of short course is its simplicity, whereas long course has the advantage of downsizing tumors thus increasing the chance of sphincter preservation. Although 2 randomized trials comparing short course and long course have been performed, the better form of preoperative treatment remains a subject of discussion. This article reviews the evidence supporting each approach, and it discusses their relative merits and future directions. PMID:27238469

  8. Involvement of promoter methylation in the regulation of Pregnane X receptor in colon cancer cells

    International Nuclear Information System (INIS)

    Pregnane X receptor (PXR) is a key transcription factor that regulates drug metabolizing enzymes such as cytochrome P450 (CYP) 3A4, and plays important roles in intestinal first-pass metabolism. Although there is a large inter-individual heterogeneity with intestinal CYP3A4 expression and activity, the mechanism driving these differences is not sufficiently explained by genetic variability of PXR or CYP3A4. We examined whether epigenetic mechanisms are involved in the regulation of PXR/CYP3A4 pathways in colon cancer cells. mRNA levels of PXR, CYP3A4 and vitamin D receptor (VDR) were evaluated by quantitative real-time PCR on 6 colon cancer cell lines (Caco-2, HT29, HCT116, SW48, LS180, and LoVo). DNA methylation status was also examined by bisulfite sequencing of the 6 cell lines and 18 colorectal cancer tissue samples. DNA methylation was reversed by the treatment of these cell lines with 5-aza-2'-deoxycytidine (5-aza-dC). The 6 colon cancer cell lines were classified into two groups (high or low expression cells) based on the basal level of PXR/CYP3A4 mRNA. DNA methylation of the CpG-rich sequence of the PXR promoter was more densely detected in the low expression cells (Caco-2, HT29, HCT116, and SW48) than in the high expression cells (LS180 and LoVo). This methylation was reversed by treatment with 5-aza-dC, in association with re-expression of PXR and CYP3A4 mRNA, but not VDR mRNA. Therefore, PXR transcription was silenced by promoter methylation in the low expression cells, which most likely led to downregulation of CYP3A4 transactivation. Moreover, a lower level of PXR promoter methylation was observed in colorectal cancer tissues compared with adjacent normal mucosa, suggesting upregulation of the PXR/CYP3A4 mRNAs during carcinogenesis. PXR promoter methylation is involved in the regulation of intestinal PXR and CYP3A4 mRNA expression and might be associated with the inter-individual variability of the drug responses of colon cancer cells

  9. Involvement of promoter methylation in the regulation of Pregnane X receptor in colon cancer cells

    Directory of Open Access Journals (Sweden)

    Otsuka Koki

    2011-02-01

    Full Text Available Abstract Background Pregnane X receptor (PXR is a key transcription factor that regulates drug metabolizing enzymes such as cytochrome P450 (CYP 3A4, and plays important roles in intestinal first-pass metabolism. Although there is a large inter-individual heterogeneity with intestinal CYP3A4 expression and activity, the mechanism driving these differences is not sufficiently explained by genetic variability of PXR or CYP3A4. We examined whether epigenetic mechanisms are involved in the regulation of PXR/CYP3A4 pathways in colon cancer cells. Methods mRNA levels of PXR, CYP3A4 and vitamin D receptor (VDR were evaluated by quantitative real-time PCR on 6 colon cancer cell lines (Caco-2, HT29, HCT116, SW48, LS180, and LoVo. DNA methylation status was also examined by bisulfite sequencing of the 6 cell lines and 18 colorectal cancer tissue samples. DNA methylation was reversed by the treatment of these cell lines with 5-aza-2'-deoxycytidine (5-aza-dC. Results The 6 colon cancer cell lines were classified into two groups (high or low expression cells based on the basal level of PXR/CYP3A4 mRNA. DNA methylation of the CpG-rich sequence of the PXR promoter was more densely detected in the low expression cells (Caco-2, HT29, HCT116, and SW48 than in the high expression cells (LS180 and LoVo. This methylation was reversed by treatment with 5-aza-dC, in association with re-expression of PXR and CYP3A4 mRNA, but not VDR mRNA. Therefore, PXR transcription was silenced by promoter methylation in the low expression cells, which most likely led to downregulation of CYP3A4 transactivation. Moreover, a lower level of PXR promoter methylation was observed in colorectal cancer tissues compared with adjacent normal mucosa, suggesting upregulation of the PXR/CYP3A4 mRNAs during carcinogenesis. Conclusions PXR promoter methylation is involved in the regulation of intestinal PXR and CYP3A4 mRNA expression and might be associated with the inter-individual variability

  10. Sphincter Preservation After Short-term Preoperative Radiotherapy for Low Rectal Cancer - Presentation of Own Data and a Literature Review

    International Nuclear Information System (INIS)

    This report is based on a series of 108 patients with clinically staged T2 (9), T3 (94) and T4 (5) rectal cancer treated with preoperative irradiation with 25 Gy, 5 Gy per fraction given for one week. In 77% of patients, the tumour was located within 7 cm of the anal verge and in 15% the anal canal was involved. Surgery was usually undertaken during the week after irradiation. For low tumours, total mesorectal excision was performed, and for middle and upper cancers, the whole circumference of the mesorectum was excised at least 2 cm below the lower pole of a tumour. Tumour was resected in 103 patients, and sphincter-preserving surgery was performed in 73% of them. In the subgroup where the tumour was located higher than 4 cm from the anal verge, sphincter-preserving surgery was performed in 95%. The follow-up period ranged from 10 to 49 months, with a median of 25 months. Local recurrences were observed in 4% of patients. Anorectal dysfunction caused impairment of social life in 40% of patients and 18% admitted that their quality of life was seriously affected - however, none of them stated that they would have preferred a colostomy. These preliminary data suggest that following high dose per fraction short-term preoperative radiotherapy a high rate of sphincter-preserving surgery can be reached, with acceptable anorectal function and an acceptable rate of local failure and late complications. The results of our own data and literature review indicate the need for a randomized clinical trial comparing high dose per fraction preoperative radiotherapy with immediate surgery with conventional preoperative radiochemotherapy with delayed surgery

  11. Cancer Therapy by Catechins Involves Redox Cycling of Copper Ions and Generation of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Mohd Farhan

    2016-02-01

    Full Text Available Catechins, the dietary phytochemicals present in green tea and other beverages, are considered to be potent inducers of apoptosis and cytotoxicity to cancer cells. While it is believed that the antioxidant properties of catechins and related dietary agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, these properties cannot account for apoptosis induction and chemotherapeutic observations. Catechin (C, epicatechin (EC, epigallocatechin (EGC and epigallocatechin-3-gallate (EGCG are the four major constituents of green tea. In this article, using human peripheral lymphocytes and comet assay, we show that C, EC, EGC and EGCG cause cellular DNA breakage and can alternatively switch to a prooxidant action in the presence of transition metals such as copper. The cellular DNA breakage was found to be significantly enhanced in the presence of copper ions. Catechins were found to be effective in providing protection against oxidative stress induced by tertbutylhydroperoxide, as measured by oxidative DNA breakage in lymphocytes. The prooxidant action of catechins involved production of hydroxyl radicals through redox recycling of copper ions. We also determined that catechins, particularly EGCG, inhibit proliferation of breast cancer cell line MDA-MB-231 leading to a prooxidant cell death. Since it is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies, cancer cells would be more subject to redox cycling between copper ions and catechins to generate reactive oxygen species (ROS responsible for DNA breakage. Such a copper dependent prooxidant cytotoxic mechanism better explains the anticancer activity and preferential cytotoxicity of dietary phytochemicals against cancer cells.

  12. Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical risks and lymph-vascular space involvement

    Institute of Scientific and Technical Information of China (English)

    Yue Wang; Guang Wang; Li-Hui Wei; Ling-Hui Huang; Jian-Liu Wang; Shi-Jun Wang; Xiao-Ping Li

    2011-01-01

    Neoadjuvant chemotherapy (NACT),which can reduce the size and therefore increase the resectability of tumors,has recently evolved as a treatment for locally advanced cervical cancer.NACT has been reported to decrease the risk of pathologic factors related to prognosis of cervical cancer.To further assess the effects of NACT on surgery and the pathologic characteristics of cervicat cancer,we reviewed 110 cases of locally advanced cervical cancer treated with radical hysterectomy with or without NACT at the People's Hospital of Peking University between January 2006 and December 2010.Of 110 patients,68 underwent platinum-based NACT prior to surgery (NACT group) and 42 underwent pdmary surgery treatment (PST group).Our results showed 48 of 68 (70.6%) patients achieved a complete response or partial response to NACT.Estimated blood loss,operation time,and number of removed lymph nodes during surgery,as well as complication rates during and after surgery were not significantly different between the NACT group and the PST group.The rates of deep stromal invasion,positive parametria,positive surgical vaginal margins,and lymph node metastasis were not significantly different between the two groups.However,the rate of lymph-vascular space involvement (LVSI) was significantly lower in the NACT group than in the PST group (P = 0.021).In addition,the response rate of NACT was significantly higher in the patients with chemotherapeutic drugs administrated via artery than via vein.Our results suggest that NACT is a safe and effective treatment for locally advanced cervical cancer and significantly decreases the rate of LVSI.

  13. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer – the RAPIDO trial

    International Nuclear Information System (INIS)

    Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative

  14. Short-term mortality in older patients treated with adjuvant chemotherapy for early-stage breast cancer.

    Science.gov (United States)

    Rosenstock, Aron S; Lei, Xiudong; Tripathy, Debu; Hortobagyi, Gabriel N; Giordano, Sharon H; Chavez-MacGregor, Mariana

    2016-06-01

    Chemotherapy for early-stage breast cancer has lowered cancer recurrence and deaths. However, short-term mortality rates due to cancer or treatment in the general population remain largely unknown. In this study, we evaluate the short-term mortality rate and the determinants of such outcome among a cohort of older breast cancer patients treated with adjuvant chemotherapy. This is a population-based study based on the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare and the Texas Cancer Registry (TCR)-Medicare databases. Patients diagnosed with early-stage breast cancer between 2003 and 2011 who were 66 years or older and were treated with adjuvant chemotherapy within 6 months of diagnosis were included. Short-term mortality was defined as death from any cause within one year of breast cancer diagnosis. Descriptive statistics and multivariable logistic regression modeling were used for the analysis. Of the 21,536 patients included, a total of 625 (2.9 %) died within one year of breast cancer diagnosis. In multivariate analysis, older age (using 66-70 as reference category; 71-75 years OR 1.31, 95 % CI 1.05-1.62; 76-80 years OR 1.73, 95 % CI 1.36-2.19; >80 years OR 3.48, 95 % CI 2.7-4.48) and higher comorbidity index (using Charlson score of 0 as a reference, those with score of 1 or >2 had higher risk OR 1.46, 95 % CI 1.19-1.8 and OR 2.98, 95 % CI 2.42-3.67, respectively) were associated with the increased risk of short-term mortality. Other factors significantly associated with the outcome were higher grade and stage, ER-negative status, poor census tract area, and mastectomy. The findings of this study revealed that, in this large cohort of older breast cancer patients treated with adjuvant chemotherapy, 2.9 % of the population died within one year of breast cancer diagnosis. Finally, it was concluded that tumor- and patient-related characteristics were associated with short-term death. Our findings add relevant information that can be

  15. NDRG2: a Myc-repressed gene involved in cancer and cell stress

    Institute of Scientific and Technical Information of China (English)

    Libo Yao; Jian Zhang; Xuewu Liu

    2008-01-01

    As a master switch for cell proliferation and differentiation,Myc exerts its biological functions mainly through transcriptional regulation of its target genes,which are involved in cells' interaction and communication with their external environment.The N-Myc downstream-regulated gene (NDRG) family is composed ofNDRG1,NDRG2,NDRG3 and NDRG4,which are important in cell proliferation and differentiation.This review summarizes the recent studies on the structure,tissue distribution and functions of NDRG2 that try to show its significance in studying cancer and its therapeutic potential.

  16. JNK signaling pathway is involved in piperlongumine-mediated apoptosis in human colorectal cancer HCT116 cells

    OpenAIRE

    Li, Wen; WEN, CHUANGYU; BAI, HAIYAN; Wang, Xiaoyan; Zhang, Xiaoli; HUANG, LANLAN; Yang, Xiangling; Iwamoto, Aikichi; Liu, Huanliang

    2015-01-01

    Piperlongumine (PPLGM), an alkaloid isolated from the long pepper (Piper longum L.), can selectively trigger cancer cell death in colorectal cancer cells. The present study investigated whether the c-Jun NH2-terminal kinase (JNK) signaling pathway is involved in PPLGM-induced apoptosis in the human colorectal cancer HCT116 cell line. The results demonstrated that PPLGM reduced the cell viability and induced cell apoptosis in a time- and concentration-dependent manner, without a significant ef...

  17. DEVELOPMENT OF THE NOMOGRAM THAT PREDICTS PATHOLOGICAL LYMPH NODE INVOLVEMENT IN BLADDER CANCER PATIENTS BASED ON CLINICAL VARIABLES

    OpenAIRE

    L. V. Mirylenko; O. G. Sukonko; A. V. Pravorov; A. I. Rolevich; A. S. Mavrichev

    2014-01-01

    Objective: to develop nomogram based on clinical variables, that predicts pathological lymph node involvement (рN+) in bladder cancer patients.Material and methods: We used data of 511 patients with bladder cancer, that have undergone radical cystectomy between 1999 and 2008 at N.N. Alexandrov National Cancer Centre. Mono- and multivariate logistic regression analyses were used for pN+ prediction on preoperative data. Coefficients from logistic regression equation were used to construct the n...

  18. 3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells.

    Science.gov (United States)

    Liu, Zhe; Sun, Yiming; Hong, Haiyu; Zhao, Surong; Zou, Xue; Ma, Renqiang; Jiang, Chenchen; Wang, Zhiwei; Li, Huabin; Liu, Hao

    2015-01-01

    Increasing evidence demonstrates that the hexokinase inhibitor 3-bromopyruvate (3-BrPA) induces the cell apoptotic death by inhibiting ATP generation in human cancer cells. Interestingly, some tumor cell lines are less sensitive to 3-BrPA-induced apoptosis than others. Moreover, the molecular mechanism of 3-BrPA-trigged apoptosis is unclear. In the present study, we examined the effects of 3-BrPA on the viability of the breast cancer cell lines MDA-MB-231 and MCF-7. We further investigated the potential roles of monocarboxylate transporter 1 (MCT1) in drug accumulation and efflux of breast cancer cells. Finally, we explored whether 3-BrPA enhanced daunorubicin (DNR)-induced cytotoxicity through regulation of MCT1 in breast cancer cells. MTT and colony formation assays were used to measure cell viability. Western blot analysis, flow cytometric analysis and fluorescent microscopy were used to determine the molecular mechanism of actions of MCT1 in different breast cancer cell lines. Whole-body bioluminescence imaging was used to investigate the effect of 3-BrPA in vivo. We found that 3-BrPA significantly inhibited cell growth and induced apoptosis in MCF-7 cell line, but not in MDA-MB-231 cells. Moreover, we observed that 3-BrPA efficiently enhanced DNR-induced cytotoxicity in MCF-7 cells by inhibiting the activity of ATP-dependent efflux pumps. We also found that MCT1 overexpression increased the efficacy of 3-BrPA in MDA-MB-231 cells. 3-BrPA markedly suppressed subcutaneous tumor growth in combination with DNR in nude mice implanted with MCF-7 cells. Lastly, our whole-body bioluminescence imaging data indicated that 3-BrPA promoted DNR accumulation in tumors. These findings collectively suggest that 3-BrPA enhanced DNR antitumor activity in breast cancer cells involved MCT-1, suggesting that inhibition of glycolysis could be an effective therapeutic approach for breast cancer treatment. PMID:26609475

  19. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer - the RAPIDO trial

    NARCIS (Netherlands)

    Nilsson, Per J.; van Etten, Boudewijn; Hospers, Geke A. P.; Pahlman, Lars; van de Velde, Cornelis J. H.; Beets-Tan, Regina G. H.; Blomqvist, Lennart; Beukema, Jannet C.; Kapiteijn, Ellen; Marijnen, Corrie A. M.; Nagtegaal, Iris D.; Wiggers, Theo; Glimelius, Bengt

    2013-01-01

    Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized

  20. Occult Pelvic Lymph Node Involvement in Bladder Cancer: Implications for Definitive Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, Benjamin; Baumann, Brian C.; He, Jiwei; Tucker, Kai; Bekelman, Justin; Deville, Curtiland; Vapiwala, Neha [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vaughn, David; Keefe, Stephen M. [Department of Medical Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas; Malkowicz, S. Bruce [Department of Urology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2014-03-01

    Purpose: To inform radiation treatment planning for clinically staged, node-negative bladder cancer patients by identifying clinical factors associated with the presence and location of occult pathologic pelvic lymph nodes. Methods and Materials: The records of patients with clinically staged T1-T4N0 urothelial carcinoma of the bladder undergoing radical cystectomy and pelvic lymphadenectomy at a single institution were reviewed. Logistic regression was used to evaluate associations between preoperative clinical variables and occult pathologic pelvic or common iliac lymph nodes. Percentages of patient with involved lymph node regions entirely encompassed within whole bladder (perivesicular nodal region), small pelvic (perivesicular, obturator, internal iliac, and external iliac nodal regions), and extended pelvic clinical target volume (CTV) (small pelvic CTV plus common iliac regions) were calculated. Results: Among 315 eligible patients, 81 (26%) were found to have involved pelvic lymph nodes at the time of surgery, with 38 (12%) having involved common iliac lymph nodes. Risk of occult pathologically involved lymph nodes did not vary with clinical T stage. On multivariate analysis, the presence of lymphovascular invasion (LVI) on preoperative biopsy was significantly associated with occult pelvic nodal involvement (odds ratio 3.740, 95% confidence interval 1.865-7.499, P<.001) and marginally associated with occult common iliac nodal involvement (odds ratio 2.307, 95% confidence interval 0.978-5.441, P=.056). The percentages of patients with involved lymph node regions entirely encompassed by whole bladder, small pelvic, and extended pelvic CTVs varied with clinical risk factors, ranging from 85.4%, 95.1%, and 100% in non-muscle-invasive patients to 44.7%, 71.1%, and 94.8% in patients with muscle-invasive disease and biopsy LVI. Conclusions: Occult pelvic lymph node rates are substantial for all clinical subgroups, especially patients with LVI on biopsy. Extended

  1. Occult Pelvic Lymph Node Involvement in Bladder Cancer: Implications for Definitive Radiation

    International Nuclear Information System (INIS)

    Purpose: To inform radiation treatment planning for clinically staged, node-negative bladder cancer patients by identifying clinical factors associated with the presence and location of occult pathologic pelvic lymph nodes. Methods and Materials: The records of patients with clinically staged T1-T4N0 urothelial carcinoma of the bladder undergoing radical cystectomy and pelvic lymphadenectomy at a single institution were reviewed. Logistic regression was used to evaluate associations between preoperative clinical variables and occult pathologic pelvic or common iliac lymph nodes. Percentages of patient with involved lymph node regions entirely encompassed within whole bladder (perivesicular nodal region), small pelvic (perivesicular, obturator, internal iliac, and external iliac nodal regions), and extended pelvic clinical target volume (CTV) (small pelvic CTV plus common iliac regions) were calculated. Results: Among 315 eligible patients, 81 (26%) were found to have involved pelvic lymph nodes at the time of surgery, with 38 (12%) having involved common iliac lymph nodes. Risk of occult pathologically involved lymph nodes did not vary with clinical T stage. On multivariate analysis, the presence of lymphovascular invasion (LVI) on preoperative biopsy was significantly associated with occult pelvic nodal involvement (odds ratio 3.740, 95% confidence interval 1.865-7.499, P<.001) and marginally associated with occult common iliac nodal involvement (odds ratio 2.307, 95% confidence interval 0.978-5.441, P=.056). The percentages of patients with involved lymph node regions entirely encompassed by whole bladder, small pelvic, and extended pelvic CTVs varied with clinical risk factors, ranging from 85.4%, 95.1%, and 100% in non-muscle-invasive patients to 44.7%, 71.1%, and 94.8% in patients with muscle-invasive disease and biopsy LVI. Conclusions: Occult pelvic lymph node rates are substantial for all clinical subgroups, especially patients with LVI on biopsy. Extended

  2. Ten Tips for Promoting Autonomous Learning and Effective Engagement in the Teaching of Statistics to Undergraduate Medical Students Involved in Short-Term Research Projects

    Science.gov (United States)

    MacDougall, Margaret

    2008-01-01

    This article seeks to present some of the key challenges in facilitating autonomous learning and effective engagement in the teaching of statistics to undergraduate medical students involved in short-term research projects. With a view to addressing these challenges, recommendations for good practice are presented in the form of ten tips for…

  3. Management of airway involvement of oesophageal cancer using covered retrievable nitinol stents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K.E. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Shin, J.H. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)], E-mail: jhshin@amc.seoul.kr; Song, H.Y. [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Kim, S.B. [Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Kim, K.R.; Kim, J. Hyoung [Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2009-02-15

    Aim: To assess the efficacy and safety of covered retrievable nitinol stents in oesophageal cancer patients with airway involvement. Materials and methods: Under fluoroscopic guidance, covered retrievable nitinol airway stents were placed in 23 oesophageal cancer patients with airway stricture and/or oesophagorespiratory fistula (ERF) over a long period of 12 years. Six patients only had aspiration by ERF and three patients had both airway stricture and asymptomatic ERF. Technical aspects, dyspnoea improvement, and/or resolution of ERF symptoms, complications, reinterventions, and survival data were evaluated. Results: A total of 27 airway stents (14 tracheal, 11 bronchial, and two hinged) were placed successfully in 23 patients with airway stricture or ERF. Dyspnoea score decreased significantly after stent placement (p < 0.001). ERF were sealed off in all nine patients. Complications included stent migration or expectoration (n = 4), haemoptysis (n = 2), sputum retention (n = 7), and tumour overgrowth (n = 1). All three migrated stents were easily removed. Twenty-one patients died, with the median survival period of 76 days (range 2-197 days). Conclusion: Placement of covered retrievable expandable nitinol stents was safe and effective for the palliative treatment of airway strictures and/or ERF, with a reasonable range of complications, in patients with advanced oesophageal cancer.

  4. Bioinformatics Analysis for Coding SNPs of the HLADQA1 Gene Involved in Susceptibility to Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    Yanyun Li; Jun Xing; Linsheng Zhao; Yanni Li; Yuchuan Wang; Weiming Zhang

    2006-01-01

    OBJECTIVE To analyze coding SNPs of the HLA-DQA1 gene involved in susceptibility for cervical cancer by a bioinformatics approach, and to choose some SNPs that may have an association with cervical cancer.METHODS By a SNPper tool we extracted SNPs from a public database (dbSNP), exporting them in FASTA formats suitable for subsequent use.Then we used PARSESNP as a tool for the analysis of the cSNPs.RESULTS In the cSNPs of the HLA-DQA1 gene, we find that rs9272693and rs9272703, are made up of missense mutations which convert a codon for one amino acid into a codon for a different amino acid. We chose a PSSM Difference >10 as a lower level for the scores of changes predicted to be deldterious.CONCLUSION We used a bioinformatics approach for cSNPs analysis of the HLA-DQA1 gene. This method can select the variants in a conserved region, and give a PSSM Difference score. But the results need to be verified in cervical cancer patients and a control population.

  5. Short-chain ceramides depress integrin cell surface expression and function in colorectal cancer cells.

    Science.gov (United States)

    Morad, Samy A F; Bridges, Lance C; Almeida Larrea, Alex D; Mayen, Anthony L; MacDougall, Matthew R; Davis, Traci S; Kester, Mark; Cabot, Myles C

    2016-07-01

    Colorectal cancer (CRC) is highly metastatic, significantly so to liver, a characteristic that embodies one of the most challenging aspects of treatment. The integrin family of cell-cell and cell-matrix adhesion receptors plays a central role in migration and invasion, functions that underlie metastatic potential. In the present work we sought to determine the impact of ceramide, which plays a key modulatory role in cancer suppression, on integrin cell surface expression and function in CRC cells in order to reveal possible ceramide-centric effects on tumor cell motility. Human CRC cells LoVo, HT-29, and HCT-116 were employed, which represent lines established from primary and metastatic sites. A cell-permeable, short-chain analog, C6-ceramide, was used as ceramide mimic. Exposure of cells to C6-ceramide (24 h) promoted a dose-dependent (2.5-10 µM) decrease in the expression of cell surface β1 and β4 integrin subunits in all cell lines; at 10 µM C6-ceramide, the decreases ranged from 30 to 50% of the control. Expression of cell surface αVβ6 integrin, which is associated with advanced invasion in CRC, was also suppressed by C6-ceramide. Decreases in integrin expression translated to diminished cellular adhesion, 50% of the control at 5 µM C6-ceramide, and markedly reduced cellular migration, approximately 30-40% of the control in all cell lines. Physicochemical examination revealed potent efficacy of nano-formulated C6-ceramide, but inferior activity of dihydro-C6-ceramide and L-C6-ceramide, compared to the unsaturated counterpart and the natural d-enantiomer, respectively. These studies demonstrate novel actions of ceramides that may have application in suppression of tumor metastasis, in addition to their known tumor suppressor effects. PMID:27045476

  6. Proteomic analysis of pathways involved in estrogen-induced growth and apoptosis of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhang-Zhi Hu

    Full Text Available BACKGROUND: Estrogen is a known growth promoter for estrogen receptor (ER-positive breast cancer cells. Paradoxically, in breast cancer cells that have been chronically deprived of estrogen stimulation, re-introduction of the hormone can induce apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Here, we sought to identify signaling networks that are triggered by estradiol (E2 in isogenic MCF-7 breast cancer cells that undergo apoptosis (MCF-7:5C versus cells that proliferate upon exposure to E2 (MCF-7. The nuclear receptor co-activator AIB1 (Amplified in Breast Cancer-1 is known to be rate-limiting for E2-induced cell survival responses in MCF-7 cells and was found here to also be required for the induction of apoptosis by E2 in the MCF-7:5C cells. Proteins that interact with AIB1 as well as complexes that contain tyrosine phosphorylated proteins were isolated by immunoprecipitation and identified by mass spectrometry (MS at baseline and after a brief exposure to E2 for two hours. Bioinformatic network analyses of the identified protein interactions were then used to analyze E2 signaling pathways that trigger apoptosis versus survival. Comparison of MS data with a computationally-predicted AIB1 interaction network showed that 26 proteins identified in this study are within this network, and are involved in signal transduction, transcription, cell cycle regulation and protein degradation. CONCLUSIONS: G-protein-coupled receptors, PI3 kinase, Wnt and Notch signaling pathways were most strongly associated with E2-induced proliferation or apoptosis and are integrated here into a global AIB1 signaling network that controls qualitatively distinct responses to estrogen.

  7. Short-course PET based simultaneous integrated boost for locally advanced cervical cancer

    International Nuclear Information System (INIS)

    Patients with large, locally advanced cervical cancers (LACC) are challenging to treat. The purpose of this work is to use 18F-FDG PET as planning basis for a short-course simultaneous integrated boost (SIB) in external beam radiotherapy of LACC in order to increase tumour shrinkage and likelihood of local control. Ten previously treated patients with LACC were included, all with pre-treatment FDG PET/CT images available. The FDG avid tumour volume, MTV50, was dose escalated in silico by intensity modulated radiotherapy from the standard 1.8 Gy to 2.8 Gy per fraction for the 10 first fractions; a short-course SIB. For the 18 remaining external fractions, standard pelvic treatment followed to total PTV and MTV50 doses of 50.4 Gy and 60.4 Gy, respectively. Photon and proton treatment were considered using volumetric modulated arc treatment (VMAT) and intensity-modulated proton therapy (IMPT), respectively. All treatment plans were generated using the Eclipse Treatment Planning System (TPS). The impact of tumour shrinkage on doses to organs at risk (OARs) was simulated in the TPS for the SIB plans. Dose escalation could be implemented using both VMAT and IMPT, with a D98 ≥ 95 % for MTV50 being achieved in all cases. The sum of the 10 fraction short-course SIB and subsequent 18 standard fractions was compared to the standard non-SIB approach by dose volume histogram (DVH) analysis. Only marginal increase of dose to OARs was found for both modalities and a small further increase estimated from tumour shrinkage. Most DVH parameters showed a mean difference below 2 %. IMPT had, compared to VMAT, reduced OAR doses in the low to intermediate dose range, but showed no additional advantage in dose escalation. Planning of dose escalation based on a FDG avid boost volume was here demonstrated feasible. The concept may allow time for enhanced tumour shrinkage before brachytherapy. Thus, this strategy may prove clinically valuable, in particular for patients with large tumours

  8. Use of spiral CT angiography to judge central pulmonary vascular involvement from lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the accuracy of spiral CT angiography (SCTA) in judging central pulmonary vascular involvement from lung cancer located in the hilum and correlate the resultant images with pathologic and surgical findings. Methods: SCTA was done in 33 patients who were preoperatively diagnosed as having lung carcinoma located in the hilum. Contrast medium was injected at a rate of 3 ml/sec with a power injector. The delay time was from 20 to 25 seconds. The pitch was 1 with 3 mm-collimation. Images of central pulmonary arteries and veins were reconstructed with shaded surface display (SSD), maximum intensity projection (MIP), curved planar reformation (CPR), and multi-planar reformation (MPR). Then the relation between tumor and vessels was assessed prospectively on both 3 mm interval axial CT and SCTA images with comparison to subsequent pathologic or surgical findings. Results: (1) In showing the integrity of central pulmonary arteries and veins, images reconstructed by different ways of SCTA had different strong and weak points. (2) The grading standard in this study, with which the relation between vessels and tumor was judged, reflected the basic and common characters of central pulmonary vascular involvement by tumor located in the hilum. compared with axial CT images, SCTA was more accurate in judging the relation between central pulmonary vessels and tumor, and the correlation of SCTA imaging features with pathological patterns and surgical findings was better than that of axial CT images, P < 0.05 and P < 0.0001, respectively. Conclusion: It was feasible to show the relation between central pulmonary vessel and lung cancer located in the hilum with SCTA. And the accuracy of judging the vascular involvement with SCTA was higher than that with axial CT

  9. Short-Term Side Effects after Radioiodine Treatment in Patients with Differentiated Thyroid Cancer.

    Science.gov (United States)

    Lu, Liyan; Shan, Fengling; Li, Wenbin; Lu, Hankui

    2016-01-01

    Objectives. I-131 therapy for differentiated thyroid cancer (DTC) could induce adverse effects. The purpose of this study was to report and analyze symptoms after I-131 treatment within the hospitalization and present relevant medical intervention. Methods. I-131 doses ranging from 3.7 to 9.25 GBq (100-250 mCi) were administrated for thyroid remnant ablation or treating DTC metastases. 117 patients with DTC for I-131 therapy were monitored through the video and intercommunicating with standardized questionnaire at different time points after I-131 oral administration. Adverse effects were recorded and relevant clinical factors were analyzed. Results. Among all the 117 patients, 55 cases complained of neck's pain or swelling and 79 cases presented with gastrointestinal symptoms. Pain or swelling of salivary gland occurred in 15 patients, headache and vertigo in 10, insomnia in 9, vocal cord paralysis in 6, fatigue or general malaise in 6, and foreign body sensation in 5. Body numbness and urinary symptoms were observed in only 1 case, respectively. Those side effects were related with sex, pre-I-131 treatment TSH levels, frequency of I-131 therapy, and lymph node metastases. Conclusions. Short-term side effects after I-131 therapy for DTC patients varied individually; severe symptoms were not uncommon but generally did not need emergent medical intervention. PMID:26989683

  10. Short-term pretreatment DCE-MRI in prediction of outcome in locally advanced cervical cancer

    International Nuclear Information System (INIS)

    Background and purpose: Several investigators have indicated that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has the potential to provide biomarkers for personalized treatment of cervical carcinoma. However, some clinical studies have suggested that treatment failure is associated with low tumor signal enhancement, whereas others have reported associations between high signal enhancement and poor outcome. The purpose of this investigation was to clear up these conflicting reports and to provide a method for identifying biomarkers that easily can be implemented in routine DCE-MRI diagnostics. Methods: The study involved 85 patients (FIGO stage IB through IVA) treated with concurrent chemoradiotherapy. Low-enhancing tumor volume (LETV) and low-enhancing tumor fraction (LETF), defined as the volume and fractional volume of low-enhancing voxels, respectively, were calculated from signal intensities recorded within 1 min after contrast administration by using two methods reported to give conflicting conclusions. Results: Multivariate analysis involving tumor volume, lymph node status, FIGO stage, and LETV or LETF revealed that LETV and LETF provided independent prognostic information on treatment outcome, independent of the method of calculation. Conclusion: Low signal enhancement is associated with poor prognosis in cervical carcinoma, and biomarkers predicting poor outcome can be provided by short-term DCE-MRI without advanced image analysis

  11. Thyroid cancer in the Marshallese: relative risk of short-lived internal emitters and external radiation exposure

    International Nuclear Information System (INIS)

    In a study of the comparative effects of internal versus external irradiation of the thyroid in young people, we determined that the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times less thyroid cancer than did the same dose of radiation given externally. The authors determined this finding for a group of 85 Marshall Islands children, who were less than 10 years of age at the time of exposure and who were accidentally exposed to internal and external thyroid radiation at an average level of 1400 rad. The external risk coefficient ranged between 2.5 and 4.9 cancers per million person-rad-years at risk, and thus, from our computations, the internal risk coefficient for the Marshallese children was estimated to range between 1.0 and 1.4 cancers per million person-rad-years at risk. In contrast, for individuals more than 10 years of age at the time of exposure, the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times more thyroid cancer than did the same dose of radiation given externally. The external risk coefficients for the older age groups were reported in the above literature to be in the range of 1.0 to 3.3 cancers per million person-rad-years-at risk. The authors computed internal risk coefficients of 3.3 to 8.1 cancers per million person-rad-years at risk for adolescent and adult groups. This higher sensitivity to cancer induction in the exposed adolescents and adults, is different from that seen in other exposed groups. The small number of cancers in the exposed population and the influence of increased levels of TSH, nonuniform irradiation of the thyroid, and thyroid cell killing at high dose make it difficult to draw firm conclusions from these studies. 14 references, 8 tables

  12. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer.

    Science.gov (United States)

    Wu, Sheng-Kai; Chiang, Chi-Feng; Hsu, Yu-Hone; Lin, Tzu-Hung; Liou, Houng-Chi; Fu, Wen-Mei; Lin, Win-Li

    2014-01-01

    The blood-brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. PMID:25278753

  13. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Science.gov (United States)

    Wu, Sheng-Kai; Chiang, Chi-Feng; Hsu, Yu-Hone; Lin, Tzu-Hung; Liou, Houng-Chi; Fu, Wen-Mei; Lin, Win-Li

    2014-01-01

    The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. PMID:25278753

  14. Recruitment strategies for a lung cancer chemoprevention trial involving ex-smokers.

    Science.gov (United States)

    Kye, Steve H; Tashkin, Donald P; Roth, Michael D; Adams, Bradley; Nie, Wen-Xian; Mao, Jenny T

    2009-09-01

    The ability to recruit qualified subjects who are willing to adhere to the study protocol in clinical trials is an essential component of translational research. Such tasks can be particularly challenging for chemoprevention studies when the targeted study population is healthy, at risk individuals who do not have signs or symptoms of the disease, and the study participation involves complex scheduling and invasive procedures such as bronchoscopy. In this report, we describe the recruitment process and evaluated the effectiveness of various recruitment strategies utilized in our National Cancer Institute sponsored lung cancer chemoprevention study with celecoxib. Heavy ex-smokers were recruited into the study through various methods such as radio advertisements, print media, mass mailings, flyers, internet postings and others. The number of inquiries, on-site screenees and randomization generated by each method determined the efficacy of that recruitment strategy. We prescreened 4470 individuals, invited 323 people for on-site screening and randomized 137 subjects. Radio advertisements (ads) generated the most inquiries (71.1%), followed by internet posting (11.8%), print media (6.0%), posted and racked flyers (4.4%), mass mailings (2.7%) and other strategies such as referrals from friends or family members or health care providers (2.3%). Radio ads, although costly, yielded the most subjects for on-site screening and randomization. Moreover, among the various types of radio stations, news radio stations were by far the most successful. Our results suggest that advertising on news radio is a highly effective recruitment method for successful accrual of ex-smokers into lung cancer chemoprevention trials. PMID:19508900

  15. NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells

    International Nuclear Information System (INIS)

    Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-κB is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-κB activation. Here, we show that the alternative pathway is constitutively activated and NF-κB-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

  16. Intensive medical student involvement in short-term surgical trips provides safe and effective patient care: a case review

    OpenAIRE

    Macleod Jana B; Wheatley Matthew A; Creighton Francis X; Leeds Ira L; Srinivasan Jahnavi; Chery Marie P; Master Viraj A

    2011-01-01

    Abstract Background The hierarchical nature of medical education has been thought necessary for the safe care of patients. In this setting, medical students in particular have limited opportunities for experiential learning. We report on a student-faculty collaboration that has successfully operated an annual, short-term surgical intervention in Haiti for the last three years. Medical students were responsible for logistics and were overseen by faculty members for patient care. Substantial pl...

  17. DUBbing Cancer: Deubiquitylating Enzymes Involved in Epigenetics, DNA Damage and the Cell Cycle As Therapeutic Targets

    Science.gov (United States)

    Pinto-Fernandez, Adan; Kessler, Benedikt M.

    2016-01-01

    Controlling cell proliferation is one of the hallmarks of cancer. A number of critical checkpoints ascertain progression through the different stages of the cell cycle, which can be aborted when perturbed, for instance by errors in DNA replication and repair. These molecular checkpoints are regulated by a number of proteins that need to be present at the right time and quantity. The ubiquitin system has emerged as a central player controlling the fate and function of such molecules such as cyclins, oncogenes and components of the DNA repair machinery. In particular, proteases that cleave ubiquitin chains, referred to as deubiquitylating enzymes (DUBs), have attracted recent attention due to their accessibility to modulation by small molecules. In this review, we describe recent evidence of the critical role of DUBs in aspects of cell cycle checkpoint control, associated DNA repair mechanisms and regulation of transcription, representing pathways altered in cancer. Therefore, DUBs involved in these processes emerge as potentially critical targets for the treatment of not only hematological, but potentially also solid tumors.

  18. Thyroid cancer in the Marshallese: relative risk of short-lived internal emitters and external radiation exposure

    International Nuclear Information System (INIS)

    In a study of the comparative effects of internal versus external irradiation of the thyroid in young people, we determined that the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times less thyroid cancer than did the same dose of radiation given externally. We determined this finding for a group of 85 Marshall Islands children, who were less than 10 years of age at the time of exposure and who were accidentially exposed to internal and external thyroid radiation at an average level of 1400 rad. The external risk coefficient ranged between 2.5 and 4.9 cancers per million person-rad-years at risk, and thus, from our computations, the internal risk coefficient for the Marshallese children was estimated to range between 1.0 and 1.4 cancers per million person-rad-years at risk. In contrast, for individual more than 10 years of age at the time of exposure, the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times more thyroid cancer than did the same dose of radiation given externally. The external risk coefficients for the older age groups were reported in the literature to be in the range of 1.0 to 3.3 cancers per million person-rad-years-at risk. We computed internal risk coefficients of 3.3 to 8.1 cancers per million person-rad-years at risk for adolescent and adult groups. This higher sensitivity to cancer induction in the exposed adolescents and adults, is different from that seen in other exposed groups. 14 refs., 8 tabs

  19. Potential signaling pathway involved in sphingosine-1-phosphate-induced epithelial-mesenchymal transition in cancer

    Science.gov (United States)

    ZENG, YE; YAO, XING-HONG; YAN, ZHI-PING; LIU, JING-XIA; LIU, XIAO-HENG

    2016-01-01

    The developmental process of epithelial-mesenchymal transition (EMT) occurs when epithelial cells acquire invasive mesenchymal cell characteristics, and the activation of this process has been indicated to be involved in tumor progression. EMT could be induced by growth factors, cytokines and matrix metalloproteinases (MMPs). sphingosine-1-phosphate (S1P) is a biologically-active lipid that plays an important role in cancer metastasis. S1P also contributes to the activation of EMT. However, the mechanism underlying S1P-induced EMT is unclear. Increased evidence has demonstrated that the cell surface glycocalyx is closed associated with S1P and plays an important role in tumor progression, suggesting that S1P-induced EMT could be Snail-MMP signaling-dependent. Thus, we hypothesize that an S1P-glycocalyx-Snail-MMP signaling axis mediates S1P-induced EMT. This is an essential step towards improved understanding of the underlying mechanism involved in S1P-regulted EMT, and the development of novel diagnostic and anticancer therapeutic strategies. PMID:27347154

  20. Accuracy of High-Resolution MRI with Lumen Distention in Rectal Cancer Staging and Circumferential Margin Involvement Prediction

    OpenAIRE

    Iannicelli, Elsa; Di Renzo, Sara; ferri, mario; Pilozzi, Emanuela; Di Girolamo, Marco; Sapori, Alessandra; Ziparo, Vincenzo; David, Vincenzo

    2014-01-01

    Objective To evaluate the accuracy of magnetic resonance imaging (MRI) with lumen distention for rectal cancer staging and circumferential resection margin (CRM) involvement prediction. Materials and Methods Seventy-three patients with primary rectal cancer underwent high-resolution MRI with a phased-array coil performed using 60-80 mL room air rectal distention, 1-3 weeks before surgery. MRI results were compared to postoperative histopathological findings. The overall MRI T staging accuracy...

  1. Downregulation of MTDH using short hairpin RNA inhibited EMT in breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Heng Cao; Zhaozhe Liu; Dongchu Ma; Zhenyu Ding; Cheng Du; Xiaodong Xie

    2013-01-01

    Objective: Metadherin (MTDH) could regulate epithelial-mesenchymal transition (EMT), and is involved in tumor metastasis.This study was designed to observe the effect of MTDH-short hairpin RNA (shRNA) on EMT, and the role of MTDH in breast tumor metastasis. Methods: RNA interference plasmid that can express shRNA targeting MTDH or shRNA-negative plasmid that does not match any known human coding mRNA was designed, constructed and named MTDH-shRNA and MTDH-shRNA-neg, which were transiently transfected into MDA-MB-231 cells using LipofectamineTM2000. After 48 h, the levels of MTDH, E-cadherin and α-SMA expression were determined by reverse transcription-polymerase chain reactin (RTPCR), Western blot. The invasion and immigration potential was examined by Transwell chamber invasion or migration assay. Results: Compared with MDA-MB-231, the MTDH mRNA level was down-regulated by 41.2%, the MTDH protein level was down-regulated by 40.3%. The invasion and immigration potential of MDA-MB-231 cells was decreased after transfection of MTDH-shRNA. Compared with MDA-MB-231 or MTDH-shRNA-neg, the mRNA and protein level of α-SMA was reduced and E-candherin were increased in MTDH-shRNA, with statistical significance. Conclusion: Downregulation of MTDH increase suppresse migration and invasion in MDA-MB-231 cells.

  2. Seasonal phenology of interactions involving short-lived annual plants, a multivoltine herbivore and its endoparasitoid wasp

    NARCIS (Netherlands)

    Fei, M.; Gols, R.; Harvey, J.A.

    2014-01-01

    Spatial-temporal realism is often missing in many studies of multitrophic interactions, which are conducted at a single time frame and/or involving interactions between insects with a single species of plant. In this scenario, an underlying assumption is that the host-plant species is ubiquitous thr

  3. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Directory of Open Access Journals (Sweden)

    Wu SK

    2014-09-01

    Full Text Available Sheng-Kai Wu,1 Chi-Feng Chiang,1 Yu-Hone Hsu,1,4 Tzu-Hung Lin,2 Houng-Chi Liou,2 Wen-Mei Fu,2 Win-Li Lin1,3 1Institute of Biomedical Engineering, College of Medicine and College of Engineering, 2Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; 4Department of Neurosurgery, Cheng-Hsin General Hospital, Taipei, Taiwan Abstract: The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The

  4. Prostate cancer multimodal therapy involvement in couple life: Open, Robotic and HIFU approach

    Directory of Open Access Journals (Sweden)

    Elisabeta Ioana Hirişcău

    2010-12-01

    Full Text Available The diagnosis and treatment of prostate cancer often results in significant physical side-effectsand associated psycho-social stressors that can interfere with the experience of sexual intimacy forcouples. Our study aims to evaluate couple’s sexual life and to determine any potential sexual dynamicdysfunctions which could occur before and after performing classic, robotic and HIFU radicalprostatectomy as a radical therapy in prostate cancer. The present article aims at the synopticpresentation of results of a statistic research done by the author regarding the factors that influencecouple’s sex life, and also at the identification of potential dynamic disorder that could come up before aradical prostatectomy (disorders that influence the sexual prognostic following the intervention. Materialand method: the research involved 28 couples (56 individuals and was conducted in The Municipal Clinicand in The Endoplus Clinic in Cluj-Napoca. The initial evaluation aimed to identify sexual dynamicdysfunctions before the intervention. The couples filled in an interview sheet before the intervention andwere informed about the immediate and long term effects of the intervention and of existing therapeuticsolutions. The confidentiality of interview answers has been insured and the interviews have beencollected and sealed the day of the intervention. The structure of the interview is based on the BASIC IDgrid proposed by Lazarus in 1973 which aims to establish a therapeutic action profile which would allow amultimodal intervention. All patients underwent the prostate cancer intervention as follows: 10 patientsunderwent open surgery, 9 patients robotic surgery and 9 patients HIFU therapy. Results: Each partnerof the couple was reevaluated two months after the radical therapy. The main goal of evaluating thesexual behavior was to obtain valid information in order to make the optimal therapeutic decision. Thepartner’s answer frequency for both pre and

  5. Short-term outcomes after laparoscopic surgery following preoperative chemoradiotherapy for rectal cancer

    OpenAIRE

    Ahn, Byong Hyon; Lee, Kyung Ha; Park, Jun Beom; Song, Min Sang; Kim, Ji Yeon; Kim, Jin Soo

    2012-01-01

    Purpose The safety and the feasibility of performing laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy (CRT) have not yet been established. Thus, the aim of this study was to evaluate the efficacy and the safety of laparoscopic rectal cancer surgery performed after preoperative CRT. Methods We enrolled 124 consecutive patients who underwent laparoscopic surgery for rectal cancer. Of these patients, 56 received preoperative CRT (CRT group), whereas 68 did not (non-CRT...

  6. Lymphoscintigraphy in breast cancer: a short review about the impact on upper limb after surgical treatment

    Directory of Open Access Journals (Sweden)

    Anke Bergmann

    2008-12-01

    Full Text Available Breast cancer is still associated with high mortality rates and one of the most important factors governing long survival is accurate and early diagnosis. In underdeveloped countries, this disease frequently is only detected in advanced stages; however, through mammography, many women have been diagnosed at early stages. In this context, the sentinel lymph node (SLN technique is associated with less postoperative morbidity compared to axillary lymphadenectomy. Lymphoscintigraphy has emerged as a method for the evaluation of lymphatic drainage chains in various tumours, being both accurate and non invasive. The aim of this work is to present the main aspects which cause controversy about SLN and lymphoscintigraphy and the impact that these procedures have had on lymphedema after surgical treatment for breast cancer. A short review including papers in English, Spanish and Portuguese, available on Lilacs and Medline database, published between January, 2000 and July, 2008 was performed. The key words breast cancer, lymphoscintigraphy, SLN biopsy, lymphedema were used. Various studies have aimed to compare the incidence and prevalence of lymphedema according to the technique used; however, the population subjected to SLN is different from the one with indication for axillary lymphadenectomy regarding staging. Moreover, little is known about long term morbidity since it is a relatively new technique. In conclusion, the development of surgical techniques has permitted to minimize deformities and the current trend is that these techniques be as conservative as possible. Thus, lymphoscintigraphy plays an important role in the identification of SLN, contributing to the prevention and minimization of postoperative complications.O câncer de mama é ainda associado com altas taxas de mortalidade e um dos mais importantes fatores de manutenção de longa sobrevivência é a precisão e o diagnóstico precoce. Em países em desenvolvimento, essa doença freq

  7. Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical risks and lymph-vascular space involvement

    OpenAIRE

    Wang, Yue; Wang, Guang; Wei, Li-Hui; Huang, Ling-Hui; Wang, Jian-Liu; Wang, Shi-Jun; Li, Xiao-Ping; Shen, Dan-Hua; Bao, Dong-Mei; Gao, Jian

    2011-01-01

    Neoadjuvant chemotherapy (NACT), which can reduce the size and therefore increase the resectability of tumors, has recently evolved as a treatment for locally advanced cervical cancer. NACT has been reported to decrease the risk of pathologic factors related to prognosis of cervical cancer. To further assess the effects of NACT on surgery and the pathologic characteristics of cervical cancer, we reviewed 110 cases of locally advanced cervical cancer treated with radical hysterectomy with or w...

  8. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    OpenAIRE

    Deniz Arslan; Mukremin Uysal; Ali Murat Tatlı; Seyda Gunduz; Sema Sezgin Goksu; Cumhur İbrahim Başsorgun; Hasan Senol Coskun; Hakan Bozcuk; Burhan Savaş

    2014-01-01

    Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM) and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding i...

  9. Intensive medical student involvement in short-term surgical trips provides safe and effective patient care: a case review

    Directory of Open Access Journals (Sweden)

    Macleod Jana B

    2011-09-01

    Full Text Available Abstract Background The hierarchical nature of medical education has been thought necessary for the safe care of patients. In this setting, medical students in particular have limited opportunities for experiential learning. We report on a student-faculty collaboration that has successfully operated an annual, short-term surgical intervention in Haiti for the last three years. Medical students were responsible for logistics and were overseen by faculty members for patient care. Substantial planning with local partners ensured that trip activities supplemented existing surgical services. A case review was performed hypothesizing that such trips could provide effective surgical care while also providing a suitable educational experience. Findings Over three week-long trips, 64 cases were performed without any reported complications, and no immediate perioperative morbidity or mortality. A plurality of cases were complex urological procedures that required surgical skills that were locally unavailable (43%. Surgical productivity was twice that of comparable peer institutions in the region. Student roles in patient care were greatly expanded in comparison to those at U.S. academic medical centers and appropriate supervision was maintained. Discussion This demonstration project suggests that a properly designed surgical trip model can effectively balance the surgical needs of the community with an opportunity to expose young trainees to a clinical and cross-cultural experience rarely provided at this early stage of medical education. Few formalized programs currently exist although the experience above suggests the rewarding potential for broad-based adoption.

  10. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp

    2015-05-15

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.

  11. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    International Nuclear Information System (INIS)

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action

  12. High Frequency of CD8 Positive Lymphocyte Infiltration Correlates with Lack of Lymph Node Involvement in Early Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Silvio Däster

    2014-01-01

    Full Text Available Aims. A trend towards local excision of early rectal cancers has prompted us to investigate if immunoprofiling might help in predicting lymph node involvement in this subgroup. Methods. A tissue microarray of 126 biopsies of early rectal cancer (T1 and T2 was stained for several immunomarkers of the innate and the adaptive immune response. Patients’ survival and nodal status were analyzed and correlated with infiltration of the different immune cells. Results. Of all tested markers, only CD8 (P=0.005 and TIA-1 (P=0.05 were significantly more frequently detectable in early rectal cancer biopsies of node negative as compared to node positive patients. Although these two immunomarkers did not display prognostic effect “per se,” CD8+ and, marginally, TIA-1 T cell infiltration could predict nodal involvement in univariate logistic regression analysis (OR 0.994; 95% CI 0.992–0.996; P=0.009 and OR 0.988; 95% CI 0.984–0.994; P=0.05, resp.. An algorithm significantly predicting the nodal status in early rectal cancer based on CD8 together with vascular invasion and tumor border configuration could be calculated (P<0.00001. Conclusion. Our data indicate that in early rectal cancers absence of CD8+ T-cell infiltration helps in predicting patients’ nodal involvement.

  13. Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

    International Nuclear Information System (INIS)

    'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4-fold

  14. Serotoninergic involvement in ethanol-induced alterations of thermoregulation in long-sleep and short-sleep mice.

    Science.gov (United States)

    French, T A; Weiner, N

    1991-11-01

    The effect of ethanol and pentobarbital on in vivo tryptophan hydroxylase activity and its relationship to drug-induced alterations of thermoregulation was examined in long-sleep (LS) and short-sleep (SS) mice. Serotonin function was measured in both the presence and absence of ethanol or pentobarbital in six discrete brain regions. Differences in basal levels of serotonin, 5-hydroxyindole acetic acid or in vivo tryptophan hydroxylase (TpH) activity were found only in the hypothalamus and dorsal raphe nuclei (SS slightly higher). Ethanol (4.2 g/kg i.p) caused significant reductions in in vivo TpH activity in the dorsal and pontine-medullary raphe nuclei and hypothalamus (putative thermoregulatory areas) in both LS (50-60% decrease) and SS (15-30% decrease) mice, but it had no effect on TpH activity in the striatum, cortex or hippocampus. The greater degree of ethanol-induced reduction in TpH activity in LS mice was associated with a greater degree of hypothermia (LS, 4.2 degrees C vs SS, 2.0 degrees C). Pentobarbital had equivalent effects in LS and SS mice on TpH activity in central nervous system thermoregulatory areas (decreases of 40-60%) and on body temperature (decreases of 6.8-7.5 degrees C). When the mice were given ethanol at an elevated environmental temperature (34 degrees C) the hypothermia was almost abolished completely, but depressant effects on TpH activity remained, suggesting that ethanol-induced decreases in TpH activity were direct effects and not secondary to hypothermia. Alterations in ethanol or pentobarbital elimination did not appear to account for the observed differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1941631

  15. Solitary axillary lymph node metastasis without breast involvement from ovarian Cancer: Case report and brief literature review

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Ji In; Kim, Soo Jin; Park, Sung Hee; Kim, Hee Sung [Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul (Korea, Republic of)

    2014-11-15

    Axillary lymph node metastasis without breast involvement from ovarian cancer is rare. We report a case of a 68-year-old woman proven as ovarian serous papillary carcinoma and metastatic papillary carcinoma of the omentum on surgical diagnostic laparoscopy. In addition, a hypermetabolic lymph node was detected in left axilla and was considered a reactive benign lesion. Mammography and ultrasonography showed no focal lesion in both breasts, but ultrasonography-guided core needle biopsy for the lymph node revealed metastatic serous papillary carcinoma from ovarian origin. Even with a low incidence of axillary lymph node metastasis without breast involvement from ovarian cancer and only marginally elevated standardized uptake value in positron emission tomography, the possibility of metastasis at axillary lymph node in patients with known primary ovarian cancer must be considered.

  16. Solitary axillary lymph node metastasis without breast involvement from ovarian Cancer: Case report and brief literature review

    International Nuclear Information System (INIS)

    Axillary lymph node metastasis without breast involvement from ovarian cancer is rare. We report a case of a 68-year-old woman proven as ovarian serous papillary carcinoma and metastatic papillary carcinoma of the omentum on surgical diagnostic laparoscopy. In addition, a hypermetabolic lymph node was detected in left axilla and was considered a reactive benign lesion. Mammography and ultrasonography showed no focal lesion in both breasts, but ultrasonography-guided core needle biopsy for the lymph node revealed metastatic serous papillary carcinoma from ovarian origin. Even with a low incidence of axillary lymph node metastasis without breast involvement from ovarian cancer and only marginally elevated standardized uptake value in positron emission tomography, the possibility of metastasis at axillary lymph node in patients with known primary ovarian cancer must be considered.

  17. The Involvement of p53-miR-34a-CDK4 Signaling During the Development of Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Huijun Zuo

    2015-01-01

    Conclusion: With the progression of cervical cancer lesions, the positive rate of p53 was greatly increased which may indicate its mutation, while miR-34a was down-regulated and CDK4 was up-regulated, which suggested that all these factors might be involved in the process of cervical oncogenesis.

  18. Involved-field radiotherapy alone for early-stage non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: To describe the outcome of involved-field radiotherapy in patients with early-stage non-small-cell lung cancer (NSCLC). Methods and Materials: A written policy for the radical treatment of early-stage NSCLC with involved-field radiotherapy was adopted at our center in 1986. The sites of known disease were treated to a dose of 52.5 Gy in 20 daily fractions over 4 weeks without elective irradiation of radiologically uninvolved regional nodes. We have reviewed the outcome of this policy in 102 patients treated with radiotherapy alone between 1986 and 1995. Results: The patients' median age was 71.5 years. The stage distribution was as follows: T1, 33.3%; T2, 56.9%; T3, 8.8%; and T4, 1.0%. Only 5 cases were N1; the remainder were N0. Most patients (76.5%) were not surgical candidates because of co-morbidity. Ninety-three percent had a CT of the thorax as part of their initial staging, while mediastinoscopy was performed in only 16.7%. Overall survival was 35% at 3 years and 16% at 5 years. Recurrence free survival was 23.9% at 3 years and 13.9% at 5 years. Cause-specific survival was 43.5% at 3 years and 26.8% at 5 years. Of those who recurred, 68.9% had a local component of failure at initial relapse, and 49.2% failed locally without evidence of regional or distant metastases. Isolated regional nodal relapse at initial failure occurred in only 6.6% of recurrences. There were no treatment interruptions due to acute toxicity and no treatment-related deaths. Conclusion: Involved-field radiotherapy alone cures a small but significant number of patients with early-stage NSCLC. This approach is recommended in patients who are unfit for surgery and who have severely compromised pulmonary function that would preclude the use of wide-field radiotherapy. The dose used in this study was well tolerated, but produced suboptimal local control rates

  19. Efficacy of psychodynamic short-term psychotherapy for depressed breast cancer patients: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Zwerenz Rüdiger

    2012-12-01

    Full Text Available Abstract Background There is a lack of psychotherapeutic trials of treatments of comorbid depression in cancer patients. Our study determines the efficacy of a manualized short-term psychodynamic psychotherapy and predictors of outcome by personality and quality of the therapeutic relationship. Methods/design Eligible breast cancer patients with comorbid depression are assigned to short-term psychodynamic psychotherapy (up to 20 + 5 sessions or to treatment as usual (augmented by recommendation for counseling center and physician information. We plan to recruit a total of 180 patients (90 per arm in two centers. Assessments are conducted pretreatment, after 6 (treatment termination and 12 months (follow-up. The primary outcome measures are reduction of the depression score in the Hospital Anxiety and Depression Scale and remission of depression as assessed by means of the Structured Clinical Interview for DSM IV Disorders by independent, blinded assessors at treatment termination. Secondary outcomes refer to quality of life. Discussion We investigate the efficacy of short-term psychodynamic psychotherapy in acute care and we aim to identify predictors for acceptance and success of treatment. Trial registration ISRCTN96793588

  20. Alcohol consumption and the risk of cancer in Brazil: A study involving 203,506 cancer patients.

    Science.gov (United States)

    de Menezes, Raquel Ferreira; Bergmann, Anke; de Aguiar, Suzana Sales; Thuler, Luiz Claudio Santos

    2015-11-01

    This study aims to analyze the association between alcohol consumption and the risk of developing the most common types of cancer in the Brazilian population. It is a case-control study in which the most common types of cancer were considered as cases and non-melanoma skin cancers as controls. Data were routinely obtained by hospital-based cancer registrars. Individuals between 18 and 100 years old, diagnosed between January 1, 2000 and December 31, 2009, with information regarding alcohol consumption, were included. The odds ratio (OR) for each type of cancer was calculated, adjusting for confounding variables. The etiologic fraction (EF) was calculated in cases with statistically significant results. The study included 203,506 individuals (110,550 women and 92,956 men), with an average age of 59 years. A statistically significant association was found between alcohol consumption and increased risk of cancers of the respiratory and digestive systems, prostate, and female breast. The association between alcohol consumption and cancers of the urinary tract, male genital organs, and other neoplasias was not statistically significant. Consumption of alcoholic beverages increased the risk of developing cancer of the nasal cavity, pyriform sinus, oral cavity, oropharynx, nasopharynx, larynx, hypopharynx, lung, esophagus, stomach, liver, pancreas, breast, prostate, colon and rectum, and anus and anal canal. PMID:26298519

  1. Ovarian ageing, follicle depletion, and cancer: a hypothesis for the aetiology of epithelial ovarian cancer involving follicle depletion

    OpenAIRE

    Smith, Elizabeth R.; Xu, Xiang-Xi

    2008-01-01

    The association between ovarian cancer risk and reproductive factors has been well established, and two main theories, incessant ovulation and gonadotropin stimulation, have been proposed to explain the mechanism. Recent studies using animal models of ovarian tumorigenesis, and analysis of ovarian tissues from prophylactic oophorectomies, suggest that depletion of ovarian follicles might underlie the epidemiological findings linking reproductive history and ovarian cancer risk.

  2. Involvement of Intercellular Adhesion Molecule-1 Up-Regulation in Bradykinin Promotes Cell Motility in Human Prostate Cancers

    Directory of Open Access Journals (Sweden)

    Chih-Hsin Tang

    2013-06-01

    Full Text Available Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to distant organs. Bradykinin (BK is an inflammatory mediator and has recently been shown to mediate tumor growth and metastasis. The adhesion molecule intercellular adhesion molecule-1 (ICAM-1 plays a critical role during tumor metastasis. The aim of this study was to examine whether BK promotes prostate cancer cell migration via ICAM-1 expression. The motility of cancer cells was increased following BK treatment. Stimulation of prostate cancer cells with BK induced mRNA and protein expression of ICAM-1. Transfection of cells with ICAM-1 small interfering RNA reduced BK-increased cell migration. Pretreatment of prostate cancer cells with B2 receptor, phosphatidylinositol 3-kinase (PI3K, Akt, and activator protein 1 (AP-1 inhibitors or mutants abolished BK-promoted migration and ICAM-1 expression. In addition, treatment with a B2 receptor, PI3K, or Akt inhibitor also reduced BK-mediated AP-1 activation. Our results indicate that BK enhances the migration of prostate cancer cells by increasing ICAM-1 expression through a signal transduction pathway that involves the B2 receptor, PI3K, Akt, and AP-1. Thus, BK represents a promising new target for treating prostate cancer metastasis.

  3. The short appendix vermiformis as a risk factor for colorectal cancer.

    Science.gov (United States)

    Cakmak, Yusuf Ozgur; Ergelen, Rabia; Ekinci, Gazanfer; Kaspar, Elif Cigdem

    2014-04-01

    The human appendix vermiformis is regarded as an evolutionarily vestigial organ, although it has presumptive immune system functions and appears to support beneficial bacterial gut flora, both of which could influence cancer progression. A review of the comparative anatomy of the mammalian appendix reveals a significantly longer appendix in herbivores than in carnivorous animals. The lengthier appendix vermiformis in herbivores has been associated with the presence of cellulose-digesting bacteria that colonize the structure. In light of recent studies that have reported the digestion of small amounts of cellulose in humans and the preventive effects of a vegetarian diet on colon cancer, we conducted a retrospective study of abdominal CT scans of 60 colon cancer patients and 60 healthy people to investigate a possible relationship between colon cancer and appendix vermiformis length. The mean length of the appendix in cancer patients [65.178 mm ± 13.46 (SD)] was shorter than that in the healthy control group [101.99 mm ± 16.58 (SD)] and the difference was statistically significant (P cancer patient group and the control group did not differ significantly (P = 0.534). The results of the present study indicate that the appendix is not merely a vestigial structure or regressed lymphoid tissue, but rather an organ that could be critical in the development of colon cancer, whether as a result of congenital or acquired appendicular factors. PMID:24497155

  4. Cancer in US Air Force veterans not involved with spraying herbicides during the Vietnam War

    Energy Technology Data Exchange (ETDEWEB)

    Pavuk, M. [SpecPro, Inc. (United States); Michalek, J.; Ketchum, N. [Air Force Research Laboratory, San Antonio, TX (United States); Akhtar, F. [The START Center, San Antonio, TX (United States)

    2004-09-15

    The Air Force Health Study is a 20-year prospective study examining the health, mortality and reproductive outcomes in US Air Force veterans of Operation Ranch Hand who sprayed herbicides in Vietnam from 1962 to 1971. Comparison veterans flew or serviced C-130 transport aircraft in Southeast Asia (SEA) during the same time period but did not spray herbicides. They were stationed mostly in Taiwan, the Philippines, Guam, Japan, and Thailand and spent on average less than 30% of their SEA service in Vietnam. Comparison veterans also spent approximately 30% more time in SEA than Ranch Hand veterans. No increases in Ranch Hand cancer mortality and morbidity were found in earlier investigations, but a recent study contrasting cancer rates in Air Force veterans and in the general US (white male) population reported increases in cancer at all SEER sites, prostate cancer and melanoma in Ranch Hand veterans and cancer at all SEER sites and prostate cancer in Comparison veterans. Associations between dioxin exposure category and cancer were found after restriction to Ranch Hand veterans who served in SEA no more than 2 years and to those who spent all of their SEA service in Vietnam. Overall cancer incidence in the general population in countries of SEA is about half of that in the United States, but cancers of the oral cavity/nasopharynx and liver are more prevalent in this region. Here we examine in more detail whether years served in SEA had any effect on the risk of cancer among Comparison veterans.

  5. A short-type peptidoglycan recognition protein from the silkworm: expression, characterization and involvement in the prophenoloxidase activation pathway.

    Science.gov (United States)

    Chen, Kangkang; Liu, Chen; He, Yan; Jiang, Haobo; Lu, Zhiqiang

    2014-07-01

    Recognition of invading microbes as non-self is the first step of immune responses. In insects, peptidoglycan recognition proteins (PGRPs) detect peptidoglycans (PGs) of bacterial cell wall, leading to the activation of defense responses. Twelve PGRPs have been identified in the silkworm, Bombyx mori, through bioinformatics analysis. However, their biochemical functions are mostly uncharacterized. In this study, we found PGRP-S5 transcript levels were up-regulated in fat body and midgut after bacterial infection. Using recombinant protein isolated from Escherichia coli, we showed that PGRP-S5 binds to PGs from certain bacterial strains and induces bacteria agglutination. Enzyme activity assay confirmed PGRP-S5 is an amidase; we also showed it is an antibacterial protein effective against both Gram-positive and -negative bacteria. Additionally, we demonstrated that specific recognition of PGs by PGRP-S5 is involved in the prophenoloxidase activation pathway. Together, these data suggest the silkworm PGRP-S5 functions as a pattern recognition receptor for the prophenoloxidase pathway initiation and as an effecter to inhibit bacterial growth as well. We finally discussed possible roles of PGRP-S5 as a receptor for antimicrobial peptide gene induction and as an immune modulator in the midgut. PMID:24508981

  6. Short- and long-term adaptation to cancer: a comparison of patients with the general population

    OpenAIRE

    Schroevers, Maatje Jannetje

    2002-01-01

    Both from a scientific and common sense point of view, there are many ideas about how patients adjust to a life-threatening disease such as cancer. However, the empirical evidence on this topic is still elusive, especially about the consequences that patients may experience in the long term. The present thesis addresses patients’ physical and psychosocial adjustment to cancer, in the first year after diagnosis onward to eight years after diagnosis.

  7. Short-Form Ron Promotes Spontaneous Breast Cancer Metastasis through Interaction with Phosphoinositide 3-Kinase

    OpenAIRE

    Liu, Xuemei; Zhao, Ling; DeRose, Yoko S.; Lin, Yi-Chun; Bieniasz, Magdalena; Eyob, Henok; Buys, Saundra S.; Neumayer, Leigh; Welm, Alana L.

    2011-01-01

    Receptor tyrosine kinases (RTKs) have been the subject of intense investigation due to their widespread deregulation in cancer and the prospect of developing targeted therapeutics against these proteins. The Ron RTK has been implicated in tumor aggressiveness and is a developing target for therapy, but its function in tumor progression and metastasis is not fully understood. We examined Ron activity in human breast cancers and found striking predominance of an activated Ron isoform known as s...

  8. Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells.

    Science.gov (United States)

    Krisnamurti, Desak Gede Budi; Louisa, Melva; Anggraeni, Erlia; Wanandi, Septelia Inawati

    2016-01-01

    Tamoxifen is the first line drug used in the treatment of estrogen receptor-positive (ER+) breast cancer. The development of multidrug resistance (MDR) to tamoxifen remains a major challenge in the treatment of cancer. One of the mechanisms related to MDR is decrease of drug influx via overexpression of drug efflux transporters such as P-glycoprotein (P-gp/MDR1), multidrug resistance associated protein (MRP), or BCRP (breast cancer resistance protein). We aimed to investigate whether the sensitivity of tamoxifen to the cells is maintained through the short period and whether the expressions of several drug efflux transporters have been upregulated. We exposed MCF7 breast cancer cells with tamoxifen 1 μM for 10 passages (MCF7 (T)). The result showed that MCF7 began to lose their sensitivity to tamoxifen from the second passage. MCF7 (T) also showed a significant increase in all transporters examined compared with MCF7 parent cells. The result also showed a significant increase of CC50 in MCF7 (T) compared to that in MCF7 (97.54 μM and 3.04 μM, resp.). In conclusion, we suggest that the expression of several drug efflux transporters such as P-glycoprotein, MRP2, and BCRP might be used and further studied as a marker in the development of tamoxifen resistance. PMID:26981116

  9. [Efficacy of Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer Involving the Superior Mesenteric Artery].

    Science.gov (United States)

    Matsukawa, Hiroyoshi; Shiozaki, Shigehiro; Satoh, Daisuke; Yoshida, Kazuhiro; Araki, Hiroyuki; Idani, Hitoshi; Ojima, Yasutomo; Harano, Masao; Kanazawa, Takashi; Tokumoto, Noriaki; Choda, Yasuhiro; Ishida, Michihiro; Miyoshi, Hisanobu; Okajima, Masazumi; Ninomiya, Motoki

    2015-11-01

    Multidisciplinary therapy is essential in the treatment of borderline resectable pancreatic cancer involving the superior mesenteric artery (BR-SMA). We analyzed the outcomes of multidisciplinary treatment for BR-SMA and evaluated the efficacy of neoadjuvant therapy (NAT). We reviewed the clinical courses of 10 patients with BR-SMA. Seven patients were treated with preoperative neoadjuvant therapy (NAT group), and 3 patients underwent radical pancreaticoduodenectomy first (SF group). In the NAT group, the rate of R0 was 7/7 (100%), the induction rate of postoperative adjuvant chemotherapy (AC) was 6/7 (86%), and the first recurrence sites were the lung in 4 patients, and the liver and peritoneum in one patient each, respectively. In the SF group, the rate of R0 was 2/3 (67%) because of a positive pathological dissecting peripancreatic margin in 1 case. The induction rate of AC was 3/3 (100%), and the first recurrence sites were the liver in 2 patients, the peritoneum in 1, and a local site in 1. The disease free survival of the NAT group (median survival time [MST] 19.3 months) was significantly better than that of the SF group (MST 5.7 months) (log rank test, p=0.002). The median overall survival of the NAT and SF groups was 51.6 months and 19.5 months, respectively (p=0.128). An R0 resection could be performed in all cases in the NAT group. The NAT extended disease-free survival. We conclude that NAT is recommended in the treatment of BR-SMA. PMID:26805071

  10. MicroRNAs are involved in cervical cancer development, progression, clinical outcome and improvement treatment response (Review).

    Science.gov (United States)

    González-Quintana, Víctor; Palma-Berré, Lizbeth; Campos-Parra, Alma D; López-Urrutia, Eduardo; Peralta-Zaragoza, Oscar; Vazquez-Romo, Rafael; Pérez-Plasencia, Carlos

    2016-01-01

    Cervical cancer (CC) is the third most diagnosed cancer among females worldwide and the fourth cause of cancer-related mortality. Prophylactic HPV vaccines and traditional pap-smear screening are undoubtedly capable of decreasing the incidence and mortality of CC. However, a large number of females succumb to the disease each year due to late diagnosis and resistance to conventional treatments. Thus, it is necessary to identify new molecular markers to predict the clinical outcome and to design powerful treatments. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are involved in the modulation of several cell pathways associated with progression from pre-malignant to invasive and metastatic disease, increasing tumor malignancy. The aim of this review was to summarize the recent data that describe the important role of miRNAS involved in CC in order to determine their potential as prognostic biomarkers and as therapy targets. Studies of >40 miRNAs with roles in cancer regulation were identified. We also identified 17 miRNAs associated with progression, 12 involved with clinical outcome and 7 that improved CC treatment response. The present review is expected to broaden understanding of the functional role and potential clinical uses of miRNAs in CC. PMID:26530778

  11. Pattern of failures in gastric cancer patients with lymph node involvement treated by surgery, intraoperative and external beam radiotherapy

    International Nuclear Information System (INIS)

    Aims: High local failure rates in gastric cancer have been reported, up to 67%. To achieve a better local control, we evaluated intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT) in association with surgery for gastric cancer patients with lymph node involvement. We report here the analysis of the patterns of failure for patients involved in this IORT protocol. Material and methods: Forty-two positive lymph node (N+) gastric cancer patients were operated on (31 total, three subtotal and eight extended gastrectomies) with IORT procedure between 1985 and 1997 (33 males, nine females, mean age 61.3 years). IORT was focused on coeliac area (mean dose 15 Gy), followed by EBRT (46 Gy) in 36 patients. Ten patients were pN1 and 32 were pN2. A concurrent systemic chemotherapy (five Fluoro-Uracil and Cisplatinum) was performed in 14 patients. Results: One patient died postoperatively. Actuarial pN+ 10 year survival rate was 44.8%. The 5 year actuarial local control and disease-free survival rates were 78.8 and 47.5%, respectively. As far as patterns of failure were explored, 5 patients have a local coeliac recurrence (12%) and 12 have distant metastases with no evidence of coeliac recurrence. Conclusion: This retrospective analysis suggests a potential effect of IORT and/or EBRT in promoting local control and long-term survival in gastric cancer patients with lymph node involvement

  12. MICAL2 is a novel human cancer gene controlling mesenchymal to epithelial transition involved in cancer growth and invasion

    Science.gov (United States)

    Vindigni, Carla; Pucci, Angela; Balsamo, Michele; Libro, Rosaliana; Senchenko, Vera; Dmitriev, Alexey; Jacchetti, Emanuela; Cecchini, Marco; Roviello, Franco; Lai, Michele; Broccoli, Vania; Andreazzoli, Massimiliano; Mazzanti, Chiara M.; Angeloni, Debora

    2016-01-01

    The MICAL (Molecules Interacting with CasL) proteins catalyze actin oxidation-reduction reactions destabilizing F-actin in cytoskeletal dynamics. Here we show for the first time that MICAL2 mRNA is significantly over-expressed in aggressive, poorly differentiated/undifferentiated, primary human epithelial cancers (gastric and renal). Immunohistochemistry showed MICAL2-positive cells on the cancer invasive front and in metastasizing cancer cells inside emboli, but not at sites of metastasis, suggesting MICAL2 expression was 'on' in a subpopulation of primary cancer cells seemingly detaching from the tissue of origin, enter emboli and travel to distant sites, and was turned 'off' upon homing at metastatic sites. In vitro, MICAL2 knock-down resulted in mesenchymal to epithelial transition, reduction of viability, and loss of motility and invasion properties of human cancer cells. Moreover, expression of MICAL2 cDNA in MICAL2-depleted cells induced epithelial to mesenchymal transition. Altogether our data indicate that MICAL2 over-expression is associated with cancer progression and metastatic disease. MICAL2 might be an important regulator of epithelial to mesenchymal transition and therefore a promising target for anti-metastatic therapy. PMID:26689989

  13. A 3-week multimodal intervention involving high-intensity interval training in female cancer survivors: a randomized controlled trial.

    Science.gov (United States)

    Schmitt, Joachim; Lindner, Nathalie; Reuss-Borst, Monika; Holmberg, Hans-Christer; Sperlich, Billy

    2016-02-01

    To compare the effects of a 3-week multimodal rehabilitation involving supervised high-intensity interval training (HIIT) on female breast cancer survivors with respect to key variables of aerobic fitness, body composition, energy expenditure, cancer-related fatigue, and quality of life to those of a standard multimodal rehabilitation program. A randomized controlled trial design was administered. Twenty-eight women, who had been treated for cancer were randomly assigned to either a group performing exercise of low-to-moderate intensity (LMIE; n = 14) or a group performing high-intensity interval training (HIIT; n = 14) as part of a 3-week multimodal rehabilitation program. No adverse events related to the exercise were reported. Work economy improved following both HIIT and LMIE, with improved peak oxygen uptake following LMIE. HIIT reduced mean total body fat mass with no change in body mass, muscle or fat-free mass (best P HIIT can be performed by female cancer survivors without adverse health effects. Here, HIIT and LMIE both improved work economy, quality of life and cancer-related fatigue, body composition or energy expenditure. Since the outcomes were similar, but HIIT takes less time, this may be a time-efficient strategy for improving certain aspects of the health of female cancer survivors. PMID:26869680

  14. Low cdc27 and high securin expression predict short survival for breast cancer patients.

    Science.gov (United States)

    Talvinen, Kati; Karra, Henna; Pitkänen, Reino; Ahonen, Ilmari; Nykänen, Marjukka; Lintunen, Minnamaija; Söderström, Mirva; Kuopio, Teijo; Kronqvist, Pauliina

    2013-10-01

    Cell cycle regulators cdc27 and securin participate in control of the mitotic checkpoint and survey the mitotic spindle to maintain chromosomal integrity. This is achieved by their functions in metaphase-anaphase transition, DNA damage repair, enhancement of mitotic arrest and apoptosis. We report on the roles of cdc27 and securin in aneuploidy and prognosis of breast cancer. The study comprises 429 breast cancer patients with up to 22 years of follow-up. DNA content was determined by image cytometry, and immunopositivity for cdc27 and securin was based on tissue microarrays. An inverse association between cdc27 and securin expression was observed in both image cytometric and immunohistochemical analyses. Low cdc27 and high securin expression identified patients with significant difference in disease outcome. Cdc27 and securin immunoexpression identified patients at risk of early cancer death within five years from diagnosis. In multivariate analysis, the combination of cdc27 and securin immunohistochemistry was the strongest predictor of cancer death after lymph node status. We demonstrate, for the first time in human breast cancer, the prognostic value of cdc27 and securin immunohistochemistry. Cdc27 and securin appear promising biomarkers for applications in predicting disease progression, prognostication of individual patients and potential in anti-mitotic drug development. PMID:23755904

  15. Knowledge, attitude, and practice of cervical cancer screening among Greek students: a short report.

    Science.gov (United States)

    Bakogianni, Giannoula D; Goutsou, Spiridoula C; Liti, Maria V; Rizopoulou, Sophia I; Nikolakopoulos, Konstantinos M; Nikolakopoulou, Nikoleta M

    2012-01-01

    Cervical cancer is a major cause of death in the developing world. The Papanicolaou (Pap) smear is a screening test that detects abnormal cells before they advance to cancer. The objective of this study was to assess the knowledge, attitude, and practice of cervical cancer screening among Greek students. A sample of 472 female students participated in the present study. Interviews were performed using a structured questionnaire. Of the participants, 94.07% were aware of the Pap test and 67.34% reported that the Pap test should be done yearly. The majority of them were informed about cervical cancer screening test by their parents. Of the participants, 44.82% had received Pap testing at least once in their life, whereas 36.2% had a Pap test yearly. The reported mean time of the respondents' first Pap test was 13.3±10.6 months after their first sexual intercourse. The reasons given by the participants for being noncompliant were lack of appreciation of the importance of the screening, embarrassment, fear, and high cost. Of the participants, 9.23% declared that those who had been administered the human papillomavirus vaccine do not need a Pap test. The results highlight the need for additional education and health promotion regarding cervical cancer screening. PMID:23183733

  16. The microbe-derived short chain fatty acid butyrate targets miRNA-dependent p21 gene expression in human colon cancer.

    Directory of Open Access Journals (Sweden)

    Shien Hu

    Full Text Available Colonic microbiota ferment non-absorbed dietary fiber to produce prodigious amounts of short chain fatty acids (SCFAs that benefit the host through a myriad of metabolic, trophic, and chemopreventative effects. The chemopreventative effects of the SCFA butyrate are, in part, mediated through induction of p21 gene expression. In this study, we assessed the role of microRNA(miRNA in butyrate's induction of p21 expression. The expression profiles of miRNAs in HCT-116 cells and in human sporadic colon cancers were assessed by microarray and quantitative PCR. Regulation of p21 gene expression by miR-106b was assessed by 3' UTR luciferase reporter assays and transfection of specific miRNA mimics. Butyrate changed the expression of 44 miRNAs in HCT-116 cells, many of which were aberrantly expressed in colon cancer tissues. Members of the miR-106b family were decreased in the former and increased in the latter. Butyrate-induced p21 protein expression was dampened by treatment with a miR-106b mimic. Mutated p21 3'UTR-reporter constructs expressed in HCT-116 cells confirmed direct miR-106b targeting. Butyrate decreased HCT-116 proliferation, an effect reversed with the addition of the miR-106b mimic. We conclude that microbe-derived SCFAs regulate host gene expression involved in intestinal homeostasis as well as carcinogenesis through modulation of miRNAs.

  17. The short-term outcomes of conventional and single-port laparoscopic surgery for rectal cancer

    DEFF Research Database (Denmark)

    Levic, Katarina; Bulut, Orhan

    2014-01-01

    BACKGROUND: Single-port laparoscopic surgery (SPLS) has evolved as an alternative method to conventional laparoscopic surgery (CLS). The aim of this study is to evaluate the results of SPLS compared to CLS in the treatment of rectal cancer. MATERIAL AND METHODS: Prospectively collected data...... of patients who had undergone either CLS (n = 194) or SPLS (n = 36) for rectal cancer in the period between 2009 and 2012 were retrospectively analyzed. RESULTS: Median operative time was higher in patients with SPLS (p = 0.01), but the median operative blood loss was significantly lower (p = 0...... cancer is a safe method in a selected group of patients. Further studies are needed to confirm the benefits of SPLS. Operative time is longer, but the intraoperative blood loss is reduced....

  18. Short term and long term radiation protection aspects of a nuclear accident: a Cd-Rom for a better stake holders' involvement

    International Nuclear Information System (INIS)

    Many players are involved in managing a nuclear accident apart from radiation protection and nuclear safety experts. In an emergency response situation, the decision making process involves many non-technical players who nonetheless have a major role to play: in France these may include the Prefet, the emergency and civil defence services, the health services, the police, the gendarmerie and local councillors, with advice from the safety and radiological protection authorities and expert evaluation organisations. Within the post-accident response, other players will be involved alongside those already described: professional bodies, particularly farming organisations, residents' associations, those responsible for environmental decontamination, agencies responsible for compensating victims, etc., etc. In both the short and the long-term phases of the crisis management process, it is essential to enable participants who may have very different backgrounds and professional experience to work together with co-operation and mutual understanding. If non-technical players are to contribute effectively, there needs to be a minimum level of mutual understanding between them and the technical players on what the nuclear risk really is and what is the rationale of the short and long term counter-measures aimed at protecting the public and restoring the contaminated environment. Local communities also need to share this basic understanding because their cooperation is required in order to implement the counter-measures properly. Conversely, if the experts are to advise the local authorities properly, they need to understand the criteria on which these local authorities and communities base their decisions: what psycho-sociological factors apply, what logistical support is needed, what are the concerns of the local communities?

  19. Short-course neutron therapy for advanced head and neck cancer

    International Nuclear Information System (INIS)

    This was a Phase I/II clinical study, concentrating mainly on the assessment of treatment tolerance, performed in a small group of patients with advanced head and neck cancer. The complete remission observed for 7 and 9 months after treatment in two out of 12 patients with very advanced head and neck cancer encourages the authors to continue further clinical trials using the high tumour dose of 12 Gy/10 F given over 2 weeks, as early cutaneous and mucosal reactions were acceptable. (author)

  20. Brain metastasis from non-small cell lung cancer (NSCLC). Prognostic importance of the number of involved extracranial organs

    Energy Technology Data Exchange (ETDEWEB)

    Gerdan, L. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Section of Nuclear Medicine, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Khoa, M.T. [Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam); Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale, AZ (United States); Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany)

    2014-01-15

    This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 x 4 Gy or 10 x 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung+bone vs. lung+lymph nodes vs. other combinations) extracranial organs. The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement. (orig.)

  1. Brain metastasis from non-small cell lung cancer (NSCLC). Prognostic importance of the number of involved extracranial organs

    International Nuclear Information System (INIS)

    This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 x 4 Gy or 10 x 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung+bone vs. lung+lymph nodes vs. other combinations) extracranial organs. The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement. (orig.)

  2. The impact of surgical adjuvant thoracic radiation therapy for non-small cell lung cancer patients with mediastinal nodal involvement

    International Nuclear Information System (INIS)

    Purpose: Since previous studies of patients with surgically resected non-small cell lung cancer have shown that patients with ipsilateral mediastinal nodal involvement (N2) have a greater rate of local recurrence compared to patients with less lymph node involvement (N0, N1), it was hypothesized that complete surgical clearance of subclinical nodal disease is difficult to achieve in these patients and therefore that they may benefit, with respect to local control and survival, from adjuvant thoracic radiotherapy (TRT). Methods: A retrospective review was performed to determine the actuarial rates of local recurrence and overall survival for patients with non-small cell lung cancer with ipsilateral mediastinal nodal involvement who underwent complete surgical resection with or without postoperative adjuvant TRT. Between the years of 1987 and 1993, 224 evaluable patients underwent complete resection of a non-small cell lung carcinoma with involvement of N2 lymph nodes. All patients underwent surgical resection at the Mayo Clinic and 98% of patients had more than one nodal station dissected. The extent of surgical resection was generally consistent during the years of this study. Of the 224 patients, 88 received adjuvant postoperative irradiation and 136 were observed. The use of TRT was variable in these patients generally due to differences in opinions of the consulting physicians. The median dose of TRT was 5040 cGy. Results: The two groups (surgery alone vs surgery + TRT) were well balanced with respect to the following prognostic factors: gender, age, histology, tumor grade, number of mediastinal nodal stations sampled, and number of involved N1 nodes. There were slightly more RLL lesions (compared to other lobes), slightly more patients with multiple involved lobes and slightly more patients with only one involved N2 lymph nodes (compared to greater than one) in the surgery alone group compared to the surgery + TRT group. The following endpoints were assessed

  3. Mortality and cancer registration experience of the Sellafield employees known to have been involved in the 1957 Windscale accident

    International Nuclear Information System (INIS)

    The mortality and cancer morbidity experience of the 470 male Sellafield employees known to be involved in the 1957 Windscale accident is reported. All these employees are known to have been involved in dealing with the fire itself, or in the clean-up operation afterwards. The size of the study population is small, leading to predicted low power to reveal any effects, but the cohort is of interest because of the involvement of the workers in the accident. For 1957-97, using rates for England and Wales to calculate the expected numbers, the all causes standardised mortality ratio (SMR) is 100 (observed=258, expected=258.80), and the all malignant neoplasms SMR is 79 (observed=58, expected=73.12) which is not significantly different from 100. For 1971-91, the all malignant neoplasms standardised registration ratio (SRR) of 85 (observed=59, expected=69.23) is not significantly different from 100. Significant excesses of deaths from diseases of the circulatory system (SMR=121) and from ischaemic heart disease (SMR=128), and a significant deficit of deaths from cancer of the genito-urinary organs (SMR=31), were found. There were no significant differences in mortality rates between workers who had received high recorded external doses during the fire and those who had received low doses, though the power of this comparison was low. Comparison of the mortality rates of workers directly involved in the accident with workers in post, but not so involved, showed no significant differences. This study has been unable to detect any effect of the 1957 fire upon the mortality and cancer morbidity experience of those workers involved in it. (author)

  4. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRi) plasmids | Office of Cancer Genomics

    Science.gov (United States)

    CTD2 researchers at the University of California in San Francisco developed a modified Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) CRISPR/dCas9 system. Catalytically inactive dCas9 enables modular and programmable RNA-guided genome regulation in eukaryotes.

  5. Detection of axillary lymph node involvement of breast cancer by Tc-99m MIBI scintimammography

    International Nuclear Information System (INIS)

    Breast cancer is the most common malignancy among women, leading to hundreds of thousands of deaths annually around the world. Lymph node status is the most important prognostic indicator in newly diagnosed breast cancer. The presence of axillary lymph node metastases has major prognostic implications in breast cancer patients, and it is an important criterion in determining the need for adjuvant chemotherapy. There is not an accurate anatomical test for detecting axillary lymph node metastasis and clinical examination has inappropriate diagnostic values. Routine lymph node dissection is the only accepted method for therapeutic decisions but it is invasive and produces significant morbidity such as lymphedema and infections. On the other hand, an important proportion of breast cancer patients are nodenegative. Ultrasonography has also been reported to be helpful, especially in conjunction with fine needle aspiration biopsy

  6. Reduced Circumferential Resection Margin Involvement in Rectal Cancer Surgery: Results of the Dutch Surgical Colorectal Audit

    NARCIS (Netherlands)

    Gietelink, L.; Wouters, M.W.; Tanis, P.J.; Deken, M.M.; Berge, M.G. Ten; Tollenaar, R.A.; Krieken, J.H.J.M. van; Noo, M.E. de

    2015-01-01

    BACKGROUND: The circumferential resection margin (CRM) is a significant prognostic factor for local recurrence, distant metastasis, and survival after rectal cancer surgery. Therefore, availability of this parameter is essential. Although the Dutch total mesorectal excision trial raised awareness ab

  7. The smoking behaviors and cancer-related disparities among urban middle aged and older males involved in the criminal justice system

    OpenAIRE

    Valera, Pamela; Anderson, Matthew; Cook, Stephanie H.; Wylie-Rosett, Judith; Rucker, Justin; Reid, Andrea E.

    2015-01-01

    This study examined cancer knowledge, mental health and smoking in formerly incarcerated men. The Cancer-Health Research Study with Formerly Incarcerated Men in New York City used a cross-sectional research design to examine knowledge and cancer prevention (CKP) outcomes among 259 justice-involved males, ages 35-67. CKP was assessed using items from the National Cancer Institute's Health Information National Trends Survey. Psychological symptoms were examined using the Brief Symptom Inventory...

  8. Short-form RON overexpression augments benzyl isothiocyanate-induced apoptosis in human breast cancer cells.

    Science.gov (United States)

    Sehrawat, Anuradha; Singh, Shivendra V

    2016-05-01

    Chemoprevention of breast cancer is feasible with the use of non-toxic phytochemicals from edible and medicinal plants. Benzyl isothiocyanate (BITC) is one such plant compound that prevents mammary cancer development in a transgenic mouse model in association with tumor cell apoptosis. Prior studies from our laboratory have demonstrated a role for reactive oxygen species (ROS)-dependent Bax activation through the intermediary of c-Jun N-terminal kinases in BITC-induced apoptosis in human breast cancer cells. The present study demonstrates that truncated Recepteur d'Origine Nantais (sfRON) is a novel regulator of BITC-induced apoptosis in breast cancer cells. Overexpression of sfRON in MCF-7 and MDA-MB-361 cells resulted in augmentation of BITC-induced apoptosis when the apoptotic fraction was normalized against vehicle control for each cell type (untransfected and sfRON overexpressing cells). ROS generation and G2 /M phase cell cycle arrest resulting from BITC treatment were significantly attenuated in sfRON overexpressing cells after normalization with vehicle control for each cell type. Increased BITC-induced apoptosis by sfRON overexpression was independent of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase hyperphosphorylation. On the other hand, activation of Bax and Bak following BITC exposure was markedly more pronounced in sfRON overexpressing cells than in controls. sfRON overexpression also augmented apoptosis induction by structurally diverse cancer chemopreventive phytochemicals including withaferin A, phenethyl isothiocyanate, and D,L-sulforaphane. In conclusion, the present study provides novel mechanistic insights into the role of sfRON in apoptosis regulation by BITC and other electrophilic phytochemicals. © 2015 Wiley Periodicals, Inc. PMID:25857724

  9. Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39-85) years. The median follow-up term was 16.3 (range, 2-53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials. (author)

  10. Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer.

    Science.gov (United States)

    Doi, Hiroshi; Beppu, Naohito; Odawara, Soichi; Tanooka, Masao; Takada, Yasuhiro; Niwa, Yasue; Fujiwara, Masayuki; Kimura, Fumihiko; Yanagi, Hidenori; Yamanaka, Naoki; Kamikonya, Norihiko; Hirota, Shozo

    2013-11-01

    The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39-85) years. The median follow-up term was 16.3 (range, 2-53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials. PMID:23658415

  11. Role of phosphoproteins involved in chemoresistance of colorectal cancer stem cells and immuno phenotypic comparative analysis

    International Nuclear Information System (INIS)

    Recent studies demonstrated that colon cancers contain a cellular subpopulation, with stem cell-like proprieties, able to initiate and sustain tumour growth. These cells, so-called Cancer Initiating Cells (CICs), express the transmembrane antigen CD133. CD133 positive cells show slow proliferation rate, high expression of ABC (ATP-binding cassette) transporters and anti-apoptotic factors making them resistant to conventional therapies

  12. Prostate cancer multimodal therapy involvement in couple life: Open, Robotic and HIFU approach

    OpenAIRE

    Elisabeta Ioana Hirişcău; Doina Cosman; Ioan Coman

    2010-01-01

    The diagnosis and treatment of prostate cancer often results in significant physical side-effectsand associated psycho-social stressors that can interfere with the experience of sexual intimacy forcouples. Our study aims to evaluate couple’s sexual life and to determine any potential sexual dynamicdysfunctions which could occur before and after performing classic, robotic and HIFU radicalprostatectomy as a radical therapy in prostate cancer. The present article aims at the synopticpresentatio...

  13. Persistent Increase in Chromosome Instability in Lung Cancer : Possible Indirect Involvement of p53 Inactivation

    OpenAIRE

    Haruki, Nobuhiro; Harano, Tomoko; Masuda, Akira; Kiyono, Tohru; TAKAHASHI, TAKAO; Tatematsu, Yoshio; Shimizu, Shigeki; Mitsudomi, Tetsuya; Konishi, Hiroyuki; Osada, Hirotaka; Fujii, Yoshitaka; Takahashi, Takashi

    2001-01-01

    Karyotype and fluorescence in situ hybridization analyses have demonstrated the frequent presence of an altered static state of the number of chromosomes (ie, aneuploidy) in lung cancer, but it has not been directly established whether aneuploidy is in fact associated with a persistent increase in the rate of chromosomal losses and gains (ie, chromosome instability, or CIN). The study presented here used a panel of 10 lung cancer cell lines to provide for the first time direct evidence that C...

  14. Evaluation of MRI findings and short-term outcome in lung cancer patients with brain metastases after stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Objective: To evaluate the treatment outcomes in lung cancer patients with brain metastases (BM) after stereotactic radiotherapy (SRT) according to magnetic resonance imaging (MRI) findings and the Response Evaluation Criteria In Solid Tumors (RECIST). Methods: A retrospective analysis was performed on 31 lung cancer patients with 60 BM lesions who were treated with SRT. Tumor responses were evaluated according to MRI findings and the RECIST. Results: The MRI after SRT showed that (1) 14 lesions recurred, with nodular enhancement in 8 lesions, homogeneous enhancement in 5 lesions, and inhomogeneous enhancement in 1 lesion; (2) 11 lesions (18%) had suspected progression, with homogeneous enhancement in 5 lesions, inhomogeneous enhancement in 3 lesions, peripheral enhancement in 2 lesions,and nodular enhancement in 1 lesion; (3) 35 lesions were controlled, with decreased volume or disappearance in 19 lesions, insignificant volume change in 10 lesions, and increased volume in 6 lesions; (4) the overall response rate was 76.7% (suspected progression + controlled). According to the RECIST, 15 lesions (25%) achieved a complete response (CR), 9 lesions (15%) achieved a partial response (PR), 12 lesions (20%) had stable disease,and 24 lesions (40%) had progressive disease, and the response rate (CR + PR) was 40%. Conclusions: There are various MRI findings for brain metastases in lung cancer patients after SRT, and 18% of the lesions are difficult to evaluate by MRI. RECIST underestimates the short-term effect of SRT. (authors)

  15. Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis

    OpenAIRE

    Moore, P S; Orlandini, S.; Zamboni, G; Capelli, P.; Rigaud, G; Falconi, M; Bassi, C.; Lemoine, N. R.; Scarpa, A.

    2001-01-01

    Alterations of K-ras, p53, p16 and DPC4/Smad4 characterize pancreatic ductal cancer (PDC). Reports of inactivation of these latter two genes in pancreatic endocrine tumours (PET) suggest that common molecular pathways are involved in the tumorigenesis of pancreatic exocrine and endocrine epithelia. We characterized 112 primary pancreatic tumours for alterations in p16 and DPC4 and immunohistochemical expression of DPC4. The cases included 34 PDC, 10 intraductal papillary-mucinous tumours (IPM...

  16. Involvement of miR-30c in resistance to doxorubicin by regulating YWHAZ in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Y. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Shen, H. [Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Cao, Y. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Li, H. [Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Qin, R. [Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Chen, Q. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Long, L. [Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Zhu, X.L. [Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Xie, C.J. [Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China); Xu, W.L. [Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu (China)

    2014-01-10

    MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover, the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.

  17. Short-term regulation of NHE3 by EGF and protein kinase C but not protein kinase A involves vesicle trafficking in epithelial cells and fibroblasts.

    Science.gov (United States)

    Donowitz, M; Janecki, A; Akhter, S; Cavet, M E; Sanchez, F; Lamprecht, G; Zizak, M; Kwon, W L; Khurana, S; Yun, C H; Tse, C M

    2000-01-01

    NHE3 is an intestinal epithelial isoform Na+/H+ exchanger that is present in the brush border of small intestinal, colonic, and gallbladder Na(+)-absorbing epithelial cells. NHE3 is acutely up- and downregulated in response to some G protein-linked receptors, tyrosine kinase receptors, and protein kinases when studied in intact ileum, when stably expressed in PS120 fibroblasts, and in the few studies reported in the human colon cancer cell line Caco-2. In most cases this is due to changes in Vmax of NHE3, although in response to cAMP and squalamine there are also changes in the K'(H+)i of the exchanger. The mechanism of the Vmax regulation as shown by cell surface biotinylation and confocal microscopy in Caco-2 cells and biotinylation in PS120 cells involves changes in the amount of NHE3 on the plasma membrane. In addition, in some cases there are also changes in turnover number of the exchanger. In some cases, the change in amount of NHE3 in the plasma membrane is associated with a change in the amount of plasma membrane. A combination of biochemical studies and transport/inhibitor studies in intact ileum and Caco-2 cells demonstrated that the increase in brush border Na+/H+ exchange caused by acute exposure to EGF was mediated by PI 3-kinase. PI 3-kinase was also involved in FGF stimulation of NHE3 expressed in fibroblasts. Thus, NHE3 is another example of a transport protein that is acutely regulated in part by changing the amount of the transporter on the plasma membrane by a process that appears to involve vesicle trafficking and also to involve changes in turnover number. PMID:11193592

  18. Statistical analysis of long- and short-range forces involved in bacterial adhesion to substratum surfaces as measured using atomic force microscopy.

    Science.gov (United States)

    Chen, Yun; Busscher, Henk J; van der Mei, Henny C; Norde, Willem

    2011-08-01

    Surface thermodynamic analyses of microbial adhesion using measured contact angles on solid substrata and microbial cell surfaces are widely employed to determine the nature of the adhesion forces, i.e., the interplay between Lifshitz-van der Waals and acid-base forces. While surface thermodynamic analyses are often viewed critically, atomic force microscopy (AFM) can also provide information on the nature of the adhesion forces by means of Poisson analysis of the measured forces. This review first presents a description of Poisson analysis and its underlying assumptions. The data available from the literature for different combinations of bacterial strains and substrata are then summarized, leading to the conclusion that bacterial adhesion to surfaces is generally dominated by short-range, attractive acid-base interactions, in combination with long-range, weaker Lifshitz-van der Waals forces. This is in line with the findings of surface thermodynamic analyses of bacterial adhesion. Comparison with single-molecule ligand-receptor forces from the literature suggests that the short-range-force contribution from Poisson analysis involves a discrete adhesive bacterial cell surface site rather than a single molecular force. The adhesion force arising from these cell surface sites and the number of sites available may differ from strain to strain. Force spectroscopy, however, involves the tedious task of identifying the minor peaks in the AFM retraction force-distance curve. This step can be avoided by carrying out Poisson analysis on the work of adhesion, which can also be derived from retraction force-distance curves. This newly proposed way of performing Poisson analysis confirms that multiple molecular bonds, rather than a single molecular bond, contribute to a discrete adhesive bacterial cell surface site. PMID:21642399

  19. Anti-tissue factor short hairpin RNA inhibits breast cancer growth in vivo

    OpenAIRE

    Bluff, J. E.; Amarzguioui, M.; Slattery, J; Reed, M.W.R.; Brown, N J; Staton, C A

    2010-01-01

    Abstract In breast cancer, there is a correlation between tissue factor (TF) expression, angiogenesis and disease progression. TF stimulates tumour angiogenesis, in part, through up-regulation of vascular endothelial growth factor (VEGF). Therefore, this study aimed to establish whether TF stimulates angiogenesis and tumour progression directly and independent of VEGF up-regulation. Initially, the effects of TF and VEGF were assessed on endothelial cell migration (Boyden chamber) a...

  20. Response of normal vs. cancer colon cells to short- and long-chain fatty acids

    Czech Academy of Sciences Publication Activity Database

    Koubková, Zuzana; Hofmanová, Jiřina; Ciganek, M.; Slavík, J.; Skender, B.; Machala, M.; Kozubík, Alois

    Budapest, 2008. s. 193. [ISAC XXIV International Congress, Cytometry in the Age of Systems Biology. 17.05.2008-21.05.2008, Budapest] R&D Projects: GA ČR(CZ) GA301/07/1557; GA ČR(CZ) GA524/07/1178; GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : PUFAs * NaBt * colon cancer Subject RIV: BO - Biophysics

  1. Comparison of treatment outcomes between involved-field and elective nodal irradiation in limited-stage small cell lung cancer

    International Nuclear Information System (INIS)

    The present study was performed to assess the usefulness of involved-field irradiation and the impact of 18F-fluorodeoxyglucose-positron emission tomography-based staging on treatment outcomes in limited-stage small cell lung cancer. Eighty patients who received definitive chemoradiotherapy for limited-stage small cell lung cancer were retrospectively analyzed. Fifty patients were treated with involved-field irradiation, which means that the radiotherapy portal includes only clinically identifiable tumors. The other 30 patients were irradiated with a comprehensive portal, including uninvolved mediastinal and/or supraclavicular lymph nodes, so-called elective nodal irradiation. No significant difference was seen in clinical factors between the two groups. At a median follow-up of 27 months (range, 5-75 months), no significant differences were observed in 3 year overall survival (44.6 vs. 54.1%, P=0.220) and 3 year progression-free survival (24.4 vs. 42.8%, P=0.133) between the involved-field irradiation group and the elective nodal irradiation group, respectively. For patients who did not undergo positron emission tomography scans, 3 year overall survival (29.3 vs. 56.3%, P=0.022) and 3 year progression-free survival (11.0 vs. 50.0%, P=0.040) were significantly longer in the elective nodal irradiation group. Crude incidences of isolated nodal failure were 6.0% in the involved-field irradiation group and 0% in the elective nodal irradiation group, respectively. All isolated nodal failures were developed in patients who had not undergone positron emission tomography scans in their initial work-ups. If patients did not undergo positron emission tomography-based staging, the omission of elective nodal irradiation resulted in impaired survival outcomes and raised the risk of isolated nodal failure. Therefore, involved-field irradiation for limited-stage small cell lung cancer might be reasonable only with positron emission tomography scan implementation. (author)

  2. Outcome of Endometrial Cancer Stage IIIA with Adnexa or Serosal Involvement Only

    Directory of Open Access Journals (Sweden)

    Jan J. Jobsen

    2011-01-01

    Methods. 67 patients with stage IIIA endometrial carcinoma were included, 46 with adnexal involvement and 21 with serosa. A central histopathological review was performed. Results. The 7-year locoregional failure rate was (LRFR 2.2% for adnexal involvement and 16.0% for involvement of the serosa (P=.0522. The 7-year distant metastasis-free survival was 72.7% for adnexal involvement and 58.7% for serosa (P=.3994. The 7-year disease-specific survival (DSS was 71.8% for patients with adnexal involvement and 75.4% for patients with serosa. Conclusion. Endometrial carcinoma stage IIIA with involvement of the adnexa or serosa showed to have a comparable disease-specific survival. Locoregional control was worse for serosa involvement compared to adnexa.

  3. Short-term outcomes of robotic radical esophagectomy for esophageal cancer by a nontransthoracic approach compared with conventional transthoracic surgery.

    Science.gov (United States)

    Mori, K; Yamagata, Y; Aikou, S; Nishida, M; Kiyokawa, T; Yagi, K; Yamashita, H; Nomura, S; Seto, Y

    2016-07-01

    Transthoracic esophagectomy (TTE) is believed to have advantages for mediastinal lymphadenectomy in the treatment of resectable esophageal cancer despite its association with a greater incidence of pulmonary complications and postoperative mortality. Transhiatal esophagectomy is regarded as less invasive, though insufficient in terms of lymph node dissection. With the aim of achieving lymph dissection equivalent to that of TTE, we have developed a nontransthoracic esophagectomy (NTTE) procedure combining a video-assisted cervical approach for the upper mediastinum and a robot-assisted transhiatal approach for the middle and lower mediastinum. We prospectively studied 22 accumulated cases of NTTE and verified feasibility by analyzing perioperative and histopathological outcomes. We compared this group's short-term outcomes with outcomes of 139 equivalent esophageal cancer cases operated on at our institution by conventional TTE (TTE group). In the NTTE group, there were no procedure-related events and no midway conversions to the conventional surgery; the mean operation time was longer (median, 524 vs. 428 minutes); estimated blood loss did not differ significantly between the two groups (median, 385 mL vs. 490 mL); in the NTTE group, the postoperative hospital stay was shorter (median, 18 days vs. 24 days). No postoperative pneumonia occurred in the NTTE group. The frequencies of other major postoperative complications did not differ significantly, nor were there differences in the numbers of harvested mediastinal lymph nodes (median, 30 vs. 29) or in other histopathology findings. NTTE offers a new radical procedure for resection of esophageal cancer combining a cervical video-assisted approach and a transhiatal robotic approach. Although further accumulation of surgical cases is needed to corroborate these results, NTTE promises better prevention of pulmonary complications in the management of esophageal cancer. PMID:25809390

  4. Short course continuous, hyperfractionated, accelerated radiation therapy (CHART) as preoperative treatment for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Brooks, S.; Glynne-Jones, R.; Harrison, M.; Makris, A. [Mount Vernon Cancer Center, Northwood, Middlesex (United Kingdom); Novell, R.; Brown, K. [Luton and Dunstable Hospital (United Kingdom)

    2006-12-15

    Determine feasibility and toxicity of preoperative short course pelvic CHART (25 Gy in 15 fractions over 5 days) for treatment of clinically resectable primary rectal tumours. Between 1998 and 2004, 20 patients with clinically staged T3 resectable rectal carcinoma were treated in this prospective pilot study with preoperative short course CHART to their pelvis. The aim was for total mesorectal excision within 7 days. Radiation toxicity, surgical morbidity, locoregional control (LRC), overall (OS), cause specific (CSS) and disease free survival (DFS) outcomes were documented. Nineteen of the 20 patients completed planned radiotherapy. One discontinued radiotherapy due to toxicity. All patients underwent potentially curative radical surgery. One patient developed grade 3, and three patients grade 2 gastrointestinal toxicity. With a median follow-up of 31 months (range 0.9-88), there is no grade 3, 4 or 5 late toxicity. Two patients experienced grade 2, and three patients grade 1 late bowel toxicity. Two patients died from postoperative complications, and two developed grade 2 abdominal wound infections. At 3 years LRC is 95% (95% CI 83-100), OS 72% (95% CI 51-94), CSS 86% (95% CI 68-100) and DFS 80% (95% CI 60-100). Two patients died from metastatic disease, one patient from a second primary and one patient is alive after successful resection of hepatic metastases. This small study suggests preoperative short course CHART for clinically resectable rectal carcinoma is feasible with acceptable compliance and tolerable side effects.

  5. 3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells

    OpenAIRE

    Zhe LIU; Sun, Yiming; Hong, Haiyu; Zhao, Surong; Zou, Xue; Ma, Renqiang; Jiang, Chenchen; Wang, Zhiwei; Li, Huabin; Liu, Hao

    2015-01-01

    Increasing evidence demonstrates that the hexokinase inhibitor 3-bromopyruvate (3-BrPA) induces the cell apoptotic death by inhibiting ATP generation in human cancer cells. Interestingly, some tumor cell lines are less sensitive to 3-BrPA-induced apoptosis than others. Moreover, the molecular mechanism of 3-BrPA-trigged apoptosis is unclear. In the present study, we examined the effects of 3-BrPA on the viability of the breast cancer cell lines MDA-MB-231 and MCF-7. We further investigated th...

  6. The Fragile X Protein binds mRNAs involved in cancer progression and modulates metastasis formation

    OpenAIRE

    Lucá, Rossella; Averna, Michele; Zalfa, Francesca; Vecchi, Manuela; Bianchi, Fabrizio; Fata, Giorgio La; Del Nonno, Franca; Nardacci, Roberta; Bianchi, Marco; Nuciforo, Paolo; Munck, Sebastian; Parrella, Paola; Moura, Rute; Signori, Emanuela; Alston, Robert

    2013-01-01

    The role of the fragile X mental retardation protein (FMRP) is well established in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost ubiquitously expressed, suggesting that, in addition to its effects in brain, it may have fundamental roles in other organs. There is evidence that FMRP expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in hepatocellular carcinoma cells. A decreased risk of cancer has been reported in patients with FXS wh...

  7. Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure

    OpenAIRE

    Moan, Johan; Porojnicu, Alina Carmen; Dahlback, Arne; Setlow, Richard B.

    2008-01-01

    Solar radiation is the main cause of skin cancers. However, it also is a main source of vitamin D for humans. Because the optimal status of vitamin D protects against internal cancers and a number of other diseases, a controversy exists: Will increased sun exposure lead to net health benefits or risks? We calculated the relative yield of vitamin D photosynthesis as a function of latitude with a radiative transfer model and cylinder geometry for the human skin surface. The annual yield of vita...

  8. Production of the Streptomyces scabies coronafacoyl phytotoxins involves a novel biosynthetic pathway with an F420 -dependent oxidoreductase and a short-chain dehydrogenase/reductase.

    Science.gov (United States)

    Bown, Luke; Altowairish, Mead S; Fyans, Joanna K; Bignell, Dawn R D

    2016-07-01

    Coronafacoyl phytotoxins are secondary metabolites that are produced by various phytopathogenic bacteria, including several pathovars of the Gram-negative bacterium Pseudomonas syringae as well as the Gram-positive potato scab pathogen Streptomyces scabies. The phytotoxins are composed of the polyketide coronafacic acid (CFA) linked via an amide bond to amino acids or amino acid derivatives, and their biosynthesis involves the cfa and cfa-like gene clusters that are found in P. syringae and S. scabies, respectively. The S. scabies cfa-like gene cluster was previously reported to contain several genes that are absent from the P. syringae cfa gene cluster, including one (oxr) encoding a putative F420 -dependent oxidoreductase, and another (sdr) encoding a predicted short-chain dehydrogenase/reductase. Using gene deletion analysis, we demonstrated that both oxr and sdr are required for normal production of the S. scabies coronafacoyl phytotoxins, and structural analysis of metabolites that accumulated in the Δsdr mutant cultures revealed that Sdr is directly involved in the biosynthesis of the CFA moiety. Our results suggest that S. scabies and P. syringae use distinct biosynthetic pathways for producing coronafacoyl phytotoxins, which are important mediators of host-pathogen interactions in various plant pathosystems. PMID:26991928

  9. Effect of short-term exposure to dichlorvos on synaptic plasticity of rat hippocampal slices: Involvement of acylpeptide hydrolase and α7 nicotinic receptors

    International Nuclear Information System (INIS)

    Dichlorvos is the active molecule of the pro-drug metrifonate used to revert the cognitive deficits associated with Alzheimer's disease. A few years ago it was reported that dichlorvos inhibits the enzyme acylpeptide hydrolase at lower doses than those necessary to inhibit acetylcholinesterase to the same extent. Therefore, the aim of our investigation was to test the hypothesis that dichlorvos can enhance synaptic efficacy through a mechanism that involves acylpeptide hydrolase instead of acetylcholinesterase inhibition. We used long-term potentiation induced in rat hippocampal slices as a model of synaptic plasticity. Our results indicate that short-term exposures (20 min) to 50 μM dichlorvos enhance long-term potentiation in about 200% compared to the control condition. This effect is correlated with approximately 60% inhibition of acylpeptide hydrolase activity, whereas acetylcholinesterase activity remains unaffected. Paired-pulse facilitation and inhibition experiments indicate that dichlorvos does not have any presynaptic effect in the CA3 → CA1 pathway nor affect gabaergic interneurons. Interestingly, the application of 100 nM methyllicaconitine, an α7 nicotinic receptor antagonist, blocked the enhancing effect of dichlorvos on long-term potentiation. These results indicate that under the exposure conditions described above, dichlorvos enhances long-term potentiation through a postsynaptic mechanism that involves (a) the inhibition of the enzyme acylpeptide hydrolase and (b) the modulation of α7 nicotinic receptors.

  10. Breast cancer patients with metastatic spinal cord compression. Number of extraspinal organs involved by metastases influences survival

    Energy Technology Data Exchange (ETDEWEB)

    Weber, A. [University of Luebeck, University Hospital Schleswig-Holstein, Campus Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Department of Medical Oncology and Hematology, Luebeck (Germany); Bartscht, T. [University of Luebeck, Department of Medical Oncology and Hematology, Luebeck (Germany); Karstens, J.H. [Hannover Medical University, Department of Radiation Oncology, Hannover (Germany); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Arizona (United States); Rades, D. [University of Luebeck, University Hospital Schleswig-Holstein, Campus Luebeck, Department of Radiation Oncology, Luebeck (Germany)

    2014-03-15

    The goal of the present work was to investigate the predictive value of the number of extraspinal organs involved by metastases for the survival of patients with metastatic spinal cord compression (MSCC) from breast cancer. Data of 145 breast cancer patients who received 10 fractions of 3 Gy of radiotherapy (RT) alone for MSCC were retrospectively analyzed. Seven potential prognostic factors were investigated including age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, interval from breast cancer diagnosis to RT of MSCC, ambulatory status prior to RT, time to developing motor deficits, and the number of involved extraspinal organs. The 1-year survival rates for involvement of 0, 1, 2, and ≥ 3 extraspinal organs were 86, 73, 36, and 16 % (p < 0.001). In the multivariate analysis, the number of involved extraspinal organs remained significant (risk ratio 2.19; 95 % confidence interval 1.61-3.00; p < 0.001). ECOG performance score (p < 0.001), ambulatory status prior to RT (p = 0.003), and the time to developing motor deficits (p < 0.001) were also significantly associated with survival in the multivariate analysis. The number of extraspinal organs involved by metastases is an independent prognostic factor of survival in patients with MSCC from breast cancer. (orig.) [German] In dieser Studie wurde die prognostische Bedeutung der Anzahl metastatisch befallener extraspinaler Organe fuer das Ueberleben von Brustkrebspatientinnen mit metastatisch bedingter Rueckenmarkskompression (MBRK) untersucht. Die Daten von 145 Brustkrebspatientinnen, die eine alleinige Strahlentherapie (RT) mit 10 Fraktionen mit je 3 Gy aufgrund einer MBRK erhielten, wurden retrospektiv ausgewertet. Sieben moegliche Prognosefaktoren wurden untersucht: Alter, Allgemeinzustand (Eastern Cooperative Oncology Group performance score = ECOG-PS), Anzahl befallener Wirbelkoerper, Intervall von der Erstdiagnose der Tumorerkrankung bis zur RT der MBRK

  11. Rationale, design, and implementation protocol of the Dutch clinical practice guideline Pain in patients with cancer: a cluster randomised controlled trial with short message service (SMS and interactive voice response (IVR

    Directory of Open Access Journals (Sweden)

    te Boveldt Nienke

    2011-12-01

    Full Text Available Abstract Background One-half of patients with cancer have pain. In nearly one out of two cancer patients with pain, this was undertreated. Inadequate pain control still remains an important problem in this group of patients. Therefore, in 2008 a national, evidence-based multidisciplinary clinical practice guideline 'pain in patients with cancer' has been developed. Yet, publishing a guideline is not enough. Implementation is needed to improve pain management. An innovative implementation strategy, Short Message Service with Interactive Voice Response (SVS-IVR, has been developed and pilot tested. This study aims to evaluate on effectiveness of this strategy to improve pain reporting, pain measurement and adequate pain therapy. In addition, whether the active role of the patient and involvement of caregivers in pain management may change. Methods/design A cluster randomised controlled trial with two arms will be performed in six oncology outpatient clinics of hospitals in the Southeastern region of the Netherlands, with three hospitals in the intervention and three in the control condition. Follow-up measurements will be conducted in all hospitals to study the long-term effect of the intervention. The intervention includes training of professionals (medical oncologists, nurses, and general practitioners and SMS-IVR to report pain in patients with cancer to improve pain reporting by patients, pain management by medical oncologists, nurses, and general practitioners, and decrease pain intensity. Discussion This innovative implementation strategy with technical tools and the involvement of patients, may enhance the use of the guideline 'pain in patients with cancer' for pain management. Short Message Service alerts may serve as a tool to support self-management of patients. Therefore, the SMS-IVR intervention may increase the feeling of having control over one's life. Trail registration Netherlands Trial Register (NTR: NTR2739

  12. Clinical short-term results of radiofrequency ablation in liver cancers

    Institute of Scientific and Technical Information of China (English)

    Hong-Chi Jiang; Lian-Xin Liu; Da-Xun Piao; Jun Xu; Min Zheng; An-Long Zhu; Shu-Yi Qi; Wei-Hui Zhang; Lin-Feng Wu

    2002-01-01

    AIM: To study local therapeutic efficacy, side effects, andcomplications of radiofrequency ablation (RFA), whichis emerging as a new method for the treatment ofpatients with hepatocellular carcinoma (HCC) withcirrhosis or chronic hepatitis and metastatic liver cancer.METHODS: Thirty-six patients with primary andsecondary liver cancers (21 with primaryhepatocellular carcinoma, 12 with colorectal cancerliver metastases and 3 with other malignant livermetastases), which were considered not suitable forcurative resection, were include in this study. Theywere treated either with RFA (RITA2000, MountainView, California, USA) percutaneously (n=20)orintraoperatively (n=16).The procedures wereperformed using the ultrasound guidance. The qualityof RFA were based on monitoring of equipments andsubject feeling of the practitioners. Patients treatedwith RFA was followed according to clinical findings,radiographic images, and tumor markers.RESULTS: Thirty-six patients underwent RFA for 48nodules. RFA was used to treat an average 1.3 lesionsper patient, and the median size of treated lesions was2.5 cm (range, 0.5-9 cm). The average hospital staywas 5.6 days overall (2.8 days for percutaneous casesand 7.9 days for open operations). Seven patientsunderwent a second RFA procedure (sequentialablations). Sixteen HCC patients with a high level ofalpha fetoprotein (AFP) and 9 colorectal cancer livermetastases patients with a high level of serumcarcinoembryonic antigen (CEA) have a great reductionbenefited from RFA. Four (11.1 %) patients hadcomplications: one skin burn; one postoperativehemorrhage; one cholecystitis and one hepatic abscessassociated with percutaneous ablations of a largelesion. There were 4 deaths: 3 patients died from localand system diseases (1 at 7 month, 1 at 9 month, and 1at 12 month), 1 patients died from cardiovascular shock,but no RFA-related death. At a median follow-up of 10months (range, 1-24 months), 6 patients (16.7 %) hadrecurrences at an RFA site, and 20

  13. The usefulness of MRI and PET imaging for the detection of parametrial involvement and lymph node metastasis in patients with cervical cancer

    International Nuclear Information System (INIS)

    The purpose of this study is to elucidate the usefulness of magnetic resonance imaging (MRI) and positron emission tomography (PET) for the detection of parametrial involvement and lymph node metastasis in patients with cervical cancer. Thirty-six patients with cervical cancer were retrospectively enrolled. MRI and PET scans were performed for all patients within a week before radical surgery. The criterion for malignancy on MRI was >1 cm short axis diameter of the suspected lymph node. On PET, only fluorodeoxyglucose (FDG) uptake was significantly higher than the background and, if this FDG uptake showed on at least two consecutive axial slices, then the lesion was considered as a malignancy. We compared the extent of tumor on the surgical findings with the International Federation of Gynecology and Obstetrics (FIGO) staging, MRI and PET scans. The accuracy of FIGO and MRI staging was 67 and 84.4%, respectively. The accuracy for detecting pelvic lymph node metastasis was better for PET than for MRI (78 versus 67%, respectively). All FDG uptake lymph nodes were confirmed as metastatic lymph nodes by pathological evaluation; this included five lymph nodes <1 cm in diameter. MRI provides an improved evaluation of local tumor extension, but PET is more useful for the evaluation of pelvic lymph nodes than MRI; however, PET still misses microscopic disease. Further studies are necessary to evaluate the usefulness of PET/computed tomography (CT) for the accuracy of the disease extension and the cost-effectiveness of MRI, PET or PET/CT in patients with cervical cancer. (author)

  14. The short effect of pelvic radiotherapy of gynecological cancers on humoral and cell mediated immunity

    International Nuclear Information System (INIS)

    An analysis of short effect of pelvic irradiation on cellular and humoral immunity was made in 24 patients treated by irradiation alone or a combination of surgery and irradiation for uterine carcinoma, at 2, 6, 12 months after loco-regional therapy. Twelve months later there is a decrease of T lymphocytes (P = 0.01), whereas the B lymphocytes count is normal; the percentage of T and B lymphocytes remains stable, but the lymphocyte response to PHA after 3 days is reduced (p = 0.03). A significant decrease of immunoglobulins G, A and M is observed

  15. Prevalence of chromosomal rearrangements involving non-ETS genes in prostate cancer

    DEFF Research Database (Denmark)

    Kluth, Martina; Galal, Rami; Krohn, Antje;

    2015-01-01

    Prostate cancer is characterized by structural rearrangements, most frequently including translocations between androgen-dependent genes and members of the ETS family of transcription factor like TMPRSS2:ERG. In a recent whole genome sequencing study we identified 140 gene fusions that were...

  16. Radiotherapy for glioblastoma: reorganization of genome maintenance mechanisms involved in the process of inhibiting cancer

    International Nuclear Information System (INIS)

    Glioblastoma is a very aggressive brain tumor, which occurs in Glial cells. The treatment consists in chemotherapy, surgery and radiotherapy. The radiotherapy is a treatment method that uses ionizing radiation to kill cancer cells. The cells have genome maintenance mechanisms (MMG) distributed in apoptosis, DNA damage response, and cell cycle pathways. These pathways are formed by sets of proteins and perform specific functions within the cell (example: induce cell death). The mutation of these proteins associated with the failure of the MMG can cause the activation of mutations and consequently induce the development of cancer. This work, objective has to identify pathways and proteins expressed in cancer treatment using free software of the statistical analysis, developed in Fortran and R platforms to show the effects caused by radiation in the proteins of cancerous tissues. The results, were fond to pathways of glioblastoma treated with radiotherapy, activation of apoptosis and response to DNA damage pathways, indicating that there is death of carcinogenic tissue caused by radiation and that some cells are triggering a process of DNA repair. (author)

  17. Association of involvement in psychological self-regulation with longer survival in patients with metastatic cancer: an exploratory study.

    Science.gov (United States)

    Cunningham, A J; Phillips, C; Lockwood, G A; Hedley, D W; Edmonds, C V

    2000-01-01

    There have been numerous anecdotal claims that when patients are dedicated users of a variety of psychological self-regulation strategies, including relaxation, mental imaging, cognitive restructuring and meditation, such dedication may have a life-prolonging effect. Our aim was to test this possibility more rigorously, in patients with metastatic cancer.A prospective, longitudinal, correlative study was carried out on 22 patients with varying kinds of medically incurable metastatic cancer. The intervention was one year of weekly group psychological therapy. Extensive verbal data (patients' written homework and therapists' notes) were collected over the year. The extent of each patient's involvement with psychological work was estimated following a qualitative analysis of these data. Patients were classed as showing high, moderate, or low involvement on the basis of a quantitative rating of categories defined by the analysis. These three subgroups did not differ significantly in their expected median survival duration as estimated from independent quantitative predictions by a large panel of oncologists who analyzed the patients' medical charts at time of study entry.A significant relationship was found between degree of involvement in psychological work and survival duration. Results are presented as Kaplan-Meier survival curves (Fig. 2;P = 0. 006, Log Rank test) and as a graphic display of the median survival of each of the three groups (Fig. 3). The main likely confounders (medical status, age, quality of life, and attendance at therapy) were similar across subgroups and did not change the relation between psychological work and survival duration. Limitations in the design are discussed. However, the strong effects observed support clinical observations that dedicated involvement in psychological self-regulation may prolong the life of some patients with metastatic cancer. PMID:11015769

  18. Involvement of multiple loci on chromosome 3 in renal cell cancer development

    NARCIS (Netherlands)

    van den Berg, Anke; Buys, CHCM

    1997-01-01

    In renal cell carcinoma (RCC), mostly occurring as sporadic cases, the short arm of chromosome 3 is a frequent target of deletion events. Taking into account cytological classifications of RCC, the deletions appear to be characteristic of clear cell or nonpapillary RCC only. This subtype constitutes

  19. Identification of possible genetic polymorphisms involved in cancer cachexia: a systematic review

    Indian Academy of Sciences (India)

    Benjamin H. L. Tan; James A. Ross; Stein Kaasa; Frank Skorpen; Kenneth C. H. Fearon; European Palliative Care Research Collaborative

    2011-04-01

    Cancer cachexia is a polygenic and complex syndrome. Genetic variations in regulation of the inflammatory response, muscle and fat metabolic pathways, and pathways in appetite regulation are likely to contribute to the susceptibility or resistance to developing cancer cachexia. A systematic search of Medline and EmBase databases, covering 1986–2008 was performed for potential candidate genes/genetic polymorphisms relating to cancer cachexia. Related genes were then identified using pathway functional analysis software. All candidate genes were reviewed for functional polymorphisms or clinically significant polymorphisms associated with cachexia using the OMIM and GeneRIF databases. Genes with variants which had functional or clinical associations with cachexia and replicated in at least one study were entered into pathway analysis software to reveal possible network associations between genes. A total of 184 polymorphisms with functional or clinical relevance to cancer cachexia were identified in 92 candidate genes. Of these, 42 polymorphisms (in 33 genes) were replicated in more than one study with 13 polymorphisms found to influence two or more hallmarks of cachexia (i.e. inflammation, loss of fat mass and/or lean mass and reduced survival). Thirty-three genes were found to be significantly interconnected in two major networks with four genes (ADIPOQ, IL6, NFKB1 and TLR4) interlinking both networks. Selection of candidate genes and polymorphisms is a key element of multigene study design. The present study provides an initial framework to select genes/polymorphisms for further study in cancer cachexia, and to develop their potential as susceptibility biomarkers of developing cachexia.

  20. Identification and Pathway Analysis of microRNAs with No Previous Involvement in Breast Cancer

    Science.gov (United States)

    Rebollar-Vega, Rosa; Quintanar-Jurado, Valeria; Maffuz-Aziz, Antonio; Jimenez-Sanchez, Gerardo; Bautista-Piña, Veronica; Arellano-Llamas, Rocio; Hidalgo-Miranda, Alfredo

    2012-01-01

    microRNA expression signatures can differentiate normal and breast cancer tissues and can define specific clinico-pathological phenotypes in breast tumors. In order to further evaluate the microRNA expression profile in breast cancer, we analyzed the expression of 667 microRNAs in 29 tumors and 21 adjacent normal tissues using TaqMan Low-density arrays. 130 miRNAs showed significant differential expression (adjusted P value = 0.05, Fold Change = 2) in breast tumors compared to the normal adjacent tissue. Importantly, the role of 43 of these microRNAs has not been previously reported in breast cancer, including several evolutionary conserved microRNA*, showing similar expression rates to that of their corresponding leading strand. The expression of 14 microRNAs was replicated in an independent set of 55 tumors. Bioinformatic analysis of mRNA targets of the altered miRNAs, identified oncogenes like ERBB2, YY1, several MAP kinases, and known tumor-suppressors like FOXA1 and SMAD4. Pathway analysis identified that some biological process which are important in breast carcinogenesis are affected by the altered microRNA expression, including signaling through MAP kinases and TP53 pathways, as well as biological processes like cell death and communication, focal adhesion and ERBB2-ERBB3 signaling. Our data identified the altered expression of several microRNAs whose aberrant expression might have an important impact on cancer-related cellular pathways and whose role in breast cancer has not been previously described. PMID:22438871

  1. Plant Toxin-Based Immunotoxins for Cancer Therapy: A Short Overview

    Directory of Open Access Journals (Sweden)

    Letizia Polito

    2016-06-01

    Full Text Available Immunotoxins are chimeric proteins obtained by linking a toxin to either an intact antibody or an antibody fragment. Conjugation can be obtained by chemical or genetic engineering, where the latter yields recombinant conjugates. An essential requirement is that the target molecule recognized by the antibody is confined to the cell population to be deleted, or at least that it is not present on stem cells or other cell types essential for the organism’s survival. Hundreds of different studies have demonstrated the potential for applying immunotoxins to many models in pre-clinical studies and in clinical trials. Immunotoxins can be theoretically used to eliminate any unwanted cell responsible for a pathological condition. The best results have been obtained in cancer therapy, especially in hematological malignancies. Among plant toxins, the most frequently employed to generate immunotoxins are ribosome-inactivating proteins, the most common being ricin. This review summarizes the various approaches and results obtained in the last four decades by researchers in the field of plant toxin-based immunotoxins for cancer therapy.

  2. Comparison of short-term outcomes between laparoscopically-assisted vs. transverse-incision open right hemicolectomy for right-sided colon cancer: a retrospective study

    OpenAIRE

    Akaraviputh Thawatchai; Chinswangwatanakul Vitoon; Lohsiriwat Darin; Lohsiriwat Varut; Lert-akyamanee Narong

    2007-01-01

    Abstract Background Laparoscopically-assisted right hemicolectomy (LRH) is an acceptable alternative to open surgery for right-sided colon cancer which offers patients less pain and faster recovery. However, special equipment and substantial surgical experience are required. The aim of the study is to compare the short-term surgical outcomes of LRH and open right hemicolectomy through right transverse skin crease incision (ORHT) for right-sided colon cancer. Patients and methods This retrospe...

  3. Aneuploidy involving chromosome 1 may be an early predictive marker of intestinal type gastric cancer

    International Nuclear Information System (INIS)

    Intestinal type gastric cancer is a significant cause of mortality, therefore a better understanding of its molecular basis is required. We assessed if either aneuploidy or activity of the oncogenic transcription factor nuclear factor kappa B (NF-κB), increased incrementally during pre-malignant gastric histological progression and also if they correlated with each other in patient samples, as they are both induced by oxygen free radicals. In a prospective study of 54 (aneuploidy) and 59 (NF-κB) consecutive patients, aneuploidy was assessed by interphase fluorescent in situ hybridisation (FISH) for chromosome 1. NF-κB was assessed by expression of interleukin-8 (IL-8), and in a subset, by immunohistochemistry (IHC) for active p65. Aneuploidy levels increased incrementally across the histological series. 2.76% of cells with normal histology (95% CI, 2.14-3.38%) showed background levels of aneuploidy, this increased to averages of 3.78% (95% CI, 3.21-4.35%), 5.89% (95% CI, 3.72-8.06%) and 7.29% (95% CI, 4.73-9.85%) of cells from patients with gastritis, Helicobacter pylori positive gastritis and atrophy/intestinal metaplasia (IM) respectively. IL-8 expression was only increased in patients with current H. pylori infection. NF-κB analysis showed some increased p65 activity in inflamed tissues. IL-8 expression and aneuploidy level were not linked in individual patients. Aneuploidy levels increased incrementally during histological progression; were significantly elevated at very early stages of neoplastic progression and could well be linked to cancer development and used to assess cancer risk. Reactive oxygen species (ROS) induced in early gastric cancer are presumably responsible for the stepwise accumulation of this particular mutation, i.e. aneuploidy. Hence, aneuploidy measured by fluorescent in situ hybridisation (FISH) coupled to brush cytology, would be worthy of consideration as a predictive marker in gastric cancer and could be clinically useful in pre

  4. Aneuploidy involving chromosome 1 may be an early predictive marker of intestinal type gastric cancer

    Energy Technology Data Exchange (ETDEWEB)

    Williams, L. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Somasekar, A. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Davies, D.J.; Cronin, J.; Doak, S.H. [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom); Alcolado, R. [Royal Glamorgan Hospital, Ynysmaerdy, Llantrisant CF72 8XR (United Kingdom); Williams, J.G. [Neath Port Talbot Hospital, Abertawe Bro Morgannwg University NHS Trust, Baglan Way, Port Talbot SA12 7BX (United Kingdom); Griffiths, A.P. [Department of Histopathology, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Baxter, J.N. [Department of Surgery, Morriston Hospital, Abertawe Bro Morgannwg University NHS Trust, Morriston, SA66NL (United Kingdom); Jenkins, G.J.S., E-mail: g.j.jenkins@swansea.ac.uk [Institute of Life Science, Swansea School of Medicine, Swansea University, Swansea SA28PP (United Kingdom)

    2009-10-02

    Intestinal type gastric cancer is a significant cause of mortality, therefore a better understanding of its molecular basis is required. We assessed if either aneuploidy or activity of the oncogenic transcription factor nuclear factor kappa B (NF-{kappa}B), increased incrementally during pre-malignant gastric histological progression and also if they correlated with each other in patient samples, as they are both induced by oxygen free radicals. In a prospective study of 54 (aneuploidy) and 59 (NF-{kappa}B) consecutive patients, aneuploidy was assessed by interphase fluorescent in situ hybridisation (FISH) for chromosome 1. NF-{kappa}B was assessed by expression of interleukin-8 (IL-8), and in a subset, by immunohistochemistry (IHC) for active p65. Aneuploidy levels increased incrementally across the histological series. 2.76% of cells with normal histology (95% CI, 2.14-3.38%) showed background levels of aneuploidy, this increased to averages of 3.78% (95% CI, 3.21-4.35%), 5.89% (95% CI, 3.72-8.06%) and 7.29% (95% CI, 4.73-9.85%) of cells from patients with gastritis, Helicobacter pylori positive gastritis and atrophy/intestinal metaplasia (IM) respectively. IL-8 expression was only increased in patients with current H. pylori infection. NF-{kappa}B analysis showed some increased p65 activity in inflamed tissues. IL-8 expression and aneuploidy level were not linked in individual patients. Aneuploidy levels increased incrementally during histological progression; were significantly elevated at very early stages of neoplastic progression and could well be linked to cancer development and used to assess cancer risk. Reactive oxygen species (ROS) induced in early gastric cancer are presumably responsible for the stepwise accumulation of this particular mutation, i.e. aneuploidy. Hence, aneuploidy measured by fluorescent in situ hybridisation (FISH) coupled to brush cytology, would be worthy of consideration as a predictive marker in gastric cancer and could be

  5. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Epidemiological studies have shown direct associations between type 2 diabetes and obesity, both conditions associated with hyperglycaemia and hyperinsulinemia, and the risk of pancreatic cancer. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent population studies indicate that the incidence of pancreatic cancer is reduced among diabetics taking metformin. In this study, the effects of exposure of pancreatic cancer cells to high glucose levels on their growth and response to metformin were investigated. The human pancreatic cancer cell lines AsPC-1, BxPC-3, PANC-1 and MIAPaCa-2 were grown in normal (5 mM) or high (25 mM) glucose conditions, with or without metformin. The influence by metformin on proliferation, apoptosis and the AMPK and IGF-IR signalling pathways were evaluated in vitro. Metformin significantly reduced the proliferation of pancreatic cancer cells under normal glucose conditions. Hyperglycaemia however, protected against the metformin-induced growth inhibition. The anti-proliferative actions of metformin were associated with an activation of AMP-activated protein kinase AMPKThr172 together with an inhibition of the insulin/insulin-like growth factor-I (IGF-I) receptor activation and downstream signalling mediators IRS-1 and phosphorylated Akt. Furthermore, exposure to metformin during normal glucose conditions led to increased apoptosis as measured by poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, exposure to high glucose levels promoted a more robust IGF-I response and Akt activation which correlated to stimulated AMPKSer485 phosphorylation and impaired AMPKThr172 phosphorylation, resulting in reduced anti-proliferative and apoptotic effects by metformin. Our results indicate that metformin has direct anti-tumour activities in pancreatic cancer cells involving AMPKThr172 activation and suppression of the insulin/IGF signalling pathways

  6. Short-Term Outcomes of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer: A Prospective Multicenter Cohort Study

    Science.gov (United States)

    Choi, Il Ju; Lee, Na Rae; Kim, Sang Gyun; Lee, Wan Sik; Park, Seun Ja; Kim, Jae J.; Lee, Jun Haeng; Kwon, Jin-Won; Park, Seung-Hee; You, Ji Hye; Kim, Ji Hyun; Lim, Chul-Hyun; Cho, Joo Young; Kim, Gwang Ha; Lee, Yong Chan; Jung, Hwoon-Yong; Kim, Ji Young; Chun, Hoon Jai; Seol, Sang-Yong

    2016-01-01

    Background/Aims Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC) that has demonstrated a minimal risk of lymph node metastasis in retrospective studies. We sought to prospectively evaluate the short-term outcomes of ESD treatment in EGCs. Methods A prospective multicenter cohort study of neoplasms 3 cm or less in diameter at endoscopic size evaluation was performed in 12 Korean ESD study group-related university hospitals and the National Cancer Center. Resected specimens were evaluated by the central pathologic review board. Results A patient cohort (n=712) with a total of 737 EGCs was analyzed. The margin-freeen bloc resection rate was 97.3%, and curative resection of 640 lesions (86.8%) was achieved. Lower curative resection rates were associated with lesions 2 to 3 cm in size prior to ESD compared with lesions 2 cm or less in size (78.6% vs 88.1%, respectively, p=0.009). Significant factors associated with noncurative resection were moderately or poorly differentiated histological type, posterior wall tumor location, tumor size larger than 3 cm, ulceration, and submucosal invasion. Delayed bleeding occurred in 49 patients (6.9%), and 12 patients (1.7%) exhibited perforations. Conclusions ESD is an effective treatment with a high curative resection rate for EGCs that meets relatively conservative pre-ESD indications. Long-term survival outcomes should be evaluated in follow-up studies. PMID:27172929

  7. Glioblastoma specific antigens, GD2 and CD90, are not involved in cancer stemness

    OpenAIRE

    Woo, Seon Rang; Oh, Young Taek; An, Jae Yeol; Kang, Bong Gu; Nam, Do-Hyun; Joo, Kyeung Min

    2015-01-01

    Glioblastoma multiforme (GBM) is the most malignant World Health Organization grade IV brain tumor. GBM patients have a poor prognosis because of its resistance to standard therapies, such as chemotherapy and radiation. Since stem-like cells have been associated with the treatment resistance of GBM, novel therapies targeting the cancer stem cell (CSC) population is critically required. However, GBM CSCs share molecular and functional characteristics with normal neural stem cells (NSCs). To el...

  8. Virtual ligand screening studies between mushroom compounds and proteins involved in breast cancer

    OpenAIRE

    Froufe, Hugo J. C.; Abreu, Rui M. V.; Ferreira, Isabel C. F. R.

    2010-01-01

    Mushrooms are a vast and yet largely untapped source of powerful new pharmaceutical products. In particular, and most importantly for modern medicine, they represent an unlimited source of compounds with antitumor and immunostimulating properties [1]. Particularly, the intake of some wild mushrooms has shown to reduce the risk of breast cancer in Chinese women [2]. A large number of LMW (low molecular weight) compounds have been "identified in wild mushrooms including phenolic ...

  9. Anti-Müllerian hormone is associated with extrauterine involvement and stage of disease in patients with endometrial cancer.

    Science.gov (United States)

    Dogan, N U; Kerimoglu, O S; Karabagli, P; Pekin, A; Yilmaz, S A; Incesu, F; Celik, C

    2015-02-01

    Our aim was to evaluate serum levels of anti-Müllerian hormone (AMH) and also immunohistochemical (IHC) staining properties of AMH receptor type II (AMHRII) in patients with endometrial cancer (EC) and a control group. Preoperatively, serum levels of AMH were assessed and AMHRII expression was evaluated by immunohistochemistry in a benign and malignant group. AMH serum levels of the control group and EC patients were comparable. For EC patients, there was no difference with respect to the AMH levels and tumour stage; grade; histological type; deep myometrial invasion; lymphovascular space invasion or lymph node involvement. However, AMH levels in patients with extrauterine involvement were higher than patients with disease confined to the uterus. EC samples were more likely to be stained positive for AMHRII than benign lesions. Also, as the stage of the lesion worsens, the rate of IHC staining of AMHRII decreases. In conclusion, AMHRII is expressed in normal endometrial cells as well as endometrial cancer cells. AMH levels increase in EC, with extrauterine involvement at least in locally advanced disease. Also AMH expression decreases as the disease is staged-up. PMID:25111828

  10. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression

    Science.gov (United States)

    Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D.; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

    2016-01-01

    The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma. Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines. We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK. Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%. Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression. Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants. In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

  11. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kuk, Deborah; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-03-15

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.

  12. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    International Nuclear Information System (INIS)

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy

  13. Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells

    International Nuclear Information System (INIS)

    A major problem with the use of current chemotherapy regimens for several cancers, including breast cancer, is development of intrinsic or acquired drug resistance, which results in disease recurrence and metastasis. However, the mechanisms underlying this drug resistance are unknown. To study the molecular mechanisms underlying the invasive and metastatic activities of drug-resistant cancer cells, we generated a doxorubicin-resistant MCF-7 breast cancer cell line (MCF-7/DOX). We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, flow cytometry assays, DNA fragmentation assays, Western blot analysis, cell invasion assays, small interfering RNA (siRNA) transfection, reverse transcription-polymerase chain reaction, experimental lung metastasis models, and gelatin and fibrinogen/plasminogen zymography to study the molecular mechanism of metastatic activities in MCF-7/DOX cells. We found that MCF-7/DOX acquired invasive activities. In addition, Western blot analysis showed increased expression of epidermal growth factor receptor (EGFR) and Cox-2 in MCF-7/DOX cells. Inhibition of Cox-2, phosphoinositide 3-kinase (PI3K)/Akt, or mitogen-activated protein kinase (MAPK) pathways effectively inhibited the invasive activities of MCF-7/DOX cells. Gelatin and fibrinogen/plasminogen zymography analysis showed that the enzymatic activities of matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator were markedly higher in MCF-7/DOX cells than in the MCF-7 cells. In vitro invasion assays and mouse models of lung metastasis demonstrated that MCF-7/DOX cells acquired invasive abilities. Using siRNAs and agonists specific for prostaglandin E (EP) receptors, we found that EP1 and EP3 played important roles in the invasiveness of MCF-7/DOX cells. We found that the invasive activity of MCF-7/DOX cells is mediated by Cox-2, which is induced by the EGFR-activated PI3K/Akt and MAPK pathways. In addition, EP1 and EP3 are important in

  14. Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

    International Nuclear Information System (INIS)

    Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells

  15. Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bing, E-mail: wangbin69@yahoo.com; Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

    2013-07-19

    Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells.

  16. PET/CT Imaging of c-Myc Transgenic Mice Identifies the Genotoxic N-Nitroso-Diethylamine as Carcinogen in a Short-Term Cancer Bioassay

    OpenAIRE

    Katja Hueper; Mahmoud Elalfy; Florian Laenger; Roman Halter; Thomas Rodt; Michael Galanski; Juergen Borlak

    2012-01-01

    BACKGROUND: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. METHODOLOGY/PRINCI...

  17. Accuracy of High-Resolution MRI with Lumen Distention in Rectal Cancer Staging and Circumferential Margin Involvement Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Iannicelli, Elsa; Di Renzo, Sara [Radiology Institute, Faculty of Medicine and Psychology, University of Rome, Sapienza, Sant' Andrea Hospital, Rome 00189 (Italy); Department of Surgical and Medical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University of Rome, Sapienza, Sant' Andrea Hospital, Rome 00189 (Italy); Ferri, Mario [Department of Surgical and Medical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University of Rome, Sapienza, Sant' Andrea Hospital, Rome 00189 (Italy); Pilozzi, Emanuela [Department of Clinical and Molecular Sciences, Faculty of Medicine and Psychology, University of Rome, Sapienza, Sant' Andrea Hospital, Rome 00189 (Italy); Di Girolamo, Marco; Sapori, Alessandra [Radiology Institute, Faculty of Medicine and Psychology, University of Rome, Sapienza, Sant' Andrea Hospital, Rome 00189 (Italy); Department of Surgical and Medical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University of Rome, Sapienza, Sant' Andrea Hospital, Rome 00189 (Italy); Ziparo, Vincenzo [Department of Surgical and Medical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University of Rome, Sapienza, Sant' Andrea Hospital, Rome 00189 (Italy); David, Vincenzo [Radiology Institute, Faculty of Medicine and Psychology, University of Rome, Sapienza, Sant' Andrea Hospital, Rome 00189 (Italy); Department of Surgical and Medical Sciences and Translational Medicine, Faculty of Medicine and Psychology, University of Rome, Sapienza, Sant' Andrea Hospital, Rome 00189 (Italy)

    2014-07-01

    To evaluate the accuracy of magnetic resonance imaging (MRI) with lumen distention for rectal cancer staging and circumferential resection margin (CRM) involvement prediction. Seventy-three patients with primary rectal cancer underwent high-resolution MRI with a phased-array coil performed using 60-80 mL room air rectal distention, 1-3 weeks before surgery. MRI results were compared to postoperative histopathological findings. The overall MRI T staging accuracy was calculated. CRM involvement prediction and the N staging, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were assessed for each T stage. The agreement between MRI and histological results was assessed using weighted-kappa statistics. The overall MRI accuracy for T staging was 93.6% (k = 0.85). The accuracy, sensitivity, specificity, PPV and NPV for each T stage were as follows: 91.8%, 86.2%, 95.5%, 92.6% and 91.3% for the group ≤ T2; 90.4%, 94.6%, 86.1%, 87.5% and 94% for T3; 98,6%, 85.7%, 100%, 100% and 98.5% for T4, respectively. The predictive CRM accuracy was 94.5% (k = 0.86); the sensitivity, specificity, PPV and NPV were 89.5%, 96.3%, 89.5%, and 96.3% respectively. The N staging accuracy was 68.49% (k = 0.4). MRI performed with rectal lumen distention has proved to be an effective technique both for rectal cancer staging and involved CRM predicting.

  18. Proteomic biomarkers predicting lymph node involvement in serum of cervical cancer patients. Limitations of SELDI-TOF MS

    Directory of Open Access Journals (Sweden)

    Van Gorp Toon

    2012-06-01

    Full Text Available Abstract Background Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. We investigated whether lymph node status can be predicted with proteomic profiling. Material & methods Serum samples of 60 cervical cancer patients (FIGO I/II were obtained before primary treatment. Samples were run through a HPLC depletion column, eliminating the 14 most abundant proteins ubiquitously present in serum. Unbound fractions were concentrated with spin filters. Fractions were spotted onto CM10 and IMAC30 surfaces and analyzed with surface-enhanced laser desorption time of flight (SELDI-TOF mass spectrometry (MS. Unsupervised peak detection and peak clustering was performed using MASDA software. Leave-one-out (LOO validation for weighted Least Squares Support Vector Machines (LSSVM was used for prediction of lymph node involvement. Other outcomes were histological type, lymphvascular space involvement (LVSI and recurrent disease. Results LSSVM models were able to determine LN status with a LOO area under the receiver operating characteristics curve (AUC of 0.95, based on peaks with m/z values 2,698.9, 3,953.2, and 15,254.8. Furthermore, we were able to predict LVSI (AUC 0.81, to predict recurrence (AUC 0.92, and to differentiate between squamous carcinomas and adenocarcinomas (AUC 0.88, between squamous and adenosquamous carcinomas (AUC 0.85, and between adenocarcinomas and adenosquamous carcinomas (AUC 0.94. Conclusions Potential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer. However, identification of the potential biomarkers was hampered by the technical limitations of SELDI-TOF MS.

  19. Accuracy of High-Resolution MRI with Lumen Distention in Rectal Cancer Staging and Circumferential Margin Involvement Prediction

    International Nuclear Information System (INIS)

    To evaluate the accuracy of magnetic resonance imaging (MRI) with lumen distention for rectal cancer staging and circumferential resection margin (CRM) involvement prediction. Seventy-three patients with primary rectal cancer underwent high-resolution MRI with a phased-array coil performed using 60-80 mL room air rectal distention, 1-3 weeks before surgery. MRI results were compared to postoperative histopathological findings. The overall MRI T staging accuracy was calculated. CRM involvement prediction and the N staging, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were assessed for each T stage. The agreement between MRI and histological results was assessed using weighted-kappa statistics. The overall MRI accuracy for T staging was 93.6% (k = 0.85). The accuracy, sensitivity, specificity, PPV and NPV for each T stage were as follows: 91.8%, 86.2%, 95.5%, 92.6% and 91.3% for the group ≤ T2; 90.4%, 94.6%, 86.1%, 87.5% and 94% for T3; 98,6%, 85.7%, 100%, 100% and 98.5% for T4, respectively. The predictive CRM accuracy was 94.5% (k = 0.86); the sensitivity, specificity, PPV and NPV were 89.5%, 96.3%, 89.5%, and 96.3% respectively. The N staging accuracy was 68.49% (k = 0.4). MRI performed with rectal lumen distention has proved to be an effective technique both for rectal cancer staging and involved CRM predicting

  20. Combination chemotherapy in the treatment of breast cancer patients with metastatic brain involvement and a poor prognosis

    Directory of Open Access Journals (Sweden)

    D. R. Naskhletashvili

    2011-01-01

    Full Text Available Radiotherapy (RT is a standard treatment for breast cancer (BC patients with metastatic brain involvement. All patients (n = 15 had already received chemotherapy (CT for the underlying disease when they were found to have brain metastases. To develop effective CT regimens for patients with recurrent brain metastases, who have received RT to the brain, is a serious problem. Combination CT with gemcitabine and cisplatin showed a high efficacy (complete and partial regressions were achieved in 47.7% of cases and fair survival rates (median 10 months in a group of patients with BC brain metastases and a poor prognosis.

  1. Short- and long-term cause-specific survival of patients with inflammatory breast cancer

    Directory of Open Access Journals (Sweden)

    Sadikov Evgeny

    2005-10-01

    Full Text Available Abstract Background Inflammatory breast cancer (IBC had been perceived to have a poor prognosis. Oncologists were not enthusiastic in the past to give aggressive treatment. Single institution studies tend to have small patient numbers and limited years of follow-up. Most studies do not report 10-, 15- or 20-year results. Methods Data was obtained from the population-based database of the Surveillance, Epidemiology, and End Results program of the National Cancer Institute from 1975–1995 using SEER*Stat5.0 software. This period of 21 years was divided into 7 periods of 3 years each. The years were chosen so that there was adequate follow-up information to 2000. ICD-O-2 histology 8530/3 was used to define IBC. The lognormal model was used for statistical analysis. Results A total of 1684 patients were analyzed, of which 84% were white, 11% were African Americans, and 5% belonged to other races. Age distribution was 70 in 21%. The lognormal model was validated for 1975–77 and for 1978–80, since the 10-, 15- and 20-year cause-specific survival (CSS rates, could be calculated using the Kaplan-Meier method with data available in 2000. The data were then used to estimate the 10-, 15- and 20-year CSS rates for the more recent years, and to study the trend of improvement in survival. There were increasing incidences of IBC: 134 patients in the 1975–77 period to 416 patients in the 1993–95 period. The corresponding 20-year CSS increased from 9% to 20% respectively with standard errors of less than 4%. Conclusion The improvement of survival during the study period may be due to introduction of more aggressive treatments. However, there seem to be no further increase of long-term CSS, which should encourage oncologists to find even more effective treatments. Because of small numbers of patients, randomized studies will be difficult to conduct. The SEER population-based database will yield the best possible estimate of the trend in improvement of

  2. Recent insight on the control of enzymes involved in estrogen formation and transformation in human breast cancer.

    Science.gov (United States)

    Pasqualini, Jorge R; Chetrite, Gérard S

    2005-02-01

    The great majority of breast cancers are in their early stage hormone-dependent and it is well accepted that estradiol (E2) plays an important role in the genesis and evolution of this tumor. Human breast cancer tissues contain all the enzymes: estrone sulfatase, 17beta-hydroxysteroid dehydrogenase, aromatase involved in the last steps of E2 bioformation. Sulfotransferases which convert estrogens into the biologically inactive estrogen sulfates are also present in this tissue. Quantitative data show that the 'sulfatase pathway', which transforms estrogen sulfates into the bioactive unconjugated E2, is 100-500 times higher than the 'aromatase pathway', which converts androgens into estrogens. The treatment of breast cancer patients with anti-aromatases is largely developed with very positive results. However, the formation of E2 via the 'sulfatase pathway' is very important in the breast cancer tissue. In recent years it was found that antiestrogens (e.g. tamoxifen, 4-hydroxytamoxifen), various progestins (e.g. promegestone, nomegestrol acetate, medrogestone, dydrogesterone, norelgestromin), tibolone and its metabolites, as well as other steroidal (e.g. sulfamates) and non-steroidal compounds, are potent sulfatase inhibitors. In another series of studies, it was found that E2 itself has a strong anti-sulfatase action. This paradoxical effect of E2 adds a new biological response of this hormone and could be related to estrogen replacement therapy in which it was observed to have either no effect or to decrease breast cancer mortality in postmenopausal women. Interesting information is that high expression of steroid sulfatase mRNA predicts a poor prognosis in patients with +ER. These progestins, as well as tibolone, can also block the conversion of estrone to estradiol by the inhibition of the 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD-1). High expressison of 17beta-HSD-1 can be an indicator of adverse prognosis in ER-positive patients. It was shown that

  3. Therapy's shadow: a short history of the study of resistance to cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Peter eKeating

    2013-05-01

    Full Text Available This article traces the history of research on resistance to drug therapy in oncology usingscientometric techniques and qualitative analysis. Using co-citation analysis, we generatemaps to visualize subdomains in resistance research in two time periods, 1975-1990 and1995-2010. These maps reveal two historical trends in resistance research: first, a shift infocus from generic mechanisms of resistance to chemotherapy to a focus on resistance totargeted therapies and molecular mechanisms of oncogenesis; and second, a movementaway from an almost exclusive reliance on animal and cell models and towards thegeneration of knowledge about resistance through clinical trial work. A close reading ofhighly cited articles within each subdomain cluster reveals specific points of transitionfrom one regime to the other, in particular the failure of several promising theories ofresistance to be translated into clinical insights and the emergence of interest in resistanceto a new generation of targeted agents such as imatinib and trastuzumab. We argue thatthe study of resistance in the oncology field has thus become more integrated withresearch into cancer therapy—rather than constituting it as a separate domain of study, asit has done in the past, contemporary research treats resistance as the flip side totreatment, as therapy’s shadow.

  4. Involvement of a Non-Human Sialic Acid in Human Cancer

    Directory of Open Access Journals (Sweden)

    AjitVarki

    2014-02-01

    Full Text Available Sialic acids are common monosaccharides that are widely expressed as outer terminal units on all vertebrate cell surfaces, and play fundamental roles in cell-cell and cell-microenvironment interactions. The predominant sialic acids on most mammalian cells are N-glycolylneuraminic acid (Neu5Gc and N-acetylneuraminic acid (Neu5Ac. Neu5Gc is notable for its deficiency in humans, due to a species-specific and species-universal inactivating deletion in the CMAH gene encoding the hydroxylase that converts CMP-Neu5Ac to CMP-Neu5Gc. However, Neu5Gc is metabolically incorporated into human tissues from dietary sources (particularly red meat, and detected at even higher levels in some human cancers. Early life exposure to Neu5Gc containing foods in the presence of certain commensal bacteria that incorporate dietary Neu5Gc into lipooligosaccharides can lead to generation of antibodies that are also cross-reactive against Neu5Gc-containing glycans in human tissues (“xeno-autoantigens”. Such anti-Neu5Gc “xeno-autoantibodies” are found in all humans, although ranging widely in levels among individuals, and displaying diverse and variable specificities for the underlying glycan. Experimental evidence in a human-like Neu5Gc deficient Cmah-/- mouse model shows that inflammation due to “xenosialitis” caused by this antigen-antibody interaction can promote tumor progression, suggesting a likely mechanism for the well-known epidemiological link between red meat consumption and carcinoma risk. In this review, we discuss the history of this field, mechanisms of Neu5Gc incorporation into tissues, the origin and specificities of human anti-Neu5Gc antibodies, their use as possible cancer biomarkers, implications of xenosialitis in cancer initiation and progression, and current and future approaches towards immunotherapy that could take advantage of this unusual human-specific phenomenon.

  5. Involvement of Notch-1 in Resistance to Regorafenib in Colon Cancer Cells.

    Science.gov (United States)

    Mirone, Giovanna; Perna, Stefania; Shukla, Arvind; Marfe, Gabriella

    2016-05-01

    Regorafenib, an oral small-molecule multi kinase inhibitor, is able to block Vascular Endothelial Growth Factor Receptors (VEGFR-1, 2, and 3), Platelet-Derived Growth Factor Receptors (PDGF), Fibroblast Growth Factor (FGF) receptor 1, Raf, TIE-2, and the kinases KIT, RET, and BRAF. Different studies have displayed its antitumor activity in several cancer models (both in vitro and in vivo), particularly in colorectal and gastrointestinal stromal cancers. The mechanism of resistance to regorafenib is largely unknown. In our investigation, we have generated regorafenib-resistant SW480 cells (Reg-R-SW480 cells) by culturing such cells with increasing concentration of regorafenib. Examination of intracellular signaling found that Akt signaling was activated in Reg-R-SW480 cells but not in wild-type SW480 cells, after regorafenib treatment as measured by Western Blot. The Notch pathway is a fundamental signaling system in the development and homeostasis of tissues since it regulates different cellular process such as proliferation, differentiation, and apoptosis and it can be a potential driver of resistance to a wide array of targeted therapies. In this study, we found that Notch-1 was significantly up-regulated in resistant tumor cells as well as HES1 and HEY. Additionally, inhibition of Notch-1 in resistant cells partially restored sensitivity to regorafenib treatment in vitro. Collectively, these data suggest a key role of Notch-1 in mediating the resistant effects of regorafenib in colorectal cancer cells, and also provide a rationale to improve the therapeutic efficacy of regorafenib. PMID:26419617

  6. The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T

    International Nuclear Information System (INIS)

    The short fatty acid, butyrate, which is produced by intestinal anaerobic bacteria in the colon, has inhibitory activity on histone deacetylases (HDACs). Treatment of the human colon cancer cell line, LS174T, with 1-2 mM sodium butyrate stimulated MUC2 mucin production, as determined by histological PAS staining of carbohydrate chains of mucin, and confirmed at the protein and mRNA levels by immunoblotting with anti-MUC2 antibody and real-time RT-PCR, respectively. Increases in acetylated histone H3 in the LS174T cells treated with butyrate suggest inhibition of HDACs in these cells. Butyrate-stimulated MUC2 production in the LS174T cells was inhibited by the MEK inhibitor, U0126, implicating the involvement of extracellular signal-regulated kinase (ERK) cascades in this process. Proliferation of the LS174T cells was inhibited by butyrate treatment. Although apoptotic nuclear DNA fragmentation could not be detected, cell-cycle arrest at the G0/G1 phase in the butyrate-treated cells was demonstrated by flow cytometry. Thus butyrate, an HDAC inhibitor, inhibits proliferation of LS174T cells but stimulates MUC2 production in individual cells

  7. Identification of eight genes that are potentially involved in tamoxifen sensitivity in breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Tyler ZARUBIN; Qing JING; Liguo NEW; Jiahuai HAN

    2005-01-01

    Although the antiestrogen agent tamoxifen has long been used to treat women with hormone receptor positive invasive breast carcinoma, the mechanisms of its action and acquired resistance to tamoxifen during treatment are largely unknown. A number of studies have revealed that over-activation of some signaling pathways can cause tamoxifen resistance; however, very little information is available regarding the genes whose loss-of-function alternation contribute to tamoxifen resistance. Here we used a forward genetic approach in vitro to generate tamoxifen resistant cells from the tamoxifen sensitive breast cancer cell line ZR-75-1, and further identified the disrupted gene in different tamoxifen resistant clones. Retinol binding protein 7, DNA polymerase-transactivated protein 3, γ-glutamyltransferase-like activity 1,slit-robo RhoGTPase-activating protein, tetraspan NET-4, HSPC 194, amiloride-sensitive epithelial sodium channel gene,and Notch2, were the eight mutated genes identified in different tamoxifen resistant clones, suggesting their requirement for tamoxifen sensitivity in ZR-75-1 cells. Since the functions of these genes are not related to each other, it suggests that multiple pathways can influence tamoxifen sensitivity in breast cancer cells.

  8. Prediction of pathological stage in prostate cancer through the percentage of involved fragments upon biopsy

    Directory of Open Access Journals (Sweden)

    Marcos F. Dall'oglio

    2005-10-01

    Full Text Available INTRODUCTION: The need for defining the extension of disease in patients undergoing radical prostatectomy due to prostate adenocarcinoma is a relevant factor cure in such individuals. In order to identify a new independent preoperative factor for predicting the extension of prostate cancer, we assessed the role of the percentage of positive fragments upon biopsy. MATERIALS AND METHODS: A retrospective study compared the percentage of positive fragments on biopsy with the extension of disease as defined by the pathological examination of the surgical specimen from 898 patients undergoing radical prostatectomy due to clinically localized prostate cancer. RESULTS: On the univariate analysis, the percentage of positive fragments on biopsy showed a statistical significance for predicting confined disease (p < 0.001, which was found in 66.7% of the cases under study. Additionally, we observed that the total number of removed fragments exerts no influence on the extension of the disease (p = 0.567. CONCLUSION: the percentage of positive fragments is an independent factor for predicting the pathological stage of prostate adenocarcinoma, and the number of removed fragments is not related to the extension of the disease.

  9. High-dose rate brachytherapy in localized penile cancer: short-term clinical outcome analysis

    International Nuclear Information System (INIS)

    To assess clinical outcomes of high-dose rate interstitial brachytherapy (HIB) in localized penile carcinoma. From 03/2006 to 08/2013, patients with biopsy-proven T1-T2 (<4 cm) non-metastatic localized penile squamous cell carcinoma underwent HIB. Under general anaesthesia, after Foley catheter placement, needles were placed in the target volume using a dedicated template. Planification was carried out with a post-implant CT-scan to deliver a total dose of 36 Gy in 9 fractions over 5 days (in adjuvant setting) or 39 Gy in 9 fractions over 5 days (as monotherapy). Dose-volume adaptation was manually achieved using graphical optimization. Dosimetric data and clinical outcomes were retrospectively analyzed. Toxicities were graded using the CTC v4.0. With a median follow-up of 27 months [5.1-83], 12 patients including 8 T1a, 3 T1b and 1 T2 N0 underwent HIB (sole therapy: 11 pts; adjuvant: 1 pt). The actuarial 5-year relapse-free, cause-specific and overall survival rates were 83%, 100% and 78% respectively. Comparing pre and post treatment evaluation, no IPSS or IIEF-5 changes were reported. Dermatitis was reported systematically 1 month after HIB including 6 G1, 5 G2 and 1 G3. Only 1 experienced long-term G3 successfully treated with hyperbaric oxygen therapy. One urethral meatus stenosis G3 required meatotomy. In selected patients with T1-T2 localized penile cancer, HIB may be considered as an optional conservative therapy. Longer follow-up is needed to confirm these encouraging preliminary results

  10. Germline polymorphisms in genes involved in the Hippo pathway as recurrence biomarkers in stages II/III colon cancer.

    Science.gov (United States)

    Sebio, A; Matsusaka, S; Zhang, W; Yang, D; Ning, Y; Stremitzer, S; Stintzing, S; Sunakawa, Y; Yamauchi, S; Fujimoto, Y; Ueno, M; Lenz, H-J

    2016-08-01

    The Hippo pathway regulates tissue growth and cell fate. In colon cancer, Hippo pathway deregulation promotes cellular quiescence and resistance to 5-Fluorouracil (5-Fu). In this study, 14 polymorphisms in 8 genes involved in the Hippo pathway (MST1, MST2, LATS1, LATS2, YAP, TAZ, FAT4 and RASSF1A) were evaluated as recurrence predictors in 194 patients with stages II/III colon cancer treated with 5-Fu-based adjuvant chemotherapy. Patients with a RASSF1A rs2236947 AA genotype had higher 3-year recurrence rate than patients with CA/CC genotypes (56 vs 33%, hazard ratio (HR): 1.87; P=0.017). Patients with TAZ rs3811715 CT or TT genotypes had lower 3-year recurrence rate than patients with a CC genotype (28 vs 40%; HR: 0.66; P=0.07). In left-sided tumors, this association was stronger (HR: 0.29; P=0.011) and a similar trend was found in an independent Japanese cohort. These promising results reveal polymorphisms in the Hippo pathway as biomarkers for stages II and III colon cancer.The Pharmacogenomics Journal advance online publication, 15 September 2015; doi:10.1038/tpj.2015.64. PMID:26370619

  11. Chest wall involvement by lung cancer. Thin-section computed tomography based on radiologic-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Kouzo; Katou, Yuji; Oshita, Fumihiro [Kanagawa Cancer Center, Yokohama (Japan)] [and others

    1996-10-01

    The aim of this retrospective study was to evaluate the role of conventional computed tomography (CT) findings and thin-section CT findings in predicting chest wall invasion by lung cancer, and the results of surgery according to the depth of chest wall involvement. We reviewed 33 patients with lung cancer adjacent to the pleural surface who underwent conventional CT scanning and subsequent thoracotomy. All the patients were examined with a TCT-900S, HELIX scanner (Toshiba, Tokyo) following bolus intravenous contrast medium administration (conventional: 60 ml; thin-section: 40 ml). The conventional CT images (taken at 10 mm intervals with 10 mm collimation) and thin-section CT images (taken at 2 mm intervals with 2 mm collimation) were reconstructed employing an extended scale (window level: 40; window width: 400) using standard images. A comparison of the diagnoses based on the thin-section CT findings and pathological examination findings showed thin-section CT to be 82% accurate for chest wall invasion compared to 48% for conventional CT. We conclude that thin-section CT is useful for the accurate evaluation of chest wall invasion in lung cancer, especially for patients in whom findings by conventional CT suggest possible tumor invasion of the chest wall. (author)

  12. Proteomics displays cytoskeletal proteins and chaperones involvement in Hedyotis corymbosa-induced photokilling in skin cancer cells.

    Science.gov (United States)

    You, Bang-Jau; Wu, Yang-Chang; Wu, Chi-Yu; Bao, Bo-Ying; Chen, Mei-Yu; Chang, Yu-Hao; Lee, Hong-Zin

    2011-08-01

    Photodynamic therapy was found to be an effective therapy for local malignant tumors. This study demonstrated that 80 μg/ml Hedyotis corymbosa extracts with 0.8 J/cm(2) fluence dose caused M21 skin cancer cell death. Photoactivated H. corymbosa-induced M21 cell death is a typical apoptosis that is accompanied by nuclear condensation, externalization of phosphatidylserine and the changes in protein expression of apoptosis-related proteins, such as Bcl-2 and caspase family members. This study applied 2D electrophoresis to analyse the proteins involved in the photoactivated H. corymbosa-induced M21 cell apoptosis. We found 12 proteins to be markedly changed. According to the results of protein sequence analysis of these altered protein spots, we identified that the expression of cytoskeletal proteins and chaperones were involved in the photoactivated H. corymbosa-induced M21 cell apoptosis. We further demonstrated that photoactivated H. corymbosa caused a significant effect on the cytoskeleton distribution and mitochondrial activity in M21 cells. Based on the above findings, this study characterized the effects and mechanisms of the photoactivated H. corymbosa-induced apoptosis in M21 skin cancer cells. PMID:21569101

  13. Nodal involvement pattern in resectable lung cancer according to tumor location

    International Nuclear Information System (INIS)

    The aim in this study was to define the pattern of lymph node metastasis according to the primary tumor location. In this retrospective cohort study, each of the operable patients diagnosed with lung cancer was grouped by tumor mass location. The International Association for the Study of Lung Cancer nodal chart with stations and zones, established in 2009, was used to define lymph node levels. From 2006 to 2010, 197 patients underwent a lobectomy with systematic nodal resection for primary lung cancer at Chiang Mai University Hospital. There were 123 male and 74 female patients, with ages ranging from 16– 85 years old and an average age of 61.31. Analyses of tumor location, histology type, and nodal metastasis were performed. The locations were the right upper lobe in 63 patients (31.98%), the right middle lobe in 18 patients (9.14%), the right lower lobe in 30 patients (15.23%), the left upper lobe in 55 patients (27.92%), the left lower lobe in 16 patients (8.12%), and mixed lobes (more than one lobe) in 15 patients (7.61%). The mean tumor size was 4.45 cm in diameter (range 1.2–16.5 cm). Adenocarcinoma was the most common histological type, which occurred in 132 cases (67.01%), followed by squamous cell carcinoma in 41 cases (20.81%), bronchiolo alveolar cell carcinoma in nine cases (4.57%), and large cell carcinoma in seven cases (3.55%). Eighteen cases (9.6%) had skip metastasis (mediastinal lymph node metastasis without hilar node metastasis). Adenocarcinoma and intratumoral lymphatic invasion were the predictors of mediastinal lymph node metastases. There were statistically significant differences between a tumor in the right upper lobe and the right lower lobe. However, there were no statistically significant differences between tumors in the other lobes. In conclusion, tumor location is not a precise predictor of the pattern of nodal metastasis. Systematic lymph node dissection is the only way to accurately determine lymph node status. Further studies

  14. Airway and esophageal stenting in patients with advanced esophageal cancer and pulmonary involvement.

    Directory of Open Access Journals (Sweden)

    Fabrice Paganin

    Full Text Available BACKGROUND: Most inoperable patients with esophageal-advanced cancer (EGC have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. METHODS AND FINDINGS: The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58+/-\\-8 years of age with esophageal stenting indication were investigated. Seven patients (group 1 were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression. Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2: stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication. Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/-10 weeks and was significantly shorter in group 1 (6+/-7.6 weeks than in group 2 (28+/-11 weeks, p<0.001. Scheduled double stenting significantly improved symptoms (95% at day 7 with a low complication rate (13%, and achieved a specific cancer treatment (84% in most cases. CONCLUSION: Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased

  15. Epigenetic Profiling of H3K4Me3 Reveals Herbal Medicine Jinfukang-Induced Epigenetic Alteration Is Involved in Anti-Lung Cancer Activity.

    Science.gov (United States)

    Lu, Jun; Zhang, Xiaoli; Shen, Tingting; Ma, Chao; Wu, Jun; Kong, Hualei; Tian, Jing; Shao, Zhifeng; Zhao, Xiaodong; Xu, Ling

    2016-01-01

    Traditional Chinese medicine Jinfukang (JFK) has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci. PMID:27087825

  16. Alterations of Phosphoproteins in NCI-H526 Small Cell Lung Cancer Cells Involved in Cytotoxicity of Cisplatin and Titanocene Y

    Directory of Open Access Journals (Sweden)

    Ulrike Olszewski

    2012-09-01

    Full Text Available First-line treatment of small cell lung cancer (SCLC with combination chemotherapy consisting of cis-diamminedichloroplatinum(II (cisplatin and etoposide is frequently followed by early relapses and a dismal prognosis. Survival of a fraction of tumor cells and development of chemoresistance may be influenced by an initial cellular stress response against the administered xenobiotics. Therefore, we compared the short-term effects of cisplatin and non-cross-resistant bis-[(p-methoxybenzylcyclopentadienyl] titanium(IV dichloride (Titanocene Y on phosphorylation of 46 sites of a total of 38 signaling proteins in tumor suppressor protein 53 (p53-wild-type NCI-H526 SCLC cells. The functional significance of selected kinases for the cytotoxicity of both drugs was tested using specific inhibitors and an activator. The cisplatin-induced cellular stress response involved activation of p38α mitogen-activated protein kinase, whereas Titanocene Y-triggered signaling affected c-Jun N-terminal kinase. Phosphorylation of adenosine monophosphate (AMP-activated protein kinase α1 (AMPKα1 was increased by both drugs, which promoted cell survival, as indicated by results obtained using AMPK inhibitor compound C and AMPK activator 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside. This is in good agreement with previous reports, where AMPKα1 was demonstrated to represent an important factor for the sensitivity to cisplatin in colon and ovarian cancers, most likely by induction of autophagy. Thus, AMPKα1 constitutes a potential target to be exploited for chemotherapeutic treatment of SCLC to circumvent resistance to metal-based compounds.

  17. Outcomes following treatment for patients with cranial nerve involvement from nasopharyngeal cancer

    International Nuclear Information System (INIS)

    Patients with locally advanced nasopharyngeal carcinoma (NPC) commonly present with cranial nerve (CN) involvement, which can cause significant morbidity. We aimed to characterise the pattern of involvement and outcomes of these patients, as well as determine if these differed according to the mode of diagnosis. Patients were included if they had non-distant metastatic NPC, presented with CN involvement and completed radiotherapy treatment between 2002 and 2008. The clinical response was categorised as complete response, partial response, stable or progressive disease. The radiological response was assessed using the Response Evaluation Criteria in Solid Tumors criteria. The loco-regional control and disease-free survival rates were estimated with the Kaplan–Meier method. Forty-seven patients fulfilled the inclusion criteria. CN lesions were diagnosed on clinical examination in 15% of patients, radiologically in 40% and both clinically and radiologically in 45% of patients. A complete or partial response of the CN lesions was seen clinically in 82% and radiologically in 95% of patients. The 3-year local relapse free survival was 64.3%, distant metastasis-free survival was 46.1% and overall survival was 82.8%. There were no differences in outcomes between patients with clinically versus radiologically detected CN lesions. Most of these patients are likely to undergo clinical and/or radiological resolution of the nerve lesions following chemoradiotherapy, but the outcome was not determined by the mode of diagnosis (radiological or clinical).

  18. Clinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Kotlinska-Lemieszek A

    2015-09-01

    Full Text Available Aleksandra Kotlinska-Lemieszek,1 Pål Klepstad,2,3,6 Dagny Faksvåg Haugen2,4,5 1Palliative Medicine Chair and Department, University Hospital of the Lord’s Transfiguration, Karol Marcinkowski University of Medical Sciences, Poznan, Poland; 2European Palliative Care Research Centre, Faculty of Medicine, Norwegian University of Science and Technology,Trondheim, Norway; 3Department of Anaesthesiology and Intensive Care Medicine, St Olavs Hospital, Trondheim, Norway; 4Regional Centre of Excellence for Palliative Care, Haukeland University Hospital, Bergen, Norway; 5Department of Clinical Medicine K1, University of Bergen, Bergen, Norway; 6Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway Background: Opioids are the most frequently used drugs to treat pain in cancer patients. In some patients, however, opioids can cause adverse effects and drug–drug interactions. No advice concerning the combination of opioids and other drugs is given in the current European guidelines. Objective: To identify studies that report clinically significant drug–drug interactions involving opioids used for pain treatment in adult cancer patients. Design and data sources: Systematic review with searches in Embase, MEDLINE, and Cochrane Central Register of Controlled Trials from the start of the databases (Embase from 1980 through January 2014. In addition, reference lists of relevant full-text papers were hand-searched. Results: Of 901 retrieved papers, 112 were considered as potentially eligible. After full-text reading, 17 were included in the final analysis, together with 15 papers identified through hand-searching of reference lists. All of the 32 included publications were case reports or case series. Clinical manifestations of drug–drug interactions involving opioids were grouped as follows: 1 sedation and respiratory depression, 2 other central nervous system symptoms, 3 impairment of pain

  19. Evaluation of cognitive function in patients with limited small cell lung cancer prior to and shortly following prophylactic cranial irradiation

    International Nuclear Information System (INIS)

    Purpose: Cognitive deficits after treatment for small cell lung cancer (SCLC) have been attributed to prophylactic cranial irradiation (PCI). A prospective study of neuropsychological function was undertaken to document the evolution and magnitude of neuropsychologic deficits. Methods and Materials: Thirty patients with limited stage SCLC who responded well (29 complete response (CR), 1 partial response (PR)) to combination chemotherapy plus thoracic irradiation or resection were studied with neuropsychological tests in the cognitive domains of intelligence, frontal lobe function, language, memory, visual-perception, and motor dexterity prior to a planned course of PCI. Nine patients had a neurologic history that could influence testing. Results: An unexpected 97% (29 out of 30) of patients had evidence of cognitive dysfunction prior to PCI. The most frequent impairment was verbal memory, followed by frontal lobe dysfunction, and fine motor incoordination. Of the patients with no prior neurologic or substance abuse history, 20 out of 21 (95%) had impairments on neuropsychological assessment. This neurologically normal group was just as impaired as the group with such a history with respect to delayed verbal memory and frontal lobe executive function. Eleven patients had neuropsychological testing 6 to 20 months after PCI; no significant differences were found from their pretreatment tests. Conclusions: A high proportion of neurologically normal patients with limited SCLC and favorable responses to combination chemotherapy have specific cognitive deficits before receiving PCI. Short-term (6 to 20 months) observations after PCI have shown no significant deterioration

  20. "An arena for sharing": Exploring the joint involvement of patients and their relatives in a cancer rehabilitation intervention study

    DEFF Research Database (Denmark)

    la Cour, Karen; Ledderer, Loni; Hansen, Helle Ploug

    2015-01-01

    : sharing cancer experiences, sharing strategies, and sharing mutual care. Conclusion: Sharing in residential rehabilitation is experienced as useful for cancer patients and their relatives, to validate cancer-related strategies and strengthen mutual understanding within relationships. Implications for...

  1. DMBT1 encodes a protein involved in the immune defense and in epithelial differentiation and is highly unstable in cancer

    DEFF Research Database (Denmark)

    Mollenhauer, J; Herbertz, S; Holmskov, U;

    2000-01-01

    that is involved in the respiratory immune defense. Immunohistochemical analyses revealed that DMBT1 is produced by both tumor-associated macrophages and tumor cells and that it is deregulated in glioblastoma multiforme in comparison to normal brain tissue. Our data further suggest that the proteins...... CRP-ductin and hensin, both of which have been implicated in epithelial differentiation, are the DMBT1 orthologs in mice and rabbits, respectively. These findings and the spatial and temporal distribution of DMBT1 in fetal and adult epithelia suggest that DMBT1 further plays a role in epithelial...... during tumorigenesis. Thus, DMBT1 is a gene that is highly unstable in cancer and encodes for a protein with at least two different functions, one in the immune defense and a second one in epithelial differentiation....

  2. Killing of Cancer Cells by the Photoactivatable Protein Kinase C Inhibitor, Calphostin C, Involves Induction of Endoplasmic Reticulum Stress

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    Aparna Kaul

    2009-09-01

    Full Text Available Calphostin C (cal-C is a photoactivatable inhibitor that binds to the regulatory domain of protein kinase C (PKC and to other proteins that contain diacylglycerol/phorbol ester binding sites. Cal-C is cytotoxic against many types of cancer cells, yet the basis for this activity remains poorly understood. Here, we show that one of the earliest effects of cal-C is an impairment of glycoprotein export from the endoplasmic reticulum (ER, accompanied by formation of ER-derived vacuoles. Vacuolization of the ER is correlated with induction of an ER stress response that includes activation of c-Jun N-terminal kinase and protein kinase R-like ER kinase, as well as increased expression of CCAAT/enhancer binding protein homologous transcription factor (CHOP; GADD153. These effects of cal-C are not mimicked by staurosporine, an inhibitor of PKC catalytic activity, indicating that ER stress is due to interaction of cal-C with targets other than PKC. In conjunction with the induction of ER stress, breast carcinoma cells undergo caspase-dependent cell death with early activation of caspases 9 and 7 and cleavage of poly(ADP-ribosepolymerase. Reduction of CHOP expression by short hairpin RNA decreases the sensitivity of the cells to cal-C, suggesting that induction of apoptosis by cal-C is related, at least in part, to ER stress triggered by disruption of ER morphology and transport function. Antineoplastic drugs that work by inducting ER stress have shown promise in preclinical and clinical trials. Thus, the present findings raise the possibility that cal-C may be useful for photodynamic therapy based on induction of ER stress in some forms of cancer.

  3. Specific genes involved in synthesis and editing of heparan sulfate proteoglycans show altered expression patterns in breast cancer

    International Nuclear Information System (INIS)

    The expression of a specific set of genes controls the different structures of heparan sulfate proteoglycans (HSPGs), which are involved in the growth, invasion and metastatic properties of cancerous cells. The purpose of this study is to increase knowledge of HSPG alterations in breast cancer. Twenty-three infiltrating ductal adenocarcinomas (IDCs), both metastatic and non-metastatic were studied. A transcriptomic approach to the structure of heparan sulfate (HS) chains was used, employing qPCR to analyze both the expression of the enzymes involved in their biosynthesis and editing, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate chains, we extended the study to include the genes involved in the biosynthesis of these glycosaminoglycans. Histochemical techniques were also used to analyze tissular expression of particular genes showing significant expression differences, of potential interest. No significant change in transcription was detected in approximately 70% of analyzed genes. However, 13 demonstrated changes in both tumor types (40% showing more intense deregulation in the metastatic), while 5 genes showed changes only in non-metastatic tumors. Changes were related to 3 core proteins: overexpression of syndecan-1 and underexpression of glypican-3 and perlecan. HS synthesis was affected by lower levels of some 3-O-sulfotransferase transcripts, the expression of NDST4 and, only in non metastatic tumors, higher levels of extracellular sulfatases. Furthermore, the expression of chondroitin sulfate also was considerably affected, involving both the synthesis of the saccharidic chains and sulfations at all locations. However, the pro-metastatic enzyme heparanase did not exhibit significant changes in mRNA expression, although in metastatic tumors it appeared related to increased levels of the most stable form of mRNA. Finally, the expression of heparanase 2, which displays anti-metastatic features

  4. Short-term effects of supplementary feeding with enteral nutrition via jejunostomy catheter on post-gastrectomy gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    WU Quan; YU Jian-chun; KANG Wei-ming; MA Zhi-qiang

    2011-01-01

    Background Most gastric cancer patients who undergo gastrectomy develop malnutrition.It is,therefore,crucial to establish an effective means to provide nutrition for these patients.To perform home enteral nutrition (EN) to ensure adequate nutritional intake in gastric cancer patients,we placed a jejunostomy catheter during gastric surgery.Most patients showed improved nutritional status.Methods Twenty-nine inpatients at our hospital underwent radical gastrectomy and jejunostomy from December 2002 to December 2007 and were designated as the jejunostomy group,and 32 matched patients without a jejunostomy tube were designated as the tube-free group.The jejunostomy group was treated with EN from 72 hours to 3 months postoperatively.The tube-free group did not receive EN.Data including preoperative and postoperative body weight,body mass index (BMI),nutrition risk screening (NRS) score,Karnofsky performance score (KPS),and laboratory biochemical indicators were documented respectively and compared.Results Compared with preoperative week 1,both groups showed decreased body weight and BMI at 3 months postoperatively.The weight loss in the jejunostomy group ((7.1±3.3) kg) was significantly less than that in the tube-free group ((9.9±3.1) kg).Similarly,BMI decreased by (2.4+1.0) kg/m2 in the jejunostomy group,which was significantly less than in the tube-free group ((3.2±0.9) kg/m2).The number of patients with postoperative NRS ≥3 was decreased in the jejunostomy group,but was increased in the tube-free group,and this difference was significant.There were no significant differences between the two groups in total lymphocyte count,hemoglobin,albumin and prealbumin,and adverse drug effects.Conclusions Short-term (3 months) EN supplementation via jejunostomy tube can reduce the risk of malnutrition and weight loss,and improve tolerance of chemotherapy.Tube feeding is reliable for achieving these goals because it is not important whether or not the patients have appetites.

  5. MDA-7/IL-24 induces Bcl-2 denitrosylation and ubiquitin-degradation involved in cancer cell apoptosis.

    Directory of Open Access Journals (Sweden)

    Hui Tian

    Full Text Available MDA-7/IL-24 was involved in the specific cancer apoptosis through suppression of Bcl-2 expression, which is a key apoptosis regulatory protein of the mitochondrial death pathway. However, the underlying mechanisms of this regulation are unclear. We report here that tumor-selective replicating adenovirus ZD55-IL-24 leads to Bcl-2 S-denitrosylation and concomitant ubiquitination, which take part in the 26S proteasome degradation. IL-24-siRNA completely blocks Bcl-2 ubiquitination via reversion of Bcl-2 S-denitrosylation and protects it from proteasomal degradation which confirmed the significant role of MDA-7/IL-24 in regulating posttranslational modification of Bcl-2 in cancer cells. Nitric oxide (NO is a key regulator of protein S-nitrosylation and denitrosylation. The NO donor, sodium nitroprusside (SNP, down-regulates Bcl-2 S-denitrosylation, attenuates Bcl-2 ubiquitination and subsequently counteracts MDA-7/IL-24 induced cancer cell apoptosis, whereas NO inhibitor 2-(4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (PTIO shows the opposite effect. At the same time, these NO modulators fail to affect Bcl-2 phosphorylation, suggesting that NO regulates Bcl-2 stability in a phosphorylation-independent manner. In addition, Bcl-2 S-nitrosylation reduction induced by ZD55-IL-24 was attributed to both iNOS decrease and TrxR1 increase. iNOS-siRNA facilitates Bcl-2 S-denitrosylation and ubiquitin-degradation, whereas the TrxR1 inhibitor auranofin prevents Bcl-2 from denitrosylation and ubiquitination, thus restrains the caspase signal pathway activation and subsequent cancer cell apoptosis. Taken together, our studies reveal that MDA-7/IL-24 induces Bcl-2 S-denitrosylation via regulation of iNOS and TrxR1. Moreover, denitrosylation of Bcl-2 results in its ubiquitination and subsequent caspase protease family activation, as a consequence, apoptosis susceptibility. These findings provide a novel insight into MDA-7/IL-24 induced growth

  6. Duration of short-course androgen suppression therapy and the risk of death as a result of prostate cancer.

    LENUS (Irish Health Repository)

    D'Amico, Anthony V

    2011-12-10

    We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories.

  7. Age dependent association of endometrial polyps with increased risk of cancer involvement

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    Martel Maritza

    2005-02-01

    Full Text Available Abstract Background Endometrial polyps (EMPs are commonly encountered in routine surgical pathology practice, but opinions differ on whether they are intrinsically a marker for concurrent or subsequent malignancy. The objectives of the present study are 1 to investigate the age-group in which EMP are most commonly encountered 2 to document the age-group in which EMP are most commonly associated with malignancies 3 To investigate whether the age of diagnosis of the various carcinoma subtypes in EMPs is congruent with published data on similar malignancies arising in non-polypoid endometrium and 4 To investigate whether the histologic subtype distribution of malignancies associated with EMPs are similar or different from the distribution of malignancies arising from non-polypoid endometrium based on published data. Patients and methods All cases of EMPs were retrieved from the files of Yale-New Haven Hospital for the period 1986–1995. The patients were divided into 5 age groups: Each group was further subclassified based on an association (or lack thereof of EMPs with endometrial carcinoma. Chi-square test was used to compare the proportion of malignancy associated EMPs between the age groups. Results We identified 513 EMPs, of which 209 (41% were from biopsy specimens and 304 (59% from hysterectomy specimens. Sixty six (13% of all EMPs were malignant. The 66 malignant EMPs included 58 endometrioid, 6 serous, 1 carcinosarcoma, and 1 clear cell carcinoma. In age group >35, only 1(2.5% of 40 EMPs was associated with endometrial malignancy. In contrast, 37(32% of 115 EMPs were associated with malignancy in the age group > 65. The frequency of malignant EMPs increased with age and reached statistical significance in the age group >65 (p Conclusions EMPs show statistically significant age dependent association with malignant tumor involvement. Careful search for malignancy, particularly in women with multiple risk factors is advised in daily practice

  8. Combining RNA interference and kinase inhibitors against cell signalling components involved in cancer

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    Hanson Bonnie J

    2005-10-01

    Full Text Available Abstract Background The transcription factor activator protein-1 (AP-1 has been implicated in a large variety of biological processes including oncogenic transformation. The tyrosine kinases of the epidermal growth factor receptor (EGFR constitute the beginning of one signal transduction cascade leading to AP-1 activation and are known to control cell proliferation and differentiation. Drug discovery efforts targeting this receptor and other pathway components have centred on monoclonal antibodies and small molecule inhibitors. Resistance to such inhibitors has already been observed, guiding the prediction of their use in combination therapies with other targeted agents such as RNA interference (RNAi. This study examines the use of RNAi and kinase inhibitors for qualification of components involved in the EGFR/AP-1 pathway of ME180 cells, and their inhibitory effects when evaluated individually or in tandem against multiple components of this important disease-related pathway. Methods AP-1 activation was assessed using an ME180 cell line stably transfected with a beta-lactamase reporter gene under the control of AP-1 response element following epidermal growth factor (EGF stimulation. Immunocytochemistry allowed for further quantification of small molecule inhibition on a cellular protein level. RNAi and RT-qPCR experiments were performed to assess the amount of knockdown on an mRNA level, and immunocytochemistry was used to reveal cellular protein levels for the targeted pathway components. Results Increased potency of kinase inhibitors was shown by combining RNAi directed towards EGFR and small molecule inhibitors acting at proximal or distal points in the pathway. After cellular stimulation with EGF and analysis at the level of AP-1 activation using a β-lactamase reporter gene, a 10–12 fold shift or 2.5–3 fold shift toward greater potency in the IC50 was observed for EGFR and MEK-1 inhibitors, respectively, in the presence of RNAi

  9. The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation.

    Science.gov (United States)

    Hinnebusch, Brian F; Meng, Shufen; Wu, James T; Archer, Sonia Y; Hodin, Richard A

    2002-05-01

    The short-chain fatty acid (SCFA) butyrate is produced via anaerobic bacterial fermentation within the colon and is thought to be protective in regard to colon carcinogenesis. Although butyrate (C4) is considered the most potent of the SCFA, a variety of other SCFA also exist in the colonic lumen. Butyrate is thought to exert its cellular effects through the induction of histone hyperacetylation. We sought to determine the effects of a variety of the SCFA on colon carcinoma cell growth, differentiation and apoptosis. HT-29 or HCT-116 (wild-type and p21-deleted) cells were treated with physiologically relevant concentrations of various SCFA, and histone acetylation state was assayed by acid-urea-triton-X gel electrophoresis and immunoblotting. Growth and apoptotic effects were studied by flow cytometry, and differentiation effects were assessed using transient transfections and Northern blotting. Propionate (C3) and valerate (C5) caused growth arrest and differentiation in human colon carcinoma cells. The magnitude of their effects was associated with a lesser degree of histone hyperacetylation compared with butyrate. Acetate (C2) and caproate (C6), in contrast, did not cause histone hyperacetylation and also had no appreciable effects on cell growth or differentiation. SCFA-induced transactivation of the differentiation marker gene, intestinal alkaline phosphatase (IAP), was blocked by histone deacetylase (HDAC), further supporting the critical link between SCFA and histones. Butyrate also significantly increased apoptosis, whereas the other SCFA studied did not. The growth arrest induced by the SCFA was characterized by an increase in the expression of the p21 cell-cycle inhibitor and down-regulation of cyclin B1 (CB1). In p21-deleted HCT-116 colon cancer cells, the SCFA did not alter the rate of proliferation. These data suggest that the antiproliferative, apoptotic and differentiating properties of the various SCFA are linked to the degree of induced histone

  10. Tissue identity testing of cancer by short tandem repeat polymorphism: pitfalls of interpretation in the presence of microsatellite instability.

    Science.gov (United States)

    Much, Melissa; Buza, Natalia; Hui, Pei

    2014-03-01

    Tissue identity testing by short tandem repeat (STR) polymorphism offers discriminating power in resolving tissue mix-up or contamination. However, one caveat is the presence of microsatellite unstable tumors, in which genetic alterations may drastically change the STR wild-type polymorphism leading to unexpected allelic discordance. We examined how tissue identity testing results can be altered by the presence of microsatellite instability (MSI). Eleven cases of MSI-unstable (9 intestinal and 2 endometrial adenocarcinomas) and 10 cases of MSI-stable tumors (all colorectal adenocarcinomas) were included. All had been previously tested by polymerase chain reaction testing at 5 National Cancer Institute (NCI) recommended MSI loci and/or immunohistochemistry for DNA mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2). Tissue identity testing targeting 15 STR loci was performed using AmpF/STR Identifiler Amplification. Ten of 11 MSI-unstable tumors demonstrated novel alleles at 5 to 12 STR loci per case and frequently with 3 or more allelic peaks. However, all affected loci showed identifiable germline allele(s) in MSI-high tumors. A wild-type allelic profile was seen in 7 of 10 MSI-stable tumors. In the remaining 3 cases, isolated novel alleles were present at a unique single locus in addition to germline alleles. Loss of heterozygosity was observed frequently in both MSI-stable (6/11 cases) and MSI-unstable tumors (8/10 cases). In conclusion, MSI may significantly alter the wild-type allelic polymorphism, leading to potential interpretation errors of STR genotyping. Careful examination of the STR allelic pattern, high index of suspicion, and follow-up MSI testing are crucial to avoid erroneous conclusions and subsequent clinical and legal consequences. PMID:24444463

  11. Is sentinel lymph node biopsy more accurate than axillary dissection for staging nodal involvement in breast cancer patients?

    Science.gov (United States)

    Marrazzo, Antonio; Taormina, Pietra; Gebbiab, Vittorio; David, Massimo; Riili, Ignazio; Lo Gerfo, Domenico; Casà, Luigi; Noto, Antonio

    2007-01-01

    Today evaluation of axillary involvement can be routinely performed with the technique of sentinel lymph node biopsy (SLNB). One of the greatest advantages of SLNB is the nearly total absence of local postoperative complications. It is important to understand whether SLNB is better than axillary lymph-node dissection (ALND) for staging axillary nodal involvement. The aim of the study was to evaluate the axillary staging accuracy comparing three different methods: axillary dissection, sentinel node biopsy with the traditional 4-6 sections and sentinel node biopsy with complete analysis of the lymph node. 527 consecutive patients (525 females and 2 males) with invasive breast cancer < or = 3 cm and clinically negative axillary nodes were divided into 3 different groups: group A treated with axillary dissection, group B treated with sentinel nodal biopsy analysed with 4-6 sections, and group C treated with sentinel node biopsy with analysis of the entire node. All patients underwent a quadrantectomy to treat the tumor. Group differences and statistical significance were assessed by ANOVA. The percentages of N+ in group A and group B were 25.80% and 28% respectively, while in the third group it rose to 45%, or almost half the patients. The differences among the three groups were statistically significant (p = 0.02). From our analysis of the data it emerges that axillary dissection and sentinel node biopsy with analysis of 4-6 sections have the same accuracy in staging the nodal status of the axilla; analysis of the entire sentinel lymph node revealed an increased number of patients with axillary nodal involvement, proving more powerful in predicting nodal stage. SLNB with complete examination of the SLN removed can be considered the best method for axillary staging in breast cancer patients with clinical negative nodes. In our study, the percentage of metastases encountered after complete examination of SLN was 45% compared to the accuracy of axillary dissection that

  12. A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors

    OpenAIRE

    Westley, Rosalyne L.; May, Felicity E. B.

    2013-01-01

    Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and bioche...

  13. A 3‐week multimodal intervention involving high‐intensity interval training in female cancer survivors: a randomized controlled trial

    OpenAIRE

    Schmitt, Joachim; Lindner, Nathalie; Reuss‐Borst, Monika; Holmberg, Hans‐Christer; Sperlich, Billy

    2016-01-01

    Abstract To compare the effects of a 3‐week multimodal rehabilitation involving supervised high‐intensity interval training (HIIT) on female breast cancer survivors with respect to key variables of aerobic fitness, body composition, energy expenditure, cancer‐related fatigue, and quality of life to those of a standard multimodal rehabilitation program. A randomized controlled trial design was administered. Twenty‐eight women, who had been treated for cancer were randomly assigned to either a ...

  14. ONE STEP NUCLEIC ACID AMPLIFICATION IN BREAST CANCER SENTINEL LYMPH NODE.A SINGLE INSTITUTIONAL EXPERIENCE AND A SHORT REVIEW.

    Directory of Open Access Journals (Sweden)

    Tatiana eBrambilla

    2015-06-01

    Full Text Available Sentinel lymph node (SLN examination is a standard in breast cancer patients, with several methods employed along its 20-years history, the last one represented by OSNA. The latter is a intra-operative molecular assay searching for CK19 mRNA as a surrogate of metastatic cells. Our 3-years experience with OSNA (1122 patients showed results overlapping those recorded in the same Institution with a morphological evaluation (930 patients of SLN. In detail the data of OSNA were almost identical to those observed with standard post-operative procedure in terms of patients with positive SLN (30% and micrometastatic/macrometastatic involvement of SLN (respectively 38-45% and 62-55%. By contrast when OSNA was compared to the standard intra-operatory procedure it was superior in terms of accuracy, prompting the use of this molecular assay as a very valid and reproducible for intra-operative evaluation of SLN.Further possibilities prompting the use of OSNA range from adhesion to quality control programs, saving of medical time, ability to predict, during surgery, additional nodal metatastis and molecular bio-banking.

  15. Sequence and expression variations in 23 genes involved in mitochondrial and non-mitochondrial apoptotic pathways and risk of oral leukoplakia and cancer.

    Science.gov (United States)

    Datta, Sayantan; Ray, Anindita; Singh, Richa; Mondal, Pinaki; Basu, Analabha; De Sarkar, Navonil; Majumder, Mousumi; Maiti, Guruparasad; Baral, Aradhita; Jha, Ganga Nath; Mukhopadhyay, Indranil; Panda, Chinmay; Chowdhury, Shantanu; Ghosh, Saurabh; Roychoudhury, Susanta; Roy, Bidyut

    2015-11-01

    Oral cancer is usually preceded by pre-cancerous lesion and related to tobacco abuse. Tobacco carcinogens damage DNA and cells harboring such damaged DNA normally undergo apoptotic death, but cancer cells are exceptionally resistant to apoptosis. Here we studied association between sequence and expression variations in apoptotic pathway genes and risk of oral cancer and precancer. Ninety nine tag SNPs in 23 genes, involved in mitochondrial and non-mitochondrial apoptotic pathways, were genotyped in 525 cancer and 253 leukoplakia patients and 538 healthy controls using Illumina Golden Gate assay. Six SNPs (rs1473418 at BCL2; rs1950252 at BCL2L2; rs8190315 at BID; rs511044 at CASP1; rs2227310 at CASP7 and rs13010627 at CASP10) significantly modified risk of oral cancer but SNPs only at BCL2, CASP1and CASP10 modulated risk of leukoplakia. Combination of SNPs showed a steep increase in risk of cancer with increase in "effective" number of risk alleles. In silico analysis of published data set and our unpublished RNAseq data suggest that change in expression of BID and CASP7 may have affected risk of cancer. In conclusion, three SNPs, rs1473418 in BCL2, rs1950252 in BCL2L2 and rs511044 in CASP1, are being implicated for the first time in oral cancer. Since SNPs at BCL2, CASP1 and CASP10 modulated risk of both leukoplakia and cancer, so, they should be studied in more details for possible biomarkers in transition of leukoplakia to cancer. This study also implies importance of mitochondrial apoptotic pathway gene (such as BCL2) in progression of leukoplakia to oral cancer. PMID:26403071

  16. Comparison of short-term outcomes between laparoscopically-assisted vs. transverse-incision open right hemicolectomy for right-sided colon cancer: a retrospective study

    Directory of Open Access Journals (Sweden)

    Akaraviputh Thawatchai

    2007-05-01

    Full Text Available Abstract Background Laparoscopically-assisted right hemicolectomy (LRH is an acceptable alternative to open surgery for right-sided colon cancer which offers patients less pain and faster recovery. However, special equipment and substantial surgical experience are required. The aim of the study is to compare the short-term surgical outcomes of LRH and open right hemicolectomy through right transverse skin crease incision (ORHT for right-sided colon cancer. Patients and methods This retrospective study included 33 patients with right-sided colon cancer who underwent elective right hemicolectomy by laparoscopic or open approaches through right transverse skin crease incision between March 2004 and September 2006 at the Department of Surgery, Faculty of Medicine Siriraj Hospital. Operative details, postoperative requirement of narcotics, recovery of bowel function, and oncological parameters were analyzed. Results Thirteen patients underwent LRH and 20 patients underwent ORHT. Both approaches achieved adequate oncological resection of the tumor. The laparoscopic group were characterized by shorter average incision lengths (7.7 vs 10.3 cm; p Conclusion LRH and ORHT for right-sided colon cancer resulted in the same short-term surgical outcomes including postoperative bowel function, narcotics consumption and length of hospital stay. However, LRH required a significantly longer operating time.

  17. A Meta-Analysis of the Short- and Long-Term Results of Randomized Controlled Trials That Compared Laparoscopy-Assisted and Conventional Open Surgery for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Hiroshi Ohtani, Yutaka Tamamori, Yuichi Arimoto, Yukio Nishiguchi, Kiyoshi Maeda, Kosei Hirakawa

    2011-01-01

    Full Text Available Purpose: We conducted a meta-analysis to evaluate and compare the short- and long-term results of laparoscopic colorectal surgery (LCRS and conventional open surgery (OCRS for colorectal cancer (CRC.Methods: We searched relevant papers published between January 1990 and May 2011. We analyzed the outcomes of each type of surgery over the short- and long-term periods.Results: In the short-term period, we found no significant differences in overall perioperative complications and anastomotic leakage between LCRS and OCRS groups. We found no significant differences in overall, distant, local and wound-site recurrence, overall mortality, 3 and 5 year disease-free survival rate, and cancer-related mortality between the 2 groups.Conclusions: LCRS has the benefits of reducing intraoperative blood loss, earlier resumption of oral intake, and shorter duration of hospital stay in the short-term. The long-term outcomes of LCRS seem to be similar to those of OCRS.

  18. The capacity of spiral CT angiography in evaluation of the central pulmonary vascular involvement from central lug cancer

    International Nuclear Information System (INIS)

    Objective: To investigate the capacity of CTA including multiplanar reconstructions (MPR) and volume rendering technique (VRT) in evaluation of the central pulmonary vascular involvement from central lung cancer (CLC), and to compare with transverse image. Methods: In a prospective series, 52 spiral CT examinations were performed on a Picker 6000 scanner for suspected CLC. Contrast medium was injected at a rate of 4 ml/s with a power injector. The scanning delay was 20 seconds. The study volume was from the arch of the aorta to the inferior pulmonary veins done in a single breath-hold, using 3 mm collimation, pitch of 1.0 and reconstructed at 1 mm intervals. 6 patients without CLC were excluded. Three radiologists compared transverse image with CTA (MPR and VR) image in a blind way, and then the findings were compared with the surgical and pathological results. Results: Reconstructed image quality was graded as excellent (50.0%) or good (41.3%), whereas motion-related artifacts led to poor image quality in 8.7% of cases. In evaluating vascular encasement of CLC, CTA was more sensitive (97.3% vs 84.0%), specific (91.1% vs 89.3%), and accurate (94.7% vs 86.3%) than transverse images. The difference in sensitivity and accuracy was statistically significant (χ2 = 7.878, P = 0.005 and χ2 = 5.532, P = 0.019, respectively). Conclusions: CTA is a more useful imaging modality before pneumonectomy, especially in pulmonary artery reconstruction and in extended resection for locally advanced lung cancer particularly when cardiopulmonary bypass is needed

  19. Inhibition of Myeloid Cell Leukemia 1 and Activation of Caspases Are Critically Involved in Gallotannin-induced Apoptosis in Prostate Cancer Cells.

    Science.gov (United States)

    Park, Eunkyung; Kwon, Hee Young; Jung, Ji Hoon; Jung, Deok-Beom; Jeong, Arong; Cheon, Jinhong; Kim, Bonglee; Kim, Sung-Hoon

    2015-08-01

    Although gallotannin contained in several medicinal plants was known to have multi-biological activities, such as antioxidant, antiinflammatory, antimicrobial, immunomodulatory, and antitumor effects, the underlying apoptotic mechanism of gallotannin is not fully understood so far. Thus, in the present study, the apoptotic mechanism of gallotannin was elucidated in DU145, PC-3, and M2182 prostate cancer cells in association with myeloid cell leukemia 1 (Mcl-1) signaling. Gallotannin exerted dose-dependent cytotoxicity in DU145, PC-3, and M2182 prostate cancer cells. Also, gallotannin showed apoptotic morphological features and increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and sub-G1 accumulation in three prostate cancer cell lines. Consistently, gallotannin cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of procaspases 9 and 3 in three prostate cancer cell lines. Furthermore, gallotannin attenuated the expression of survival genes such as Mcl-1, B-cell lymphoma 2, and B-cell lymphoma 2 extra large in three prostate cancer cell lines. Interestingly, overexpression of Mcl-1 reversed the ability of gallotannin to cleave PARP and increase sub-G1 population in three prostate cancer cell lines. Conversely, silencing of Mcl-1 enhanced apoptosis by gallotannin in three prostate cancer cell lines by FACSCalibur (Becton Dickinson, Franklin Lakes, NJ, USA). Taken together, our findings demonstrate that inhibition of Mcl-1 and activation of caspases are critically involved in gallotannin-induced apoptosis in prostate cancer cells. PMID:26014377

  20. High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival

    DEFF Research Database (Denmark)

    Johansen, Julia S; Christensen, Ib Jarle; Riisbro, Rikke;

    2003-01-01

    normal serum YKL-40. In the present study we evaluated the associations of preoperative serum YKL-40 in 271 patients with primary breast cancer in relation to relapse-free survival and overall survival. The median follow-up time was 5.9 years. There were 77 relapses and 69 patients died. The median serum......YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum YKL-40 in patients with metastatic breast cancer and colorectal cancer is associated with a poorer prognosis as compared to patients with...... YKL-40 in patients with primary breast cancer at time of operation is only elevated in a small group of patients, but these patients have a shorter recurrence free interval. Further studies are required to determine the biological function of YKL-40 in breast cancer....

  1. Prognostic Significance of Subtype Classification for Short- and Long-Term Survival in Breast Cancer: Survival Time Holds the Key

    OpenAIRE

    Ambs, Stefan

    2010-01-01

    Stefan Ambs provides a perspective on a recent research article by Paul Pharoah and colleagues that evaluated the prognostic significance of immunohistochemical subtype classification in early breast cancer.

  2. Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival.

    Directory of Open Access Journals (Sweden)

    Emma Hörnberg

    Full Text Available BACKGROUND: Constitutively active androgen receptor variants (AR-V lacking the ligand binding domain (LBD may promote the development of castration-resistant prostate cancer (CRPC. The expression of AR-Vs in the clinically most important metastatic site, the bone, has, however, not been well documented. Our aim was therefore to compare levels of AR-Vs in hormone-naive (HN and CRPC bone metastases in comparison to primary PC and non-malignant prostate tissue, as well as in relation to AR protein expression, whole-genome transcription profiles and patient survival. METHODOLOGY/PRINCIPAL FINDINGS: Hormone-naïve (n = 10 and CRPC bone metastases samples (n = 30 were obtained from 40 patients at metastasis surgery. Non-malignant and malignant prostate samples were acquired from 13 prostatectomized men. Levels of full length AR (ARfl and AR-Vs termed AR-V1, AR-V7, and AR-V567es mRNA were measured with RT-PCR and whole-genome transcription profiles with an Illumina Beadchip array. Protein levels were examined by Western blotting and immunohistochemistry. Transcripts for ARfl, AR-V1, and AR-V7 were detected in most primary tumors and metastases, and levels were significantly increased in CRPC bone metastases. The AR-V567es transcript was detected in 23% of the CRPC bone metastases only. A sub-group of CRPC bone metastases expressed LBD-truncated AR proteins at levels comparable to the ARfl. Detectable AR-V567es and/or AR-V7 mRNA in the upper quartile, seen in 1/3 of all CRPC bone metastases, was associated with a high nuclear AR immunostaining score, disturbed cell cycle regulation and short survival. CONCLUSIONS/SIGNIFICANCE: Expression of AR-Vs is increased in CRPC compared to HN bone metastases and associated with a particularly poor prognosis. Further studies are needed to test if patients expressing such AR-Vs in their bone metastases benefit more from drugs acting on or down-stream of these AR-Vs than from therapies inhibiting androgen synthesis.

  3. Fractionated stereotactic radiosurgery for patients with skull base metastases from systemic cancer involving the anterior visual pathway

    International Nuclear Information System (INIS)

    To analyze the tumor control, survival outcomes, and toxicity after stereotactic radiosurgery (SRS) for skull base metastases from systemic cancer involving the anterior visual pathway. We have analyzed 34 patients (23 females and 11 males, median age 59 years) who underwent multi-fraction SRS for a skull base metastasis compressing or in close proximity of optic nerves and chiasm. All metastases were treated with frameless LINAC-based multi-fraction SRS in 5 daily fractions of 5 Gy each. Local control, distant failure, and overall survival were estimated using the Kaplan-Meier method calculated from the time of SRS. Prognostic variables were assessed using log-rank and Cox regression analyses. At a median follow-up of 13 months (range, 2–36.5 months), twenty-five patients had died and 9 were alive. The 1-year and 2-year local control rates were 89% and 72%, and respective actuarial survival rates were 63% and 30%. Four patients recurred with a median time to progression of 12 months (range, 6–27 months), and 17 patients had new brain metastases at distant brain sites. The 1-year and 2-year distant failure rates were 50% and 77%, respectively. On multivariate analysis, a Karnofsky performance status (KPS) >70 and the absence of extracranial metastases were prognostic factors associated with lower distant failure rates and longer survival. After multi-fraction SRS, 15 (51%) out of 29 patients had a clinical improvement of their preexisting cranial deficits. No patients developed radiation-induced optic neuropathy during the follow-up. Multi-fraction SRS (5 x 5 Gy) is a safe treatment option associated with good local control and improved cranial nerve symptoms for patients with a skull base metastasis involving the anterior visual pathway

  4. Epigenetic mechanisms involved in differential MDR1 mRNA expression between gastric and colon cancer cell lines and rationales for clinical chemotherapy

    Directory of Open Access Journals (Sweden)

    Kim Kyung-Jong

    2008-08-01

    Full Text Available Abstract Background The membrane transporters such as P-glycoprotein (Pgp, the MDR1 gene product, are one of causes of treatment failure in cancer patients. In this study, the epigenetic mechanisms involved in differential MDR1 mRNA expression were compared between 10 gastric and 9 colon cancer cell lines. Methods The MDR1 mRNA levels were determined using PCR and real-time PCR assays after reverse transcription. Cytotoxicity was performed using the MTT assay. Methylation status was explored by quantification PCR-based methylation and bisulfite DNA sequencing analyses. Results The MDR1 mRNA levels obtained by 35 cycles of RT-PCR in gastric cancer cells were just comparable to those obtained by 22 cycles of RT-PCR in colon cancer cells. Real-time RT-PCR analysis revealed that MDR1 mRNA was not detected in the 10 gastric cancer cell lines but variable MDR1 mRNA levels in 7 of 9 colon cancer cell lines except the SNU-C5 and HT-29 cells. MTT assay showed that Pgp inhibitors such as cyclosporine A, verapamil and PSC833 sensitized Colo320HSR (colon, highest MDR1 expression but not SNU-668 (gastric, highest and SNU-C5 (gastric, no expression to paclitaxel. Quantification PCR-based methylation analysis revealed that 90% of gastric cancer cells, and 33% of colon cancer cells were methylated, which were completely matched with the results obtained by bisulfite DNA sequencing analysis. 5-aza-2'-deoxcytidine (5AC, a DNA methyltransferase inhibitor increased the MDR1 mRNA levels in 60% of gastric cells, and in 11% of colon cancer cells. Trichostatin A (TSA, histone deacetylase inhibitor increased the MDR1 mRNA levels in 70% of gastric cancer cells and 55% of colon cancer cells. The combined treatment of 5AC with TSA increased the MDR1 mRNA levels additively in 20% of gastric cancer cells, but synergistically in 40% of gastric and 11% of colon cancer cells. Conclusion These results indicate that the MDR1 mRNA levels in gastric cancer cells are significantly

  5. Notch Signaling Activation in Cervical Cancer Cells Induces Cell Growth Arrest with the Involvement of the Nuclear Receptor NR4A2

    Science.gov (United States)

    Sun, Lichun; Liu, Mingqiu; Sun, Guang-Chun; Yang, Xu; Qian, Qingqing; Feng, Shuyu; Mackey, L. Vienna; Coy, David H.

    2016-01-01

    Cervical cancer is a second leading cancer death in women world-wide, with most cases in less developed countries. Notch signaling is highly conserved with its involvement in many cancers. In the present study, we established stable cervical cell lines with Notch activation and inactivation and found that Notch activation played a suppressive role in cervical cancer cells. Meanwhile, the transient overexpression of the active intracellular domain of all four Notch receptors (ICN1, 2, 3, and 4) also induced the suppression of cervical cancer Hela cell growth. ICN1 also induced cell cycle arrest at phase G1. Notch1 signaling activation affected the expression of serial genes, especially the genes associated with cAMP signaling, with an increase of genes like THBS1, VCL, p63, c-Myc and SCG2, a decrease of genes like NR4A2, PCK2 and BCL-2. Particularly, The nuclear receptor NR4A2 was observed to induce cell proliferation via MTT assay and reduce cell apoptosis via FACS assay. Furthermore, NR4A2's activation could reverse ICN1-induced suppression of cell growth while erasing ICN1-induced increase of tumor suppressor p63. These findings support that Notch signaling mediates cervical cancer cell growth suppression with the involvement of nuclear receptor NR4A2. Notably, Notch/NR4A2/p63 signaling cascade possibly is a new signling pathway undisclosed. PMID:27471554

  6. Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

    OpenAIRE

    Sun, Mingjuan; Zhang, Ning; Wang, Xiaolong; Li, Yaming; Qi, Wenwen; Zhang, Hanwen; Li, Zengjun; Yang, Qifeng

    2016-01-01

    Background The complications of clinical metastatic disease are responsible for the majority of breast cancer related deaths, and fewer therapies substantially prolong survival. Nitidine chloride (NC), a natural polyphenolic compound, has been shown to exhibit potent anticancer effects in many cancer types, including breast cancer. The epithelial-mesenchymal transition (EMT) and the acquisition of cancer stem cells (CSCs)-like properties emerge as critical steps in the metastasis of human can...

  7. ROLE OF TARGETED THERAPY IN THE COMBINATION TREATMENT OF PATIENTS WITH KIDNEY CANCER AND METASTATIC BRAIN INVOLVEMENT

    Directory of Open Access Journals (Sweden)

    D. R. Naskhletashvili

    2015-04-01

    Full Text Available In patients with kidney cancer (KC, the rate of metastatic brain involvement is 2-11%, is steadily growing, and is one of the important reasons for treatment failures in these patients. Surgery and radiotherapy, including radiosurgery, must be considered as optimal treatments for patients with KC and brain metastases. Systemic drug therapy has recently played a more and more increasing role in the treatment of patients with a progressive brain tumor process. At the same time, there are no exact pharmacokinetic data on drugs registered for the treatment of disseminated KC in respect to their concentration in the human central nervous when they are used in therapeutic doses. On the basis of the data of the literature review and the results of the authors’ studies, it may be concluded that while none of the target agents has still shown any significant advantage over others in treating KC patients with brain metastases. All the drugs have demonstrated their ability to achieve a clinical and X-ray verified objective effect (as stabilizations in most cases in treating brain metastases. The most data are available on the therapeutic efficacy of sunitinib and sorafenib. In case of progressive brain tumor process, drug treatment should be individually discussed in each situation in accordance with standard approaches to treating patients with disseminated KC. 

  8. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved

    OpenAIRE

    Bastide, Nadia; Pierre, Fabrice; Corpet, Denis E

    2011-01-01

    Red meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The summary relative risk of colon cancer was 1.18 [95%C.I.: 1.06-1.32] for subjects in the hi...

  9. An ADP-Ribosylation Factor GTPase-activating Protein Git2-short/KIAA0148 Is Involved in Subcellular Localization of Paxillin and Actin Cytoskeletal Organization

    OpenAIRE

    Mazaki, Yuichi; Hashimoto, Shigeru; Okawa, Katsuya; Tsubouchi, Asako; Nakamura, Kuniaki; Yagi, Ryohei; Yano, Hajime; Kondo, Akiko; Iwamatsu, Akihiro; Mizoguchi, Akira; Sabe, Hisataka

    2001-01-01

    Paxillin acts as an adaptor protein in integrin signaling. We have shown that paxillin exists in a relatively large cytoplasmic pool, including perinuclear areas, in addition to focal complexes formed at the cell periphery and focal adhesions formed underneath the cell. Several ADP-ribosylation factor (ARF) GTPase-activating proteins (GAPs; ARFGAPs) have been shown to associate with paxillin. We report here that Git2-short/KIAA0148 exhibits properties of a paxillin...

  10. Involvement of Histone Demethylase LSD1 in Short-Time-Scale Gene Expression Changes during Cell Cycle Progression in Embryonic Stem Cells

    OpenAIRE

    Nair, Venugopalan D; Ge, Yongchao; Balasubramaniyan, Natarajan; Kim, Jaeyun; Okawa, Yuya; Chikina, Maria; Troyanskaya, Olga; Sealfon, Stuart C.

    2012-01-01

    The histone demethylase LSD1, a component of the CoREST (corepressor for element 1-silencing transcription factor) corepressor complex, plays an important role in the downregulation of gene expression during development. However, the activities of LSD1 in mediating short-time-scale gene expression changes have not been well understood. To reveal the mechanisms underlying these two distinct functions of LSD1, we performed genome-wide mapping and cellular localization studies of LSD1 and its di...

  11. Metabolomics reveals an involvement of pantothenate for male production responding to the short-day stimulus in the water flea, Daphnia pulex.

    Science.gov (United States)

    Toyota, Kenji; Gavin, Alex; Miyagawa, Shinichi; Viant, Mark R; Iguchi, Taisen

    2016-01-01

    Under favorable conditions, the micro-crustacean Daphnia pulex produces female offspring by parthenogenesis, whereas under unfavorable conditions, they produce male offspring to induce sexual reproduction (environmental sex determination: ESD). We recently established a suitable system for ESD studies using D. pulex WTN6 strain, in which the sex of the offspring can be regulated by alterations in day-length; long-day and short-day conditions can induce female and male offspring, respectively. Taking advantage of this system, we have already demonstrated that methyl farnesoate (MF) synthesis is necessary for male offspring production, and identified ionotropic glutamate receptors as an upstream regulator of MF signaling. Despite these findings, the molecular mechanisms associated with MF signaling have not yet been well elucidated. In this study, we analyzed the whole metabolic profiles of mother daphnids reared under long-day (female-producing) and short-day (male-producing) conditions, and discovered that pantothenate (vitamin B5), a known precursor to coenzyme A, was significantly accumulated in response to the short-day condition. To confirm the innate role of pantothenate in D. pulex, this metabolite was administered to mother daphnids resulting in a significantly increased proportion of male offspring producing mothers. This study provides novel insights of the metabolic mechanisms of the ESD system in D. pulex. PMID:27113113

  12. PET/CT imaging of c-Myc transgenic mice identifies the genotoxic N-nitroso-diethylamine as carcinogen in a short-term cancer bioassay.

    Directory of Open Access Journals (Sweden)

    Katja Hueper

    Full Text Available BACKGROUND: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. METHODOLOGY/PRINCIPAL FINDINGS: μCT and ¹⁸F-FDG μPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced μCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: The present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgenic animal models may possibly enable short-term cancer bioassays to significantly improve hazard identification and follow-up examinations of different organs by non-invasive methods.

  13. Bronchial artery infusion of Gemcitabine and Cisplatin combined with systemic chemotherapy for advanced non-small cell lung cancer: its short-term efficacy

    International Nuclear Information System (INIS)

    Objective: To assess the short-term efficacy of bronchial artery infusion (BAI) of Gemcitabine (GEM) plus Cisplatin (DDP) combined with systemic chemotherapy of GEM for advanced non-small cell lung cancer (NSCLC). Methods: A total of 60 patients with pathologically proved primary NSCLC were randomly selected. BAI with GEM (1000 mg/m2) and DDP (DDP 50 mg/m2) was performed on the first day, and systemic chemotherapy of GEM (1000 mg/m2) was carried out on the eighth day. The clinical results were analyzed. Results: Of the 60 patients, CR, PR, SD and PD were obtained in 3, 35, 17 and 5, respectively, with an overall effective rate of 63%. Twenty-two patients had adenocarcinoma and the effective rate of them was 45%. Thirty-eight patients had squamous cell carcinoma and their effective rate was 74%. The difference in the effective rate between the above two pathologic types was significant (P<0.05). Central type lung cancer was seen in 37 cases, their effective rate was 73%. The peripheral type lung cancer was seen in the remaining 23 patients and the effective rate was 48%. The difference in the effective rate was statistically significant between the central type and the peripheral type (P<0.05). Conclusion: The combination of bronchial artery infusion with systemic chemotherapy by using GP plan is an effective, feasible approach in the treatment of advanced non-small cell lung cancer. The short-term efficacy of the treatment bears a close relationship to the anatomical location and pathological type of the cancer. (authors)

  14. Survival of non-Western first generations immigrants with stomach cancer in North East Netherlands: Short communication

    NARCIS (Netherlands)

    Siemerink, E.J.M.; Aa, van der M.A.; Siesling, S.; Hospers, G.A.P.; Mulder, N.H.

    2011-01-01

    Background: Isolated groups, such as first generation non-Western immigrants, are at risk for suboptimal utilisation of the health care system resulting in a worse outcome. Methods: From 1989 to 2007, all patients with stomach cancer were selected from the Comprehensive Cancer Centre North-East c

  15. A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Qiaoyuan [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China); Xu, Enwu [Department of Thoracic Surgery, General Hospital of Guangzhou Military Command of Chinese People' s Liberation Army, Guangzhou 510010 (China); Dai, Jiabin; Liu, Binbin; Han, Zhiyuan; Wu, Jianjun; Zhang, Shaozhu; Peng, Baoying [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China); Zhang, Yajie [Department of Pathology, Guangzhou Medical University, Guangzhou 510182 (China); Jiang, Yiguo, E-mail: jiangyiguo@vip.163.com [Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510182 (China)

    2015-06-01

    Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 μmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G{sub 0}/G{sub 1} in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer. - Highlights: • LncRNA AK001796 played an oncogenic role in lung carcinogenesis. • LncRNA AK001796 was downregulated in resveratrol-treated lung cancer cells. • LncRNA AK001796 was involved in the inhibition of cell growth by resveratrol.

  16. A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer

    International Nuclear Information System (INIS)

    Lung cancer is the most common form of cancer throughout the world. The specific targeting of long noncoding RNAs (lncRNAs) by resveratrol opened a new avenue for cancer chemoprevention. In this study, we found that 21 lncRNAs were upregulated and 19 lncRNAs were downregulated in lung cancer A549 cells with 25 μmol/L resveratrol treatment determined by microarray analysis. AK001796, the lncRNA with the most clearly altered expression, was overexpressed in lung cancer tissues and cell lines, but its expression was downregulated in resveratrol-treated lung cancer cells. By monitoring cell proliferation and growth in vitro and tumor growth in vivo, we observed a significant reduction in cell viability in lung cancer cells and a slow growth in the tumorigenesis following AK001796 knockdown. We also found that AK001796 knockdown caused a cell-cycle arrest, with significant increases in the percentage of cells in G0/G1 in lung cancer cells. By using cell cycle pathway-specific PCR arrays, we detected changes in a number of cell cycle-related genes related to lncRNA AK001796 knockdown. We further investigated whether AK001796 participated in the anticancer effect of resveratrol and the results showed that reduced lncRNA AK001796 level potentially impaired the inhibitory effect of resveratrol on cell proliferation. To our knowledge, this is the first study to report the changes in an lncRNA expression profile induced by resveratrol in lung cancer. - Highlights: • LncRNA AK001796 played an oncogenic role in lung carcinogenesis. • LncRNA AK001796 was downregulated in resveratrol-treated lung cancer cells. • LncRNA AK001796 was involved in the inhibition of cell growth by resveratrol

  17. Molecular mechanisms involved in the inhibition of MDA-MB-435 breast cancer cells by phenolic acids from the red-flesh peach BY00P6653

    Science.gov (United States)

    A wide variety of fruits and vegetables extracts have been shown to protect against cancer cell growth in vitro. Increasing evidence suggests that phenolics compounds found in fruits and vegetables may have anticancer properties. However, the molecular mechanisms involved in the anti-proliferative...

  18. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Osorio, Ana; Milne, Roger L; Kuchenbaecker, Karoline;

    2014-01-01

    Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of th...

  19. Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LARVMAT-to-LAR3D-CRT) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different

  20. Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

    Energy Technology Data Exchange (ETDEWEB)

    Filippi, Andrea Riccardo, E-mail: andreariccardo.filippi@unito.it [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Ragona, Riccardo; Piva, Cristina; Scafa, Davide; Fiandra, Christian [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Fusella, Marco; Giglioli, Francesca Romana [Medical Physics, AOU Città della Salute e della Scienza Hospital, Torino (Italy); Lohr, Frank [Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy)

    2015-05-01

    Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by

  1. Short-term Intensive Neoadjuvant Chemotherapy Improving 10-year Survival for Patients with Stage Ⅱ and Operable Stage Ⅲ Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    BinZhang; YueCai; QiZhang; ZiweiYing; ShulingJiang; HongXu; YongxueZheng; DaqingJiang

    2004-01-01

    OBJECTIVE To evaluate the 10-year curative effects of short-term intensive neoadjuvant chemotherapy for operable breast cancer. METHODS A total of 510 patients with stagell and operable stagelll breast cancer were divided into group A (preoperative neoadjuvant chemotherapy 251 cases) and group B (postoperative adjuvant chemotherapy 259 cases). The patients in group A received short-term and intensive neoadjuvant chemotherapy for 4 weeks followed by modified radical mastectomy two weeks after the chemotherapy. The postoperative adjuvant chemotherapy began within two weeks after surgery. The same chemotherapeutic regimen was used for both groups. RESULTS For stage Ⅲ in group A the 5-year overall survival rate (OS) and disease-free survival rate (DFS) were 59.2% and 54.9% respectively which were higher than those in group B (28.3% and 20.8% respectively, P<0.05). The 10-year OS and DFS were 78.1% and 73.5% respectively for stage Ⅱ in group A which were higher than those in group B (68.4% and 60.7%, P<0.05). The 10-year OS and DFS were 42.3% and 40.4% respectively forstage Ⅲ in group A which were higher than those in group B (20.4% and 18.4% respectively, P<0.05). CONCLUSION The results showed that intensive neoadjuvant chemotherapy can improve the 10-year survival for patients with stage Ⅱ and operablestage Ⅲ breast cancer.

  2. Mesenteric ischemia after capecitabine treatment in rectal cancer and resultant short bowel syndrome is not an absolute contraindication for radical oncological treatment

    International Nuclear Information System (INIS)

    Thrombotic events, arterial or venous in origin, still remain a source of substantial morbidity and mortality in cancer patients. The propensity for their development in oncology patients is partially a consequence of the disease itself and partially a result of our attempts to treat it. One of the rarest and deadliest thromboembolic complications is arterial mesenteric ischemia. The high mortality rate is caused by its rarity and by its non-specific clinical presentation, both of which make early diagnosis and treatment difficult. Hence, most diagnoses and treatments occur late in the course of the disease. The issue survivors of arterial mesenteric ischemia may face is short bowel syndrome, which has become a chronic condition after the introduction of parenteral nutrition at home. We present a 73-year-old rectal cancer patient who developed acute arterial mesenteric thrombosis at the beginning of the pre-operative radiochemotherapy. Almost the entire length of his small intestine, except for the proximal 50 cm of it, and the ascending colon had to be resected. After multiorgan failure his condition improved, and he was able to successfully complete radical treatment (preoperative radiotherapy and surgery) for the rectal carcinoma, despite developing short bowel syndrome (SBS) and being dependent upon home-based parenteral nutrition to fully cover his nutritional needs. Mesenteric ischemia and resultant short bowel syndrome are not absolute contraindications for radical oncological treatment since such patients can still achieve long-term remission

  3. Cleft Lip/Palate, Short Stature, and Developmental Delay in a Boy with a 5.6-Mb Interstitial Deletion Involving 10p15.3p14

    Science.gov (United States)

    Gamba, Bruno F.; Rosenberg, Carla; Costa, Silvia; Richieri-Costa, Antonio; Ribeiro-Bicudo, Lucilene A.

    2015-01-01

    The chromosome interval 10p15.3p14 harbors about a dozen genes. This region has been implicated in a few well-known human phenotypes, namely HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) and DGS2 (DiGeorge syndrome 2), but a number of variable phenotypes have also been reported. Cleft lip/palate seems to be a very unusual finding within the clinical spectrum of patients with this deletion. Here, we report a male child born with short stature, cleft lip/palate, and feeding problems who was found to have a 5.6-Mb deletion at 10p15.3p14. PMID:25852446

  4. Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107

    OpenAIRE

    Barbie, Thanh U.; Barbie, David A; MacLaughlin, David T.; Maheswaran, Shyamala; Donahoe, Patricia K.

    2003-01-01

    In addition to causing regression of the Mullerian duct in the male embryo, Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian cancer cells, which are known to be of Mullerian origin. Because the uterine cervix is derived from the same Mullerian duct precursor as the epithelium of the ovary, we tested the hypothesis that cervical cancer cells might also respond to MIS. A number of cervical cancer cell lines express the MIS type II receptor, and MIS inhibits the gro...

  5. Nelfinavir and other protease inhibitors in cancer: mechanisms involved in anticancer activity [v2; ref status: indexed, http://f1000r.es/536

    Directory of Open Access Journals (Sweden)

    Tomas Koltai

    2015-03-01

    Full Text Available Objective: To review the mechanisms of anti-cancer activity of nelfinavir and other protease inhibitors (PIs based on evidences reported in the published literature. Methods: We extensively reviewed the literature concerning nelfinavir (NFV as an off target anti-cancer drug and other PIs. A classification of PIs based on anti-cancer mode of action was proposed. Controversies regarding nelfinavir mode of action were also addressed. Conclusions: The two main mechanisms involved in anti-cancer activity are endoplasmic reticulum stress-unfolded protein response pathway and Akt inhibition. However there are many other effects, partially dependent and independent of those mentioned, that may be useful in cancer treatment, including MMP-9 and MMP-2 inhibition, down-regulation of CDK-2, VEGF, bFGF, NF-kB, STAT-3, HIF-1 alfa, IGF, EGFR, survivin, BCRP, androgen receptor, proteasome, fatty acid synthase (FAS, decrease in cellular ATP concentration and upregulation of TRAIL receptor DR5, Bax, increased radiosensitivity, and autophagy. The end result of all these effects is slower growth, decreased angiogenesis, decreased invasion and increased apoptosis, which means reduced proliferation and increased cancer cells death. PIs may be classified according to their anticancer activity at clinically achievable doses, in AKT inhibitors, ER stressors and Akt inhibitors/ER stressors. Beyond the phase I trials that have been recently completed, adequately powered and well-designed clinical trials are needed in the various cancer type settings, and specific trials where NFV is tested in association with other known anti-cancer pharmaceuticals should be sought, in order to find an appropriate place for NFV in cancer treatment. The analysis of controversies on the molecular mechanisms of NFV hints to the possibility that NFV works in a different way in tumor cells and in hepatocytes and adipocytes.

  6. p38MAPK activation is involved in androgen-independent proliferation of human prostate cancer cells by regulating IL-6 secretion

    International Nuclear Information System (INIS)

    Increased levels of serum interleukin-6 (IL-6) are frequently observed in patients with advanced, hormone-refractory prostate cancer. However, the precise mechanism of IL-6 regulation is still largely unknown. Since prostate cancer gradually progresses to an androgen-independent state despite the stress caused by various therapeutic agents, we hypothesized the stress-activated protein kinases (SAPKs) involvement in androgen-independent growth or IL-6 secretion of prostate cancer cells. Using PC-3 and DU145 human prostate cancer cells, we analyzed the role of SAPKs in IL-6 mediated cell growth and found that the p38MAPK and JNK are involved in androgen-independent cancer cell growth. Furthermore, IL-6 secretion by PC-3 and DU145 cells was significantly suppressed by SAPKs inhibitor, especially by p38MAPK inhibitor SB203580, but not by JNK inhibitor SP600125 nor by MEK inhibitor, PD98059. These results raised the possibility that the IL-6 mediated androgen-independent proliferation of PC-3 and DU145 cells is regulated at least partly via SAPKs signaling pathway especially through p38MAPK activation

  7. Effect of a short-term gaseous hypoxia (7.4-8.2%O2) on the body of a healthy person and a cancer patient

    International Nuclear Information System (INIS)

    A clinical investigation of the tolerance of a short-term (15-30 min) normobaric gaseous hypoxia caused by the inhalation of mixtures containing 7.4-8.2% O2 was conducted. Cerebral and liver hemodynamics, function of the cardiovascular system, some biochemical and hematological indicators were studied in 20 healthy volunteers and 18 cancer patients. It was noted that breathing with this mixture was worse tolerated than with that containing 10% O2, however no stable functional changes in the human body were observed. A conclusion is made that the gaseous mixture containing 8% O2 can be used in radiation therapy of cancer patients for the protection of normal tissues

  8. Short-term intravenous antimicrobial prophylaxis for elective rectal cancer surgery: results of a prospective randomized non-inferiority trial

    OpenAIRE

    ISHIBASHI, KEIICHIRO; Ishida, Hideyuki; KUWABARA, KOUKI; OHSAWA, TOMONORI; OKADA, NORIMICHI; Yokoyama, Masaru; Kumamoto, Kensuke

    2013-01-01

    Purpose To investigate the non-inferiority of postoperative single-dose intravenous antimicrobial prophylaxis to multiple-dose intravenous antimicrobial prophylaxis in terms of the incidence of surgical site infections (SSIs) in patients undergoing elective rectal cancer surgery by a prospective randomized study. Methods Patients undergoing elective surgery for rectal cancer were randomized to receive a single intravenous injection of flomoxef (group 1) or five additional doses (group 2) of f...

  9. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling

    International Nuclear Information System (INIS)

    PCA3 is a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, but its functional role is unknown. To investigate its putative function in PCa biology, we used gene expression knockdown by small interference RNA, and also analyzed its involvement in androgen receptor (AR) signaling. LNCaP and PC3 cells were used as in vitro models for these functional assays, and three different siRNA sequences were specifically designed to target PCA3 exon 4. Transfected cells were analyzed by real-time qRT-PCR and cell growth, viability, and apoptosis assays. Associations between PCA3 and the androgen-receptor (AR) signaling pathway were investigated by treating LNCaP cells with 100 nM dihydrotestosterone (DHT) and with its antagonist (flutamide), and analyzing the expression of some AR-modulated genes (TMPRSS2, NDRG1, GREB1, PSA, AR, FGF8, CdK1, CdK2 and PMEPA1). PCA3 expression levels were investigated in different cell compartments by using differential centrifugation and qRT-PCR. LNCaP siPCA3-transfected cells significantly inhibited cell growth and viability, and increased the proportion of cells in the sub G0/G1 phase of the cell cycle and the percentage of pyknotic nuclei, compared to those transfected with scramble siRNA (siSCr)-transfected cells. DHT-treated LNCaP cells induced a significant upregulation of PCA3 expression, which was reversed by flutamide. In siPCA3/LNCaP-transfected cells, the expression of AR target genes was downregulated compared to siSCr-transfected cells. The siPCA3 transfection also counteracted DHT stimulatory effects on the AR signaling cascade, significantly downregulating expression of the AR target gene. Analysis of PCA3 expression in different cell compartments provided evidence that the main functional roles of PCA3 occur in the nuclei and microsomal cell fractions. Our findings suggest that the ncRNA PCA3 is involved in the control of PCa cell survival, in part through modulating AR signaling, which may raise new

  10. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling

    Directory of Open Access Journals (Sweden)

    Ferreira Luciana Bueno

    2012-11-01

    Full Text Available Abstract Background PCA3 is a non-coding RNA (ncRNA that is highly expressed in prostate cancer (PCa cells, but its functional role is unknown. To investigate its putative function in PCa biology, we used gene expression knockdown by small interference RNA, and also analyzed its involvement in androgen receptor (AR signaling. Methods LNCaP and PC3 cells were used as in vitro models for these functional assays, and three different siRNA sequences were specifically designed to target PCA3 exon 4. Transfected cells were analyzed by real-time qRT-PCR and cell growth, viability, and apoptosis assays. Associations between PCA3 and the androgen-receptor (AR signaling pathway were investigated by treating LNCaP cells with 100 nM dihydrotestosterone (DHT and with its antagonist (flutamide, and analyzing the expression of some AR-modulated genes (TMPRSS2, NDRG1, GREB1, PSA, AR, FGF8, CdK1, CdK2 and PMEPA1. PCA3 expression levels were investigated in different cell compartments by using differential centrifugation and qRT-PCR. Results LNCaP siPCA3-transfected cells significantly inhibited cell growth and viability, and increased the proportion of cells in the sub G0/G1 phase of the cell cycle and the percentage of pyknotic nuclei, compared to those transfected with scramble siRNA (siSCr-transfected cells. DHT-treated LNCaP cells induced a significant upregulation of PCA3 expression, which was reversed by flutamide. In siPCA3/LNCaP-transfected cells, the expression of AR target genes was downregulated compared to siSCr-transfected cells. The siPCA3 transfection also counteracted DHT stimulatory effects on the AR signaling cascade, significantly downregulating expression of the AR target gene. Analysis of PCA3 expression in different cell compartments provided evidence that the main functional roles of PCA3 occur in the nuclei and microsomal cell fractions. Conclusions Our findings suggest that the ncRNA PCA3 is involved in the control of PCa cell survival

  11. α-Santalol, a skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.

    Science.gov (United States)

    Santha, Sreevidya; Dwivedi, Chandradhar

    2013-01-01

    This study is designed to investigate the chemopreventive effect and molecular mechanisms of α-santalol on UVB-induced skin tumor development in SKH-1 hairless mouse, a widely used model for human photocarcinogenesis. A dose of UVB radiation (30 mJ cm(-2) day(-1)) that is in the range of human sunlight exposure was used for the initiation and promotion of tumor. Topical treatment of mice with α-santalol (10%, wt/vol in acetone) caused reduction in tumor incidence, multiplicity and volume. In our study, the anticarcinogenic action of α-santalol against UVB-induced photocarcinogenesis was found to be associated with inhibition of inflammation and epidermal cell proliferation, cell cycle arrest and induction of apoptosis. α-Santalol pretreatment strongly inhibited UVB-induced epidermal hyperplasia and thickness of the epidermis, expression of proliferation and inflammation markers proliferating cell nuclear antigen (PCNA), Ki-67 and cyclooxygenase 2 (Cox-2). Significant decrease in the expression of cyclins A, B1, D1 and D2 and cyclin-dependent kinases (Cdk)s Cdk1 (Cdc2), Cdk2, Cdk4 and Cdk6 and an upregulated expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21 were found in α-santalol pretreated group. Furthermore, an elevated level of cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) were observed in α-santalol-treated group. Our data suggested that α-santalol is a safer and promising skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis. PMID:23480292

  12. Short-term effects of ultrahigh concentration cationic silica nanoparticles on cell internalization, cytotoxicity, and cell integrity with human breast cancer cell line (MCF-7)

    International Nuclear Information System (INIS)

    High concentrations of cationic colloidal silica nanoparticles (CCS-NPs) have been widely used for the enrichment of plasma membrane proteins. However, the interaction between the CCS-NPs and cells under the required concentration for the isolation of plasma membrane are rarely investigated. We evaluated the internalization and toxicity of the 15 nm CCS-NPs which were exposed at high concentrations with short time in human breast cancer cells (MCF-7) with transmission electron microscopy, energy dispersive X-ray spectroscopy, inductively coupled plasma atomic emission spectroscopy, and colorimetric assays. The NPs were observed throughout the cells, particularly in the cytoplasm and the nucleus, after short incubation periods. Additionally, the NPs significantly influenced the membrane integrity of the MCF-7 cells

  13. Na, Al, K, Mn, Mg, Br, Ca, And Cl Concentration Values in the whole Blood Samples of Human Cancer using Short Time Neutron Irradiation Facility of ETRR-2

    International Nuclear Information System (INIS)

    The National Cancer Institute of Egypt submit us with 18 blood samples (11 Breast),(2 Prostate),(2 Colon),(1 Pancreatic),(1 Ovarian) and one samples from random person to estimate the concentration values of Na, Al ,K , Mn , Mg ,Br and Cl. The pneumatic irradiation rabbit system (PIRS) built in the vertical thermal column of the ETRR-2 reactor is used for short time irradiation at constant power. Elemental concentrations were estimated from measurements of the gamma ray spectra of the product short lived isotopes in the samples. The thermal to epithermal neutron flux ratio was calculated f (169) at irradiation position. The obtained concentration was calculated using kθ standardization method. Fortran and Axel programs were constructed for the determination of neutron fluxes and for elemental concentration values .For sake of comparisons the obtained results, the elemental concentrations of the random sample using (kθ - NAA) compared with the concentrations obtained by (ICP-MS) technique.

  14. Short-term effects of ultrahigh concentration cationic silica nanoparticles on cell internalization, cytotoxicity, and cell integrity with human breast cancer cell line (MCF-7)

    Energy Technology Data Exchange (ETDEWEB)

    Seog, Ji Hyun [Korea Advanced Institute of Science and Technology, Graduate School of Nanoscience and Technology (Korea, Republic of); Kong, Bokyung [Corning Precision Materials (Korea, Republic of); Kim, Dongheun [Korea Advanced Institute of Science and Technology, Graduate School of Nanoscience and Technology (Korea, Republic of); Graham, Lauren M. [University of Maryland, Department of Chemistry and Biochemistry (United States); Choi, Joon Sig [Chungnam National University, Department of Biochemistry (Korea, Republic of); Lee, Sang Bok, E-mail: slee@umd.edu [Korea Advanced Institute of Science and Technology, Graduate School of Nanoscience and Technology (Korea, Republic of)

    2015-01-15

    High concentrations of cationic colloidal silica nanoparticles (CCS-NPs) have been widely used for the enrichment of plasma membrane proteins. However, the interaction between the CCS-NPs and cells under the required concentration for the isolation of plasma membrane are rarely investigated. We evaluated the internalization and toxicity of the 15 nm CCS-NPs which were exposed at high concentrations with short time in human breast cancer cells (MCF-7) with transmission electron microscopy, energy dispersive X-ray spectroscopy, inductively coupled plasma atomic emission spectroscopy, and colorimetric assays. The NPs were observed throughout the cells, particularly in the cytoplasm and the nucleus, after short incubation periods. Additionally, the NPs significantly influenced the membrane integrity of the MCF-7 cells.

  15. Epigenetic Profiling of H3K4Me3 Reveals Herbal Medicine Jinfukang-Induced Epigenetic Alteration Is Involved in Anti-Lung Cancer Activity

    Directory of Open Access Journals (Sweden)

    Jun Lu

    2016-01-01

    Full Text Available Traditional Chinese medicine Jinfukang (JFK has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P<0.05. Gene Ontology analysis indicates that these genes are involved in tumor-related pathways, including pathway in cancer, basal cell carcinoma, apoptosis, induction of programmed cell death, regulation of transcription (DNA-templated, intracellular signal transduction, and regulation of peptidase activity. In particular, we found that the levels of H3K4Me3 at the promoters of SUSD2, CCND2, BCL2A1, and TMEM158 are significantly altered in A549, NCI-H1975, NCI-H1650, and NCI-H2228 cells, when treated with JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci.

  16. Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients

    OpenAIRE

    Napolitano, Maria; D'Alterio, Crescenzo; Cardone, Eleonora; Trotta, Anna Maria; Pecori, Biagio; Rega, Daniela; PACE, UGO; Scala, Dario; Scognamiglio, Giosuè; Tatangelo, Fabiana; Cacciapuoti, Carmela; Pacelli, Roberto; Delrio, Paolo; Scala, Stefania

    2015-01-01

    Short-course preoperative radiotherapy (SC-RT) followed by total mesorectal excision (TME) is one therapeutic option for locally advanced rectal cancer (LARC) patients. Since radio-induced DNA damage may affect tumor immunogenicity, Myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) were evaluated in 13 patients undergoing SC-RT and TME for LARC. Peripheral Granulocytic-MDSCs (G-MDSC) [LIN−/HLA-DR−/CD11b+/CD14−/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR−/lowCD11b+/CD3...

  17. ARBRE monitoring - ecology of short rotation coppice. Four year study involving wildlife monitoring of commercial SCR plantations planted on arable land and arable control plots

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham, M.D.; Bishop, J.D.; McKay, H.V.; Sage, R.B.

    2004-07-01

    This report summarises the findings of the UK Department of Trade and Industry (DTI) funded project monitoring wildlife within and around a number of commercially managed Short Rotation Coppice (SRC) plantations aimed at using the information gathered to assess the ecological impact of SRC plantations on the wildlife in the area. The background to the study is traced, and details are given of the monitoring programme examining the distribution of flora and fauna within the plantations, and the monitoring of birds, plants, insects and butterflies. The greater diversity of wildlife and plants in the SRC plots, the higher densities of birds, and the increasing number of butterfly species are discussed along with the increased mean number of invertebrate orders with subsequent growth of willow coppices, and the habitats at the edges of the plots and at headlands designed for access to machinery within the plots.

  18. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

    Directory of Open Access Journals (Sweden)

    Ana Osorio

    2014-04-01

    Full Text Available Single Nucleotide Polymorphisms (SNPs in genes involved in the DNA Base Excision Repair (BER pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase, and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2. Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2 gene (HR: 1.09, 95% CI (1.03-1.16, p = 2.7 × 10(-3 for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3. DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

  19. Does it make sense to target one tumor cell chemotactic factor or its receptor when several chemotactic axes are involved in metastasis of the same cancer?

    Science.gov (United States)

    Ratajczak, Mariusz Z; Suszynska, Malwina; Kucia, Magda

    2016-12-01

    The major problem with cancer progression and anti-cancer therapy is the inherent ability of cancer cells to migrate and establish distant metastases. This ability to metastasize correlates with the presence in a growing tumor of cells with a more malignant phenotype, which express certain cancer stem cell markers. The propensity of malignant cells to migrate and their resistance to radio-chemotherapy somewhat mimics the properties of normal developmentally early stem cells that migrate during organogenesis in the developing embryo. In the past, several factors, including cell migration-promoting cytokines, chemokines, growth factors, bioactive lipids, extracellular nucleotides, and even H(+) ions, were found to influence the metastasis of cancer cells. This plethora of pro-migratory factors demonstrates the existence of significant redundancy in the chemoattractants for cancer cells. In spite of this obvious fact, significant research effort has been dedicated to demonstrating the crucial involvement of particular pro-metastatic factor-receptor axes and the development of new drugs targeting one receptor or one chemoattractant. Based on our own experience working with a model of metastatic rhabdomyosarcoma as well as the work of others, in this review we conclude that targeting a single receptor-ligand pro-metastatic axis will not effectively prevent metastasis and that we should seek other more effective therapeutic options. PMID:27510263

  20. Carcinogen-specific gene expression profiles in short-term treated Eker and wild-type rats indicative of pathways involved in renal tumorigenesis.

    Science.gov (United States)

    Stemmer, Kerstin; Ellinger-Ziegelbauer, Heidrun; Ahr, Hans-Juergen; Dietrich, Daniel R

    2007-05-01

    Eker rats heterozygous for a dominant germline mutation in the tuberous sclerosis 2 (Tsc2) tumor suppressor gene were used as a model to study renal carcinogenesis. Eker and corresponding wild-type rats were exposed to genotoxic aristolochic acid (AA) or non-genotoxic ochratoxin A (OTA) to elucidate early carcinogen-specific gene expression changes and to test whether Eker rats are more sensitive to carcinogen-induced changes in gene expression. Male Eker and wild-type rats were gavaged daily with AA (10 mg/kg body weight) or OTA (210 microg/kg body weight). After 1, 3, 7, and 14 days of exposure, renal histopathology, tubular cell proliferation, and Affymetrix gene expression profiles from renal cortex/outer medulla were analyzed. AA-treated Eker and wild-type rats were qualitatively comparable in all variables assessed, suggesting a Tsc2-independent mechanism of action. OTA treatment resulted in slightly increased cortical pathology and significantly elevated cell proliferation in both strains, although Eker rats were more sensitive. Deregulated genes involved in the phosphatidylinositol 3-kinase-AKT-Tsc2-mammalian target of rapamycin signaling, among other important genes prominent in tumorigenesis, in conjunction with the enhanced cell proliferation and presence of preneoplastic lesions suggested involvement of Tsc2 in OTA-mediated toxicity and carcinogenicity, especially as deregulation of genes involved in this pathway was more prominent in the Tsc2 mutant Eker rat. PMID:17483316

  1. A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness

    Science.gov (United States)

    Yi, Cao; Li, Chen Chen; Yu, Patricia; Arakelian, Ani; Tanvir, Imrana; Khan, Haseeb Ahmed; Rabbani, Shafaat

    2015-01-01

    Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from non-invasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes in cellular invasiveness from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness. SUMMARY Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins that could serve as drug targets. PMID:26427334

  2. Downregulation of Smurf2, a tumor-suppressive ubiquitin ligase, in triple-negative breast cancers: Involvement of the RB-microRNA axis

    International Nuclear Information System (INIS)

    The HECT family ubiquitin ligase Smurf2 regulates cell polarity, migration, division, differentiation and death, by targeting diverse substrates that are critical for receptor signaling, cytoskeleton, chromatin remodeling and transcription. Recent studies suggest that Smurf2 functions as a tumor suppressor in mice. However, no inactivating mutation of SMURF2 has been reported in human, and information about Smurf2 expression in human cancer remains limited or complicated. Here we demonstrate that Smurf2 expression is downregulated in human breast cancer tissues, especially of the triple-negative subtype, and address the mechanism of Smurf2 downregulation in triple-negative breast cancer cells. Human breast cancer tissues (47 samples expressing estrogen receptor (ER) and 43 samples with triple-negative status) were examined by immunohistochemistry for the expression of Smurf2. Ten widely-studied human breast cancer cell lines were examined for the expression of Smurf2. Furthermore, microRNA-mediated regulation of Smurf2 was investigated in triple-negative cancer cell lines. Immunohistochemical analysis showed that benign mammary epithelial cells expressed high levels of Smurf2, so did cells in ductal carcinomas in situ. In contrast, invasive ductal carcinomas showed focal or diffuse decrease in Smurf2 expression, which was observed more frequently in triple-negative tumors than in ER-positive tumors. Consistently, human triple-negative breast cancer cell lines such as BT549, MDA-MB-436, DU-4475 and MDA-MB-468 cells showed significantly lower expression of Smurf2 protein, compared to ER + or HER2+ cell lines. Studies using quantitative PCR and specific microRNA inhibitors indicated that increased expression of miR-15a, miR-15b, miR-16 and miR-128 was involved in Smurf2 downregulation in those triple-negative cancer cell lines, which have mutations in the retinoblastoma (RB) gene. Forced expression of RB increased levels of Smurf2 protein with concomitant decreases in

  3. Role of MRI in detecting involvement of the uterine internal os in uterine cervical cancer: Systematic review of diagnostic test accuracy

    International Nuclear Information System (INIS)

    Purpose: In patients with uterine cervical cancer, pretreatment recognition of uterine extension is crucial in treatment decision-making for fertility-sparing surgery and for target delineation in radiotherapy. Although MRI is generally considered the most reliable method, its value for detecting involvement of the uterine internal os is unclear. Methods: Medline, Embase and Cochrane databases were systematically searched (January 1997–December 2012) for MRI studies that measured the accuracy of involvement of the uterine internal os compared to histopathology as reference standard in patients with uterine cervical cancer. Data were assessed using the QUADAS tool. Accuracy concerned either involvement (yes/no) of the uterine internal os, or measuring invasion distance toward the uterine corpus. Results: Two retrospective and two prospective studies described 366 patients diagnosed with uterine cervical cancer FIGO stage IIB or below, in whom 64 (17%) had uterine internal os involvement. For three studies the summary estimates of specificity, sensitivity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were 91%, 97%, 99%, 79% and 95%, respectively; one study had an area under the curve (AUC) of 0.8. Conclusion: MRI has a high level of accuracy; however, data are limited and for validation a large prospective study is needed that compares actual measurements on MRI with histopathological examination

  4. A comparison of long-term survivors and short-term survivors with glioblastoma, subventricular zone involvement: a predictive factor for survival?

    International Nuclear Information System (INIS)

    Long-term survival is rare in patients with glioblastoma (GBM). We set out to determine prognostic factors for patients with favorable and poor prognosis in regard of tumor localization to the subventricular zone (SZV). We reviewed the clinical records, pre-operative and post-operative MRI imaging of 50 LTS long-term survivors (LTS) (> 3 years) and 50 short-term survivors (STS) (< 1 year) with glioblastoma. These groups were matched for clinical characteristics being consistently associated with prolonged or shortened survival. All patients had undergone initial surgery or biopsy to confirm GBM diagnosis followed by radio- or chemoradiotherapy. LTS had a median progression-free survival PFS of 25, 4 months (2, 3–97, 8 months) and overall-survival (OS) of 55, 9 months (38, 2-98, 6 months) compared to STS who had a significantly lower PFS of 4, 2 months (1, 4–10, 2 months) and OS of 6, 6 months (2, 2–11, 6 months) (each p < 0,001). Survival analysis showed that age under 60 years (p < 0,001), total resection status (p < 0,001) and tumor localization without SVZ contact (p = 0,05) were significant factors for prolonged survival. Our findings underline that survival in GBM patients is heterogeneous and influenced by multiple factors. This study confirms that tumor location with regard to the SVZ is significantly associated with survival

  5. Synthesis, structures, and selective toxicity to cancer cells of gold(I) complexes involving N-heterocyclic carbene ligands.

    Science.gov (United States)

    Boselli, Luca; Ader, Isabelle; Carraz, Maëlle; Hemmert, Catherine; Cuvillier, Olivier; Gornitzka, Heinz

    2014-10-01

    New gold(I) complexes containing two 1-[2-(diethylamino)ethyl]imidazolydene ligands have been synthesized and characterized. The X-ray structures of two key compounds are presented. All complexes have been tested for their antiproliferative activities in prostate cancer cell line PC-3. Lipophilicity (Log P) has been determined for these complexes. The most active complex has been tested for the cytotoxic activities in five human cancer cell lines and primary endothelial cells. The most active complex demonstrated a potent selectivity for cancer cells. PMID:25078312

  6. Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study

    Directory of Open Access Journals (Sweden)

    Acampa Olga

    2005-07-01

    Full Text Available Abstract Background Non-invasive diagnostic strategies aimed at identifying biomarkers of lung cancer are of great interest for early cancer detection. The aim of this study was to set up a new method for identifying and quantifying volatile organic compounds (VOCs in exhaled air of patients with non-small cells lung cancer (NSCLC, by comparing the levels with those obtained from healthy smokers and non-smokers, and patients with chronic obstructive pulmonary disease. The VOC collection and analyses were repeated three weeks after the NSCLC patients underwent lung surgery. Methods The subjects' breath was collected in a Teflon® bulb that traps the last portion of single slow vital capacity. The 13 VOCs selected for this study were concentrated using a solid phase microextraction technique and subsequently analysed by means of gas cromatography/mass spectrometry. Results The levels of the selected VOCs ranged from 10-12 M for styrene to 10-9 M for isoprene. None of VOCs alone discriminated the study groups, and so it was not possible to identify one single chemical compound as a specific lung cancer biomarker. However, multinomial logistic regression analysis showed that VOC profile can correctly classify about 80 % of cases. Only isoprene and decane levels significantly decreased after surgery. Conclusion As the combination of the 13 VOCs allowed the correct classification of the cases into groups, together with conventional diagnostic approaches, VOC analysis could be used as a complementary test for the early diagnosis of lung cancer. Its possible use in the follow-up of operated patients cannot be recommended on the basis of the results of our short-term nested study.

  7. Assessment of nodal involvement and survival analysis in breast cancer patients using image cytometric data: statistical, neural network and fuzzy approaches.

    Science.gov (United States)

    Seker, Huseyin; Odetayo, Michael O; Petrovic, Dobrila; Naguib, Raouf N G; Bartoli, C; Alasio, L; Lakshmi, M S; Sherbet, G V

    2002-01-01

    Accurate and reliable decision making in breast cancer prognosis can help in the planning of suitable surgery and therapy and, generally, optimise patient management through the different stages of the disease. In recent years, several prognostic factors have been used as indicators of disease progression in breast cancer. In this paper we investigate a fuzzy method, namely fuzzy k-nearest neighbour technique for breast cancer prognosis, and for determining the significance of prognostic markers and subsets of the markers, which include histology type, tumour grade, DNA ploidy, S-phase fraction, G0G1/G2M ratio, and minimum (start) and maximum (end) nuclear pleomorphism indices. We also compare the method with (a) logistic regression as a statistical method, and (b) multilayer feed forward backpropagation neural networks as an artificial neural network tool, the latter two techniques having been widely used for cancer prognosis. Nodal involvement and survival analyses in breast cancer are carried out for 100 women who were clinically diagnosed with breast disease in the form of carcinoma and benign conditions, and seven prognostic markers collected for each patient. For nodal involvement analysis, node positive and negative patients are predicted whereas survival analysis is carried out for two categories: whether a patient is alive or dead within 5 years of diagnosis. The results obtained show that the fuzzy method yields the highest predictive accuracy of 88% for both nodal involvement and survival analyses obtained from the subsets of [tumour grade, S-phase fraction, minimum (start) nuclear pleomorphism index] and [tumour histology type, DNA ploidy, S-phase fraction, G0G1/G2M ratio], respectively. We believe that this technique has produced more reliable prognostic factor models than those obtained using either the statistical or artificial neural networks-based methods. PMID:12017328

  8. Roe Protein Hydrolysates of Giant Grouper (Epinephelus lanceolatus) Inhibit Cell Proliferation of Oral Cancer Cells Involving Apoptosis and Oxidative Stress

    Science.gov (United States)

    Yang, Jing-Iong; Tang, Jen-Yang; Liu, Ya-Sin; Wang, Hui-Ru; Lee, Sheng-Yang; Yen, Ching-Yu

    2016-01-01

    Roe protein hydrolysates were reported to have antioxidant property but the anticancer effects were less addressed, especially for oral cancer. In this study, we firstly used the ultrafiltrated roe hydrolysates (URH) derived from giant grouper (Epinephelus lanceolatus) to evaluate the impact of URH on proliferation against oral cancer cells. We found that URH dose-responsively reduced cell viability of two oral cancer cells (Ca9-22 and CAL 27) in terms of ATP assay. Using flow cytometry, URH-induced apoptosis of Ca9-22 cells was validated by morphological features of apoptosis, sub-G1 accumulation, and annexin V staining in dose-responsive manners. URH also induced oxidative stress in Ca9-22 cells in terms of reactive oxygen species (ROS)/superoxide generations and mitochondrial depolarization. Taken together, these data suggest that URH is a potential natural product for antioral cancer therapy. PMID:27195297

  9. A quinazoline-based HDAC inhibitor affects gene expression pathways involved in cholesterol biosynthesis and mevalonate in prostate cancer cells.

    Science.gov (United States)

    Lin, Z; Bishop, K S; Sutherland, H; Marlow, G; Murray, P; Denny, W A; Ferguson, L R

    2016-03-01

    Chronic inflammation can lead to the development of cancers and resolution of inflammation is an ongoing challenge. Inflammation can result from dysregulation of the epigenome and a number of compounds that modify the epigenome are in clinical use. In this study the anti-inflammatory and anti-cancer effects of a quinazoline epigenetic-modulator compound were determined in prostate cancer cell lines using a non-hypothesis driven transcriptomics strategy utilising the Affymetrix PrimeView® Human Gene Expression microarray. GATHER and IPA software were used to analyse the data and to provide information on significantly modified biological processes, pathways and networks. A number of genes were differentially expressed in both PC3 and DU145 prostate cancer cell lines. The top canonical pathways that frequently arose across both cell lines at a number of time points included cholesterol biosynthesis and metabolism, and the mevalonate pathway. Targeting of sterol and mevalonate pathways may be a powerful anticancer approach. PMID:26759180

  10. Cytotoxic Effect of Luteolin on Human Colorectal Cancer Cell Line (HCT-15: Crucial Involvement of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Pandurangan

    2013-10-01

    Full Text Available Background: Colorectal cancer, a major health concern worldwide, is the third mostcommon form of cancer and second leading cause of cancer-related deaths. Theflavonoids are naturally occurring diphenylpropanoids ubiquitous in plant foods andimportant components of the human diet. Luteolin, a bioflavonoid, possesses manybeneficial effects including antioxidant, anti-inflammatory, anti-allergic activities. Methods:We used the HCT-15 colon adenocarcinoma cell line in this study. Cellswere treated with luteolin (100 µM. Results: Membrane damage markers such as alkaline phosphatase and lactatedehydrogenase were analyzed in a time-dependent manner. Luteolin increased reactiveoxygen species in a time-dependent manner. DNA damage, a hallmark of apoptosis,was induced by luteolin as analyzed by agarose gel electrophoresis. Conclusion: Luteolin acts as a potential cytotoxic agent that can be used to treatcolorectal cancer.

  11. Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl/Hes genes.

    Directory of Open Access Journals (Sweden)

    Ben E Housden

    Full Text Available Dynamic activity of signaling pathways, such as Notch, is vital to achieve correct development and homeostasis. However, most studies assess output many hours or days after initiation of signaling, once the outcome has been consolidated. Here we analyze genome-wide changes in transcript levels, binding of the Notch pathway transcription factor, CSL [Suppressor of Hairless, Su(H, in Drosophila], and RNA Polymerase II (Pol II immediately following a short pulse of Notch stimulation. A total of 154 genes showed significant differential expression (DE over time, and their expression profiles stratified into 14 clusters based on the timing, magnitude, and direction of DE. E(spl genes were the most rapidly upregulated, with Su(H, Pol II, and transcript levels increasing within 5-10 minutes. Other genes had a more delayed response, the timing of which was largely unaffected by more prolonged Notch activation. Neither Su(H binding nor poised Pol II could fully explain the differences between profiles. Instead, our data indicate that regulatory interactions, driven by the early-responding E(splbHLH genes, are required. Proposed cross-regulatory relationships were validated in vivo and in cell culture, supporting the view that feed-forward repression by E(splbHLH/Hes shapes the response of late-responding genes. Based on these data, we propose a model in which Hes genes are responsible for co-ordinating the Notch response of a wide spectrum of other targets, explaining the critical functions these key regulators play in many developmental and disease contexts.

  12. Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites

    Directory of Open Access Journals (Sweden)

    Pierce Levi CT

    2009-01-01

    Full Text Available Abstract Background Gene rearrangements such as chromosomal translocations have been shown to contribute to cancer development. Human chromosomal fragile sites are regions of the genome especially prone to breakage, and have been implicated in various chromosome abnormalities found in cancer. However, there has been no comprehensive and quantitative examination of the location of fragile sites in relation to all chromosomal aberrations. Results Using up-to-date databases containing all cancer-specific recurrent translocations, we have examined 444 unique pairs of genes involved in these translocations to determine the correlation of translocation breakpoints and fragile sites in the gene pairs. We found that over half (52% of translocation breakpoints in at least one gene of these gene pairs are mapped to fragile sites. Among these, we examined the DNA sequences within and flanking three randomly selected pairs of translocation-prone genes, and found that they exhibit characteristic features of fragile DNA, with frequent AT-rich flexibility islands and the potential of forming highly stable secondary structures. Conclusion Our study is the first to examine gene pairs involved in all recurrent chromosomal translocations observed in tumor cells, and to correlate the location of more than half of breakpoints to positions of known fragile sites. These results provide strong evidence to support a causative role for fragile sites in the generation of cancer-specific chromosomal rearrangements.

  13. Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells.

    Science.gov (United States)

    Chon, Hae Jung; Lee, Yura; Bae, Kyoung Jun; Byun, Byung Jin; Kim, Soon Ae; Kim, Jiyeon

    2016-07-01

    Traf2- and Nck-interacting kinase (TNIK) is a member of the germinal center kinase family. TNIK was first identified as a kinase that is involved in regulating cytoskeletal organization in many types of cells, and it was recently proposed as a novel therapeutic target in several types of human cancers. Although previous studies suggest that TNIK plays a pivotal role in cancer cell survival and prognosis, its function in hematological cancer cell survival has not been investigated. Here we investigated the relationship between TNIK function and cell viability in multiple myeloma IM-9 cells using TNIK small interfering RNA (siRNA) transfection and dovitinib treatment. Treatment of IM-9 cells with TNIK siRNA and dovitinib treatment reduced cell proliferation. The ATP competing kinase assay and western blot analysis showed that dovitinib strongly inhibited both the interaction of TNIK with ATP (K i, 13 nM) and the activation of Wnt signaling effectors such as β-catenin and TCF4. Dovitinib also induced caspase-dependent apoptosis in IM-9 cells without significant cytotoxicity in PBMCs. Our results provide new evidence that TNIK may be involved in the proliferation of multiple myeloma IM-9 cells and in the anti-cancer activity of dovitinib via inhibition of the endogenous Wnt signaling pathway. PMID:26995282

  14. Quality of life is an important criterion for the efficiency of targeted therapy for metastatic skeletal involvement in breast cancer

    OpenAIRE

    T. Yu. Semiglazova; V. V. Semiglazov; L V Filatova; P. V. Krivorotko; V. V. Kolarkova; V. F. Semiglazov

    2013-01-01

    Assessment of quality of life is an important, valid, informative, and cost-effective procedure for evaluating the efficiency of treatment in patients with breast cancer metastasizing to the bone, receiving therapy with bone-modifying agents, including targeted therapy with denosumab. The administration of denosumab significantly improves quality of life in patients with breast cancer metastasizing to the bone, by maintaining their general status, reducing the intensity of pain syndrome, and ...

  15. Synthesis, structures, and selective toxicity to cancer cells of gold(I) complexes involving N-heterocyclic carbene ligands

    OpenAIRE

    L. Boselli; Ader, I.; Carraz, Maëlle; Hemmert, C.; Cuvillier, O.; Gornitzka, H.

    2014-01-01

    New gold(I) complexes containing two 1-[2-(diethylamino)ethyl]imidazolydene ligands have been synthesized and characterized. The X-ray structures of two key compounds are presented. All complexes have been tested for their antiproliferative activities in prostate cancer cell line PC-3. Lipophilicity (Log P) has been determined for these complexes. The most active complex has been tested for the cytotoxic activities in five human cancer cell lines and primary endothelial cells. The most active...

  16. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    International Nuclear Information System (INIS)

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC

  17. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui, E-mail: baohuihan1@163.com

    2014-01-17

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  18. A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

    OpenAIRE

    Xu Tony; Pintilie Melania; Brenner David J; Tsang Richard W; Sachs Rainer K; Heydarian Mostafa; Tran Tu; Koh Eng-Siew; Chung June; Paul Narinder; Hodgson David C

    2007-01-01

    Abstract Background Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no es...

  19. Is Short-Interval Mammography Necessary After Breast Conservation Surgery and Radiation Treatment in Breast Cancer Patients?

    International Nuclear Information System (INIS)

    Purpose: The optimum timing and frequency of mammography in breast cancer patients after breast-conserving therapy (BCT) are controversial. The American Society of Clinical Oncology recommends the first posttreatment mammogram 1 year after diagnosis but no earlier than 6 months after completion of radiotherapy. The National Comprehensive Cancer Network recommends annual mammography. Intermountain Healthcare currently follows a more frequent mammography schedule during the first 2 years in BCT patients. This retrospective study was undertaken to determine the cancer yield mammography during the first 2 years after BCT. Methods and Materials: 1,435 patients received BCT at Intermountain Healthcare between 2003 and 2007, inclusive. Twenty-three patients had bilateral breast cancer (1,458 total breasts). Patients were followed up for 24 months after diagnosis. The 1- and 2-year mammography yields were determined and compared with those of the general screening population. Results: 1,079 breasts had mammography at less than 1 year, and two ipsilateral recurrences (both noninvasive) were identified; 1,219 breasts had mammography during the second year, and nine recurrences (three invasive, six noninvasive) were identified. Of the 11 ipsilateral recurrences during the study, three presented with symptoms and eight were identified by mammography alone. The mammography yield was 1.9 cancers per 1,000 breasts the first year and 4.9 per 1,000 the second year. Conclusions: These data demonstrate that the mammography yield during the first 2 years after BCT is not greater than that in the general population, and they support the policy for initiating followup mammography at 1 year after BCT.

  20. Is Short-Interval Mammography Necessary After Breast Conservation Surgery and Radiation Treatment in Breast Cancer Patients?

    Energy Technology Data Exchange (ETDEWEB)

    Hymas, Richard V.; Gaffney, David K. [Department of Radiation Oncology, University of Utah, Salt Lake City, UT (United States); Parkinson, Brett T.; Belnap, Thomas W. [Intermountain Medical Center, Salt Lake City, UT (United States); Sause, William T., E-mail: william.sause@imail.org [Intermountain Medical Center, Salt Lake City, UT (United States)

    2012-06-01

    Purpose: The optimum timing and frequency of mammography in breast cancer patients after breast-conserving therapy (BCT) are controversial. The American Society of Clinical Oncology recommends the first posttreatment mammogram 1 year after diagnosis but no earlier than 6 months after completion of radiotherapy. The National Comprehensive Cancer Network recommends annual mammography. Intermountain Healthcare currently follows a more frequent mammography schedule during the first 2 years in BCT patients. This retrospective study was undertaken to determine the cancer yield mammography during the first 2 years after BCT. Methods and Materials: 1,435 patients received BCT at Intermountain Healthcare between 2003 and 2007, inclusive. Twenty-three patients had bilateral breast cancer (1,458 total breasts). Patients were followed up for 24 months after diagnosis. The 1- and 2-year mammography yields were determined and compared with those of the general screening population. Results: 1,079 breasts had mammography at less than 1 year, and two ipsilateral recurrences (both noninvasive) were identified; 1,219 breasts had mammography during the second year, and nine recurrences (three invasive, six noninvasive) were identified. Of the 11 ipsilateral recurrences during the study, three presented with symptoms and eight were identified by mammography alone. The mammography yield was 1.9 cancers per 1,000 breasts the first year and 4.9 per 1,000 the second year. Conclusions: These data demonstrate that the mammography yield during the first 2 years after BCT is not greater than that in the general population, and they support the policy for initiating followup mammography at 1 year after BCT.

  1. Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

    Energy Technology Data Exchange (ETDEWEB)

    Yeo, Seung-Gu [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan (Korea, Republic of); Oh, Jae Hwan [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Kim, Dae Yong, E-mail: radiopiakim@hanmail.net [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Baek, Ji Yeon; Kim, Sun Young; Park, Ji Won; Kim, Min Ju; Chang, Hee Jin; Kim, Tae Hyun [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Lee, Jong Hoon; Jang, Hong Seok [Department of Radiation Oncology, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Kim, Jun-Gi [Department of Surgery, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Lee, Myung Ah [Department of Internal Medicine, Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Nam, Taek-Keun [Department of Radiation Oncology, Chonnam National University Hospital, Gwang-Ju (Korea, Republic of)

    2013-05-01

    Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m{sup 2}/day) and leucovorin (20 mg/m{sup 2}/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique.

  2. Preoperative Short-Course Concurrent Chemoradiation Therapy Followed by Delayed Surgery for Locally Advanced Rectal Cancer: A Phase 2 Multicenter Study (KROG 10-01)

    International Nuclear Information System (INIS)

    Purpose: A prospective phase 2 multicenter trial was performed to investigate the efficacy and safety of preoperative short-course concurrent chemoradiation therapy (CRT) followed by delayed surgery for patients with locally advanced rectal cancer. Methods and Materials: Seventy-three patients with cT3-4 rectal cancer were enrolled. Radiation therapy of 25 Gy in 5 fractions was delivered over 5 consecutive days using helical tomotherapy. Concurrent chemotherapy was administered on the same 5 days with intravenous bolus injection of 5-fluorouracil (400 mg/m2/day) and leucovorin (20 mg/m2/day). After 4 to 8 weeks, total mesorectal excision was performed. The primary endpoint was the pathologic downstaging (ypStage 0-I) rate, and secondary endpoints included tumor regression grade, tumor volume reduction rate, and toxicity. Results: Seventy-one patients completed the planned preoperative CRT and surgery. Downstaging occurred in 20 (28.2%) patients, including 1 (1.4%) with a pathologic complete response. Favorable tumor regression (grade 4-3) was observed in 4 (5.6%) patients, and the mean tumor volume reduction rate was 62.5 ± 21.3%. Severe (grade ≥3) treatment toxicities were reported in 27 (38%) patients from CRT until 3 months after surgery. Conclusions: Preoperative short-course concurrent CRT followed by delayed surgery for patients with locally advanced rectal cancer demonstrated poor pathologic responses compared with conventional long-course CRT, and it yielded considerable toxicities despite the use of an advanced radiation therapy technique

  3. Results of Neoadjuvant Short-Course Radiation Therapy Followed by Transanal Endoscopic Microsurgery for T1-T2 N0 Extraperitoneal Rectal Cancer

    International Nuclear Information System (INIS)

    Purpose: This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer. Methods and Materials: We planned a prospective pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality were compared with historical groups of patients with similar rectal cancer stage and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM), TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME) at our institution. Results: The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks follow-up, associated with an enterocutaneous fistula in the sacral area in 2 cases. One patient required a colostomy. Quality of life at 1-month follow-up, according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM patients (P=.0277) or TEM patients (P=.0004), whereas no differences were observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6-26 months), we observed 1 (7%) local recurrence at 6 months that was treated with abdominoperineal resection. Conclusions: SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and enterocutaneous

  4. Results of Neoadjuvant Short-Course Radiation Therapy Followed by Transanal Endoscopic Microsurgery for T1-T2 N0 Extraperitoneal Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Arezzo, Alberto, E-mail: alberto.arezzo@unito.it [General Surgery I, Department of Surgical Sciences, University of Torino, Torino (Italy); Arolfo, Simone; Allaix, Marco Ettore [General Surgery I, Department of Surgical Sciences, University of Torino, Torino (Italy); Munoz, Fernando [Radiation Oncology, Department of Oncology, University of Torino, Torino (Italy); Cassoni, Paola [Pathology Unit, Department of Medical Sciences, University of Torino, Torino (Italy); Monagheddu, Chiara [Clinical Epidemiology Unit, Piedmont Reference Centre for Epidemiology and Cancer Prevention, City of Health and Science Hospital of Torino, Torino (Italy); Ricardi, Umberto [Radiation Oncology, Department of Oncology, University of Torino, Torino (Italy); Ciccone, Giovannino [Clinical Epidemiology Unit, Piedmont Reference Centre for Epidemiology and Cancer Prevention, City of Health and Science Hospital of Torino, Torino (Italy); Morino, Mario [General Surgery I, Department of Surgical Sciences, University of Torino, Torino (Italy)

    2015-06-01

    Purpose: This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer. Methods and Materials: We planned a prospective pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality were compared with historical groups of patients with similar rectal cancer stage and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM), TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME) at our institution. Results: The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks follow-up, associated with an enterocutaneous fistula in the sacral area in 2 cases. One patient required a colostomy. Quality of life at 1-month follow-up, according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM patients (P=.0277) or TEM patients (P=.0004), whereas no differences were observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6-26 months), we observed 1 (7%) local recurrence at 6 months that was treated with abdominoperineal resection. Conclusions: SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and enterocutaneous

  5. Disruption of human papillomavirus 16 E6 gene by clustered regularly interspaced short palindromic repeat/Cas system in human cervical cancer cells

    Directory of Open Access Journals (Sweden)

    Yu L

    2014-12-01

    Full Text Available Lan Yu, Xiaoli Wang, Da Zhu, Wencheng Ding, Liming Wang, Changlin Zhang, Xiaohui Jiang, Hui Shen, Shujie Liao, Ding Ma, Zheng Hu, Hui Wang Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China Abstract: High-risk human papillomavirus (HPV, especially HPV16, is considered a main causative agent of cervical cancer. Upon HPV infection, the viral oncoprotein E6 disrupts the host tumor-suppressor protein p53, thus promoting malignant transformation of normal cervical cells. Here, we used the newly developed programmable ribonucleic acid-guided clustered regularly interspaced short palindromic repeat (CRISPR/Cas system to disrupt the HPV16 E6 gene. We showed that HPV16 E6 deoxyribonucleic acid was cleaved at specific sites, leading to apoptosis and growth inhibition of HPV16-positive SiHa and CaSki cells, but not HPV-negative C33A or human embryonic kidney 293 cells. We also observed downregulation of the E6 protein and restoration of the p53 protein. These data proved that the HPV16 E6 ribonucleic acid-guided CRISPR/Cas system might be an effective therapeutic agent in treating HPV infection-related cervical malignancy. Keywords: CRISPR/Cas system, E6, p53, SiHa, CaSki, cervical cancer

  6. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer.

    LENUS (Irish Health Repository)

    Armstrong, John G

    2010-08-24

    PURPOSE: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. METHODS AND MATERIALS: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng\\/mL, Gleason score >\\/=7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. RESULTS: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. CONCLUSION: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  7. Implantation of 125I seeds for the treatment of non-small cell lung cancer: evaluation of short-term effect

    International Nuclear Information System (INIS)

    Objective: To assess the short-term effect, feasibility and safety of 125I seeds implantation in treating non-small cell lung cancer. Methods: During the period from June 2010 to December 2012 a total of 353 patients with lung cancer were admitted to authors' hospital, of whom 56 met the study standards. The 56 cases were divided into study group (n=24) and control group (n=32). Bronchial artery chemotherapy with subsequent 125I seeds implantation was carried out in the patients of study group, while only bronchial artery chemotherapy was performed in the patients of control group. The median survival time was compared between the two groups. Results: The median survival time of the study group and the control group was (22.8±1.9) months and (14.2±1.3) months respectively. The median survival time of the study group was significantly higher than that of the control group (P=0.006). Conclusion: Compared with simple bronchial artery chemotherapy, permanent implantation of 125I seeds combined with bronchial artery chemotherapy can significantly improve the quality of life and prolong the survival time as well. Therefore, this technique is an effective therapy for advanced lung cancer and should be recommended in clinical practice. (authors)

  8. Class II phosphoinositide 3-kinase C2β regulates a novel signaling pathway involved in breast cancer progression

    Science.gov (United States)

    Abbott, Jonathan J.; Piñeiro, Roberto; Buus, Richard; Iezzi, Manuela; Ricci, Francesca; Bergamaschi, Daniele; Ostano, Paola; Chiorino, Giovanna; Lattanzio, Rossano; Broggini, Massimo; Piantelli, Mauro; Maffucci, Tania; Falasca, Marco

    2016-01-01

    It is now well established that the enzymes phosphoinositide 3-kinases (PI3Ks) have a key role in the development and progression of many cancer types and indeed PI3Ks inhibitors are currently being tested in clinical trials. Although eight distinct PI3K isoforms exist, grouped into three classes, most of the evidence currently available are focused on one specific isoform with very little known about the potential role of the other members of this family in cancer. Here we demonstrate that the class II enzyme PI3K-C2β is overexpressed in several human breast cancer cell lines and in human breast cancer specimens. Our data indicate that PI3K-C2β regulates breast cancer cell growth in vitro and in vivo and that PI3K-C2β expression in breast tissues is correlated with the proliferative status of the tumor. Specifically we show that downregulation of PI3K-C2β in breast cancer cell lines reduces colony formation, induces cell cycle arrest and inhibits tumor growth, in particular in an estrogen-dependent in vivo xenograft. Investigation of the mechanism of the PI3K-C2β-dependent regulation of cell cycle progression and cell growth revealed that PI3K-C2β regulates cyclin B1 protein levels through modulation of microRNA miR-449a levels. Our data further demonstrate that downregulation of PI3K-C2β inhibits breast cancer cell invasion in vitro and breast cancer metastasis in vivo. Consistent with this, PI3K-C2β is highly expressed in lymph-nodes metastases compared to matching primary tumors. These data demonstrate that PI3K-C2β plays a pivotal role in breast cancer progression and in metastasis development. Our data indicate that PI3K-C2β may represent a key molecular switch that regulates a rate-limiting step in breast tumor progression and therefore it may be targeted to limit breast cancer spread. PMID:26934321

  9. A network of clinically and functionally relevant genes is involved in the reversion of the tumorigenic phenotype of MDA-MB-231 breast cancer cells after transfer of human chromosome 8.

    Science.gov (United States)

    Seitz, Susanne; Frege, Renate; Jacobsen, Anja; Weimer, Jörg; Arnold, Wolfgang; von Haefen, Clarissa; Niederacher, Dieter; Schmutzler, Rita; Arnold, Norbert; Scherneck, Siegfried

    2005-01-27

    Several investigations have supposed that tumor suppressor genes might be located on human chromosome 8. We used microcell-mediated transfer of chromosome 8 into MDA-MB-231 breast cancer cells and generated independent hybrids with strongly reduced tumorigenic potential. Loss of the transferred chromosome results in reappearance of the malignant phenotype. Expression analysis identified a set of 109 genes (CT8-ps) differentially expressed in microcell hybrids as compared to the tumorigenic MDA-MB-231 and rerevertant cells. Of these, 44.9% are differentially expressed in human breast tumors. The expression pattern of CT8-ps was associated with prognostic factors such as tumor size and grading as well as loss of heterozygosity at the short arm of chromosome 8. We identified CT8-ps networks suggesting that these genes act cooperatively to cause reversion of tumorigenicity in MDA-MB-231 cells. Our findings provide a conceptual basis and experimental system to identify and evaluate genes and gene networks involved in the development and/or progression of breast cancer. PMID:15580292

  10. Overexpression of SOX2 is involved in paclitaxel resistance of ovarian cancer via the PI3K/Akt pathway.

    Science.gov (United States)

    Li, Yang; Chen, Kangdong; Li, Lei; Li, Rui; Zhang, Juxin; Ren, Wu

    2015-12-01

    Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Sex-determining region Y-box 2 (SOX2) is of vital importance in the regulation of stem cell proliferation and carcinogenesis. The aim of this study was to evaluate the role of SOX2 in ovarian cancer tumorigenesis and paclitaxel resistance. In the present study, the expression of SOX2 was examined by immunohistochemistry (IHC) and real-time PCR in 40 clinical samples and in SKOV3 cells and SKOV3/TAX cells (paclitaxel-resistant human ovarian adenocarcinoma cell line). The effects of SOX2 knockdown on ovarian cancer cell proliferation, migration, and invasion were also studied. The IHC and real-time PCR results showed that the difference of SOX2 expression between ovarian cancer and the adjacent non-tumorous ovarian tissues was statistically significant. Western blot analysis revealed that the PI3K/Akt signaling pathway was inhibited in cells overexpressing SOX2. Western blot analysis showed that the SOX2 protein was overexpressed in paclitaxel-resistant cells and weakly detectable in paclitaxel-sensitive cells. SOX2 silencing significantly potentiated apoptosis induced by paclitaxel in SKOV3-TR with SOX2 knockdown compared to SKOV3-TR transfected with control small interfering RNA (siRNA). Our work indicates SOX2 will become both a rational indicator of ovarian cancer prognosis and a promising target for ovarian cancer gene therapy. PMID:26159849

  11. Short- and long-term outcomes of laparoscopic surgery vs open surgery for transverse colon cancer: a retrospective multicenter study

    Directory of Open Access Journals (Sweden)

    Kim JW

    2016-04-01

    Full Text Available Jong Wan Kim,1 Jeong Yeon Kim,1 Byung Mo Kang,2 Bong Hwa Lee,3 Byung Chun Kim,4 Jun Ho Park5 1Department of Surgery, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwaseong Si, 2Department of Surgery, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon Si, 3Department of Surgery, Hallym Sacred Heart Hospital, College of Medicine, Hallym University, Anyang Si, 4Department of Surgery, Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, 5Department of Surgery, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Republic of Korea Purpose: The purpose of the present study was to compare the perioperative and oncologic outcomes between laparoscopic surgery and open surgery for transverse colon cancer.Patients and methods: We conducted a retrospective review of patients who underwent surgery for transverse colon cancer at six Hallym University-affiliated hospitals between January 2005 and June 2015. The perioperative outcomes and oncologic outcomes were compared between laparoscopic and open surgery.Results: Of 226 patients with transverse colon cancer, 103 underwent laparoscopic surgery and 123 underwent open surgery. There were no differences in the patient characteristics between the two groups. Regarding perioperative outcomes, the operation time was significantly longer in the laparoscopic group than in the open group (267.3 vs 172.7 minutes, P<0.001, but the time to soft food intake (6.0 vs 6.6 days, P=0.036 and the postoperative hospital stay (13.7 vs 15.7 days, P=0.018 were shorter in the laparoscopic group. The number of harvested lymph nodes was lower in the laparoscopic group than in the open group (20.3 vs 24.3, P<0.001. The 5-year overall survival (90.8% vs 88.6%, P=0.540 and disease-free survival (86.1% vs 78.9%, P=0.201 rates were similar in both groups.Conclusion: The present study showed that laparoscopic surgery is associated

  12. High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

    DEFF Research Database (Denmark)

    Nielsen, Boye Schnack; Jørgensen, Stine; Fog, Jacob Ulrik;

    2011-01-01

    situ hybridization assay using high-affinity Locked Nucleic Acid (LNA) probes that specifically detect miR-21 in formalin-fixed paraffin embedded (FFPE) tissue samples. The expression of miR-21 was analyzed by in situ hybridization on 130 stage II colon and 67 stage II rectal cancer specimens. The mi...

  13. Differentiation and apoptotic response of colon cancer cell lines to short- and long-chain fatty acids

    Czech Academy of Sciences Publication Activity Database

    Stixová, Lenka; Hofmanová, Jiřina; Netíková, Jaromíra; Kozubík, Alois

    Olomouc, 2009. s. 110. ISBN 978-80-254-2561-5. [Analytical Cytometry V. 05.09.2009-08.09.2009, Olomouc] R&D Projects: GA ČR(CZ) GA524/07/1178; GA ČR(CZ) GA305/09/1526; GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : colon cancer * differentiation * apoptosis Subject RIV: BO - Biophysics

  14. What is Prostate Cancer?

    Science.gov (United States)

    ... Research Get Involved Find Local ACS Learn About Cancer » Prostate Cancer » Detailed Guide » What is prostate cancer? Share ... how cancers start and spread, see What Is Cancer? Prostate cancer begins when cells in the prostate gland ...

  15. Sintomas depressivos no câncer de mama: Inventário de Depressão de Beck - Short Form Depressive symptoms in breast cancer: Beck Depression Inventory - Short Form

    Directory of Open Access Journals (Sweden)

    Renata de Oliveira Cangussu

    2010-01-01

    Full Text Available OBJETIVOS: Verificar a prevalência de sintomas depressivos em mulheres com câncer de mama e identificar os fatores de risco associados à sua ocorrência. MÉTODOS: Foi realizado um estudo transversal, em que foram entrevistadas 71 mulheres com câncer de mama. Foram empregados dois instrumentos: um questionário para verificar os dados sociodemográficos e clínicos e o Inventário de Depressão de Beck - Short Form (BDI-SF, para avaliação dos sintomas depressivos. Para análise dos dados, utilizaram-se medidas descritivas e o teste de qui-quadrado, que avaliou a associação entre variáveis sociodemográficas e clínicas e os sintomas depressivos. O nível de significância considerado foi de 5%. RESULTADOS: A prevalência de sintomas depressivos foi de 29,6%. Os fatores associados à presença desses sintomas foram o tratamento quimioterápico (p = 0,021, presença de dor (p = 0,018 e limitação do movimento do membro superior (p = 0,010 e pior percepção da saúde (p = 0,018. CONCLUSÃO: Sintomas depressivos são frequentes no câncer de mama, assim a saúde mental das mulheres com esse tipo de câncer deve ser investigada e tratada quando necessário, reduzindo o impacto desses sintomas na vida da mulher.OBJECTIVES: To verify the prevalence of depressive symptoms in women with breast cancer and identify risk factors associated to its occurrence. METHODS: It was a transversal study where 71 women with breast cancer were interviewed. Two instruments were applied, being one questionnaire used to verify sociodemographic and clinical data, and the Beck Depression Inventory - Short Form to evaluate depressive symptoms. Descriptive methods and chi-square test were utilized to analyze data, evaluating association between depressive symptoms, sociodemographic and clinical data. Significance level was considered of 5%. RESULTS: Depressive symptoms prevalence was 29,6%. Factors associated to the presence of this kind of symptoms were

  16. Comparison of perioperative and short-term outcomes between robotic and conventional laparoscopic surgery for colonic cancer: a systematic review and meta-analysis

    Science.gov (United States)

    Lim, Sungwon; Kim, Jin Hee; Baek, Se-Jin; Kim, Seon-Hahn

    2016-01-01

    Purpose Reports from several case series have described the feasibility and safety of robotic surgery (RS) for colonic cancer. Experience is still limited in robotic colonic surgery, and a few meta-analysis has been conducted to integrate the results for colon cancer specifically. We conducted a systematic review of the available evidence comparing the surgical safety and efficacy of RS with that of conventional laparoscopic surgery (CLS) for colonic cancer. Methods We searched English databases (MEDLINE, Embase, and Cochrane Library), and Korean databases (KoreaMed, KMbase, KISS, RISS, and KisTi). Dichotomous variables were pooled using the risk ratio, and continuous variables were pooled using the mean difference (MD). Results The present study found that the RS group had a shorter time to resumption of a regular diet (MD, –0.62 days; 95% CI, –0.97 to –0.28), first passage of flatus (MD, –0.44 days; 95% CI, –0.66 to –0.23) and defecation (MD, –0.62 days; 95% CI, –0.77 to –0.47). Also, RS was associated with a shorter hospital stay (MD, –0.69 days; 95% CI, –1.12 to –0.26), a lower estimated blood loss (MD, –19.49 mL; 95% CI, –27.10 to –11.89) and a longer proximal margin (MD, 2.29 cm; 95% CI, 1.11-3.47). However, RS was associated with a longer surgery time (MD, 51.00 minutes; 95% CI, 39.38–62.62). Conclusion We found that the potential benefits of perioperative and short-term outcomes for RS than for CLS. For a more accurate understanding of RS for colonic cancer patients, robust comparative studies and randomized clinical trials are required. PMID:27274509

  17. An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

    Energy Technology Data Exchange (ETDEWEB)

    McCready, Jessica [Department of Natural Sciences, Assumption College, Worcester, MA 01609 (United States); Wong, Daniel S. [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Burlison, Joseph A.; Ying, Weiwen [Synta Pharmaceuticals, Lexington, MA 02421 (United States); Jay, Daniel G., E-mail: daniel.jay@tufts.edu [Department of Developmental Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Cell and Molecular Physiology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States)

    2014-04-30

    Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion.

  18. An Impermeant Ganetespib Analog Inhibits Extracellular Hsp90-Mediated Cancer Cell Migration that Involves Lysyl Oxidase 2-like Protein

    International Nuclear Information System (INIS)

    Extracellular Hsp90 (eHsp90) activates a number of client proteins outside of cancer cells required for migration and invasion. Therefore, eHsp90 may serve as a novel target for anti-metastatic drugs as its inhibition using impermeant Hsp90 inhibitors would not affect the numerous vital intracellular Hsp90 functions in normal cells. While some eHsp90 clients are known, it is important to establish other proteins that act outside the cell to validate eHsp90 as a drug target to limit cancer spread. Using mass spectrometry we identified two precursor proteins Galectin 3 binding protein (G3BP) and Lysyl oxidase 2-like protein (LOXL2) that associate with eHsp90 in MDA-MB231 breast cancer cell conditioned media and confirmed that LOXL2 binds to eHsp90 in immunoprecipitates. We introduce a novel impermeant Hsp90 inhibitor STA-12-7191 derived from ganetespib and show that it is markedly less toxic to cells and can inhibit cancer cell migration in a dose dependent manner. We used STA-12-7191 to test if LOXL2 and G3BP are potential eHsp90 clients. We showed that while LOXL2 can increase wound healing and compensate for STA-12-7191-mediated inhibition of wound closure, addition of G3BP had no affect on this assay. These findings support of role for LOXL2 in eHsp90 stimulated cancer cell migration and provide preliminary evidence for the use of STA-12-7191 to inhibit eHsp90 to limit cancer invasion

  19. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK–NF-κB signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan; He, Yin-Yan; Lu, Wen; Liao, Yun [Department of Obstetrics and Gynecology, Shanghai First People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai (China); Gu, Wei, E-mail: krisgu70@163.com [Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai (China); Wan, Xiao-Ping, E-mail: wanxp@sjtu.edu.cn [Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital Affiliated to Tong Ji University, Shanghai (China)

    2014-03-28

    Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.

  20. Interleukin 6 promotes endometrial cancer growth through an autocrine feedback loop involving ERK–NF-κB signaling pathway

    International Nuclear Information System (INIS)

    Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In this study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma

  1. Quality of life is an important criterion for the efficiency of targeted therapy for metastatic skeletal involvement in breast cancer

    Directory of Open Access Journals (Sweden)

    T. Yu. Semiglazova

    2013-01-01

    Full Text Available Assessment of quality of life is an important, valid, informative, and cost-effective procedure for evaluating the efficiency of treatment in patients with breast cancer metastasizing to the bone, receiving therapy with bone-modifying agents, including targeted therapy with denosumab. The administration of denosumab significantly improves quality of life in patients with breast cancer metastasizing to the bone, by maintaining their general status, reducing the intensity of pain syndrome, and prevents osseous complications: pathological fractures, spinal cord compression, hypercalcemia, as well as the need for radiotherapy or surgery for bone metastases.

  2. Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient mice

    DEFF Research Database (Denmark)

    Lund, Anders H; Turner, Geoffrey; Trubetskoy, Alla; Verhoeven, Els; Wientjens, Ellen; Hulsman, Danielle; Russell, Robert; DePinho, Ronald A; Lenz, Jack; van Lohuizen, Maarten

    2002-01-01

    retroviral integration sites and mapped them against the mouse genome sequence databases from Celera and Ensembl. In addition to 17 insertions targeting gene loci known to be cancer-related, we identified a total of 37 new common insertion sites (CISs), of which 8 encode components of signaling pathways that...... that large-scale retroviral insertional mutagenesis in genetically predisposed mice is useful both as a system for identifying genes underlying cancer and as a genetic framework for the assignment of such genes to specific oncogenic pathways....

  3. Involving users in the design of a randomised controlled trial of an intervention to promote early presentation in breast cancer: qualitative study

    Directory of Open Access Journals (Sweden)

    Tompkins Charlotte

    2010-12-01

    Full Text Available Abstract Background The purpose of this study was to explore women's views of the design of a large pragmatic cost-effectiveness randomised controlled trial of the policy of offering a health professional-delivered intervention to promote early presentation with breast symptoms in older women and thereby improve survival, with a view to informing protocol development. The trial will recruit over 100,000 healthy women aged 67+, and outcome data will be collected on those who develop breast cancer. The scale of the trial and the need for long-term follow-up presented a number of design challenges in relation to obtaining consent, ascertaining and contacting participants who developed breast cancer, and collecting outcome data. Methods Qualitative study involving 69 women participating in 7 focus groups and 17 in-depth interviews. 15 women had a previous diagnosis of breast cancer and 54 did not. Results The women held strong views and had a good understanding of the rationale of the design of clinical trials. The women recognised that in a very large trial with long-term follow-up it was necessary to incorporate design features to make the trial feasible and efficient. Most strikingly, they supported the idea of opt-out consent and identifying women with breast cancer using routine datasets. Conclusions This model of user involvement engaged women well with the design challenges of the trial and led to improvements to the protocol. The study strengthens the case for user involvement, in particular through focus groups and in-depth interviews, in the design of trials.

  4. A retrospective analysis of the prognosis of prostate cancer patients with lymph node involvement on MR lymphography: who might be cured

    International Nuclear Information System (INIS)

    The prognosis of prostate cancer patients with lymph node metastases so small they can only be visualized by new imaging techniques as MR lymphography (MRL) is unknown. The purpose of this study was to investigate the prognosis of prostate cancer patients with non-enlarged metastatic lymph nodes on MRL and to identify a subgroup of MRL-positive patients who might be candidates for curative treatment. The charts of 138 prostate cancer patients without enlarged lymph nodes on CT, in whom a pre-treatment MRL was performed were reviewed. Endpoints were distant metastases-free survival and overall survival. Relation between the following factors and outcome were investigated: T-stage, PSA value at diagnosis, Gleason score, diameter (short axis and long axis) of the largest MRL-positive lymph node, number of MRL-positive lymph nodes, the presence of extra-pelvic nodal disease, and the extent of resection of the positive lymph nodes. Kaplan-Meier analysis was performed to estimate the survival functions. Of the 138 patients, 24 (17%) had a positive MRL. Patients with a short axis of the largest positive lymph node of ≤8 mm had a significantly better 5-year distant metastases-free (79% vs 16%) and overall survival (81% vs 36%) than patients with larger positive lymph nodes. This also accounted for patients with a largest long axis of ≤10 mm (71% vs 20% and 73% vs 40%, respectively). Outcome was also better in patients in whom all positive lymph nodes had been resected. A selection of MRL-positive patients with a good prognosis could be identified, consisting of patients with small positive lymph nodes. In these patients, cure might be pursued

  5. Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways.

    Science.gov (United States)

    Dhillon, Harsharan; Mamidi, Sujan; McClean, Phillip; Reindl, Katie M

    2016-06-01

    Piperlongumine (PL), an alkaloid obtained from long peppers, displays antitumorigenic properties for a variety of human cell- and animal-based models. The aim of this study was to identify the underlying molecular mechanisms for PL anticancer effects on human pancreatic cancer cells. RNA sequencing (RNA-seq) was used to identify the effects of PL on the transcriptome of MIA PaCa-2 human pancreatic cancer cells. PL treatment of pancreatic cancer cells resulted in differential expression of 683 mRNA transcripts with known protein functions, 351 of which were upregulated and 332 of which were downregulated compared to control-treated cells. Transcripts associated with oxidative stress, endoplasmic reticulum (ER) stress, and unfolded protein response pathways were significantly overexpressed with PL treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to validate the RNA-seq results, which included upregulation of HO-1, IRE1α, cytochrome c, and ASNS. The results provide key insight into the mechanisms by which PL alters cancer cell physiology and identify that activation of oxidative stress and ER stress pathways is a critical avenue for PL anticancer effects. PMID:27119744

  6. Mitochondrial and caspase pathways are involved in the induction of apoptosis by IB-MECA in ovarian cancer cell lines.

    Science.gov (United States)

    Abedi, Hamideh; Aghaei, Mahmoud; Panjehpour, Mojtaba; Hajiahmadi, Sima

    2014-11-01

    A3 adenosine receptor agonist (IB-MECA) has been shown to play important roles in cell proliferation and apoptosis in a variety of cancer cell lines. The present study was designed to understand the mechanism underlying IB-MECA-induced apoptosis in human ovarian cancer cell lines. The messenger RNA (mRNA) and protein expression levels of A3 adenosine receptor were detected in OVCAR-3 and Caov-4 ovarian cancer cells. IB-MECA was capable of decreasing intracellular cyclic adenosine monophosphate (cAMP) that was the reason for the presence of functional A3 adenosine receptor on the cell lines. IB-MECA significantly reduced cell viability in a dose-dependent manner. Cytotoxicity of IB-MECA was suppressed by MRS1220, an A3 adenosine receptor antagonist. The growth inhibition effect of IB-MECA was related to the induction of cell apoptosis, which was manifested by annexin V-FITC staining, activation of caspase-3 and caspase-9, and loss of mitochondrial membrane potentials (ΔΨm). In addition, downregulation of the regulatory protein Bcl-2 and upregulation of Bax protein by IB-MECA were also observed. These findings demonstrated that IB-MECA induces apoptosis via the mitochondrial signaling pathway. These suggest that A3 adenosine receptor agonists may be a potential agent for induction of apoptosis in human ovarian cancer cells. PMID:25095978

  7. Diagnostic accuracy of touch imprint and frozen section analysis in mediastinal lymph node involvement: lung cancer patients

    Directory of Open Access Journals (Sweden)

    Bannazadeh M

    2008-05-01

    Full Text Available Background: It is well known that, at the time of the initial presentation of patients with non-small cell lung cancer, N-status is very important in accurate staging and avoiding inappropriate surgical procedures. Also, if mediastinal lymph node metastasis (N2 of non-small cell lung cancer (stage IIIA is present, neoadjuvant (preoperative chemora-diotherapy is indicated; therefore a quick and accurate N-status determination is critical before thoracotomy. We compared the usefulness and accuracy of touch imprint and frozen section analysis for this purpose.Methods: During 2006, fifty eight mediastinal lymph node specimens from 27 patients with lung cancer were excised. After touch imprint preparation, half of each lymph node was sent for frozen section and finally permanent histology.Results: Frozen section and touch imprint had only one and two false negative results, respectively, but neither had false positive reports. The sensitivity, specificity and accuracy of the frozen section evaluation was 95.5%, 100% and 98.2%, respectively, and those of touch imprint were, 90.9%, 100% and 96.4%. The differences in the sensitivity, specificity and accuracy between the two methods were not significant (p>0.05.Conclusion: Frozen section and touch imprint have similarly high accuracies for detecting mediastinal lymph node metastasis in lung cancer. However, since the touch imprint method is more rapid and simple, it maybe method of choice.

  8. Growth inhibition and apoptosis in cancer cells induced by polyphenolic compounds of Acacia hydaspica: Involvement of multiple signal transduction pathways.

    Science.gov (United States)

    Afsar, Tayyaba; Trembley, Janeen H; Salomon, Christine E; Razak, Suhail; Khan, Muhammad Rashid; Ahmed, Khalil

    2016-01-01

    Acacia hydaspica R. Parker is known for its medicinal uses in multiple ailments. In this study, we performed bioassay-guided fractionation of cytotoxic compounds from A. hydaspica and investigated their effects on growth and signaling activity in prostate and breast cancer cell lines. Four active polyphenolic compounds were identified as 7-O-galloyl catechin (GC), catechin (C), methyl gallate (MG), and catechin-3-O-gallate (CG). The four compounds inhibited prostate cancer PC-3 cell growth in a dose-dependent manner, whereas CG and MG inhibited breast cancer MDA-MB-231 cell growth. All tested compounds inhibited cell survival and colony growth in both cell lines, and there was evidence of chromatin condensation, cell shrinkage and apoptotic bodies. Further, acridine orange, ethidium bromide, propidium iodide and DAPI staining demonstrated that cell death occurred partly via apoptosis in both PC-3 and MDA-MB-231 cells. In PC-3 cells treatment repressed the expression of anti-apoptotic molecules Bcl-2, Bcl-xL and survivin, coupled with down-regulation of signaling pathways AKT, NFκB, ERK1/2 and JAK/STAT. In MDA-MB-231 cells, treatment induced reduction of CK2α, Bcl-xL, survivin and xIAP protein expression along with suppression of NFκB, JAK/STAT and PI3K pathways. Our findings suggest that certain polyphenolic compounds derived from A. hydaspica may be promising chemopreventive/therapeutic candidates against cancer. PMID:26975752

  9. The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer.

    Science.gov (United States)

    Klenova, Elena M; Morse, Herbert C; Ohlsson, Rolf; Lobanenkov, Victor V

    2002-10-01

    CTCF is a ubiquitous 11 zinc finger (ZF) protein with highly versatile functions: in addition to transcriptional silencing or activating in a context-dependent fashion, it organizes epigenetically controlled chromatin insulators that regulate imprinted genes in soma. Recently, we have identified a CTCF paralogue, termed BORIS for Brother of the Regulator of Imprinted Sites, that is expressed only in the testis. BORIS has the same exons encoding the 11 ZF domain as mammalian CTCF genes, and hence interacts with similar cis elements, but encodes amino and carboxy termini distinct from those in CTCF. Normally, CTCF and BORIS are expressed in a mutually exclusive pattern that correlates with re-setting of methylation marks during male germ cell differentiation. The antagonistic features of these two gene siblings are underscored by showing that while CTCF overexpression blocks cell proliferation, expression of BORIS in normally BORIS-negative cells promotes cell growth which can lead to transformation. The suggestion that BORIS directs epigenetic reprogramming at CTCF target sites impinges on the observations that human BORIS is not only abnormally activated in a wide range of human cancers, but also maps to the cancer-associated amplification region at 20q13. The sibling rivalry occasioned by aberrant expression of BORIS in cancer may interfere with normal functions of CTCF including growth suppression, and contribute to epigenetic dysregulation which is a common feature in human cancer. PMID:12191639

  10. Measurement equivalence of the Patient Reported Outcomes Measurement Information System® (PROMIS® Pain Interference short form items: Application to ethnically diverse cancer and palliative care populations

    Directory of Open Access Journals (Sweden)

    Jeanne A. Teresi

    2016-06-01

    Full Text Available Reducing the response burden of standardized pain measures is desirable, particularly for individuals who are frail or live with chronic illness, e.g., those suffering from cancer and those in palliative care. The Patient Reported Outcome Measurement Information System® (PROMIS® project addressed this issue with the provision of computerized adaptive tests (CAT and short form measures that can be used clinically and in research. Although there has been substantial evaluation of PROMIS item banks, little is known about the performance of PROMIS short forms, particularly in ethnically diverse groups. Reviewed in this article are findings related to the differential item functioning (DIF and reliability of the PROMIS pain interference short forms across diverse socio-demographic groups. Methods: DIF hypotheses were generated for the PROMIS short form pain interference items. Initial analyses tested item response theory (IRT model assumptions of unidimensionality and local independence. Dimensionality was evaluated using factor analytic methods; local dependence (LD was tested using IRT-based LD indices. Wald tests were used to examine group differences in IRT parameters, and to test DIF hypotheses. A second DIF-detection method used in sensitivity analyses was based on ordinal logistic regression with a latent IRT-derived conditioning variable. Magnitude and impact of DIF were investigated, and reliability and item and scale information statistics were estimated. Results: The reliability of the short form item set was excellent. However, there were a few items with high local dependency, which affected the estimation of the final discrimination parameters. As a result, the item, “How much did pain interfere with enjoyment of social activities?” was excluded in the DIF analyses for all subgroup comparisons. No items were hypothesized to show DIF for race and ethnicity; however, five items showed DIF after adjustment for multiple comparisons in

  11. The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells and increases the short term effects of ionizing radiation

    International Nuclear Information System (INIS)

    The phosphatidylinositol-3-kinase (PI3K)/Akt pathway is frequently deregulated in prostate cancer and associated with neoplastic transformation, malignant progression, and enhanced resistance to classical chemotherapy and radiotherapy. Thus, it is a promising target for therapeutic intervention. In the present study, the cytotoxic action of the Akt inhibitor Erufosine (ErPC3) was analyzed in prostate cancer cells and compared to the cytotoxicity of the PI3K inhibitor LY294002. Moreover, the efficacy of combined treatment with Akt inhibitors and ionizing radiation in prostate cancer cells was examined. Prostate cancer cell lines PC3, DU145, and LNCaP were treated with ErPC3 (1-100 µM), LY294002 (25-100 µM), irradiated (0-10 Gy), or subjected to combined treatments. Cell viability was determined by the WST-1 assay. Apoptosis induction was analyzed by flow cytometry after staining with propidium iodide in a hypotonic citrate buffer, and by Western blotting using antibodies against caspase-3 and its substrate PARP. Akt activity and regulation of the expression of Bcl-2 family members and key downstream effectors involved in apoptosis regulation were examined by Western blot analysis. The Akt inhibitor ErPC3 exerted anti-neoplastic effects in prostate cancer cells, however with different potency. The anti-neoplastic action of ErPC3 was associated with reduced phosphoserine 473-Akt levels and induction of apoptosis. PC3 and LNCaP prostate cancer cells were also sensitive to treatment with the PI3K inhibitor LY294002. However, the ErPC3-sensitive PC3-cells were less susceptible to LY294002 than the ErPC3-refractory LNCaP cells. Although both cell lines were largely resistant to radiation-induced apoptosis, both cell lines showed higher levels of apoptotic cell death when ErPC3 was combined with radiotherapy. Our data suggest that constitutive Akt activation and survival are controlled by different different molecular mechanisms in the two prostate cancer cell lines

  12. Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society

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    Loy Volker

    2009-02-01

    Full Text Available Abstract Background The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC dramatically. But a major achievement has been the development of total mesorectal excision (TME as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy, initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT was better than postoperative radiochemotherapy in terms of local control. Methods and design Patients with histological proven rectal cancer staged T2N+ or T3 are randomized to receive either SCRT (25 Gy in five fractions of 5 Gy plus TME-surgery within 5 days or RCT (50.4 Gy in 28 fractions of 1.8 Gy, continuous infusion 5-fluorouracil plus TME-surgery 4–6 weeks later. All patients receive adjuvant chemotherapy (12 weeks continuous infusional 5-FU and are followed up for 5 years. TME-quality is independently documented by the surgeon and the pathologist. Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years. Secondary endpoints are overall survival, disease-free survival, complete resection rate (R0 resection, rate of sphincter saving resection, acute and late toxicity (radiation related side effects, and quality of life (including long term bowel function. Discussion Similar long-term survival, local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies. In addition to other ongoing (and recently published comparative trials

  13. Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE2 pathways in human M4Beu melanoma cancer cells.

    Science.gov (United States)

    Hassan, Lama; Pinon, Aline; Limami, Youness; Seeman, Josiane; Fidanzi-Dugas, Chloe; Martin, Frederique; Badran, Bassam; Simon, Alain; Liagre, Bertrand

    2016-07-01

    Melanoma is one of the most aggressive forms of cancer with a continuously growing incidence worldwide and is usually resistant to chemotherapy agents, which is due in part to a strong resistance to apoptosis. Previously, we had showed that B16-F0 murine melanoma cells undergoing apoptosis are able to delay their own death induced by ursolic acid (UA), a natural pentacyclic triterpenoid compound. We had demonstrated that tyrosinase and TRP-1 up-regulation in apoptotic cells and the subsequent production of melanin were implicated in an apoptosis resistance mechanism. Several resistance mechanisms to apoptosis have been characterized in melanoma such as hyperactivation of DNA repair mechanisms, drug efflux systems, and reinforcement of survival signals (PI3K/Akt, NF-κB and Raf/MAPK pathways). Otherwise, other mechanisms of apoptosis resistance involving different proteins, such as cyclooxygenase-2 (COX-2), have been described in many cancer types. By using a strategy of specific inhibition of each ways, we suggested that there was an interaction between melanogenesis and COX-2/PGE2 pathway. This was characterized by analyzing the COX-2 expression and activity, the expression of tyrosinase and melanin production. Furthermore, we showed that anti-proliferative and proapoptotic effects of UA were mediated through modulation of multiple signaling pathways including Akt and ERK-1/2 proteins. Our study not only uncovers underlying molecular mechanisms of UA action in human melanoma cancer cells but also suggest its great potential as an adjuvant in treatment and cancer prevention. PMID:27262506

  14. Butanol-Partitioned Extraction from Aqueous Extract of Gracilaria tenuistipitata Inhibits Cell Proliferation of Oral Cancer Cells Involving Apoptosis and Oxidative Stress.

    Science.gov (United States)

    Yeh, Chi-Chen; Li, Kun-Tzu; Tang, Jen-Yang; Wang, Hui-Ru; Liu, Jing-Ru; Huang, Hurng-Wern; Chang, Fang-Rong; Tsai, Cheng-En; Lo, I-Wen; Huang, Ming-Yii; Chang, Hsueh-Wei

    2016-05-01

    We have previously found that the aqueous extract of Gracilaria tenuistipitata (AEGT) and its partitioned fractions had antioxidant properties in biochemical assays. Although the butanol-partitioned fraction of AEGT (AEGT-pBuOH) had a stronger antioxidant performance than AEGT, its biological effects are still unknown. In this study, the cellular responses of oral cancer cells to AEGT-pBuOH were monitored in terms of cell viability, cell cycle progression, apoptosis, and oxidative stress responses. In an ATP content assay, the cell viability of oral cancer cells treated with AEGT-pBuOH was dose responsively inhibited (p < 0.005). For flow cytometry, AEGT-pBuOH was also found to dose responsively induce cell cycle disturbance by propidium iodide (PI) staining and to induce apoptosis by annexin V/PI and pan-caspase staining (p < 0.005). In AEGT-pBuOH-treated oral cancer cells, the reactive oxygen species (ROS) was increased and mitochondrial membrane potential was decreased in a dose-response manner (p < 0.005). These results suggest that AEGT-pBuOH inhibited the proliferation and induced apoptosis of oral cancer cells involving the ROS generation and mitochondrial depolarization. PMID:27138906

  15. Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g

    International Nuclear Information System (INIS)

    Background and purpose: Preoperative chemoradiotherapy (CRT) represents the standard treatment for locally advanced rectal cancer. Tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this diversity. Material and methods: Genome-wide microRNA (miRNA) profiling was performed for 12 colorectal cancer (CRC) cell lines and an individual in vitro signature of chemoradiosensitivity was established. Functional relevance of selected miRNAs was established by transfecting miRNA-mimics into SW480 and SW837 cells. The prognostic value of selected miRNAs was assessed in 128 pretherapeutic patient biopsies. Results: Thirty-six miRNAs were identified to significantly correlate with sensitivity to CRT (Q < 0.05) including miR-320a and other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Transfection of selected miRNAs (let-7g, miR-132, miR-224, miR-320a) each induced a shift of sensitivity. High expression of let-7g was associated with a good prognosis in rectal cancer patients (P = 0.03). Conclusions: This is the first report of a miRNA expression signature for in vitro chemoradiosensitivity of CRC cell lines. Many of the identified miRNAs have not been linked to the response to CRT and may represent potential molecular targets to sensitize resistant cancers. If further validated, let7g expression may serve as predictive biomarker

  16. Measurement of DNA Double-Strand Break Yield in Human Cancer Cells by High-Current, Short-Duration Bunches of Laser-Accelerated Protons

    Science.gov (United States)

    Yogo, Akifumi; Sato, Katsutoshi; Nishikino, Masaharu; Maeda, Takuya; Sakaki, Hironao; Hori, Toshihiko; Ogura, Koichi; Nishiuchi, Mamiko; Teshima, Teruki; Nishimura, Hiroaki; Kondo, Kiminori; Bolton, Paul R.; Kawanishi, Shunichi

    2011-10-01

    To investigate the radiobiological effects of high dose rates that are attributed to high current, short bunch beam generation with laser-dreven ion acceleration, we have developed an experimental setup that uses laser-accelerated protons. In-vitro human lung cancer cells: A549 pulmonary adenocarcinoma are irradiated with a laser-accelerated proton bunches with a duration of 2×10-8 s and flux of ˜1015 cm-2 s-1, amounting to single bunch absorbed dose at the 1 Gy level. The double-strand break (DSB) yield in cell DNA is analyzed for the laser-accelerated proton beam at an average LET of 41 keV/µm.

  17. Multifunctional gold nanorods for selective plasmonic photothermal therapy in pancreatic cancer cells using ultra-short pulse near-infrared laser irradiation

    Science.gov (United States)

    Patino, Tania; Mahajan, Ujjwal; Palankar, Raghavendra; Medvedev, Nikolay; Walowski, Jakob; Münzenberg, Markus; Mayerle, Julia; Delcea, Mihaela

    2015-03-01

    Gold nanorods (AuNRs) have attracted considerable attention in plasmonic photothermal therapy for cancer treatment by exploiting their selective and localized heating effect due to their unique photophysical properties. Here we describe a strategy to design a novel multifunctional platform based on AuNRs to: (i) specifically target the adenocarcinoma MUC-1 marker through the use of the EPPT-1 peptide, (ii) enhance cellular uptake through a myristoylated polyarginine peptide (MPAP) and (iii) selectively induce cell death by ultra-short near infrared laser pulses. We used a biotin-avidin based approach to conjugate EPPT-1 and MPAP to AuNRs. Dual-peptide (EPPT-1 + MPAP) labelled AuNRs showed a significantly higher uptake by pancreatic ductal adenocarcinoma cells when compared to their single peptide or avidin conjugated counterparts. In addition, we selectively induced cell death by ultra-short near infrared laser pulses in small target volumes (~1 μm3), through the creation of plasmonic nanobubbles that lead to the destruction of a local cell environment. Our approach opens new avenues for conjugation of multiple ligands on AuNRs targeting cancer cells and tumors and it is relevant for plasmonic photothermal therapy.Gold nanorods (AuNRs) have attracted considerable attention in plasmonic photothermal therapy for cancer treatment by exploiting their selective and localized heating effect due to their unique photophysical properties. Here we describe a strategy to design a novel multifunctional platform based on AuNRs to: (i) specifically target the adenocarcinoma MUC-1 marker through the use of the EPPT-1 peptide, (ii) enhance cellular uptake through a myristoylated polyarginine peptide (MPAP) and (iii) selectively induce cell death by ultra-short near infrared laser pulses. We used a biotin-avidin based approach to conjugate EPPT-1 and MPAP to AuNRs. Dual-peptide (EPPT-1 + MPAP) labelled AuNRs showed a significantly higher uptake by pancreatic ductal adenocarcinoma

  18. Laparoscopic surgery for patients with colorectal cancer produces better short-term outcomes with similar survival outcomes in elderly patients compared to open surgery.

    Science.gov (United States)

    Moon, Soo Yun; Kim, Sohee; Lee, Soo Young; Han, Eon Chul; Kang, Sung-Bum; Jeong, Seung-Yong; Park, Kyu Joo; Oh, Jae Hwan

    2016-06-01

    The number of operations on elderly colorectal cancer (CRC) patients has increased with the aging of the population. The aim of this study was to evaluate surgical outcomes in elderly patients who underwent laparoscopic or open surgery for CRC. We analyzed the data of 280 patients aged 80 or over who underwent surgery for CRC between January 2001 and December 2010. Seventy-one pairs were selected after propensity score matching for laparoscopic or open surgery. Operative time, return to normal bowel function, length of hospital stay, postoperative complications, overall survival (OS), recurrence-free survival (RFS), and prognostic factors affecting survival were investigated. In matched cohorts, operative time in the laparoscopic group was longer than in the open group (P surgery for CRC in elderly patients may be safe and feasible, with better short-term outcomes. OS and RFS, however, were not different in both groups. PMID:26923309

  19. Mesenteric ischemia after capecitabine treatment in rectal cancer and resultant short bowel syndrome is not an absolute contraindication for radical oncological treatment

    Directory of Open Access Journals (Sweden)

    Perpar Ana

    2015-06-01

    Full Text Available Background. Thrombotic events, arterial or venous in origin, still remain a source of substantial morbidity and mortality in cancer patients. The propensity for their development in oncology patients is partially a consequence of the disease itself and partially a result of our attempts to treat it. One of the rarest and deadliest thromboembolic complications is arterial mesenteric ischemia. The high mortality rate is caused by its rarity and by its non-specific clinical presentation, both of which make early diagnosis and treatment difficult. Hence, most diagnoses and treatments occur late in the course of the disease. The issue survivors of arterial mesenteric ischemia may face is short bowel syndrome, which has become a chronic condition after the introduction of parenteral nutrition at home.

  20. Design, synthesis, and anti-breast cancer evaluation of new triarylethylene analogs bearing short alkyl- and polar amino-/amido-ethyl chains.

    Science.gov (United States)

    Kaur, Gurleen; Mahajan, Mohinder P; Pandey, Manoj K; Singh, Parvesh; Ramisetti, Srinivasa R; Sharma, Arun K

    2016-04-15

    The synthesis of novel triarylethylene analogs, designed based on well-known Selective Estrogen Receptor Modulators (SERMs), i.e., ospemifene and tamoxifen, as potential anti-breast cancer agents is described. The cytotoxic potential of these analogs against ER-positive (MCF-7) and ER-negative (MDA-MB-231) human breast cancer cell lines was determined and compared with the standards, ospemifene and tamoxifen. In initial screening, analogs 5, 14 and 15 were found to be much more effective than the standards against both the cell lines. The results showed that these novel analogs inhibit the expression of proteins involved in the migration and metastasis, compound 5 being most effective. Compound 5 inhibited the expression of MMP-9, c-Myc and Caveolin in both MCF-7 and MDA-MB-231 cells, and suppressed the invasion of ER-negative cells in a dose dependent manner. Finally, in silico docking simulations of the representative compounds in the binding sites of the estrogen receptors (ERs) indicated a good binding affinity of the compounds with the ERs, and supported their experimental toxicity against MCF-7 cancer cell lines. PMID:26972118

  1. Effect of short message service as a reminder on breast self-examination in breast cancer patients: a randomized controlled trial.

    Science.gov (United States)

    Chung, Il Yong; Kang, Eunyoung; Yom, Cha Kyong; Kim, Dongwon; Sun, Young; Hwang, Yoonsun; Jang, Jin Youn; Kim, Sung-Won

    2015-04-01

    This study was a single-blind randomized controlled trial to assess the effectiveness of SMS as a reminder for breast self-examination (BSE). Participants who underwent surgery for breast cancer were recruited and randomized to the intervention group or the control group. Subjects in the intervention group received one text message on the first day of every month that reminded them to complete monthly BSE and the other text message on the fifteenth day of every month that contained information about breast cancer. Primary and secondary outcomes were self-reported BSE adherence and the frequency of BSE over 6 months. Between August 2010 and December 2011, 216 patients were randomly assigned to the SMS group (n = 110) or the control group (n = 106). A total of 202 patients were included in the final analysis. Self-reported BSE adherence and the frequency of BSE over the past six months were significantly higher in the intervention group than in the control group. Multivariate analysis showed that the SMS was the only significant factor for BSE adherence (p < 0.001). The short-term results of our study suggest that SMS is an effective and low-cost method to enhance adherence to BSE with existing information technology infrastructure. PMID:25697492

  2. Clinical aspects of intraoperative radiotherapy in early breast cancer: short-term complications after IORT in women treated with low energy x-rays

    International Nuclear Information System (INIS)

    To assess postoperative complications, clinical outcome and histological findings in patients undergoing intraoperative radiotherapy with low energy x-rays for early breast cancer. We retrospectively analysed data of 208 women who underwent intraoperative irradiation during breast conserving surgery (BCS) between 2002 and 2007. Demographic, clinical and surgical parameters as well as short-term complications within the first postoperative week and histological findings were evaluated. Toxicities were assessed using the CTC/EORTC Score. Postoperative complications were rare and the immediate toxicity low, without any grade 3/4 acute toxicity. The most frequent postoperative side effects were suggillation (24%) and palpable seroma (17.3%). In 78.6% of the axillary seroma and in 25% of the breast seroma a needle aspiration was inevitable. Erythema grade I-II of the breast was found in 27 women (13%); whereas in 7 patients (3.4%), mastitis was confirmed. In 57.7% of the cases, the pathological assessment revealed ductal invasive breast cancer and tumour size ranged between 0.1 and 4.5 cm (mean = 1.6 cm). IORT using Intrabeam® during BCS is safe, although it is associated with postoperative adverse events such as seroma. These should be mentioned and explained to women in detail during the preoperative discussion. This explicitly clinical description is useful for daily clinical practice; especially for giving a detailed analysis of the postoperative side effects during preoperative counselling

  3. Involvement of CUL4A in Regulation of Multidrug Resistance to P-gp Substrate Drugs in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yunshan Wang

    2013-12-01

    Full Text Available CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described in this report we aimed to clarify whether CUL4A participates in multiple drug resistance (MDR in breast cancer cells. We first transfected vectors carrying CUL4A and specific shCUL4A into breast cancer cells and corresponding Adr cells respectively. Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1/P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays. On the other hand, silencing CUL4A in MCF7/Adr and MDA-MB-468/Adr cells led to the opposite effect. Moreover, ERK1/2 in CUL4A-overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A-induced expression of MDR1/P-gp was decreased significantly. Lastly, immunohistochemistry in breast cancer tissues showed that P-gp expression had a positive correlation with the expression of CUL4A and ERK1/2. Thus, these results implied that CUL4A and ERK1/2 participated in multi-drug resistance in breast cancer through regulation of MDR1/P-gp expression.

  4. The mitochondrial pathway is involved in American ginseng-induced apoptosis of SW-480 colon cancer cells

    OpenAIRE

    Wang, Chong-Zhi; Li, Xiao-Li; Wang, Qian-fei; MEHENDALE, SANGEETA R.; FISHBEIN, ANNA B.; HAN, AUNG H.; SUN, SHI; Yuan, Chun-Su

    2009-01-01

    Numerous effective anticancer drugs have been developed from botanical sources, and there remains a significant untapped resource in herbal medicines. In this study, we evaluated the chemical composition of extracts from American ginseng after steaming, the antiproliferative effects of the ginsenosides in the extracts on SW-480 human colorectal cancer cells, and their apoptotic mechanisms. American ginseng roots were steamed at 120°C for 2 or 4 h. Representative ginsenosides in the unsteamed ...

  5. Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation.

    Science.gov (United States)

    Kim, Hyun Ji; Kang, Gyeoung Jin; Kim, Eun Ji; Park, Mi Kyung; Byun, Hyun Jung; Nam, Seungyoon; Lee, Ho; Lee, Chang Hoon

    2016-09-01

    Sphingosylphosphorylcholine (SPC) participates in several cellular processes including metastasis. SPC induces keratin reorganization and regulates the viscoelasticity of metastatic cancer cells including PANC-1 cancer cells leading to enhanced migration and invasion. The role of SPC and the relevant mechanism in invasion of breast cell are as yet unknown. SPC dose-dependently induces invasion of breast cancer cells or breast immortalized cells. Reverse transcription polymerase chain reaction and Western blot analyses of MCF10A and ZR-75-1 cells indicated that SPC induces expression and secretion of matrix metalloproteinase-3 (MMP3). From online KMPLOT, relapse free survival is high in patients having low MMP3 expressed basal breast cancer (n=581, p=0.032). UK370106 (MMP3 inhibitor) or gene silencing of MMP3 markedly inhibited the SPC-induced invasion of MCF10A cells. An extracellular signal-regulated kinase (ERK) inhibitor, PD98059, significantly suppressed the secretion and the gelatinolytic activity of MMP3, and invasion in MCF10A cells. Over-expression of ERK1 and ERK2 promoted both the expression and secretion of MMP3. In contrast, gene silencing of ERK1 and ERK2 attenuated the secretion of MMP3 in MCF10A cells. The effects of SPC-induced MMP3 secretion on β-catenin and TCF/lymphoid enhancer factor (LEF) promoter activity were examined since MMP3 indirectly activates canonical Wnt signaling. SPC induced translocation of β-catenin to nucleus and increased TCF/LEF promoter activity. These events were suppressed by UK370106 or PD98059. Wnt inhibitor, FH535 inhibited SPC-induced MMP3 secretion and invasion. Taken together, these results suggest that SPC induces MMP3 expression and secretion via ERK leading to Wnt activation. PMID:27216977

  6. Primary and secondary malignant involvement of gynaecological organs at radical cystectomy for bladder cancer: review of literature and retrospective analysis of 360 cases.

    Science.gov (United States)

    Salem, H; El-Mazny, A

    2012-08-01

    The pathological analysis of cystectomy specimens from 360 female patients who underwent radical cystectomy for bladder cancer was retrospectively reported. The uterus was not available in 29 specimens, while one ovary was absent in 18 specimens and the two ovaries were absent in 20 specimens. Uterine involvement was observed in one case of transitional cell carcinoma, and benign uterine pathology was detected in 37 cases. All patients had normal ovaries, while the vagina was involved in 13 cases. A total of 12% of the patients had urethral involvement. None of the 29 patients, in whom the internal genitalia were totally or partially preserved, had late ovarian, vaginal or uterine recurrence at the last follow-up. Thus, the preservation of female internal genitalia in young patients undergoing radical cystectomy should be considered under strict criteria (low-grade, low-stage tumours away from the bladder neck). This will improve the quality-of-life (QoL) and the functional outcome without compromising cancer control. PMID:22779969

  7. Nodes-and-connections RNAi knockdown screening: identification of a signaling molecule network involved in fulvestrant action and breast cancer prognosis.

    Science.gov (United States)

    Miyoshi, N; Wittner, B S; Shioda, K; Hitora, T; Ito, T; Ramaswamy, S; Isselbacher, K J; Sgroi, D C; Shioda, T

    2015-01-01

    Although RNA interference (RNAi) knockdown screening of cancer cell cultures is an effective approach to predict drug targets or therapeutic/prognostic biomarkers, interactions among identified targets often remain obscure. Here, we introduce the nodes-and-connections RNAi knockdown screening that generates a map of target interactions through systematic iterations of in silico prediction of targets and their experimental validation. An initial RNAi knockdown screening of MCF-7 human breast cancer cells targeting 6560 proteins identified four signaling molecules required for their fulvestrant-induced apoptosis. Signaling molecules physically or functionally interacting with these four primary node targets were computationally predicted and experimentally validated, resulting in identification of four second-generation nodes. Three rounds of further iterations of the prediction-validation cycle generated third, fourth and fifth generation of nodes, completing a 19-node interaction map that contained three predicted nodes but without experimental validation because of technical limitations. The interaction map involved all three members of the death-associated protein kinases (DAPKs) as well as their upstream and downstream signaling molecules (calmodulins and myosin light chain kinases), suggesting that DAPKs play critical roles in the cytocidal action of fulvestrant. The in silico Kaplan-Meier analysis of previously reported human breast cancer cohorts demonstrated significant prognostic predictive power for five of the experimentally validated nodes and for three of the prediction-only nodes. Immunohistochemical studies on the expression of 10 nodal proteins in human breast cancer tissues not only supported their prognostic prediction power but also provided statistically significant evidence of their synchronized expression, implying functional interactions among these nodal proteins. Thus, the Nodes-and-Connections approach to RNAi knockdown screening yields

  8. Dimethoxycurcumin, a metabolically stable analogue of curcumin enhances the radiosensitivity of cancer cells: Possible involvement of ROS and thioredoxin reductase.

    Science.gov (United States)

    Jayakumar, Sundarraj; Patwardhan, R S; Pal, Debojyoti; Sharma, Deepak; Sandur, Santosh K

    2016-09-01

    Dimethoxycurcumin (DIMC), a structural analogue of curcumin, has been shown to have more stability, bioavailability, and effectiveness than its parent molecule curcumin. In this paper the radiosensitizing effect of DIMC has been investigated in A549 lung cancer cells. As compared to its parent molecule curcumin, DIMC showed a very potent radiosensitizing effect as seen by clonogenic survival assay. DIMC in combination with radiation significantly increased the apoptosis and mitotic death in A549 cells. This combinatorial treatment also lead to effective elimination of cancer stem cells. Further, there was a significant increase in cellular ROS, decrease in GSH to GSSG ratio and also significant slowdown in DNA repair when DIMC was combined with radiation. In silico docking studies and in vitro studies showed inhibition of thioredoxin reductase enzyme by DIMC. Overexpression of thioredoxin lead to the abrogation of radiosensitizing effect of DIMC underscoring the role of thioredoxin reductase in radiosensitization. Our results clearly demonstrate that DIMC can synergistically enhance the cancer cell killing when combined with radiation by targeting thioredoxin system. PMID:27381867

  9. Pharmacologic regulation of AMPK in breast cancer affects cytoskeletal properties involved with microtentacle formation and re-attachment.

    Science.gov (United States)

    Chakrabarti, Kristi R; Whipple, Rebecca A; Boggs, Amanda E; Hessler, Lindsay K; Bhandary, Lekhana; Vitolo, Michele I; Thompson, Keyata; Martin, Stuart S

    2015-11-01

    The presence of tumor cells in the circulation is associated with a higher risk of metastasis in patients with breast cancer. Circulating breast tumor cells use tubulin-based structures known as microtentacles (McTNs) to re-attach to endothelial cells and arrest in distant organs. McTN formation is dependent on the opposing cytoskeletal forces of stable microtubules and the actin network. AMP-activated protein kinase (AMPK) is a cellular metabolic regulator that can alter actin and microtubule organization in epithelial cells. We report that AMPK can regulate the cytoskeleton of breast cancer cells in both attached and suspended conditions. We tested the effects of AMPK on microtubule stability and the actin-severing protein, cofilin. AMPK inhibition with compound c increased both microtubule stability and cofilin activation, which also resulted in higher McTN formation and re-attachment. Conversely, AMPK activation with A-769662 decreased microtubule stability and cofilin activation with concurrent decreases in McTN formation and cell re-attachment. This data shows for the first time that AMPK shifts the balance of cytoskeletal forces in suspended breast cancer cells, which affect their ability to form McTNs and re-attach. These results support a model where AMPK activators may be used therapeutically to reduce the metastatic efficiency of breast tumor cells. PMID:26431377

  10. Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells

    International Nuclear Information System (INIS)

    Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines. Affymetrix datasets about metastasis and/or hypoxia were downloaded from GEO and ArrayExpress. AffyProbeMiner and GCRMA packages were used for pre-processing and the Window Welch t test was used for processing. Three approaches of meta-analysis were eventually used for the selection of genes of interest. Three complementary approaches were used, that eventually selected 183 genes of interest. Out of these 183 genes, 99, among which the well known JUNB, FOS and TP63, have already been described in the literature to be involved in cancer. Moreover, 39 genes of those, such as SERPINE1 and MMP7, are known to regulate metastasis. Twenty-one genes including VEGFA and ID2 have also been described to be involved in the response to hypoxia. Lastly, DAVID classified those 183 genes in 24 different pathways, among which 8 are directly related to cancer while 5 others are related to proliferation and cell motility. A negative control composed of 183 random genes failed to provide such results. Interestingly, 6 pathways retrieved by DAVID with the 183 genes of interest concern pathogen recognition and phagocytosis. The proposed methodology was able to find genes actually known to be involved in cancer, metastasis and hypoxia and, thus, we propose that the other genes selected based on the same methodology are of prime interest in

  11. Involvement of tumor necrosis factor-α in the upregulation of CXCR4 expression in gastric cancer induced by Helicobacter pylori

    International Nuclear Information System (INIS)

    H. pylori, whose infection increases tumor invasiveness and metastasis, is generally labelled as the strongest risk factor for the development of gastric cancer. It appears not to be a coincidence that there is also an overexpression of CXCR4 and an obvious involvement in gastric cancer metastasis. The aim of this study attempts to investigate and further to establish a link between them. With H. pylori being a potent inducer of TNF-α, whether TNF-α, a tumor promoter, is involved in the induction of CXCR4 expression by H. pylori was also under research in this study. Expression of CXCR4, TNF-α, IL-6 and IL-1β mRNA was determined by real-time PCR. CXCR4 protein expression was detected by Western blotting. Concentrations of TNF-α, IL-6 and IL-1β in cell culture supernatants were measured using the Quantikine Elisa kit. To abrogate TNF-α expression in HGC27 cells, TNF-α RNAi plasmid was used to transfect them. Levels of CXCR4 and TNF-α mRNA were significantly higher in H. pylori-positive gastric cancers (n = 19) compared to H. pylori-negative ones (n = 15). A subsequently Spearman's rank correlation test showed there was a positive correlation between the level of CXCR4 mRNA and that of TNF-α in 34 primary gastric cancers. Other results followed: Expression of CXCR4 and TNF-α was upregulated in gastric cancer cell MKN45 and HGC27 after infection with H. pylori 26695 (cag PAI+ ) or Tx30a (cag PAI- ); The induction of CXCR4 expression by H. pylori was inhibited significantly by a neutralizing TNF-α antibody, infliximab; CXCR4 expression was upregulated in MKN45 cells after treatment with exogenous TNF-α or co-culture with macrophage, and was downregulated in HGC27 cells after transfection with TNF-α RNAi plasmid. There was a significant increase in the migration of MKN45 cells treated with H. pylori 26695, and a strong inhibition when AMD 3100, a CXCR4 antagonist, or infliximab, was added. Our findings demonstrated that H. pylori upregulates CXCR4

  12. Involvement of ROS-p38-H2AX axis in novel curcumin analogues-induced apoptosis in breast cancer cells.

    Science.gov (United States)

    Dong, Yinhui; Yin, Shutao; Song, Xinhua; Huo, Yazhen; Fan, Lihong; Ye, Min; Hu, Hongbo

    2016-04-01

    Curcumin-based structural modification for developing more effective curcumin analogues has been drawning increasing attention. As alternative approach, using LC/MS guided purification, we previously obtained a series of novel natural terpene-conjugated curcuminoids from turmeric, and some of them exhibited even more potent anti-cancer activity against multiple types of cancer cells than curcumin. The purpose of this follow-up study was designed to decipher the mechanisms involved in anti-cancer activity of these novel curcumin analogues. Apoptosis was evaluated using sub-G1 analysis by flow cytometry and Cell Death ELISA Kit. Changes of protein expression were analyzed by western blotting. RNA interference was employed to inhibit expression of specific protein. We found that bisabolocurcumin ether (T1) and demethoxybisabolocurcumin ether (T2) were able to trigger much stronger apoptosis induction in multiple types of cancer cells than curcumin, which was attributed to persistent and stronger ROS generation. ROS induction by T1 resulted in activation of p38/H2AX axis and p53. Inhibition of p38/H2AX led to a significant reduction of apoptosis, whereas inactivation of p53 caused a dramatically enhanced H2AX phosphorylation and apoptosis induction, suggesting activation of p38/H2AX contributed to apoptosis induction by T1, whereas p53 activation protected novel curcumins-induced apoptosis via suppression of H2AX activation. Our findings provide mechanistic support for the potential use of terpene-conjugated curcuminoids as a novel class of cancer chemopreventive agents. © 2015 Wiley Periodicals, Inc. PMID:25647442

  13. Short-Course Treatment With Gefitinib Enhances Curative Potential of Radiation Therapy in a Mouse Model of Human Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the combination of radiation and an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in preclinical models of human non-small cell lung cancer. Methods and Materials: Sensitivity to an EGFR TKI (gefitinib) or radiation was assessed using proliferation assays and clonogenic survival assays. Effects on receptor signal transduction pathways (pEGFR, pAKT, pMAPK) and apoptosis (percentage of cleaved PARP Poly (ADP-ribose) polymerase (PARP)) were assessed by Western blotting. Radiation-induced DNA damage was assessed by γH2AX immunofluorescence. Established (≥100 mm3) EGFR-mutated (HCC287) or EGFR wild-type (A549) subcutaneous xenografts were treated with radiation (10 Gy, day 1) or gefitinib (50 mg/kg, orally, on days 1-3) or both. Results: In non-small cell lung cancer (NSCLC) cell lines with activating EGFR mutations (PC9 or HCC827), gefitinib treatment markedly reduced pEGFR, pAKT, and pMAPK levels and was associated with an increase in cleaved PARP but not in γH2AX foci. Radiation treatment increased the mean number of γH2AX foci per cell but did not significantly affect EGFR signaling. In contrast, NSCLC cell lines with EGFR T790M (H1975) or wild-type EGFR (A549) were insensitive to gefitinib treatment. The combination of gefitinib and radiation treatment in cell culture produced additive cell killing with no evidence of synergy. In xenograft models, a short course of gefitinib (3 days) did not significantly increase the activity of radiation treatment in wild-type EGFR (A549) tumors (P=.27), whereas this combination markedly increased the activity of radiation (P<.001) or gefitinib alone (P=.002) in EGFR-mutated HCC827 tumors, producing sustained tumor regressions. Conclusions: Gefitinib treatment increases clonogenic cell killing by radiation but only in cell lines sensitive to gefitinib alone. Our data suggest additive rather than synergistic interactions between gefitinib and radiation and that a combination

  14. Short-Course Treatment With Gefitinib Enhances Curative Potential of Radiation Therapy in a Mouse Model of Human Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bokobza, Sivan M.; Jiang, Yanyan; Weber, Anika M.; Devery, Aoife M.; Ryan, Anderson J., E-mail: anderson.ryan@oncology.ox.ac.uk

    2014-03-15

    Purpose: To evaluate the combination of radiation and an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in preclinical models of human non-small cell lung cancer. Methods and Materials: Sensitivity to an EGFR TKI (gefitinib) or radiation was assessed using proliferation assays and clonogenic survival assays. Effects on receptor signal transduction pathways (pEGFR, pAKT, pMAPK) and apoptosis (percentage of cleaved PARP Poly (ADP-ribose) polymerase (PARP)) were assessed by Western blotting. Radiation-induced DNA damage was assessed by γH2AX immunofluorescence. Established (≥100 mm{sup 3}) EGFR-mutated (HCC287) or EGFR wild-type (A549) subcutaneous xenografts were treated with radiation (10 Gy, day 1) or gefitinib (50 mg/kg, orally, on days 1-3) or both. Results: In non-small cell lung cancer (NSCLC) cell lines with activating EGFR mutations (PC9 or HCC827), gefitinib treatment markedly reduced pEGFR, pAKT, and pMAPK levels and was associated with an increase in cleaved PARP but not in γH2AX foci. Radiation treatment increased the mean number of γH2AX foci per cell but did not significantly affect EGFR signaling. In contrast, NSCLC cell lines with EGFR T790M (H1975) or wild-type EGFR (A549) were insensitive to gefitinib treatment. The combination of gefitinib and radiation treatment in cell culture produced additive cell killing with no evidence of synergy. In xenograft models, a short course of gefitinib (3 days) did not significantly increase the activity of radiation treatment in wild-type EGFR (A549) tumors (P=.27), whereas this combination markedly increased the activity of radiation (P<.001) or gefitinib alone (P=.002) in EGFR-mutated HCC827 tumors, producing sustained tumor regressions. Conclusions: Gefitinib treatment increases clonogenic cell killing by radiation but only in cell lines sensitive to gefitinib alone. Our data suggest additive rather than synergistic interactions between gefitinib and radiation and that a

  15. Circulating tumor cells in breast cancer at the diagnosis are associated with lymph node involvement, tumor size and negative ER status

    Directory of Open Access Journals (Sweden)

    P. Ferro

    2011-01-01

    Full Text Available We investigated the association of circulating tumor cells (CTC with poor prognostic markers in breast cancer (BC at time of diagnosis. Peripheral blood (PB samples from 190 patients with invasive BC, 12 patients with in situ BC, before theraphy and/or surgery, and 330 from patients without BC were tested for CTCs by RT-PCR for human mammaglobin (hMAM. hMAM was expressed only in PB of invasive BC (9.5% and a significant correlation was found between CTCs with lymph node involvement, tumour size and negative ER. We conclude that CTC detention in invasive BC may be an additional poor prognostic indicator.

  16. Involvement of CtBP1 in the Transcriptional Activation of the MDR1 Gene in Human Multidrug Resistant Cancer Cells

    OpenAIRE

    Jin, Wei; Scotto, Kathleen W.; Hait, William N.; Yang, Jin-Ming

    2007-01-01

    Drug resistance caused by overexpression of P-glycoprotein (P-gp), the MDR1 (ABCB1) gene product, limits the therapeutic outcome. Expression of MDR1 can be induced by divergent stimuli, and involves a number of transcriptional factors. We found that the expression of CtBP1 (C-terminal-binding protein 1), a transcriptional co-regulator, was increased (~4 – fold) in human multidrug resistant (MDR) cancer cell lines, NCI/ADR-RES and A2780/DX, as compared to their sensitive counterparts. Silencin...

  17. Deep sequencing identifies deregulation of microRNAs involved with vincristine drug-resistance of colon cancer cells

    OpenAIRE

    Dong, Wei-Hua; Li, Qin; Zhang, Xiao-Yan; Guo, Qing; Li, Huizheng; Wang, Tian-Yun

    2015-01-01

    Background: Vincristine (VCR) is a chemical that is widely used in tumor therapy. While long-term use can make tumor cells resistant to VCR, the underlying mechanisms of this resistance are still unclear. Objective: This study aimed at investigating the role of microRNA (miRNA) in colon cancer drug resistance. Methods: HCT-8 colon carcinoma cells were cultured and treated with different VCR concentrations to establish an HCT-8/VCR resistant cell line. Whole-genome screens, HiSeq 2500 sequenci...

  18. Enhanced lipoxygenase activity is involved in the stress response but not in the harmful lipid peroxidation and cell death of short-term cadmium-treated barley root tip.

    Science.gov (United States)

    Liptáková, Ľubica; Huttová, Jana; Mistrík, Igor; Tamás, Ladislav

    2013-05-01

    Root growth inhibition and radial root swelling were the characteristic symptoms of barley root tips after the short-term exposure of roots to 15 and 30μM Cd. Higher Cd concentrations caused extensive cell death and root growth arrest. Enhanced lipid peroxidation was observed as early as 1h after the short-term treatment in a Cd concentration-dependent manner. In contrast to lipid peroxidation, the induction of lipoxygenase activity was detected only 3h after the exposure of roots to 15 or 30μM Cd. In addition, it was not observed in 60μM Cd-treated root tips. The highest lipoxygenase activity was detected 6h after 15μM Cd treatment in the meristematic and elongation zone of root tip and was probably associated with the radial expansion of cells. Our results indicate that the upregulation of lipoxygenase is an important component of stress response in barley roots to toxic Cd. It is probably involved in the morphological stress response of root tips or/and in the alleviation of Cd-induced toxic alterations in plant cell membranes, but it is not responsible for the Cd-induced harmful lipid peroxidation and cell death. PMID:23395539

  19. Involvement of CDX2 in the cross talk between TNF-α and Wnt signaling pathway in the colon cancer cell line Caco-2

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Olsen, Anders Krüger; Bzorek, Michael;

    2014-01-01

    Tumor necrosis factor-α (TNF-α) is highly upregulated in inflammation and reduces the expression of the intestinal transcription factor, Caudal-related homeobox transcription factor 2 (CDX2). Wnt/β-catenin signaling is critical for intestinal cell proliferation, but a decreased CDX2 expression has...... the signaling pathways involved in the TNF-α-mediated downregulation of CDX2, and its influence on Wnt/β-catenin signaling components in colon cancer cells. The expression of TNF-α and CDX2 at the invasive front were evaluated by immunohistochemical staining and showed reduced CDX2-positive cells in...... are involved in the TNF-α-dependent downregulation of CDX2. Furthermore, TNF-α-mediated downregulation of CDX2 was found to significantly decrease the mRNA levels of adenomatous polyposis coli (APC), axis inhibition protein 2 (AXIN2) and glycogen synthase kinase-3 beta (GSK3β), whereas the mRNA levels...

  20. Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer

    International Nuclear Information System (INIS)

    Purpose: In this phase I study, we sought to determine the feasibility and tolerability of neoadjuvant short course radiotherapy (SC-CRT) delivered with photon RT with concurrent capecitabine for resectable pancreatic adenocarcinoma. Materials and methods: Ten patients with localized, resectable pancreatic adenocarcinoma were enrolled from December 2009 to August 2011. In dose level I, patients received 3 Gy × 10. In dose level 2, patients received 5 Gy × 5 (every other day). In dose level 3, patients received 5 Gy × 5 (consecutive days). Capecitabine was given during weeks 1 and 2. Surgery was performed 1–3 weeks after completion of chemotherapy. Results: With an intended accrual of 12 patients, the study was closed early due to unexpected intraoperative complications. Compared to the companion phase I proton study, patients treated with photons had increased intraoperative RT fibrosis reported by surgeons (27% vs. 63%). Among those undergoing a Whipple resection, increased RT fibrosis translated to an increased mean OR time of 69 min. Dosimetric comparison revealed significantly increased low dose exposure to organs at risk for patients treated with photon RT. Conclusions: This phase I experience evaluating the tolerability of neoadjuvant SC-CRT with photon RT closed early due to unexpected intraoperative complications

  1. Identifications of novel mechanisms in breast cancer cells involving duct-like multicellular spheroid formation after exposure to the Random Positioning Machine

    DEFF Research Database (Denmark)

    Kopp, Sascha; Slumstrup, Lasse; Corydon, Thomas J;

    2016-01-01

    clarify the underlying mechanisms, we harvested MCS and AD cells separately from each RPM-culture and measured the expression of 29 selected genes with a known involvement in MCS formation. qPCR analyses indicated that cytoskeletal genes were unaltered in short-term samples. IL8, VEGFA, and FLT1 were...... upregulated in 2 h/4 h AD-cultures. The ACTB, TUBB, EZR, RDX, FN1, VEGFA, FLK1 Casp9, Casp3, PRKCA mRNAs were downregulated in 5d-MCS-samples. ESR1 was upregulated in AD, and PGR1 in both phenotypes after 5d. A pathway analysis revealed that the corresponding gene products are involved in organization and...

  2. XPD Lys751Gln polymorphism and esophageal cancer risk: A meta-analysis involving 2288 cases and 4096 controls

    Institute of Scientific and Technical Information of China (English)

    Ling Yuan; Dan Cui; Er-Jiang Zhao; Chen-Zhi Jia; Li-Dong Wang; Wei-Quan Lu

    2011-01-01

    AIM: To evaluate the association between xeroderma pigmentosum group D (XPD), genetic polymorphism Lys751Gln and esophageal cancer risk. METHODS: We searched PubMed up to September 1, 2010 to identify eligible studies. A total of 10 casecontrol studies including 2288 cases and 4096 controls were included in the meta-analysis. Statistical analysis was performed with Review Manage version 4.2. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association.RESULTS: The results suggested that there is no significant association between XPD Lys751Gln polymorphism and esophageal cancer susceptibility in the overall population. However, in subgroup analysis by histology type, a significant association was found between XPD Lys751Gln polymorphism and esophageal adenocarcinoma (for CC vs AA: OR = 1.25, 95% CI = 1.01-1.55, P = 0.05 for heterogeneity). CONCLUSION: Our meta-analysis suggested that XPD Lys751Gln polymorphism may be associated with increased risk of esophageal adenocarcinoma.

  3. Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: involvement of the tumor suppressor miR30a and its target gene SOX4.

    Science.gov (United States)

    Zhang, Jing; Shen, Chengwu; Wang, Lin; Ma, Quanping; Xia, Pingtian; Qi, Mei; Yang, Muyi; Han, Bo

    2014-09-26

    Tumor metastasis is the leading cause of mortality and morbidity of prostate cancer (PCa) patients. Epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. Recent evidence suggested that diabetic patients treated with metformin have lower PCa risk and better prognosis. This study was aimed to investigate the effects of metformin on EMT in PCa cells and the possible microRNA (miRNA)-based mechanisms. MiRNAs have been shown to regulate various processes of cancer metastasis. We herein showed that metformin significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell cycle arrest and inhibits invasiveness and motility capacity of Vcap cells. Metformin could inhibit TGF-β-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p=0.013), Vimentin (p=0.002) and the decrease of E-cadherin (p=0.0023) and β-catenin (p=0.034) at mRNA and protein levels. Notably, we demonstrated significant upregulation of miR30a levels by metformin (Pmetformin in PCa cells may involve upregulation of miR30a and downregulation of SOX4. PMID:25201727

  4. Significance of mesorectal volume in staging of rectal cancer with magnetic resonance imaging and the assessment of involvement of the mesorectal fascia

    International Nuclear Information System (INIS)

    The aim was to study the influence of mesorectal volume, as estimated by magnetic resonance imaging (MRI), that is to be removed during total mesorectal excision (TME), on the accuracy of the first preoperative MRI of rectal cancer compared to histopathology, and its correlation to locoregional prognostic factors. A total of 267 rectal cancer patients from a multinational study (MERCURY or MRI equivalence study) had their mesorectal volume retrospectively estimated by researchers without knowledge of the assessments made by the radiologist or the pathologist. The evaluations made by the pathologist and the radiologist were then compared, including T- and N-staging, assessment of extent of extramural tumor invasion (the largest portion of the tumor beyond the muscularis propria or EMI) and distance to mesorectal fascia; the discrepancies in the results were correlated to the mesorectal volume. T- or N-staging accuracy by MRI and the difference between the EMI as measured by the pathologist and the radiologist were not dependent on individual mesorectal volume. There was no correlation between assessment of involvement of mesorectal fascia or local neighboring organs by MRI and histopathology with mesorectal volume. Mesorectal volume does not affect locoregional prognostic factors or the accuracy of local staging of rectal cancer. (orig.)

  5. The role of the maximum involvement of biopsy core in predicting outcome for patients treated with dose-escalated radiation therapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Murgic Jure

    2012-08-01

    Full Text Available Abstract Purpose To evaluate the influence of the maximum involvement of biopsy core (MIBC on outcome for prostate cancer patients treated with dose-escalated external beam radiotherapy (EBRT. Methods and materials The outcomes of 590 men with localized prostate cancer treated with EBRT (≥75 Gy at a single institution were retrospectively analyzed. The influence of MIBC on freedom from biochemical failure (FFBF, freedom from metastasis (FFM, cause-specific survival (CSS, and overall survival (OS was compared to other surrogates for biopsy tumor volume, including the percentage of positive biopsy cores (PPC and the total percentage of cancer volume (PCV. Results MIBC correlated with PSA, T-stage, Gleason score, NCCN risk group, PPC, PCV, and treatment related factors. On univariate analysis, MIBC was prognostic for all endpoints except OS; with greatest impact in those with Gleason scores of 8–10. However, on multivariate analysis, MIBC was only prognostic for FFBF (hazard ratio [HR] 1.9, p = 0.008, but not for FFM (p = 0.19, CSS (p = 0.16, and OS (p = 0.99. Conclusions In patients undergoing dose-escalated EBRT, MIBC had the greatest influence in those with Gleason scores of 8–10 but provided no additional prognostic data as compared to PPC and PCV, which remain the preferable prognostic variables in this patient population.

  6. Transferrin facilitates the formation of DNA double-strand breaks via transferrin receptor 1: the possible involvement of transferrin in carcinogenesis of high-grade serous ovarian cancer.

    Science.gov (United States)

    Shigeta, S; Toyoshima, M; Kitatani, K; Ishibashi, M; Usui, T; Yaegashi, N

    2016-07-01

    Fallopian tubal epithelium is a candidate for the origin of high-grade serous ovarian cancer. Transferrin-containing follicular fluid and/or retrograde menstrual blood are possible risk factors for carcinogenesis. Accumulation of DNA double-strand breaks (DNA-DSBs) in the fallopian tubal epithelium is considered to play an important role in the development of cancer. However, the mechanisms by which DNA-DSBs accumulate have not yet been fully elucidated. The hydroxyl radical, which is produced in a Fenton reaction catalyzed by an iron ion, serves as a potent DNA-DSB-inducing molecule, raising the potential of an iron ion transporter of transferrin in the formation of DNA-DSBs. We studied the potential involvement of transferrin in DNA damage and the development of ovarian cancer. Treatment with transferrin facilitated the formation of histone 2AX phosphorylated at Serine 139 (γH2AX), which is known as a DNA-DSB marker, in human fallopian tube secretory epithelial cells and A2780 ovarian cancer cells. Knockdown of transferrin receptor 1 (TfR1), but not transferrin receptor 2, suppressed the transferrin uptake and consequent formation of γH2AX. As hydroxyl radicals in reactive oxygen species (ROS) are involved in DNA-DSBs, the formation of ROS was determined. Treatment with TfR1-specific small interference RNAs significantly diminished transferrin-induced formation of ROS. Moreover, TfR1-dependent uptake of transferrin was revealed to augment the formation of DNA-DSBs in the presence of hydrogen peroxide, which served as a substrate for the Fenton reaction. An ex vivo study with murine fallopian tubes further demonstrated that transferrin treatment introduced DNA-DSBs in the fallopian tubal epithelium. Collectively, these data suggested that the transferrin-TfR1 axis accounts for the induction of DNA-DSBs that potentially lead to DNA damage/genome instability. These findings also suggested that exposure to transferrin initiates and promotes the development of

  7. Short-hairpin RNA-mediated Heat shock protein 90 gene silencing inhibits human breast cancer cell growth in vitro and in vivo

    International Nuclear Information System (INIS)

    Highlights: ► Hsp90 is over-expressed in human breast cancer. ► The shRNA-mediated gene silencing of Hsp90 resulted in inhibition of cell growth. ► Akt and NF-kB were down-regulation after transfection due to Hsp90 silencing. ► The tumor growth ratio was decline due to Hsp90 silencing. ► The PCNA expression was down-regulation due to Hsp90 silencing. -- Abstract: Hsp90 interacts with proteins that mediate signaling pathways involved in the regulation of essential processes such as proliferation, cell cycle control, angiogenesis and apoptosis. Hsp90 inhibition is therefore an attractive strategy for blocking abnormal pathways that are crucial for cancer cell growth. In the present study, the role of Hsp90 in human breast cancer MCF-7 cells was examined by stably silencing Hsp90 gene expression with an Hsp90-silencing vector (Hsp90-shRNA). RT-PCR and Western blot analyses showed that Hsp90-shRNA specifically and markedly down-regulated Hsp90 mRNA and protein expression. NF-kB and Akt protein levels were down-regulated in Hsp90-shRNA transfected cells, indicating that Hsp90 knockout caused a reduction of survival factors and induced apoptosis. Treatment with Hsp90-shRNA significantly increased apoptotic cell death and caused cell cycle arrest in the G1/S phase in MCF-7 cells, as shown by flow cytometry. Silencing of Hsp90 also reduced cell viability, as determined by MTT assay. In vivo experiments showed that MCF-7 cells stably transfected with Hsp90-shRNA grew slowly in nude mice as compared with control groups. In summary, the Hsp90-shRNA specifically silenced the Hsp90 gene, and inhibited MCF-7 cell growth in vitro and in vivo. Possible molecular mechanisms underlying the effects of Hsp90-shRNA include the degradation of Hsp90 breast cancer-related client proteins, the inhibition of survival signals and the upregulation of apoptotic pathways. shRNA-mediated interference may have potential therapeutic utility in human breast cancer.

  8. Short-term resveratrol exposure causes in vitro and in vivo growth inhibition and apoptosis of bladder cancer cells.

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    Mo-Li Wu

    Full Text Available Conventional adjuvant chemotherapies for bladder transitional cell carcinomas (TCCs may cause strong systemic toxicity and local irritation. Non-toxic resveratrol inhibits TCC cell growth but its feasibility in clinical management of TCCs remains obscure. This study aimed to evaluate the safety and anti-TCC efficacy of resveratrol, using the experimental models closer to the clinical treatment condition. Human TCC EJ cells were exposed to 100 µM, 150 µM and 200 µM resveratrol respectively for 1 hour and 2 hours to mimic intravesical drug instillation and the cell responses were analyzed by multiple experimental approaches. An orthotopic TCC nude mouse model was established by injecting EJ cells into the sub-urothelial layer and used for short-term intravesical resveratrol instillation. The safety of resveratrol instillation was evaluated and compared with that of MCC. The results revealed that 2 h 150 µM or 200 µM resveratrol treatment leaded to remarkable S phase arrest and apoptosis at 72 h time-point, accompanied with attenuated phosphorylation, nuclear translocation and transcription of STAT3, down-regulation of STAT3 downstream genes (survivin, cyclinD1, c-Myc and VEGF and nuclear translocations of Sirt1 and p53. The importance of STAT3 signaling in cell growth was confirmed by treating EJ cells with JAK2 inhibitor tyrphostin AG490. The efficacy and safety of resveratrol instillation were proved by the findings from nude mouse orthotopic xenograft models, because this treatment caused growth suppression, distinctive apoptosis and STAT3 inactivation of the transplanted tumors without affecting normal urothelium. Our results thus suggest for the first time the practical values of resveratrol as a safe and effective agent in the post-operative treatment of TCCs.

  9. Epidermal growth factor potentiates in vitro metastatic behaviour of human prostate cancer PC-3M cells: involvement of voltage-gated sodium channel

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    Uysal-Onganer Pinar

    2007-11-01

    Full Text Available Abstract Background Although a high level of functional voltage-gated sodium channel (VGSC expression has been found in strongly metastatic human and rat prostate cancer (PCa cells, the mechanism(s responsible for the upregulation is unknown. The concentration of epidermal growth factor (EGF, a modulator of ion channels, in the body is highest in prostatic fluid. Thus, EGF could be involved in the VGSC upregulation in PCa. The effects of EGF on VGSC expression in the highly metastatic human PCa PC-3M cell line, which was shown previously to express both functional VGSCs and EGF receptors, were investigated. A quantitative approach, from gene level to cell behaviour, was used. mRNA levels were determined by real-time PCR. Protein expression was studied by Western blots and immunocytochemistry and digital image analysis. Functional assays involved measurements of transverse migration, endocytic membrane activity and Matrigel invasion. Results Exogenous EGF enhanced the cells' in vitro metastatic behaviours (migration, endocytosis and invasion. Endogenous EGF had a similar involvement. EGF increased VGSC Nav1.7 (predominant isoform in PCa mRNA and protein expressions. Co-application of the highly specific VGSC blocker tetrodotoxin (TTX suppressed the effect of EGF on all three metastatic cell behaviours studied. Conclusion 1 EGF has a major involvement in the upregulation of functional VGSC expression in human PCa PC-3M cells. (2 VGSC activity has a significant intermediary role in potentiating effect of EGF in human PCa.

  10. Involved-field irradiation concurrently combined with nedaplatin/5-fluorouracil for inoperable esophageal cancer on basis of 18FDG-PET scans: A phase II study

    International Nuclear Information System (INIS)

    Purpose: A prospective study was performed on chemoradiotherapy (CRT) for esophageal cancer using involved-field radiation therapy (IFRT) based on 18-fluorodeoxyglucose positron-emission tomography. The goal of this phase II study was to evaluate the efficacy of the IFRT procedure in newly diagnosed esophageal cancer. Patients and methods: Eligible patients were adults with newly diagnosed untreated, inoperable esophageal cancer in stages I–IV with lymph node metastases. Patients received nedaplatin 80 mg/m2 per day on day 1, 5-fluorouracil 800 mg/m2 on days 1–4 intravenously repeated every 28 days for 2–4 cycles, and combined IFRT. Elective nodal irradiation was not performed. Irradiation was applied only to the primary tumor and positive lymph nodes. Results: From September 2009 to July 2012, of the 63 patients enrolled, 58 were evaluable for response. The primary end point of isolated out-of-field loco-regional nodal recurrence was seen in only two patients. The expectant rate was assumed to be less than 5%. The threshold value was set as 10% to calculate the number of registrations. Progression-free and overall survival rates at 36 months were 47.7% and 51.1%, respectively. The median progression-free survival was 34.6 months, and overall survival was 38.4 months. Salvage surgery was tried for 11 patients (17.5%) due to residual or recurrent disease. Conclusion: The primary end point of the trial was demonstrated, indicating the efficacy of IFRT in the treatment of inoperable esophageal cancer mostly of squamous cell carcinoma

  11. A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

    International Nuclear Information System (INIS)

    Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. Organ-specific dose-volume histograms (DVH) were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR) for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2%) reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment

  12. Cytotoxicity of obacunone and obacunone glucoside in human prostate cancer cells involves Akt-mediated programmed cell death

    International Nuclear Information System (INIS)

    Highlights: • Possible mechanism of inhibiting LNCaP cells proliferation by obacunone and obacunone glucoside is demonstrated for the first time. • Inhibition of LNCaP cells by limonoids though induction of programmed cell death, inhibition of cell signaling and inflammatory pathways. • Limonoids exhibited multi-mode inhibition of androgen expression in LNCaP cells. - Abstract: Obacunone and obacunone glucoside (OG) are naturally occurring triterpenoids commonly found in citrus and other plants of the Rutaceae family. The current study reports the mechanism of cytotoxicity of citrus-derived obacunone and OG on human androgen-dependent prostate cancer LNCaP cells. Both limonoids exhibited time- and dose-dependent inhibition of cell proliferation, with more than 60% inhibition of cell viability at 100 μM, after 24 and 48 h. Analysis of fragmentation of DNA, activity of caspase-3, and cytosolic cytochrome-c in the cells treated with limonoids provided evidence for activation of programmed cell death by limonoids. Treatment of LNCaP cells with obacunone and OG resulted in dose-dependent changes in expression of proteins responsible for the induction of programmed cell death through the intrinsic pathway and down-regulation of Akt, a key molecule in cell signaling pathways. In addition, obacunone and OG also negatively regulated an inflammation-associated transcription factor, androgen receptor, and prostate-specific antigen, and activated proteins related to the cell cycle, confirming the ability of limonoids to induce cytotoxicity through multiple pathways. The results of this study provided, for the first time, an evidence of the cytotoxicity of obacunone and OG in androgen-dependent human prostate cancer cells

  13. Polyamine biosynthesis inhibitors alter protein-protein interactions involving estrogen receptor in MCF-7 breast cancer cells.

    Science.gov (United States)

    Thomas, T; Shah, N; Klinge, C M; Faaland, C A; Adihkarakunnathu, S; Gallo, M A; Thomas, T J

    1999-04-01

    We investigated the effects of polyamine biosynthesis inhibition on the estrogenic signaling pathway of MCF-7 breast cancer cells using a protein-protein interaction system. Estrogen receptor (ER) linked to glutathione-S-transferase (GST) was used to examine the effects of two polyamine biosynthesis inhibitors, difluoromethylornithine (DFMO) and CGP 48664. ER was specifically associated with a 45 kDa protein in control cells. In cells treated with estradiol, nine proteins were associated with ER. Cells treated with polyamine biosynthesis inhibitors in the absence of estradiol retained the binding of their ER with a 45 kDa protein and the ER also showed low-affinity interactions with a number of cellular proteins; however, these associations were decreased by the presence of estradiol and the inhibitors. When samples from the estradiol+DFMO treatment group were incubated with spermidine prior to GST-ER pull down assay, an increased association of several proteins with ER was detected. The intensity of the ER-associated 45 kDa protein increased by 10-fold in the presence of 1000 microM spermidine. These results indicate a specific role for spermidine in ER association of proteins. Western blot analysis of samples eluted from GST-ER showed the presence of chicken ovalbumin upstream promoter-transcription factor, an orphan nuclear receptor, and the endogenous full-length ER. These results show that multiple proteins associate with ER and that the binding of some of these proteins is highly sensitive to intracellular polyamine concentrations. Overall, our results indicate the importance of the polyamine pathway in the gene regulatory function of estradiol in breast cancer cells. PMID:10194516

  14. Recursive Partitioning Analysis of Mediastinal N2 Lymph Node Involvement with Selected Biological Markers in Operable Non-small Cell Lung Cancer: A Correlative Study

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    Hakan Bozcuk

    2007-01-01

    Full Text Available Background: Expressions of various biomarkers in non-small cell lung cancer (NSCLC have been linked with the prognosis and involvement of mediastinal lymph nodes.Methods: In this study, we utilized recursive partitioning analysis (RPA by using P53, c-erb-B2, and P-glycoprotein (PGP expressions evaluated by immunohistochemistry to estimate retrospectively the likelihood of the occult N2 mediastinal lymph node involvement in patients with operable NSCLC.Results: In univariate tests, immunohistochemical staining of the primary tumor for these 3 markers in 61 patients undergoing surgery revealed no direct relationship with the N2 involvement. However, RPA demonstrated in patients aged 75 and with 4 mediastinal lymph nodes removed that, high PGP expression frequency (20% predicted an increased likelihood of the N2 involvement (46.7%, R2 = 0.25. Univariate nominal logistic regression analysis revealed that RPA group affiliation, and the number of mediastinal lymph nodes resected (logarithmic transformation were associated with the metastasis to N2 lymph nodes (χ2 = 17.59, p = 0.0005, and χ2 = 2.40, p = 0.0654, respectively. Multivariate analysis confirmed that only RPA group affiliation predicted the N2 involvement (χ2 = 14.63, p = 0.0022.Conclusion: This study shows for the first time that PGP expression of the primary tumor may help to predict the occult N2 mediastinal lymph node involvement in NSCLC. Thus, further research is required to understand whether PGP expression may aid in the decision process for preoperative mediastinoscopy.

  15. Lack of benefit from a short course of androgen deprivation for unfavorable prostate cancer patients treated with an accelerated hypofractionated regime

    International Nuclear Information System (INIS)

    Purpose: High-dose radiotherapy, delivered in an accelerated hypofractionated course, was utilized to treat prostate cancer. Therapy consisted of external beam radiotherapy (EBRT) and transrectal ultrasound (TRUS)-guided conformally modulated high-dose rate (HDR) brachytherapy. The purpose of this report is (1) to assess long-term comparative outcomes from three trials using similar accelerated hypofractionated regimes; and (2) to examine the long-term survival impact of a short course of ≤6 months adjuvant/concurrent androgen deprivation when a very high radiation dose was delivered. Methods and Materials: Between 1986 and 2000, 1,260 patients were treated at three institutions with pelvic EBRT (36-50 Gy) integrated with HDR prostate brachytherapy. The total dose including brachytherapy was given over 5 weeks. The biologic equivalent EBRT dose ranged between 90 and 123 Gy (median, 102 Gy) using an α /β of 1.2. Patient eligibility criteria included a pretreatment prostate-specific antigen ≥10, Gleason score ≥7, or clinical stage ≥T2b. A total of 1,260 patients were treated, and 934 meet the criteria. Kiel University Hospital treated 198 patients; William Beaumont Hospital, 315; and California Endocurietherapy Cancer Center, 459 patients. Brachytherapy dose regimes were somewhat different between centers and the dose was escalated from 5.5 x 3 to 15 Gy x 2 Gy. Patients were divided for analysis between the 406 who received up to 6 months of androgen deprivation therapy and the 528 patients who did not. All patients had a minimum follow-up of 18 months (3 times the exposure to androgen deprivation therapy). The American Society for Therapeutic Radiology and Oncology biochemical failure definition was used. Results: Mean age was 69 years. Median follow-up time was 4.4 years (range, 1.5-14.5); 4 years for androgen deprivation therapy patients and 4.9 for radiation alone. There was no difference at 5 and 8 years in overall survival, cause-specific survival, or

  16. Long-term quality-of-life after neoadjuvant short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate long-term quality-of-life (QoL) after neoadjuvant short-course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for locally advanced rectal cancer. Methods: Between 1999 and 2008, 225 patients were treated with curative intent for locally advanced rectal cancer using neoadjuvant SC-RT (n = 108) or LC-RCHT (n = 117). SC-RT delivered 10 × 2.9 Gy twice daily with immediate surgery. LC-RCHT delivered 28 × 1.8 Gy concomitant with 5-FU based chemotherapy and delayed surgery. A cross-sectional QoL analysis was performed in disease-free patients using the EORTC-QLQ-C30 and EORTC-QLQ-CR29 questionnaires. Results: After a median follow-up of 67 months, 133 patients were disease-free of which 120 (90%) returned the QoL questionnaires. Patients in the LC-RCHT cohort had a higher rate of uT4, uN+ and low tumor location. No difference in QoL was observed between SC-RT and LC-RCHT except an improved physical functioning in the LC-RCHT group (p = 0.04). Comparing our total patient cohort with the general German population showed no difference in global health status but decreased QoL in several functional and bowel symptom scores. Conclusions: The finding of comparable long-term QoL after SC-RT and LC-RCHT adds to our knowledge of equivalent oncological outcome and may be useful in the decision making process between the two neoadjuvant approaches

  17. A novel short anionic antibacterial peptide isolated from the skin of Xenopus laevis with broad antibacterial activity and inhibitory activity against breast cancer cell.

    Science.gov (United States)

    Li, Siming; Hao, Linlin; Bao, Wanguo; Zhang, Ping; Su, Dan; Cheng, Yunyun; Nie, Linyan; Wang, Gang; Hou, Feng; Yang, Yang

    2016-07-01

    A vastarray of bioactive peptides from amphibian skin secretions is attracting increasing attention due to the growing problem of bacteria resistant to conventional antibiotics. In this report, a small molecular antibacterial peptide, named Xenopus laevis antibacterial peptide-P1 (XLAsp-P1), was isolated from the skin of Xenopus laevis using reversed-phase high-performance liquid chromatography. The primary structure of XLAsp-P1, which has been proved to be a novel peptide by BLAST search in AMP database, was DEDDD with a molecular weight of 607.7 Da analysed by Edman degradation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). The highlight of XLAsp-P1 is the strong in vitro potency against a variety of Gram-positive and Gram-negative bacteria with minimum inhibitory concentrations (MICs) starting at 10 μg/mL and potent inhibitory activity against breast cancer cell at tested concentrations from 5 to 50 μg/mL. In addition, only 6.2 % of red blood cells was haemolytic when incubated with 64 μg/mL (higher than MICs of all bacterial strain) of XLAsp-P1. The antimicrobial mechanism for this novel peptide was the destruction of the cell membrane investigated by transmission electron microscopy. All these showed that XLAsp-P1 is a novel short anionic antibacterial peptide with broad antibacterial activity and inhibitory activity against breast cancer cell. PMID:26952034

  18. A biologically competitive 21 days hypofractionation scheme with weekly concomitant boost in breast cancer radiotherapy feasibility acute sub-acute and short term late effects

    International Nuclear Information System (INIS)

    Radiation therapy after lumpectomy is a standard part of breast conserving therapy for invasive breast carcinoma. The most frequently used schedule worldwide is 60 Gy in 30 fractions in 6 weeks, a time commitment that sporadically may dissuade some otherwise eligible women from undertaking treatment. The purpose and primary endpoint of this perspective study is to evaluate feasibility and short-term late toxicity in a hypofractionated whole breast irradiation schedule. Between February and October 2008 we treated 65 consecutive patients with operable invasive early-stage breast cancer with a hypofractionated schedule of external beam radiation therapy. All patients were assigned to 39 Gy in 13 fractions in 3 weeks to the whole breast plus a concomitant weekly boost dose to the lumpectomy cavity of 3 Gy in 3 fractions. All the patients had achieved a median follow up of 24 months (range 21-29 months). At the end of treatment 52% presented grade 0 acute toxicity 39% had grade 1 and 9% had grade 2. At 6 months with all the patients assessed there were 34% case of grade 1 subacute toxicity and 6% of grade 2. At 12 months 43% and 3% of patients presented with clinical grade 1 and grade 2 fibrosis respectively and 5% presented grade 1 hyperpigmentation. The remaining patients were free of side effects. At 24 months, with 56 assessed, just 2 patients (3%) showed grade 2 of late fibrosis. The clinical results observed showed a reasonably good feasibility of the accelerated hypofractionated schedule in terms of acute, subacute and short-term late toxicity. This useful 13 fractions with a concomitant boost schedule seems, in selected patients, a biologically acceptable alternative to the traditional 30 days regime

  19. Inhibitive effect of 3-bromopyruvic acid on human breast cancer MCF-7 cells involves cell cycle arrest and apoptotic induction

    Institute of Scientific and Technical Information of China (English)

    LIU Xiao-hong; ZHENG Xue-fang; WANG Yong-li

    2009-01-01

    Background Breast cancer is one of the most common malignancies in women and is highly resistant to chemotherapy. Due to its high tumour selectivity, 3-bromopyruvic acid (3-BrPA), a well-known inhibitor of energy metabolism has been proposed as a specific anticancer agent. The present study determined the effect of 3-BrPA on proliferation, cell cycle and apoptosis in the human breast cancer MCF-7 cell line and other antitumour mechanisms. Methods MCF-7 cells were treated with various concentrations of 3-BrPA for 1-4 days, and cell growth was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. Marked morphological changes in MCF-7 cells after treatment with 3-BrPA were observed using transmission electron microscopy. The distributions of the cell cycle and apoptosis were analyzed by flow cytometry. Immunohistochemistry was used to indicate the changes in the expression of Bcl-2, c-Myc, and mutant p53. Results 3-BrPA (25 μg/ml) significantly inhibited the proliferation of MCF-7 cells in a time-dependent manner. The MCF-7 cells exposed to 3-BrPA showed the typical morphological characteristics of apoptosis, including karyopycnosis, nuclear condensation and oversize cytoplasmic particles. In addition, flow cytometric assay also showed more apoptotic cells after 3-BrPA stimulation. The cells at the GO and G1 phases were dramatically decreased while cells at the S and G2/M phases were increased in response to 3-BrPA treatment after 48 hours. Furthermore, 3-BrPA stimulation decreased the expressions of Bcl-2, c-Myc and mutant p53, which were strongly associated with the programmed cell death signal transduction pathway. Conclusion 3-BrPA inhibits proliferation, induces S phase and G2/M phase arrest, and promotes apoptosis in MCF-7 cells, which processes might be mediated by the downregulation of the expressions of Bcl-2, c-Myc and mutant p53.

  20. A homologue of the breast cancer-associated gene BARD1 is involved in DNA repair in plants

    OpenAIRE

    Reidt, Wim; Wurz, Rebecca; Wanieck, Kristina; Ha Chu, Hoang; Puchta, Holger

    2007-01-01

    hBRCA1 and hBARD1 are tumor suppressor proteins that are involved as heterodimer via ubiquitinylation in many cellular processes, such as DNA repair. Loss of BRCA1 or BARD1 results in early embryonic lethality and chromosomal instability. The Arabidopsis genome carries a BRCA1 homologue, and we were able to identify a BARD1 homologue. AtBRCA1 and the putative AtBARD1 protein are able to interact with each other as indicated by in vitro and in planta experiments. We have identified T-DNA inser...

  1. Identification and characterization of a novel gene, c1orf109, encoding a CK2 substrate that is involved in cancer cell proliferation

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    Liu Shan-shan

    2012-05-01

    Full Text Available Abstract Background In the present study we identified a novel gene, Homo Sapiens Chromosome 1 ORF109 (c1orf109, GenBank ID: NM_017850.1, which encodes a substrate of CK2. We analyzed the regulation mode of the gene, the expression pattern and subcellular localization of the predicted protein in the cell, and its role involving in cell proliferation and cell cycle control. Methods Dual-luciferase reporter assay, chromatin immunoprecipitation and EMSA were used to analysis the basal transcriptional requirements of the predicted promoter regions. C1ORF109 expression was assessed by western blot analysis. The subcellular localization of C1ORF109 was detected by immunofluorescence and immune colloidal gold technique. Cell proliferation was evaluated using MTT assay and colony-forming assay. Results We found that two cis-acting elements within the crucial region of the c1orf109 promoter, one TATA box and one CAAT box, are required for maximal transcription of the c1orf109 gene. The 5′ flanking region of the c1orf109 gene could bind specific transcription factors and Sp1 may be one of them. Employing western blot analysis, we detected upregulated expression of c1orf109 in multiple cancer cell lines. The protein C1ORF109 was mainly located in the nucleus and cytoplasm. Moreover, we also found that C1ORF109 was a phosphoprotein in vivo and could be phosphorylated by the protein kinase CK2 in vitro. Exogenous expression of C1ORF109 in breast cancer Hs578T cells induced an increase in colony number and cell proliferation. A concomitant rise in levels of PCNA (proliferating cell nuclear antigen and cyclinD1 expression was observed. Meanwhile, knockdown of c1orf109 by siRNA in breast cancer MDA-MB-231 cells confirmed the role of c1orf109 in proliferation. Conclusions Taken together, our findings suggest that C1ORF109 may be the downstream target of protein kinase CK2 and involved in the regulation of cancer cell proliferation.

  2. Increased Histone Deacetylase Activity Involved in the Suppressed Invasion of Cancer Cells Survived from ALA-Mediated Photodynamic Treatment

    Science.gov (United States)

    Li, Pei-Tzu; Tsai, Yi-Jane; Lee, Ming-Jen; Chen, Chin-Tin

    2015-01-01

    Previously, we have found that cancer cells survived from 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) have abnormal mitochondrial function and suppressed cellular invasiveness. Here we report that both the mRNA expression level and enzymatic activity of histone deacetylase (HDAC) were elevated in the PDT-derived variants with dysfunctional mitochondria. The activated HDAC deacetylated histone H3 and further resulted in the reduced migration and invasion, which correlated with the reduced expression of the invasion-related genes, matrix metalloproteinase 9 (MMP9), paternally expressed gene 1 (PEG1), and miR-355, the intronic miRNA. Using chromatin immunoprecipitation, we further demonstrate the reduced amount of acetylated histone H3 on the promoter regions of MMP9 and PEG1, supporting the down-regulation of these two genes in PDT-derived variants. These results indicate that HDAC activation induced by mitochondrial dysfunction could modulate the cellular invasiveness and its related gene expression. This argument was further verified in the 51-10 cybrid cells with the 4977 bp mtDNA deletion and A375 ρ0 cells with depleted mitochondria. These results indicate that mitochondrial dysfunction might suppress tumor invasion through modulating histone acetylation. PMID:26473836

  3. Inhibitory effect of genistein on mouse colon cancer MC-26 cells involved TGF-β1/Smad pathway

    International Nuclear Information System (INIS)

    TGF-β1/signaling has been shown to be associated with proapoptotic and antimitotic activities in epithelial tissues. Genistein, a major component of soybean isoflavone, has multiple functions resulting in anticancer proliferation. We herein showed that genistein dose-dependently increased TGF-β1 mRNA expression in mouse colon cancer MC-26 cells. A mouse monoclonal anti-TGF-β1 neutralizing antibody partially, but not completely, blocked the growth inhibition by genistein. By using adenoviral vector, we demonstrated that Smad7 overexpression attenuated genistein-induced growth inhibition and apoptosis as determined by MTT and apoptosis ELISA. Smad7 overexpression also inhibited upregulation of p21 and caspase-3 activity by geinistein. To further confirm inhibitory effect of genistein in MC-26 cells require TGF-β1/Smad signaling, we employed Western blot and electrophoretic mobility shift assay to detect formation of Smad-DNA complexes and phosphorylation of Smad2 and Smad3, respectively. Data revealed that genistein induced an evident formation of Smad-DNA complexes and phosphorylation of Smad2 and Smad3, indicating increased TGF-β1 signaling. Taken together, these findings first provided insights into possible molecular mechanisms of growth inhibition by genistein that required Smad signaling, which could aid in its evaluation for colon tumor prevention

  4. Intraoperative Radiation Therapy Reduces Local Recurrence Rates in Patients With Microscopically Involved Circumferential Resection Margins After Resection of Locally Advanced Rectal Cancer

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    Alberda, Wijnand J.; Verhoef, Cornelis [Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam (Netherlands); Nuyttens, Joost J. [Department of Radiotherapy, Erasmus MC Cancer Institute, Rotterdam (Netherlands); Meerten, Esther van [Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam (Netherlands); Rothbarth, Joost [Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam (Netherlands); Wilt, Johannes H.W. de [Department of Surgery, Division of Surgical Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands); Burger, Jacobus W.A., E-mail: j.burger@erasmusmc.nl [Department of Surgery, Division of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam (Netherlands)

    2014-04-01

    Purpose: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. Methods and Materials: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. Results: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) Conclusion: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM.

  5. Intraoperative Radiation Therapy Reduces Local Recurrence Rates in Patients With Microscopically Involved Circumferential Resection Margins After Resection of Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Purpose: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. Methods and Materials: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. Results: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) Conclusion: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM

  6. Intrinsic, pro-apoptotic effects of IGFBP-3 on breast cancer cells are reversible: Involvement of PKA, Rho and ceramide.

    Directory of Open Access Journals (Sweden)

    Claire M Perks

    2011-05-01

    Full Text Available We established previously that IGFBP-3 could exert positive or negative effects on cell function depending upon the extracellular matrix composition and by interacting with integrin signalling. To elicit its pro-apoptotic effects IGFBP-3 bound to caveolin-1 and the beta 1 integrin receptor and increased their association culminating in MAPK activation. Disruption of these complexes or blocking the beta 1 integrin receptor reversed these intrinsic actions of IGFBP-3. In this study we have examined the signalling pathway between integrin receptor binding and MAPK activation that mediates the intrinsic, pro-apoptotic actions of IGFBP-3. We found on inhibiting protein kinase A(PKA, Rho associated kinase (ROCK and ceramide, the accentuating effects of IGFBP-3 on apoptotic triggers were reversed, such that IGFBP-3 then conferred cell survival. We established that IGFBP-3 activated Rho, the upstream regulator of ROCK and that beta1 integrin and PKA were upstream of Rho activation, whereas the involvement of ceramide was downstream. The beta 1 integrin, PKA, Rho and ceramide were all upstream of MAPK activation. These data highlight key components involved in the pro-apoptotic effects of IGFBP-3 and that inhibiting them leads to a reversal in the action of IGFBP-3.

  7. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non–small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1–4 N2–3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients’ conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07–0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06–1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11–4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33–1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38–1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58–1.61]), and tumor size (HR: 1.04 [CI: 0.94–1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic

  8. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Annemarie T. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Mitra, Nandita [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Xanthopoulos, Eric [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Evans, Tracey; Stevenson, James; Langer, Corey [Department of Medical Oncology, University of Pennsylvania, Philadelphia, PA (United States); Kucharczuk, John C. [Department of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA (United States); Lin, Lilie; Rengan, Ramesh [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)

    2012-05-01

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III

  9. Diagnostic Value of Pelvic MRI for Assessment of the Depth of Myometrial Invasion and Cervical Involvement in Endometrial Cancer: Comparison of New Versus Old FIGO Staging

    International Nuclear Information System (INIS)

    Endometrial carcinoma is a highly prevalent gynecologic malignancy. The International Federation of Gynecology and Obstetrics (FIGO) staging system underwent significant revision on 2009. Key changes in the FIGO staging system include simplification of stage I endometrial cancer and removal of cervical mucosal invasion as a separate stage. MRI is a noninvasive diagnostic method for preoperative staging of endometrial cancer. The main purpose of this study was to investigate the diagnostic efficacy of pelvic MRI in determining the depth of myometrial invasion and cervical involvement in endometrial carcinoma. The other aim was to compare the accuracy of pelvic MRI using the old and new FIGO staging systems in endometrial carcinoma. Between November 2010 and January 2012, 54 patients underwent primary surgical staging in our department due to endometrial adenocarcinoma. Pre-operative pelvic MRI was performed and MRI staging was done according to old and new FIGO staging, separately. The sensitivity, specificity, positive and negative predictive values as well as the accuracy of MRI for deep myometrial invasion and cervical infiltration were calculated. MRI accuracy was also compared for old and new FIGO staging. Pathological staging was the standard of reference. The mean age was 53.31 (SD = 11.52) and the most common histological subtype was the endometrioid type of endometrial adenocarcinoma (90.8%). In the evaluation of deep tumoral invasion of the myometrium (> 50%), sensitivity, specificity, diagnostic accuracy and positive and negative predictive values of MRI were 82.35%, 94.59%, 90.74%, 87.5% and 92.1%, respectively. For cervical stromal involvement, these values were 54.54%, 100%, 90.74%, 100% and 89.58%, respectively. In case of cervical mucosal involvement (in old FIGO staging), the positive predictive value was only 50% and the accuracy decreased to 74.07%. Agreement between MRI and the final histology using the old and new FIGO classification was

  10. Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

    Science.gov (United States)

    Liu, B; Lee, K-W; Anzo, M; Zhang, B; Zi, X; Tao, Y; Shiry, L; Pollak, M; Lin, S; Cohen, P

    2007-03-15

    Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer. PMID:16983336

  11. IL-17A-producing T cells and associated cytokines are involved in the progression of gastric cancer.

    Science.gov (United States)

    Zhong, Fengyun; Cui, Dawei; Tao, Hong; Du, Hong; Xing, Chungen

    2015-11-01

    Interleukin-17A-producing T cells (IL-17A+ T) (IL-17A+CD4+ Th17, IL-17A+CD8+ Tc17 and IL-17A+ γδT17 cells) and associated cytokines (IL-17A, IL-23 and IL-1β) play crucial roles in inflammation-associated diseases, such as infection, autoimmunity and tumors. Th17 cells promote human gastric cancer (GC), although the source of intracellular IL‑17A and the roles of Tc17 and γδT17 cells remain poorly understood. In this study, the frequencies of circulating Th17 and γδT17 cells in patients with GC were found to be significantly increased compared to those in healthy donors; however, Tc17 cells were decreased in these patients, and a negative relationship was found between the frequencies of Th17 and Tc17 cells. Moreover, the cytokine IL‑17A was found to be produced mainly by Th17 cells in human peripheral blood. Similarly, serum cytokine levels and relative mRNA expression levels of IL‑17A, IL‑23 and IL‑1β were significantly increased in patients with GC, and the frequency of Th17 cells was closely associated with serum IL‑17A concentrations in patients with GC. Additionally, Th17 cells and associated cytokines were present at significantly different levels during the progression and metastasis of GC, as were Tc17 and γδT17 cells. Taken together, these findings suggest that IL-17A+ T cells and associated cytokines might play crucial roles in human GC progression and metastasis and thus represent potential targets for treatment. PMID:26352729

  12. Twice-Weekly Hypofractionated Intensity-Modulated Radiotherapy for Localized Prostate Cancer With Low-Risk Nodal Involvement: Toxicity and Outcome From a Dose Escalation Pilot Study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy (IMRT). Methods and Materials: Between 2003 and 2006, 82 prostate cancer patients with a nodal involvement risk ≤20% (Roach index) have been treated to the prostate with or without seminal vesicles with 56 Gy (4 Gy/fraction twice weekly) and an overall treatment time of 6.5 weeks. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) grading system. Median follow-up was 48 months (range, 9-67 months). Results: All patients completed the treatment without interruptions. No patient presented with Grade ≥3 acute GU or GI toxicity. Of the patients, 4% presented with Grade 2 GU or GI persistent acute toxicity 6 weeks after treatment completion. The estimated 4-year probability of Grade ≥2 late GU and GI toxicity-free survival were 94.2% ± 2.9% and 96.1% ± 2.2%, respectively. One patient presented with Grade 3 GI and another patient with Grade 4 GU late toxicity, which were transitory in both cases. The 4-year actuarial biochemical relapse-free survival was 91.3% ± 5.9%, 76.4% ± 8.8%, and 77.5% ± 8.9% for low-, intermediate-, and high-risk groups, respectively. Conclusions: In patients with localized prostate cancer, acute and late toxicity were minimal after dose-escalation administering twice-weekly 4 Gy to a total dose of 56 Gy, with IMRT. Further prospective trials are warranted to further assess the best fractionation schemes for these patients.

  13. A case of reversible posterior leukoencephalopathy syndrome which developed during chemoradiotherapy for head and neck cancer. The involvement of bacterial translocation was considered

    International Nuclear Information System (INIS)

    Combination therapy such as chemotherapy and radiotherapy is often chosen, depending on the case, for head and neck cancer in view of the preservation of potency. However, on the other hand, it is necessary to note the onset of therapeutic side effects. The patient was a 35-year-old woman. During chemoradiotherapy for mesopharyngeal carcinoma, she suddenly developed shock and multiple organ failure, requiring intensive treatment. She also developed reversible central nerve symptoms during the course. The involvement of bacterial translocation was thought to be the cause of shock, and the reversible central nerve symptoms were considered to be a pathological condition, known as reversible posterior leukoencephalopathy syndrome. We discuss these conditions on the basis of the clinical features, and the process that led to diagnosis in this case. (author)

  14. Wortmannin induces MCF-7 breast cancer cell death via the apoptotic pathway, involving chromatin condensation, generation of reactive oxygen species, and membrane blebbing

    Directory of Open Access Journals (Sweden)

    Akter R

    2012-07-01

    Full Text Available Rozina Akter,1 Md. Zakir Hossain,2 Maurice G Kleve,3 Michael A Gealt31Applied Biosciences Emphasis, Department of Applied Science, 2Graduate Institute of Technology, 3Department of Biology, College of Science and of Mathematics, University Arkansas at Little Rock, Little Rock, AR, USABackground: Apoptosis can be used as a reliable marker for evaluating potential chemotherapeutic agents. Because wortmannin is a microbial steroidal metabolite, it specifically inhibits the phosphatidyl inositol 3-kinase pathway, and could be used as a promising apoptosis-based therapeutic agent in the treatment of cancer. The objective of this study was to investigate the biomolecular mechanisms involved in wortmannin-induced cell death of breast cancer-derived MCF-7 cells.Methods and results: Our experimental results demonstrate that wortmannin has strong apoptotic effects through a combination of different actions, including reduction of cell viability in a dose-dependent manner, inhibition of proliferation, and enhanced generation of intracellular reactive oxygen species.Conclusion: Our findings suggest that wortmannin induces MCF-7 cell death via a programmed pathway showing chromatin condensation, nuclear fragmentation, reactive oxygen species, and membrane blebbing, which are characteristics typical of apoptosis.Keywords: wortmannin, human breast adenocarcinoma, apoptosis, reactive oxygen species, flow cytometry

  15. Cancer

    Science.gov (United States)

    ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ... the case with skin cancers , as well as cancers of the lung, breast, and colon. If the tumor has spread ...

  16. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  17. Epithelial-mesenchymal transition and cancer stem cells, mediated by a long non-coding RNA, HOTAIR, are involved in cell malignant transformation induced by cigarette smoke extract

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yi; Luo, Fei; Xu, Yuan; Wang, Bairu; Zhao, Yue; Xu, Wenchao; Shi, Le; Lu, Xiaolin; Liu, Qizhan, E-mail: drqzliu@hotmail.com

    2015-01-01

    The incidence of lung diseases, including cancer, caused by cigarette smoke is increasing, but the molecular mechanisms of gene regulation induced by cigarette smoke remain unclear. This report describes a long noncoding RNA (lncRNA) that is induced by cigarette smoke extract (CSE) and experiments utilizing lncRNAs to integrate inflammation with the epithelial-mesenchymal transition (EMT) in human bronchial epithelial (HBE) cells. The present study shows that, induced by CSE, IL-6, a pro-inflammatory cytokine, leads to activation of STAT3, a transcription activator. A ChIP assay determined that the interaction of STAT3 with the promoter regions of HOX transcript antisense RNA (HOTAIR) increased levels of HOTAIR. Blocking of IL-6 with anti-IL-6 antibody, decreasing STAT3, and inhibiting STAT3 activation reduced HOTAIR expression. Moreover, for HBE cells cultured in the presence of HOTAIR siRNA for 24 h, the CSE-induced EMT, formation of cancer stem cells (CSCs), and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates HOTAIR in an autocrine manner, contributes to the EMT and to CSCs induced by CSE. These data define a link between inflammation and EMT, processes involved in the malignant transformation of cells caused by CSE. This link, mediated through lncRNAs, establishes a mechanism for CSE-induced lung carcinogenesis. - Highlights: • STAT3 directly regulates the levels of LncRNA HOTAIR. • LncRNA HOTAIR mediates the link between inflammation and EMT. • LncRNA HOTAIR is involved in the malignant transformation of cells caused by CSE.

  18. Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and γ-radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, University of Science and Technology (UST), 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Kim, Seo Yoen [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Kim, Hyun A; Kim, Jeong Yul [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Lee, Jae Ha; Choi, Soo Im [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Department of Radiation Biotechnology and Applied Radioisotope, University of Science and Technology (UST), 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Han, Jeong Ran; Kim, Kug Chan [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of); Cho, Eun Wie [Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806 (Korea, Republic of)

    2014-01-03

    Highlights: •DKK1 was expressed differently among non-small-cell lung cancer cell lines. •DKK1 negatively regulated ROMO1 gene expression. •Disturbance of DKK1 level induced the imbalance of cellular ROS. •DKK1/ROMO1-induced ROS imbalance is involved in cell survival in NSCLC. -- Abstract: Dickkopf1 (DKK1), a secreted protein involved in embryonic development, is a potent inhibitor of the Wnt signaling pathway and has been postulated to be a tumor suppressor or tumor promoter depending on the tumor type. In this study, we showed that DKK1 was expressed differently among non-small-cell lung cancer cell lines. The DKK1 expression level was much higher in A549 cells than in H460 cells. We revealed that blockage of DKK1 expression by silencing RNA in A549 cells caused up-regulation of intracellular reactive oxygen species (ROS) modulator (ROMO1) protein, followed by partial cell death, cell growth inhibition, and loss of epithelial–mesenchymal transition property caused by ROS, and it also increased γ-radiation sensitivity. DKK1 overexpression in H460 significantly inhibited cell survival with the decrease of ROMO1 level, which induced the decrease of cellular ROS. Thereafter, exogenous N-acetylcysteine, an antioxidant, or hydrogen peroxide, a pro-oxidant, partially rescued cells from death and growth inhibition. In each cell line, both overexpression and blockage of DKK1 not only elevated p-RB activation, which led to cell growth arrest, but also inactivated AKT/NF-kB, which increased radiation sensitivity and inhibited cell growth. This study is the first to demonstrate that strict modulation of DKK1 expression in different cell types partially maintains cell survival via tight regulation of the ROS-producing ROMO1 and radiation resistance.

  19. Epithelial-mesenchymal transition and cancer stem cells, mediated by a long non-coding RNA, HOTAIR, are involved in cell malignant transformation induced by cigarette smoke extract

    International Nuclear Information System (INIS)

    The incidence of lung diseases, including cancer, caused by cigarette smoke is increasing, but the molecular mechanisms of gene regulation induced by cigarette smoke remain unclear. This report describes a long noncoding RNA (lncRNA) that is induced by cigarette smoke extract (CSE) and experiments utilizing lncRNAs to integrate inflammation with the epithelial-mesenchymal transition (EMT) in human bronchial epithelial (HBE) cells. The present study shows that, induced by CSE, IL-6, a pro-inflammatory cytokine, leads to activation of STAT3, a transcription activator. A ChIP assay determined that the interaction of STAT3 with the promoter regions of HOX transcript antisense RNA (HOTAIR) increased levels of HOTAIR. Blocking of IL-6 with anti-IL-6 antibody, decreasing STAT3, and inhibiting STAT3 activation reduced HOTAIR expression. Moreover, for HBE cells cultured in the presence of HOTAIR siRNA for 24 h, the CSE-induced EMT, formation of cancer stem cells (CSCs), and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates HOTAIR in an autocrine manner, contributes to the EMT and to CSCs induced by CSE. These data define a link between inflammation and EMT, processes involved in the malignant transformation of cells caused by CSE. This link, mediated through lncRNAs, establishes a mechanism for CSE-induced lung carcinogenesis. - Highlights: • STAT3 directly regulates the levels of LncRNA HOTAIR. • LncRNA HOTAIR mediates the link between inflammation and EMT. • LncRNA HOTAIR is involved in the malignant transformation of cells caused by CSE

  20. Electric pulses used in electrochemotherapy and electrogene therapy do not significantly change the expression profile of genes involved in the development of cancer in malignant melanoma cells

    Directory of Open Access Journals (Sweden)

    Glavac Damjan

    2009-08-01

    Full Text Available Abstract Background Electroporation is a versatile method for in vitro or in vivo delivery of different molecules into cells. However, no study so far has analysed the effects of electric pulses used in electrochemotherapy (ECT pulses or electric pulses used in electrogene therapy (EGT pulses on malignant cells. We studied the effect of ECT and EGT pulses on human malignant melanoma cells in vitro in order to understand and predict the possible effect of electric pulses on gene expression and their possible effect on cell behaviour. Methods We used microarrays with 2698 different oligonucleotides to obtain the expression profile of genes involved in apoptosis and cancer development in a malignant melanoma cell line (SK-MEL28 exposed to ECT pulses and EGT pulses. Results Cells exposed to ECT pulses showed a 68.8% average survival rate, while cells exposed to EGT pulses showed a 31.4% average survival rate. Only seven common genes were found differentially expressed in cells 16 h after exposure to ECT and EGT pulses. We found that ECT and EGT pulses induce an HSP70 stress response mechanism, repress histone protein H4, a major protein involved in chromatin assembly, and down-regulate components involved in protein synthesis. Conclusion Our results show that electroporation does not significantly change the expression profile of major tumour suppressor genes or oncogenes of the cell cycle. Moreover, electroporation also does not changes the expression of genes involved in the stability of DNA, supporting current evidence that electroporation is a safe method that does not promote tumorigenesis. However, in spite of being considered an isothermal method, it does to some extent induce stress, which resulted in the expression of the environmental stress response mechanism, HSP70.

  1. Electric pulses used in electrochemotherapy and electrogene therapy do not significantly change the expression profile of genes involved in the development of cancer in malignant melanoma cells

    International Nuclear Information System (INIS)

    Electroporation is a versatile method for in vitro or in vivo delivery of different molecules into cells. However, no study so far has analysed the effects of electric pulses used in electrochemotherapy (ECT pulses) or electric pulses used in electrogene therapy (EGT pulses) on malignant cells. We studied the effect of ECT and EGT pulses on human malignant melanoma cells in vitro in order to understand and predict the possible effect of electric pulses on gene expression and their possible effect on cell behaviour. We used microarrays with 2698 different oligonucleotides to obtain the expression profile of genes involved in apoptosis and cancer development in a malignant melanoma cell line (SK-MEL28) exposed to ECT pulses and EGT pulses. Cells exposed to ECT pulses showed a 68.8% average survival rate, while cells exposed to EGT pulses showed a 31.4% average survival rate. Only seven common genes were found differentially expressed in cells 16 h after exposure to ECT and EGT pulses. We found that ECT and EGT pulses induce an HSP70 stress response mechanism, repress histone protein H4, a major protein involved in chromatin assembly, and down-regulate components involved in protein synthesis. Our results show that electroporation does not significantly change the expression profile of major tumour suppressor genes or oncogenes of the cell cycle. Moreover, electroporation also does not changes the expression of genes involved in the stability of DNA, supporting current evidence that electroporation is a safe method that does not promote tumorigenesis. However, in spite of being considered an isothermal method, it does to some extent induce stress, which resulted in the expression of the environmental stress response mechanism, HSP70

  2. Mitochondria-acting hexokinase II peptides carried by short-length carbon nanotubes with increased cellular uptake, endosomal evasion, and enhanced bioactivity against cancer cells

    Science.gov (United States)

    Yoong, Sia Lee; Lau, Wei Liang; Liu, Ang Yu; Prendergast, D'arcy; Ho, Han Kiat; Yu, Victor Chun Kong; Lee, Chengkuo; Ang, Wee Han; Pastorin, Giorgia

    2015-08-01

    Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its involvement in metabolic reprogramming and also apoptosis prevention. The peptide derived from the fifteen amino acid sequence in the HKII N-terminal region [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and trigger apoptosis. However, this peptide is not cell-permeable. In this study, multi-walled carbon nanotubes (MWCNTs) were used to effectively deliver HKII(pep) across cellular barriers without compromising their bioactivity. The peptide was conjugated on either oxidized MWCNTs or 2,2'-(ethylenedioxy)bis(ethylamine)-functionalized MWCNTs, yielding MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep), respectively. Both conjugates were shown to be internalized by breast cancer MCF-7 cells using confocal microscopy. Moreover, these nanoconjugates seemed to have escaped from endosomes and be in the vicinity of mitochondria. The WST-1 cytotoxicity assay conducted on MCF-7 and colon carcinoma HCT116 cells revealed that MWCNT-peptide conjugates were significantly more effective in curbing cancer cell growth compared to a commercially available cell permeable HKII fusion peptide. In addition, both nanoconjugates displayed an enhanced ability in eliciting apoptosis and depleting the ATP level in HCT116 cells compared to the mere HKII peptide. Importantly, hexokinase II release from mitochondria was demonstrated in MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep) treated cells, highlighting that the structure and bioactivity of HKII(pep) were not compromised after covalent conjugation to MWCNTs.Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its involvement in metabolic reprogramming and also apoptosis prevention. The peptide derived from the fifteen amino acid sequence in the HKII N-terminal region [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and trigger apoptosis. However, this peptide is not cell-permeable. In this study

  3. Metformin inhibits epithelial–mesenchymal transition in prostate cancer cells: Involvement of the tumor suppressor miR30a and its target gene SOX4

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jing; Shen, Chengwu [Department of Pharmacy, Shandong Provincial Hospital, Shandong University, Jinan 250021 (China); Wang, Lin [Department of Pathology, School of Medicine, Shandong University, Jinan 250012 (China); Research Center for Medicinal Biotechnology, Shandong Academy of Medicinal Sciences, Jinan 250012 (China); Ma, Quanping [Department of Clinical Laboratory, The Fourth People’s Hospital of Jinan, Jinan 250031 (China); Xia, Pingtian; Qi, Mei; Yang, Muyi [Department of Pathology, School of Medicine, Shandong University, Jinan 250012 (China); Han, Bo, E-mail: boh@sdu.edu.cn [Department of Pathology, School of Medicine, Shandong University, Jinan 250012 (China); Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012 (China)

    2014-09-26

    Highlights: • Metformin inhibits TGF-β-induced EMT in prostate cancer (PCa) cells. • Metformin upregulates tumor suppressor miR30a and downregulates SOX4 in PCa cells. • SOX4 is a target gene of miR30a. - Abstract: Tumor metastasis is the leading cause of mortality and morbidity of prostate cancer (PCa) patients. Epithelial–mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. Recent evidence suggested that diabetic patients treated with metformin have lower PCa risk and better prognosis. This study was aimed to investigate the effects of metformin on EMT in PCa cells and the possible microRNA (miRNA)-based mechanisms. MiRNAs have been shown to regulate various processes of cancer metastasis. We herein showed that metformin significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell cycle arrest and inhibits invasiveness and motility capacity of Vcap cells. Metformin could inhibit TGF-β-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p = 0.013), Vimentin (p = 0.002) and the decrease of E-cadherin (p = 0.0023) and β-catenin (p = 0.034) at mRNA and protein levels. Notably, we demonstrated significant upregulation of miR30a levels by metformin (P < 0.05) and further experiments indicated that miR30a significantly inhibits proliferation and EMT process of Vcap cells. Interestingly, we identified that SOX4, a previously reported oncogenic transcriptional factor and modulator of EMT, is a direct target gene of miR30a. Finally, we screened the expression of miR30a and SOX4 in 84 PCa cases with radical prostatectomy. Of note, SOX4 overexpression is significantly associated with decreased levels of miR30a in PCa cases. In all, our study suggested that inhibition of EMT by metformin in PCa cells may involve upregulation of miR30a and downregulation of SOX4.

  4. Metformin inhibits epithelial–mesenchymal transition in prostate cancer cells: Involvement of the tumor suppressor miR30a and its target gene SOX4

    International Nuclear Information System (INIS)

    Highlights: • Metformin inhibits TGF-β-induced EMT in prostate cancer (PCa) cells. • Metformin upregulates tumor suppressor miR30a and downregulates SOX4 in PCa cells. • SOX4 is a target gene of miR30a. - Abstract: Tumor metastasis is the leading cause of mortality and morbidity of prostate cancer (PCa) patients. Epithelial–mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. Recent evidence suggested that diabetic patients treated with metformin have lower PCa risk and better prognosis. This study was aimed to investigate the effects of metformin on EMT in PCa cells and the possible microRNA (miRNA)-based mechanisms. MiRNAs have been shown to regulate various processes of cancer metastasis. We herein showed that metformin significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell cycle arrest and inhibits invasiveness and motility capacity of Vcap cells. Metformin could inhibit TGF-β-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p = 0.013), Vimentin (p = 0.002) and the decrease of E-cadherin (p = 0.0023) and β-catenin (p = 0.034) at mRNA and protein levels. Notably, we demonstrated significant upregulation of miR30a levels by metformin (P < 0.05) and further experiments indicated that miR30a significantly inhibits proliferation and EMT process of Vcap cells. Interestingly, we identified that SOX4, a previously reported oncogenic transcriptional factor and modulator of EMT, is a direct target gene of miR30a. Finally, we screened the expression of miR30a and SOX4 in 84 PCa cases with radical prostatectomy. Of note, SOX4 overexpression is significantly associated with decreased levels of miR30a in PCa cases. In all, our study suggested that inhibition of EMT by metformin in PCa cells may involve upregulation of miR30a and downregulation of SOX4

  5. Involvement of 1,25D3-MARRS (membrane associated, rapid response steroid-binding), a novel vitamin D receptor, in growth inhibition of breast cancer cells

    International Nuclear Information System (INIS)

    In addition to classical roles in calcium homeostasis and bone development, 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] inhibits the growth of several cancer types, including breast cancer. Although cellular effects of 1,25(OH)2D3 traditionally have been attributed to activation of a nuclear vitamin D receptor (VDR), a novel receptor for 1,25(OH)2D3 called 1,25D3-MARRS (membrane-associated, rapid response steroid-binding) protein was identified recently. The purpose of this study was to determine if the level of 1,25D3-MARRS expression modulates 1,25(OH)2D3 activity in breast cancer cells. Relative levels of 1,25D3-MARRS protein in MCF-7, MDA MB 231, and MCF-10A cells were estimated by real-time RT-PCR and Western blotting. To determine if 1,25D3-MARRS receptor was involved in the growth inhibitory effects of 1,25(OH)2D3 in MCF-7 cells, a ribozyme construct designed to knock down 1,25D3-MARRS mRNA was stably transfected into MCF-7 cells. MCF-7 clones in which 1,25D3-MARRS receptor expression was reduced showed increased sensitivity to 1,25(OH)2D3 ( IC50 56 ± 24 nM) compared to controls (319 ± 181 nM; P 3-MARRS receptor lengthened the doubling time in transfectants treated with 1,25(OH)2D3. Knockdown of 1,25D3-MARRS receptor also increased the sensitivity of MCF-7 cells to the vitamin D analogs KH1060 and MC903, but not to unrelated agents (all-trans retinoic acid, paclitaxel, serum/glucose starvation, or the isoflavone, pomiferin). These results suggest that 1,25D3-MARRS receptor expression interferes with the growth inhibitory activity of 1,25(OH)2D3 in breast cancer cells, possibly through the nuclear VDR. Further research should examine the potential for pharmacological or natural agents that modify 1,25D3-MARRS expression or activity as anticancer agents.

  6. Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial

    International Nuclear Information System (INIS)

    TomoBreast is a unicenter, non-blinded randomized trial comparing conventional radiotherapy (CR) vs. hypofractionated Tomotherapy (TT) for post-operative treatment of breast cancer. The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities. The trial started inclusion in May 2007 and reached its recruitment in August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely resected by tumorectomy (BCS) or by mastectomy (MA) who consented to participate were randomized, according to a prescribed computer-generated randomization schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall, plus supraclavicular-axillary field if node-positive, and sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks), versus experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3 weeks). Outcomes evaluated were the pulmonary and heart function. Comparison of proportions used one-sided Fisher's exact test. By May 2010, 70 patients were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases, 32 were assigned to CR (21 BCS, 11 MA), 37 to TT (20 BCS, 17 MA). Skin toxicity of grade ≥1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed no significant difference for left ventricular ejection fraction at 2 years, CR 4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT (P = 0.05). There were no unexpected severe toxicities. Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities. Pulmonary tests showed a slight trend in favor of Tomotherapy, which will need confirmation with longer follow-up of patients. ClinicalTrials.gov NCT00459628

  7. Can Prostate Cancer Be Found Early?

    Science.gov (United States)

    ... Research Get Involved Find Local ACS Learn About Cancer » Prostate Cancer » Detailed Guide » Can prostate cancer be found ... and symptoms of prostate cancer Tests for prostate cancer Prostate cancer stages Survival rates for prostate cancer Previous ...

  8. What Are Oral Cavity and Oropharyngeal Cancers?

    Science.gov (United States)

    ... Research Get Involved Find Local ACS Learn About Cancer » Oral Cavity and Oropharyngeal Cancer » Detailed Guide » What are ... how cancers start and spread, see What Is Cancer? Oral cavity cancer, or just oral cancer, is cancer ...

  9. Tc-99m MIBI imaging for secondary skeletal involvement in breast and prostate cancers and multiple myeloma

    International Nuclear Information System (INIS)

    Objective:The Objective of the study was to evaluate the role of Tc-99m MIBI whole body imaging in assessing secondary osseous involvement in patients with malignancy of breast, prostate or multiple myeloma. In this study a total of 41 patients were included. Out of these 18 had breast carcinoma, 12 had prostate carcinoma and 11 were diagnosed cases of multiple myeloma. All patients had their whole body MIBI imaging done which was compared with MDP bone scan by employing some other diagnostic modality (plain radiographs, CT scan, MRI scan or histopathological evidence) to confirm the lesions detected by either of the scans. The results of all the studies were evaluated qualitatively by assessing the number of lesions visually by three experienced nuclear physicians. Quantitative analysis of the lesions was also done, by calculating the lesion to normal uptake ratio, to augment the findings of visual assessment and for statistical analysis. Results: Results obtained in this study by MIBI and MDP imaging varied significantly among different groups and subgroups of patients depending on the primary malignancy and stage of therapy. However results obtained by imaging of patients within a group and subgroup were consistent with each other. MIBI scan showed a sensitivity of 99% in cases of multiple myeloma, where MDP scan was only 16% sensitive. In case of pre-therapy patients of breast and prostate carcinoma, the sensitivity of MIBI scan came out to be 80% and 74% respectively. In patients who were on chemo/radiotherapy MIBI scan was 54% sensitive in patients with breast carcinoma and 38% sensitive in patients with prostate carcinoma. MDP scan showed a sensitivity of 100% in all the groups. The positive predictive value of MIBI scan came out to be 100% but that of MDP was 42-76% in different groups. It is therefore concluded that the most significant role of MIBI imaging is in detection of bone metastases secondary to breast and prostate carcinoma in pre

  10. Phase 1/2 study of valproic acid and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer-V-shoRT-R3 (Valproic acid - short RadioTherapy - rectum 3rd trial)

    OpenAIRE

    Avallone, Antonio; Piccirillo, Maria Carmela; Delrio, Paolo; Pecori, Biagio; Di Gennaro, Elena; Aloj, Luigi; Tatangelo, Fabiana; D’Angelo, Valentina; Granata, Cinzia; Cavalcanti, Ernesta; Maurea, Nicola; Maiolino, Piera; Bianco, Franco; Montano, Massimo; Silvestro, Lucrezia

    2014-01-01

    Background Locally advanced rectal cancer (LARC) is a heterogeneous group of tumors where a risk-adapted therapeutic strategy is needed. Short-course radiotherapy (SCRT) is a more convenient option for LARC patients than preoperative long-course RT plus capecitabine. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with RT and chemotherapy in the treatment of solid tumors. Valproic acid (VPA) is an anti-epileptic drug with HDACi and anticancer activity. In preclinical...

  11. therapeutic effect of three-dimensional conformal involved-field radiotherapy combined with chemotherapy on limited disease stage small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To analyze the therapeutic effect of three-dimensional conformal involved-field radiotherapy (3D-CRT) combined with chemotherapy on limited disease stage small cell lung cancer (LD-SCLC). Methods: The clinical data of 85 patients of LD-SCLC treated with 3D-CRT at the dose of 2 Gy/fraction, 5 fractions per week for 5-7 weeks, with the median dose of 50 Gy (46-66 Gy), combined with 4-8 cycles chemotherapy, 64 males and 21 females, aged 29-76, were collected and analyzed. Results: The complete remission rate, partial remission rate, stability rate, and total effective rate were 36.5%, 52.9%, 10.6%, and 89.4%, respectively. The median survival time was 18 months, with the 1-, 2-, and 3-year overall survival rates of 65.9%, 33.8%, and 15.9%, respectively. The local recurrence rate, distant metastasis rate, and local recurrence + distant metastasis rate were 15.2% (9/85), 49.2% (29/85), and 35.6% (21/85), respectively. Body weight,response to therapy, cycles for chemotherapy, and concurrent chemo-radiotherapy were all independent prognostic factors for LD-SCLC. Cox multivariable regression was used to analyze the prognostic factors. Conclusions: Involved-field radiotherapy is effective for LD-SCLC. Distance metastasis is the main cause of treatment failure. (authors)

  12. Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Men With Intermediate-Risk Prostate Cancer: Analysis of Short- and Medium-Term Toxicity and Quality of Life

    International Nuclear Information System (INIS)

    Purpose: To determine the short- and medium-term effects of a single high-dose-rate brachytherapy fraction of 15Gy and hypofractionated external beam radiation therapy for prostate cancer. Methods and Materials: Eligible patients had localized prostate cancer with a Gleason score of 7 and a prostate-specific antigen (PSA) concentration of 21), 8% of patients developed mild to moderate dysfunction, and 27% of patients developed severe erectile dysfunction. Baseline EPIC bowel, urinary, and sexual bother scores decreased by 9, 7, and 19 points, respectively, at 1 year. No patient has experienced biochemical failure, and 16 of the first 17 biopsy results showed no malignancy. Conclusions: Treatment is well tolerated in the short and medium term, with low toxicity and encouraging early indicators of disease control.

  13. Determination of HER2 amplification in primary breast cancer using dual-colour chromogenic in situ hybridization is comparable to fluorescence in situ hybridization: a European multicentre study involving 168 specimens

    OpenAIRE

    García-Caballero, Tomás; Grabau, Dorthe; Green, Andrew R.; Gregory, John; Schad, Arno; Kohlwes, Elke; Ellis, Ian O; Watts, Sarah; Mollerup, Jens

    2010-01-01

    García-Caballero T, Grabau D, Green A R, Gregory J, Schad A, Kohlwes E, Ellis I O, Watts S & Mollerup J (2010) Histopathology 56, 472–480 Determination of HER2 amplification in primary breast cancer using dual-colour chromogenic in situ hybridization is comparable to fluorescence in situ hybridization: a European multicentre study involving 168 specimens Aims: Fluorescence in situ hybridization (FISH) can be used to reveal several genomic imbalances relevant to proper cancer diagnosis and to ...

  14. Scapula alata in early breast cancer patients enrolled in a randomized clinical trial of post-surgery short-course image-guided radiotherapy

    Directory of Open Access Journals (Sweden)

    Adriaenssens Nele

    2012-05-01

    Full Text Available Abstract Background Scapula alata (SA is a known complication of breast surgery associated with palsy of the serratus anterior, but it is seldom mentioned. We evaluated the risk factors associated with SA and the relationship of SA with ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of post-surgery radiotherapy (RT. Methods The trial randomized women with completely resected stage I-II breast cancer to short-course image-guided RT, versus conventional RT. SA, arm volume and shoulder-arm mobility were measured prior to RT and at one to three months post-RT. Shoulder/arm morbidities were computed as a post-RT percentage change relative to pre-RT measurements. Results Of 119 evaluable patients, 13 (= 10.9% had pre-RT SA. Age younger than 50 years old, a body mass index less than 25 kg/m2, and axillary lymph node dissection were significant risk factors, with odds ratios of 4.8 (P = 0.009, 6.1 (P = 0.016, and 6.1 (P = 0.005, respectively. Randomization group was not significant. At one to three months’ post-RT, mean arm volume increased by 4.1% (P = 0.036 and abduction decreased by 8.6% (P = 0.046 among SA patients, but not among non-SA patients. SA resolved in eight, persisted in five, and appeared in one patient. Conclusion The relationship of SA with lower body mass index suggests that SA might have been underestimated in overweight patients. Despite apparent resolution of SA in most patients, pre-RT SA portended an increased risk of shoulder/arm morbidity. We argue that SA warrants further investigation. Incidentally, the observation of SA occurring after RT in one patient represents the second case of post-RT SA reported in the literature.

  15. Robotic versus laparoscopic surgery for mid or low rectal cancer in male patients after neoadjuvant chemoradiation therapy: comparison of short-term outcomes.

    Science.gov (United States)

    Serin, Kursat Rahmi; Gultekin, Fatma Ayca; Batman, Burçin; Ay, Serden; Kapran, Yersu; Saglam, Sezer; Asoglu, Oktar

    2015-09-01

    The aim of our study was to compare short-term outcomes of robotic and laparoscopic sphincter-saving total mesorectal excision (TME) in male patients with mid-low rectal cancer (RC) after neadjuvant chemoradiotherapy (NCRT). The study was conducted as a retrospective review of a prospectively maintained database, and we analyzed 14 robotic and 65 laparoscopic sphincter saving TME (R-TME and L-TME, respectively) performed by one surgeon between 2005 and 2013. Patient characteristics, perioperative recovery, postoperative complications and and pathology results were compared between the two groups. The patient characteristics did not differ significantly between the two groups. Median operating time was longer in the R-TME than in the L-TME group (182 min versus 140 min). Only two conversions occurred in the L-TME group. No difference was found between groups regarding perioperative recovery and postoperative complication rates. The median number of harvested lymph nodes was higher in the RTME than in the L-TME group (32 versus 23, p = 0.008). The median circumferential margin (CRM) was 10 mm in the R-TME group, 6.5 mm in the L-TME group (p = 0.047. The median distal resection margin (DRM) was 27.5 mm in the R-TME, 15 mm in the L-TME group (p = 0.014). Macroscopic grading of the specimen in the R-TME group was complete in all patients. In the L-TME group, grading was complete in 52 (80%) and incomplete in 13 (20%) cases (p = 0.109). R-TME is a safe and feasible procedure that facilitates performing of TME in male patients with mid-low RC after NCRT. PMID:26531198

  16. Bloodstream Infection in Neutropenic Cancer Patients Related to Short-Term Nontunnelled Catheters Determined by Quantitative Blood Cultures, Differential Time to Positivity, and Molecular Epidemiological Typing with Pulsed-Field Gel Electrophoresis

    OpenAIRE

    Seifert, Harald; Cornely, Oliver; Seggewiss, Kerstin; Decker, Mathias; Stefanik, Danuta; Wisplinghoff, Hilmar; Fätkenheuer, Gerd

    2003-01-01

    To determine the rate of catheter-related bloodstream infection (CRBSI) among cases of primary bloodstream infection (BSI) in febrile neutropenic cancer patients with short-term nontunnelled catheters, quantitative paired blood cultures (Isolator) from the central venous catheter (CVC) and peripheral vein were obtained between November 1999 and January 2001. Bactec blood culture bottles were obtained to determine the differential time to positivity (DTP). CRBSI was defined as a quantitative b...

  17. Involved-field radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer: disease control, patterns of failure and survival

    International Nuclear Information System (INIS)

    Full text: Introduction: Major randomised trials have employed elective nodal irradiation as part of combined modality therapy for limited-stage small-cell lung cancer (SCLC). The present investigation describes patterns of failure, disease control, and survival outcomes for involved-field radiotherapy with concurre chemotherapy, without elective irradiation of uninvolved mediastinal nodal regions. Methods: Retrospective analysis of SCLC patients treated with curative-in en accelerated, twice-daily radiotherapy and concurrent platinum-based chemotherapy at an academic institution. Treatment fields were reviewed, and patients who completed 242 Gy in 1.5 Gy twice-daily fractions to involved fields (without elective irradiation of uninvolved mediastinal lymphatic regions) were included in the present analysis. Initial patterns of failure, disease control and overall survival were recorded. Results: Fifty-two patients fulfilled study criteria and were included in the present analysis. All but one patient completed three to four cycles of chemotherapy, and 10 patients experienced grade 3 acute esophagitis. At a