WorldWideScience

Sample records for cancer updating validation

  1. Breast Cancer Research Update

    Science.gov (United States)

    ... JavaScript on. Feature: Breast Cancer Breast Cancer Research Update Winter 2017 Table of Contents National Cancer Institute ... Addressing Breast Cancer's Unequal Burden / Breast Cancer Research Update Winter 2017 Issue: Volume 11 Number 4 Page ...

  2. Model validation: Correlation for updating

    Indian Academy of Sciences (India)

    D J Ewins

    2000-06-01

    In this paper, a review is presented of the various methods which are available for the purpose of performing a systematic comparison and correlation between two sets of vibration data. In the present case, the application of interest is in conducting this correlation process as a prelude to model correlation or updating activity.

  3. Updates on Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ojas Vyas

    2014-05-01

    Full Text Available Pancreatic adenocarcinoma remains a therapeutic challenge. The American Cancer Society estimates that in 2014 about 46,420 people will be diagnosed with pancreatic cancer and about 39,590 people will die of pancreatic cancer in the United States [1]. The incidence of pancreatic carcinoma has markedly increased over the past several decades and it now ranks as the fourth leading cause of cancer-related death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood. Although progress in the development of new cytotoxic and biological drugs for the treatment of pancreatic cancer continues, the outcome remains grim. Many organizations and associations have taken an effort to improve knowledge, understanding and outcome of patients with pancreatic cancer. Pancreas Club, since its founding in 1966, is aimed to promote the interchange of ideas between physicians and scientists focused on pancreas throughout the world in an informal “club” atmosphere. We attended the 48th Annual Meeting of Pancreas Club in Chicago and reviewed many interesting posters and oral presentations. Here we discuss a few selected abstracts.

  4. Lung cancer screening: Update

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)

    2015-09-15

    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

  5. Updating risk prediction tools: a case study in prostate cancer.

    Science.gov (United States)

    Ankerst, Donna P; Koniarski, Tim; Liang, Yuanyuan; Leach, Robin J; Feng, Ziding; Sanda, Martin G; Partin, Alan W; Chan, Daniel W; Kagan, Jacob; Sokoll, Lori; Wei, John T; Thompson, Ian M

    2012-01-01

    Online risk prediction tools for common cancers are now easily accessible and widely used by patients and doctors for informed decision-making concerning screening and diagnosis. A practical problem is as cancer research moves forward and new biomarkers and risk factors are discovered, there is a need to update the risk algorithms to include them. Typically, the new markers and risk factors cannot be retrospectively measured on the same study participants used to develop the original prediction tool, necessitating the merging of a separate study of different participants, which may be much smaller in sample size and of a different design. Validation of the updated tool on a third independent data set is warranted before the updated tool can go online. This article reports on the application of Bayes rule for updating risk prediction tools to include a set of biomarkers measured in an external study to the original study used to develop the risk prediction tool. The procedure is illustrated in the context of updating the online Prostate Cancer Prevention Trial Risk Calculator to incorporate the new markers %freePSA and [-2]proPSA measured on an external case-control study performed in Texas, U.S.. Recent state-of-the art methods in validation of risk prediction tools and evaluation of the improvement of updated to original tools are implemented using an external validation set provided by the U.S. Early Detection Research Network.

  6. Breast Cancer and Estrogen-Alone Update

    Science.gov (United States)

    ... Issues Research News From NIH Breast Cancer and Estrogen-Alone Update Past Issues / Summer 2006 Table of ... version of this page please turn Javascript on. Estrogen-alone hormone therapy does not increase the risk ...

  7. An update on inflammatory breast cancer

    Directory of Open Access Journals (Sweden)

    P. Thapaliya

    2011-12-01

    Full Text Available Inflammatory breast cancer is one of the most aggressive forms of breast cancer. Once considered to be a uniformly fatal disease, treatment of this entity has evolved significantly over the last two decades. In this article, we review the epidemiology, pathology, biologic underpinnings, radiologic advances, and treatment modalities for inflammatory breast cancer. Updates in surgical therapy, medical oncologic therapy and radiation therapy are reviewed. Emphasis is on cutting edge information regarding inflammatory breast cancer. The management of inflammatory breast cancer is best served by a multidisciplinary team. Continued research into molecular pathways and potential targets is imperative. Future clinical trials should include evaluation of conventional therapy with targeted therapies.

  8. Updates on esophageal and gastric cancers

    Institute of Scientific and Technical Information of China (English)

    Amy Gallo; Charles Cha

    2006-01-01

    Esophageal and gastric cancers are both common and deadly. Patients present most often after disease progression and survival is therefore poor. Due to demographic variability and recent changes in disease incidence, much emphasis has been placed on studying risk factors for both esophageal and gastric cancers.However, with increasing understanding of these diseases, low survival rates persist and continued intensive studies are necessary to optimize treatment plans. This review article discusses updates in the evolving epidemiology, clinical presentation, risk factors,and diagnostic and treatment modalities of esophageal and gastric cancers.

  9. Pharmacogenomics Update in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Aditi Puri

    2014-03-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related deaths in United States. Despite advances in understandingcancer biology and therapeutics, this malignancy carries a grave prognosis with a poor overall survival rate. This is especiallytrue for patients with locally advanced and metastatic disease that are not amenable to surgical resection. Given advances inhuman genome sequencing and pharmacogenomics, we now better understand the complex genetic makeup of these tumorsand numerous gene mutations have been identified that could be potential targets for drug development. In this review, wediscuss two abstract (Abstracts #208 and #192 presented at the 2014 ASCO Gastrointestinal Cancers Symposium aboutpancreatic cancer genome sequencing and their implications for the future of this disease. We discuss what is known aboutthe genome of pancreatic tumors, including common mutations like KRAS, TP53 and SMAD4, as well as discovery ofadditional mutations. In particular, KRAS2 mutations in a subset of patients with pancreatic cancer are discussed. Whilelimited in size and clinical correlativity, these abstracts provide at least seven novel/targetable mutations and elucidatebiologic differences in tumors with wild type and mutant KRAS. These are important steps in understanding tumor biologyand genetic basis of pancreatic cancer to help develop targeted drug therapies in the fast approaching era of personalizedmedicine.

  10. ANALYTICAL METHOD VALIDATION: AN UPDATED REVIEW

    Directory of Open Access Journals (Sweden)

    G. Lavanya, M. Sunil, M.M. Eswarudu*, M. C. Eswaraiah, K. Harisudha and B. Naga Spandana

    2013-04-01

    Full Text Available ABSTRACT: The development of sound Analytical method(s is of supreme importance during the process of drug discovery, release to market and development, culminating in a marketing approval. The objective of this paper is to review the method development, optimize and validation of the method for the drug product from the developmental stage of the formulation to commercial batch of the product. Method development for the interested component in finished product or in process tests and the sample preparation of drug product and to provide practical approaches for determining selectivity, specificity, limit of detection, limit of quantitation, linearity, range accuracy, precision, recovery solution stability, ruggedness, and robustness of liquid chromatographic methods to support the Routine, in process and stability analysis.

  11. [Pregnancy after breast cancer: an update].

    Science.gov (United States)

    Margulies, A-L; Berveiller, P; Mir, O; Uzan, C; Chabbert-Buffet, N; Rouzier, R

    2012-09-01

    Breast cancers account for one third of cancer patients of childbearing age. Given the trend for women to delay childbearing, many of them will not fulfill their parental project at diagnosis of a potential breast cancer. Thus, planning pregnancies in young patients with a history of breast cancer is increasingly becoming a common situation. In this difficult context, several issues have to be discussed with the patient, such as post-chemotherapy premature ovarian failure, fertility-sparing techniques, risk of cancer recurrence or optimal time between cancer and future pregnancy. Potential obstetrical complications, long-term teratogenicity of anti-cancer drugs or breast-feeding are another points that have to be discussed with the patient and her husband. The aim of this updated review of literature was to provide answers to the numerous questions that may be encountered in this type of highly difficult situation. Thus, planning a pregnancy in breast cancer patients seems to be possible with, in one hand, a multidisciplinary approach in order to answer different questions and to avoid side effects of chemotherapy. In the other hand, a close and specialized obstetrical monitoring should be proposed in order to anticipate potential obstetrical complications.

  12. Novel therapies in genitourinary cancer: an update

    Directory of Open Access Journals (Sweden)

    Wu Shenhong

    2008-08-01

    Full Text Available Abstract In recent years, new treatment for renal cell carcinoma (RCC has been a spotlight in the field of cancer therapeutics. With several emerging agents branded as 'targeted therapy' now available, both medical oncologists and urologists are progressively more hopeful for better outcomes. The new remedies may provide patients with improved survival and at the same time less toxicity when compared to traditional cytotoxic agents. This article will center on current and emerging treatment strategies for advanced RCC and other GU malignancies with updates from 2008 annual ASCO meeting.

  13. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg;

    2015-01-01

    BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps...... in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

  14. Validation and update of OMI Total Column Water Vapor product

    Science.gov (United States)

    Wang, Huiqun; Gonzalez Abad, Gonzalo; Liu, Xiong; Chance, Kelly

    2016-09-01

    The collection 3 Ozone Monitoring Instrument (OMI) Total Column Water Vapor (TCWV) data generated by the Smithsonian Astrophysical Observatory's (SAO) algorithm version 1.0 and archived at the Aura Validation Data Center (AVDC) are compared with NCAR's ground-based GPS data, AERONET's sun-photometer data, and Remote Sensing System's (RSS) SSMIS data. Results show that the OMI data track the seasonal and interannual variability of TCWV for a wide range of climate regimes. During the period from 2005 to 2009, the mean OMI-GPS over land is -0.3 mm and the mean OMI-AERONET over land is 0 mm. For July 2005, the mean OMI-SSMIS over the ocean is -4.3 mm. The better agreement over land than over the ocean is corroborated by the smaller fitting residuals over land and suggests that liquid water is a key factor for the fitting quality over the ocean in the version 1.0 retrieval algorithm. We find that the influence of liquid water is reduced using a shorter optimized retrieval window of 427.7-465 nm. As a result, the TCWV retrieved with the new algorithm increases significantly over the ocean and only slightly over land. We have also made several updates to the air mass factor (AMF) calculation. The updated version 2.1 retrieval algorithm improves the land/ocean consistency and the overall quality of the OMI TCWV data set. The version 2.1 OMI data largely eliminate the low bias of the version 1.0 OMI data over the ocean and are 1.5 mm higher than RSS's "clear" sky SSMIS data in July 2005. Over the ocean, the mean of version 2.1 OMI-GlobVapour is 1 mm for July 2005 and 0 mm for January 2005. Over land, the version 2.1 OMI data are about 1 mm higher than GlobVapour when TCWV 15 mm.

  15. Breast and cervical cancer risk in India: An update

    Directory of Open Access Journals (Sweden)

    Smita Asthana

    2014-01-01

    Full Text Available Background: Breast and cervical cancers are two major cancers among Indian women. Analysis of trends would help in planning and organization of programs for control of these cancers. Objective: The objective of the following study is to compute risk of breast and cervical cancers using updated data from different cancer registries of India and study of its trends. Materials and Methods: Data on incidence rates of breast and cervical cancers were obtained from six major cancer registries of India for the years 1982-2008 and from the recently initiated cancer registries, North Eastern Registries of India with a total of 21 registries. Annual percent change in incidence and risk in terms of one in number of women likely to develop cancer was estimated for both the cancers in various registries. Results: The annual percentage change in incidence ranged from 0.46 to 2.56 and −1.14 to −3.4 for breast and cervical cancers respectively. Trends were significant for both cancers in the registries of Chennai, Bangalore, Mumbai and Delhi except Barshi and Bhopal. North East region showed decrease in risk for breast and cervical cancers whereas increasing trend was observed in Imphal (West and for cervical cancer in Silchar. Conclusion: North Eastern region recorded decline in the incidence of breast cancer which is contrary to the observation in other registries, which showed increase in breast cancer and decline in cervical cancer incidences.

  16. Update from the Commission on Cancer.

    Science.gov (United States)

    Clive, R E

    1997-02-01

    A model for an integrated, comprehensive program for high-quality, cost-effective patient care can be found in cancer programs approved by the Commission on Cancer. A key component in assessing the effectiveness of the model is the cancer registry. Changes in the health care delivery system are behind increased demands for and use of cancer registry data. To support this shift and expanded activity, the Commission on Cancer has instituted a series of initiatives. These steps address refinements of the standards for approval, collaborative relationships, performance measurement information, new educational opportunities, and an organized communications campaign.

  17. [Update on current care guidelines: ovarian cancer].

    Science.gov (United States)

    Leminen, Arto; Auranen, Annika; Bützow, Ralf; Hietanen, Sakari; Komulainen, Marja; Kuoppala, Tapio; Mäenpää, Johanna; Puistola, Ulla; Vuento, Maarit; Vuorela, Piia; Yliskoski, Merja

    2012-01-01

    Ovarian cancer is the most lethal gynaecological cancer. It appears that seemingly ovarian or primary peritoneal carcinomas, in fact, originate from fimbriae. BRCA1/2 mutation carriers are recommended for the removal of ovaries and fimbriae, to reduce the risk of cancer. Treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy. The residual tumour volume at the primary operation is the most important predictive factor of survival. The best response at the primary treatment is observed with combination chemotherapy with taxane and platinum. Adding bevacitzumab to first line chemotherapy may improve survival.

  18. Updates in Tumor Profiling in Gastrointestinal Cancers.

    Science.gov (United States)

    Perez, Kimberly; Safran, Howard P

    2015-10-01

    In the last decade there has been a focus on biomarkers that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression of cancers. Characterization of genomes by next-generation sequencing (NGS) has permitted significant advances in gastrointestinal cancer care. These discoveries have fueled the development of novel therapeutics and have laid the groundwork for the development of new treatment strategies. Work in colorectal cancer (CRC) has been in the forefront of these advances. With the continued development of NGS technology and the positive clinical experience in CRC, genome work has begun in esophagogastric, pancreatic, and hepatocellular carcinomas as well.

  19. Updates in colorectal cancer stem cell research

    Directory of Open Access Journals (Sweden)

    Chun-Jie Li

    2014-01-01

    Full Text Available Colorectal cancer (CRC is one of the world most common malignant tumors, also is the main disease, which cause tumor-associated death. Surgery and chemotherapy are the most used treatment of CRC. Recent research reported that, cancer stem cells (CSCs are considered as the origin of tumor genesis, development, metastasis and recurrence in theory. At present, it has been proved that, CSCs existed in many tumors including CRC. In this review, we summary the identification of CSCs according to the cell surface markers, and the development of drugs that target colorectal cancer stem cells.

  20. Intracystic papillary breast cancer: a clinical update

    Science.gov (United States)

    Reefy, Sara Al; Kameshki, Rashid; Sada, Dhabya Al; Elewah, Abdullah Al; Awadhi, Arwa Al; Awadhi, Kamil Al

    2013-01-01

    Introduction: Intracystic (encysted) papillary cancer (IPC) is a rare entity of breast cancer accounting for approximately (1–2%) of all breast tumours [1], usually presenting in postmenopausal women and having an elusive natural history. The prediction of the biological behaviour of this rare form of breast cancer and the clinical outcome showed its overall favourable prognosis; however, its consideration as a form of ductal carcinoma in situ with non-invasive nature is to be reconsidered as it has been shown to present histologically with invasion of basement membrane and even metastasis [2]. The objective of this review is to shed some light on this rare, diagnostically challenging form of breast cancer, including its radiological, histological, and molecular characteristics and its pathological classification. The final goal is to optimize the clinical management including the role of sentinel lymph node biopsy (SLNB), general management with adjuvant radiotherapy (RT), mammary ductoscopy, and hormonal treatment. Methods: A literature review, facilitated by Medline, PubMed, and the Cochrane database, was carried out using the terms ‘Intracystic (encysted) papillary breast cancer’. Results: Intracystic papillary breast cancer (IPC) is best managed in the context of a multidisciplinary team. Surgical excision of the lump with margins in excess of 2 mm is considered satisfactory. Sentinel lymph node biopsy (SLNB) is recommended as data have shown the possibility of the presence of invasive cancer in the final histology. RT following IPC alone is of uncertain significance as this form of cancer is usually low grade and rarely recurs. However, if it is associated with DCIS or invasive cancer and found in young women, radiotherapy may be prudent to reduce local recurrence. Large tumours, centrally located or in cases where breast conserving surgery is unable to achieve a favourable aesthetic result, a skin sparing mastectomy with the opportunity for immediate

  1. Eicosanoid pathway in colorectal cancer: Recent updates.

    Science.gov (United States)

    Tuncer, Sinem; Banerjee, Sreeparna

    2015-11-07

    Enzymatic metabolism of the 20C polyunsaturated fatty acid (PUFA) arachidonic acid (AA) occurs via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways, and leads to the production of various bioactive lipids termed eicosanoids. These eicosanoids have a variety of functions, including stimulation of homeostatic responses in the cardiovascular system, induction and resolution of inflammation, and modulation of immune responses against diseases associated with chronic inflammation, such as cancer. Because chronic inflammation is essential for the development of colorectal cancer (CRC), it is not surprising that many eicosanoids are implicated in CRC. Oftentimes, these autacoids work in an antagonistic and highly temporal manner in inflammation; therefore, inhibition of the pro-inflammatory COX-2 or 5-LOX enzymes may subsequently inhibit the formation of their essential products, or shunt substrates from one pathway to another, leading to undesirable side-effects. A better understanding of these different enzymes and their products is essential not only for understanding the importance of eicosanoids, but also for designing more effective drugs that solely target the inflammatory molecules found in both chronic inflammation and cancer. In this review, we have evaluated the cancer promoting and anti-cancer roles of different eicosanoids in CRC, and highlighted the most recent literature which describes how those molecules affect not only tumor tissue, but also the tumor microenvironment. Additionally, we have attempted to delineate the roles that eicosanoids with opposing functions play in neoplastic transformation in CRC through their effects on proliferation, apoptosis, motility, metastasis, and angiogenesis.

  2. Nutrition and Gastric Cancer Risk: An Update

    Science.gov (United States)

    Data from epidemiologic, experimental, and animal studies indicate that diet plays an important role in the etiology of gastric cancer. High intake of fresh fruit and vegetable, lycopene and lycopene-containing food products, and potentially vitamin C and selenium may reduce the risk for gastric can...

  3. PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE

    Science.gov (United States)

    Agostinis, Patrizia; Berg, Kristian; Cengel, Keith A.; Foster, Thomas H.; Girotti, Albert W.; Gollnick, Sandra O.; Hahn, Stephen M.; Hamblin, Michael R.; Juzeniene, Asta; Kessel, David; Korbelik, Mladen; Moan, Johan; Mroz, Pawel; Nowis, Dominika; Piette, Jacques; Wilson, Brian C.; Golab, Jakub

    2011-01-01

    Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. PMID:21617154

  4. Leuprorelin Acetate in Prostate Cancer: a European Update

    OpenAIRE

    Persad R

    2002-01-01

    This review provides an update on leuprorelin acetate, the world's most widely prescribed depot luteinising hormone-releasing hormone analogue. Leuprorelin acetate has been in clinical use in the palliative treatment of prostate cancer for more than 20 years, but advances continue to be made in terms of convenience and flexibility of administration, and in the incorporation of leuprorelin acetate into novel treatment regimens. The drug is administered in the form of a depot injection containi...

  5. Prostate cancer immunology - an update for Urologists.

    Science.gov (United States)

    Rajarubendra, Nieroshan; Lawrentschuk, Nathan; Bolton, Damien M; Klotz, Laurence; Davis, Ian D

    2011-04-01

    A better understanding of the immune processes in the pathogenesis and progression of prostate cancer (CaP) may point the way towards improved treatment modalities. The challenge is to amplify immune responses to combat tumour escape mechanisms. Infection and inflammation may have a role in prostate carcinogenesis, including the newly discovered xenotropic murine leukaemia virus (XMRV). These inflammatory states damage defence mechanisms and induce a high proliferative state favouring further mutation and impaired immune surveillance. With this knowledge we are able to explore the use of immunotherapy to rejuvenate the immune system in combating CaP. Recently Sipuleucel-T, an immunotherapeutic agent for metastatic androgen independent CaP, has resulted in improved survival and might be the first immunotherapeutic agent to obtain approval for CaP treatment. This short review will focus on the growing body of evidence suggesting an immunity-based link between CaP and inflammation and infection.

  6. Update on prevention and screening of cervical cancer

    Science.gov (United States)

    McGraw, Shaniqua L; Ferrante, Jeanne M

    2014-01-01

    Cervical cancer is the third most common cause of cancer in women in the world. During the past few decades tremendous strides have been made toward decreasing the incidence and mortality of cervical cancer with the implementation of various prevention and screening strategies. The causative agent linked to cervical cancer development and its precursors is the human papillomavirus (HPV). Prevention and screening measures for cervical cancer are paramount because the ability to identify and treat the illness at its premature stage often disrupts the process of neoplasia. Cervical carcinogenesis can be the result of infections from multiple high-risk HPV types that act synergistically. This imposes a level of complexity to identifying and vaccinating against the actual causative agent. Additionally, most HPV infections spontaneously clear. Therefore, screening strategies should optimally weigh the benefits and risks of screening to avoid the discovery and needless treatment of transient HPV infections. This article provides an update of the preventative and screening methods for cervical cancer, mainly HPV vaccination, screening with Pap smear cytology, and HPV testing. It also provides a discussion of the newest United States 2012 guidelines for cervical cancer screening, which changed the age to begin and end screening and lengthened the screening intervals. PMID:25302174

  7. An Update on Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors: Opportunities and Challenges in Cancer Therapy.

    Science.gov (United States)

    Wang, Ying-Qing; Wang, Ping-Yuan; Wang, Yu-Ting; Yang, Guang-Fu; Zhang, Ao; Miao, Ze-Hong

    2016-11-10

    Poly(ADP-ribose)polymerase-1 (PARP-1) is a critical DNA repair enzyme in the base excision repair pathway. Inhibitors of this enzyme comprise a new type of anticancer drug that selectively kills cancer cells by targeting homologous recombination repair defects. Since 2010, important advances have been achieved in PARP-1 inhibitors. Specifically, the approval of olaparib in 2014 for the treatment of ovarian cancer with BRCA mutations validated PARP-1 as an anticancer target and established its clinical importance in cancer therapy. Here, we provide an update on PARP-1 inhibitors, focusing on breakthroughs in their clinical applications and investigations into relevant mechanisms of action, biomarkers, and drug resistance. We also provide an update on the design strategies and the structural types of PARP-1 inhibitors. Opportunities and challenges in PARP-1 inhibitors for cancer therapy will be discussed based on the above advances.

  8. Updated Delft Mass Transport model DMT-2: computation and validation

    Science.gov (United States)

    Hashemi Farahani, Hassan; Ditmar, Pavel; Inacio, Pedro; Klees, Roland; Guo, Jing; Guo, Xiang; Liu, Xianglin; Zhao, Qile; Didova, Olga; Ran, Jiangjun; Sun, Yu; Tangdamrongsub, Natthachet; Gunter, Brian; Riva, Ricardo; Steele-Dunne, Susan

    2014-05-01

    A number of research centers compute models of mass transport in the Earth's system using primarily K-Band Ranging (KBR) data from the Gravity Recovery And Climate Experiment (GRACE) satellite mission. These models typically consist of a time series of monthly solutions, each of which is defined in terms of a set of spherical harmonic coefficients up to degree 60-120. One of such models, the Delft Mass Transport, release 2 (DMT-2), is computed at the Delft University of Technology (The Netherlands) in collaboration with Wuhan University. An updated variant of this model has been produced recently. A unique feature of the computational scheme designed to compute DMT-2 is the preparation of an accurate stochastic description of data noise in the frequency domain using an Auto-Regressive Moving-Average (ARMA) model, which is derived for each particular month. The benefits of such an approach are a proper frequency-dependent data weighting in the data inversion and an accurate variance-covariance matrix of noise in the estimated spherical harmonic coefficients. Furthermore, the data prior to the inversion are subject to an advanced high-pass filtering, which makes use of a spatially-dependent weighting scheme, so that noise is primarily estimated on the basis of data collected over areas with minor mass transport signals (e.g., oceans). On the one hand, this procedure efficiently suppresses noise, which are caused by inaccuracies in satellite orbits and, on the other hand, preserves mass transport signals in the data. Finally, the unconstrained monthly solutions are filtered using a Wiener filter, which is based on estimates of the signal and noise variance-covariance matrices. In combination with a proper data weighting, this noticeably improves the spatial resolution of the monthly gravity models and the associated mass transport models.. For instance, the computed solutions allow long-term negative trends to be clearly seen in sufficiently small regions notorious

  9. High-speed AMB machining spindle model updating and model validation

    Science.gov (United States)

    Wroblewski, Adam C.; Sawicki, Jerzy T.; Pesch, Alexander H.

    2011-04-01

    High-Speed Machining (HSM) spindles equipped with Active Magnetic Bearings (AMBs) have been envisioned to be capable of automated self-identification and self-optimization in efforts to accurately calculate parameters for stable high-speed machining operation. With this in mind, this work presents rotor model development accompanied by automated model-updating methodology followed by updated model validation. The model updating methodology is developed to address the dynamic inaccuracies of the nominal open-loop plant model when compared with experimental open-loop transfer function data obtained by the built in AMB sensors. The nominal open-loop model is altered by utilizing an unconstrained optimization algorithm to adjust only parameters that are a result of engineering assumptions and simplifications, in this case Young's modulus of selected finite elements. Minimizing the error of both resonance and anti-resonance frequencies simultaneously (between model and experimental data) takes into account rotor natural frequencies and mode shape information. To verify the predictive ability of the updated rotor model, its performance is assessed at the tool location which is independent of the experimental transfer function data used in model updating procedures. Verification of the updated model is carried out with complementary temporal and spatial response comparisons substantiating that the updating methodology is effective for derivation of open-loop models for predictive use.

  10. Dietary acrylamide and cancer risk: an updated meta-analysis.

    Science.gov (United States)

    Pelucchi, Claudio; Bosetti, Cristina; Galeone, Carlotta; La Vecchia, Carlo

    2015-06-15

    The debate on the potential carcinogenic effect of dietary acrylamide is open. In consideration of the recent findings from large prospective investigations, we conducted an updated meta-analysis on acrylamide intake and the risk of cancer at several sites. Up to July 2014, we identified 32 publications. We performed meta-analyses to calculate the summary relative risk (RR) of each cancer site for the highest versus lowest level of intake and for an increment of 10 µg/day of dietary acrylamide, through fixed-effects or random-effects models, depending on the heterogeneity test. Fourteen cancer sites could be examined. No meaningful associations were found for most cancers considered. The summary RRs for high versus low acrylamide intake were 0.87 for oral and pharyngeal, 1.14 for esophageal, 1.03 for stomach, 0.94 for colorectal, 0.93 for pancreatic, 1.10 for laryngeal, 0.88 for lung, 0.96 for breast, 1.06 for endometrial, 1.12 for ovarian, 1.00 for prostate, 0.93 for bladder and 1.13 for lymphoid malignancies. The RR was of borderline significance only for kidney cancer (RR = 1.20; 95% confidence interval, CI, 1.00-1.45). All the corresponding continuous estimates ranged between 0.95 and 1.03, and none of them was significant. Among never-smokers, borderline associations with dietary acrylamide emerged for endometrial (RR = 1.23; 95% CI, 1.00-1.51) and ovarian (RR = 1.39; 95% CI, 0.97-2.00) cancers. This systematic review and meta-analysis of epidemiological studies indicates that dietary acrylamide is not related to the risk of most common cancers. A modest association for kidney cancer, and for endometrial and ovarian cancers in never smokers only, cannot be excluded.

  11. Validation of Biomarkers for Prostate Cancer Prognosis

    Science.gov (United States)

    2015-11-01

    example the OncotypeDx assay has been calibrated and already validated precisely for this purpose. In addition, multiparametric MRI shows good ...testing. Cancer 119: 3906-3909, 2013. Zuxiong Chen, Zulfiqar G. Gulzar, Catherine A. St. Hill, Bruce Walcheck, James D. Brooks: Increased expression...Jamaspishvili T, Wei W, Feng Z, Good J, Hawley S, Fazli L, McKenney J, Simko J, Hurtado-Coll A, Carroll P, Gleave M, Lance R, Lin D, Nelson P, Thompson I

  12. Colorectal cancer incidence among polypropylene manufacturing workers. An update.

    Science.gov (United States)

    Lewis, R J; Schnatter, A R; Lerman, S E

    1994-06-01

    This study updates an earlier investigation that found a sixfold excess incidence of colorectal cancer among polypropylene workers for the period January 1960 to September 1985. The study cohort comprised 412 male workers with at least 6 months employment and 10 years latency. For the extended follow-up period (October 1985 to May 1992), the standardized incidence ratio (SIR) based on state comparison rates was slightly elevated and not statistically significant (SIR = 1.5, 95% confidence interval [CI] = 0.5 to 3.5). A 2.3-fold excess was observed among process workers (95% CI = 0.3 to 8.2), but this was based on only two cases. Risk among process/mechanical workers was greater for short-term workers ( or = 10 years, SIR = 0.7, 95% CI = 0.02 to 4.0). Overall, the update findings do not suggest an occupationally related risk. Possible influences of company-sponsored colorectal cancer screening, the polyolefin unit shutdown, and other factors are discussed.

  13. Leuprorelin Acetate in Prostate Cancer: a European Update

    Directory of Open Access Journals (Sweden)

    Persad R

    2002-01-01

    Full Text Available This review provides an update on leuprorelin acetate, the world's most widely prescribed depot luteinising hormone-releasing hormone analogue. Leuprorelin acetate has been in clinical use in the palliative treatment of prostate cancer for more than 20 years, but advances continue to be made in terms of convenience and flexibility of administration, and in the incorporation of leuprorelin acetate into novel treatment regimens. The drug is administered in the form of a depot injection containing leuprorelin acetate microspheres, and is at least as effective in suppressing testosterone secretion as orchiectomy. In patients with prostate cancer, serum testosterone levels are reduced to castrate levels (= 50 ng/dl within 2-3 weeks of the first one-month depot injection of 3.75 mg or three-month depot injection of 11.25 mg. Both the one-month and three-month formulations are effective in delaying tumour progression and alleviating symptoms of locally advanced and metastatic prostate cancer. Tolerability is generally good, with side-effects reflecting effective testosterone suppression. Recent studies have investigated the place of leuprorelin acetate as part of continuous or intermittent maximal androgen blockade (MAB and in neoadjuvant therapy (ie, to reduce the size of the prostate and downsize the tumour before radiotherapy. Additional formulations and presentations are in development, including a six-month injection, with the aim of adding to the clinical flexibility and patient acceptability of this important palliative treatment for prostate cancer.

  14. Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement.

    Science.gov (United States)

    Saslow, Debbie; Andrews, Kimberly S; Manassaram-Baptiste, Deana; Loomer, Lacey; Lam, Kristina E; Fisher-Borne, Marcie; Smith, Robert A; Fontham, Elizabeth T H

    2016-09-01

    Answer questions and earn CME/CNE The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. CA Cancer J Clin 2016;66:375-385. © 2016 American Cancer Society.

  15. Physical Activity and Prostate Cancer: An Updated Review.

    Science.gov (United States)

    Shephard, Roy J

    2016-11-14

    Prostate cancer affects a major proportion of older men, and effective preventive measures are few. Earlier suggestions of 10-30% risk reduction from vigorous physical activity thus merit further analysis. This narrative review updates information on associations between physical activity and prostate cancer, seeking activity patterns associated with maximal risk reduction. Systematic searches of Ovid/MEDLINE and PubMed databases from 1996 to June 2016 have linked the terms prostate neoplasms/prostate cancer with occupation, occupational title, sedentary job or heavy work, exercise, physical activity, sports, athletes, physical education/training or aerobic fitness. Combining these searches with findings from earlier reviews, 85 analyses were captured, although three were repeat analyses of the same data set. Seven analyses reported increased risk, and a further 31 showed no clear relationship. However, 24 analyses found a trend to diminished risk, and 21 a significant decrease (10-30% or more) in at least some subject subsets. Benefit was seen more consistently in occupational than in leisure studies, usually with adolescence or the early 20 s as the optimal age for preventive activity. In general, benefit showed a dose-response relationship, with vigorous activity required for maximal effect. Furthermore, several recent observational studies have indicated that physical activity is beneficial in preventing disease recurrence and improving survival following the diagnosis and treatment of prostate cancer. Despite continued research, conclusive proof of an association between regular physical activity and a low risk of prostate cancer remains elusive. However, reports that exercise exacerbates risk are few, and despite issues around controls, covariates, and co-morbidities, an impressive number of studies have now found significant benefit, suggesting that regular physical activity is important in terms of disease development, progression, and therapy. Given also

  16. Discovery and validation of breast cancer subtypes

    Directory of Open Access Journals (Sweden)

    Bukholm Ida RK

    2006-09-01

    Full Text Available Abstract Background Previous studies demonstrated breast cancer tumor tissue samples could be classified into different subtypes based upon DNA microarray profiles. The most recent study presented evidence for the existence of five different subtypes: normal breast-like, basal, luminal A, luminal B, and ERBB2+. Results Based upon the analysis of 599 microarrays (five separate cDNA microarray datasets using a novel approach, we present evidence in support of the most consistently identifiable subtypes of breast cancer tumor tissue microarrays being: ESR1+/ERBB2-, ESR1-/ERBB2-, and ERBB2+ (collectively called the ESR1/ERBB2 subtypes. We validate all three subtypes statistically and show the subtype to which a sample belongs is a significant predictor of overall survival and distant-metastasis free probability. Conclusion As a consequence of the statistical validation procedure we have a set of centroids which can be applied to any microarray (indexed by UniGene Cluster ID to classify it to one of the ESR1/ERBB2 subtypes. Moreover, the method used to define the ESR1/ERBB2 subtypes is not specific to the disease. The method can be used to identify subtypes in any disease for which there are at least two independent microarray datasets of disease samples.

  17. Cancer cachexia update in head and neck cancer: Definitions and diagnostic features.

    Science.gov (United States)

    Couch, Marion E; Dittus, Kim; Toth, Michael J; Willis, Monte S; Guttridge, Denis C; George, Jonathan R; Barnes, Christie A; Gourin, Christine G; Der-Torossian, Hirak

    2015-04-01

    Cachexia is a profoundly debilitating wasting syndrome that affects patients with head and neck cancer and often contributes to their demise. A comprehensive literature search was performed up to April 2013 using PubMed, the Cochrane Library, CINAHL, and the Google search engine. For the meta-analyses, pooled prevalence estimates were calculated with a confidence interval of 95% (95% CI) by using random effects modeling. In this review, we outlined the unique challenges of cancer cachexia among patients with head and neck cancer by reviewing its impacts on quality of life (QOL), morbidity, and mortality. We explored the prevalence of different clinical markers of cachexia at the time of diagnosis and before and after treatment. Finally, we present updates regarding the diagnosis of cancer cachexia and recent findings, such as cardiac dysfunction that warrant clinical attention to more carefully identify patients at risk and potentially lead to better outcomes.

  18. Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database

    DEFF Research Database (Denmark)

    Petri, A.L.; Kjaer, S.K.; Christensen, I.J.;

    2009-01-01

    OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality......: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology Udgivelsesdato: 2009...

  19. Validation of epithelial ovarian cancer and fallopian tube cancer and ovarian borderline tumor data in the Danish Gynecological Cancer Database

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Kjaer, Susanne Krüger; Christensen, Ib J;

    2009-01-01

    OBJECTIVE: To validate the data on epithelial ovarian cancer, fallopian tube cancer and borderline ovarian tumors registered in the nationwide Danish Gynecological Cancer Database (DGCD) in 2005 and 2006. The DGCD is a multidisciplinary database that contains data for research and quality......: The validity of ovarian cancer data in the DGCD is sufficient for quality monitoring in gynecological oncology....

  20. Cancer vaccines: an update with special focus on ganglioside antigens.

    Science.gov (United States)

    Bitton, Roberto J; Guthmann, Marcel D; Gabri, Mariano R; Carnero, Ariel J L; Alonso, Daniel F; Fainboim, Leonardo; Gomez, Daniel E

    2002-01-01

    Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules. Most of the vaccines are still experimental and not approved by the US or European Regulatory Agencies. In this work, we will offer an update in the knowledge in cancer immunology and all the anticancer vaccine approaches, with special emphasis in ganglioside based vaccines. It has been demonstrated that quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Malignant transformation appears to activate enzymes associated with ganglioside glycosylation, resulting in altered patterns of ganglioside expression in tumors. Direct evidence of the importance of gangliosides as potential targets for active immunotherapy has been suggested by the observation that human monoclonal antibodies against these glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, therefore representing a new target for anticancer therapy. Since 1993 researchers at the University of Buenos Aires and the University of Quilmes (Argentina), have taken part in a project carried out by

  1. Development and validation of the Cancer Exercise Stereotypes Scale.

    Science.gov (United States)

    Falzon, Charlène; Sabiston, Catherine; Bergamaschi, Alessandro; Corrion, Karine; Chalabaev, Aïna; D'Arripe-Longueville, Fabienne

    2014-01-01

    The objective of this study was to develop and validate a French-language questionnaire measuring stereotypes related to exercise in cancer patients: The Cancer Exercise Stereotypes Scale (CESS). Four successive steps were carried out with 806 participants. First, a preliminary version was developed on the basis of the relevant literature and qualitative interviews. A test of clarity then led to the reformulation of six of the 30 items. Second, based on the modification indices of the first confirmatory factorial analysis, 11 of the 30 initial items were deleted. A new factorial structure analysis showed a good fit and validated a 19-item instrument with five subscales. Third, the stability of the instrument was tested over time. Last, tests of construct validity were conducted to examine convergent validity and discriminant validity. The French-language CESS appears to have good psychometric qualities and can be used to test theoretical tenets and inform intervention strategies on ways to foster exercise in cancer patients.

  2. Validation of Biomarkers for Prostate Cancer Prognosis

    Science.gov (United States)

    2013-10-01

    incontinence and urinary urgency as well as sexual dysfunction. Furthermore, evidence from many sources suggests that most prostate cancers are...mainly surgery and radiation therapy, result in well documented significant morbidities, including significant lower urinary tract symptoms such as

  3. Update on the Development and Validation of MERCURY: A Modern, Monte Carlo Particle Transport Code

    Energy Technology Data Exchange (ETDEWEB)

    Procassini, R J; Taylor, J M; McKinley, M S; Greenman, G M; Cullen, D E; O' Brien, M J; Beck, B R; Hagmann, C A

    2005-06-06

    An update on the development and validation of the MERCURY Monte Carlo particle transport code is presented. MERCURY is a modern, parallel, general-purpose Monte Carlo code being developed at the Lawrence Livermore National Laboratory. During the past year, several major algorithm enhancements have been completed. These include the addition of particle trackers for 3-D combinatorial geometry (CG), 1-D radial meshes, 2-D quadrilateral unstructured meshes, as well as a feature known as templates for defining recursive, repeated structures in CG. New physics capabilities include an elastic-scattering neutron thermalization model, support for continuous energy cross sections and S ({alpha}, {beta}) molecular bound scattering. Each of these new physics features has been validated through code-to-code comparisons with another Monte Carlo transport code. Several important computer science features have been developed, including an extensible input-parameter parser based upon the XML data description language, and a dynamic load-balance methodology for efficient parallel calculations. This paper discusses the recent work in each of these areas, and describes a plan for future extensions that are required to meet the needs of our ever expanding user base.

  4. External validation and updating of a Dutch prediction model for low hemoglobin deferral in Irish whole blood donors

    NARCIS (Netherlands)

    Baart, A.M.; Atsma, F.; McSweeney, E.N.; Moons, K.G.; Vergouwe, Y.; Kort, W.L. de

    2014-01-01

    BACKGROUND: Recently, sex-specific prediction models for low hemoglobin (Hb) deferral have been developed in Dutch whole blood donors. In the present study, we validated and updated the models in a cohort of Irish whole blood donors. STUDY DESIGN AND METHODS: Prospectively collected data from 45,031

  5. Director's Update - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (NCI-CPTAC) has recently begun the proteomic interrogation of genomically-characterized tumors from The Cancer Genome Atlas.

  6. ACE-FTS version 3.0 data set: validation and data processing update

    Directory of Open Access Journals (Sweden)

    Claire Waymark

    2014-01-01

    Full Text Available On 12 August 2003, the Canadian-led Atmospheric Chemistry Experiment (ACE was launched into a 74° inclination orbit at 650 km with the mission objective to measure atmospheric composition using infrared and UV-visible spectroscopy (Bernath et al. 2005. The ACE mission consists of two main instruments, ACE-FTS and MAESTRO (McElroy et al. 2007, which are being used to investigate the chemistry and dynamics of the Earth’s atmosphere.  Here, we focus on the high resolution (0.02 cm-1 infrared Fourier Transform Spectrometer, ACE-FTS, that measures in the 750-4400 cm-1 (2.2 to 13.3 µm spectral region.  This instrument has been making regular solar occultation observations for more than nine years.  The current ACE-FTS data version (version 3.0 provides profiles of temperature and volume mixing ratios (VMRs of more than 30 atmospheric trace gas species, as well as 20 subsidiary isotopologues of the most abundant trace atmospheric constituents over a latitude range of ~85°N to ~85°S.  This letter describes the current data version and recent validation comparisons and provides a description of our planned updates for the ACE-FTS data set. [...

  7. Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update

    Directory of Open Access Journals (Sweden)

    Arif Malik

    2016-01-01

    Full Text Available Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.

  8. Nutrition and cancer - global and African perspectives: a focused update.

    Science.gov (United States)

    Wiseman, Martin J

    2015-11-01

    The burden of cancer worldwide is predicted to almost double by 2030 to nearly 23 million cases annually. The great majority of this increase is expected to occur in less economically developed countries, where access to expensive medical, surgical and radiotherapeutic interventions is likely to be limited to a small proportion of the population. This emphasises the need for preventive measures, as outlined in the declaration from the United Nations 2011 High Level Meeting on Non-communicable Diseases. The rise in incidence is proposed to follow from increasing numbers of people reaching middle and older ages, together with increasing urbanisation of the population with a nutritional transition from traditional diets to a more globalised 'Western' pattern, with a decrease in physical activity. This is also expected to effect a change in the pattern of cancers from a predominantly smoking and infection dominated one, to a smoking and obesity dominated one. The World Cancer Research Fund estimates that about a quarter to a third of the commonest cancers are attributable to excess body weight, physical inactivity and poor diet, making this the most common cause of cancers after smoking. These cancers are potentially preventable, but knowledge of the causes of cancer has not led to effective policies to prevent the export of a 'Western' pattern of cancers in lower income countries such as many in Africa.

  9. Trastuzumab: updated mechanisms of action and resistance in breast cancer

    Directory of Open Access Journals (Sweden)

    Francois X. Claret

    2012-06-01

    Full Text Available HER2-postitive breast cancer has the second-poorest prognosis among breast cancer subtypes. One of the most effective targeted therapies for patients with HER2-positive breast cancer is trastuzumab-based. However, primary or acquired resistance to trastuzumab has been a major obstacle in the clinical management of this disease. Therefore, to better control HER2-postitive breast cancer, it is necessary to gain a deeper understanding of trastuzumab’s actions and the pathways that cancer cells use to dodge its effects. In this review, we attempt to give an overview of the widely accepted and currently proposed molecular mechanisms for these actions and highlight recent advances in our understanding of HER2 targeted therapies.

  10. Pancreatic Cancer: Updates on Translational Research and Future Applications

    Directory of Open Access Journals (Sweden)

    Evangelos G Sarris

    2013-03-01

    Full Text Available Pancreatic cancer is one of the most lethal malignancies with a mortality rate almost equal to its incidence. It is ranked as the fourth leading cause of cancer-related deaths in the United States, and despite intensive basic and clinical research over the last few years, the survival benefit for the majority of patients with pancreatic cancer is still disappointing. Due to the absence of specific symptoms and the lack of early detection tests, pancreatic cancer is usually diagnosed at an advanced inoperrable stage and palliative chemotherapy with the purine analogue gemcitabine in combination with the targeted agent erlotinib, remains the mainstay method in the management of these patients. Therefore, there is an imperative need for new findings in the translational research field with prognostic, predictive and therapeutic value. In this paper we summarize five most interesting research abstracts as presented at the 2013 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium. In particular, we focus on Abstract #141 which investigates the interaction between liver and pancreatic organ damage in patients with pancreatic cancer and the potential contribution of the patatin-like phospholipase domain containing 3 (PNPLA3 gene variation in pancreatic cancer development and on Abstract #149, in which, the prognostic and predictive role of SWI/SNF complex, a chromatin-remodeling complex, is examined. The key role of pharmacogenomics, in terms of predicting response and resistance to chemotherapy in pancreatic cancer patients, is analyzed in Abstract #142 and the contribution of circulating tumor cell detection in the early diagnosis of pancreatic cancer, allowing the avoidance of more invasive procedures like EUS-FNA, is discussed in Abstract #157. Lastly, in Abstract #164, the diagnostic utility of YKL-40 and IL-6 in pancreatic cancer patients is investigated.

  11. American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.

    Science.gov (United States)

    Robson, Mark E; Bradbury, Angela R; Arun, Banu; Domchek, Susan M; Ford, James M; Hampel, Heather L; Lipkin, Stephen M; Syngal, Sapna; Wollins, Dana S; Lindor, Noralane M

    2015-11-01

    The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencing-also known as next-generation sequencing-to cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services.

  12. The expanding role of metformin in cancer: an update on antitumor mechanisms and clinical development.

    Science.gov (United States)

    Gong, Jun; Kelekar, Gauri; Shen, James; Shen, John; Kaur, Sukhpreet; Mita, Monica

    2016-08-01

    Metformin has been used for nearly a century to treat type 2 diabetes mellitus. Epidemiologic studies first identified the association between metformin and reduced risk of several cancers. The anticancer mechanisms of metformin involve both indirect or insulin-dependent pathways and direct or insulin-independent pathways. Preclinical studies have demonstrated metformin's broad anticancer activity across a spectrum of malignancies. Prospective clinical trials involving metformin in the chemoprevention and treatment of cancer now number in the hundreds. We provide an update on the anticancer mechanisms of metformin and review the results thus far available from prospective clinical trials investigating metformin's efficacy in cancer.

  13. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Science.gov (United States)

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  14. Update on immune checkpoint inhibitors in gynecological cancers

    Science.gov (United States)

    2017-01-01

    In recent years, progress in our understanding of immune-modulatory signaling pathways in immune cells and the tumor microenvironment (TME) has led to rejuvenated interest in cancer immunotherapy. In particular, immunotherapy targeting the immune checkpoint receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell-death 1 (PD-1), and programmed cell-death ligand 1 (PD-L1) have demonstrated clinical activity in a wide variety of tumors, including gynecological cancers. This review will focus on the emerging clinical data on the therapeutic role of immune checkpoint inhibitors, and potential strategies to enhance the efficacy of this class of compounds, in the context of gynecological cancers. It is anticipated that future biomarker-directed clinical trials will provide further insights into the mechanisms underlying response and resistance to immunotherapy, and help guide our approach to designing therapeutic combinations that have the potential to enhance the benefit of immunotherapy in patients with gynecologic cancers. PMID:28028993

  15. An updated report on the trends in cancer incidence and mortality in Japan, 1958-2013.

    Science.gov (United States)

    Katanoda, Kota; Hori, Megumi; Matsuda, Tomohiro; Shibata, Akiko; Nishino, Yoshikazu; Hattori, Masakazu; Soda, Midori; Ioka, Akiko; Sobue, Tomotaka; Nishimoto, Hiroshi

    2015-04-01

    The analysis of cancer trends in Japan requires periodic updating. Herein, we present a comprehensive report on the trends in cancer incidence and mortality in Japan using recent population-based data. National cancer mortality data between 1958 and 2013 were obtained from published vital statistics. Cancer incidence data between 1985 and 2010 were obtained from high-quality population-based cancer registries of three prefectures (Yamagata, Fukui and Nagasaki). Joinpoint regression analysis was performed to examine the trends in age-standardized rates of cancer incidence and mortality. All-cancer mortality decreased from the mid-1990s, with an annual percent change of -1.3% (95% confidence interval [CI]: -1.4, -1.3). During the most recent 10 years, over 60% of the decrease in cancer mortality was accounted for by a decrease in stomach and liver cancers (63% for males and 66% for females). The long-term increase in female breast cancer mortality, beginning in the 1960s, plateaued in 2008. All-cancer incidence continuously increased, with annual percent changes of 0.6% (95% CI: 0.5, 0.8) between 1985 and 2005, and 1.8% (95% CI: 0.6, 2.9) between 2005 and 2010. During the most recent 10 years, almost half of the increase in cancer incidence was accounted for by an increase in prostate cancer (60%) in males and breast cancer (46%) in females. The cancer registry quality indices also began to increase from ∼2005. Decreases in stomach and liver cancers observed for incidence and mortality reflect the reduced attribution of infection-related factors (i.e. Helicobacter pylori and hepatitis virus). However, it should be noted that cervical cancer incidence and mortality rates began to increase from ∼1990.

  16. Systemic treatment for hereditary cancers: a 2012 update

    OpenAIRE

    Imyanitov, Evgeny N; Byrski, Tomasz

    2013-01-01

    The history of specific therapy for hereditary tumors dates back to mid 1980s and involves a number of reports demonstrating regression of familial colon polyps upon administration of sulindac. Virtually no clinical studies on other hereditary cancer types were available until the year 2009, when Byrski et al. presented the data on unprecedented sensitivity of BRCA1-associated breast malignancies to cisplatin. This breakthrough has revived interest to the treatment of cancer in germ-line muta...

  17. Endocrine resistance in breast cancer--An overview and update.

    Science.gov (United States)

    Clarke, Robert; Tyson, John J; Dixon, J Michael

    2015-12-15

    Tumors that express detectable levels of the product of the ESR1 gene (estrogen receptor-α; ERα) represent the single largest molecular subtype of breast cancer. More women eventually die from ERα+ breast cancer than from either HER2+ disease (almost half of which also express ERα) and/or from triple negative breast cancer (ERα-negative, progesterone receptor-negative, and HER2-negative). Antiestrogens and aromatase inhibitors are largely indistinguishable from each other in their abilities to improve overall survival and almost 50% of ERα+ breast cancers will eventually fail one or more of these endocrine interventions. The precise reasons why these therapies fail in ERα+ breast cancer remain largely unknown. Pharmacogenetic explanations for Tamoxifen resistance are controversial. The role of ERα mutations in endocrine resistance remains unclear. Targeting the growth factors and oncogenes most strongly correlated with endocrine resistance has proven mostly disappointing in their abilities to improve overall survival substantially, particularly in the metastatic setting. Nonetheless, there are new concepts in endocrine resistance that integrate molecular signaling, cellular metabolism, and stress responses including endoplasmic reticulum stress and the unfolded protein response (UPR) that provide novel insights and suggest innovative therapeutic targets. Encouraging evidence that drug combinations with CDK4/CDK6 inhibitors can extend recurrence free survival may yet translate to improvements in overall survival. Whether the improvements seen with immunotherapy in other cancers can be achieved in breast cancer remains to be determined, particularly for ERα+ breast cancers. This review explores the basic mechanisms of resistance to endocrine therapies, concluding with some new insights from systems biology approaches further implicating autophagy and the UPR in detail, and a brief discussion of exciting new avenues and future prospects.

  18. Update on skin cancer incidence and mortality in Europe

    OpenAIRE

    2014-01-01

    The epidemiology of skin cancer shows interplay between host susceptibility, (ultraviolet) environment, socioeconomical conditions and behavioural patterns. Its etiology is not yet fully elucidated and reveals intriguing questions. Fair-skinned populations have experienced over the last 60 years a rapid increase in the incidence of melanoma which is unparalleled by any other cancer, although signs of levelling off and stabilization in incidence have recently been observed in some countries. ...

  19. Natural products as potential cancer therapy enhancers: A preclinical update.

    Science.gov (United States)

    Agbarya, Abed; Ruimi, Nili; Epelbaum, Ron; Ben-Arye, Eran; Mahajna, Jamal

    2014-01-01

    Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  20. Natural products as potential cancer therapy enhancers: A preclinical update

    Directory of Open Access Journals (Sweden)

    Abed Agbarya

    2014-09-01

    Full Text Available Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects.

  1. Completeness and validity in a national clinical thyroid cancer database

    DEFF Research Database (Denmark)

    Londero, Stefano Christian; Mathiesen, Jes Sloth; Krogdahl, Annelise

    2014-01-01

    BACKGROUND: Although a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid...... and extended governmental databases, it is possible to establish national clinical cancer databases with a satisfactory completeness and validity. The DATHYRCA database is considered reliable in terms of describing thyroid carcinoma at a national level....... cancer database: DATHYRCA. STUDY DESIGN AND SETTING: National prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used...

  2. Systemic treatment for hereditary cancers: a 2012 update.

    Science.gov (United States)

    Imyanitov, Evgeny N; Byrski, Tomasz

    2013-04-01

    The history of specific therapy for hereditary tumors dates back to mid 1980s and involves a number of reports demonstrating regression of familial colon polyps upon administration of sulindac. Virtually no clinical studies on other hereditary cancer types were available until the year 2009, when Byrski et al. presented the data on unprecedented sensitivity of BRCA1-associated breast malignancies to cisplatin. This breakthrough has revived interest to the treatment of cancer in germ-line mutation carriers. Recent trials and clinical observations have confirmed the efficacy of platinating agents and PARP inhibitors in BRCA1/2-driven breast, ovarian and pancreatic carcinomas. Pegylated liposomal doxorubicin may be considered as a promising treatment option for BRCA1/2-related ovarian cancer after the failure of platinum-containing therapy. Several novel drugs have been recently introduced in the management of rare familial tumor syndromes. Vandetanib, a low-molecular weight RET kinase inhibitor, demonstrated substantial efficacy in the treatment of hereditary and sporadic medullary thyroid cancer. Vismodegib, an inhibitor of SMO oncoprotein, caused regression of basal-cell carcinomas in patients with Gorlin syndrome. Down-regulation of mTOR kinase by everolimus has been successfully used for the therapy of subependymal giant-cell astrocytomas in patients with tuberous sclerosis. The achievements in the prevention, diagnostics and treatment of hereditary cancers may serve as an excellent example of triumph of translational medicine.

  3. Clinical trials update: Medical management of advanced breast cancer.

    Science.gov (United States)

    Major, Maureen A

    2003-12-01

    Selection of treatment for metastatic breast cancer depends on several factors: the status of estrogen receptors or progesterone receptors on breast cancer cells and the expression levels of human epidermal growth factor receptor-2. The presence of estrogen or progesterone receptors typically indicates slower-growing tumors that may be amenable to hormonal manipulation, which provides significant disease control while offering a better toxicity profile than conventional chemotherapy. The understanding of hormonal therapies in patients with postmenopausal metastatic breast cancer has advanced greatly in the past several decades. Aromatase inhibitors, although used initially as second-line therapy, recently have proved to be as effective as tamoxifen, if not superior to it, as first-line therapy for metastatic breast cancer. New data also suggest that letrozole provides significantly better objective responses than anastrozole as second-line therapy. Exemestane, a steroidal aromatase inhibitor, is an effective third-line therapy. Fulvestrant, an estrogen receptor antagonist with no known agonist effect, provides a new option for hormonal therapy. For patients with metastatic breast cancer and overexpression of human epidermal growth factor receptor-2 on tumor cells, the monoclonal antibody trastuzumab is the preferred option, either in combination with paclitaxel as first-line treatment, or as a single agent for second-line therapy. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed, potentially extending patient survival rates and improving quality of life.

  4. Validity of patient skin cancer report among organ transplant recipients.

    Science.gov (United States)

    Dybbro, Eric; Mihalis, Eva; Hirose, Ryutaro; Arron, Sarah T

    2012-01-01

    Skin cancer is a common, potentially life-threatening malignancy in organ transplant recipients (OTR), and it is important for transplant physicians to be aware of patient history of skin cancer. Patient self-report represents a quick method of obtaining past medical history of skin cancer but no study has validated the self-report of skin cancer among OTR. Among 339 OTR with a history of skin cancer, the sensitivity and specificity of self-report of non-melanoma skin cancer (NMSC) were 1.00 and 0.92, with a correct classification rate of 0.92. Breakdown of NMSC into squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) resulted in a decrease in correct classification, to 0.83 for SCC and 0.74 for BCC. For SCC, sensitivity was 0.81 and specificity was 0.83, while BCC had a sensitivity of 0.52 and specificity of 0.86. Melanoma self-report had a sensitivity of 0.90 and specificity of 0.86, with a correct classification rate of 0.90. Overall, OTR have comparable accuracy of self-report with the general population. Owing to the high prevalence and increased risk of metastatic potential of skin cancer in this population, the ability to distinguish between cancer types is an important consideration in the dermatologic care of OTR.

  5. mTOR pathway in colorectal cancer: an update.

    Science.gov (United States)

    Francipane, Maria Giovanna; Lagasse, Eric

    2014-01-15

    The mammalian target of rapamycin (mTOR) has emerged as a potential target for drug development, particularly due to the fact that it plays such a crucial role in cancer biology. In addition, next-generation mTOR inhibitors have become available, marking an exciting new phase in mTOR-based therapy. However, the verdict on their therapeutic effectiveness remains unclear. Here we review phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling as one of the primary mechanisms for sustaining tumor outgrowth and metastasis, recent advances in the development of mTOR inhibitors, and current studies addressing mTOR activation/inhibition in colorectal cancer (CRC). We will also discuss our recent comparative study of different mTOR inhibitors in a population of colon cancer stem cells (CSCs), and current major challenges for achieving individualized drug therapy using kinase inhibitors.

  6. Validation of colorectal cancer surgery data from administrative data sources

    Directory of Open Access Journals (Sweden)

    Li Xue

    2012-07-01

    Full Text Available Abstract Background Surgery is the primary treatment for colorectal cancer for both curative and palliative intent. Availability of high quality surgery data is essential for assessing many aspects of the quality of colorectal cancer care. The objective of this study was to determine the quality of different administrative data sources in identifying surgery for colorectal cancer with respect to completeness and accuracy. Methods All residents in Alberta, Canada who were diagnosed with invasive colorectal cancer in years 2000-2005 were identified from the Alberta Cancer Registry and included in the study. Surgery data for these patients were obtained from the Cancer Registry (which collects the date of surgery for which the primary tumor was removed and compared to surgery data obtained from two different administrative data sources: Physician Billing and Hospital Inpatient data. Sensitivity, specificity, positive predictive value, negative predictive value and observed agreement were calculated compared to the Cancer Registry data. Results The Physician Billing data alone or combined with Hospital Inpatient data demonstrated equally high sensitivity (97% for both and observed agreement with the Cancer Registry data (93% for both for identifying surgeries. The Hospital Inpatient data, however, had the highest specificity (80%. The positive predictive value varied by disease stage and across data sources for stage IV (99% for stages I-III and 83-89% for stage IV, the specificity is better for colon cancer surgeries (72-85% than for rectal cancer surgeries (60-73%; validation measures did not vary over time. Conclusion Physician Billing data identify the colorectal cancer surgery more completely than Hospital Inpatient data although both sources have a high level of completeness.

  7. Cancer gene therapy targeting angiogenesis: An updated review

    Institute of Scientific and Technical Information of China (English)

    Ching-Chiu Liu; Zan Shen; Hsiang-Fu Kung; Marie CM Lin

    2006-01-01

    Since the relationship between angiogenesis and tumor growth was established by Folkman in 1971,scientists have made efforts exploring the possibilities in treating cancer by targeting angiogenesis. Inhibition of angiogenesis growth factors and administration of angiogenesis inhibitors are the basics of antiangiogenesis therapy. Transfer of anti-angiogenesis genes has Received attention recently not only because of the advancement of recombinant vectors, but also because of the localized and sustained expression of therapeutic gene product inside the tumor after gene transfer. This review provides the up-to-date information about the strategies and the vectors studied in the field of anti-angiogenesis cancer gene therapy.

  8. Evolving role of adiponectin in cancer-controversies and update

    Institute of Scientific and Technical Information of China (English)

    Arnav Katira; Peng H Tan

    2016-01-01

    Adiponectin (APN), an adipokine produced by adipocytes, has been shown to have a critical role in the pathogenesis of obesity-associated malignancies. Through its receptor interactions, APN may exert its anti-carcinogenic effects including regulating cell survival, apoptosis and metastasis via a plethora of signalling pathways. Despite the strong evidence supporting this notion, some work may indicate otherwise. Our review addresses all controversies critically. On the whole, hypoadiponectinaemia is associated with increased risk of several malignancies and poor prognosis. In addition, various genetic polymorphisms may predispose individuals to increased risk of obesity-associated malignancies. We also provide an updated summary on therapeutic interventions to increase APN levels that are of key interest in this field. To date efforts to manipulate APN levels have been promising, but much work remains to be done.

  9. Cancers related to Immunodeficiencies:Update and perspectives

    Directory of Open Access Journals (Sweden)

    Esmaeil Mortaz

    2016-09-01

    Full Text Available The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. Whilst, the incidence of primary immunodeficiencies (PIDs is 1:10.000 births, that of secondary immunodeficiencies is more common and are associated with post transplantation immune dysfunction or with immunosuppressive medication for human immunodeficiency virus (HIV or with human T-cell lymphotropic virus (HTLV infection.After infection, malignancy is the most prevalent cause of death in both children and adults with primary immunodeficiency disorders (PIDs. PIDs more often associated with cancer include common variable immunodeficiency (CVID, Wiskott Aldrich syndrome (WAS, ataxia-telangiectasia (AT and severe combined immunodeficiency (SCID. This suggests that a protective immune response against both infectious non-self (pathogens and malignant self-challenges (cancer exist. The increased incidence of cancer has been attributed to defective elimination of altered or transformed cells and/or defective immunity towards cancer cells. The concept of abberant immune surveillance occurring in PIDs is supported by evidence in mice and from patients undergoing immunosuppression after transplantation. Here, we discuss the importance of PID defects in the development of malignancies, the current limitations associated with molecular pathogenesis of these diseases and emphasize the need for further knowledge of how specific mutations can modulate the immune system to alter immunosurveillance and thereby play a key role in the etiology of malignancies in PID patients.

  10. Pomegranate for Prevention and Treatment of Cancer: An Update

    Directory of Open Access Journals (Sweden)

    Pooja Sharma

    2017-01-01

    Full Text Available Cancer is the second leading cause of death in the United States, and those who survive cancer may experience lasting difficulties, including treatment side effects, as well as physical, cognitive, and psychosocial struggles. Naturally-occurring agents from dietary fruits and vegetables have received considerable attention for the prevention and treatment of cancers. These natural agents are safe and cost efficient in contrast to expensive chemotherapeutic agents, which may induce significant side effects. The pomegranate (Punica granatum L. fruit has been used for the prevention and treatment of a multitude of diseases and ailments for centuries in ancient cultures. Pomegranate exhibits strong antioxidant activity and is a rich source of anthocyanins, ellagitannins, and hydrolysable tannins. Studies have shown that the pomegranate fruit as well as its juice, extract, and oil exert anti-inflammatory, anti-proliferative, and anti-tumorigenic properties by modulating multiple signaling pathways, which suggest its use as a promising chemopreventive/chemotherapeutic agent. This review summarizes preclinical and clinical studies highlighting the role of pomegranate in prevention and treatment of skin, breast, prostate, lung, and colon cancers.

  11. Update on epidemiology classification, and management of thyroid cancer

    Directory of Open Access Journals (Sweden)

    Heitham Gheriani

    2006-06-01

    Full Text Available Thyroid cancer represents approximately 0.5–1% of all human malignancy1. In the UK the incidence of thyroid cancer is 2-3 per 100,000 populations 2. In geographical areas of low iodine intake and in areas exposed to nuclear disasters the incidence of thyroid cancer is higher. Benign thyroid conditions are much more common. In the UK approximately 8 % of the population have nodular thyroid disease2. Nodular thyroid disease increases with age and is also more common in females and in geographical areas of low iodine intake. Primary thyroid malignancy can be broadly divided into 2 groups. The first group, which generally have much better prognosis, are the well-differentiated thyroid carcinoma, which includes papillary carcinoma, follicular carcinoma and Hürthle cell tumours. The second group includes the poorly differentiated thyroid carcinoma like medullary thyroid carcinoma and the anaplastic thyroid carcinoma. Other rare tumours such as sarcomas, lymphomas and the extremely rare primary squamous cell carcinoma of the thyroid should be included in the second group. Secondary or metastatic thyroid cancer can be from breast, lung, colon and kidney malignancies.

  12. Brachytherapy for Patients With Prostate Cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update.

    Science.gov (United States)

    Chin, Joseph; Rumble, R Bryan; Kollmeier, Marisa; Heath, Elisabeth; Efstathiou, Jason; Dorff, Tanya; Berman, Barry; Feifer, Andrew; Jacques, Arthur; Loblaw, D Andrew

    2017-03-27

    Purpose To jointly update the Cancer Care Ontario guideline on brachytherapy for patients with prostate cancer to account for new evidence. Methods An Update Panel conducted a targeted systematic literature review and identified more recent randomized controlled trials comparing dose-escalated external beam radiation therapy (EBRT) with brachytherapy in men with prostate cancer. Results Five randomized controlled trials provided the evidence for this update. Recommendations For patients with low-risk prostate cancer who require or choose active treatment, low-dose rate brachytherapy (LDR) alone, EBRT alone, and/or radical prostatectomy (RP) should be offered to eligible patients. For patients with intermediate-risk prostate cancer choosing EBRT with or without androgen-deprivation therapy, brachytherapy boost (LDR or high-dose rate [HDR]) should be offered to eligible patients. For low-intermediate risk prostate cancer (Gleason 7, prostate-specific antigen < 10 ng/mL or Gleason 6, prostate-specific antigen, 10 to 20 ng/mL), LDR brachytherapy alone may be offered as monotherapy. For patients with high-risk prostate cancer receiving EBRT and androgen-deprivation therapy, brachytherapy boost (LDR or HDR) should be offered to eligible patients. Iodine-125 and palladium-103 are each reasonable isotope options for patients receiving LDR brachytherapy; no recommendation can be made for or against using cesium-131 or HDR monotherapy. Patients should be encouraged to participate in clinical trials to test novel or targeted approaches to this disease. Additional information is available at www.asco.org/Brachytherapy-guideline and www.asco.org/guidelineswiki .

  13. Cancer-preventing attributes of probiotics: an update.

    Science.gov (United States)

    Kumar, Manoj; Kumar, Ashok; Nagpal, Ravinder; Mohania, Dheeraj; Behare, Pradip; Verma, Vinod; Kumar, Pramod; Poddar, Dev; Aggarwal, P K; Henry, C J K; Jain, Shalini; Yadav, Hariom

    2010-08-01

    Cancer is a serious global public health problem. Cancer incidence and mortality have been steadily rising throughout the past century in most places of the world. There are several epidemiological evidences that support a protective role of probiotics against cancer. Lactic acid bacteria and their probioactive cellular substances exert many beneficial effects in the gastrointestinal tract, and also release various enzymes into the intestinal lumen and exert potential synergistic (LAB) effects on digestion and alleviate symptoms of intestinal malabsorption. Consumption of fermented dairy products with LAB may elicit anti-tumor effects. These effects are attributed to the inhibition of mutagenic activity, the decrease in several enzymes implicated in the generation of carcinogens, mutagens, or tumor-promoting agents, suppression of tumors, and epidemiology correlating dietary regimes and cancer. Specific cellular components in lactic acid bacteria seem to induce strong adjuvant effects including modulation of cell-mediated immune responses, activation of the reticulo-endothelial system, augmentation of cytokine pathways, and regulation of interleukins and tumor necrosis factors. Studies on the effect of probiotic consumption on cancer appear promising, since recent in vitro and in vivo studies have indicated that probiotic bacteria might reduce the risk, incidence and number of tumors of the colon, liver and bladder. The protective effect against cancer development may be ascribed to binding of mutagens by intestinal bacteria, may suppress the growth of bacteria that convert procarcinogens into carcinogens, thereby reducing the amount of carcinogens in the intestine, reduction of the enzymes beta-glucuronidase and beta-glucosidase and deconjugation of bile acids, or merely by enhancing the immune system of the host. There are isolated reports citing that administration of LAB results in increased activity of anti-oxidative enzymes or by modulating circulatory

  14. Modern management of rectal cancer: A 2006 update

    Institute of Scientific and Technical Information of China (English)

    Glen C Balch; Alex De Meo; Jose G Guillem

    2006-01-01

    The goal of this review is to outline some of the important surgical issues surrounding the management of patients with early (T1/T2 and NO), as well as locally advanced (T3/T4 and/or N1) rectal cancer. Surgery for rectal cancer continues to develop towards the ultimate goals of improved local control and overall survival, maintaining quality of life, and preserving sphincter, genitourinary, and sexual function. Information concerning the depth of tumor penetration through the rectal wall, lymph node involvement, and presence of distant metastatic disease is of crucial importance when planning a curative rectal cancer resection.Preoperative staging is used to determine the indication for neoadjuvant therapy as well as the indication for local excision versus radical cancer resection. Local excision is likely to be curative in most patients with a primary tumor which is limited to the submucosa (T1NOM0), without high-risk features and in the absence of metastatic disease. In appropriate patients, minimally invasive procedures, such as local excision, TEM, and laparoscopic resection allow for improved patient comfort, shorter hospital stays, and earlier return to preoperative activity level. Once the tumor invades the muscularis propria (T2), radical rectal resection in acceptable operative candidates is recommended.In patients with transmural and/or node positive disease (T3/T4 and/or N1) with no distant metastases,preoperative chemoradiation followed by radical resection according to the principles of TME has become widely accepted. During the planning and conduct of a radical operation for a locally advanced rectal cancer, a number of surgical management issues are considered,including: (1) total mesorectal excision (TME); (2)autonomic nerve preservation (ANP); (3) circumferential resection margin (CRM); (4) distal resection margin;(5) sphincter preservation and options for restoration of bowel continuity; (6) laparoscopic approaches; and (7)postoperative quality

  15. Validity of the stage of lung cancer in records of the Maastricht Cancer Registry, the Netherlands

    NARCIS (Netherlands)

    Schouten, LJ; Langendijk, JA; Jager, JJ; vandenBrandt, PA

    1997-01-01

    Information collected in a clinical study on a random sample of 99 patients with inoperable lung cancer, treated with radiotherapy, was compared to the staging information in the Maastricht cancer registry. Validity of sex (0% disagreements), date of birth (0%), histology (1% major disagreements) an

  16. An update on PARP inhibitors for the treatment of cancer

    Directory of Open Access Journals (Sweden)

    Benafif S

    2015-02-01

    Full Text Available Sarah Benafif, Marcia Hall Mount Vernon Cancer Centre, Northwood, Middlesex, UK Abstract: The development of poly (adenosine diphosphate [ADP] ribose polymerase (PARP inhibitors (PARPi has progressed greatly over the last few years and has shown encouraging results in the BRCA1/2 mutation–related cancers. This article attempts to summarize the rationale and theory behind PARPi, the clinical trials already reported, as well as ongoing studies designed to determine the role of PARPi in patients with and without germline mutations of BRCA genes. Future plans for PARPi both as monotherapy and in combination with standard cytotoxics, other biological agents, and as radiosensitizers are also covered. The widening scope of PARPi adds another important targeted agent to the growing list of molecular inhibitors; future and ongoing trials will identify the most effective role for PARPi, including for patients other than BRCA germline mutation carriers. Keywords: PARPi, BRCA genes, germline mutations, cytotoxics, radiosensitizers, BRCA germline mutation carriers

  17. Stereotactic body radiotherapy in lung cancer: an update *

    Science.gov (United States)

    Abreu, Carlos Eduardo Cintra Vita; Ferreira, Paula Pratti Rodrigues; de Moraes, Fabio Ynoe; Neves, Wellington Furtado Pimenta; Gadia, Rafael; Carvalho, Heloisa de Andrade

    2015-01-01

    Abstract For early-stage lung cancer, the treatment of choice is surgery. In patients who are not surgical candidates or are unwilling to undergo surgery, radiotherapy is the principal treatment option. Here, we review stereotactic body radiotherapy, a technique that has produced quite promising results in such patients and should be the treatment of choice, if available. We also present the major indications, technical aspects, results, and special situations related to the technique. PMID:26398758

  18. Stereotactic body radiotherapy in lung cancer: an update

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Carlos Eduardo Cintra Vita; Ferreira, Paula Pratti Rodrigues; Moraes, Fabio Ynoe de; Neves Junior, Wellington Furtado Pimenta; Carvalho, Heloisa de Andrade, E-mail: heloisa.carvalho@hc.fm.usp.br [Hospital Sirio-Libanes, Sao Paulo, SP (Brazil). Departamento de Radioterapia; Gadia, Rafael [Hospital Sirio-Libanes, Brasilia, DF (Brazil). Departamento de Radioterapia; Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Departamento de Radiologia e Oncologia. Servico de Radioterapia

    2015-07-15

    For early-stage lung cancer, the treatment of choice is surgery. In patients who are not surgical candidates or are unwilling to undergo surgery, radiotherapy is the principal treatment option. Here, we review stereotactic body radiotherapy, a technique that has produced quite promising results in such patients and should be the treatment of choice, if available. We also present the major indications, technical aspects, results, and special situations related to the technique. (author)

  19. Thorotrast induced liver cancer: update of German thorotrast study

    Energy Technology Data Exchange (ETDEWEB)

    Kaick, G. van; Wesch, H. [Deutsches Krebsforschungszentrum Heidelberg (Germany). Dept. of Radiological Diagnostics and Therapy

    1999-02-01

    The German Thorotrast study was started in 1968. It comprises 2,326 Thorotrast patients and 1,890 contemporary matched controls group. 899 Thorotrast patients and 662 patients of the control group have been examined clinically and biophysically every two years. The evaluation of the causes of death demonstrates a statistically significant excess rate of malignant liver tumors, liver cirrhoses, myeloid leukaemias and bone marrow failures. The annual dose after an injection of two ampoules (24 ml) is about 25 cGy for the liver, 70 cGy for the spleen and 9 cGy for the bone marrow. Animal experiments demonstrated that non-radiation effects can be neglected. Correlation exists between the calculated dose to the liver and the frequency of liver cancer. The cumulative risk estimate for liver cancer of about 600 per 10{sup 4} person Gy comes close to the values which were calculated based on the epidemiological results of the Japanese bomb survivors when a quality factor of 20 for alpha radiation and a low dose rate reduction factor of 2 were applied. Dose and frequency of liver cirrhosis are also correlated. Liver cirrhosis is often combined with liver cancer but is not a prerequisite for tumor induction. (orig.) [Deutsch] Die Deutsche Thorotraststudie begann 1968. Sie umfasst 2326 Thorotrastpatienten und 1890 nach Alter und Geschlecht angepasste Kontrollpatienten. Die zu Beginn der Studie noch lebenden Thorotrastpatienten (n=899) und Patienten der Kontrollgruppe (n=622) wurden soweit moeglich in zweijaehrigen Abstaenden ambulant klinisch und biophysikalisch untersucht. Die Recherche der Todesursachen der verstorbenen Patienten ergab eine statistisch signifikante Exzessrate bei primaeren malignen Lebertumoren, Leberzirrhosen, myeloischen Leukaemien und Knochenmarksinsuffizienz. Die jaehrliche Dosis nach Injektion von zwei Ampullen (24 ml) betraegt etwa 25 cGy fuer die Leber, 70 cGy fuer die Milz und 9 cGy fuer das rote Knochenmark. Tierexperimente belegten, dass

  20. Pharmacogenomics in the treatment of lung cancer: an update.

    Science.gov (United States)

    Morales-Espinosa, Daniela; García-Román, Silvia; Karachaliou, Niki; Rosell, Rafael

    2015-01-01

    Significant advances have been made in the analysis of the human genome in the first decades of the 21st century and understanding of tumor biology has matured greatly. The identification of tumor-associated mutations and the pathways involved has led to the development of targeted anticancer therapies. However, the challenge now in using chemotherapy to treat nonsmall-cell lung cancer is to identify more molecular markers predictive of drug sensitivity and determine the optimal drug sequences in order to tailor treatment to each patient. This approach could permit selection of patients who could benefit most from a specific type of chemotherapy by matching their tumor and individual genetic profile. Nevertheless, this potential has been limited so far by reliance on the single biomarker approach, though this is now on the way to being overcome through whole genome studies.

  1. [PET/CT in breast cancer: an update].

    Science.gov (United States)

    Groheux, D; Moretti, J-L; Giacchetti, S; Hindié, E; Teyton, P; Cuvier, C; Bousquet, G; Misset, J-L; Boin, C; Espié, M

    2009-11-01

    The authors discuss the various roles of 18F-FDG PET/CT in the management of breast cancer. Roles of new tracers such as F-18 fluoro-L-thymidine (a marker of cell proliferation), 18-fluoro-17-B-estradiol (marker of estrogen receptor) and sodium fluoride (marker of bone matrix) are also mentioned. There is little justification for the use of FDG-PET/CT in patient with clinically T1 (occult distant metastases, notably, early osteomedullary infiltration. Thus, for these tumors, initial PET/CT can enable better intramodality treatment planning or a change in treatment. PET/CT as a whole-body examination is also very efficient in case of suspicion of recurrence. On the other hand, many studies show that this functional imaging could be used to assess early response to neoadjuvant chemotherapy or to chemotherapy of metastatic disease. 18FDG-PET/CT could thus become an unavoidable modality to answer various clinical situations.

  2. Targeted therapy in biliary tract cancer: 2009 update.

    Science.gov (United States)

    Tonini, Giuseppe; Virzì, Vladimir; Fratto, Maria Elisabetta; Vincenzi, Bruno; Santini, Daniele

    2009-12-01

    Biliary tract cancers (BTCs) include cholangiocarcinoma (intrahepatic, perihilar and extrahepatic), carcinoma of the gall bladder and ampullary carcinoma. In patients with advanced disease the prognosis is poor. There is not a consensus regarding treatment strategy. Chemotherapy has only limited efficacy. This review summarizes the new approaches for BTC patients and the rationale for targeted therapies. The prognostic factors and the molecular features of BTC are analyzed. The clinical trials evaluating the targeted agents are accurately described, especially those assessing the role of anti-EGFR and antiangiogenic drugs. The ongoing trials are also analyzed. In fact, only the results of these trials will establish which is the most effective agent or combination for this setting.

  3. External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement.

    Directory of Open Access Journals (Sweden)

    David Hajage

    Full Text Available BACKGROUND: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors. PATIENTS AND METHODS: The French data set is composed of 456 women with early breast cancer. The Dutch data set is composed of 295 women less than 52 years of age. Agreement between observation and Adjuvant! Online prediction was checked, and logistic models were performed to estimate the prognostic information added by risk factors to Adjuvant! Online prediction. RESULTS: Adjuvant! Online prediction was overall well-calibrated in the French data set but failed in some subgroups of such high grade and HER2 positive patients. HER2 status, Mitotic Index and Ki67 added significant information to Adjuvant! Online prediction. In the Dutch data set, the overall 10-year survival was overestimated by Adjuvant! Online, particularly in patients less than 40 years old. CONCLUSION: Adjuvant! Online needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider new predictors such as Ki67, HER2 and Mitotic Index.

  4. Relevance of the Measles Virus Expression in Cancer - an Update.

    Science.gov (United States)

    Benharroch, Daniel; Ariad, Samuel; Tadmor, Noa; Nalbandyan, Karen; Lazarev, Irena

    2016-10-01

    Evidence of an association between classical Hodgkin lymphoma and the measles virus has previously been presented by our group. Arguments held against our thesis were reevaluated. Substantiation of a relationship between the measles virus and additional solid tumors was submitted. Moreover, a pathogenic pathway was suggested to support a possible contribution of the measles virus to the development of classical Hodgkin lymphoma. We have chosen to exclude a discussion of measles virotherapy, since this carries distinct implications. We now add new evidence regarding the expression of the measles virus phosphoprotein in a few cancers. We also suggest a role in this context for atypical measles syndrome in malignant tumors. Last, we propose a collaboration which may make the best, on the one hand of our cohort of classical Hodgkin lymphoma, half of which carry the measles virus expression in their tumor cells. The planned study will also look into the patients vaccination records and into a previous history of the measles disease. On the other hand, cohorts of patients diagnosed with late onset measles will be assessed for the eventual diagnosis of atypical measles syndrome and will be followed up for the subsequent development of a malignant tumor.

  5. Review:Proteomic technology for biomarker profiling in cancer: an update

    Institute of Scientific and Technical Information of China (English)

    ALAOUI-JAMALI Moulay A.; XU Ying-jie

    2006-01-01

    The progress in the understanding of cancer progression and early detection has been slow and frustrating due to the complex multifactorial nature and heterogeneity of the cancer syndrome. To date, no effective treatment is available for advanced cancers, which remain a major cause of morbidity and mortality. Clearly, there is urgent need to unravel novel biomarkers for early detection.Most of the functional information of the cancer-associated genes resides in the proteome. The later is an exceptionally complex biological system involving several proteins that function through posttranslational modifications and dynamic intermolecular collisions with partners. These protein complexes can be regulated by signals emanating from cancer cells, their surrounding tissue microenvironment, and/or from the host. Some proteins are secreted and/or cleaved into the extracellular milieu and may represent valuable serum biomarkers for diagnosis purpose. It is estimated that the cancer proteome may include over 1.5million proteins as a result of posttranslational processing and modifications. Such complexity clearly highlights the need for ultra-high resolution proteomic technology for robust quantitative protein measurements and data acquisition. This review is to update the current research efforts in high-resolution proteomic technology for discovery and monitoring cancer biomarkers.

  6. Update on vaccine development for renal cell cancer

    Directory of Open Access Journals (Sweden)

    Nina Chi

    2010-08-01

    Full Text Available Nina Chi1, Jodi K Maranchie2,3, Leonard J Appleman3,4, Walter J Storkus1,3,51Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 2Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 3University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States; 4Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States; 5Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USAAbstract: Renal cell carcinoma (RCC remains a significant health concern that frequently presents as metastatic disease at the time of initial diagnosis. Current first-line therapeutics for the advanced-stage RCC include antiangiogenic drugs that have yielded high rates of objective clinical response; however, these tend to be transient in nature, with many patients becoming refractory to chronic treatment with these agents. Adjuvant immunotherapies remain viable candidates to sustain disease-free and overall patient survival. In particular, vaccines designed to optimize the activation, maintenance, and recruitment of specific immunity within or into the tumor site continue to evolve. Based on the integration of increasingly refined immunomonitoring systems in both translational models and clinical trials, allowing for the improved understanding of treatment mechanism(s of action, further refined (combinational vaccine protocols are currently being developed and evaluated. This review provides a brief history of RCC vaccine development, discusses the successes and limitations in such approaches, and provides a rationale for developing combinational vaccine approaches that may provide improved clinical benefits to patients with RCC.Keywords: renal cell carcinoma, vaccines, immunotherapy, combinational therapy, cellular immunity

  7. Valid and complete data on endometrial cancer in the Danish Gynaecological Cancer Database

    DEFF Research Database (Denmark)

    Juhl, Caroline Sollberger; Hansen, Estrid S; Høgdall, Claus K;

    2014-01-01

    concerning data reported and comparability between the DGCD and a definite reference. MATERIAL AND METHODS: DGCD data on women with endometrial cancer or adenomatous hyperplasia supplemented with patient charts for data on recurrence were retrieved and compared with a definite reference (the pathology report......INTRODUCTION: It is a comparative register study designed for data validation of surgery, pathology and recurrence for endometrial cancer in the Danish Gynaecological Cancer Database (DGCD) in the 2005-2009 period. The main outcomes were completeness of the data registered in the DGCD, agreement...... was 71.6%. Completeness could not be determined due to the design of the database, where recurrence is composed of optional variables only. CONCLUSION: The data on endometrial cancer registered in the DGCD regarding surgery and pathology are valid and complete, and they provide a solid base for research...

  8. Validity of data in the Danish Colorectal Cancer Screening Database

    Directory of Open Access Journals (Sweden)

    Thomsen MK

    2017-02-01

    Full Text Available Mette Kielsholm Thomsen,1 Sisse Helle Njor,1 Morten Rasmussen,2 Dorte Linnemann,3 Berit Andersen,4 Gunnar Baatrup,5,6 Lennart Jan Friis-Hansen,7 Jens Christian Riis Jørgensen,8 Ellen Margrethe Mikkelsen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, 2Department of Digestive Diseases K, Bispebjerg Hospital, Copenhagen, 3Department of Pathology, Herlev and Gentofte Hospital, Herlev, 4Department of Public Health Programs, Randers Regional Hospital, Randers, 5Department of Surgery, Odense University Hospital, 6Department of Clinical Science, University of Southern Denmark, Odense, 7Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, 8Department of Colorectal Cancer Surgery, Vejle Hospital, Vejle, Denmark Background: In Denmark, a nationwide screening program for colorectal cancer was implemented in March 2014. Along with this, a clinical database for program monitoring and research purposes was established. Objective: The aim of this study was to estimate the agreement and validity of diagnosis and procedure codes in the Danish Colorectal Cancer Screening Database (DCCSD. Methods: All individuals with a positive immunochemical fecal occult blood test (iFOBT result who were invited to screening in the first 3 months since program initiation were identified. From these, a sample of 150 individuals was selected using stratified random sampling by age, gender and region of residence. Data from the DCCSD were compared with data from hospital records, which were used as the reference. Agreement, sensitivity, specificity and positive and negative predictive values were estimated for categories of codes “clean colon”, “colonoscopy performed”, “overall completeness of colonoscopy”, “incomplete colonoscopy”, “polypectomy”, “tumor tissue left behind”, “number of polyps”, “lost polyps”, “risk group of polyps” and “colorectal cancer and polyps/benign tumor

  9. Thyroid cancer in dogs: an update based on 638 cases (1995-2005).

    Science.gov (United States)

    Wucherer, Katja L; Wilke, Vicki

    2010-01-01

    The goal of this study was to update the descriptive statistics of thyroid cancer by using data from multiple institutions collected through the Veterinary Medical Database (VMDB). Information was collected and reported from cases of canine thyroid cancer submitted to the VMDB between January 1, 1995 and December 31, 2005. Odds ratio (OR) analysis was performed on breeds that had > or =3% of the total number of dogs with thyroid cancer; ORs for each age category were also determined. Thyroid cancer represented 1.1% of all neoplasms during the time period of interest. Golden retrievers, beagles, and Siberian huskies all had significantly increased ORs for developing thyroid cancer. No sex predisposition was evident, but dogs between 10 and 15 years of age had a significantly increased chance of developing thyroid disease. Carcinomas and adenocarcinomas represented 90% of thyroid cancers, while adenomas represented 9.3%. Thyroid carcinoma and adenocarcinoma continue to be uncommon in our canine population. Older dogs are still more commonly affected, and this study is in agreement with previous studies that golden retrievers and beagles are overrepresented. A new finding is that Siberian huskies are also overrepresented. Carcinomas represent a much higher proportion of thyroid cancers than previously reported, and adenomas are likely incidental findings on necropsy. Thyroid cancer should be high on the list of differentials for a neck mass in older, large-breed dogs, as they make up 1.1% of the cancer cases reported. The overwhelming majority of thyroid cancers are carcinomas, and they are most common in golden retrievers, beagles, and Siberian huskies.

  10. An updated meta-analysis of fatal adverse events caused by bevacizumab therapy in cancer patients.

    Directory of Open Access Journals (Sweden)

    Hongxin Huang

    Full Text Available BACKGROUND: The risk of fatal adverse events (FAEs due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue. METHODS: An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of randomized controlled trials on bevacizumab treatment on cancer patients. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio (RR of FAEs due to the use of bevacizumab. RESULTS: Thirty-four trials were included. Allocation to bevacizumab therapy significantly increased the risk of FAEs; the RR was 1.29 (95% CI:1.05-1.57. This association varied significantly with tumor types (P=0.002 and chemotherapeutic agents (P=0.005 but not with bevacizumab dose (P=0.90. Increased risk was seen in patients with non-small cell lung cancer, pancreatic cancer, prostate cancer, and ovarian cancer. However, FAEs were lower in breast cancer patients treated with bevacizumab. In addition, bevacizumab was associated with an increased risk of FAEs in patients who received concomitant agents of taxanes and/or platinum. CONCLUSION: Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs among patients with special tumor types, particularly when combined with chemotherapeutic agents such as platinum.

  11. The health economics of bladder cancer: an updated review of the published literature.

    Science.gov (United States)

    Yeung, Christina; Dinh, Tuan; Lee, Joseph

    2014-11-01

    The purpose of this paper is to provide a current view of the economic burden of bladder cancer, with a focus on the cost effectiveness of available interventions. This review updates a previous systematic review and includes 72 new papers published between 2000 and 2013. Bladder cancer continues to be one of the most common and expensive malignancies. The annual cost of bladder cancer in the USA during 2010 was $US4 billion and is expected to rise to $US5 billion by 2020. Ten years ago, urinary markers held the potential to lower treatment costs of bladder cancer. However, subsequent real-world experiments have demonstrated that further work is necessary to identify situations in which these technologies can be applied in a cost-effective manner. Adjunct cytology remains a part of diagnostic standard of care, but recent research suggests that it is not cost effective due to its low diagnostic yield. Analysis of intravesical chemotherapy after transurethral resection of bladder tumor (TURBT), neo-adjuvant therapy for cystectomy, and robot-assisted laparoscopic cystectomy suggests that these technologies are cost effective and should be implemented more widely for appropriate patients. The existing literature on the cost effectiveness of bladder cancer treatments has improved substantially since 2000. The body of work now includes many new models, registry analyses, and real-world studies. However, there is still a need for new implementation guidelines, new risk modeling tools, and a better understanding of the empirical burden of bladder cancer.

  12. Update on the validation and regulatory acceptance of alternative tests for skin corrosion and irritation.

    Science.gov (United States)

    Fentem, Julia H; Botham, Philip A

    2004-06-01

    The European Centre for the Validation of Alternative Methods (ECVAM) has supported validation studies on in vitro tests for skin corrosion, resulting in the validities of four alternative tests being endorsed. The US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) has also evaluated the validity of these alternative methods for skin corrosion testing. In the European Union, a new Test Method on Skin Corrosion (B.40), incorporating the rat skin transcutaneous electrical resistance and human skin model assays, was included in Annex V of Directive 67/548/EEC in mid-2000. At an international level, two OECD Test Guidelines (430 and 431) on these alternative methods have been approved as of May 2002. To date, there are no validated in vitro tests for predicting the dermal irritancy of chemicals. ECVAM supported prevalidation studies on five in vitro tests for acute skin irritation during 1999-2001. These tests were based on human, pig and mouse skin. However, none of them met the criteria set for inclusion in a large-scale formal validation study. Following additional work on the test protocols and/or prediction models, it appears that several modified tests could now be ready for validation in 2003.

  13. The criterion-related validity of integrity tests: an updated meta-analysis.

    Science.gov (United States)

    Van Iddekinge, Chad H; Roth, Philip L; Raymark, Patrick H; Odle-Dusseau, Heather N

    2012-05-01

    Integrity tests have become a prominent predictor within the selection literature over the past few decades. However, some researchers have expressed concerns about the criterion-related validity evidence for such tests because of a perceived lack of methodological rigor within this literature, as well as a heavy reliance on unpublished data from test publishers. In response to these concerns, we meta-analyzed 104 studies (representing 134 independent samples), which were authored by a similar proportion of test publishers and non-publishers, whose conduct was consistent with professional standards for test validation, and whose results were relevant to the validity of integrity-specific scales for predicting individual work behavior. Overall mean observed validity estimates and validity estimates corrected for unreliability in the criterion (respectively) were .12 and .15 for job performance, .13 and .16 for training performance, .26 and .32 for counterproductive work behavior, and .07 and .09 for turnover. Although data on restriction of range were sparse, illustrative corrections for indirect range restriction did increase validities slightly (e.g., from .15 to .18 for job performance). Several variables appeared to moderate relations between integrity tests and the criteria. For example, corrected validities for job performance criteria were larger when based on studies authored by integrity test publishers (.27) than when based on studies from non-publishers (.12). In addition, corrected validities for counterproductive work behavior criteria were larger when based on self-reports (.42) than when based on other-reports (.11) or employee records (.15).

  14. An update on the biology of cancer stem cells in breast cancer.

    Science.gov (United States)

    García Bueno, José María; Ocaña, Alberto; Castro-García, Paola; Gil Gas, Carmen; Sánchez-Sánchez, Francisco; Poblet, Enrique; Serrano, Rosario; Calero, Raúl; Ramírez-Castillejo, Carmen

    2008-12-01

    Breast cancer stem cells are defined as cancer cells with self-renewal capacity. These cells represent a small subpopulation endowed with the ability to form new tumours when injected in nude mice. Markers of differentiation have been used to identify these cancer cells. In the case of breast cancer, CD44+/CD24- select a population with stem cell properties. The fact that these cells have self-renewal ability has suggested that this population could be responsible for new tumour formation and cancer relapse. These cells have been shown to be more resistant to chemotherapy and radiotherapy than normal cancer cells. The identification of the molecular druggable alterations responsible for the initiation and maintenance of cancer stem cells is an important goal. In this article we will review all these points with special emphasis on the possible role of new drugs designed to interact with molecular pathways of cancer stem cells.

  15. Circadian Disruption and Prostate Cancer Risk: An Updated Review of Epidemiological Evidences.

    Science.gov (United States)

    Wendeu-Foyet, Méyomo G; Menegaux, Florence

    2017-04-04

    Since the publication of the IARC Monograph in 2007 classifying night shift work leading to a disruption of circadian rhythm as probably carcinogenic to humans, there is an increasingly growing interest in understanding how circadian disruption may play a role in cancer development. This systematic review provides a comprehensive update on epidemiological evidences on circadian disruption and prostate cancer since the last review published in 2012. We identified 12 new studies evaluating the effects of several circadian disruptors such as night shift work, sleep patterns, and circadian genes in prostate cancer risk. In contrast, no new studies have focused on exposure to light at night. Several convincing and biologically plausible hypotheses have been proposed to understand how circadian disruption may be related to cancer. However, the current difficulty of concluding on the role of circadian disruption on prostate cancer risk requires further studies including a better characterization of the different night shift systems, data on sleep patterns and chronotype, measurement of biomarkers and investigations of polymorphisms in the genes regulating the biological clock.

  16. Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus.

    Science.gov (United States)

    Rosário, Pedro Weslley; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa Maria Z; Maia, Ana Luiza; Vaisman, Mário

    2013-06-01

    Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.

  17. Content validity across methods of malnutrition assessment in patients with cancer is limited

    NARCIS (Netherlands)

    Sealy, Martine J.; Nijholt, Willemke; Stuiver, Martijn M.; van der Berg, Marit M.; Roodenburg, Jan L. N.; Schans, van der Cees P.; Ottery, Faith D.; Jager-Wittenaar, Harriet

    2016-01-01

    Objective: To identify malnutrition assessment methods in cancer patients and assess their content validity based on internationally accepted definitions for malnutrition. Study Design and Setting: Systematic review of studies in cancer patients that operationalized malnutrition as a variable, publi

  18. Validation and updating of detailed kinetic mechanisms: The case of ethane oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Rota, R.; Bonini, F.; Servida, A.; Morbidelli, M.; Carra, S. (Politecnico di Milano (Italy). Dipt. di Chimica Fisica Applicata)

    1994-11-01

    The authors have investigated experimentally the oxidation of ethane in a perfectly stirred reactor in the temperature range 870--1,080 K and for fuel-air stoichiometric ratio ranging from 0.25 to 1.27. The concentrations of the main molecular species have been measured by probe sampling and GC analysis. These experimental results have been compared with predictions of three popular detailed kinetic mechanisms previously presented in the literature. A reasonable agreement between the experimental results and the model predictions has been found for almost all the species and the mechanisms. The only relevant exception is acetylene, which is greatly overpredicted by one of the mechanisms for all the investigated conditions. Parametric sensitivity analysis has been used for updating such a mechanism in order to improve the agreement with the experimental observations.

  19. Solar ultraviolet radiation, vitamin D and skin cancer surveillance in organ transplant recipients (OTRs): an update.

    Science.gov (United States)

    Reichrath, Jörg

    2014-01-01

    During the last decades, the annual numbers of performed solid organ transplants have continuously increased world-wide. Solid organ transplant recipients (OTR) have a greater risk to develop malignancies, with skin cancer representing the most common neoplasia. Additionally, OTRs in general develop a more aggressive form of malignancies. In consequence, dermatologic surveillance is of high importance for OTRs and these patients represent an increasing and significant challenge to clinicians including dermatologists. In OTRs, patient and organ survival have increased considerably and continuously over the past two decades as a result of better immunosuppressive regimens and better posttransplant care. Great progress has been made in our understanding that individual immunosuppressive regiments differ in their effect on skin cancer risk in OTRs, and that effects of individual immunosuppressive regiments on skin cancer risk depend on various other factors including viral infections. Since sunlight is the major source of vitamin D for most humans, OTRs, who have to protect themselves consequently against solar or artificial UV radiation, are at high risk of developing vitamin D deficiency. Vitamin D deficiency is not only associated with increased risk for metabolic bone disease, but with other severe health problems including various types of malignancies. As a consequence, screening for and treatment of vitamin D deficiency is warranted in OTRs. In this review, we give an update on our present understanding of skin cancer surveillance in OTRs.

  20. Validation of updated RANNS with effect of oxygen-dissolved metallic Zircaloy-4 under LOCA quench condition

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hsingtzu; Udagawa, Yutaka; Narukawa, Takafumi; Amaya, Masaki, E-mail: amaya.masaki@jaea.go.jp

    2016-04-15

    Highlights: • Equations about the impact of the oxygen-dissolved Zircaloy-4 metallic layer which are newly added to RANNS code are described. • Validation of RANNS code using LOCA quench experimental data is presented. • The impact of the oxygen-dissolved metallic layer and the oxide layer formed on the surface of cladding on its axial load is discussed. - Abstract: Loss-of-Coolant-Accident (LOCA) is a design basis accident considered in LWR safety analyses, and LOCA simulation technique can be used to gain a better understanding of local cladding behaviors. This paper first summarizes equations regarding the oxygen-dissolved metallic Zircaloy-4 which have been implemented into the updated RANNS code. It is then validated using experimental data. The oxidation temperature is about 1473 K, the oxidation time is about 182.5 s and the quench temperature is about 973 K. The difference between the measured axial load and the RANNS computation as the cladding surface temperature reaches about 373 K is about 18.7%. In addition, the updated RANNS code is used to examine the influence of the oxygen absorbed into cladding on its axial load under LOCA quench conditions with oxidation time up to 674 s. The results suggest that the contributions of both the oxygen-dissolved metallic layer and the oxide layer to the axial load increase with oxidation time. The former corresponds to about a tenth of the computed axial load. These findings are considered useful for improving the accuracy of the analyses of the fuel rod behaviors during LOCA conditions.

  1. Validity and reproducibility of motion sensors in youth: A systematic update

    NARCIS (Netherlands)

    Vries, S.I. de; Hirtum, H.W.J.E.M. van; Bakker, I.; Hopman-Rock, M.; Hirasing, R.A.; Mechelen, W. van

    2009-01-01

    Purpose: To review recently published studies on the reproducibility, validity, and feasibility of motion sensors used to assess physical activity in healthy children and adolescents (2-18 yr). Methods: On October 2004, a systematic literature search in PubMed, EMBASE, and PsycINFO was performed. Th

  2. The Reliability and Validity of Protocols for the Assessment of Endurance Sports Performance: An Updated Review

    Science.gov (United States)

    Stevens, Christopher John; Dascombe, Ben James

    2015-01-01

    Sports performance testing is one of the most common and important measures used in sport science. Performance testing protocols must have high reliability to ensure any changes are not due to measurement error or inter-individual differences. High validity is also important to ensure test performance reflects true performance. Time-trial…

  3. Tumor Budding, uPA, and PAI-1 in Colorectal Cancer: Update of a Prospective Study.

    Science.gov (United States)

    Märkl, Bruno; Hardt, Jochen; Franz, Simon; Schaller, Tina; Schenkirsch, Gerhard; Kriening, Bernadette; Hoffmann, Reinhard; Rüth, Stefan

    2017-01-01

    Aims. The prognostic role of the proteases uPA and PAI-1, as well as tumor budding, in colon cancer, has been investigated previously. Methods. We provide 6-year follow-up data and results of the validation set. The initial test set and validation set consisted of 55 colon cancers and 68 colorectal cancers, respectively. Tissue samples were analyzed for uPA and PAI-1 using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA). Tumor budding was analyzed on cytokeratin-stained slides. Survival analyses were performed using cut-offs that were determined previously. Results. uPA was not prognostic for outcome. PAI-1 showed a trend towards reduced cancer specific survival in PAI-1 high-grade cases (68 versus 83 months; P = 0.091). The combination of high-grade PAI-1 and tumor budding was associated with significantly reduced cancer specific survival (60 versus 83 months; P = 0.021). After pooling the data from both sets, multivariate analyses revealed that the factors pN-stage, V-stage, and a combination of tumor budding and PAI-1 were independently prognostic for the association with distant metastases. Conclusions. A synergistic adverse effect of PAI-1 and tumor budding in uni- and multivariable analyses was found. PAI-1 could serve as a target for anticancer therapy.

  4. Adherence to Mediterranean diet and risk of cancer: an updated systematic review and meta-analysis of observational studies.

    Science.gov (United States)

    Schwingshackl, Lukas; Hoffmann, Georg

    2015-12-01

    The aim of the present systematic review and meta-analysis of observational studies was to gain further insight into the effects of adherence to Mediterranean Diet (MD) on overall cancer mortality, incidence of different types of cancer, and cancer mortality risk in cancer survivors. Literature search was performed using the electronic databases PubMed, and EMBASE until 2 July 2015. We included either cohort (for specific tumors only incidence cases were used) or case-control studies. Study specific risk ratios, hazard ratios, and odds ratios (RR/HR/OR) were pooled using a random effect model. The updated review process showed 23 observational studies that were not included in the previous meta-analysis (total number of studies evaluated: 56 observational studies). An overall population of 1,784,404 subjects was included in the present update. The highest adherence score to an MD was significantly associated with a lower risk of all-cause cancer mortality (RR: 0.87, 95% CI 0.81-0.93, I(2) = 84%), colorectal cancer (RR: 0.83, 95% CI 0.76-0.89, I(2) = 56%), breast cancer (RR: 0.93, 95% CI 0.87-0.99, I(2) =15%), gastric cancer (RR: 0.73, 95% CI 0.55-0.97, I(2) = 66%), prostate cancer (RR: 0.96, 95% CI 0.92-1.00, I(2) = 0%), liver cancer (RR: 0.58, 95% CI 0.46-0.73, I(2) = 0%), head and neck cancer (RR: 0.40, 95% CI 0.24-0.66, I(2) = 90%), pancreatic cancer (RR: 0.48, 95% CI 0.35-0.66), and respiratory cancer (RR: 0.10, 95% CI 0.01-0.70). No significant association could be observed for esophageal/ovarian/endometrial/and bladder cancer, respectively. Among cancer survivors, the association between the adherence to the highest MD category and risk of cancer mortality, and cancer recurrence was not statistically significant. The updated meta-analyses confirm a prominent and consistent inverse association provided by adherence to an MD in relation to cancer mortality and risk of several cancer types.

  5. [The guidelines and other scientific technical instruments for improving, updating and validating the Occupational Physician activities].

    Science.gov (United States)

    Apostoli, P

    2008-01-01

    From 2002 to 2007 the Italian Society of Industrial Medicine and Industrial Hygiene (S.I.M.L.I.I.) produced, in the context of the specific Education and Accreditation Programme for occupational physicians, more than 20 guide lines and consensus document on the most important and controversial themes for our Discipline. These instruments have aimed not only to improve the effectiveness of preventive actions but also to constantly adopt rigorous methodologies based where possible on evidence based medicine procedures. The Italian Occupational physicians agree with guidelines of our Scientific Society, but it appears now to be necessary to critically evaluate our experience, at the light of the new Framework Act for the occupational safety and health "Decreto legislativo 81/08" signed by the President of the Italian Republic on April 9, 2008, which firstly included in a legislative act terms such as technical normative, good practices, guide lines. Another important, mandatory reference, for a Medical Discipline as Occupational Medcine remains, in this debate is, in our Country, the National Program for Guide Lines edited By Italian National Health Institute since 2002 and part of current National System of Guide Lines concerning preparation, dissemination, updating, implementation of guide lines in Medicine. In this paper the main aspects related to different kind of instruments such as guide lines, consensus conference reports, technology assessment, good practices, technical normative, focusing in particular the argument identification, methodology, relationship between different instruments and their production and diffusion, economical and ethical issues and possible conflict of interest.

  6. Cancer cachexia update in head and neck cancer: Pathophysiology and treatment.

    Science.gov (United States)

    Couch, Marion E; Dittus, Kim; Toth, Michael J; Willis, Monte S; Guttridge, Denis C; George, Jonathan R; Chang, Eric Y; Gourin, Christine G; Der-Torossian, Hirak

    2015-07-01

    The pathophysiology of cancer cachexia remains complex. A comprehensive literature search was performed up to April 2013 using PubMed, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and the Google search engine. In this review, we focus on the different mediators of impaired anabolism and upregulated catabolism that alter the skeletal muscle homeostasis resulting in the wasting of cancer cachexia. We present recent evidence of targeted treatment modalities from clinical trials along with their potential mechanisms of action. We also report on the most current evidence from randomized clinical trials using multimodal treatments in patients with cancer cachexia, but also the evidence from head and neck cancer-specific trials. A more complete understanding of the pathophysiology of the syndrome may lead to more effective targeted therapies and improved outcomes for patients.

  7. Validate and update of 3D urban features using multi-source fusion

    Science.gov (United States)

    Arrington, Marcus; Edwards, Dan; Sengers, Arjan

    2012-06-01

    As forecast by the United Nations in May 2007, the population of the world transitioned from a rural to an urban demographic majority with more than half living in urban areas.1 Modern urban environments are complex 3- dimensional (3D) landscapes with 4-dimensional patterns of activity that challenge various traditional 1-dimensional and 2-dimensional sensors to accurately sample these man-made terrains. Depending on geographic location, data resulting from LIDAR, multi-spectral, electro-optical, thermal, ground-based static and mobile sensors may be available with multiple collects along with more traditional 2D GIS features. Reconciling differing data sources over time to correctly portray the dynamic urban landscape raises significant fusion and representational challenges particularly as higher levels of spatial resolution are available and expected by users. This paper presents a framework for integrating the imperfect answers of our differing sensors and data sources into a powerful representation of the complex urban environment. A case study is presented involving the integration of temporally diverse 2D, 2.5D and 3D spatial data sources over Kandahar, Afghanistan. In this case study we present a methodology for validating and augmenting 2D/2.5D urban feature and attribute data with LIDAR to produce validated 3D objects. We demonstrate that nearly 15% of buildings in Kandahar require understanding nearby vegetation before 3-D validation can be successful. We also address urban temporal change detection at the object level. Finally we address issues involved with increased sampling resolution since urban features are rarely simple cubes but in the case of Kandahar involve balconies, TV dishes, rooftop walls, small rooms, and domes among other things.

  8. Benchmarking Exercises To Validate The Updated ELLWF GoldSim Slit Trench Model

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, G. A.; Hiergesell, R. A.

    2013-11-12

    The Savannah River National Laboratory (SRNL) results of the 2008 Performance Assessment (PA) (WSRC, 2008) sensitivity/uncertainty analyses conducted for the trenches located in the EArea LowLevel Waste Facility (ELLWF) were subject to review by the United States Department of Energy (U.S. DOE) Low-Level Waste Disposal Facility Federal Review Group (LFRG) (LFRG, 2008). LFRG comments were generally approving of the use of probabilistic modeling in GoldSim to support the quantitative sensitivity analysis. A recommendation was made, however, that the probabilistic models be revised and updated to bolster their defensibility. SRS committed to addressing those comments and, in response, contracted with Neptune and Company to rewrite the three GoldSim models. The initial portion of this work, development of Slit Trench (ST), Engineered Trench (ET) and Components-in-Grout (CIG) trench GoldSim models, has been completed. The work described in this report utilizes these revised models to test and evaluate the results against the 2008 PORFLOW model results. This was accomplished by first performing a rigorous code-to-code comparison of the PORFLOW and GoldSim codes and then performing a deterministic comparison of the two-dimensional (2D) unsaturated zone and three-dimensional (3D) saturated zone PORFLOW Slit Trench models against results from the one-dimensional (1D) GoldSim Slit Trench model. The results of the code-to-code comparison indicate that when the mechanisms of radioactive decay, partitioning of contaminants between solid and fluid, implementation of specific boundary conditions and the imposition of solubility controls were all tested using identical flow fields, that GoldSim and PORFLOW produce nearly identical results. It is also noted that GoldSim has an advantage over PORFLOW in that it simulates all radionuclides simultaneously - thus avoiding a potential problem as demonstrated in the Case Study (see Section 2.6). Hence, it was concluded that the follow

  9. Compliance update--valid types of signatures in this modern era.

    Science.gov (United States)

    Hammon, Marilyn

    2005-05-01

    Proper signatures in the medical record is an area of concern because they are included in the Office of Inspector General (OIG) Compliance Guidance as a potential risk area effecting physician practices. One of the four areas identified by OIG is timely, accurate and complete documentation, which includes "date and legible identity of the observer." Federal auditors deny claims and require refunds if signatures are omitted from documentation of services. The vision of the current President is for all Americans to have Electronic Health Records (EHR) within a decade; this implies a growing use of electronic signatures. What constitutes a valid signature, and what regulations affect the use and type of signature? Businesses require signatures on many forms and documents. However, what if a check is not signed; can it be cashed? If a contract is not signed, is it binding? Similarly, if the medical record is not signed, will it withstand scrutiny in court? What is the significance of a signature? How important is it to authenticate or sign a report? To authenticate means to verify that the message/report comes from its stated source; therefore the author stands behind the documentation as written. The type of signature that is acceptable is variable, depending on the facility and the form payer requires.

  10. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update.

    Science.gov (United States)

    Takebe, Naoko; Miele, Lucio; Harris, Pamela Jo; Jeong, Woondong; Bando, Hideaki; Kahn, Michael; Yang, Sherry X; Ivy, S Percy

    2015-08-01

    During the past decade, cancer stem cells (CSCs) have been increasingly identified in many malignancies. Although the origin and plasticity of these cells remain controversial, tumour heterogeneity and the presence of small populations of cells with stem-like characteristics is established in most malignancies. CSCs display many features of embryonic or tissue stem cells, and typically demonstrate persistent activation of one or more highly conserved signal transduction pathways involved in development and tissue homeostasis, including the Notch, Hedgehog (HH), and Wnt pathways. CSCs generally have slow growth rates and are resistant to chemotherapy and/or radiotherapy. Thus, new treatment strategies targeting these pathways to control stem-cell replication, survival and differentiation are under development. Herein, we provide an update on the latest advances in the clinical development of such approaches, and discuss strategies for overcoming CSC-associated primary or acquired resistance to cancer treatment. Given the crosstalk between the different embryonic developmental signalling pathways, as well as other pathways, designing clinical trials that target CSCs with rational combinations of agents to inhibit possible compensatory escape mechanisms could be of particular importance. We also share our views on the future directions for targeting CSCs to advance the clinical development of these classes of agents.

  11. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.

    Science.gov (United States)

    van der Post, Rachel S; Vogelaar, Ingrid P; Carneiro, Fátima; Guilford, Parry; Huntsman, David; Hoogerbrugge, Nicoline; Caldas, Carlos; Schreiber, Karen E Chelcun; Hardwick, Richard H; Ausems, Margreet G E M; Bardram, Linda; Benusiglio, Patrick R; Bisseling, Tanya M; Blair, Vanessa; Bleiker, Eveline; Boussioutas, Alex; Cats, Annemieke; Coit, Daniel; DeGregorio, Lynn; Figueiredo, Joana; Ford, James M; Heijkoop, Esther; Hermens, Rosella; Humar, Bostjan; Kaurah, Pardeep; Keller, Gisella; Lai, Jennifer; Ligtenberg, Marjolijn J L; O'Donovan, Maria; Oliveira, Carla; Pinheiro, Hugo; Ragunath, Krish; Rasenberg, Esther; Richardson, Susan; Roviello, Franco; Schackert, Hans; Seruca, Raquel; Taylor, Amy; Ter Huurne, Anouk; Tischkowitz, Marc; Joe, Sheena Tjon A; van Dijck, Benjamin; van Grieken, Nicole C T; van Hillegersberg, Richard; van Sandick, Johanna W; Vehof, Rianne; van Krieken, J Han; Fitzgerald, Rebecca C

    2015-06-01

    Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, including diet post gastrectomy. The updated guidelines include revised CDH1 testing criteria (taking into account first-degree and second-degree relatives): (1) families with two or more patients with gastric cancer at any age, one confirmed DGC; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and LBC (one diagnosis before the age of 50). Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a centre of expertise is advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation is recommended. Standardised endoscopic surveillance in experienced centres is recommended for those opting not to have gastrectomy at the current time, those with CDH1 variants of uncertain significance and those that fulfil hereditary DGC criteria without germline CDH1 mutations. Expert histopathological confirmation of (early) signet ring cell carcinoma is recommended. The impact of gastrectomy and mastectomy should not be underestimated; these can have severe consequences on a psychological, physiological and metabolic level. Nutritional problems should be carefully monitored.

  12. Update on options for treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Prakash Vishnu

    2010-03-01

    Full Text Available Prakash Vishnu, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Prostate cancer is one of the most common cancers in men in US and European countries. Despite having a favorable prognosis, the incidence of incurable metastatic disease and mortality in the US is about 28,000 per year. Although hormone-based androgen deprivation therapies typically result in rapid responses, nearly all patients eventually develop progressive castration-resistant disease state. With readily available prostate-specific antigen (PSA testing, most of these patients are asymptomatic and manifest progression simply as a rising PSA. In patients with castration-resistant prostate cancer (CRPC, the median survival is about 1–2 years, with improvements in survival seen mostly with docetaxel-based regimens. The purpose of this article is to review the recent developments in the treatment of advanced CRPC.Recent findings: Since the two landmark trials (TAX-327 and Southwest Oncology Group 99–16 in CRPC, several newer cytotoxic drugs (epothilones, satraplatin, targeted agents (abiraterone, MDV3100 and vaccines have been tested in phase II and III setting with promising results.Conclusions: The role of newer agents in the treatment of CRPC still needs to be validated by phase III trials, which are currently ongoing. Whilst the novel biomarkers, ‘circulating tumor cells’, have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making, their exact utility and relevance calls for a larger prospective validation.Keywords: castration-resistant prostate cancer, novel therapies, mechanisms of resistance, circulating tumor cells

  13. Nuclear insertions of mitochondrial origin: Database updating and usefulness in cancer studies.

    Science.gov (United States)

    Ramos, Amanda; Barbena, Elena; Mateiu, Ligia; del Mar González, María; Mairal, Quim; Lima, Manuela; Montiel, Rafael; Aluja, Maria Pilar; Santos, Cristina

    2011-11-01

    Nuclear insertions of mitochondrial origin (NUMTs) can be useful tools in evolution and population studies. However, due to their similarity to mitochondrial DNA (mtDNA), NUMTs may also be a source of contamination in mtDNA studies. The main goal of this work is to present a database of NUMTs, based on the latest version of the human genome-GRCh37 draft. A total of 755 insertions were identified. There are 33 paralogous sequences with over 80% sequence similarity and of a greater length than 500bp. The non-identical positions between paralogous sequences are listed for the first time. As an application example, the described database is used to evaluate the impact of NUMT contamination in cancer studies. The evaluation reveals that 220 positions from 256 with zero hits in the current mtDNA phylogeny could in fact be traced to one or more nuclear insertions of mtDNA. This is due to they are located in non-identical positions between mtDNA and nuclear DNA (nDNA). After in silico primer validation of each revised cancer study, risk of co-amplification between mtDNA and nDNA was detected in some cases, whereas in others no risk of amplification was identified. This approach to cancer studies clearly proves the potential of our NUMT database as a valuable new tool to validate mtDNA mutations described in different contexts. Moreover, due to the amount of information provided for each nuclear insertion, this database should play an important role in designing evolutionary, phylogenetic and epidemiological studies.

  14. dbDEMC 2.0: updated database of differentially expressed miRNAs in human cancers

    Science.gov (United States)

    Yang, Zhen; Wu, Liangcai; Wang, Anqiang; Tang, Wei; Zhao, Yi; Zhao, Haitao; Teschendorff, Andrew E.

    2017-01-01

    MicroRNAs (miRNAs) are often deregulated in cancer and are thought to play an important role in cancer development. Large amount of differentially expressed miRNAs have been identified in various cancers by using high-throughput methods. It is therefore quite important to make a comprehensive collection of these miRNAs and to decipher their roles in oncogenesis and tumor progression. In 2010, we presented the first release of dbDEMC, representing a database for collection of differentially expressed miRNAs in human cancers obtained from microarray data. Here we describe an update of the database. dbDEMC 2.0 documents 209 expression profiling data sets across 36 cancer types and 73 subtypes, and a total of 2224 differentially expressed miRNAs were identified. An easy-to-use web interface was constructed that allows users to make a quick search of the differentially expressed miRNAs in certain cancer types. In addition, a new function of ‘meta-profiling’ was added to view differential expression events according to user-defined miRNAs and cancer types. We expect this database to continue to serve as a valuable source for cancer investigation and potential clinical application related to miRNAs. dbDEMC 2.0 is freely available at http://www.picb.ac.cn/dbDEMC. PMID:27899556

  15. Development and validation of the Cancer Dyspnoea Scale: a multidimensional, brief, self-rating scale

    OpenAIRE

    K. Tanaka; Akechi, T.; T. Okuyama; Nishiwaki,Y; Uchitomi, Y

    2000-01-01

    Dyspnoea is one of the most frequent and refractory symptoms in cancer patients. Lack of an appropriate assessment tool for dyspnoea seems to disturb establishment of management strategy. The purpose of this study was to develop and validate a brief self-rating scale to assess the multidimensional nature of dyspnoea in cancer patients. We developed a 12-item scale, the Cancer Dyspnoea Scale (CDS), composed of three factors (sense of effort/sense of anxiety/sense of discomfort), by using facto...

  16. Validity and Reliability of Psychosocial Factors Related to Breast Cancer Screening.

    Science.gov (United States)

    Zapka, Jane G.; And Others

    1991-01-01

    The construct validity of hypothesized survey items and data reduction procedures for selected psychosocial constructs frequently used in breast cancer screening research were investigated in telephone interviews with randomly selected samples of 1,184 and 903 women and a sample of 169 Hispanic clinic clients. Validity of the constructs is…

  17. Update of potency factors for asbestos-related lung cancer and mesothelioma.

    Science.gov (United States)

    Berman, D Wayne; Crump, Kenny S

    2008-01-01

    The most recent update of the U.S. Environmental Protection Agency (EPA) health assessment document for asbestos (Nicholson, 1986, referred to as "the EPA 1986 update") is now 20 years old. That document contains estimates of "potency factors" for asbestos in causing lung cancer (K(L)'s) and mesothelioma (K(M)'s) derived by fitting mathematical models to data from studies of occupational cohorts. The present paper provides a parallel analysis that incorporates data from studies published since the EPA 1986 update. The EPA lung cancer model assumes that the relative risk varies linearly with cumulative exposure lagged 10 years. This implies that the relative risk remains constant after 10 years from last exposure. The EPA mesothelioma model predicts that the mortality rate from mesothelioma increases linearly with the intensity of exposure and, for a given intensity, increases indefinitely after exposure ceases, approximately as the square of time since first exposure lagged 10 years. These assumptions were evaluated using raw data from cohorts where exposures were principally to chrysotile (South Carolina textile workers, Hein et al., 2007; mesothelioma only data from Quebec miners and millers, Liddell et al., 1997) and crocidolite (Wittenoom Gorge, Australia miners and millers, Berry et al., 2004) and using published data from a cohort exposed to amosite (Paterson, NJ, insulation manufacturers, Seidman et al., 1986). Although the linear EPA model generally provided a good description of exposure response for lung cancer, in some cases it did so only by estimating a large background risk relative to the comparison population. Some of these relative risks seem too large to be due to differences in smoking rates and are probably due at least in part to errors in exposure estimates. There was some equivocal evidence that the relative risk decreased with increasing time since last exposure in the Wittenoom cohort, but none either in the South Carolina cohort up to 50

  18. Measuring dispositional cancer worry in China and Belgium: a cross-cultural validation.

    Science.gov (United States)

    Bernat, Jennifer Kim; Jensen, Jakob D

    2014-01-01

    Dispositional cancer worry (DCW) is the uncontrollable tendency to dwell on cancer independent of relevant stimuli (e.g., diagnosis of the disease). Past research has suggested that DCW has two underlying dimensions: severity and frequency. Available measures of DCW severity and frequency were translated and validated in two countries: China and Belgium. Participants (N = 623) completed translated scales, as well as measures of general dispositional worry, cancer fear, and perceived risk. In both locations, DCW measures were reliable (Cronbach's alphas ranged from .78 - .93) and demonstrated strong convergent, divergent, and concurrent validity. Severity and frequency factors loaded as expected in exploratory factor analysis. Future research should pursue longitudinal tests of DCW's predictive validity and explore DCW in theoretical models predicting the relationship between worry and cancer prevention and early detection behaviors.

  19. Identification of certain cancer-mediating genes using Gaussian fuzzy cluster validity index

    Indian Academy of Sciences (India)

    Anupam Ghosh; Rajat K De

    2015-10-01

    In this article, we have used an index, called Gaussian fuzzy index (GFI), recently developed by the authors, based on the notion of fuzzy set theory, for validating the clusters obtained by a clustering algorithm applied on cancer gene expression data. GFI is then used for the identification of genes that have altered quite significantly from normal state to carcinogenic state with respect to their mRNA expression patterns. The effectiveness of the methodology has been demonstrated on three gene expression cancer datasets dealing with human lung, colon and leukemia. The performance of GFI is compared with 19 exiting cluster validity indices. The results are appropriately validated biologically and statistically. In this context, we have used biochemical pathways, -value statistics of GO attributes, -test and -score for the validation of the results. It has been reported that GFI is capable of identifying high-quality enriched clusters of genes, and thereby is able to select more cancer-mediating genes.

  20. Measuring quality of life in patients with head and neck cancer: Update of the EORTC QLQ-H&N Module, Phase III

    DEFF Research Database (Denmark)

    Singer, Susanne; Araújo, Cláudia; Arraras, Juan Ignacio;

    2015-01-01

    BACKGROUND: The objective of this study was to pilot test an updated version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-H&N60). METHODS: Patients with head and neck cancer were asked to complete a list of 60 head...

  1. BRCA mutations and survival in breast cancer: an updated systematic review and meta-analysis.

    Science.gov (United States)

    Zhu, Yaning; Wu, Jian; Zhang, Chengwan; Sun, Suan; Zhang, Jian; Liu, Wenjie; Huang, Jian; Zhang, Zhihong

    2016-10-25

    BRCA mutations occur frequently in breast cancer (BC), but their prognostic impact on outcomes of BC has not been determined. We conducted an updated meta-analysis on the association between BRCA mutations and survival in patients with BC. Electronic databases were searched. The primary outcome measure was overall survival (OS), and the secondary outcome measures included breast cancer-specific survival (BCSS) and event-free survival (EFS). Hazard ratios (HR) and 95% confidence interval (CI) were abstracted and pooled with random-effect modeling. Data from 297, 402 patients with BC were pooled from 34 studies. The median prevalence rates of BRCA1 and BRCA2 mutations were 14.5% and 8.3%, respectively. BRCA mutations were associated with worse OS (BRCA1: HR = 1.69, 95% CI, 1.35 to 2.12, p BRCA2: HR = 1.50, 95% CI 1.03 to 2.19, p = 0.034). However, this did not translate into poor BCSS (BRCA1: HR = 1.14, 95% CI, 0.81 to 1.16, p = 0.448; BRCA2: HR = 1.16; 95% CI 0.82 to 1.66, p = 0.401) or EFS (BRCA1: HR = 1.10, 95% CI, 0.86 to 1.41, p = 0.438; BRCA2: HR= 1.09; 95% CI 0.81 to 1.47, p = 0.558). Several studies analyzed BRCA1 and BRCA2 mutations together and found no impact on OS (HR = 1.21; 95% CI, 0.73 to 2.00, p = 0.454) or EFS (HR = 0.94; 95% CI, 0.60 to 1.48, p = 0.787). BRCA1 and BRCA2 mutations were associated with poor OS in patients with BC, but had no significant impact on BCSS or EFS. An improved survival was observed in BC patients who had BRCA1 mutation and treated with endocrinotherapy. The results may have therapeutic and prognostic implications important for BRCA mutation carriers with BC.

  2. DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach

    Science.gov (United States)

    Hubers, A J; Heideman, D A M; Burgers, S A; Herder, G J M; Sterk, P J; Rhodius, R J; Smit, H J; Krouwels, F; Welling, A; Witte, B I; Duin, S; Koning, R; Comans, E F I; Steenbergen, R D M; Postmus, P E; Meijer, G A; Snijders, P J F; Smit, E F; Thunnissen, E

    2015-01-01

    Background: Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer. Methods: DNA hypermethylation of RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities. Results: In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set. Conclusions: Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer. PMID:25719833

  3. Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression.

    Science.gov (United States)

    Cai, Xianlei; Wang, Chen; Yu, Wanqi; Fan, Wenjie; Wang, Shan; Shen, Ning; Wu, Pengcheng; Li, Xiuyang; Wang, Fudi

    2016-01-20

    The objective of this study was to investigate the associations between selenium exposure and cancer risk. We identified 69 studies and applied meta-analysis, meta-regression and dose-response analysis to obtain available evidence. The results indicated that high selenium exposure had a protective effect on cancer risk (pooled OR = 0.78; 95%CI: 0.73-0.83). The results of linear and nonlinear dose-response analysis indicated that high serum/plasma selenium and toenail selenium had the efficacy on cancer prevention. However, we did not find a protective efficacy of selenium supplement. High selenium exposure may have different effects on specific types of cancer. It decreased the risk of breast cancer, lung cancer, esophageal cancer, gastric cancer, and prostate cancer, but it was not associated with colorectal cancer, bladder cancer, and skin cancer.

  4. Survival nomogram for curatively resected Korean gastric cancer patients: multicenter retrospective analysis with external validation.

    Directory of Open Access Journals (Sweden)

    Bang Wool Eom

    Full Text Available A small number of nomograms have been previously developed to predict the individual survival of patients who undergo curative resection for gastric cancer. However, all were derived from single high-volume centers. The aim of this study was to develop and validate a nomogram for gastric cancer patients using a multicenter database.We reviewed the clinicopathological and survival data of 2012 patients who underwent curative resection for gastric cancer between 2001 and 2006 at eight centers. Among these centers, six institutions were randomly assigned to the development set, and the other two centers were assigned to the validation set. Multivariate analysis using the Cox proportional hazard regression model was performed, and discrimination and calibration were evaluated by external validation.Multivariate analyses revealed that age, tumor size, lymphovascular invasion, depth of invasion, and metastatic lymph nodes were significant prognostic factors for overall survival. In the external validation, the concordance index was 0.831 (95% confidence interval, 0.784-0.878, and Hosmer-Lemeshow chi-square statistic was 3.92 (P = 0.917.We developed and validated a nomogram to predict 5-year overall survival after curative resection for gastric cancer based on a multicenter database. This nomogram can be broadly applied even in general hospitals and is useful for counseling patients, and scheduling follow-up.

  5. Emerging aspects of oesophageal and gastro-oesophageal junction cancer histopathology – an update for the surgical oncologist

    Directory of Open Access Journals (Sweden)

    Mapstone Nicholas P

    2006-11-01

    Full Text Available Abstract Adenocarcinoma of the oesophagus and gastro-oesophageal junction are rapidly increasing in incidence and have a well described sequence of carcinogenesis: the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. During recent years there have been changes in the knowledge surrounding disease progression, cancer management and histopathology specimen reporting. Tumours around the gastro-oesophageal junction (GOJ pose several specific challenges. Numerous difficulties arise when the existing TNM staging systems for gastric and oesophageal cancers are applied to GOJ tumours. The issues facing the current TNM staging and GOJ tumour classification systems are reviewed in this article. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as circumferential resection margin status and lymph node metastases, have implications for specimen reporting. With the rising use of multimodal treatments for oesophageal cancer it is important that the response of the tumour to this therapy is carefully documented pathologically. In addition, several controversial and novel areas such as endoscopic mucosal resection, lymph node micrometastases and the sentinel node concept are being studied. We aim to review these aspects, with special relevance to oesophageal and gastro-oesophageal cancer specimen reporting, to update the surgical oncologist with an interest in upper gastrointestinal cancer.

  6. Validation of Candidate Serum Ovarian Cancer Biomarkers for Early Detection

    Directory of Open Access Journals (Sweden)

    Feng Su

    2007-01-01

    Full Text Available Objective: We have previously analyzed protein profi les using Surface Enhanced Laser Desorption and Ionization Time-Of-Flight Mass Spectroscopy (SELDI-TOF-MS [Kozak et al. 2003, Proc. Natl. Acad. Sci. U.S.A. 100:12343–8] and identified 3 differentially expressed serum proteins for the diagnosis of ovarian cancer (OC [Kozak et al. 2005, Proteomics, 5:4589–96], namely, apolipoprotein A-I (apoA-I, transthyretin (TTR and transferin (TF. The objective of the present study is to determine the efficacy of the three OC biomarkers for the detection of early stage (ES OC, in direct comparison to CA125.Methods: The levels of CA125, apoA-I, TTR and TF were measured in 392 serum samples [82 women with normal ovaries (N, 24 women with benign ovarian tumors (B, 85 women with ovarian tumors of low malignant potential (LMP, 126 women with early stage ovarian cancer (ESOC, and 75 women with late stage ovarian cancer (LSOC], obtained through the GOG and Cooperative Human Tissue Network. Following statistical analysis, multivariate regression models were built to evaluate the utility of the three OC markers in early detection.Results: Multiple logistic regression models (MLRM utilizing all biomarker values (CA125, TTR, TF and apoA-I from all histological subtypes (serous, mucinous, and endometrioid adenocarcinoma distinguished normal samples from LMP with 91% sensitivity (specifi city 92%, and normal samples from ESOC with a sensitivity of 89% (specifi city 92%. MLRM, utilizing values of all four markers from only the mucinous histological subtype showed that collectively, CA125, TTR, TF and apoA-I, were able to distinguish normal samples from mucinous LMP with 90% sensitivity, and further distinguished normal samples from early stage mucinous ovarian cancer with a sensitivity of 95%. In contrast, in serum samples from patients with mucinous tumors, CA125 alone was able to distinguish normal samples from LMP and early stage ovarian cancer with a sensitivity of

  7. Cancer megafunds with in silico and in vitro validation: accelerating cancer drug discovery via financial engineering without financial crisis.

    Science.gov (United States)

    Yang, Xianjin; Debonneuil, Edouard; Zhavoronkov, Alex; Mishra, Bud

    2016-09-06

    Advances in financial engineering are radically reshaping the biomedical marketplace. For instance, new methods of pooling diversified drug development programs by placing them in a special purpose vehicle (SPV) have been proposed to create a securitized cancer megafund allowing for debt and equity participation. In this study, we perform theoretical and numerical simulations that highlight the role of empirical validation of the projects comprising a cancer megafund. We quantify the degree to which the deliberately designed structure of derivatives and investments is key to its liquidity. Research megafunds with comprehensive in silico and laboratory validation protocols and ability to issue both debt, and equity as well as hybrid financial products may enable conservative investors including pension funds and sovereign government funds to profit from unique securitization opportunities. Thus, while hedging investor's longevity risk, such well-validated megafunds will contribute to health, well being and longevity of the global population.

  8. Cancer megafunds with in silico and in vitro validation: Accelerating cancer drug discovery via financial engineering without financial crisis

    KAUST Repository

    Yang, Xianjin

    2016-06-03

    Advances in financial engineering are radically reshaping the biomedical marketplace. For instance, new methods of pooling diversified drug development programs by placing them in a special purpose vehicle (SPV) have been proposed to create a securitized cancer megafund allowing for debt and equity participation. In this study, we perform theoretical and numerical simulations that highlight the role of empirical validation of the projects comprising a cancer megafund. We quantify the degree to which the deliberately designed structure of derivatives and investments is key to its liquidity. Research megafunds with comprehensive in silico and laboratory validation protocols and ability to issue both debt, and equity as well as hybrid financial products may enable conservative investors including pension funds and sovereign government funds to profit from unique securitization opportunities. Thus, while hedging investor\\'s longevity risk, such well-validated megafunds will contribute to health, well being and longevity of the global population.

  9. Comparative validation of the IPAQ and the 7-Day PAR among women diagnosed with breast cancer

    Directory of Open Access Journals (Sweden)

    Rock Cheryl L

    2006-03-01

    Full Text Available Abstract Background The criterion-related validity and measurement bias of the long form of the International Physical Activity Questionnaire (IPAQ was compared to the 7-Day Physical Activity Recall (PAR. Methods Participants were women who have been diagnosed with breast cancer and enrolled in the ongoing Women's Healthy Eating and Living Study. Women (N = 159, average age 57 years wore an accelerometer for one week and then completed the IPAQ or the PAR. Results The validity correlation of the PAR was significantly higher (p Conclusion The PAR was superior to the IPAQ in terms of validity, measurement bias, and screening statistics.

  10. Validation of Reference Genes for Oral Cancer Detection Panels in a Prospective Blinded Cohort.

    Directory of Open Access Journals (Sweden)

    Jack L Martin

    Full Text Available Reference genes are needed as internal controls to determine relative expression for clinical application of gene expression panels. Candidate constitutively expressed genes must be validated as suitable reference genes in each body fluid and disease entity. Prior studies have predominantly validated oral squamous cell carcinoma associated messenger RNAs (mRNAs based on quantitative polymerase chain reaction (qPCR quantification cycle (Cq values without adjustment for housekeeping genes.One hundred sixty eight patients had saliva collected before clinically driven biopsy of oral lesions suspicious for cancer. Seven potential housekeeping mRNAs and six pre-specified oral cancer associated mRNAs were measured with qPCR by personnel blinded to tissue diagnosis. Housekeeping gene stability was determined with the NormFinder program in a training set of 12 randomly selected cancer and 24 control patients. Genes with stability indices 0.02 in the training set and were not further tested. MT-ATP6, RPL30, RPL37A, RPLP0 and RPS17 all had stability indices <0.02 in the training set and in the verification set. The geNorm M values were all ≤1.10. All six pre-specified cancer genes (IL8, IL1, SAT, OAZ1, DUSP1 and S100P were up-regulated in cancer versus control patients with from nearly twofold to over threefold higher levels (p<0.01 for all based on delta Cq values.Five reference genes are validated for use in oral cancer salivary gene expression panels. Six pre-specified oral carcinoma associated genes are demonstrated to be highly significantly up-regulated in cancer patients based on delta Cq values. These cancer and reference genes are suitable for inclusion in gene expression panels for research and clinical applications.ClinicalTrials.gov NCT01587573.

  11. Validation of methylation biomarkers that distinguish normal colon mucosa of cancer patients from normal colon mucosa of patients without cancer.

    Science.gov (United States)

    Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

    2014-07-01

    We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of patients with colon cancer and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 patients with cancer and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of ten of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r = 0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy.

  12. Validation of a Milk Consumption Stage of Change Algorithm among Adolescent Survivors of Childhood Cancer

    Science.gov (United States)

    Mays, Darren; Gerfen, Elissa; Mosher, Revonda B.; Shad, Aziza T.; Tercyak, Kenneth P.

    2012-01-01

    Objective: To assess the construct validity of a milk consumption Stages of Change (SOC) algorithm among adolescent survivors of childhood cancer ages 11 to 21 years (n = 75). Methods: Baseline data from a randomized controlled trial designed to evaluate a health behavior intervention were analyzed. Assessments included a milk consumption SOC…

  13. Validation of the Adherence Determinants Questionnaire scale among women with breast and cervical cancer

    Directory of Open Access Journals (Sweden)

    Paula Renata Amorim Lessa

    2015-10-01

    Full Text Available Objectives: the aim was to translate and culturally adapt the Adherence Determinants Questionnaire scale for the Portuguese language in the Brazilian context, and to check its reliability and validity to analyze the elements of the adherence of patients to the clinical treatment for breast and cervical cancer.Method: this was a methodological study, carried out in two oncology reference centers. The sample consisted of 198 participants, with 152 being treated for breast cancer and 46 being treated for cervical cancer. The content validation was performed by a committee of experts. The construct validation was demonstrated through factor analysis and the reliability was analyzed using Cronbach's alpha.Results: the committee of experts made the necessary adjustments so that the scale was adapted to the Brazilian context. The factor analysis suggested a reduction from seven to five factors and the maintenance of 38 items similar to those of the original scale. The reliability, investigated through Cronbach's alpha, was .829, showing high internal consistency.Conclusion: it was concluded that the Brazilian version of the Adherence Determinants Questionnaire scale is a valid and reliable instrument that is able to measure the elements of adherence to the treatment for breast and cervical cancer.

  14. Update of research on the role of EZH2 in cancer progression

    Directory of Open Access Journals (Sweden)

    Shen L

    2013-04-01

    Full Text Available Liang Shen,1 Jing Cui,2 Shumei Liang,3 Yingxin Pang,1 Peishu Liu11Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 2Department of Oral and Maxillofacial Surgery, Jinan Stomatologic Hospital, 3Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of ChinaAbstract: Accumulating evidence shows that enhancer of zeste homolog 2 (E2H2 is upregulated in a broad range of cancer types, such as breast cancer, prostate cancer, ovarian cancer, and colon cancer. Therefore, inhibiting EZH2 expression may be a promising strategy for anticancer therapy. This review focuses on the current understanding of the mechanisms underlying EZH2 regulation that are involved in cancer progression. Also, it introduces two EZH2 inhibitors that target EZH2 and could be potentially applied in the treatment of cancer in the future.Keywords: EZH2, PRC2, cancer

  15. GSTM1 null genotype and gastric cancer risk in the Chinese population: an updated meta-analysis and review.

    Science.gov (United States)

    Zhang, Xi-Liang; Cui, Yong-Hui

    2015-01-01

    Although a number of studies have been conducted on the association between the GSTM1 null genotype and gastric cancer in People's Republic of China, this association remains elusive and controversial. To clarify the effects of the GSTM1 null genotype on the risk of gastric cancer, an updated meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) up to November 5, 2014. A total of 25 studies including 3,491 cases and 5,921 controls were included in this meta-analysis. Overall, a significant association (odds ratio [OR] =1.47, 95% CI: 1.28-1.69) was found between the null GSTM1 and gastric cancer risk when all studies in Chinese population were pooled into the meta-analysis. In subgroup analyses stratified by quality score, geographic area, and source of controls, the same results were observed. Additionally, a significant association was found both in smokers and non-smokers. This meta-analysis showed that the null GSTM1 may be a potential biomarker for gastric cancer risk in Chinese, and further studies with gene-gene and gene-environment interactions are required for definite conclusions.

  16. Anti-cancer drug discovery: update and comparisons in yeast, Drosophila, and zebrafish.

    Science.gov (United States)

    Gao, Guangxun; Chen, Liang; Huang, Chuanshu

    2014-01-01

    Discovery of novel cancer chemotherapeutics focuses on screening and identifying compounds that can target 'cancer-specific' biological processes while causing minimal toxicity to non-tumor cells. Alternatively, model organisms with highly conserved cancer-related cellular processes relative to human cells may offer new opportunities for anticancer drug discovery when combined with chemical screening. Some organisms used for chemotherapeutic discovery include yeast, Drosophila, and zebrafish which are similar in important ways relevant to cancer study but offer distinct advantages as well. Here, we describe these model attributes and the rationale for using them in cancer drug screening research.

  17. Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment

    Science.gov (United States)

    Wang, Xin; Robertson, Alex D.; Haas, Kevin R.; Theilmann, Mark R.; Spurka, Lindsay; Grauman, Peter V.; Lai, Henry H.; Jeon, Diana; Haliburton, Genevieve; Leggett, Matt; Chu, Clement S.; Iori, Kevin; Maguire, Jared R.; Ready, Kaylene; Evans, Eric A.; Haque, Imran S.

    2017-01-01

    The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy number variants (CNVs) in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers. To determine test accuracy and reproducibility, we performed a rigorous analytical validation across 341 samples, including 118 cell lines and 223 patient samples. The screen achieved 100% test sensitivity across different mutation types, with high specificity and 100% concordance with conventional Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). We also demonstrated the screen’s high intra-run and inter-run reproducibility and robust performance on blood and saliva specimens. Furthermore, we showed that pathogenic Alu element insertions can be accurately detected by our test. Overall, the validation in our clinical laboratory demonstrated the analytical performance required for collecting and reporting genetic information related to risk of developing hereditary cancers. PMID:28243543

  18. Psychometric validation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24)

    DEFF Research Database (Denmark)

    Greimel, Elfriede; Nordin, Andy; Lanceley, Anne

    2011-01-01

    A validation study was conducted to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24). This module was designed to assess disease and treatment specific aspects...... of the quality of life (QoL) of patients with endometrial cancer....

  19. [Standardization of syndrome differentiation based on stages for breast cancer: a significant and updating topic on mastology of traditional Chinese medicine].

    Science.gov (United States)

    Lin, Yi; Chen, Qian-Jun; Liu, Peng-Xi

    2006-09-01

    The incidence of breast cancer increased rapidly in recent years. Breast cancer has become the most frequent malignant tumor of female especially in the developed regions. Traditional Chinese medicine (TCM) is effective in treating breast cancer, but its theories appear hysteretic, restricting the progress in clinical practice, teaching and research of TCM in the treatment of breast cancer. This article described the significance and urgency to work out the standardization of syndrome differentiation based on stages for breast cancer and put it into practice. It also analyzed the foundations, ideas and approaches of the research of standardization of syndrome differentiation based on stages for breast cancer in light of the changes of spectrum of diseases, the weaknesses of modern medicine in treating breast cancer, and the existed problems in the update clinical practice.

  20. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Pearce, C L; Near, A M; Van Den Berg, D J;

    2009-01-01

    The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had...... been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P... and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted....

  1. Cranberries and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents

    Directory of Open Access Journals (Sweden)

    Katherine M. Weh

    2016-08-01

    Full Text Available Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques, whereas in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy in high risk cohorts should be considered.

  2. Curcumin: Updated Molecular Mechanisms and Intervention Targets in Human Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hong Yin

    2012-03-01

    Full Text Available Curcumin, a yellow pigment derived from Curcuma longa Linn, has attracted great interest in the research of cancer during the past decades. Extensive studies documented that curcumin attenuates cancer cell proliferation and promotes apoptosis in vivo and in vitro. Curcumin has been demonstrated to interact with multiple molecules and signal pathways, which makes it a potential adjuvant anti-cancer agent to chemotherapy. Previous investigations focus on the mechanisms of action for curcumin, which is shown to manipulate transcription factors and induce apoptosis in various kinds of human cancer. Apart from transcription factors and apoptosis, emerging studies shed light on latent targets of curcumin against epidermal growth factor receptor (EGFR, microRNAs (miRNA, autophagy and cancer stem cell. The present review predominantly discusses significance of EGFR, miRNA, autophagy and cancer stem cell in lung cancer therapy. Curcumin as a natural phytochemicals could communicate with these novel targets and show synergism to chemotherapy. Additionally, curcumin is well tolerated in humans. Therefore, EGFR-, miRNA-, autophagy- and cancer stem cell-based therapy in the presence of curcumin might be promising mechanisms and targets in the therapeutic strategy of lung cancer.

  3. GSTM1 null genotype and gastric cancer risk in the Chinese population: an updated meta-analysis and review

    Directory of Open Access Journals (Sweden)

    Zhang XL

    2015-04-01

    Full Text Available Xi-Liang Zhang, Yong-Hui Cui Department of Gastroenterology, The First People’s Hospital of Shangqiu City, Shangqiu, Henan, People’s Republic of China Abstract: Although a number of studies have been conducted on the association between the GSTM1 null genotype and gastric cancer in People’s Republic of China, this association remains elusive and controversial. To clarify the effects of the GSTM1 null genotype on the risk of gastric cancer, an updated meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI, and Chinese Biology Medicine (CBM up to November 5, 2014. A total of 25 studies including 3,491 cases and 5,921 controls were included in this meta-analysis. Overall, a significant association (odds ratio [OR] =1.47, 95% CI: 1.28–1.69 was found between the null GSTM1 and gastric cancer risk when all studies in Chinese population were pooled into the meta-analysis. In subgroup analyses stratified by quality score, geographic area, and source of controls, the same results were observed. Additionally, a significant association was found both in smokers and non-smokers. This meta-analysis showed that the null GSTM1 may be a potential biomarker for gastric cancer risk in Chinese, and further studies with gene–gene and gene–environment interactions are required for definite conclusions. Keywords: meta-analysis, GSTM1, polymorphism, gastric cancer

  4. Health-related quality of life in non-small-cell lung cancer: An update of a systematic review on methodologic issues in randomized controlled trials

    NARCIS (Netherlands)

    L. Claassens (Lily); J. van Meerbeeck (Jan); C. Coens (Corneel); C. Quinten (Chantal); I. Ghislain (Irina); E.K. Sloan (Elizabeth); X.S. Wang (Xin Shelly); G. Velikova (Galina); A. Bottomley (Andrew)

    2011-01-01

    textabstractPurpose This study is an update of a systematic review of health-related quality-of-life (HRQOL) methodology reporting in non-small-cell lung cancer (NSCLC) randomized controlled trials (RCTs). The objective was to evaluate HRQOL methodology reporting over the last decade and its benefit

  5. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer.

    Science.gov (United States)

    Azzoli, Christopher G; Baker, Sherman; Temin, Sarah; Pao, William; Aliff, Timothy; Brahmer, Julie; Johnson, David H; Laskin, Janessa L; Masters, Gregory; Milton, Daniel; Nordquist, Luke; Pfister, David G; Piantadosi, Steven; Schiller, Joan H; Smith, Reily; Smith, Thomas J; Strawn, John R; Trent, David; Giaccone, Giuseppe

    2009-12-20

    The purpose of this article is to provide updated recommendations for the treatment of patients with stage IV non-small-cell lung cancer. A literature search identified relevant randomized trials published since 2002. The scope of the guideline was narrowed to chemotherapy and biologic therapy. An Update Committee reviewed the literature and made updated recommendations. One hundred sixty-two publications met the inclusion criteria. Recommendations were based on treatment strategies that improve overall survival. Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life. For first-line therapy in patients with performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For patients with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs. Data are insufficient to recommend routine use of molecular markers to select chemotherapy.

  6. An updated validation of Promega's PowerPlex 16 System: high throughput databasing under reduced PCR volume conditions on Applied Biosystem's 96 capillary 3730xl DNA Analyzer.

    Science.gov (United States)

    Spathis, Rita; Lum, J Koji

    2008-11-01

    The PowerPlex 16 System from Promega Corporation allows single tube multiplex amplification of sixteen short tandem repeat (STR) loci including all 13 core combined DNA index system STRs. This report presents an updated validation of the PowerPlex 16 System on Applied Biosystem's 96 capillary 3730xl DNA Analyzer. The validation protocol developed in our laboratory allows for the analysis of 1536 loci (96 x 16) in c. 50 min. We have further optimized the assay by decreasing the reaction volume to one-quarter that recommended by the manufacturer thereby substantially reducing the total cost per sample without compromising reproducibility or specificity. This reduction in reaction volume has the ancillary benefit of dramatically increasing the sensitivity of the assay allowing for accurate analysis of lower quantities of DNA. Due to its substantially increased throughput capability, this extended validation of the PowerPlex 16 System should be useful in reducing the backlog of unanalyzed DNA samples currently facing public DNA forensic laboratories.

  7. An updated review on cancer risk associated with incretin mimetics and enhancers.

    Science.gov (United States)

    Tseng, Chin-Hsiao; Lee, Kuo-Yang; Tseng, Farn-Hsuan

    2015-01-01

    Incretin-based therapies, including the use of incretin mimetics of glucagon-like peptide-1 receptor (GLP-1R) agonists and incretin enhancers of dipeptidyl-peptidase 4 (DPP-4) inhibitors, are widely used by clinicians for glucose lowering in patients with type 2 diabetes mellitus. These agents have benefits of a lower risk of hypoglycemia, being neutral for body weight for DPP-4 inhibitors and having a potential for weight reduction with GLP-1R agonists. They may also have a neutral or beneficial cardiovascular effect. Despite these benefits, an increased risk of cancer (especially pancreatic cancer and thyroid cancer) associated with incretin-based therapies has been reported. In this article, we reviewed related literature of experimental animal and observational human studies, clinical trials, and meta-analyses published until December 15, 2014. Current studies suggested a probable role of GLP-1R activation on the development of pancreatic cancer and thyroid cancer in rodents, but such an effect in humans is not remarkable due to the lower or lack of expression of GLP-1R on human pancreatic ductal cells and thyroid tissues. Findings in human studies are controversial and inconclusive. In the analyses of the US Food and Drug Administration adverse events reporting system, a significantly higher risk of pancreatic cancer was observed for GLP-1R agonists and DPP-4 inhibitors, but a significantly higher risk of thyroid cancer was only observed for GLP-1R agonists. Such a higher risk of pancreatic cancer or thyroid cancer could not be similarly demonstrated in other human observational studies or analyses of data from clinical trials. With regards to cancers other than pancreatic cancer and thyroid cancer, available studies supported a neutral association in humans. Some preliminary studies even suggested a potentially beneficial effect on the development of other cancers with the use of incretins. Based on current evidence, continuous monitoring of the cancer issues

  8. Rapid target gene validation in complex cancer mouse models using re-derived embryonic stem cells.

    Science.gov (United States)

    Huijbers, Ivo J; Bin Ali, Rahmen; Pritchard, Colin; Cozijnsen, Miranda; Kwon, Min-Chul; Proost, Natalie; Song, Ji-Ying; de Vries, Hilda; Badhai, Jitendra; Sutherland, Kate; Krimpenfort, Paul; Michalak, Ewa M; Jonkers, Jos; Berns, Anton

    2014-02-01

    Human cancers modeled in Genetically Engineered Mouse Models (GEMMs) can provide important mechanistic insights into the molecular basis of tumor development and enable testing of new intervention strategies. The inherent complexity of these models, with often multiple modified tumor suppressor genes and oncogenes, has hampered their use as preclinical models for validating cancer genes and drug targets. In our newly developed approach for the fast generation of tumor cohorts we have overcome this obstacle, as exemplified for three GEMMs; two lung cancer models and one mesothelioma model. Three elements are central for this system; (i) The efficient derivation of authentic Embryonic Stem Cells (ESCs) from established GEMMs, (ii) the routine introduction of transgenes of choice in these GEMM-ESCs by Flp recombinase-mediated integration and (iii) the direct use of the chimeric animals in tumor cohorts. By applying stringent quality controls, the GEMM-ESC approach proofs to be a reliable and effective method to speed up cancer gene assessment and target validation. As proof-of-principle, we demonstrate that MycL1 is a key driver gene in Small Cell Lung Cancer.

  9. Cancer Appetite and Symptom Questionnaire (CASQ) for Brazilian Patients: Cross-Cultural Adaptation and Validation Study

    Science.gov (United States)

    Serrano, Sergio Vicente; Halliday, Vanessa; Maroco, João; Campos, Juliana Alvares Duarte Bonini

    2016-01-01

    Background Appetite and symptoms, conditions generally reported by the patients with cancer, are somewhat challenging for professionals to measure directly in clinical routine (latent conditions). Therefore, specific instruments are required for this purpose. This study aimed to perform a cultural adaptation of the Cancer Appetite and Symptom Questionnaire (CASQ), into Portuguese and evaluate its psychometric properties on a sample of Brazilian cancer patients. Methods This is a validation study with Brazilian cancer patients. The face, content, and construct (factorial and convergent) validities of the Cancer Appetite and Symptom Questionnaire, the study tool, were estimated. Further, a confirmatory factor analysis (CFA) was conducted. The ratio of chi-square and degrees of freedom (χ2/df), comparative fit index (CFI), goodness of fit index (GFI) and root mean square error of approximation (RMSEA) were used for fit model assessment. In addition, the reliability of the instrument was estimated using the composite reliability (CR) and Cronbach’s alpha coefficient (α), and the invariance of the model in independent samples was estimated by a multigroup analysis (Δχ2). Results Participants included 1,140 cancer patients with a mean age of 53.95 (SD = 13.25) years; 61.3% were women. After the CFA of the original CASQ structure, 2 items with inadequate factor weights were removed. Four correlations between errors were included to provide adequate fit to the sample (χ2/df = 8.532, CFI = .94, GFI = .95, and RMSEA = .08). The model exhibited a low convergent validity (AVE = .32). The reliability was adequate (CR = .82 α = .82). The refined model showed strong invariance in two independent samples (Δχ2: λ: p = .855; i: p = .824; Res: p = .390). A weak stability was obtained between patients undergoing chemotherapy and radiotherapy (Δχ2: λ: p = .155; i: p < .001; Res: p < .001), and between patients undergoing chemotherapy combined with radiotherapy and

  10. Magnetic resonance only workflow and validation of dose calculations for radiotherapy of prostate cancer

    DEFF Research Database (Denmark)

    Christiansen, Rasmus Lübeck; Jensen, Henrik R.; Brink, Carsten

    2017-01-01

    Background: Current state of the art radiotherapy planning of prostate cancer utilises magnetic resonance (MR) for soft tissue delineation and computed tomography (CT) to provide an electron density map for dose calculation. This dual scan workflow is prone to setup and registration error....... This study evaluates the feasibility of an MR-only workflow and the validity of dose calculation from an MR derived pseudo CT. Material and methods: Thirty prostate cancer patients were CT and MR scanned. Clinical treatment plans were generated on CT using a single 18 MV arc volumetric modulated arc therapy...

  11. Psychological impact of genetic testing for cancer susceptibility: an update of the literature.

    Science.gov (United States)

    Meiser, Bettina

    2005-12-01

    This article presents an overview of the rapidly evolving body of literature on the psychological impact of genetic testing for hereditary breast/ovarian cancer susceptibility, hereditary non-polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). Uptake of genetic testing for BRCA1/2 and HNPCC-related mutations is more consistently related to psychological factors, rather than sociodemographic variables. Most studies on the psychological impact of genetic testing amongst individuals who have never been affected by cancer demonstrate that non-carriers derive significant psychological benefits from genetic testing, while no adverse effects have been observed amongst carriers. These benefits are more clear-cut for HNPCC, compared to hereditary breast/ovarian cancer, reflecting differences in risk management options. The few studies available on individuals affected with cancer indicate that the impact of genetic testing is mediated and amplified by their former experience of cancer. Future directions and challenges of research in this area are reviewed. In particular, more empirical data are needed on the broader impact of genetic testing on those with inconclusive results or results of uncertain significance. As genetic testing is becoming available for other types of familial cancer, additional investigations will be needed as there is evidence to suggest that the impact of genetic testing may be unique to each type of familial cancer.

  12. Eribulin for the treatment of metastatic breast cancer: an update on its safety and efficacy

    Directory of Open Access Journals (Sweden)

    Doherty MK

    2015-01-01

    Full Text Available Mark K Doherty, Patrick G Morris Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland Abstract: Breast cancer remains a leading cause of cancer-related death internationally. Treatment approaches for metastatic breast cancer have evolved in recent years; however chemotherapy remains a core component for the majority of patients. Agents such as anthracyclines and taxanes have been extensively studied and form standard treatment. Eribulin mesylate is a novel synthetic microtubule-directed chemotherapy, based on a naturally-occurring compound. Through phase I studies, eribulin was found to be tolerable and activity was seen in patients with metastatic breast cancer. Phase II studies in metastatic breast cancer further demonstrated its efficacy, with responses and survival which compare favorably with other studied chemotherapy agents. The phase III EMBRACE study showed superior survival for patients treated with eribulin compared with those who received a physician’s choice control. This led to its approval for use in many countries in this setting. Its toxicity profile is well established and manageable for the most part, with the commonest reported toxicities being alopecia, fatigue, neutropenia and peripheral neuropathy. A second reported phase III study comparing eribulin to capecitabine failed to show an improvement in survival in pretreated patients. This article reviews the clinical pharmacology and mechanism of action of eribulin, and summarizes the results of the major preclinical and clinical studies of eribulin in metastatic breast cancer. Keywords: eribulin, breast cancer, metastatic breast cancer, review, new treatments, chemotherapy

  13. Role of multiparametric MRI in the diagnosis of prostate cancer: update.

    Science.gov (United States)

    Rosi, Giovanni; Indino, Elena Lucia; Salvo, Vincenzo; Colarieti, Anna; Fierro, Davide; Scialpi, Michele; Panebianco, Valeria

    2016-05-24

    Prostate cancer is the most common malignancy of the male gender. The role of magnetic resonance imaging has evolved very rapidly over the years to be currently recognized as a fundamental tool in the diagnosis, treatment and follow-up of prostate cancer.

  14. Newer therapies for the treatment of metastatic breast cancer: A clinical update

    Directory of Open Access Journals (Sweden)

    Anjana Mohan

    2013-01-01

    Full Text Available Breast cancer is the foremost common malignancy among the female population around the world. Female breast cancer incidence rates have increased since 1980, slowed in 1990, the rate of increase have leveled off since 2001. In spite of the advances in the early detection, treatment, surgery and radiation support, almost 70% of the patients develop metastasis and die of the disease. Around 10% of the patients when diagnosed with breast cancer have metastases. Survival among the breast cancer patients have increased due to the introduction of novel single agent, combination of chemotherapeutic agents and targeted biologic agents, which is breast cancer specific. The staging of tumor-node-metastasis is significant for the prognosis and treatment. Predominantly the combination of chemotherapeutic regimen is given to improve the rate of clinical benefit and the overall survival rate. Novel mono-therapeutic options are being used often in metastatic setting as they will not be able to endure the toxicity of the combination regimen. Usually, endocrine therapy is recommended for hormone-responsive breast cancer due to efficacy and favorable side effect profile but chemotherapy becomes an option when endocrine therapy fails. This review summarizes the newer therapeutic options for early breast cancer and advanced breast cancer that are pretreated heavily on other chemotherapeutic agents. Further it provides monotherapies and other emerging novel combination regime which can be opted for first line or second line setting.

  15. Fruit and vegetable consumption and lung cancer risk: updated information from the European Prospective Investigation into Cancer and Nutrition (EPIC).

    NARCIS (Netherlands)

    Linseisen, J.; Rohrmann, S.; Miller, A.B.; Bueno-De-Mesquita, H.B.; Buchner, F.L.; Vineis, P.; Agudo, A.; Gram, I.T.; Janson, L.; Krogh, V.; Overvad, K.; Rasmuson, T.; Schulz, M.; Pischon, T.; Kaaks, R.; Nieters, A.; Allen, N.E.; Key, T.J.; Bingham, S.; Khaw, K.T.; Amiano, P.; Barricarte, A.; Martinez, C.; Navarro, C.; Quiros, R.; Clavel-Chapelon, F.; Boutron-Ruault, M.C.; Touvier, M.; Peeters, P.H.; Berglund, G.; Hallmans, G.; Lund, E.; Palli, D.; Panico, S.; Tumino, R.; Tjonneland, A.; Olsen, A.; Trichopoulou, A.; Trichopoulos, D.; Autier, P.; Boffetta, P.; Slimani, N.; Riboli, E.

    2007-01-01

    The association of fruit and vegetable consumption and lung cancer incidence was evaluated using the most recent data from the European Prospective Investigation into Cancer and Nutrition (EPIC), applying a refined statistical approach (calibration) to account for measurement error potentially intro

  16. Cardio-Oncology: An Update on Cardiotoxicity of Cancer-Related Treatment.

    Science.gov (United States)

    Lenneman, Carrie G; Sawyer, Douglas B

    2016-03-18

    Through the success of basic and disease-specific research, cancer survivors are one of the largest growing subsets of individuals accessing the healthcare system. Interestingly, cardiovascular disease is the second leading cause of morbidity and mortality in cancer survivors after recurrent malignancy. This recognition has helped stimulate a collaboration between oncology and cardiology practitioners and researchers, and the portmanteau cardio-oncology (also known as onco-cardiology) can now be found in many medical centers. This collaboration promises new insights into how cancer therapies impact cardiovascular homeostasis and long-term effects on cancer survivors. In this review, we will discuss the most recent views on the cardiotoxicity related to various classes of chemotherapy agents and radiation. We will also discuss broadly the current strategies for treating and preventing cardiovascular effects of cancer therapy.

  17. Imaging prostate cancer: an update on positron emission tomography and magnetic resonance imaging

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Turkbey, Baris; Choyke, Peter;

    2010-01-01

    Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an essential role in the clinical management of patients. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis of anatomic, functional......, and molecular imaging information. Developments in imaging technologies, specifically magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT), have improved the detection rate of prostate cancer. MRI has improved lesion detection and local staging. Furthermore, MRI...... allows functional assessment with techniques such as diffusion-weighted MRI, MR spectroscopy, and dynamic contrast-enhanced MRI. The most common PET radiotracer, (18)F-fluorodeoxyglucose, is not very useful in prostate cancer. However, in recent years other PET tracers have improved the accuracy of PET...

  18. Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

    Science.gov (United States)

    2015-10-01

    biomarkers to determine the presence of or progression to aggressive disease. ( Lead site: FHCRC) Milestone 2. Execute collaboration agreement with...panel of four-kallikrein plasma-based markers to determine the presence of or progression to clinically relevant prostate cancer. ( Lead site: FHCRC... Lead site: FHCRC) Milestone 10. Urine specimens identified for analysis. Due 12/30/2014 COMPLETED Milestone 11. PCA3 and TMPRSS2:ERG validation

  19. Stress and breast cancer: a systematic update on the current knowledge

    DEFF Research Database (Denmark)

    Nielsen, Naja Rod; Grønbaek, Morten

    2006-01-01

    A vast body of research has been carried out to examine the relationship between psychological stress and the risk of breast cancer. Previous reviews on this issue have mainly focused on stressful life events and have included both prospective and retrospective studies. The results from...... these reviews have revealed conflicting data. We evaluate whether stressful life events, work-related stress, or perceived global stress are differentially associated with breast cancer incidence and breast cancer relapse in prospective studies. Systematic and explicit methods were used to identify, select......, and critically appraise relevant studies. The substantial variability in the manner in which stress was conceptualized and measured did not allow for the calculation of a quantitative summary estimate for the association between stress and breast cancer. Despite the heterogeneity in the results obtained...

  20. End-of-life hospital care for cancer patients: an update.

    Science.gov (United States)

    Dudevich, Alexey; Chen, Allie; Gula, Cheryl; Fagbemi, Josh

    2014-01-01

    Cancer is the leading cause of death in Canada, and the number of new cases is expected to increase as the population ages and grows. This study examined the use of hospital services in the last month of life by adult cancer patients who died in Canadian acute care hospitals in fiscal year 2012-2013. Almost 25,000 Canadian cancer patients - excluding those in Quebec - died in acute care hospitals, representing approximately 45% of the estimated cancer deaths in 2012-2013. The proportion of in-hospital deaths varied across jurisdictions. Twenty-three percent of these patients were admitted to acute care multiple times in their last 28 days of life, with a higher percentage for rural (29%) compared to urban (21%) patients. Relatively few patients used intensive care units or received inpatient chemotherapy in their last 14 days of life.

  1. U.S. Department of Energy's regional carbon sequestration partnership initiative: Update on validation and development phases

    Science.gov (United States)

    Rodosta, T.; Litynski, J.; Plasynski, S.; Spangler, L.; Finley, R.; Steadman, E.; Ball, D.; Gerald, H.; McPherson, B.; Burton, E.; Vikara, D.

    2011-01-01

    The U.S. Department of Energy (DOE) is the lead federal agency for the development and deployment of carbon sequestration technologies. The Regional Carbon Sequestration Partnerships (RCSPs) are the mechanism DOE utilizes to prove the technology and to develop human capital, stakeholder networks, information for regulatory policy, best practices documents and training to work toward the commercialization of carbon capture and storage (CCS). The RCSPs are tasked with determining the most suitable technologies, regulations, and infrastructure for carbon capture, transport, and storage in their respective geographic areas of responsibility. The seven partnerships include more than 400 state agencies, universities, national laboratories, private companies, and environmental organizations, spanning 43 states and four Canadian provinces. The Regional Partnerships Initiative is being implemented in three phases: Characterization, Validation, and Development. The initial Characterization Phase began in 2003 and was completed in 2005 and focused on characterization of CO2 storage potential within each region. It was followed by the Validation Phase, which began in 2005 and is nearing completion in 2011. The focus of the Validation Phase has been on small-scale field tests throughout the seven partnerships in various formation types such as saline, oil-bearing, and coal seams. The Validation Phase has characterized suitable CO2 storage reservoirs and identified the need for comprehensive legal and regulatory frameworks to enable commercial-scale CCS deployment. Finally, the Development Phase will consist of a series of large-scale, one-million-ton, injection tests throughout the United States and Canada. The objective of these large-scale tests is to identify the regulatory path or challenges in permitting CCS projects, to demonstrate the technology can inject CO2 safely, and to verify its permanence in geologic formations in preparation for the commercialization of geologic

  2. The effect of neuraxial anesthesia on cancer recurrence and survival after cancer surgery: an updated meta-analysis

    Science.gov (United States)

    Weng, Meilin; Chen, Wankun; Hou, Wenting; Li, Lihong; Ding, Ming; Miao, Changhong

    2016-01-01

    Several animal and observational studies have evaluated the effects of neuraxial anesthesia on the recurrence and survival of cancer surgery; studies reported benefit, whereas others did not. To provide further evidence that neuraxial anesthesia(combined with or without general anesthesia (GA))may be associated with reduced cancer recurrence and long-term survival after cancer surgery, we conducted this meta-analysis. A total of 21 studies were identified and analyzed, based on searches conducted using PubMed, Web of Science, EMBASE database and the Cochrane Database of Systematic Reviews. After data abstraction, adjusted hazard ratios (HR) with 95% confidence intervals (CIs) were used to assess the impact of neuraxial anesthesia (combined with or without GA) and GA on oncological outcomes after cancer surgery. For overall survival (OS), a potential association between neuraxial anesthesia and improved OS (HR 0.853, CI 0.741-0.981, P = 0.026, the random-effects model) was observed compared with GA. Specifically, we found a positive association between neuraxial anesthesia and improved OS in colorectal cancer (HR 0.653, CI 0.430-0.991, P = 0.045, the random-effects model). For recurrence-free survival (RFS), a significant association between neuraxial anesthesia and improved RFS (HR 0.846, CI 0.718-0.998, P = 0.047, the random-effects model) was detected compared with GA. Our meta-analysis suggests that neuraxial anesthesia may be associated with improved OS in patients with cancer surgery, especially for those patients with colorectal cancer. It also supports a potential association between neuraxial anesthesia and a reduced risk of cancer recurrence. More prospective studies are needed to elucidate whether the association between neuraxial use and survival is causative. PMID:26918830

  3. The Distress Thermometer and its validity: a first psychometric study in Indonesian women with breast cancer.

    Directory of Open Access Journals (Sweden)

    Aulia Iskandarsyah

    Full Text Available PURPOSE: This study aims to translate the Distress Thermometer (DT into Indonesian, test its validity in Indonesian women with breast cancer and determine norm scores of the Indonesian DT for clinically relevant distress. METHODS: First, the original version of the DT was translated using a forward and backward translation procedure according to the guidelines. Next, a group of 120 breast cancer patients who were treated at the Outpatient Surgical Oncology Clinic in Hasan Sadikin Hospital in Indonesia completed a standard socio-demographic form, the DT and the Problem List, the Hospital Anxiety and Depression Scale (HADS and the WHO Quality of Life (WHOQOL-BREF. RESULTS: Receiver operating characteristic (ROC curve analyses identified an area under the curve = 0.81 when compared to the HADS cutoff score of 15. A cutoff score of 5 on the DT had the best sensitivity (0.81 and specificity (0.64. Patients who scored above this cutoff reported more problems in the practical, family, emotional, spiritual/religious and physical domains (30 out of 36 problems, p-value<0.05 than patients below the cutoff score. Patients at advanced stages of cancer experienced more emotional and physical problems. Patient's distress level was negatively correlated with overall quality of life, general health and all quality of life domains. CONCLUSIONS: The DT was found to be a valid tool for screening distress in Indonesian breast cancer patients. We recommend using a cutoff score of 5 in this population.

  4. Validating a Prognostic Scoring System for Postmastectomy Locoregional Recurrence in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Skye Hung-Chun, E-mail: skye@kfsyscc.org [Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Clinical Research Office, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Tsai, Stella Y. [Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Yu, Ben-Long [Department of Surgery, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Horng, Cheng-Fang [Clinical Research Office, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Chen, Chii-Ming [Department of Surgery, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Jian, James J. [Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Chu, Nan-Min [Department of Medical Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Tsou, Mei-Hua [Department of Pathology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Liu, Mei-Ching [Department of Medical Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Huang, Andrew T. [Department of Medical Oncology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan (China); Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Prosnitz, Leonard R. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2013-03-15

    Purpose: This study is designed to validate a previously developed locoregional recurrence risk (LRR) scoring system and further define which groups of patients with breast cancer would benefit from postmastectomy radiation therapy (PMRT). Methods and Materials: An LRR risk scoring system was developed previously at our institution using breast cancer patients initially treated with modified radical mastectomy between 1990 and 2001. The LRR score comprised 4 factors: patient age, lymphovascular invasion, estrogen receptor negativity, and number of involved lymph nodes. We sought to validate the original study by examining a new dataset of 1545 patients treated between 2002 and 2007. Results: The 1545 patients were scored according to the previously developed criteria: 920 (59.6%) were low risk (score 0-1), 493 (31.9%) intermediate risk (score 2-3), and 132 (8.5%) were high risk (score ≥4). The 5-year locoregional control rates with and without PMRT in low-risk, intermediate-risk, and high-risk groups were 98% versus 97% (P=.41), 97% versus 91% (P=.0005), and 89% versus 50% (P=.0002) respectively. Conclusions: This analysis of an additional 1545 patients treated between 2002 and 2007 validates our previously reported LRR scoring system and suggests appropriate patients for whom PMRT will be beneficial. Independent validation of this scoring system by other institutions is recommended.

  5. Standards and options: recommendations for the use of erythropoiesis-stimulating agents (ESA) in anemic cancer patients undergoing radiotherapy (2007 update); Standards, options: recommandations 2007. Indication des agents stimulants l'erythropoiese (ASE) dans la prise en charge de l'anemie induite par la radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Marchal, Ch. [Centre Alexis-Vautrin, 54 - Vandoeuvre-les-Nancy (France); Misset, J.L. [Hopital Saint-Louis, 75 - Paris (France); Casadevall, N. [Hopital Saint Antoine, 75 - Paris (France); Marec-Berard, P.; Ray-Coquard, I. [Centre de Lutte Contre le Cancer Leon-Berard, 69 - Lyon (France); Chastagner, P. [Hopital d' Enfants Nancy, 54 (France); Kassab-Chahmi, D. [Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC), 75 - Paris (France)

    2008-03-15

    Introduction. - Beginning 1998, a working group of specialists convened by the guidelines department (Standards, Options and Recommendations: S.O.R.) of the National French Federation of Comprehensive Cancer Centres (F.N.C.L.C.C.) published then regularly updated Recommendations relative to the use of ESA (epoetin alfa, epoetin beta, darbepoetin) in anemic patients with cancer. This article presents the updated Recommendations set up in 2007. Methods. - This updating process is based on the methodology developed and used in the 'Standards, Options: Recommendations' programme. The methodological approach combines systematic review with the judgement of a multidisciplinary group of experts. On the basis of analysis of literature, the conclusions and their level of evidence are established. Then, the conclusions accompanied by experts judgement lead to the Recommendations. A Recommendation is a proposal of one or several clinical attitudes intended to improve cancer patient care. Before publication, the R.P.C.-S.O.R. are re-examined by independent reviewers selected according to the same principles as the group of expert writers. Results. - New data, relative to the 'use of ESA in anemic cancer patients undergoing radiotherapy', did not lead to update the latest Recommendations validated in 2003. However, new data relative to the 'use of ESA in anaemia prophylaxis among adult patients with cancer' and to the 'use of iron with ESA in cancer patients' were sufficient to generate either major or minor modifications to the initial Recommendations. Conclusions. - Thus, it appears relevant to re-examine these Recommendations according to a systematic monitoring process which should be renewed in two years. (authors)

  6. Myeloperoxidase polymorphism, menopausal status, and breast cancer risk: an update meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xue Qin

    Full Text Available Myeloperoxidase (MPO is a metabolic/oxidative lysosomal enzyme secreted by reactive neutrophils at the sites of inflamed organs and tissues during phagocytosis. MPO has been either directly or indirectly linked to neoplasia, which is a well-established risk factor for many types of cancer. A large number of studies have reported the role of MPO G-463A polymorphism regarding breast-cancer risk. However, the published findings are inconsistent. Therefore, we conducted a meta-analysis to determine more precise estimations for the relationship. Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. According to the inclusion criteria and exclusion criteria, a total of five eligible studies were included in the pooled analyses. When the five eligible studies concerning MPO G-463A polymorphism were pooled into this meta-analysis, there was no evidence found for a significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. We also categorized by ethnicity (Caucasian or Asian for subgroup analysis; according to this subgroup analysis, we found no significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. However, in the stratified analysis for the premenopausal group, women carrying the AA genotype were found to have a significantly reduced risk (OR = 0.56, 95% CI 0.34-0.94, p = 0.027. Under the recessive model, there was a significant association between MPO G-463A polymorphism and breast-cancer risk (OR = 0.57, 95% CI 0.34-0.93, p = 0.025. We conclude that MPO-G463A polymorphism might not be a good predictor of breast-cancer risk, though menopausal status modified women's risk of developing breast cancer.

  7. Fruit and vegetable consumption and lung cancer risk: updated information from the European Prospective Investigation into Cancer and Nutrition (EPIC).

    Science.gov (United States)

    Linseisen, Jakob; Rohrmann, Sabine; Miller, Anthony B; Bueno-de-Mesquita, H Bas; Büchner, Frederike L; Vineis, Paolo; Agudo, Antonio; Gram, Inger T; Janson, Lars; Krogh, Vittorio; Overvad, Kim; Rasmuson, Torgny; Schulz, Mandy; Pischon, Tobias; Kaaks, Rudolf; Nieters, Alexandra; Allen, Naomi E; Key, Timothy J; Bingham, Sheila; Khaw, Kay-Tee; Amiano, Pilar; Barricarte, Aurelio; Martinez, Carmen; Navarro, Carmen; Quirós, Ramón; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Touvier, Mathilde; Peeters, Petra H M; Berglund, Göran; Hallmans, Göran; Lund, Eiliv; Palli, Domenico; Panico, Salvatore; Tumino, Rosario; Tjønneland, Anne; Olsen, Anja; Trichopoulou, Antonia; Trichopoulos, Dimitrios; Autier, Philippe; Boffetta, Paolo; Slimani, Nadia; Riboli, Elio

    2007-09-01

    The association of fruit and vegetable consumption and lung cancer incidence was evaluated using the most recent data from the European Prospective Investigation into Cancer and Nutrition (EPIC), applying a refined statistical approach (calibration) to account for measurement error potentially introduced by using food frequency questionnaire data. Between 1992 and 2000, detailed information on diet and life-style of 478,590 individuals participating in EPIC was collected. During a median follow-up of 6.4 years, 1,126 lung cancer cases were observed. Multivariate Cox proportional hazard models were applied for statistical evaluation. In the whole study population, fruit consumption was significantly inversely associated with lung cancer risk while no association was found for vegetable consumption. In current smokers, however, lung cancer risk significantly decreased with higher vegetable consumption; this association became more pronounced after calibration, the hazard ratio (HR) being 0.78 (95% CI 0.62-0.98) per 100 g increase in daily vegetable consumption. In comparison, the HR per 100 g fruit was 0.92 (0.85-0.99) in the entire cohort and 0.90 (0.81-0.99) in smokers. Exclusion of cases diagnosed during the first 2 years of follow-up strengthened these associations, the HR being 0.71 (0.55-0.94) for vegetables (smokers) and 0.86 (0.78-0.95) for fruit (entire cohort). Cancer incidence decreased with higher consumption of apples and pears (entire cohort) as well as root vegetables (smokers). In addition to an overall inverse association with fruit intake, the results of this evaluation add evidence for a significant inverse association of vegetable consumption and lung cancer incidence in smokers.

  8. Epidemiologic evidence of cancer risk in textile industry workers: a review and update.

    Science.gov (United States)

    Mastrangelo, Giuseppe; Fedeli, Ugo; Fadda, Emanuela; Milan, Giovanni; Lange, John H

    2002-05-01

    A meta-analysis of epidemiologic studies for textile industry workers was undertaken in an attempt to evaluate whether the cancer risk varies within the textile industry in relation to the job held or the textile fiber used. We combined studies published up until 1990, when an ad hoc IARC Monograph was issued, and those published after 1990 with the aim of appreciating evidence of reversing trends in cancer risk. Observed and expected cases reported in the original studies were summed up and the totals were divided to obtain a pooled relative risk (PRR) with a 95% confidence interval (CI) estimated with a fixed-effect model. We calculated a chi-square test (chi2) of heterogeneity among studies. When PRR and chi2 were both significant, PRR and CI were calculated with a random-effect model and the source of heterogeneity was investigated. Lung cancer risk was around 0.4 in the first study on cotton workers published in 1936, around 0.7 in subsequent studies, mostly published in the 1970s and 1980s, and around 1.0 in the last studies published in the 1990s. Papers published in the 1970s and 1980s produced consistent risk estimates for lung cancer risk, which was significantly lower than 1.0 in workers exposed to cotton (PRR = 0.77; CI = 0.69-0.86) and wool dust (0.71; 0.50-0.92), as well as in carders and fiber preparers (0.73; 0.54-0.91), weavers (0.71; 0.56-0.85), and spinners and weavers (0.78; 0.66-0.91). Lung cancer PRRs did not significantly deviate from 1.0 in textile workers using synthetic fibers or silk, and in dyers. Increased PRRs were found for sinonasal cancer in workers exposed to cotton dust, and in workers involved in spinning or weaving (4.14; 1.80-6.49). PRR was 1.46 (1.10-1.82) for cancer of the digestive system in textile workers using synthetic fibers or silk, and 1.34 (1.10-1.59) for colorectal cancer in spinners and weavers. The increased bladder cancer PRR in dyers (1.39; 1.07-1.71) is generally attributed to textile dye exposure. In studies

  9. Skin cancer in skin of color: an update on current facts, trends, and misconceptions.

    Science.gov (United States)

    Battie, Claire; Gohara, Mona; Verschoore, Michèle; Roberts, Wendy

    2013-02-01

    For many fair-skinned individuals around the world, skin cancer is the leading malignancy. Although skin cancer comprises only 1% to 2% of all malignancies in those with darker complexions, the mortality rates in this subgroup are substantially higher when compared with their Caucasian counterparts. This discrepancy is largely as a result of delayed detection/treatment, and a false perception among patient and physician that brown skin confers complete protection against skin cancer. Recent studies show that 65% of surveyed African Americans never wore sunscreen, despite living in sunny climates, and that more than 60% of minority respondents erroneously believed that they were not at risk for skin cancer. Dark skin offers some protection from ultraviolet (UV) light. However, there is considerable heterogeneity in skin of color, a phenomenon that is accentuated by mixed heritage. Ethnicity does not confer skin type anymore. People of color do experience sunburn, and from a biological point of view, all skin types appear to be sensitive to UV-induced DNA damage, with an inverse relationship between skin color and sensitivity to UV light. Our population is changing rapidly, and within the next few decades minority populations will become the majority. It is therefore imperative to educate both physicians and patients on the perceived immunity against cutaneous malignancies, the need for sun protection, and the clinical signs of skin cancer in non-Caucasian people, so that future unnecessary mortality can be avoided.

  10. Immunotherapy and therapeutic vaccines in prostate cancer:an update on current strategies and clinical implications

    Institute of Scientific and Technical Information of China (English)

    B Harpreet Singh; James L Gulley

    2014-01-01

    In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical beneift.

  11. Immunotherapy and therapeutic vaccines in prostate cancer: an update on current strategies and clinical implications

    Directory of Open Access Journals (Sweden)

    B Harpreet Singh

    2014-06-01

    Full Text Available In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit.

  12. Meta-analysis of black tea consumption and breast cancer risk: update 2013.

    Science.gov (United States)

    Nie, Xiao-Cui; Dong, Dao-Song; Bai, Yang; Xia, Pu

    2014-01-01

    Black tea is a commonly consumed beverage in the world, comprising approximately 80% of all tea consumed. We sought to examine the association between black tea consumption and risk of breast cancer, using all available epidemiologic evidence to date. PubMed, EMBASE, ISI Web of Science, Chinese National Knowledge Infrastructure Database, and China Biological Medicine Database were used to search for citations using the MeSH terms as "breast neoplasm" AND "black tea." Then we performed a meta-analysis of studies of breast cancer risk published between 1985 and 2013 by using RevMan 5.0 software. The results showed that no association between black tea consumption and breast cancer risk in overall [odds ratio (OR) = 0.97; 95% confidence interval (CI) = 0.89-1.05]. We further performed a stratified analysis according to region (United States/Europe). Black tea consumption did not decrease breast cancer risk in the United States (OR = 0.91; 95% CI = 0.78-1.07) and in Europe (OR = 0.99; 95% CI = 0.93-1.06). In addition, the summary OR from all cohort studies (OR = 1.04, 95% CI = 0.91-1.18) or all case-control studies (OR = 0.95, 95% CI = 0.88-1.02) showed black tea intake has no effects on breast cancer risk. However, the association between black tea consumption and breast cancer incidence remains unclear based on the current evidence. Further well-designed large studies are needed to confirm our result.

  13. Using method triangulation to validate a new instrument (CPWQ-com) assessing cancer patients' satisfaction with communication

    DEFF Research Database (Denmark)

    Ross, Lone; Lundstrøm, Louise Hyldborg; Petersen, Morten Aagaard

    2012-01-01

    Patients' perceptions of care including the communication with health care staff is recognized as an important aspect of the quality of cancer care. Using mixed methods, we developed and validated a short instrument assessing this communication.......Patients' perceptions of care including the communication with health care staff is recognized as an important aspect of the quality of cancer care. Using mixed methods, we developed and validated a short instrument assessing this communication....

  14. Sentinel lymph node biopsy in bladder cancer: Systematic review and technology update

    OpenAIRE

    Liss, Michael A.; Noguchi, Jonathan; Lee, Hak J.; Vera, David R.; Kader, A. Karim

    2015-01-01

    A sentinel lymph node (SLN) is the first lymph node to drain a solid tumor and likely the first place metastasis will travel. SLN biopsy has been well established as a staging tool for melanoma and breast cancer to guide lymph node dissection (LND); its utility in bladder cancer is debated. We performed a systematic search of PubMed for both human and animal studies that looked at SLN detection in cases of urothelial carcinoma of the bladder. We identified a total of nine studies that assesse...

  15. Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Sudhanshu Shukla

    2016-08-01

    Full Text Available Rapid advances in the discovery of long noncoding RNAs (lncRNAs have identified lineage- and cancer-specific biomarkers that may be relevant in the clinical management of prostate cancer (PCa. Here we assembled and analyzed a large RNA-seq dataset, from 585 patient samples, including benign prostate tissue and both localized and metastatic PCa to discover and validate differentially expressed genes associated with disease aggressiveness. We performed Sample Set Enrichment Analysis (SSEA and identified genes associated with low versus high Gleason score in the RNA-seq database. Comparing Gleason 6 versus 9+ PCa samples, we identified 99 differentially expressed genes with variable association to Gleason grade as well as robust expression in prostate cancer. The top-ranked novel lncRNA PCAT14, exhibits both cancer and lineage specificity. On multivariate analysis, low PCAT14 expression independently predicts for BPFS (P = .00126, PSS (P = .0385, and MFS (P = .000609, with trends for OS as well (P = .056. An RNA in-situ hybridization (ISH assay for PCAT14 distinguished benign vs malignant cases, as well as high vs low Gleason disease. PCAT14 is transcriptionally regulated by AR, and endogenous PCAT14 overexpression suppresses cell invasion. Thus, Using RNA-sequencing data we identify PCAT14, a novel prostate cancer and lineage-specific lncRNA. PCAT14 is highly expressed in low grade disease and loss of PCAT14 predicts for disease aggressiveness and recurrence.

  16. Validation of the state version questionnaire on autonomic regulation (state-aR for cancer patients

    Directory of Open Access Journals (Sweden)

    Kröz M

    2011-10-01

    Full Text Available Abstract Objectives Current quality of life inventories used in oncology mainly measure the effects of chemo- or radiotherapy alongside functional and role scales. A new approach is to measure the autonomic state of regulation with the trait-inventory of autonomic regulation (Trait-aR. Loss of Trait-aR has been shown in different medical conditions such as breast cancer (BC but not in colorectal cancer patients (CRC. In this paper we report the validation of a new state autonomic regulation scale (State-aR of the last week. Methods Study 1 included 114 participants: (41 women/16 men with cancer and 57 age- and gender-matched healthy people to conduct a reliability-, factor- and validity-analysis. Concurrent and convergent validity was evaluated with Trait-aR, Fatigue-Numeri-cal-Scale, Hospital Anxiety and Depression Scale (HADS-D and the self-regulation scale, 65 participants were retested. Study 2 completed 42 participants: 17 with BC and 25 with CRC receiving chemotherapy. The State-aR was administered prior, during and after chemotherapy for measuring responsiveness. Results The factor analysis loaded to four subscales of State-aR (rest-activity, orthostatic-circulatory, thermosweating and digestive regulation with a: Cronbach-α rα = 0.77-0.83 and a test-retest-reliability rrt = 0.60-0.80. The sum- and sub scales correlated with their concurrent subscales in the Trait-aR (0.48-0.74 and with the sum-scale moderately with all convergent criteria (r = 0.41 --0.44; p Conclusions These findings support that the state autonomic regulation scale has satisfactory to good reliability, good validity and acceptable responsiveness in the context of chemotherapy treatment.

  17. Hereditary diffuse gastric cancer : updated clinical guidelines with an emphasis on germline CDH1 mutation carriers

    NARCIS (Netherlands)

    van der Post, Rachel S.; Vogelaar, Ingrid P.; Carneiro, Fatima; Guilford, Parry; Huntsman, David; Hoogerbrugge, Nicoline; Caldas, Carlos; Schreiber, Karen E. Chelcun; Hardwick, Richard H.; Ausems, Margreet G. E. M.; Bardram, Linda; Benusiglio, Patrick R.; Bisseling, Tanya M.; Blair, Vanessa; Bleiker, Eveline; Boussioutas, Alex; Cats, Annemieke; Coit, Daniel; DeGregorio, Lynn; Figueiredo, Joana; Ford, James M.; Heijkoop, Esther; Hermens, Rosella; Humar, Bostjan; Kaurah, Pardeep; Keller, Gisella; Lai, Jennifer; Ligtenberg, Marjolijn J. L.; O'Donovan, Maria; Oliveira, Carla; Pinheiro, Hugo; Ragunath, Krish; Rasenberg, Esther; Richardson, Susan; Roviello, Franco; Schackert, Hans; Seruca, Raquel; Taylor, Amy; ter Huurne, Anouk; Tischkowitz, Marc; Joe, Sheena Tjon A.; van Dijck, Benjamin; van Grieken, Nicole C. T.; van Hillegersberg, Richard; van Sandick, Johanna W.; Vehof, Rianne; van Krieken, J. Han; Fitzgerald, Rebecca C.

    2015-01-01

    Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, inc

  18. Benefit risk assessment and update on the use of docetaxel in the management of breast cancer

    Directory of Open Access Journals (Sweden)

    Alken S

    2013-10-01

    Full Text Available Scheryll Alken, Catherine M KellyDepartment of Medical Oncology, Mater Misericordiae University Hospital, Dublin, IrelandAbstract: The objective of this paper is to review the data supporting the use of docetaxel in the treatment of breast cancer, focusing on pharmacokinetics, efficacy in adjuvant and metastatic trials alone and in combination with chemotherapeutic and targeted agents, and the toxicity of docetaxel in comparison to paclitaxel. Docetaxel is a semisynthetic product derived from the European yew tree Taxus baccata L. It promotes the assembly of microtubules, stabilizes them, and thereby prevents their depolymerization. Docetaxel has been incorporated into neo-adjuvant chemotherapy regimens, both with and without anthracyclines. The inclusion of taxanes such as docetaxel in polychemotherapy regimens in early breast cancer is associated with a statistically significant reduction in mortality. As a single agent, docetaxel is highly active in the treatment of metastatic breast cancer. In first-line treatment of metastatic breast cancer, the combination of docetaxel and capecitabine was associated with an improvement in overall survival; however, toxicity was higher. The toxicity profile of docetaxel has been well documented and is predictable; the most frequent adverse effects are neutropenia and febrile neutropenia. Taxane-specific adverse effects, such as peripheral neuropathy, are also expected but are manageable with appropriate dosing and scheduling.Keywords: taxanes, docetaxel, clinical trial, adverse effects, peripheral neuropathy, neutropenia

  19. Coffee Consumption and Risk of Gastric Cancer: A Large Updated Meta-Analysis of Prospective Studies

    Directory of Open Access Journals (Sweden)

    Feiyue Xie

    2014-09-01

    Full Text Available The potential role of coffee consumption in the development of various types of cancer has been extensively investigated in epidemiologic studies. How coffee consumption may modulate risk of gastric cancer, however, remains a subject open for investigation. To better quantify this relation, we quantitatively summarized evidence from prospective studies. Eligible studies were identified on PubMed and Embase databases. The summary risk estimates were obtained using the random-effects model. Subgroup, sensitivity and dose-response analyses were conducted. The present meta-analysis included 12 prospective cohort studies. A pooled analysis of these studies suggested that coffee consumption (highest vs. lowest consumption was not associated with risk of gastric cancer (RR = 1.12, 95% CI = 0.93–1.36. In the subgroup analysis, significant increased risk was detected in the U.S. studies (RR = 1.36, 95% CI = 1.06–1.74 and in the studies with <10 years of follow-up (RR = 1.24, 95% CI = 1.00–1.54, and the greatest increase in risk was observed in those studies without adjustment for smoking (RR = 1.48, 95% CI = 1.13–1.93. There was some evidence of publication bias (P for Egger’s test = 0.03. Cumulative evidence from prospective studies suggests that coffee consumption is not associated with risk of gastric cancer. The observed positive results may be confounded by smoking and need further investigation.

  20. Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers

    NARCIS (Netherlands)

    Post, R.S. van der; Vogelaar, I.P.; Carneiro, F.; Guilford, P.; Huntsman, D.; Hoogerbrugge, N.; Caldas, C.; Schreiber, K.E.; Hardwick, R.H.; Ausems, M.G.; Bardram, L.; Benusiglio, P.R.; Bisseling, T.M.; Blair, V.; Bleiker, E.; Boussioutas, A.; Cats, A.; Coit, D.; DeGregorio, L.; Figueiredo, J.; Ford, J.M.; Heijkoop, E.; Hermens, R.; Humar, B.; Kaurah, P.; Keller, G.; Lai, J.; Ligtenberg, M.J.; O'Donovan, M.; Oliveira, C.; Pinheiro, H.; Ragunath, K.; Rasenberg, E.; Richardson, S.; Roviello, F.; Schackert, H.; Seruca, R.; Taylor, A.; Huurne, A. Ter; Tischkowitz, M.; Joe, S.T.; Dijck, B. van; Grieken, N.C. van; Hillegersberg, R. van; Sandick, J.W. van; Vehof, R.; Krieken, J.H.J.M. van; Fitzgerald, R.C.

    2015-01-01

    Germline CDH1 mutations confer a high lifetime risk of developing diffuse gastric (DGC) and lobular breast cancer (LBC). A multidisciplinary workshop was organised to discuss genetic testing, surgery, surveillance strategies, pathology reporting and the patient's perspective on multiple aspects, inc

  1. TIMP-1 as a tumor marker in breast cancer - an update

    DEFF Research Database (Denmark)

    Würtz, Sidse Ørnbjerg; Rasmussen, Anne-Sofie Schrohl; Mouridsen, Henning;

    2008-01-01

    Improvement of the management of breast cancer patients has high priority. In this regard, prognostic stratification needs to be improved in order to ensure proper medical treatment of all patients and furthermore predictors of response to chemotherapy are urgently needed. As new treatment opport...

  2. Risser patient satisfaction scale: a validation study in Greek cancer patients

    Directory of Open Access Journals (Sweden)

    Charalambous Andreas

    2012-11-01

    Full Text Available Abstract Background The current healthcare climate is characterized by a constant battle for the provision of quality care with limited resources and with patient satisfaction receiving increased attention, there is a need for reliable and valid assessment measures. This study describes the adaptation, testing and validation of the Risser Patient satisfaction Scale in an oncology care setting in Greece. The rationale for this study lies in the scarcity of such measures in the Greek language. Methods This is a test retest validation study in Greece. Data were collected from 298 hospitalized cancer patients. The validation methodology included the assessment of the item internal consistency, using the Cronbach alpha coefficient. The test-retest reliability was tested by the Kappa correlation coefficient. Results The scale demonstrated very good psychometric properties. The internal consistency of the instrument was good, Cronbach’s alpha was found to be 0.78 (p Conclusion The findings demonstrated strong agreement of the scale, suggesting that the Greek version offers substantial reliability. This study provides a valid and reliable tool to assess patient satisfaction in oncology settings. Means to monitor patient satisfaction, a key aspect of the policy agenda for quality care remain important for nurse leaders to develop better care in oncology settings.

  3. UPDATE February 2012 - The Food Crises: Predictive validation of a quantitative model of food prices including speculators and ethanol conversion

    CERN Document Server

    Lagi, Marco; Bertrand, Karla Z; Bar-Yam, Yaneer

    2012-01-01

    Increases in global food prices have led to widespread hunger and social unrest---and an imperative to understand their causes. In a previous paper published in September 2011, we constructed for the first time a dynamic model that quantitatively agreed with food prices. Specifically, the model fit the FAO Food Price Index time series from January 2004 to March 2011, inclusive. The results showed that the dominant causes of price increases during this period were investor speculation and ethanol conversion. The model included investor trend following as well as shifting between commodities, equities and bonds to take advantage of increased expected returns. Here, we extend the food prices model to January 2012, without modifying the model but simply continuing its dynamics. The agreement is still precise, validating both the descriptive and predictive abilities of the analysis. Policy actions are needed to avoid a third speculative bubble that would cause prices to rise above recent peaks by the end of 2012.

  4. Psychometric validation of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24)

    DEFF Research Database (Denmark)

    Greimel, Elfriede; Nordin, Andy; Lanceley, Anne;

    2011-01-01

    A validation study was conducted to evaluate the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24). This module was designed to assess disease and treatment specific aspects...

  5. Validation of the French translation-adaptation of the impact of cancer questionnaire version 2 (IOCv2) in a breast cancer survivor population

    NARCIS (Netherlands)

    Blanchin, M.; Dauchy, S.; Cano, A.; Brédart, A.; Aaronson, N.K.; Hardouin, J.B.

    2015-01-01

    Background: The Impact of Cancer version 2 (IOCv2) was designed to assess the physical and psychosocial health experience of cancer survivors through its positive and negative impacts. Although the IOCv2 is available in English and Dutch, it has not yet been validated for use in French-speaking popu

  6. Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation.

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    Kazufumi Honda

    Full Text Available BACKGROUND: Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection. METHODS: We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1 using a newly developed matrix-assisted laser desorption/ionization (oMALDI QqTOF (quadrupole time-of-flight mass spectrometry (MS system. RESULTS: We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z, unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z, and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10(-21, P = 4.35×10(-14, and P = 1.83×10(-24 (Mann-Whitney U-test; area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103 and Cohort 3 (n = 163] and a prospective cohort [Cohort 4 (n = 833] collected from 8 medical institutions in Japan and Germany. CONCLUSIONS: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.

  7. Assessment of validation of health-economics decision models in intervention studies of seasonal influenza and breast cancer

    NARCIS (Netherlands)

    De Boer, P.T.; Frederix, G.W.; Al, M.J.; Feenstra, T.F.; Vemer, P.

    2015-01-01

    Objectives: We aimed to review recently published health-economic (HE) decision models to assess the reporting of validation efforts. An infectious disease (seasonal influenza, SI) and a chronic disease (breast cancer, BC) were used as examples, giving a preliminary insight in the reporting of valid

  8. Metal complexes in cancer therapy – an update from drug design perspective

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    Ndagi U

    2017-03-01

    Full Text Available Umar Ndagi, Ndumiso Mhlongo, Mahmoud E Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, South Africa Abstract: In the past, metal-based compounds were widely used in the treatment of disease conditions, but the lack of clear distinction between the therapeutic and toxic doses was a major challenge. With the discovery of cisplatin by Barnett Rosenberg in 1960, a milestone in the history of metal-based compounds used in the treatment of cancers was witnessed. This forms the foundation for the modern era of the metal-based anticancer drugs. Platinum drugs, such as cisplatin, carboplatin and oxaliplatin, are the mainstay of the metal-based compounds in the treatment of cancer, but the delay in the therapeutic accomplishment of other metal-based compounds hampered the progress of research in this field. Recently, however, there has been an upsurge of activities relying on the structural information, aimed at improving and developing other forms of metal-based compounds and nonclassical platinum complexes whose mechanism of action is distinct from known drugs such as cisplatin. In line with this, many more metal-based compounds have been synthesized by redesigning the existing chemical structure through ligand substitution or building the entire new compound with enhanced safety and cytotoxic profile. However, because of increased emphasis on the clinical relevance of metal-based complexes, a few of these drugs are currently on clinical trial and many more are awaiting ethical approval to join the trial. In this review, we seek to give an overview of previous reviews on the cytotoxic effect of metal-based complexes while focusing more on newly designed metal-based complexes and their cytotoxic effect on the cancer cell lines, as well as on new approach to metal-based drug design and molecular target in cancer therapy. We are optimistic that the concept of selective

  9. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer

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    Moira Ragazzi

    2014-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

  10. Updates in advanced diffusion-weighted magnetic resonance imaging techniques in the evaluation of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Hebert; Alberto; Vargas; Edward; Malnor; Lawrence; Yousef; Mazaheri; Evis; Sala

    2015-01-01

    Diffusion-weighted magnetic resonance imaging(DWMRI) is considered part of the standard imaging protocol for the evaluation of patients with prostate cancer.It has been proven valuable as a functional tool for qualitative and quantitative analysis of prostate cancer beyond anatomical MRI sequences such as T2-weighted imaging. This review discusses ongoing controversies in DW-MRI acquisition, including the optimal number of b-values to be used for prostate DWI, and summarizes the current literature on the use of advanced DWMRI techniques. These include intravoxel incoherent motion imaging, which better accounts for the nonmono-exponential behavior of the apparent diffusion coefficient as a function of b-value and the influence of perfusion at low b-values. Another technique is diffusion kurtosis imaging(DKI). Metrics from DKI reflect excess kurtosis of tissues, representing its deviation from Gaussian diffusion behavior. Preliminary results suggest that DKI findings may have more value than findings from conventional DW-MRI for the assessment of prostate cancer.

  11. Ten years of "Optimal Therapy in Advanced Ovarian Cancer. Update" meeting.

    Science.gov (United States)

    Poveda, A

    2008-01-01

    The International Symposium on Advanced Ovarian Cancer: Optimal Therapy was founded by Dr. Andrés Poveda and Prof. Jan B. Vermorken, and each edition has been directed by them. The 6th edition was held on March 2, 2007. This symposium is organized every other year by GEICO (Grupo Español de Investigación de Cáncer de Ovario/Spanish Ovarian Cancer Research Group), under the auspices of the Spanish Society of Medical Oncology (SEOM), the Gynecologic Cancer Intergroup (GCIG), and the European Society of Medical Oncology (ESMO) Educational Committee for its Medical Oncology Recertification Approval (ESMO/MORA) Program. One hundred and fifty people attended the symposium's 1st edition, held in 1996. Since then, the interest in this meeting has increased. Last year, almost three hundred people coming not only from Spain but also from Europe, North and Latin America, Asia, and Australia were present in the symposium. This is a great challenge for us. Some important international cooperative groups from Europe, America, and Australia collaborate with this symposium, such as GOG, NCIC, EORTC, AGO, Scottish Group, ICON, GINECO, NSGO, ANZGOG, and others.

  12. External validation of a claims-based algorithm for classifying kidney-cancer surgeries

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    Deapen Dennis

    2009-06-01

    Full Text Available Abstract Background Unlike other malignancies, there is no literature supporting the accuracy of medical claims data for identifying surgical treatments among patients with kidney cancer. We sought to validate externally a previously published Medicare-claims-based algorithm for classifying surgical treatments among patients with early-stage kidney cancer. To achieve this aim, we compared procedure assignments based on Medicare claims with the type of surgery specified in SEER registry data and clinical operative reports. Methods Using linked SEER-Medicare data, we calculated the agreement between Medicare claims and SEER data for identification of cancer-directed surgery among 6,515 patients diagnosed with early-stage kidney cancer. Next, for a subset of 120 cases, we determined the agreement between the claims algorithm and the medical record. Finally, using the medical record as the reference-standard, we calculated the sensitivity, specificity, and positive and negative predictive values of the claims algorithm. Results Among 6,515 cases, Medicare claims and SEER data identified 5,483 (84.1% and 5,774 (88.6% patients, respectively, who underwent cancer-directed surgery (observed agreement = 93%, κ = 0.69, 95% CI 0.66 – 0.71. The two data sources demonstrated 97% agreement for classification of partial versus radical nephrectomy (κ = 0.83, 95% CI 0.81 – 0.86. We observed 97% agreement between the claims algorithm and clinical operative reports; the positive predictive value of the claims algorithm exceeded 90% for identification of both partial nephrectomy and laparoscopic surgery. Conclusion Medicare claims represent an accurate data source for ascertainment of population-based patterns of surgical care among patients with early-stage kidney cancer.

  13. Blinded Validation of Breath Biomarkers of Lung Cancer, a Potential Ancillary to Chest CT Screening.

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    Michael Phillips

    Full Text Available Breath volatile organic compounds (VOCs have been reported as biomarkers of lung cancer, but it is not known if biomarkers identified in one group can identify disease in a separate independent cohort. Also, it is not known if combining breath biomarkers with chest CT has the potential to improve the sensitivity and specificity of lung cancer screening.Model-building phase (unblinded: Breath VOCs were analyzed with gas chromatography mass spectrometry in 82 asymptomatic smokers having screening chest CT, 84 symptomatic high-risk subjects with a tissue diagnosis, 100 without a tissue diagnosis, and 35 healthy subjects. Multiple Monte Carlo simulations identified breath VOC mass ions with greater than random diagnostic accuracy for lung cancer, and these were combined in a multivariate predictive algorithm. Model-testing phase (blinded validation: We analyzed breath VOCs in an independent cohort of similar subjects (n = 70, 51, 75 and 19 respectively. The algorithm predicted discriminant function (DF values in blinded replicate breath VOC samples analyzed independently at two laboratories (A and B. Outcome modeling: We modeled the expected effects of combining breath biomarkers with chest CT on the sensitivity and specificity of lung cancer screening.Unblinded model-building phase. The algorithm identified lung cancer with sensitivity 74.0%, specificity 70.7% and C-statistic 0.78. Blinded model-testing phase: The algorithm identified lung cancer at Laboratory A with sensitivity 68.0%, specificity 68.4%, C-statistic 0.71; and at Laboratory B with sensitivity 70.1%, specificity 68.0%, C-statistic 0.70, with linear correlation between replicates (r = 0.88. In a projected outcome model, breath biomarkers increased the sensitivity, specificity, and positive and negative predictive values of chest CT for lung cancer when the tests were combined in series or parallel.Breath VOC mass ion biomarkers identified lung cancer in a separate independent cohort

  14. Validation of the Japanese version of the Pediatric Quality of Life Inventory (PedsQL Cancer Module

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    Kaneko Takashi

    2011-04-01

    Full Text Available Abstract Background The PedsQL 3.0 Cancer Module is a widely used instrument to measure pediatric cancer specific health-related quality of life (HRQOL for children aged 2 to 18 years. We developed the Japanese version of the PedsQL Cancer Module and investigated its reliability and validity among Japanese children and their parents. Methods Participants were 212 children with cancer and 253 of their parents. Reliability was determined by internal consistency using Cronbach's coefficient alpha and test-retest reliability using intra-class correlation coefficient (ICC. Validity was assessed through factor validity, convergent and discriminant validity, concurrent validity, and clinical validity. Factor validity was examined by exploratory factor analysis. Convergent and discriminant validity were examined by multitrait scaling analysis. Concurrent validity was assessed using Spearman's correlation coefficients between the Cancer Module and Generic Core Scales, and the comparison of the scores of child self-reports with those of other self-rating depression scales for children. Clinical validity was assessed by comparing the on- and off- treatment scores using Kruskal-Wallis and Mann-Whitney U tests. Results Cronbach's coefficient alpha was over 0.70 for the total scale and over 0.60 for each subscale by age except for the 'pain and hurt' subscale for children aged 5 to 7 years. For test-retest reliability, the ICC exceeded 0.70 for the total scale for each age. Exploratory factor analysis demonstrated sufficient factorial validity. Multitrait scaling analysis showed high success rates. Strong correlations were found between the reports by children and their parents, and the scores of the Cancer Module and the Generic Core Scales except for 'treatment anxiety' subscales for child reports. The Depression Self-Rating Scale for Children (DSRS-C scores were significantly correlated with emotional domains and the total score of the cancer module

  15. The Danish version of the Medication Adherence Report Scale: preliminary validation in cancer pain patients

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona Louring;

    2009-01-01

    OBJECTIVE: To examine the psychometric properties of the Danish version of the Medication Adherence Report Scale (DMARS-4) adapted to measure adherence to analgesic regimen among cancer patients. METHODS: The validated English version of the Medication Adherence Report Scale was translated...... into Danish following the repeated back-translation procedure. Cancer patients for the study were recruited from specialized pain management facilities. Thirty-three patients responded to the DMARS-4, the Danish Barriers Questionnaire II, The Danish version of Patient Perceived Involvement in Care Scale...... measuring the quality of patient-physician pain communication, and the Danish Brief Pain Inventory pain severity scale. RESULTS: A factor analysis of the DMARS-4 resulted in one factor. Mean (SD) score on the cumulative scale ranging from 4 to 20, with higher scores indicating better medication adherence...

  16. Discovery and validation of DNA hypomethylation biomarkers for liver cancer using HRM-specific probes.

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    Barbara Stefanska

    Full Text Available Poor prognosis of hepatocellular carcinoma (HCC associated with late diagnosis necessitates the development of early diagnostic biomarkers. We have previously delineated the landscape of DNA methylation in HCC patients unraveling the importance of promoter hypomethylation in activation of cancer- and metastasis-driving genes. The purpose of the present study was to test the feasibility that genes that are hypomethylated in HCC could serve as candidate diagnostic markers. We use high resolution melting analysis (HRM as a simple translatable PCR-based method to define methylation states in clinical samples. We tested seven regions selected from the shortlist of genes hypomethylated in HCC and showed that HRM analysis of several of them distinguishes methylation states in liver cancer specimens from normal adjacent liver and chronic hepatitis in the Shanghai area. Such regions were identified within promoters of neuronal membrane glycoprotein M6-B (GPM6B and melanoma antigen family A12 (MAGEA12 genes. Differences in HRM in the immunoglobulin superfamily Fc receptor (FCRL1 separated invasive tumors from less invasive HCC. The identified biomarkers differentiated HCC from chronic hepatitis in another set of samples from Dhaka. Although the main thrust in DNA methylation diagnostics in cancer is on hypermethylated genes, our study for the first time illustrates the potential use of hypomethylated genes as markers for solid tumors. After further validation in a larger cohort, the identified DNA hypomethylated regions can become important candidate biomarkers for liver cancer diagnosis and prognosis, especially in populations with high risk for HCC development.

  17. Biomarker Validation for Aging: Lessons from mtDNA Heteroplasmy Analyses in Early Cancer Detection

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    Peter E. Barker

    2009-11-01

    Full Text Available The anticipated biological and clinical utility of biomarkers has attracted significant interest recently. Aging and early cancer detection represent areas active in the search for predictive and prognostic biomarkers. While applications differ, overlapping biological features, analytical technologies and specific biomarker analytes bear comparison. Mitochondrial DNA (mtDNA as a biomarker in both biological models has been evaluated. However, it remains unclear whether mtDNA changes in aging and cancer represent biological relationships that are causal, incidental, or a combination of both. This article focuses on evaluation of mtDNA-based biomarkers, emerging strategies for quantitating mtDNA admixtures, and how current understanding of mtDNA in aging and cancer evolves with introduction of new technologies. Whether for cancer or aging, lessons from mtDNA based biomarker evaluations are several. Biological systems are inherently dynamic and heterogeneous. Detection limits for mtDNA sequencing technologies differ among methods for low-level DNA sequence admixtures in healthy and diseased states. Performance metrics of analytical mtDNA technology should be validated prior to application in heterogeneous biologically-based systems. Critical in evaluating biomarker performance is the ability to distinguish measurement system variance from inherent biological variance, because it is within the latter that background healthy variability as well as high-value, disease-specific information reside.

  18. Meaningful prevention of breast cancer metastasis: candidate therapeutics, preclinical validation, and clinical trial concerns.

    Science.gov (United States)

    Zimmer, Alexandra S; Steeg, Patricia S

    2015-01-01

    The development of drugs to treat breast and other cancers proceeds through phase I dose finding, phase II efficacy, and phase III comparative studies in the metastatic setting, only then asking if metastasis can be prevented in adjuvant trials. Compounds without overt cytotoxic activity, such as those developed to inhibit metastatic colonization, will likely fail to shrink established lesions in the metastatic setting and never be tested in a metastasis prevention scenario where they were preclinically validated. We and others have proposed phase II primary and secondary metastasis prevention studies to address this need. Herein, we have asked whether preclinical metastasis prevention data agrees with the positive adjuvant setting trials. The data are limited but complimentary. We also review fundamental pathways involved in metastasis, including Src, integrins, focal adhesion kinase (FAK), and fibrosis, for their clinical progress to date and potential for metastasis prevention. Issues of inadequate preclinical validation and clinical toxicity profiles are discussed.

  19. Editorial: risk scoring for colon cancer screening: validated, but still not ready for prime time.

    Science.gov (United States)

    Lin, Otto S

    2011-06-01

    Risk stratification for colorectal cancer screening would allow us to use less expensive screening tests, such as sigmoidoscopy with or without fecal blood testing, on lower risk individuals, and reserve colonoscopy for those at higher risk. In this issue, Levitzky et al. validates a risk score that was previously developed by Imperiale et al., finding similar results among three ethnic groups. Risk scoring would detect 82-87% of proximal advanced neoplasia while decreasing colonoscopy use by 33-46%. However, before risk scoring is ready for widespread use, sigmoidoscopy access and performance issues need to be addressed, and we must be comfortable with missing some proximal neoplasms.

  20. Validated Competing Event Model for the Stage I-II Endometrial Cancer Population

    Energy Technology Data Exchange (ETDEWEB)

    Carmona, Ruben; Gulaya, Sachin; Murphy, James D. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Rose, Brent S. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Wu, John; Noticewala, Sonal [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); McHale, Michael T. [Department of Reproductive Medicine, Division of Gynecologic Oncology, University of California San Diego, La Jolla, California (United States); Yashar, Catheryn M. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Vaida, Florin [Department of Family and Preventive Medicine, Biostatistics and Bioinformatics, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

    2014-07-15

    Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification.

  1. Integration and Validation of the Genome-Scale Metabolic Models of Pichia pastoris: A Comprehensive Update of Protein Glycosylation Pathways, Lipid and Energy Metabolism.

    Directory of Open Access Journals (Sweden)

    Màrius Tomàs-Gamisans

    Full Text Available Genome-scale metabolic models (GEMs are tools that allow predicting a phenotype from a genotype under certain environmental conditions. GEMs have been developed in the last ten years for a broad range of organisms, and are used for multiple purposes such as discovering new properties of metabolic networks, predicting new targets for metabolic engineering, as well as optimizing the cultivation conditions for biochemicals or recombinant protein production. Pichia pastoris is one of the most widely used organisms for heterologous protein expression. There are different GEMs for this methylotrophic yeast of which the most relevant and complete in the published literature are iPP668, PpaMBEL1254 and iLC915. However, these three models differ regarding certain pathways, terminology for metabolites and reactions and annotations. Moreover, GEMs for some species are typically built based on the reconstructed models of related model organisms. In these cases, some organism-specific pathways could be missing or misrepresented.In order to provide an updated and more comprehensive GEM for P. pastoris, we have reconstructed and validated a consensus model integrating and merging all three existing models. In this step a comprehensive review and integration of the metabolic pathways included in each one of these three versions was performed. In addition, the resulting iMT1026 model includes a new description of some metabolic processes. Particularly new information described in recently published literature is included, mainly related to fatty acid and sphingolipid metabolism, glycosylation and cell energetics. Finally the reconstructed model was tested and validated, by comparing the results of the simulations with available empirical physiological datasets results obtained from a wide range of experimental conditions, such as different carbon sources, distinct oxygen availability conditions, as well as producing of two different recombinant proteins. In

  2. SurvExpress: an online biomarker validation tool and database for cancer gene expression data using survival analysis.

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    Raul Aguirre-Gamboa

    Full Text Available Validation of multi-gene biomarkers for clinical outcomes is one of the most important issues for cancer prognosis. An important source of information for virtual validation is the high number of available cancer datasets. Nevertheless, assessing the prognostic performance of a gene expression signature along datasets is a difficult task for Biologists and Physicians and also time-consuming for Statisticians and Bioinformaticians. Therefore, to facilitate performance comparisons and validations of survival biomarkers for cancer outcomes, we developed SurvExpress, a cancer-wide gene expression database with clinical outcomes and a web-based tool that provides survival analysis and risk assessment of cancer datasets. The main input of SurvExpress is only the biomarker gene list. We generated a cancer database collecting more than 20,000 samples and 130 datasets with censored clinical information covering tumors over 20 tissues. We implemented a web interface to perform biomarker validation and comparisons in this database, where a multivariate survival analysis can be accomplished in about one minute. We show the utility and simplicity of SurvExpress in two biomarker applications for breast and lung cancer. Compared to other tools, SurvExpress is the largest, most versatile, and quickest free tool available. SurvExpress web can be accessed in http://bioinformatica.mty.itesm.mx/SurvExpress (a tutorial is included. The website was implemented in JSP, JavaScript, MySQL, and R.

  3. ANITA-2000 activation code package - updating of the decay data libraries and validation on the experimental data of the 14 MeV Frascati Neutron Generator

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    Frisoni Manuela

    2016-01-01

    Full Text Available ANITA-2000 is a code package for the activation characterization of materials exposed to neutron irradiation released by ENEA to OECD-NEADB and ORNL-RSICC. The main component of the package is the activation code ANITA-4M that computes the radioactive inventory of a material exposed to neutron irradiation. The code requires the decay data library (file fl1 containing the quantities describing the decay properties of the unstable nuclides and the library (file fl2 containing the gamma ray spectra emitted by the radioactive nuclei. The fl1 and fl2 files of the ANITA-2000 code package, originally based on the evaluated nuclear data library FENDL/D-2.0, were recently updated on the basis of the JEFF-3.1.1 Radioactive Decay Data Library. This paper presents the results of the validation of the new fl1 decay data library through the comparison of the ANITA-4M calculated values with the measured electron and photon decay heats and activities of fusion material samples irradiated at the 14 MeV Frascati Neutron Generator (FNG of the NEA-Frascati Research Centre. Twelve material samples were considered, namely: Mo, Cu, Hf, Mg, Ni, Cd, Sn, Re, Ti, W, Ag and Al. The ratios between calculated and experimental values (C/E are shown and discussed in this paper.

  4. Validation that Metabolic Tumor Volume Predicts Outcome in Head and Neck Cancer

    Science.gov (United States)

    Tang, Chad; Murphy, James D.; Khong, Brian; La, Trang H.; Kong, Christina; Fischbein, Nancy J.; Colevas, A. Dimitrios; Iagaru, Andrei H.; Graves, Edward E.; Loo, Billy W.; Le, Quynh-Thu

    2011-01-01

    Purpose We have previously reported that metabolic tumor volume (MTV) obtained from pre-treatment FDG PET/CT predicted outcome in patients with head-and-neck cancer (HNC). The purpose of this study is to validate these results on an independent dataset, determine if the primary tumor or nodal MTV drives this correlation, and explore the interaction with p16INK4a status as a surrogate marker for HPV. Methods and Materials The validation dataset in this study included 83 patients with squamous cell HNC who had a FDG PET/CT scan prior to definitive radiotherapy. MTV and SUVmax were calculated for the primary tumor, involved nodes, and the combination of both. The primary endpoint was to validate that MTV predicted progression-free survival and overall survival. Secondary analyses included determining the prognostic utility of primary tumor versus nodal MTV. Results Similar to our prior findings, an increase in total MTV of 17 cm3 (difference between 75th and 25th percentile) was associated with a 2.1 fold increase in the risk of disease progression (p=0.0002), and a 2.0 fold increase in the risk of death (p=0.0048). SUVmax was not associated with either outcome. Primary tumor MTV predicted progression-free (HR=1.94; p<0.0001) and overall (HR=1.57; p<0.0001) survival, whereas nodal MTV did not. In addition, MTV predicted progression-free (HR=4.23; p<0.0001) and overall (HR=3.21; p=0.0029) survival in patients with p16INK4a positive oropharyngeal cancer. Conclusions This study validates our previous findings that MTV independently predicts outcomes in HNC. MTV should be considered as a potential risk stratifying biomarker in future studies of HNC. PMID:22270174

  5. Development and validation of a treatment planning model for magnetic nanoparticle hyperthermia cancer therapy

    Science.gov (United States)

    Stigliano, Robert Vincent

    The use of magnetic nanoparticles (mNPs) to induce local hyperthermia has been emerging in recent years as a promising cancer therapy, in both a stand-alone and combination treatment setting, including surgery radiation and chemotherapy. The mNP solution can be injected either directly into the tumor, or administered intravenously. Studies have shown that some cancer cells associate with, internalize, and aggregate mNPs more preferentially than normal cells, with and without antibody targeting. Once the mNPs are delivered inside the cells, a low frequency (30-300kHz) alternating electromagnetic field is used to activate the mNPs. The nanoparticles absorb the applied field and provide localized heat generation at nano-micron scales. Treatment planning models have been shown to improve treatment efficacy in radiation therapy by limiting normal tissue damage while maximizing dose to the tumor. To date, there does not exist a clinical treatment planning model for magnetic nanoparticle hyperthermia which is robust, validated, and commercially available. The focus of this research is on the development and experimental validation of a treatment planning model, consisting of a coupled electromagnetic and thermal model that predicts dynamic thermal distributions during treatment. When allowed to incubate, the mNPs are often sequestered by cancer cells and packed into endosomes. The proximity of the mNPs has a strong influence on their ability to heat due to interparticle magnetic interaction effects. A model of mNP heating which takes into account the effects of magnetic interaction was developed, and validated against experimental data. An animal study in mice was conducted to determine the effects of mNP solution injection duration and PEGylation on macroscale mNP distribution within the tumor, in order to further inform the treatment planning model and future experimental technique. In clinical applications, a critical limiting factor for the maximum applied field is

  6. Malignant mesothelioma as an oxidative stress-induced cancer: An update.

    Science.gov (United States)

    Chew, Shan Hwu; Toyokuni, Shinya

    2015-09-01

    Malignant mesothelioma (MM) is a relatively rare cancer that occurs almost exclusively following respiratory exposure to asbestos in humans. Its pathogenesis is closely associated with iron overload and oxidative stress in mesothelial cells. On fiber exposure, mesothelial cells accumulate fibers simultaneously with iron, which either performs physical scissor function or catalyzes free radical generation, leading to oxidative DNA damage such as strand breaks and base modifications, followed by activation of intracellular signaling pathways. Chrysotile, per se without iron, causes massive hemolysis and further adsorbs hemoglobin. Exposure to indigestible foreign materials also induces chronic inflammation, involving consistent generation of free radicals and subsequent activation of NALP3 inflammasomes in macrophages. All of these contribute to mesothelial carcinogenesis. Genomic alterations most frequently involve homozygous deletion of INK4A/4B, and other pathways such as Hippo and TGF-β pathways are also affected in MM. Recently, analyses of familial MM sorted out BAP1 as a novel responsible tumor suppressor gene, whose function is not fully elucidated. Five-year survival of mesothelioma is still ~8%, and this cancer is increasing worldwide. Connective tissue growth factor, a secretory protein creating a vicious cycle mediated by β-catenin, has been recognized as a hopeful target for therapy, especially in sarcomatoid subtype. Recent research outcomes related to microRNAs and cancer stem cells also offer additional novel targets for the treatment of MM. Iron reduction as chemoprevention of mesothelioma is helpful at least in an animal preclinical study. Integrated approaches to fiber-induced oxidative stress would be necessary to overcome this currently fatal disease.

  7. Sentinel lymph node biopsy in bladder cancer: Systematic review and technology update

    Directory of Open Access Journals (Sweden)

    Michael A Liss

    2015-01-01

    Full Text Available A sentinel lymph node (SLN is the first lymph node to drain a solid tumor and likely the first place metastasis will travel. SLN biopsy has been well established as a staging tool for melanoma and breast cancer to guide lymph node dissection (LND; its utility in bladder cancer is debated. We performed a systematic search of PubMed for both human and animal studies that looked at SLN detection in cases of urothelial carcinoma of the bladder. We identified a total of nine studies that assessed a variety of imaging techniques to identify SLNs in patients with urothelial carcinoma of the bladder. Eight studies investigated human patients while one looked at animal (dog models. Seven studies representing 156 patients noted the negative predictive value of the SLN to predict a metastasis free state was 92% (92/100. The SLN biopsy was less accurate in metastatic patients with a positive predictive value of only 77% (43/56 with a false negative range of in individual studies of 0-19%. Clinically, positive nodes routinely do not take up the pharmaceutical agent for SLN. Therefore, SLN biopsy is a promising concept with a 92% negative predictive value; however, the false negative rates are high which may be improved by standardizing populations and indications. Novel technologies are improving the detection of SLN and may provide the surgeon with an improved ability to detect micrometastasis, guide surgery, and reduce patient morbidity.

  8. Management of complications related to central venous catheters in cancer patients: an update.

    Science.gov (United States)

    Linnemann, Birgit

    2014-04-01

    Central venous catheters (CVCs) are important for the treatment of patients with cancer, especially in the perioperative and palliative care settings. These devices not only allow for the administration of chemotherapy, parenteral nutrition, and other intravenous therapies, but they may also improve the patients' quality of life by reducing the need for repeated peripheral venipunctures. Thrombotic and infectious complications are common, especially in the long-term use of CVCs. There are different types of thrombotic complications associated with CVCs, that is, a thrombotic occlusion of the catheter, a mural thrombus at the catheter tip and classical deep vein thrombosis, which occurs most frequently in the upper extremity where the majority of long-term catheters are inserted. Infections are common complications associated with CVCs. Patients with cancer who receive intensive chemotherapy and those patients who undergo hematopoietic stem cell transplantation have a markedly increased risk for insertion site and bloodstream infections. In this review, the epidemiology and risk factors that predispose patients to CVC-related thrombosis and infection are discussed. The diagnostic and therapeutic options according to the published data and the current guidelines are summarized and data for establishing primary and secondary preventative strategies are provided.

  9. Breast cancer in European Union: an update of screening programmes as of March 2014 (review).

    Science.gov (United States)

    Altobelli, E; Lattanzi, A

    2014-11-01

    Breast cancer, a major cause of female morbidity and mortality, is a global health problem; 2008 data show an incidence of ~450,000 new cases and 140,000 deaths (mean incidence rate 70.7 and mortality rate 16.7, world age-standardized rate per 100,000 women) in European Union Member States. Incidence rates in Western Europe are among the highest in the world. We review the situation of BC screening programmes in European Union. Up to date information on active BC screening programmes was obtained by reviewing the literature and searching national health ministries and cancer service websites. Although BC screening programmes are in place in nearly all European Union countries there are still considerable differences in target population coverage and age and in the techniques deployed. Screening is a mainstay of early BC detection whose main weakness is the rate of participation of the target population. National policies and healthcare planning should aim at maximizing participation in controlled organized screening programmes by identifying and lowering any barriers to adhesion, also with a view to reducing healthcare costs.

  10. Lung cancer risks from plutonium: an updated analysis of data from the Mayak worker cohort.

    Science.gov (United States)

    Gilbert, E S; Sokolnikov, M E; Preston, D L; Schonfeld, S J; Schadilov, A E; Vasilenko, E K; Koshurnikova, N A

    2013-03-01

    Workers at the Mayak nuclear facility in the Russian Federation offer a unique opportunity to evaluate health risks from exposure to inhaled plutonium. Risks of mortality from lung cancer, the most serious carcinogenic effect of plutonium, were evaluated in 14,621 Mayak workers who were hired in the period from 1948-1982, followed for at least 5 years, and either monitored for plutonium or never worked with plutonium. Over the follow-up period from 1953-2008, there were 486 deaths from lung cancer, 446 of them in men. In analyses that were adjusted for external radiation dose and smoking, the plutonium excess relative risk (ERR) per Gy declined with attained age and was higher for females than for males. The ERR per Gy for males at age 60 was 7.4 (95% CI: 5.0-11) while that for females was 24 (95% CI: 11-56). When analyses were restricted to plutonium doses plutonium exposure and 29 (6%) to external exposure. Analyses of the 12,708 workers with information on smoking indicated that the relationship of plutonium exposure and smoking was likely sub-multiplicative (P = 0.011) and strongly indicated that it was super-additive (P plutonium dose estimates in this cohort, they are nevertheless subject to large uncertainties. Large bioassay measurement errors alone are likely to have resulted in serious underestimation of risks, whereas other sources of uncertainty may have biased results in ways that are difficult to predict.

  11. Updates on surgical management of advanced gastric cancer: new evidence and trends. Insights from the First International Course on Upper Gastrointestinal Surgery--Varese (Italy), December 2, 2011.

    Science.gov (United States)

    Rausei, Stefano; Dionigi, Gianlorenzo; Sano, Takeshi; Sasako, Mitsuru; Biondi, Alberto; Morgagni, Paolo; Garofalo, Alfredo; Boni, Luigi; Frattini, Francesco; D'Ugo, Domenico; Preston, Shaun; Marrelli, Daniele; Degiuli, Maurizio; Capella, Carlo; Sacco, Rosario; Ruspi, Laura; De Manzoni, Giovanni; Roviello, Franco; Pinotti, Graziella; Rovera, Francesca; Noh, Sung Hoon; Coit, Daniel; Dionigi, Renzo

    2013-11-01

    Between the Ninth International Gastric Cancer Congress (IGCC) in South-Korea (Seoul, 2011) and the Tenth IGCC in Italy (Verona, 2013), the Insubria University organized the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011), with the patronage of Italian Research Group for Gastric Cancer (IRGGC) and the International Gastric Cancer Association (IGCA). The Course was intended to be a comprehensive update and review on advanced gastric cancer (GC) staging and treatment from well-known international experts. Clinical, research, and educational aspects of the surgeon's role in the era of stage-adapted therapy were discussed. As highlighted in the meeting, in this final document we summarize and thoroughly analyze (with references only for well-acquired randomized control trials) the new and old open problems in surgical management of advanced GC. Between the Ninth (Seoul, 2011) and the Tenth (Verona,2013) International Gastric Cancer Congress, the First International Course on Upper Gastrointestinal Surgery (Varese, December 2, 2011) was organized by the University of Insubria. This congress received the patronage of the International Gastric Cancer Association and the Italian Research Group for Gastric Cancer. The aim was to discuss open issues in surgical management of advanced gastric malignancies. We considered the opinions of several recognized experts in the field from both the Eastern and Western world, focused on definition problems and oncological and technical issues to define the current principles of advanced gastric cancer (GC) surgery.

  12. Validated biomarkers: The key to precision treatment in patients with breast cancer.

    Science.gov (United States)

    Duffy, Michael J; O'Donovan, Norma; McDermott, Enda; Crown, John

    2016-10-01

    Recent DNA sequencing and gene expression studies have shown that at a molecular level, almost every case of breast cancer is unique and different from other breast cancers. For optimum management therefore, every patient should receive treatment that is guided by the molecular composition of their tumor, i.e., precision treatment. While such a scenario is still some distance into the future, biomarkers are beginning to play an important role in preparing the way for precision treatment. In particular, biomarkers are increasingly being used for predicting patient outcome and informing as to the most appropriate type of systemic therapy to be administered. Mandatory biomarkers for every newly diagnosed case of breast cancer are estrogen receptors and progesterone receptors in selecting patients for endocrine treatment and HER2 for identifying patients likely to benefit from anti-HER2 therapy. Amongst the best validated prognostic biomarker tests are uPA/PAI-1, MammaPrint and Oncotype DX. Although currently, there are no biomarkers available for predicting response to specific forms of chemotherapy, uPA/PAI-1 and Oncotype DX can aid the identification of lymph node-negative patients that are most likely to benefit from adjuvant chemotherapy, in general. In order to accelerate progress towards precision treatment for women with breast cancer, we need additional predictive biomarkers, especially for enhancing the positive predictive value for endocrine and anti-HER2 therapies, as well as biomarkers for predicting response to specific forms of chemotherapy. The ultimate biomarker test for achieving the goal of precision treatment for patients with breast cancer will likely require a combination of gene sequencing and transcriptomic analysis of every patient's tumor.

  13. The validation and clinical implementation of BRCAplus: a comprehensive high-risk breast cancer diagnostic assay.

    Directory of Open Access Journals (Sweden)

    Hansook Kim Chong

    Full Text Available Breast cancer is the most commonly diagnosed cancer in women, with 10% of disease attributed to hereditary factors. Although BRCA1 and BRCA2 account for a high percentage of hereditary cases, there are more than 25 susceptibility genes that differentially impact the risk for breast cancer. Traditionally, germline testing for breast cancer was performed by Sanger dideoxy terminator sequencing in a reflexive manner, beginning with BRCA1 and BRCA2. The introduction of next-generation sequencing (NGS has enabled the simultaneous testing of all genes implicated in breast cancer resulting in diagnostic labs offering large, comprehensive gene panels. However, some physicians prefer to only test for those genes in which established surveillance and treatment protocol exists. The NGS based BRCAplus test utilizes a custom tiled PCR based target enrichment design and bioinformatics pipeline coupled with array comparative genomic hybridization (aCGH to identify mutations in the six high-risk genes: BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11. Validation of the assay with 250 previously characterized samples resulted in 100% detection of 3,025 known variants and analytical specificity of 99.99%. Analysis of the clinical performance of the first 3,000 BRCAplus samples referred for testing revealed an average coverage greater than 9,000X per target base pair resulting in excellent specificity and the sensitivity to detect low level mosaicism and allele-drop out. The unique design of the assay enabled the detection of pathogenic mutations missed by previous testing. With the abundance of NGS diagnostic tests being released, it is essential that clinicians understand the advantages and limitations of different test designs.

  14. A validated gene expression profile for detecting clinical outcome in breast cancer using artificial neural networks.

    Science.gov (United States)

    Lancashire, L J; Powe, D G; Reis-Filho, J S; Rakha, E; Lemetre, C; Weigelt, B; Abdel-Fatah, T M; Green, A R; Mukta, R; Blamey, R; Paish, E C; Rees, R C; Ellis, I O; Ball, G R

    2010-02-01

    Gene expression microarrays allow for the high throughput analysis of huge numbers of gene transcripts and this technology has been widely applied to the molecular and biological classification of cancer patients and in predicting clinical outcome. A potential handicap of such data intensive molecular technologies is the translation to clinical application in routine practice. In using an artificial neural network bioinformatic approach, we have reduced a 70 gene signature to just 9 genes capable of accurately predicting distant metastases in the original dataset. Upon validation in a follow-up cohort, this signature was an independent predictor of metastases free and overall survival in the presence of the 70 gene signature and other factors. Interestingly, the ANN signature and CA9 expression also split the groups defined by the 70 gene signature into prognostically distinct groups. Subsequently, the presence of protein for the principal prognosticator gene was categorically assessed in breast cancer tissue of an experimental and independent validation patient cohort, using immunohistochemistry. Importantly our principal prognosticator, CA9, showed that it is capable of selecting an aggressive subgroup of patients who are known to have poor prognosis.

  15. Reliability and validity of the valued activity inventory for adults with cancer.

    Science.gov (United States)

    Lyons, Kathleen Doyle; Hegel, Mark T; Hull, Jay G; Li, Zhongze; Balan, Stefan; Bartels, Stephen

    2012-01-01

    The authors assessed the psychometric properties of the Valued Activity Inventory for Adults With Cancer (VAI-AC), a self-report instrument that measures activity limitations. Participants included 50 older adults undergoing chemotherapy who completed the VAI-AC and measures of physical and mental function, symptom intensity, and mood 3 days before and the day of chemotherapy. Test-retest reliability was assessed by determining the average number of items for which the importance of an activity was rated consistently and by calculating the intraclass correlation coefficient (ICC) for the first and second VAI-AC scores. Convergent validity was assessed by correlating the VAI-AC scores with the other measures. Participants consistently rated the importance of 90% of the items. The 72-hour test-retest reliability ICC was 0.67. Participants with fewer activity limitations indicated better physical function (r = 0.58, p < .001), better mental function (r = 0.55, p < .001), lower symptom intensity (r = -0.57, p < .001), and fewer depressive symptoms (r = -0.68, p < .001). The VAI-AC demonstrated evidence of test-retest reliability and convergent validity in this convenience sample of older adults undergoing chemotherapy for cancer.

  16. Face Validity of the Functional Assessment of Cancer Therapy-Breast Symptom Index (FACT- B into Formal Arabic

    Directory of Open Access Journals (Sweden)

    Loulou Kobeissi

    2014-06-01

    Full Text Available Background: Breast cancer affects over one million women annually and is the most common global malignancy among women. Extensive improvements have taken place in the management of breast cancer in recent years and a higher percentage of women are cured from this disease. A proper assessment of the quality of life of women with breast cancer is an essential component in disease management. The Functional Assessment of Cancer Therapy- Breast Symptom Index has been commonly used and well-validated among English speaking populations as well as other populations. To date, no formal translation and evaluation of the Functional Assessment of Cancer Therapy-Breast System Index exists in Arabic. Therefore, this study intends to translate, adapt and face-validate the Functional Assessment of Cancer Therapy-Breast System Index into Arabic, specifically in the context of the Lebanese culture. Methods: We conducted forward and backward translation in Arabic, combined with face validity by clinicians. This was followed by pre-testing to ensure the instrument’s adequacy and cultural sensitivity conducted by the administration of face-to-face interviews with individual breast cancer patients (n=33 and two focus groups (4 women/group to evaluate the relevance and appropriateness of each item and words used in the questionnaire. Results: Study results reinforced the value of the Arabic translated version of the Functional Assessment of Cancer Therapy-Breast System Index in capturing the quality of life of women with breast cancer in Lebanon. Conclusion: The instrument was perceived to be adequate, appropriate for use, culturally sensitive, simple as well as exhaustive. Suggestions have been made to enrich the instruments’ ability to incorporate other quality of life dimensions not captured, as well to enhance the cultural specificity of the Functional Assessment of Cancer Therapy-Breast System Index, when administered among Lebanese women diagnosed with

  17. Validation of quality of life questionnaire for patients with cancer - Indian scenario

    Directory of Open Access Journals (Sweden)

    Vidhubala E

    2005-01-01

    Full Text Available BACKGROUND: Quality of Life (QOL is an important health outcome measure in oncology. Given the underlying pressure of individual geo-political entities, a universal solution may not be applicable and hence there is a need to develop a regional tool and standardize the same to address the linguistic and socio-cultural factors. OBJECTIVE: To standardize a tool to assess the QOL of patients with cancer to suit the Indian scenario. Materials and METHODS: The samples were collected from the Cancer Institute (WIA, Chennai. Samples comprise of 400 patients with all sites and stages of cancer. Period: January 2001 to January 2002. Patients were in the age range of 41-60 years. Thirty-eight items were pooled from existing tools, reviews, and the field trial, by which face and factorial validity were established. Reliability of the tool was also tested. Correlation analysis was done to find out the relation between the domains of QOL. Statistics used: Principal component method with varimax rotation was used. Spearmen product moment correlation and Cronbach alpha coefficient were used for reliability analysis. RESULTS: Ten factors emerged with Eigen values ranging from 8.55 to 1.10 and accounted for 62.6% of variance. The first factor contributed maximally, 22% of variance. The remaining nine factors contributed totally to 40% of the variance on QOL. The ten factors that emerged were psychological well being, self-adequacy, physical well being, confidence in self-ability, external support, pain, mobility, optimism and belief, interpersonal relationship and self-sufficiency and independence. The internal consistency using Cronbach alpha test was 0.90 and split-half reliability was 0.74. CONCLUSION: The tool was found to be highly reliable and valid. It was feasible to administer it at clinical settings.

  18. The meaning and validation of social support networks for close family of persons with advanced cancer

    Directory of Open Access Journals (Sweden)

    Sjolander Catarina

    2012-09-01

    Full Text Available Abstract Background To strengthen the mental well-being of close family of persons newly diagnosed as having cancer, it is necessary to acquire a greater understanding of their experiences of social support networks, so as to better assess what resources are available to them from such networks and what professional measures are required. The main aim of the present study was to explore the meaning of these networks for close family of adult persons in the early stage of treatment for advanced lung or gastrointestinal cancer. An additional aim was to validate the study’s empirical findings by means of the Finfgeld-Connett conceptual model for social support. The intention was to investigate whether these findings were in accordance with previous research in nursing. Methods Seventeen family members with a relative who 8–14 weeks earlier had been diagnosed as having lung or gastrointestinal cancer were interviewed. The data were subjected to qualitative latent content analysis and validated by means of identifying antecedents and critical attributes. Results The meaning or main attribute of the social support network was expressed by the theme Confirmation through togetherness, based on six subthemes covering emotional and, to a lesser extent, instrumental support. Confirmation through togetherness derived principally from information, understanding, encouragement, involvement and spiritual community. Three subthemes were identified as the antecedents to social support: Need of support, Desire for a deeper relationship with relatives, Network to turn to. Social support involves reciprocal exchange of verbal and non-verbal information provided mainly by lay persons. Conclusions The study provides knowledge of the antecedents and attributes of social support networks, particularly from the perspective of close family of adult persons with advanced lung or gastrointestinal cancer. There is a need for measurement instruments that could

  19. The Danish version of the questionnaire on pain communication: preliminary validation in cancer patients

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona Louring;

    2009-01-01

    BACKGROUND: The modified version of the patients' Perceived Involvement in Care Scale (M-PICS) is a tool designed to assess cancer patients' perceptions of patient-health care provider pain communication process. The objective of this study was to examine the psychometric properties of the shorte......BACKGROUND: The modified version of the patients' Perceived Involvement in Care Scale (M-PICS) is a tool designed to assess cancer patients' perceptions of patient-health care provider pain communication process. The objective of this study was to examine the psychometric properties...... of the shortened Danish version of the M-PICS (SDM-PICS). METHODS: The validated English version of the M-PICS was translated into Danish following the repeated back-translation procedure. Cancer patients were recruited for the study from specialized pain management facilities. RESULTS: Thirty-three patients...... responded to the SDM-PICS, Danish Barriers Questionnaire II, Hospital Anxiety and Depression Scale, and Brief Pain Inventory Pain Severity Scale. A factor analysis of the SDM-PICS resulted in two factors: Factor one, patient information, consisted of four items assessing the extent to which the patient...

  20. Prediction of prostate cancer recurrence using quantitative phase imaging: Validation on a general population

    Science.gov (United States)

    Sridharan, Shamira; Macias, Virgilia; Tangella, Krishnarao; Melamed, Jonathan; Dube, Emily; Kong, Max Xiangtian; Kajdacsy-Balla, André; Popescu, Gabriel

    2016-09-01

    Prediction of biochemical recurrence risk of prostate cancer following radical prostatectomy is critical for determining whether the patient would benefit from adjuvant treatments. Various nomograms exist today for identifying individuals at higher risk for recurrence; however, an optimistic under-estimation of recurrence risk is a common problem associated with these methods. We previously showed that anisotropy of light scattering measured using quantitative phase imaging, in the stromal layer adjacent to cancerous glands, is predictive of recurrence. That nested-case controlled study consisted of specimens specifically chosen such that the current prognostic methods fail. Here we report on validating the utility of optical anisotropy for prediction of prostate cancer recurrence in a general population of 192 patients, with 17% probability of recurrence. Our results show that our method can identify recurrent cases with 73% sensitivity and 72% specificity, which is comparable to that of CAPRA-S, a current state of the art method, in the same population. However, our results show that optical anisotropy outperforms CAPRA-S for patients with Gleason grades 7–10. In essence, we demonstrate that anisotropy is a better biomarker for identifying high-risk cases, while Gleason grade is better suited for selecting non-recurrence. Therefore, we propose that anisotropy and current techniques be used together to maximize prediction accuracy.

  1. Age-Adjusted PSA Levels in Prostate Cancer Prediction: Updated Results of the Tyrol Prostate Cancer Early Detection Program.

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    Isabel Heidegger

    Full Text Available To reduce the number of unnecessary biopsies in patients with benign prostatic disease, however, without missing significant PCa the present study re-evaluates the age-dependent PSA cut-offs in the Tyrol Prostate Cancer (PCa early detection program.The study population included 2225 patients who underwent prostate biopsy due to elevated PSA levels at our department. We divided our patient collective into four age groups: ≤49 years (n = 178, 50-59 years (n = 597, 60-69 years (n = 962 and ≥70 years (n = 488. We simulated different scenarios for PSA cut-off values between 1.25 and 6 ng/mL and fPSA% between 15 and 21% for all four age groups and calculated sensitivity, specificity, confidence intervals and predictive values.PCa was detected in 1218 men (54.7%. We found that in combination with free PSA ≤21% the following PSA cut-offs had the best cancer specificity: 1.75 ng/ml for men ≤49 years and 50-59 years, 2.25 ng/ml for men aged 60-69 years and 3.25 ng/ml for men ≥70 years. Using these adjusted PSA cut-off values all significant tumors are recognized in all age groups, yet the number of biopsies is reduced. Overall, one biopsy is avoided in 13 to 14 men (number needed to screen = 13.3, reduction of biopsies = 7.5% when decision regarding biopsy is done according to the "new" cut-off values instead of the "old" ones. For the different age groups the number needed to screen to avoid one biopsy varied between 9.2 (≤49 years and 17.4 (50-59 years.With "new", fine-tuned PSA cut-offs we detect all relevant PCa with a significant reduction of biopsies compared to the "old" cut-off values. Optimization of age-specific PSA cut-offs is one step towards a smarter strategy in the Tyrol PCa Early Detection Program.

  2. Axillary reverse mapping in axillary surgery for breast cancer: an update of the current status.

    Science.gov (United States)

    Beek, Martinus A; Gobardhan, Paul D; Schoenmaeckers, Ernst J P; Klompenhouwer, Elisabeth G; Rutten, Harm J T; Voogd, Adri C; Luiten, Ernest J T

    2016-08-01

    Axillary reverse mapping (ARM) is a technique by which the lymphatic drainage of the upper extremity that traverses the axillary region can be differentiated from the lymphatic drainage of the breast during axillary lymph node dissection (ALND). Adding this procedure to ALND may reduce upper extremity lymphedema by preserving upper extremity drainage. This review of the current literature on the ARM procedure discusses the feasibility, safety and relevance of this technique. A PubMed literature search was performed until 12 August 2015. A total of 31 studies were included in this review. The studies indicated that the ARM procedure adequately identifies the upper extremity lymph nodes and lymphatics in the axillary basin using blue dye or fluorescence. Preservation of ARM lymph nodes and corresponding lymphatics was proven to be oncologically safe in clinically node-negative breast cancer patients with metastatic lymph node involvement in the sentinel lymph node (SLN) who are advised to undergo a completion ALND. The ARM procedure is technically feasible with a high visualisation rate using blue dye or fluorescence. ALND combined with ARM can be regarded as a promising surgical refinement in order to reduce the incidence of upper extremity lymphedema in selected groups of patients.

  3. Intensity-Modulated Radiotherapy in the Treatment of Oropharyngeal Cancer: An Update of the Memorial Sloan-Kettering Cancer Center Experience

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    Setton, Jeremy; Caria, Nicola; Romanyshyn, Jonathan; Koutcher, Lawrence; Wolden, Suzanne L.; Zelefsky, Michael J.; Rowan, Nicholas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Sherman, Eric J.; Fury, Matthew G.; Pfister, David G. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Wong, Richard J.; Shah, Jatin P.; Kraus, Dennis H. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Shi Weiji; Zhang Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Schupak, Karen D.; Gelblum, Daphna Y.; Rao, Shyam D. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Lee, Nancy Y., E-mail: Leen2@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-01-01

    Purpose: To update the Memorial Sloan-Kettering Cancer Center's experience with intensity-modulated radiotherapy (IMRT) in the treatment of oropharyngeal cancer (OPC). Methods and Materials: Between September 1998 and April 2009, 442 patients with histologically confirmed OPC underwent IMRT at our center. There were 379 men and 63 women with a median age of 57 years (range, 27-91). The disease was Stage I in 2%, Stage II in 4%, Stage III in 21%, and Stage IV in 73% of patients. The primary tumor subsite was tonsil in 50%, base of tongue in 46%, pharyngeal wall in 3%, and soft palate in 2%. The median prescription dose to the planning target volume of the gross tumor was 70 Gy for definitive (n = 412) cases and 66 Gy for postoperative cases (n = 30). A total 404 patients (91%) received chemotherapy, including 389 (88%) who received concurrent chemotherapy, the majority of which was platinum-based. Results: Median follow-up among surviving patients was 36.8 months (range, 3-135). The 3-year cumulative incidence of local failure, regional failure, and distant metastasis was 5.4%, 5.6%, and 12.5%, respectively. The 3-year OS rate was 84.9%. The incidence of late dysphagia and late xerostomia {>=}Grade 2 was 11% and 29%, respectively. Conclusions: Our results confirm the feasibility of IMRT in achieving excellent locoregional control and low rates of xerostomia. According to our knowledge, this study is the largest report of patients treated with IMRT for OPC.

  4. Role of IL-17A rs2275913 and IL-17F rs763780 polymorphisms in risk of cancer development: an updated meta-analysis

    Science.gov (United States)

    Dai, Zhi-Ming; Zhang, Tian-Song; Lin, Shuai; Zhang, Wang-Gang; Liu, Jie; Cao, Xing-Mei; Li, Hong-Bao; Wang, Meng; Liu, Xing-Han; Liu, Kang; Li, Shan-Li; Dai, Zhi-Jun

    2016-01-01

    Single nucleotide polymorphisms (SNPs) in the interleukin-17 (IL-17) gene have been shown to be correlated with susceptibility to cancer. However, various studies report different results of this association. The aim of the present work was to clarify the effects of IL-17A G197A (rs2275913) and IL-17F T7488C (rs763780) polymorphisms on cancer risk. We performed systematic searches of the PubMed and CNKI databases to obtain relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association of rs2275913 and rs763780 polymorphisms with cancer risk. Data were extracted from the selected studies, and statistical analysis was conducted using the STATA software. Our results indicated that rs2275913 and rs763780 polymorphisms significantly increase cancer risk, especially in gastric cancers. Subgroup analysis suggested the existence of a significant correlation between rs763780 polymorphism and cancer susceptibility in Caucasian populations. This updated meta-analysis confirms that rs2275913 and rs763780 polymorphisms are highly associated with increased risk for multiple forms of cancer. PMID:26843459

  5. Pathology findings and validation of gastric and esophageal cancer cases in a European cohort (EPIC/EUR-GAST)

    DEFF Research Database (Denmark)

    Carneiro, Fátima; Moutinho, Cátia; Pera, Guillem

    2007-01-01

    OBJECTIVE: Cardia, non-cardia and intestinal and diffuse subtypes of gastric cancer may have different trends and etiological factors. However, the available information is not always collected in population cancer registries, and heterogeneous criteria have been applied for the histopathological...... classification of tumors. We describe the pathological features of incident gastric and esophageal cancers identified within the European Prospective Investigation into Cancer and Nutrition (EPIC). MATERIAL AND METHODS: In an investigation on gastric and esophageal cancer (EUR-GAST) in the EPIC project......, a validation study of diagnoses reported by EPIC centers was conducted by a European panel of pathologists. Original pathology reports, stained slides of tumors and the respective paraffin blocks were requested from the centers. RESULTS: The whole series encompassed 467 cancer cases (gastric and esophageal...

  6. Establishment and validation of an updated diagnostic FCM scoring system based on pooled immunophenotyping in CD34+ blasts and its clinical significance for myelodysplastic syndromes.

    Directory of Open Access Journals (Sweden)

    Feng Xu

    Full Text Available Abnormal immunophenotypes of hematopoietic cells can be detected by flow cytometry (FCM to assist the diagnosis of myelodysplastic syndromes (MDS. We previously established a FCM scoring system for the diagnosis of low-grade MDS. In this study, additional valuable antigens were involved in an updated FCM scoring system (u-FCMSS for all MDS subtypes. The u-FCMSS showed better sensitivity and specificity (89.4% and 96.5% in distinguishing MDS from non-clonal cytopenia diseases. Validation analysis of u-FCMSS exhibited comparable sensitivity and specificity (86.7% and 93.3% and high agreement rate (88.9% of FCM diagnosis with morphological diagnosis at optimal cut-off (score 3. The distribution of FCM scores in different disease stages was also analyzed. The results suggested that early scoring from abnormal expression of mature myeloid/lymphoid antigens and advanced scoring from abnormal expression of stem/progenitor antigens expression constituted the majority of FCM scores of low-grade and high-grade MDS, respectively. High early scoring was generally accompanied by low IPSS-R score and superior survival, whereas high advanced scoring was accompanied by high IPSS-R score and inferior survival. In addition, the low-risk MDS patients with high early scoring and low advanced scoring were revealed as candidates for immunosuppressive therapy, whereas those with high advanced scoring and low early scoring may be more suitable for decitabine treatment. In conclusion, the u-FCMSS is a useful tool for diagnosis, prognosis and treatment selection in MDS. Differences in classes of antigens expressed and in distribution of FCM scores may reflect distinctive stage characteristics of MDS during disease progression.

  7. Update on the Role of Imaging in Management of Metastatic Colorectal Cancer

    Science.gov (United States)

    Tirumani, Sree Harsha; Kim, Kyung Won; Nishino, Mizuki; Howard, Stephanie A.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Cleary, James M.; Ramaiya, Nikhil H.

    2014-01-01

    Evolution in the treatment of metastatic colorectal cancer (mCRC) has led to significant improvement in the survival of these patients. Surgery is useful in patients with resectable disease. Liver-directed therapies such as hepatic arterial infusion, transarterial radio- and chemoembolization, and percutaneous ablation are sometimes used by oncologists when the liver is the only site of metastatic disease. Unresectable mCRC is typically treated with systemic chemotherapy. First-line systemic chemotherapeutic regimens for mCRC are FOLFOX (combination of 5-fluorouracil/leucovorin [5-FU/LV] and oxaliplatin) and FOLFIRI (combination of 5-FU/LV and irinotecan) combined with molecular targeted drugs. Molecular targeted therapies that are effective in treating mCRC include antiangiogenic agents such as bevacizumab—an antibody against vascular endothelial growth factor—and antibodies directed against epidermal growth factor receptor (EGFR). EGFR-directed antibodies such as cetuximab and panitumumab have been shown to produce activity only in wild-type KRAS tumors. Imaging modalities such as multidetector computed tomography (CT), magnetic resonance imaging, and positron emission tomography/CT play a major role in the selection of appropriate treatment strategies. Assessment of treatment response in patients who undergo liver-directed and systemic therapy requires imaging at regular intervals. Recent studies have shown that alternative treatment response criteria may be more predictive of pathologic response in mCRC than conventional criteria such as Response Evaluation Criteria in Solid Tumors. Awareness of unusual response patterns, as well as of complications and toxicities, is helpful in guiding patient management. ©RSNA, 2014 PMID:25384292

  8. Second primary cancer following Hodgkin's disease: Updated results of an Italian multicentric study

    Energy Technology Data Exchange (ETDEWEB)

    Cimino, G.; Papa, G.; Tura, S.; Mazza, P.; Rossi Ferrini, P.L.; Bosi, A.; Amadori, S.; Lo Coco, F.; D' Arcangelo, E.; Giannarelli, D. (Univ. La Sapienza, Rome (Italy))

    1991-03-01

    The risk of second primary cancer (SPC) was evaluated in 947 patients treated for Hodgkin's disease (HD) during the period January 1969 to December 1979. The median follow-up of this series was 10.5 years (range, 9 to 19). Treatment categories included radiotherapy (RT) alone (115 patients, 12%), chemotherapy (CHT) alone (161 patients, 17%), combined RT plus CHT (381 patients, 40%), and salvage treatment for resistant or relapsing HD (290 patients, 30.6%). Fifty-six SPCs were observed, occurring between 1 and 17 years from initial treatment. Among these, secondary acute nonlymphoid leukemia (s-ANLL) was the most frequent SPC (23 cases). Secondary non-Hodgkin's lymphoma (s-NHL) occurred in 5 patients, whereas a secondary solid tumor (s-ST) was observed in 28 patients. The calculated actuarial risk (+/- SE) of developing SPC was 5.0% (+/- 0.9%) and 23.1% (+/- 5.8%) at 10 and 19 years, respectively. Concerning treatment modalities and s-ANLL risk, no cases were observed in the radiotherapy group, whereas CHT plus RT and salvage groups showed the highest actuarial risk. This was, in fact, at 10 and 19 years, 3.1% (+/- 0.9%) and 8.1% (+/- 4.0%) in the former group, and 1.8% (+/- 1.0%) and 16% (+/- 9.0%) in the latter. A statistically significant difference was observed when the CHT plus RT group was compared with CHT and RT groups (P = .04). Concerning the relationships with chemotherapeutic regimens, 12 s-ANLL cases occurred in the mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus RT group, and only one case in the group receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus RT. A statistically significant difference of s-ANLL actuarial risk was found comparing patients receiving MOPP plus RT to all other treatment groups (P = .04).

  9. Reliability and Validity of Amharic Version of EORTC QLQ-C 30 Questionnaire among Gynecological Cancer Patients in Ethiopia.

    Directory of Open Access Journals (Sweden)

    Birhanu Abera Ayana

    Full Text Available Cancer is a growing public health problem worldwide. The focus of cancer treatment, in addition to curation, is improving the quality of life (QOL. This study aimed to assess the reliability and validity of Amharic version of European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30 among gynecological cancer patients in Ethiopia.A facility-based cross-sectional study was conducted using the Amharic version of EORTC QLQ-C30 on 153 gynecological cancer patients in Tikur Anbassa Specialized Hospital (TASH, Addis Ababa, Ethiopia. Descriptive statistics, correlation analysis and multivariable linear regression were employed in statistical analysis.The Amharic version of EORTC QLQ-C30 had a Cronbach's α value of 0.81. The internal consistency for each domain of EORTC QLQ-C30 was also acceptable (Cronbach's α >0.7 except for cognitive function domain (Cronbach's α = 0.29. Stepwise multivariable linear regression analysis showed that emotional functioning (p<0.001, fatigue (p<0.001 and social functioning (p = 0.004 were the determinative scales of EORTC QLQ-C30 on global health status (GHS. The clinical validity test (Known group validity showed that there were significant differences in score for twelve out of 15 domains, between surgery and radiation scheduled patients. All items of emotional function, role function, fatigue, and GHS meet the discriminate validity criterion.The Amharic version of EORTC QLQ-C30 found to be reliable and had an acceptable validity to assess the QOL for gynecological cancer patients. We recommend further work on the validity and responsiveness of the EORTC QLQ-C30 with stronger design.

  10. Validation of the CAchexia SCOre (CASCO). Staging Cancer Patients: The Use of miniCASCO as a Simplified Tool

    Science.gov (United States)

    Argilés, Josep M.; Betancourt, Angelica; Guàrdia-Olmos, Joan; Peró-Cebollero, Maribel; López-Soriano, Francisco J.; Madeddu, Clelia; Serpe, Roberto; Busquets, Sílvia

    2017-01-01

    The CAchexia SCOre (CASCO) was described as a tool for the staging of cachectic cancer patients. The aim of this study is to show the metric properties of CASCO in order to classify cachectic cancer patients into three different groups, which are associated with a numerical scoring. The final aim was to clinically validate CASCO for its use in the classification of cachectic cancer patients in clinical practice. We carried out a case -control study that enrolled prospectively 186 cancer patients and 95 age-matched controls. The score includes five components: (1) body weight loss and composition, (2) inflammation/metabolic disturbances/immunosuppression, (3) physical performance, (4) anorexia, and (5) quality of life. The present study provides clinical validation for the use of the score. In order to show the metric properties of CASCO, three different groups of cachectic cancer patients were established according to the results obtained with the statistical approach used: mild cachexia (15 ≤ × ≤ 28), moderate cachexia (29 ≤ × ≤ 46), and severe cachexia (47 ≤ × ≤ 100). In addition, a simplified version of CASCO, MiniCASCO (MCASCO), was also presented and it contributes as a valid and easy-to-use tool for cachexia staging. Significant statistically correlations were found between CASCO and other validated indexes such as Eastern Cooperative Oncology Group (ECOG) and the subjective diagnosis of cachexia by specialized oncologists. A very significant estimated correlation between CASCO and MCASCO was found that suggests that MCASCO might constitute an easy and valid tool for the staging of the cachectic cancer patients. CASCO and MCASCO provide a new tool for the quantitative staging of cachectic cancer patients with a clear advantage over previous classifications. PMID:28261113

  11. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Directory of Open Access Journals (Sweden)

    Stephanie H Greco

    Full Text Available Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  12. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Science.gov (United States)

    Greco, Stephanie H; Tomkötter, Lena; Vahle, Anne-Kristin; Rokosh, Rae; Avanzi, Antonina; Mahmood, Syed Kashif; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Ochi, Atsuo; Zambirinis, Constantinos; Mohaimin, Tasnima; Rendon, Mauricio; Levie, Elliot; Pansari, Mridul; Torres-Hernandez, Alejandro; Daley, Donnele; Barilla, Rocky; Pachter, H Leon; Tippens, Daniel; Malik, Hassan; Boutajangout, Allal; Wisniewski, Thomas; Miller, George

    2015-01-01

    Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  13. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer.

    Science.gov (United States)

    Vogel, Victor G; Costantino, Joseph P; Wickerham, D Lawrence; Cronin, Walter M; Cecchini, Reena S; Atkins, James N; Bevers, Therese B; Fehrenbacher, Louis; Pajon, Eduardo R; Wade, James L; Robidoux, André; Margolese, Richard G; James, Joan; Runowicz, Carolyn D; Ganz, Patricia A; Reis, Steven E; McCaskill-Stevens, Worta; Ford, Leslie G; Jordan, V Craig; Wolmark, Norman

    2010-06-01

    The selective estrogen-receptor modulator (SERM) tamoxifen became the first U.S. Food and Drug Administration (FDA)-approved agent for reducing breast cancer risk but did not gain wide acceptance for prevention, largely because it increased endometrial cancer and thromboembolic events. The FDA approved the SERM raloxifene for breast cancer risk reduction following its demonstrated effectiveness in preventing invasive breast cancer in the Study of Tamoxifen and Raloxifene (STAR). Raloxifene caused less toxicity (versus tamoxifen), including reduced thromboembolic events and endometrial cancer. In this report, we present an updated analysis with an 81-month median follow-up. STAR women were randomly assigned to receive either tamoxifen (20 mg/d) or raloxifene (60 mg/d) for 5 years. The risk ratio (RR; raloxifene:tamoxifen) for invasive breast cancer was 1.24 (95% confidence interval [CI], 1.05-1.47) and for noninvasive disease, 1.22 (95% CI, 0.95-1.59). Compared with initial results, the RRs widened for invasive and narrowed for noninvasive breast cancer. Toxicity RRs (raloxifene:tamoxifen) were 0.55 (95% CI, 0.36-0.83; P = 0.003) for endometrial cancer (this difference was not significant in the initial results), 0.19 (95% CI, 0.12-0.29) for uterine hyperplasia, and 0.75 (95% CI, 0.60-0.93) for thromboembolic events. There were no significant mortality differences. Long-term raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive disease and grew closer over time to tamoxifen in preventing noninvasive disease, with far less toxicity (e.g., highly significantly less endometrial cancer). These results have important public health implications and clarify that both raloxifene and tamoxifen are good preventive choices for postmenopausal women with elevated risk for breast cancer.

  14. Predictive Accuracy of the PanCan Lung Cancer Risk Prediction Model -External Validation based on CT from the Danish Lung Cancer Screening Trial

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde M.; van Riel, Sarah J.; Saghir, Zaigham

    2015-01-01

    ; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (p = 0.047 and p = 0.040) in the DLCST. Conclusions: High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were......Objectives: Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. Methods: From...... used to evaluate risk discrimination. Results: AUCs of 0.826–0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer...

  15. Discovery and validation of an INflammatory PROtein-driven GAstric cancer Signature (INPROGAS) using antibody microarray-based oncoproteomics

    OpenAIRE

    Puig-Costa, Manuel; Codina-Cazador, Antonio; Cortés-Pastoret, Elisabet; Oliveras-Ferraros, Cristina; Cufí, Sílvia; Flaquer, Sílvia; Llopis-Puigmarti, Francesca; Pujol-Amado, Eulalia; Corominas-Faja, Bruna; Cuyàs, Elisabet; Ortiz, Rosa; Lopez-Bonet, Eugeni; Queralt, Bernardo; Guardeño, Raquel; Martin-Castillo, Begoña

    2014-01-01

    This study aimed to improve gastric cancer (GC) diagnosis by identifying and validating an INflammatory PROtein-driven GAstric cancer Signature (hereafter INPROGAS) using low-cost affinity proteomics. The detection of 120 cytokines, 43 angiogenic factors, 41 growth factors, 40 inflammatory factors and 10 metalloproteinases was performed using commercially available human antibody microarray-based arrays. We identified 21 inflammation-related proteins (INPROGAS) with significant differences in...

  16. Validation that Metabolic Tumor Volume Predicts Outcome in Head-and-Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chad; Murphy, James D.; Khong, Brian; La, Trang H. [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Kong, Christina [Department of Pathology, Stanford University, Stanford, CA (United States); Fischbein, Nancy J. [Department of Radiology, Stanford University, Stanford, CA (United States); Colevas, A. Dimitrios [Division of Medical Oncology, Department of Medicine, Stanford University, Stanford, CA (United States); Iagaru, Andrei H. [Department of Radiology, Stanford University, Stanford, CA (United States); Graves, Edward E.; Loo, Billy W. [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Le, Quynh-Thu, E-mail: qle@stanford.edu [Department of Radiation Oncology, Stanford University, Stanford, CA (United States)

    2012-08-01

    Purpose: We have previously reported that metabolic tumor volume (MTV) obtained from pretreatment {sup 18}F-fluorodeoxydeglucose positron emission tomography (FDG PET)/ computed tomography (CT) predicted outcome in patients with head-and-neck cancer (HNC). The purpose of this study was to validate these results on an independent dataset, determine whether the primary tumor or nodal MTV drives this correlation, and explore the interaction with p16{sup INK4a} status as a surrogate marker for human papillomavirus (HPV). Methods and Materials: The validation dataset in this study included 83 patients with squamous cell HNC who had a FDG PET/CT scan before receiving definitive radiotherapy. MTV and maximum standardized uptake value (SUV{sub max}) were calculated for the primary tumor, the involved nodes, and the combination of both. The primary endpoint was to validate that MTV predicted progression-free survival and overall survival. Secondary analyses included determining the prognostic utility of primary tumor vs. nodal MTV. Results: Similarly to our prior findings, an increase in total MTV of 17 cm{sup 3} (difference between the 75th and 25th percentiles) was associated with a 2.1-fold increase in the risk of disease progression (p = 0.0002) and a 2.0-fold increase in the risk of death (p = 0.0048). SUV{sub max} was not associated with either outcome. Primary tumor MTV predicted progression-free (hazard ratio [HR] = 1.94; p < 0.0001) and overall (HR = 1.57; p < 0.0001) survival, whereas nodal MTV did not. In addition, MTV predicted progression-free (HR = 4.23; p < 0.0001) and overall (HR = 3.21; p = 0.0029) survival in patients with p16{sup INK4a}-positive oropharyngeal cancer. Conclusions: This study validates our previous findings that MTV independently predicts outcomes in HNC. MTV should be considered as a potential risk-stratifying biomarker in future studies of HNC.

  17. Targeted therapies for cancer

    Science.gov (United States)

    ... types of these cancers: Leukemia and lymphoma Breast cancer Colon cancer Skin cancer Lung cancer Prostate Other cancers ... ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 44. Review Date 9/13/2015 Updated by: Todd Gersten, ...

  18. Adaptation of the Body Image after Breast Cancer Questionnaire in the Polish context: factorial structure and validity of the scale

    Directory of Open Access Journals (Sweden)

    Romuald Derbis

    2016-01-01

    Full Text Available Background Valid assessment of body image is salient in therapy and rehabilitation of women suffering from breast cancer. Adequate instruments are still lacking in this domain. To overcome this limitation two aims were formulated in the study. First, we tested the factorial structure of the Body Image after Breast Cancer Questionnaire (BIBCQ developed by Baxter (1998 in Canada, in the Polish context. Then, we tested the construct validity of the scale. The scale is based on a multidimensional concept of the body image of chronically ill individuals proposed by Vamos (1993. Participants and procedure A group of 270 women at the mean age of 55 (range of 23-81 with breast cancer who underwent conservation, mastectomy, or lumpectomy surgery was sampled in the Amazonki community. Results Confirmatory factor analysis was used to test the factorial structure of the instrument. To test the convergent validity, scales assessing body self, body image, self-esteem, and depression were used. Divergent validity was analyzed in the context of the social desirability construct. Discriminant validity was based on comparisons between women who had undergone lumpectomy or mastectomy surgery. The results showed that within two out of six subscales proposed by Baxter, two additional subscales had to be distinguished. However, some differences in comparisons with previous validation studies were also found. Conclusions The BIBCQ scale was found to be a valid multidimensional tool of body image assessment in the Polish context. The results are discussed in terms of cross-cultural differences in body image perception in breast cancer patients and guidelines for the scale’s implementation in the Polish context.

  19. Validating a benchmarking tool for audit of early outcomes after operations for head and neck cancer.

    Science.gov (United States)

    Tighe, D; Sassoon, I; McGurk, M

    2017-04-01

    INTRODUCTION In 2013 all UK surgical specialties, with the exception of head and neck surgery, published outcome data adjusted for case mix for indicator operations. This paper reports a pilot study to validate a previously published risk adjustment score on patients from separate UK cancer centres. METHODS A case note audit was performed of 1,075 patients undergoing 1,218 operations for head and neck squamous cell carcinoma under general anaesthesia in 4 surgical centres. A logistic regression equation predicting for all complications, previously validated internally at sites A-C, was tested on a fourth external validation sample (site D, 172 operations) using receiver operating characteristic curves, Hosmer-Lemeshow goodness of fit analysis and Brier scores. RESULTS Thirty-day complication rates varied widely (34-51%) between the centres. The predictive score allowed imperfect risk adjustment (area under the curve: 0.70), with Hosmer-Lemeshow analysis suggesting good calibration. The Brier score changed from 0.19 for sites A-C to 0.23 when site D was also included, suggesting poor accuracy overall. CONCLUSIONS Marked differences in operative risk and patient case mix captured by the risk adjustment score do not explain all the differences in observed outcomes. Further investigation with different methods is recommended to improve modelling of risk. Morbidity is common, and usually has a major impact on patient recovery, ward occupancy, hospital finances and patient perception of quality of care. We hope comparative audit will highlight good performance and challenge underperformance where it exists.

  20. Fully Automated Fluorescent in situ Hybridization (FISH) Staining and Digital Analysis of HER2 in Breast Cancer : A Validation Study

    NARCIS (Netherlands)

    van der Logt, Elise M. J.; Kuperus, Deborah A. J.; van Setten, Jan W.; van den Heuvel, Marius C.; Boers, James. E.; Schuuring, Ed; Kibbelaar, Robby E.

    2015-01-01

    HER2 assessment is routinely used to select patients with invasive breast cancer that might benefit from HER2-targeted therapy. The aim of this study was to validate a fully automated in situ hybridization (ISH) procedure that combines the automated Leica HER2 fluorescent ISH system for Bond with su

  1. Validation of fully automated VMAT plan generation for library-based plan-of-the-day cervical cancer radiotherapy

    NARCIS (Netherlands)

    A.W.M. Sharfo (Abdul Wahab M.); S. Breedveld (Sebastiaan); P.W.J. Voet (Peter W.J.); S.T. Heijkoop (Sabrina); J.W.M. Mens (Jan); M.S. Hoogeman (Mischa); B.J.M. Heijmen (Ben)

    2016-01-01

    textabstractPurpose: To develop and validate fully automated generation of VMAT plan-libraries for plan-of-the-day adaptive radiotherapy in locally-advanced cervical cancer. Material and Methods: Our framework for fully automated treatment plan generation (Erasmus-iCycle) was adapted to create dual-

  2. Votes on cancer. Extremely low frequency electromagnetic fields and health. An update; Stemmen over kanker. Extreem-laagfrequente elektromagnetische velden en gezondheid. Update

    Energy Technology Data Exchange (ETDEWEB)

    Passchier, W.F. [Capaciteitsgroep Gezondheidsrisico-analyse en Toxicologie, Universiteit Maastricht, Maastricht (Netherlands)

    1999-11-01

    In the 1970's the United States became uneasy about the impact of high voltage power transmission lines on public health. That uneasiness, which also spread to Europe, now appears to be subsiding. however, recently a group of scientists voted, at the invitation of the American Congress, on the carcinogenicity of electromagnetic fields from electricity producing businesses. The statement that the extremely low frequency electromagnetic fields can cause blood cancer got 19 of the 30 votes. Results of studies on the title subject so far are discussed. 13 refs.

  3. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S)

    DEFF Research Database (Denmark)

    O'Sullivan, Brian; Huang, Shao Hui; Su, Jie

    2016-01-01

    ; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients' HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status....... We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory...... training cohort to assess relevance within the ICON-S classification. FINDINGS: Of 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III...

  4. The value of TOP2A gene copy number variation as a biomarker in breast cancer: Update of DBCG trial 89D

    DEFF Research Database (Denmark)

    Nielsen, K.V.; Ejlertsen, B.; Moller, S.

    2008-01-01

    BACKGROUND: Previous analyses of TOP2A and HER2 in the Danish Breast Cancer Coopererative Group (DBCG) trial 89D suggested that TOP2A amplifications and possible also deletions are predictive markers for the effect of adjuvant epirubicin in patients with primary breast cancer. We present an updated...... and extended statistical analysis, requested for IVD-labeling of TOP2A testing. MATERIAL AND METHODS: In the DBCG trial 89D 980 Danish patients were randomly assigned to nine cycles of intravenous CMF (cyclophosphamide, methotrexate, and fluorouracil) or CEF (cyclophosphamide, epirubicin, and fluorouracil......). Archival tumor tissue was collected retrospectively from 806 of these patients in a prospectively designed, biological sub-study, and was successfully analyzed for TOP2A aberrations and HER2 status in 773 samples (96%). Recurrence-free survival (RFS) was the primary endpoint. RESULTS: TOP2A aberrations...

  5. Reproducibility, reliability and validity of population-based administrative health data for the assessment of cancer non-related comorbidities

    Science.gov (United States)

    Fowler, Helen

    2017-01-01

    Background Patients with comorbidities do not receive optimal treatment for their cancer, leading to lower cancer survival. Information on individual comorbidities is not straightforward to derive from population-based administrative health datasets. We described the development of a reproducible algorithm to extract the individual Charlson index comorbidities from such data. We illustrated the algorithm with 1,789 laryngeal cancer patients diagnosed in England in 2013. We aimed to clearly set out and advocate the time-related assumptions specified in the algorithm by providing empirical evidence for them. Methods Comorbidities were assessed from hospital records in the ten years preceding cancer diagnosis and internal reliability of the hospital records was checked. Data were right-truncated 6 or 12 months prior to cancer diagnosis to avoid inclusion of potentially cancer-related comorbidities. We tested for collider bias using Cox regression. Results Our administrative data showed weak to moderate internal reliability to identify comorbidities (ICC ranging between 0.1 and 0.6) but a notably high external validity (86.3%). We showed a reverse protective effect of non-cancer related Chronic Obstructive Pulmonary Disease (COPD) when the effect is split into cancer and non-cancer related COPD (Age-adjusted HR: 0.95, 95% CI:0.7–1.28 for non-cancer related comorbidities). Furthermore, we showed that a window of 6 years before diagnosis is an optimal period for the assessment of comorbidities. Conclusion To formulate a robust approach for assessing common comorbidities, it is important that assumptions made are explicitly stated and empirically proven. We provide a transparent and consistent approach useful to researchers looking to assess comorbidities for cancer patients using administrative health data. PMID:28263996

  6. Redesign and Validation of Sisom, an Interactive Assessment and Communication Tool for Children With Cancer

    Science.gov (United States)

    2016-01-01

    Background Children with cancer undergo intensive and long treatment periods that expose them and their families to a number of difficult physical, mental, and social challenges. Empowering children by actively involving them in their care can help them to cope with these challenges. It can, however, be difficult for children to be involved and talk about their illness experiences in a “traditional” conversation with health care professionals, especially for younger children. Sisom (Norwegian acronym “Si det som det er” or “Tell it how it is”) is an interactive computer-based assessment and communication tool to give children (aged 6-12 years) with cancer a “voice” in their care. Because of technological advances and widespread use of mobile devices Sisom had to be redesigned to better meet the needs of children of today. Objective To redesign Sisom for use on mobile devices and to validate and adapt it for use in a Swedish population of children with cancer. Methods A user-experience design was used. Content adaptation included forward-backward translation by Swedish and Norwegian translators. Healthy children (n=5), children with experiences of cancer treatment (n=5) and their parents (n=5), and pediatric nurses (n=2) were then involved in culturally adapting Sisom to the Swedish context. The iterative low- and high-fidelity evaluation was supported by a think aloud method, semistructured interviews, and drawings to capture children’s views of Sisom. The redesign and evaluation continued until no further changes or improvements were identified by the participants or the researchers. Results Children, parents, and pediatric nurses offered many suggestions for improvements to the original version in terms of content, aesthetics, and usability of Sisom. The most significant change that emerged through user input was a modification that entailed not using problem-focused statements in the assessment items. The parents and pediatric nurses considered

  7. Validation of the distress thermometer for use among adolescents and young adults with cancer in Australia: a multicenter study protocol

    Directory of Open Access Journals (Sweden)

    Patterson P

    2015-07-01

    Full Text Available Pandora Patterson,1,2 Fiona EJ McDonald,1,2 Antoinette Anazodo,3 Daniel SJ Costa,4 Claire E Wakefield,5,6 Kate White,2 Kate Thompson,7 Michael P Osborn8 1Research, Evaluation and Social Policy, CanTeen Australia, Sydney, NSW, Australia; 2Cancer Nursing Research Unit, Sydney Nursing School, The University of Sydney, Sydney, NSW, Australia; 3Sydney Youth Cancer Service, Sydney Children's Hospital and Prince of Wales Hospital, Randwick, NSW, Australia; 4Psycho-oncology Co-operative Research group, School of Psychology, The University of Sydney, Sydney, NSW, Australia; 5School of Women's and Children's Health, UNSW Medicine, University of New South Wales, Kensington, NSW, Australia; 6Behavioural Sciences Unit, Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW, Australia; 7Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; 8Youth Cancer Service SA/NT, Royal Adelaide Hospital, Adelaide, SA, Australia Background: Adolescents and young adults (AYAs diagnosed with cancer commonly experience elevated levels of distress. Routinely administered distress screening tools can be effective in identifying individuals in need of referral to psychosocial services. The distress thermometer and problem checklist are widely used screening tools that have been validated among some cancer populations, but which have not to date been validated for use among AYAs with cancer. The primary aim of this study is to validate the distress thermometer and a modified problem checklist for use with AYA cancer patients, aged 15–25 years. Specifically, we aim to 1 determine appropriate cutoffs for clinical referral on the distress thermometer; 2 investigate the content validity of the modified problem checklist; and 3 assess the clinical utility of the tool from the perspectives of both patients and health care professionals. The secondary aims of the study are to 4 establish prevalence and predictors of distress in AYA cancer patients and 5 examine the

  8. PET-Based Treatment Response Evaluation in Rectal Cancer: Prediction and Validation

    Energy Technology Data Exchange (ETDEWEB)

    Janssen, Marco H.M., E-mail: marco.janssen@maastro.nl [Department of Radiation Oncology (MAASTRO), GROW Research Institute, University Medical Centre Maastricht, Maastricht (Netherlands); Oellers, Michel C.; Stiphout, Ruud G.P.M. van [Department of Radiation Oncology (MAASTRO), GROW Research Institute, University Medical Centre Maastricht, Maastricht (Netherlands); Riedl, Robert G. [Department of Pathology, University Medical Centre Maastricht, Maastricht (Netherlands); Bogaard, Jorgen van den; Buijsen, Jeroen; Lambin, Philippe; Lammering, Guido [Department of Radiation Oncology (MAASTRO), GROW Research Institute, University Medical Centre Maastricht, Maastricht (Netherlands)

    2012-02-01

    Purpose: To develop a positron emission tomography (PET)-based response prediction model to differentiate pathological responders from nonresponders. The predictive strength of the model was validated in a second patient group, treated and imaged identical to the patients on which the predictive model was based. Methods and Materials: Fifty-one rectal cancer patients were prospectively included in this study. All patients underwent fluorodeoxyglucose (FDG) PET-computed tomography (CT) imaging both before the start of chemoradiotherapy (CRT) and after 2 weeks of treatment. Preoperative treatment with CRT was followed by a total mesorectal excision. From the resected specimen, the tumor regression grade (TRG) was scored according to the Mandard criteria. From one patient group (n = 30), the metabolic treatment response was correlated with the pathological treatment response, resulting in a receiver operating characteristic (ROC) curve based cutoff value for the reduction of maximum standardized uptake value (SUV{sub max}) within the tumor to differentiate pathological responders (TRG 1-2) from nonresponders (TRG 3-5). The applicability of the selected cutoff value for new patients was validated in a second patient group (n = 21). Results: When correlating the metabolic and pathological treatment response for the first patient group using ROC curve analysis (area under the curve = 0.98), a cutoff value of 48% SUV{sub max} reduction was selected to differentiate pathological responders from nonresponders (specificity of 100%, sensitivity of 64%). Applying this cutoff value to the second patient group resulted in a specificity and sensitivity of, respectively, 93% and 83%, with only one of the pathological nonresponders being false positively predicted as pathological responding. Conclusions: For rectal cancer, an accurate PET-based prediction of the pathological treatment response is feasible already after 2 weeks of CRT. The presented predictive model could be used to

  9. Decentral gene expression analysis: analytical validation of the Endopredict genomic multianalyte breast cancer prognosis test

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    Kronenwett Ralf

    2012-10-01

    Full Text Available Abstract Background EndoPredict (EP is a clinically validated multianalyte gene expression test to predict distant metastasis in ER-positive, HER2-negative breast cancer treated with endocrine therapy alone. The test is based on the combined analysis of 12 genes in formalin-fixed, paraffin-embedded (FFPE tissue by reverse transcription-quantitative real-time PCR (RT-qPCR. Recently, it was shown that EP is feasible for reliable decentralized assessment of gene expression. The aim of this study was the analytical validation of the performance characteristics of the assay and its verification in a molecular-pathological routine laboratory. Methods Gene expression values to calculate the EP score were assayed by one-step RT-qPCR using RNA from FFPE tumor tissue. Limit of blank, limit of detection, linear range, and PCR efficiency were assessed for each of the 12 PCR assays using serial samples dilutions. Different breast cancer samples were used to evaluate RNA input range, precision and inter-laboratory variability. Results PCR assays were linear up to Cq values between 35.1 and 37.2. Amplification efficiencies ranged from 75% to 101%. The RNA input range without considerable change of the EP score was between 0.16 and 18.5 ng/μl. Analysis of precision (variation of day, day time, instrument, operator, reagent lots resulted in a total noise (standard deviation of 0.16 EP score units on a scale from 0 to 15. The major part of the total noise (SD 0.14 was caused by the replicate-to-replicate noise of the PCR assays (repeatability and was not associated with different operating conditions (reproducibility. Performance characteristics established in the manufacturer’s laboratory were verified in a routine molecular pathology laboratory. Comparison of 10 tumor samples analyzed in two different laboratories showed a Pearson coefficient of 0.995 and a mean deviation of 0.15 score units. Conclusions The EP test showed reproducible performance

  10. Validation and practical implementation of a multidisciplinary cancer distress screening questionnaire

    Energy Technology Data Exchange (ETDEWEB)

    Kirchheiner, K.; Czajka, A.; Komarek, E.; Hohenberg, G.; Poetter, R. [Medical University of Vienna (Austria). Dept. of Radiation Oncology; Ponocny-Seliger, E. [Sigmund Freud Private University, Vienna (Austria). Dept. of Psychology; Doerr, W. [Medical University of Vienna (Austria). Dept. of Radiation Oncology; Medical University of Vienna (Austria). Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology

    2013-07-15

    Background: In order to identify cancer patients with psychosocial needs during radiotherapy, a routine screening questionnaire is widely recommended in the literature. Several tools focusing mainly on psychological issues have been developed during the past decade. However, problems with their implementation into clinical routine have been repeatedly reported, due to a lack of practicability for clinicians and nurses. This study reports the compilation of a multidisciplinary screening questionnaire and an analysis of the effectiveness of its implementation into clinical routine at the Department of Radiotherapy, Medical University of Vienna. Materials and methods: The screening questionnaire is based on a compilation of several subscales from established and validated assessment tools. It focuses on comprehensive information with high a clinical relevance for all professions. In a pilot study, patients' acceptance was assessed qualitatively. Analysis of missing screening data in consecutively admitted patients reflects the effectiveness of implementation and representativity of the data. A validation analysis of the psychological subscales was performed using external criteria and its internal consistency was tested with Cronbachs' {alpha}. Results: Qualitative patient acceptance of the screening questionnaire is good. The overall response rate in the screening procedure was 75 %. Missing patient screening data sets arose randomly - mainly due to organizational problems - and did not result in systematic errors. The psychological subscales identify highly distressed patients with a sensitivity of 89 and 78 %, and an internal consistency of 0.843 and 0.617. Conclusion: The multidisciplinary screening questionnaire compiled in this study has a high patient acceptance, provides reliable and representative data and identifies highly distressed patients with excellent sensitivity. Although requiring additional personnel resources, it can be implemented

  11. Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.

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    Laetitia Marisa

    Full Text Available BACKGROUND: Colon cancer (CC pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses. METHODS AND FINDINGS: Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays. 566 samples fulfilled RNA quality requirements. Unsupervised consensus hierarchical clustering applied to gene expression data from a discovery subset of 443 CC samples identified six molecular subtypes. These subtypes were associated with distinct clinicopathological characteristics, molecular alterations, specific enrichments of supervised gene expression signatures (stem cell phenotype-like, normal-like, serrated CC phenotype-like, and deregulated signaling pathways. Based on their main biological characteristics, we distinguished a deficient mismatch repair subtype, a KRAS mutant subtype, a cancer stem cell subtype, and three chromosomal instability subtypes, including one associated with down-regulated immune pathways, one with up-regulation of the Wnt pathway, and one displaying a normal-like gene expression profile. The classification was validated in the remaining 123 samples plus an independent set of 1,058 CC samples, including eight public datasets. Furthermore, prognosis was analyzed in the subset of stage II-III CC samples. The subtypes C4 and C6, but not the subtypes C1, C2, C3, and C5, were independently associated with shorter relapse

  12. Validation of the memorial Sloan-Kettering Cancer Center nomogram to predict disease-specific survival after R0 resection in a Chinese gastric cancer population.

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    Donglai Chen

    Full Text Available BACKGROUND: Prediction of disease-specific survival (DSS for individual patient with gastric cancer after R0 resection remains a clinical concern. Since the clinicopathologic characteristics of gastric cancer vary widely between China and western countries, this study is to evaluate a nomogram from Memorial Sloan-Kettering Cancer Center (MSKCC for predicting the probability of DSS in patients with gastric cancer from a Chinese cohort. METHODS: From 1998 to 2007, clinical data of 979 patients with gastric cancer who underwent R0 resection were retrospectively collected from Peking University Cancer Hospital & Institute and used for external validation. The performance of the MSKCC nomogram in our population was assessed using concordance index (C-index and calibration plot. RESULTS: The C-index for the MSKCC predictive nomogram was 0.74 in the Chinese cohort, compared with 0.69 for American Joint Committee on Cancer (AJCC staging system (P<0.0001. This suggests that the discriminating value of MSKCC nomogram is superior to AJCC staging system for prognostic prediction in the Chinese population. Calibration plots showed that the actual survival of Chinese patients corresponded closely to the MSKCC nonogram-predicted survival probabilities. Moreover, MSKCC nomogram predictions demonstrated the heterogeneity of survival in stage IIA/IIB/IIIA/IIIB disease of the Chinese patients. CONCLUSION: In this study, we externally validated MSKCC nomogram for predicting the probability of 5- and 9-year DSS after R0 resection for gastric cancer in a Chinese population. The MSKCC nomogram performed well with good discrimination and calibration. The MSKCC nomogram improved individualized predictions of survival, and may assist Chinese clinicians and patients in individual follow-up scheduling, and decision making with regard to various treatment options.

  13. Validation of the chinese version of the EORTC QLQ-CR29 in patients with colorectal cancer

    Science.gov (United States)

    Lin, Jin-Bo; Zhang, Lei; Wu, Dong-Wen; Xi, Zhou-Huan; Wang, Xue-Jun; Lin, Yun-Shou; Fujiwara, Wakana; Tian, Jing-Ru; Wang, Min; Peng, Peng; Guo, Ai; Yang, Zhen; Luo, Le; Jiang, Ling-Ya; Li, Qia-Qia; Zhang, Xue-Ying; Zhang, Yun-Feng; Xu, Hou-Wei; Yang, Bing; Li, Xun-Lin; Lei, Yi-Xiong

    2017-01-01

    AIM To assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29) in Chinese patients with colorectal cancer (CRC). METHODS From March 2014 to January 2015, 356 patients with CRC from four different hospitals in China were enrolled in the study, and all patients self-administered the EORTC QLQ-CR29 and the quality of life core questionnaire (EORTC QLQ-C30). Evaluation of the scores was based on the Karnofsky Performance Scale (KPS). The reliability and validity of the questionnaires were assessed by Cronbach’s α coefficient, the Spearman correlation test and Wilcoxon rank sum test. RESULTS The EORTC QLQ-CR29 showed satisfactory reliability (α > 0.7), although the urinary frequency and blood and mucus in stool dimensions had only moderate reliability (α = 0.608). The multitrait scaling analyses showed good convergent (r > 0.4) and discriminant validity. Significant differences were obtained for each item in the different KPS subgroups (KPS ≤ 80; KPS > 80). Body image and most single-item dimensions showed statistically significant differences in patients with a stoma compared with the rest of the patients. CONCLUSION The EORTC QLQ-CR29 exhibits high validity and reliability in Chinese patients with CRC, and can therefore be recommended as a valuable tool for the assessment of quality of life in these patients.

  14. The validity and reliability of the 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN)

    DEFF Research Database (Denmark)

    Lund, Line; Ross, Lone; Petersen, Morten A;

    2014-01-01

    and reliability of the multi-item scales in the CaTCoN using psychometric analyses as well as tests of convergent and discriminant validity with the existing instruments FAMCARE and Family Inventory of Needs (FIN). Material and methods. Based on theoretical considerations, a subscale structure in the Ca......TCoN and the existing questionnaires FAMCARE and FIN. Conclusion. Taken together the psychometric analyses and tests of convergent and discriminant validity indicate that the validity and reliability of the CaTCoN are satisfactory.......Background. Caregivers are often involved in and affected by the patient's disease. The questionnaire 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN) was developed to measure caregivers' experiences. The aim of this study is to evaluate the construct validity...

  15. Portuguese validation of the Symptom Inventory of the M.D. Anderson Cancer Center

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    Adriane Cristina Bernat Kolankiewicz

    2014-12-01

    Full Text Available Objective To analyze the reliability and validity of the psychometric properties of the Brazilian version of the instrument for symptom assessment, titled MD Anderson Symptom Inventory - core. Method A cross-sectional study with 268 cancer patients in outpatient treatment, in the municipality of Ijuí, state of Rio Grande do Sul, Brazil. Results The Cronbach’s alpha for the MDASI general, symptoms and interferences was respectively (0.857, (0.784 and (0.794. The factor analysis showed adequacy of the data (0.792. In total, were identified four factors of the principal components related to the symptoms. Factor I: sleep problems, distress (upset, difficulties in remembering things and sadness. Factor II: dizziness, nausea, lack of appetite and vomiting. Factor III: drowsiness, dry mouth, numbness and tingling. Factor IV: pain, fatigue and shortness of breath. A single factor was revealed in the component of interferences with life (0.780, with prevalence of activity in general (59.7%, work (54.9% and walking (49.3%. Conclusion The Brazilian version of the MD Anderson Symptom Inventory - core showed adequate psychometric properties in the studied population.

  16. Development and External Validation of the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer: Comparison with Two Western Risk Calculators in an Asian Cohort

    Science.gov (United States)

    Yoon, Sungroh; Park, Man Sik; Choi, Hoon; Bae, Jae Hyun; Moon, Du Geon; Hong, Sung Kyu; Lee, Sang Eun; Park, Chanwang

    2017-01-01

    Purpose We developed the Korean Prostate Cancer Risk Calculator for High-Grade Prostate Cancer (KPCRC-HG) that predicts the probability of prostate cancer (PC) of Gleason score 7 or higher at the initial prostate biopsy in a Korean cohort (http://acl.snu.ac.kr/PCRC/RISC/). In addition, KPCRC-HG was validated and compared with internet-based Western risk calculators in a validation cohort. Materials and Methods Using a logistic regression model, KPCRC-HG was developed based on the data from 602 previously unscreened Korean men who underwent initial prostate biopsies. Using 2,313 cases in a validation cohort, KPCRC-HG was compared with the European Randomized Study of Screening for PC Risk Calculator for high-grade cancer (ERSPCRC-HG) and the Prostate Cancer Prevention Trial Risk Calculator 2.0 for high-grade cancer (PCPTRC-HG). The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots. Results PC was detected in 172 (28.6%) men, 120 (19.9%) of whom had PC of Gleason score 7 or higher. Independent predictors included prostate-specific antigen levels, digital rectal examination findings, transrectal ultrasound findings, and prostate volume. The AUC of the KPCRC-HG (0.84) was higher than that of the PCPTRC-HG (0.79, pcancer prediction model in Korea. It had higher predictive accuracy than PCPTRC-HG in a Korean population and showed similar performance with ERSPCRC-HG in a Korean population. This prediction model could help avoid unnecessary biopsy and reduce overdiagnosis and overtreatment in clinical settings. PMID:28046017

  17. Extending the validity of the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) at the time of prostate biopsy in a racially-mixed population.

    Science.gov (United States)

    Dale, William; Hemmerich, Joshua; Meltzer, David

    2007-05-01

    The Memorial Anxiety Scale for Prostate Cancer (MAX-PC) has been validated for assessing men with prostate cancer for cancer-specific anxiety. It was originally validated in a predominantly white population. The MAX-PC Prostate Cancer Anxiety Subscale (MAX-PC-PCAS) may be relevant for measuring cancer-specific anxiety in undiagnosed men at risk for prostate cancer. We assess the validity of the MAX-PC-PCAS at the time of prostate biopsy (n = 178). Questions assessed socio-demographic information, health status, patient-estimated risk of cancer, the Hospital Anxiety and Depression Scale--Anxiety Subscale (HADS-A), and the MAX-PC-PCAS. The patients' most recent PSA was recorded. Cronbach's alpha, inter-item correlations, and Pearson correlations with both the HADS-A and clinical variables were compared with the original validation sample. Our sample was younger (63.1 vs 71.1 years), had a larger fraction of African-Americans (43 vs 10%), and had higher PSAs. Cronbach's alpha was equivalent (0.91 vs 0.90), median inter-item correlation was equivalent (0.63 vs 0.61), and Pearson correlation with HADS-A was higher (0.71 vs 0.57). Anxiety levels were not correlated with PSA levels, and there were minor differences in the validation findings by race. The validity of the MAX-PC-PCAS extends to men without cancer undergoing biopsy and to African-Americans.

  18. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america.

    Science.gov (United States)

    Freifeld, Alison G; Bow, Eric J; Sepkowitz, Kent A; Boeckh, Michael J; Ito, James I; Mullen, Craig A; Raad, Issam I; Rolston, Kenneth V; Young, Jo-Anne H; Wingard, John R

    2011-02-15

    This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are

  19. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  20. External validation of the Prostate Cancer Prevention Trial and the European Randomized Study of Screening for Prostate Cancer risk calculators in a Chinese cohort

    Institute of Scientific and Technical Information of China (English)

    Yao Zhu; Ding-Wei Ye; Jin-You Wang; Yi-Jun Shen; Bo Dai; Chun-Guang Ma; Wen-Jun Xiao; Guo-Wen Lin; Xu-Dong Yao; Shi-Lin Zhang

    2012-01-01

    Several prediction models have been developed to estimate the outcomes of prostate biopsies.Most of these teels were designed for use with Western populations and have not been validated across different ethnic groups.Therefore,we evaluated the predictive value of the Prostate Cancer Prevention Trial (PCPT) and the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators in a Chinese cohort.Clinicopathological information was obtained from 495 Chinese men who had undergone extended prostate biopsies between January 2009 and March 2011.The estimated probabilities of prostate cancer and high-grade disease (Gleason >6) were calculated using the PCPT and ERSPC risk calculators.Overall measures,discrimination,calibration and clinical usefulness were assessed for the model evaluation.Of these patients,28.7% were diagnosed with prostate cancer and 19.4% had high-grade disease.Compared to the PCPT model and the prostate-specific antigen (PSA) threshold of 4 ng ml-1,the ERSPC risk calculator exhibited better discriminative ability for predicting positive biopsies and high-grade disease (the area under the curve was 0.831 and 0.852,respectively,P<0.01 for both).Decision curve analysis also suggested the favourable clinical utility of the ERSPC calculator in the validation dataset.Both prediction models demonstrated miscalibration:the risk of prostate cancer and high-grade disease was overestimated by approximately 20% for a wide range of predicted probabilities.In conclusion,the ERSPC risk calculator outperformed both the PCPT model and the PSA threshold of 4 ng ml-1 in predicting prostate cancer and high-grade disease in Chinese patients.However,the prediction tools derived from Western men significantly overestimated the probability of prostate cancer and high-grade disease compared to the outcomes of biopsies in a Chinese cohort.

  1. Actualización de la estadificación del cáncer de pulmón Lung cancer staging: an update

    Directory of Open Access Journals (Sweden)

    Christian González

    2012-12-01

    Full Text Available The International Association for the Study of Lung Cancer (IASLC, junto con The International Union Against Cancer (UICC y The American Joint Committee on Cancer (AJCC, crearon un Comité Internacional de Estadificación (ISC que recopiló retrospectivamente y analizó los datos procedentes de pacientes de diferentes partes del mundo, con el propósito de efectuar cambios en la 6a edición del TNM de cáncer de pulmón. La misma había sido publicada en el 2002 y no había tenido modificaciones desde 1997 (5a edición, por lo que con la actualización se buscó establecer una estadificación adecuada y segura, necesaria para describir en forma estandarizada la extensión de la enfermedad, predecir el pronóstico, seleccionar la terapéutica y evaluar los resultados en ensayos clínicos retrospectivos. La 7a edición del TNM de cáncer de pulmón, publicada a fines de 2009 y vigente desde el 1° de enero de 2010, ha incorporado en la estadificación del cáncer de pulmón cambios sustanciales (especialmente referidos al tamaño tumoral y mapeo ganglionar, proponiendo además una nueva agrupación de estadios.The International Association for the Study of Lung Cancer (IASLC together with The International Union Against Cancer (UICC and The American Joint Committee on Cancer (AJCC created an International Staging Committee (ISC that retrospectively collected and analyzed data from patients worldwide with the purpose of introducing changes to the 6th edition of the TNM staging for lung cancer published in 2002, which was not changed since 1997 (5th Edition. The updating was intended to provide an adequate and safe staging, which is necessary to describe, in a standardized manner, the extent of disease, predict prognosis, select therapy, and assess outcomes in prospective clinical trials. The 7th edition of the TNM staging for lung cancer published in late 2009 and effective as of January 1, 2010, have incorporated substantial changes in the staging

  2. A Translational Approach to Validate In Vivo Anti-Tumor Effects of Chloroquine on Breast Cancer Risk

    Science.gov (United States)

    2015-07-01

    birth control pills or other hormonal contraceptives for at least one month for any reason? These include pills , injections, implants, and patches...Question 50. r Refuse to answer Skip to Question 50. 48. How old were you when you started taking birth control pills /hormonal contraceptives ...AWARD NUMBER: W81XWH-12-1-0144 TITLE: A Translational Approach to Validate In Vivo Anti-Tumor Effects of Chloroquine on Breast Cancer Risk

  3. Development and external validation of a faecal immunochemical test-based prediction model for colorectal cancer detection in symptomatic patients

    OpenAIRE

    Alves, Maria Teresa; Álvarez-Sánchez, Victoria; Ferrandez, Ángel; Rodríguez-Alcalde, Daniel; ,; Cubiella, Joaquín; Vega, Pablo; Salve, María; Díaz-Ondina, Marta; Blanco, Irene; Macía, Pedro; Sánchez, Eloy; Fernández-Seara, Javier; Alves, María Teresa; Quintero, Enrique

    2016-01-01

    Background Risk prediction models for colorectal cancer (CRC) detection in symptomatic patients based on available biomarkers may improve CRC diagnosis. Our aim was to develop, compare with the NICE referral criteria and externally validate a CRC prediction model, COLONPREDICT, based on clinical and laboratory variables. Methods This prospective cross-sectional study included consecutive patients with gastrointestinal symptoms referred for colonoscopy between March 2012 and September 2013 in ...

  4. Updating and validating a new framework for restoring and analyzing latency-variable ERP components from single trials with residue iteration decomposition (RIDE).

    Science.gov (United States)

    Ouyang, Guang; Sommer, Werner; Zhou, Changsong

    2015-06-01

    Trial-to-trial latency variability pervades cognitive EEG responses and may mix and smear ERP components but is usually ignored in conventional ERP averaging. Existing attempts to decompose temporally overlapping and latency-variable ERP components show major limitations. Here, we propose a theoretical framework and model of ERPs consisting of temporally overlapping components locked to different external events or varying in latency from trial to trial. Based on this model, a new ERP decomposition and reconstruction method was developed: residue iteration decomposition (RIDE). Here, we describe an update of the method and compare it to other decomposition methods in simulated and real datasets. The updated RIDE method solves the divergence problem inherent to previous latency-based decomposition methods. By implementing the model of ERPs as consisting of time-variable and invariable single-trial component clusters, RIDE obtains latency-corrected ERP waveforms and topographies of the components, and yields dynamic information about single trials.

  5. Cancer mortality among radiological technologists in Japan. Updated analysis of follow-up data from 1969 to 1993

    Energy Technology Data Exchange (ETDEWEB)

    Yoshinaga, Shinji; Yoshimoto, Yasuhiko [National Inst. of Radiological Sciences, Chiba (Japan); Aoyama, Takashi; Sugahara, Tsutomu

    1999-04-01

    A retrospective cohort study was conducted for 12,195 male radiological technologists who received the occupational exposure to low dose radiation over a long term. A total of 1,097 deaths including 435 from cancer were ascertained by Koseki and death certificates from 1969 to 1993. Cancer mortality among the study population was basically compared with that of whole Japanese men. The significant low SMRs were obtained for all cancers, stomach and lung cancer partly due to Healthy Worker Effect, unlike the results of the early reports with some inappropriateness in the methods. Apparent high risks of lymphatic and hematopoietic cancers were observed, although none of site-specific cancers revealed the statistically significant increase. For these cancers, the SMRs among old sub-cohort were somewhat higher than those of young sub-cohort, whereas similar SMRs for solid cancer were obtained between the two sub cohorts. The SMR for leukemia reached statistically significant level of 1.75 (95%Cl: 1.07-2.71) when using whole professional and technical workers as a standard population. The study results might suggest that the chronic exposure to low-dose radiation enhanced the risk of lymphatic and hematopoietic cancers. (author)

  6. Glutathione S-transferase P1, gene-gene interaction, and lung cancer susceptibility in the Chinese population: An updated meta-analysis and review

    Directory of Open Access Journals (Sweden)

    Xue-Ming Li

    2015-01-01

    Full Text Available Aim of Study: To assess the impact of glutathione S-transferase P1 (GSTP1 Ile105Val polymorphism on the risk of lung cancer in the Chinese population, an updated meta-analysis and review was performed. Materials and Methods: Relevant studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine published through January 22, 2015. The odds ratios (ORs and 95% confidence intervals (CIs were calculated to estimate the strength of the associations. Results: A total of 13 case-control studies, including 2026 lung cancer cases and 2451 controls, were included in this meta-analysis. Overall, significantly increased lung cancer risk was associated with the variant genotypes of GSTP1 polymorphism in the Chinese population (GG vs. AA: OR = 1.36, 95% CI = 1.01-1.84. In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies (GG vs. AA: OR = 1.62, 95% CI: 1.13-2.31; GG vs. AG: OR = 1.49, 95% CI: 1.03-2.16; GG vs. AA + AG: OR = 1.55, 95% CI: 1.12-2.26. A gene-gene interaction analysis showed that there was an interaction for individuals with combination of GSTM1 (or GSTT1 null genotype and GSTP1 (AG + GG mutant genotype for lung cancer risk in Chinese. Conclusion: This meta-analysis suggests that GSTP1 Ile105Val polymorphism may increase the risk of lung cancer in the Chinese population.

  7. Actualización de la estadificación de cáncer de cuello uterino Classification and staging of cervical cancer: an update

    Directory of Open Access Journals (Sweden)

    Claudia Álvarez

    2012-06-01

    Full Text Available A pesar de los avances en la detección y prevención del cáncer de cuello uterino, éste continúa siendo una gran amenaza para la salud de las mujeres a nivel mundial. Una correcta evaluación de los factores pronósticos es crucial para la elección y planificación de un tratamiento adecuado. La estadificación del cáncer de cuello uterino ha sufrido modificaciones en la 7° edición del TNM, reflejando la nueva clasificación adoptada por la Federación Internacional de Ginecología y Obstetricia (FIGO. En este artículo presentamos el sistema actualizado y unificado de estadificación para cáncer de cuello uterino.Despite advances in screening and prevention, cervical cancer remains a major threat to women's health worldwide. A correct evaluation of prognostic factors is crucial for choosing and planning the most appropriate treatment. Cervical cancer staging has undergone modifications in the 7th edition of TNM, reflecting the new classification adopted by the International Federation of Gynecology and Obstetrics (FIGO. In this paper we present the updated and consolidated system of cervical cancer staging.

  8. Predictive accuracy of the PanCan lung cancer risk prediction model - external validation based on CT from the Danish Lung Cancer Screening Trial

    Energy Technology Data Exchange (ETDEWEB)

    Winkler Wille, Mathilde M.; Dirksen, Asger [Gentofte Hospital, Department of Respiratory Medicine, Hellerup (Denmark); Riel, Sarah J. van; Jacobs, Colin; Scholten, Ernst T.; Ginneken, Bram van [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Saghir, Zaigham [Herlev Hospital, Department of Respiratory Medicine, Herlev (Denmark); Pedersen, Jesper Holst [Copenhagen University Hospital, Department of Thoracic Surgery, Rigshospitalet, Koebenhavn Oe (Denmark); Hohwue Thomsen, Laura [Hvidovre Hospital, Department of Respiratory Medicine, Hvidovre (Denmark); Skovgaard, Lene T. [University of Copenhagen, Department of Biostatistics, Koebenhavn Oe (Denmark)

    2015-10-15

    Lung cancer risk models should be externally validated to test generalizability and clinical usefulness. The Danish Lung Cancer Screening Trial (DLCST) is a population-based prospective cohort study, used to assess the discriminative performances of the PanCan models. From the DLCST database, 1,152 nodules from 718 participants were included. Parsimonious and full PanCan risk prediction models were applied to DLCST data, and also coefficients of the model were recalculated using DLCST data. Receiver operating characteristics (ROC) curves and area under the curve (AUC) were used to evaluate risk discrimination. AUCs of 0.826-0.870 were found for DLCST data based on PanCan risk prediction models. In the DLCST, age and family history were significant predictors (p = 0.001 and p = 0.013). Female sex was not confirmed to be associated with higher risk of lung cancer; in fact opposing effects of sex were observed in the two cohorts. Thus, female sex appeared to lower the risk (p = 0.047 and p = 0.040) in the DLCST. High risk discrimination was validated in the DLCST cohort, mainly determined by nodule size. Age and family history of lung cancer were significant predictors and could be included in the parsimonious model. Sex appears to be a less useful predictor. (orig.)

  9. Validating the use of Medicare Australia billing data to examine trends in skin cancer [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2015-11-01

    Full Text Available Background:  Epidemiological data surrounding non-melanomatous skin cancer (NMSC is highly variable, in part due to the lack of government cancer registries. Several studies employ the use of Medical Australia (MA rebate data in assessing such trends, the validity of which has not been studied in the past. Conversely, melanoma skin cancer is a notifiable disease, and thus, MA and cancer registry data is readily available. The aim of the current study is to assess the use of MA for epidemiological measures for skin cancers, by using melanoma as a disease sample.   Methods:  Following ethics approval, data from MA and Victorian Cancer Registry (VCR from 2004-2008 were extracted. Incidence of MA and VCR unique melanoma cases were compared and stratified by age and local government area (LGA. Regression and a paired-samples t-test were performed.   Results: During the study period; 15,150 and 13,886 unique melanoma patients were identified through VCR and MA data sources respectively. An outlier in the >80­ year age group was noted between MA and VCR data. When stratified by age, significant correlation between MA and VCR was observed for all patients (gradient 0.91, R²= 0.936 and following exclusion of >80 patients (gradient 0.96, R²= 0.995. When stratified by LGA, a high degree of observation was observed for all patients (gradient 0.94, R²= 0.977 and following exclusion of >80 patients (gradient 0.996, R²= 0.975.   Conclusion: Despite the inclusion of outlier data groups, acceptable correlation between MA and VCR melanoma data was observed, suggesting that MA may be suitable for assessing epidemiological trends. Such principals may be used to validate the use of MA data for similar calculations assessing NMSC trends.

  10. Discovery and validation of an INflammatory PROtein-driven GAstric cancer Signature (INPROGAS) using antibody microarray-based oncoproteomics

    Science.gov (United States)

    Puig-Costa, Manuel; Codina-Cazador, Antonio; Cortés-Pastoret, Elisabet; Oliveras-Ferraros, Cristina; Cufí, Sílvia; Flaquer, Sílvia; Llopis-Puigmarti, Francesca; Pujol-Amado, Eulalia; Corominas-Faja, Bruna; Cuyàs, Elisabet; Ortiz, Rosa; Lopez-Bonet, Eugeni; Queralt, Bernardo; Guardeño, Raquel; Martin-Castillo, Begoña; Roig, Josep; Joven, Jorge; Menendez, Javier A.

    2014-01-01

    This study aimed to improve gastric cancer (GC) diagnosis by identifying and validating an INflammatory PROtein-driven GAstric cancer Signature (hereafter INPROGAS) using low-cost affinity proteomics. The detection of 120 cytokines, 43 angiogenic factors, 41 growth factors, 40 inflammatory factors and 10 metalloproteinases was performed using commercially available human antibody microarray-based arrays. We identified 21 inflammation-related proteins (INPROGAS) with significant differences in expression between GC tissues and normal gastric mucosa in a discovery cohort of matched pairs (n=10) of tumor/normal gastric tissues. Ingenuity pathway analysis confirmed the “inflammatory response”, “cellular movement” and “immune cell trafficking” as the most overrepresented biofunctions within INPROGAS. Using an expanded independent validation cohort (n = 22), INPROGAS classified gastric samples as “GC” or “non-GC” with a sensitivity of 82% (95% CI 59-94) and a specificity of 73% (95% CI 49-89). The positive predictive value and negative predictive value in this validation cohort were 75% (95% CI 53-90) and 80% (95% CI 56-94), respectively. The positive predictive value and negative predictive value in this validation cohort were 75% (95% CI 53-90) and 80% (95% CI 56-94), respectively. Antibody microarray analyses of the GC-associated inflammatory proteome identified a 21-protein INPROGAS that accurately discriminated GC from noncancerous gastric mucosa. PMID:24722433

  11. Do GPs know their patients with cancer? Assessing the quality of cancer registration in Dutch primary care: a cross-sectional validation study

    Science.gov (United States)

    Sollie, Annet; Roskam, Jessika; Sijmons, Rolf H; Numans, Mattijs E; Helsper, Charles W

    2016-01-01

    Objectives To assess the quality of cancer registry in primary care. Design and setting A cross-sectional validation study using linked data from primary care electronic health records (EHRs) and the Netherlands Cancer Registry (NCR). Population 290 000 patients, registered with 120 general practitioners (GPs), from 50 practice centres in the Utrecht area, the Netherlands, in January 2013. Intervention Linking the EHRs of all patients in the Julius General Practitioners’ Network database at an individual patient level to the full NCR (∼1.7 million tumours between 1989 and 2011), to determine the proportion of matching cancer diagnoses. Full-text EHR extraction and manual analysis for non-matching diagnoses. Main outcome measures Proportions of matching and non-matching breast, lung, colorectal and prostate cancer diagnoses between 2007 and 2011, stratified by age category, cancer type and EHR system. Differences in year of diagnosis between the EHR and the NCR. Reasons for non-matching diagnoses. Results In the Primary Care EHR, 60.6% of cancer cases were registered and coded in accordance with the NCR. Of the EHR diagnoses, 48.9% were potentially false positive (not registered in the NCR). Results differed between EHR systems but not between age categories or cancer types. The year of diagnosis corresponded in 80.6% of matching coded diagnoses. Adding full-text EHR analysis improved results substantially. A national disease registry (the NCR) proved incomplete. Conclusions Even though GPs do know their patients with cancer, only 60.6% are coded in concordance with the NCR. Reusers of coded EHR data should be aware that 40% of cases can be missed, and almost half can be false positive. The type of EHR system influences registration quality. If full-text manual EHR analysis is used, only 10% of cases will be missed and 20% of cases found will be wrong. EHR data should only be reused with care. PMID:27633642

  12. Telerobotic-assisted laparoscopic abdominoperineal resection for low rectal cancer: Report of the first case in Hong Kong and China with an updated literature review

    Institute of Scientific and Technical Information of China (English)

    Simon Siu-Man Ng; Janet Fung-Yee Lee; Raymond Ying-Chang Yiu; Jimmy Chak-Man Li; Sophie Sok-Fei Hon

    2007-01-01

    Telerobotic surgery is the most advanced development in the field of minimally invasive surgery. The da Vinci surgical system, which is currently the most widely used telerobotic device, was approved by the Food and Drug Administration of the United States of America for clinical use in all abdominal operations in July 2000. The first da Vinci surgical system in China was installed in November 2005 at our institution. We herein report the first telerobotic-assisted laparoscopic abdominoperineal resection using the 3-arm da Vinci surgical system for low rectal cancer in Hong Kong and China, which was performed in August 2006. The operative time and blood loss were 240 min and 200 mL, respectively. There was no complication, and the patient was discharged on postoperative day five. An updated review of published literature on telerobotic-assisted colorectal surgery is included in this report, with special emphasis on its advantages and limitations.

  13. External validation of nomograms for predicting cancer-specific mortality in penile cancer patients treated with definitive surgery

    Institute of Scientific and Technical Information of China (English)

    Yao Zhu; Wei-Jie Gu; Ding-Wei Ye; Xu-Dong Yao; Shi-Lin Zhang; Bo Dai; Hai-Liang Zhang; Yi-Jun Shen

    2014-01-01

    Using a population-based cancer registry, Thuret et al. developed 3 nomograms for estimating cancer-specific mortality in men with penile squamous cell carcinoma. In the initial cohort, only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage. To generalize the prediction models in clinical practice, we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery. Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008. The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade. Discrimination, calibration, and clinical usefulness were assessed to compare model performance. The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging (Harrell’s concordance index = 0.817 and 0.832, respectively), whereas it was inferior for the Surveillance, Epidemiology and End Results staging (Harrel ’s concordance index = 0.728). Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade, which also achieved favorable clinical net benefit, with a threshold probability in the range of 0 to 42%. The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery. Our data support the integration of this model in decision-making and trial design.

  14. Identification and Validation of a New Set of Five Genes for Prediction of Risk in Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Giorgio Mustacchi

    2013-05-01

    Full Text Available Molecular tests predicting the outcome of breast cancer patients based on gene expression levels can be used to assist in making treatment decisions after consideration of conventional markers. In this study we identified a subset of 20 mRNA differentially regulated in breast cancer analyzing several publicly available array gene expression data using R/Bioconductor package. Using RTqPCR we evaluate 261 consecutive invasive breast cancer cases not selected for age, adjuvant treatment, nodal and estrogen receptor status from paraffin embedded sections. The biological samples dataset was split into a training (137 cases and a validation set (124 cases. The gene signature was developed on the training set and a multivariate stepwise Cox analysis selected five genes independently associated with DFS: FGF18 (HR = 1.13, p = 0.05, BCL2 (HR = 0.57, p = 0.001, PRC1 (HR = 1.51, p = 0.001, MMP9 (HR = 1.11, p = 0.08, SERF1a (HR = 0.83, p = 0.007. These five genes were combined into a linear score (signature weighted according to the coefficients of the Cox model, as: 0.125FGF18 − 0.560BCL2 + 0.409PRC1 + 0.104MMP9 − 0.188SERF1A (HR = 2.7, 95% CI = 1.9–4.0, p < 0.001. The signature was then evaluated on the validation set assessing the discrimination ability by a Kaplan Meier analysis, using the same cut offs classifying patients at low, intermediate or high risk of disease relapse as defined on the training set (p < 0.001. Our signature, after a further clinical validation, could be proposed as prognostic signature for disease free survival in breast cancer patients where the indication for adjuvant chemotherapy added to endocrine treatment is uncertain.

  15. Development of a novel location-based assessment of sensory symptoms in cancer patients: preliminary reliability and validity assessment.

    Science.gov (United States)

    Burkey, Adam R; Kanetsky, Peter A

    2009-05-01

    We report on the development of a novel location-based assessment of sensory symptoms in cancer (L-BASIC) instrument, and its initial estimates of reliability and validity. L-BASIC is structured so that patients provide a numeric score and an adjectival description for any sensory symptom, including both pain and neuropathic sensations, present in each of the 10 predefined body areas. Ninety-seven patients completed the baseline questionnaire; 39 completed the questionnaire on two occasions. A mean of 3.5 body parts was scored per patient. On average, 2.7 (of 11) descriptor categories were used per body part. There was good internal consistency (Cronbach's alpha=0.74) for a four-item scale that combined location-specific metrics. Temporal stability was adequate (kappa>0.50 and r>0.60 for categorical and continuous variables, respectively) among patients without observed or reported subjective change in clinical status between L-BASIC administrations. We compared our four-item scale against scores obtained from validated pain and quality-of-life (QOL) scales, and as expected, correlations were higher for pain-related items than for QOL-related items. We detected differences in L-BASIC responses among patients with cancer-related head or neck pain, chemotherapy-related neuropathy and breast cancer-related lymphedema. We conclude that L-BASIC provides internally consistent and temporally stable responses, while acknowledging that further refinement and testing of this novel instrument are necessary. We anticipate that future versions of L-BASIC will provide reliable and valid syndrome-specific measurement of defined clinical pain and symptom constructs in the cancer population, which may be of particular value in assessing treatment response in patients with such multiple complaints.

  16. Measuring religious faith in cancer patients: reliability and construct validity of the Santa Clara Strength of Religious Faith questionnaire.

    Science.gov (United States)

    Sherman, A C; Simonton, S; Adams, D C; Latif, U; Plante, T G; Burns, S K; Poling, T

    2001-01-01

    Growing attention has focused on associations between religious involvement and health outcomes for cancer patients. Unfortunately, research has been hampered by lack of measures suitable for use in oncology settings. This study examined the performance of one recently developed measure, the Santa Clara Strength of Religious Faith Questionnaire (SCSORF). Initial investigations with cancer patients in a bone marrow transplant program and with non-oncology patients yielded promising results. This study provided additional information about temporal stability and convergent validity. The measure was evaluated in two well-defined samples: (1) 95 breast cancer patients, and (2) 53 healthy young adults. Most of the cancer patients had recent diagnoses and localized or regional disease. In each sample, the instrument demonstrated high test-retest reliability (r's=0.82-0.93) and internal consistency (r's=0.95-0.97). It displayed strong correlations with measures of intrinsic religiosity (r's=0.67-0.82, p<0.0001), and moderate correlations with organizational religiosity (r's=0.61-069, p<0.0001), non-organizational religiosity (r's=0.52-0.55, p<0.0001), comfort from religion (r=0.58, p<0.0001), and ratings of self as religious (r=0.58, p<0.0001). Among cancer patients, scores were significantly associated with optimism (r=0.30, p<0.01), but not with openness of family communication about cancer or perceived social support. These data build on previous findings with cancer patients, and suggest that the SCSORF may be a useful measure of religious faith in oncology settings.

  17. Identification of valid reference genes for gene expression studies of human stomach cancer by reverse transcription-qPCR

    Directory of Open Access Journals (Sweden)

    Lee Yeon-Su

    2010-05-01

    Full Text Available Abstract Background Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR is a powerful method for the analysis of gene expression. Target gene expression levels are usually normalized to a consistently expressed reference gene also known as internal standard, in the same sample. However, much effort has not been expended thus far in the search for reference genes suitable for the study of stomach cancer using RT-qPCR, although selection of optimal reference genes is critical for interpretation of results. Methods We assessed the suitability of six possible reference genes, beta-actin (ACTB, glyceraldehydes-3-phosphate dehydrogenase (GAPDH, hypoxanthine phosphoribosyl transferase 1 (HPRT1, beta-2-microglobulin (B2M, ribosomal subunit L29 (RPL29 and 18S ribosomal RNA (18S rRNA in 20 normal and tumor stomach tissue pairs of stomach cancer patients and 6 stomach cancer cell lines, by RT-qPCR. Employing expression stability analyses using NormFinder and geNorm algorithms we determined the order of performance of these reference genes and their variation values. Results This RT-qPCR study showed that there are statistically significant (p Conclusion This study validated RPL29 and RPL29-B2M as the best single reference genes and combination, for RT-qPCR analysis of 'all stomach tissues', and B2M and B2M-GAPDH as the best single reference gene and combination, for 'stomach cancer cell lines'. Use of these validated reference genes should provide more exact interpretation of differential gene expressions at transcription level in stomach cancer.

  18. Contribution of capecitabine for therapy of patients with gastroesophageal cancer: an update of recent phase III results

    Directory of Open Access Journals (Sweden)

    Putao Cen

    2008-03-01

    Full Text Available Putao Cen, Eric D Tetzlaff, Jaffer A AjaniDepartment of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center, Houston, TX, USABackground: Capecitabine, an orally administered fluoropyrimidines, is widely used in the treatment of multiple malignancies. It has been extensively evaluated in patients with gastroesophageal carcinoma. Since recent reviews have discussed phase I/II trials (Cancer 107:221–231, 2006; Drugs 67:601–610, 2007, we focus on the impact of the results of the most current phase III trials using capectiabine in the treatment of advanced gastroesophageal cancers, primarily in the first-line setting.Methods: To find published phase III trials, Medline was searched for English-language clinical trials published from 1996 through June 2007 along with relevant abstracts presented at the American Society of Clinical Oncology, and meetings of the European Cancer Conference and European Society of Medical Oncology. Only representative trials were chosen for this manuscript.Results: The most frequently investigated combinations are capecitabine with taxanes, platinols, and camptothecins. Recent results of a large phase III trial (REAL-2 in untreated patients with gastroesophageal cancer suggest that capecitabine is a non-inferior substitute for intravenous 5-fluorouracil. These results of REAL-2 trial are substantiated by a smaller phase III trial. Previous analysis of multiple trials had suggested that capecitabine, when combined in doses lower than 1250 mg/m2 twice daily, consistently resulted in lower frequency of Grade 3 or 4 toxic effects.Conclusions: Capecitabine provides much needed convenience to patients with gastroesophageal cancer. The recent data derived from two phase III trials confirm that capecitabine is a suitable substitute for intravenous 5-fluorouracil in patients whose swallowing is not greatly affected. Capecitabine remains a subject of further

  19. Circular Updates

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Circular Updates are periodic sequentially numbered instructions to debriefing staff and observers informing them of changes or additions to scientific and specimen...

  20. Website updates

    Data.gov (United States)

    National Aeronautics and Space Administration — Updates to Website: (Please add new items at the top of this description with the date of the website change) May 9, 2012: Uploaded experimental data in matlab...

  1. Initial prostate biopsy: development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay

    NARCIS (Netherlands)

    Hansen, J.; Auprich, M.; Ahyai, S.A.; Taille, A. De La; Poppel, H. van; Marberger, M.; Stenzl, A.; Mulders, P.F.A.; Huland, H.; Fisch, M.; Abbou, C.C.; Schalken, J.A.; Fradet, Y.; Marks, L.S.; Ellis, W.; Partin, A.W.; Pummer, K.; Graefen, M.; Haese, A.; Walz, J.; Briganti, A.; Shariat, S.F.; Chun, F.K.

    2013-01-01

    BACKGROUND: Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX). OBJECTIVE: To develop and validate internally the first IBX-specific PCA3-based nomo

  2. Development and internal validation of a multivariable prediction model for biochemical failure after whole-gland salvage iodine-125 prostate brachytherapy for recurrent prostate cancer

    NARCIS (Netherlands)

    Peters, M; van der Voort van Zyp, J R N; Moerland, M A; Hoekstra, C J; van de Pol, S; Westendorp, H; Maenhout, M; Kattevilder, R; Verkooijen, H M; van Rossum, P S N; Ahmed, H U; Shah, T T; Emberton, M; van Vulpen, M

    2016-01-01

    BACKGROUND: Localized recurrent prostate cancer after primary radiotherapy can be curatively treated using salvage iodine-125 ((125)I) brachytherapy. Selection is hampered by a lack of predictive factors for cancer control. This study aims to develop and internally validate a prognostic model for bi

  3. Pioglitazone prescription increases risk of bladder cancer in patients with type 2 diabetes: an updated meta-analysis.

    Science.gov (United States)

    He, Shiyao; Tang, Yu-hong; Zhao, Guobin; Yang, Xiaolong; Wang, Dehou; Zhang, Ye

    2014-03-01

    Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence regarding the association between pioglitazone and bladder cancer risk is confusing. A systematic search of databases was carried out, and other relevant papers were also identified. Then, the analyses were conducted according to the PRISMA and MOOSE guidelines. After quality assessment, nine datasets from 10 available studies were included on the basis of inclusion criteria. The incidence of bladder cancer among pioglitazone ever users and never users, pooled from four cohort and one randomized studies, were 84.51 and 66.68 per 100,000 person-years, respectively. Nine studies representing 2,596,856 diabetic patients were recognized as eligible for overall study; the result suggested an increased risk of bladder cancer in patients exposed to pioglitazone. A persistent significance was detected after being adjusted by age, gender, and use of other diabetes medications. Subgroup analyses indicated that the significantly increased incidence of bladder cancer was found in men, but not in women. Additionally, the analyses addressing increasing exposure to pioglitazone observed a dose-response relation between exclusive ever use of pioglitazone and bladder cancer in terms of cumulative duration of use and cumulative dosage. With some limitations, our results suggest an increased risk of bladder cancer in diabetic patients using pioglitazone, especially for men with long-term and high-dose exposure. Additional studies are needed to provide more precise evidences to support our results.

  4. Assessing dentists' knowledge about oral cancer: translation and linguistic validation of a standardized questionnaire from American English into German.

    Science.gov (United States)

    Hertrampf, Katrin; Wenz, Hans-Jürgen; Koller, Michael; Springer, Ingo; Jargot, Anke; Wiltfang, Jörg

    2009-10-01

    Oral cancer represents a considerable health problem with more than 10,000 new cases each year in Germany. Nevertheless, little information is available on the knowledge of dentists and the public on oral cancer. This project aims at investigating the knowledge and opinions of dentists via a questionnaire. The present article describes the translation process of an internationally accepted instrument into German. The translation was carried out by the Mapi Research Institute, Lyon, France. The translation procedure followed an established linguistic validation process, consisting of the conceptual analysis of the source instrument, a forward and backward translation, the clinicians' review, proofreading, and the finalization. The institute identified nine cultural adaptations. After forward and backward translations, the clinical reviewers suggested 16 stylistic changes, four alternative wordings, two more cultural adaptations, and five changes of nomenclature. After debriefing, the translated questionnaire involved nine stylistic changes, four alternative wordings, and 11 changes for cultural adaptation. The described translation and validation procedure guarantees a high-quality standard instrument for the evaluation of dentists' knowledge and opinions on oral cancer in Germany and prevents misinterpretations due to cultural differences, which allows an international comparison of the data.

  5. Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer

    LENUS (Irish Health Repository)

    Rexhepaj, Elton

    2010-11-23

    Abstract Background Conflicting data exist regarding the prognostic and predictive impact of survivin (BIRC5) in breast cancer. We previously reported survivin cytoplasmic-to-nuclear ratio (CNR) as an independent prognostic indicator in breast cancer. Here, we validate survivin CNR in a separate and extended cohort. Furthermore, we present new data suggesting that a low CNR may predict outcome in tamoxifen-treated patients. Methods Survin expression was assessed using immunhistochemistry on a breast cancer tissue microarray (TMA) containing 512 tumours. Whole slide digital images were captured using an Aperio XT scanner. Automated image analysis was used to identify tumour from stroma and then to quantify tumour-specific nuclear and cytoplasmic survivin. A decision tree model selected using a 10-fold cross-validation approach was used to identify prognostic subgroups based on nuclear and cytoplasmic survivin expression. Results Following optimisation of the staining procedure, it was possible to evaluate survivin protein expression in 70.1% (n = 359) of the 512 tumours represented on the TMA. Decision tree analysis predicted that nuclear, as opposed to cytoplasmic, survivin was the most important determinant of overall survival (OS) and breast cancer-specific survival (BCSS). The decision tree model confirmed CNR of 5 as the optimum threshold for survival analysis. Univariate analysis demonstrated an association between a high CNR (>5) and a prolonged BCSS (HR 0.49, 95% CI 0.29-0.81, p = 0.006). Multivariate analysis revealed a high CNR (>5) was an independent predictor of BCSS (HR 0.47, 95% CI 0.27-0.82, p = 0.008). An increased CNR was associated with ER positive (p = 0.045), low grade (p = 0.007), Ki-67 (p = 0.001) and Her2 (p = 0.026) negative tumours. Finally, a high CNR was an independent predictor of OS in tamoxifen-treated ER-positive patients (HR 0.44, 95% CI 0.23-0.87, p = 0.018). Conclusion Using the same threshold as our previous study, we have

  6. Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer

    Directory of Open Access Journals (Sweden)

    Duffy Michael J

    2010-11-01

    Full Text Available Abstract Background Conflicting data exist regarding the prognostic and predictive impact of survivin (BIRC5 in breast cancer. We previously reported survivin cytoplasmic-to-nuclear ratio (CNR as an independent prognostic indicator in breast cancer. Here, we validate survivin CNR in a separate and extended cohort. Furthermore, we present new data suggesting that a low CNR may predict outcome in tamoxifen-treated patients. Methods Survin expression was assessed using immunhistochemistry on a breast cancer tissue microarray (TMA containing 512 tumours. Whole slide digital images were captured using an Aperio XT scanner. Automated image analysis was used to identify tumour from stroma and then to quantify tumour-specific nuclear and cytoplasmic survivin. A decision tree model selected using a 10-fold cross-validation approach was used to identify prognostic subgroups based on nuclear and cytoplasmic survivin expression. Results Following optimisation of the staining procedure, it was possible to evaluate survivin protein expression in 70.1% (n = 359 of the 512 tumours represented on the TMA. Decision tree analysis predicted that nuclear, as opposed to cytoplasmic, survivin was the most important determinant of overall survival (OS and breast cancer-specific survival (BCSS. The decision tree model confirmed CNR of 5 as the optimum threshold for survival analysis. Univariate analysis demonstrated an association between a high CNR (>5 and a prolonged BCSS (HR 0.49, 95% CI 0.29-0.81, p = 0.006. Multivariate analysis revealed a high CNR (>5 was an independent predictor of BCSS (HR 0.47, 95% CI 0.27-0.82, p = 0.008. An increased CNR was associated with ER positive (p = 0.045, low grade (p = 0.007, Ki-67 (p = 0.001 and Her2 (p = 0.026 negative tumours. Finally, a high CNR was an independent predictor of OS in tamoxifen-treated ER-positive patients (HR 0.44, 95% CI 0.23-0.87, p = 0.018. Conclusion Using the same threshold as our previous study, we have

  7. Emerging treatments in management of prostate cancer: biomarker validation and endpoints for immunotherapy clinical trial design

    Directory of Open Access Journals (Sweden)

    Slovin SF

    2013-12-01

    Full Text Available Susan F SlovinGenitourinary Oncology Service, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: The rapidly emerging field of immunotherapy and the development of novel immunologic agents that have been approved in melanoma and successfully studied in lung cancer, kidney cancer, and prostate cancer have mandated that there be uniformity in clinical trial analysis beyond conventional survival endpoints and imaging. This includes some measure of determining whether the immunologic target is hit and how the treatment has impacted on the immune system in toto. While melanoma is leading the field towards these ends, there is some doubt that not all of the recent successes with immune therapies, for example, checkpoint inhibitors, will be effective for every cancer, and that the toxicities may also be different depending on the malignancy. This review serves to elucidate the current issues facing clinical investigators who perform immunologic trials targeted at patients with prostate cancer and discusses the challenges in assessing the right immunologic endpoints to demonstrate biologic/immunologic targeting leading to clinical benefit.Keywords: sipuleucel-T, prostate-specific antigen, prostate cancer, biomarkers, monoclonal antibodies, vaccines, cellular therapy

  8. Biomarker validation for intraductal papillary mucinous neoplasms of the pancreas | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): A critical component to successful cancer screening is the identification of a lesion for which intervention will result in prolonged survival or cure.The five-year survival of patients with resected stage IA pancreas cancer (the earliest identifiable lesion and |

  9. Is thrombocytosis a valid indicator of advanced stage and high mortality of gynecological cancer?

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Eskelund, Christian W.; Siersma, Volkert Dirk;

    2015-01-01

    Objective: Thrombocytosis has been associated with higher stage and mortality of cancer, however, the evidence is conflicting. We examined the stage distribution and prognosis of gynecologic cancer according to levels of prediagnostic platelet count. Methods: In a primary care resource with blood...... cell counts from more than 500,000 individuals, we identified 581 women with a primary diagnosis of gynecological cancer. We divided the pre-diagnostic mean platelet count derived from the 3-year period prior to cancer diagnosis into three categories of thrombocytosis (no, 150–400 × 109 /L; mild, N400......–550 × 109 /L; severe, N550 × 109 /L). Logistic regression models were used to calculate odds ratios (ORs) for the association of prediagnostic platelet counts with stage at diagnosis. Subsequently, we estimated hazard ratios (HRs) for all-cause or gynecological cancer-specific mortality by level...

  10. DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update

    Directory of Open Access Journals (Sweden)

    Laird-Offringa Ite A

    2008-10-01

    Full Text Available Abstract Lung cancer is the number one cancer killer in the United States. This disease is clinically divided into two sub-types, small cell lung cancer, (10–15% of lung cancer cases, and non-small cell lung cancer (NSCLC; 85–90% of cases. Early detection of NSCLC, which is the more common and less aggressive of the two sub-types, has the highest potential for saving lives. As yet, no routine screening method that enables early detection exists, and this is a key factor in the high mortality rate of this disease. Imaging and cytology-based screening strategies have been employed for early detection, and while some are sensitive, none have been demonstrated to reduce lung cancer mortality. However, mortality might be reduced by developing specific molecular markers that can complement imaging techniques. DNA methylation has emerged as a highly promising biomarker and is being actively studied in multiple cancers. The analysis of DNA methylation-based biomarkers is rapidly advancing, and a large number of potential biomarkers have been identified. Here we present a detailed review of the literature, focusing on DNA methylation-based markers developed using primary NSCLC tissue. Viable markers for clinical diagnosis must be detectable in 'remote media' such as blood, sputum, bronchoalveolar lavage, or even exhaled breath condensate. We discuss progress on their detection in such media and the sensitivity and specificity of the molecular marker panels identified to date. Lastly, we look to future advancements that will be made possible with the interrogation of the epigenome.

  11. Association between NFKB1 −94ins/del ATTG Promoter Polymorphism and Cancer Susceptibility: An Updated Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiao Yang

    2014-01-01

    Full Text Available Nuclear factor-κB is associated with the pathogenesis of numerous malignancies, and the functional polymorphism −94ins/del ATTG (rs28362491 in the human NFKB1 gene is associated with cancer risk. Previous studies on the association between the −94ins/del ATTG polymorphism and cancer risk reported conflicting results. To clarify this relationship, we performed a meta-analysis of 21 case-control studies involving 6127 cases and 9238 controls. We used pooled odds ratios (ORs with their 95% confidence intervals (95% CIs to assess the association. We found that the NFKB1 promoter −94ins/del ATTG polymorphism was significantly associated with cancer risk in four genetic models (ins/ins versus del/del, OR = 1.47, 95% CI = 1.11–1.93; dominant model, OR = 1.26, 95% CI = 1.03–1.53; recessive model, OR = 1.26, 95% CI = 1.05–1.51; ins allele versus del allele, OR = 1.19, 95% CI = 1.05–1.35. Stratified analyses revealed a significant association between the polymorphism and ovarian, oral, and prostate cancers. Similar results were determined in an Asian population and not in a Caucasian population. Thus, our results suggested that the polymorphism can contribute to cancer risk. Moreover, the polymorphism can exert race- and cancer-specific effects on cancer risk. Further large-scale and functional studies are necessary to elucidate this possible effect.

  12. Captan: transition from 'B2' to 'not likely'. How pesticide registrants affected the EPA Cancer Classification Update.

    Science.gov (United States)

    Gordon, Elliot

    2007-01-01

    On 24 November 2004 EPA changed the cancer classification of captan from a 'probable human carcinogen' (Category B2) to 'not likely' when used according to label directions. The new cancer classification considers captan to be a potential carcinogen at prolonged high doses that cause cytotoxicity and regenerative cell hyperplasia. These high doses of captan are many orders of magnitude above those likely to be consumed in the diet, or encountered by individuals in occupational or residential settings. This revised cancer classification reflects EPA's implementation of their new cancer guidelines. The procedures involved in the reclassification effort were agreed upon with EPA and involved an Independent Transparent Review as it related to four components that formed the basis of the original 1986 B2 classification: mouse tumors; rat tumors; mutagenicity; and structural similarity to other carcinogens. A Peer Review Panel organized and administered by Toxicology Excellence for Risk Assessment (TERA) met on 2-3 September 2003. The Panel concluded that captan acted through a non-mutagenic threshold mode of action that required prolonged irritation of the duodenal villi as the initial key event. EPA's Cancer Assessment Review Committee (CARC) met on 9 June 2004 and endorsed the Peer Review findings. EPA intended to have the FIFRA Scientific Advisory Panel (SAP) consider the basis for this reclassification but found the science was robust and judged that a SAP review was not warranted. Using the revised classification, the margin of exposure is approximately 1,200,000, supporting the 'not likely' characterization.

  13. Updating lung cancer mortality among a cohort of man-made mineral fibre production workers in seven European countries.

    Science.gov (United States)

    Simonato, L; Fletcher, A C; Cherrie, J; Andersen, A; Bertazzi, P A; Charney, N; Claude, J; Dodgson, J; Esteve, J; Frentzel-Beyme, R

    1986-02-01

    A historical cohort of 21,967 workers ever employed in 13 European factories manufacturing various types of man-made mineral fibres (MMMF) was observed until 1982. Overall there were 2719 deaths (standardised mortality ratio (SMR) = 111) of which 189 were from lung cancer (SMR = 125). For the glasswool and rockwool/slagwool production subcohorts the lung cancer SMRs rose with time since first exposure, exceeding 170 for the period of 30 or more years. Adjustment for regional variations in mortality substantially reduced the excess in the glasswool group, but not in the rockwool/slagwool. In neither subgroup was there any relationship of lung cancer mortality with length of employment. During the early years of rockwool/slagwool production there was the potential for much higher fibrous dust exposure than at present, because of the absence of dust suppressing oil and/or the use of a batch production process. In addition slag was widely used as a raw material. Amongst workers employed during the early phase, there were 10 lung cancer deaths giving SMRs of 270 and 244 for the periods 20-29 and 30 or more years since first exposure. This group accounts for most of the absolute excess of lung cancer for the rockwool/slagwool plants.

  14. Five-Factor Screener in the 2005 National Health Interview Survey Cancer Control Supplement: Validation Results

    Science.gov (United States)

    Risk Factor Assessment Branch staff have assessed indirectly the validity of parts of the Five-Factor Screener in two studies: NCI's Observing Protein and Energy (OPEN) Study and the Eating at America's Table Study (EATS). In both studies, multiple 24-hour recalls in conjunction with a measurement error model were used to assess validity.

  15. Validation study of the modified injection technique for internal mammary sentinel lymph node biopsy in breast cancer

    Directory of Open Access Journals (Sweden)

    Cong BB

    2015-09-01

    Full Text Available Bin-Bin Cong,1,2,* Xiao-Shan Cao,1,2,* Peng-Fei Qiu,1 Yan-Bing Liu,1 Tong Zhao,1 Peng Chen,1 Chun-Jian Wang,1 Zhao-Peng Zhang,1 Xiao Sun,1 Yong-Sheng Wang1 1Breast Cancer Center, Shandong Cancer Hospital and Institute, 2School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this study Abstract: According to the hypothesis of internal mammary sentinel lymph node (IM-SLN lymphatic drainage pattern, a modified radiotracer injection technique (periareolar intraparenchyma, high volume, and ultrasonographic guidance was established. To verify the accuracy of the hypothesis and validate the modified radiotracer injection technique and to observe whether the lymphatic drainage of the whole breast parenchyma could reach to the same IM-SLN, different tracers were injected into different locations of the breast. The validation study results showed that the correlation and the agreement of the radiotracer and the fluorescence tracer are significant (case-base, rs =0.808, P<0.001; Kappa =0.79, P<0.001. It proved that the lymphatic drainage from different location of the breast (the primary tumor, the subareolar plexus reached the same IM-SLNs and the hypothesis of IM-SLN lymphatic drainage pattern (ie, IM-SLN receives lymphatic drainage from not only the primary tumor area, but also the entire breast parenchyma. In other words, it validated the accuracy of our modified radiotracer injection technique. Keywords: breast cancer, internal mammary, sentinel lymph node biopsy, visualization rate

  16. Validity and reliability testing of two instruments to measure breast cancer patients' concerns and information needs relating to radiation therapy

    Directory of Open Access Journals (Sweden)

    Kristjanson Linda J

    2007-11-01

    Full Text Available Abstract Background It is difficult to determine the most effective approach to patient education or tailor education interventions for patients in radiotherapy without tools that assess patients' specific radiation therapy information needs and concerns. Therefore, the aim of this study was to develop psychometrically sound tools to adequately determine the concerns and information needs of cancer patients during radiation therapy. Patients and Methods Two tools were developed to (1 determine patients concerns about radiation therapy (RT Concerns Scale and (2 ascertain patient's information needs at different time point during their radiation therapy (RT Information Needs Scale. Tools were based on previous research by the authors, published literature on breast cancer and radiation therapy and information behaviour research. Thirty-one breast cancer patients completed the questionnaire on one occasion and thirty participants completed the questionnaire on a second occasion to facilitate test-retest reliability. One participant's responses were removed from the analysis. Results were analysed for content validity, internal consistency and stability over time. Results Both tools demonstrated high internal consistency and adequate stability over time. The nine items in the RT Concerns Scale were retained because they met all pre-set psychometric criteria. Two items were deleted from the RT Information Needs Scale because they did not meet content validity criteria and did not achieve pre-specified criteria for internal consistency. This tool now contains 22 items. Conclusion This paper provides preliminary data suggesting that the two tools presented are reliable and valid and would be suitable for use in trials or in the clinical setting.

  17. Validity of physical activity and cardiorespiratory fitness in the Danish cohort 'Diet, Cancer and Health - Next Generations'

    DEFF Research Database (Denmark)

    Lerche, Lene; Olsen, Anja; Petersen, Kristina Elin Nielsen

    2017-01-01

    the Danish step test, the physical activity questionnaire Active-Q and self-rated fitness against directly measured maximal oxygen uptake (VO2 max). A population based subsample (n=125) was included from the 'Diet, Cancer and Health - Next Generations' (DCH-NG) cohort which is under establishment. Validity......). When validating the questionnaire-derived measures of PA, leisure time physical activity was not correlated with VO2 max. Positive correlations were found for sports overall, but these were only significant for men: total hours per week of sports (r=0.26), MET-hours per week of sports (r=0.......28) and vigorous sports (0.28) alone were positively correlated with VO2 max. Finally, the percentage of misclassification was low for self-rated fitness (women: 9% and men: 13%). Thus, self-rated fitness was found to be a superior method to the Danish step test, as well as being less cost prohibitive and more...

  18. Evaluation and validation of candidate endogenous control genes for real-time quantitative PCR studies of breast cancer

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    Miller Nicola

    2007-11-01

    Full Text Available Abstract Background Real-time quantitative PCR (RQ-PCR forms the basis of many breast cancer biomarker studies and novel prognostic assays, paving the way towards personalised cancer treatments. Normalisation of relative RQ-PCR data is required to control for non-biological variation introduced during sample preparation. Endogenous control (EC genes, used in this context, should ideally be expressed constitutively and uniformly across treatments in all test samples. Despite widespread recognition that the accuracy of the normalised data is largely dependent on the reliability of the EC, there are no reports of the systematic validation of genes commonly used for this purpose in the analysis of gene expression by RQ-PCR in primary breast cancer tissues. The aim of this study was to identify the most suitable endogenous control genes for RQ-PCR analysis of primary breast tissue from a panel of eleven candidates in current use. Oestrogen receptor alpha (ESR1 was used a target gene to compare the effect of choice of EC on the estimate of gene quantity. Results The expression and validity of candidate ECs (GAPDH, TFRC, ABL, PPIA, HPRT1, RPLP0, B2M, GUSB, MRPL19, PUM1 and PSMC4 was determined in 6 benign and 21 malignant primary breast cancer tissues. Gene expression data was analysed using two different statistical models. MRPL19 and PPIA were identified as the most stable and reliable EC genes, while GUSB, RPLP0 and ABL were least stable. There was a highly significant difference in variance between ECs. ESR1 expression was appreciably higher in malignant compared to benign tissues and there was a significant effect of EC on the magnitude of the error associated with the relative quantity of ESR1. Conclusion We have validated two endogenous control genes, MRPL19 and PPIA, for RQ-PCR analysis of gene expression in primary breast tissue. Of the genes in current use in this field, the above combination offers increased accuracy and resolution in the

  19. Validation of three early ejaculation diagnostic tools: a composite measure is accurate and more adequate for diagnosis by updated diagnostic criteria.

    Directory of Open Access Journals (Sweden)

    Patrick Jern

    Full Text Available PURPOSE: To validate three early ejaculation diagnostic tools, and propose a new tool for diagnosis in line with proposed changes to diagnostic criteria. Significant changes to diagnostic criteria are expected in the near future. Available screening tools do not necessarily reflect proposed changes. MATERIALS AND METHODS: Data from 148 diagnosed early ejaculation patients (M age = 42.8 and 892 controls (M age = 33.1 years from a population-based sample were used. Participants responded to three different questionnaires (Premature Ejaculation Profile; Premature Ejaculation Diagnostic Tool; Multiple Indicators of Premature Ejaculation. Stopwatch measured ejaculation latency times were collected from a subsample of early ejaculation patients. We used two types of responses to the questionnaires depending on the treatment status of the patients 1 responses regarding the situation before starting pharmacological treatment and 2 responses regarding current situation. Logistic regressions and Receiver Operating Characteristics were used to assess ability of both the instruments and individual items to differentiate between patients and controls. RESULTS: All instruments had very good precision (Areas under the Curve ranging from .93-.98. A new five-item instrument (named CHecklist for Early Ejaculation Symptoms - CHEES consisting of high-performance variables selected from the three instruments had validity (Nagelkerke R (2 range .51-.79 for backwards/forwards logistic regression equal to or slightly better than any individual instrument (i.e., had slightly higher validity statistics, but these differences did not achieve statistical significance. Importantly, however, this instrument was more in line with proposed changes to diagnostic criteria. CONCLUSIONS: All three screening tools had good validity. A new 5-item diagnostic tool (CHEES based on the three instruments had equal or somewhat more favorable validity statistics compared to the other three

  20. Hydromorphone in the management of cancer-related pain: an update on routes of administration and dosage forms.

    Science.gov (United States)

    Kumar, Maansi G; Lin, Senshang

    2007-01-01

    Pain is experienced by a majority of cancer patients. As life expectancy has increased in developed and developing countries, cancer-related pain has become a major health concern. Despite the use of the three-step analgesic ladder proposed by the World Health Organization, pain still remains under treated. Morphine, the gold standard against which all other opioids has been compared is considered the first choice for management of cancer-related pain. However, recently focus has shifted to the use of hydromorphone, a semi-synthetic derivative of morphine, which is more potent, more soluble and has a comparable side-effect profile. This review focuses on the use of hydromorphone for the management of cancer-related pain emphasizing on the various routes of administration as well as dosage forms, and providing a direction for the preference of a particular route depending on the need for a rapid effect and the individual's situation. Various approaches used to modify the release of hydromorphone from the drug delivery systems with the perspective of improving patient compliance are also being discussed.

  1. An update on TroVax® for the treatment of progressive castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Abern M

    2011-05-01

    Full Text Available Michael Abern1, Howard L Kaufman2, Kalyan Latchamsetty11Department of Urology, Rush University Medical Center, Chicago, IL, USA; 2Department of General Surgery and Immunology and Microbiology, Rush University Medical Center, Chicago, IL, USAAbstract: Prostate cancer is a common human malignancy with few effective therapeutic options for treating advanced castration-resistant disease. The potential therapeutic effectiveness of immunotherapy and vaccines, in particular, has gained popularity based on the identification of prostate-associated antigens, potent expression vectors for vaccination, and data from recent clinical trials. A modified vaccinia Ankara (MVA virus expressing 5T4, a tumor-associated glycoprotein, has shown promise in preclinical studies and clinical trials in patients with colorectal and renal cell carcinoma. This review will discuss the rationale for immunotherapy in prostate cancer and describe preclinical and limited clinical data in prostate cancer for the MVA-5T4 (TroVax® vaccine.Keywords: castration resistance, prostate cancer, TroVax, vaccine

  2. Validation of proposed prostate cancer biomarkers with gene expression data: a long road to travel.

    Science.gov (United States)

    Amaro, Adriana; Esposito, Alessia Isabella; Gallina, Anna; Nees, Matthias; Angelini, Giovanna; Albini, Adriana; Pfeffer, Ulrich

    2014-09-01

    Biomarkers are important for early detection of cancer, prognosis, response prediction, and detection of residual or relapsing disease. Special attention has been given to diagnostic markers for prostate cancer since it is thought that early detection and surgery might reduce prostate cancer-specific mortality. The use of prostate-specific antigen, PSA (KLK3), has been debated on the base of cohort studies that show that its use in preventive screenings only marginally influences mortality from prostate cancer. Many groups have identified alternative or additional markers, among which PCA3, in order to detect early prostate cancer through screening, to distinguish potentially lethal from indolent prostate cancers, and to guide the treatment decision. The large number of markers proposed has led us to the present study in which we analyze these indicators for their diagnostic and prognostic potential using publicly available genomic data. We identified 380 markers from literature analysis on 20,000 articles on prostate cancer markers. The most interesting ones appeared to be claudin 3 (CLDN3) and alpha-methysacyl-CoA racemase highly expressed in prostate cancer and filamin C (FLNC) and keratin 5 with highest expression in normal prostate tissue. None of the markers proposed can compete with PSA for tissue specificity. The indicators proposed generally show a great variability of expression in normal and tumor tissue or are expressed at similar levels in other tissues. Those proposed as prognostic markers distinguish cases with marginally different risk of progression and appear to have a clinically limited use. We used data sets sampling 152 prostate tissues, data sets with 281 prostate cancers analyzed by microarray analysis and a study of integrated genomics on 218 cases to develop a multigene score. A multivariate model that combines several indicators increases the discrimination power but does not add impressively to the information obtained from Gleason

  3. Cancer treatment: fertility and sexual side effects in women

    Science.gov (United States)

    ... Alternative Names Radiotherapy - fertility; Radiation - fertility; Chemotherapy - fertility; Sexual dysfunction - cancer treatment References American Cancer Society. Fertility and women with cancer. Updated November 6, 2013. www.cancer. ...

  4. Update on taxanes in the first-line treatment of advanced non-small-cell lung cancer

    OpenAIRE

    Socinski, M A

    2014-01-01

    Based on demonstrated favourable risk–benefit profiles, taxanes remain a key component in the first-line standard of care for advanced non-small-cell lung cancer (nsclc) and nsclc subtypes. In 2012, a novel taxane, nab-paclitaxel (Abraxane: Celgene Corporation, Summit, NJ, U.S.A.), was approved, in combination with carboplatin, for the first-line treatment of locally advanced or meta-static nsclc. The approval was granted because of demonstrated improved antitumour activity and tolerability c...

  5. Altered mitochondrial DNA copy number contributes to human cancer risk: evidence from an updated meta-analysis

    Science.gov (United States)

    Hu, Liwen; Yao, Xinyue; Shen, Yi

    2016-01-01

    Accumulating epidemiological evidence indicates that the quantitative changes in human mitochondrial DNA (mtDNA) copy number could affect the genetic susceptibility of malignancies in a tumor-specific manner, but the results are still elusive. To provide a more precise estimation on the association between mtDNA copy number and risk of diverse malignancies, a meta-analysis was conducted by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95% CI). A total of 36 case-control studies involving 11,847 cases and 15,438 controls were finally included in the meta-analysis. Overall analysis of all studies suggested no significant association between mtDNA content and cancer risk (OR = 1.044, 95% CI = 0.866–1.260, P = 0.651). Subgroup analyses by cancer types showed an obvious positive association between mtDNA content and lymphoma and breast cancer (OR = 1.645, 95% CI = 1.117–2.421, P = 0.012; OR = 1.721, 95% CI = 1.130–2.622, P = 0.011, respectively), and a negative association for hepatic carcinoma. Stratified analyses by other confounding factors also found increased cancer risk in people with drinking addiction. Further analysis using studies of quartiles found that populations with the highest mtDNA content may be under more obvious risk of melanoma and that Western populations were more susceptible than Asians. PMID:27775013

  6. Endometrial cancer

    Science.gov (United States)

    ... to be at a higher risk of endometrial cancer: Colon or breast cancer Diabetes Gallbladder disease High blood ... laparoscopic - discharge Hysterectomy - vaginal - discharge Pelvic radiation - discharge Review Date 4/5/2016 Updated by: Irina Burd, ...

  7. Activated Ras signaling pathways and reovirus oncolysis: an update on the mechanism of preferential reovirus replication in cancer cells

    Directory of Open Access Journals (Sweden)

    Jun eGong

    2014-06-01

    Full Text Available The development of wild-type, unmodified Type 3 Dearing (T3D strain reovirus as an anticancer agent has currently expanded to 32 clinical trials (both completed and ongoing involving reovirus in the treatment of cancer. It has been more than 30 years since the potential of reovirus as an anticancer agent was first identified in studies that demonstrated the preferential replication of reovirus in transformed cell lines but not in normal cells. Later investigations have revealed the involvement of activated Ras signaling pathways (both upstream and downstream and key steps of the reovirus infectious cycle in promoting preferential replication in cancer cells with reovirus-induced cancer cell death occurring through necrotic, apoptotic, and autophagic pathways. There is increasing evidence that reovirus-induced antitumor immunity involving both innate and adaptive responses also contributes to therapeutic efficacy though this discussion is beyond the scope of this article. Here we review our current understanding of the mechanism of oncolysis contributing to the broad anticancer activity of reovirus. Further understanding of reovirus oncolysis is critical in enhancing the clinical development and efficacy of reovirus.

  8. Fruit and vegetable consumption and risk of bladder cancer: an updated meta-analysis of observational studies.

    Science.gov (United States)

    Liu, Huan; Wang, Xing-Chun; Hu, Guang-Hui; Guo, Zhui-Feng; Lai, Peng; Xu, Liang; Huang, Tian-Bao; Xu, Yun-Fei

    2015-11-01

    This meta-analysis was conducted to assess the association between fruit and vegetable intake and bladder cancer risk. Eligible studies published up to August 2014 were retrieved both through a computer search of PubMed, Embase and the Cochrane library and through a manual review of references. The summary relative risks with 95% confidence intervals (CIs) for the highest versus the lowest intakes of fruits and vegetables were calculated with random-effects models. Heterogeneity and publication bias were also evaluated. Potential sources of heterogeneity were detected with metaregression. Subgroup analyses and sensitivity analyses were also performed. A total of 27 studies (12 cohort and 15 case-control studies) were included in this meta-analysis. The summary relative risks for the highest versus lowest were 0.84 (95% CI: 0.72-0.96) for vegetable intake and 0.81 (95% CI: 0.73-0.89) for fruit intake. The dose-response analysis showed that the risk of bladder cancer decreased by 8% (relative risk=0.92; 95% CI: 0.87-0.97) and 9% (relative risk=0.91; 95% CI: 0.83-0.99) for every 200 g/day increment in vegetable and fruit consumption, respectively. Sensitivity analysis confirmed the stability of the results. Our findings suggest that intake of vegetables and fruits may significantly reduce the risk of bladder cancer. Further well-designed prospective studies are warranted to confirm these findings.

  9. Update on the treatment of non-small-cell lung cancer: focus on the cost-effectiveness of new agents

    Directory of Open Access Journals (Sweden)

    Vergnenègre A

    2013-04-01

    Full Text Available A Vergnenègre,1,4 I Borget,2 C Chouaid3,4 1Service de Pathologie Respiratoire et d'Allergologie, CHU Dupuytren, Limoges, France; 2Etudes et Recherche en Économie de la Santé, Institut Gustave Roussy, Villejuif, France; 3Service de Pneumologie, CHU Saint-Antoine, Paris, France; 4Inserm, U707, Paris, France Background: The incidence of lung cancer and the cost of drug treatment have increased dramatically in the last decade. This article examines the costs of new target agents, such as tyrosine kinase inhibitors (TKIs and anti-angiogenic drugs. Methods: This study uses PubMed research to focus on the topics of lung cancer, economics, and new targeted therapies. Results: The published papers only addressed TKIs and anti-angiogenic antibodies. For gefitinib, the results favored a clinical-based selection, despite the low number of studies. Erlotinib was studied in second line and as a maintenance treatment (with the studies reaching opposite conclusions in terms of cost-effectiveness. Economic analyses were not in favor of bevacizumab, but the studies on this topic were very heterogeneous. Conclusion: The economic impact of a drug depends on the health care system organization. Future clinical trials must include economic analyses, particularly with TKIs in the first line. Keywords: lung cancer, new target agents, tyrosine kinase inhibitors, anti-angiogenic, bevacizumab

  10. Breast cancer screening in women at increased risk according to different family histories: an update of the Modena Study Group experience

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    Cortesi Laura

    2006-08-01

    Full Text Available Abstract Background Breast cancer (BC detection in women with a genetic susceptibility or strong family history is considered mandatory compared with BC screening in the general population. However, screening modalities depend on the level of risk. Here we present an update of our screening programs based on risk classification. Methods We defined different risk categories and surveillance strategies to identify early BC in 1325 healthy women recruited by the Modena Study Group for familial breast and ovarian cancer. Four BC risk categories included BRCA1/2 carriers, increased, intermediate, and slightly increased risk. Women who developed BC from January 1, 1994, through December 31, 2005 (N = 44 were compared with the number of expected cases matched for age and period. BRCA1/2 carriers were identified by mutational analysis. Other risk groups were defined by different levels of family history for breast or ovarian cancer (OC. The standardized incidence ratio (SIR was used to evaluate the observed and expected ratio among groups. All statistical tests were two-sided. Results After a median follow-up of 55 months, there was a statistically significant difference between observed and expected incidence [SIR = 4.9; 95% confidence interval (CI = 1.6 to 7.6; p P P P = 0.0018 was higher than expected, while the difference between observed and expected among women at slightly increased risk was not statistically significant (SIR = 2.4, 95% CI = 0.9 to 8.3; P = .74. Conclusion The rate of cancers detected in women at high risk according to BRCA status or strong family history, as defined according to our operational criteria, was significantly higher than expected in an age-matched general population. However, we failed to identify a greater incidence of BC in the slightly increased risk group. These results support the effectiveness of the proposed program to identify and monitor individuals at high risk, whereas prospective trials are needed for

  11. Breast cancer screening in women at increased risk according to different family histories: an update of the Modena Study Group experience

    Science.gov (United States)

    Cortesi, Laura; Turchetti, Daniela; Marchi, Isabella; Fracca, Antonella; Canossi, Barbara; Rachele, Battista; Silvia, Ruscelli; Rita, Pecchi Anna; Pietro, Torricelli; Massimo, Federico

    2006-01-01

    Background Breast cancer (BC) detection in women with a genetic susceptibility or strong family history is considered mandatory compared with BC screening in the general population. However, screening modalities depend on the level of risk. Here we present an update of our screening programs based on risk classification. Methods We defined different risk categories and surveillance strategies to identify early BC in 1325 healthy women recruited by the Modena Study Group for familial breast and ovarian cancer. Four BC risk categories included BRCA1/2 carriers, increased, intermediate, and slightly increased risk. Women who developed BC from January 1, 1994, through December 31, 2005 (N = 44) were compared with the number of expected cases matched for age and period. BRCA1/2 carriers were identified by mutational analysis. Other risk groups were defined by different levels of family history for breast or ovarian cancer (OC). The standardized incidence ratio (SIR) was used to evaluate the observed and expected ratio among groups. All statistical tests were two-sided. Results After a median follow-up of 55 months, there was a statistically significant difference between observed and expected incidence [SIR = 4.9; 95% confidence interval (CI) = 1.6 to 7.6; p < 0.001]. The incidence observed among BRCA carriers (SIR = 20.3; 95% CI = 3.1 to 83.9; P < 0.001), women at increased (SIR = 4.5; 95% CI = 1.5 to 8.3; P < 0.001) or intermediate risk (SIR = 7.0, 95% CI = 2.0 to 17.1; P = 0.0018) was higher than expected, while the difference between observed and expected among women at slightly increased risk was not statistically significant (SIR = 2.4, 95% CI = 0.9 to 8.3; P = .74). Conclusion The rate of cancers detected in women at high risk according to BRCA status or strong family history, as defined according to our operational criteria, was significantly higher than expected in an age-matched general population. However, we failed to identify a greater incidence of BC in

  12. Validation of expression patterns for nine miRNAs in 204 lymph-node negative breast cancers.

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    Kristin Jonsdottir

    Full Text Available INTRODUCTION: Although lymph node negative (LN- breast cancer patients have a good 10-years survival (∼85%, most of them still receive adjuvant therapy, while only some benefit from this. More accurate prognostication of LN- breast cancer patient may reduce over- and under-treatment. Until now proliferation is the strongest prognostic factor for LN- breast cancer patients. The small molecule microRNA (miRNA has opened a new window for prognostic markers, therapeutic targets and/or therapeutic components. Previously it has been shown that miR-18a/b, miR-25, miR-29c and miR-106b correlate to high proliferation. METHODS: The current study validates nine miRNAs (miR-18a/b miR-25, miR-29c, miR-106b, miR375, miR-424, miR-505 and let-7b significantly correlated with established prognostic breast cancer biomarkers. Total RNA was isolated from 204 formaldehyde-fixed paraffin embedded (FFPE LN- breast cancers and analyzed with quantitative real-time Polymerase Chain Reaction (qPCR. Independent T-test was used to detect significant correlation between miRNA expression level and the different clinicopathological features for breast cancer. RESULTS: Strong and significant associations were observed for high expression of miR-18a/b, miR-106b, miR-25 and miR-505 to high proliferation, oestrogen receptor negativity and cytokeratin 5/6 positivity. High expression of let-7b, miR-29c and miR-375 was detected in more differentiated tumours. Kaplan-Meier survival analysis showed that patients with high miR-106b expression had an 81% survival rate vs. 95% (P = 0.004 for patients with low expression. CONCLUSION: High expression of miR-18a/b are strongly associated with basal-like breast cancer features, while miR-106b can identify a group with higher risk for developing distant metastases in the subgroup of Her2 negatives. Furthermore miR-106b can identify a group of patients with 100% survival within the otherwise considered high risk group of patients with

  13. Validity and reliability of the Korean version of the Speech Handicap Index in patients with oral cavity cancer.

    Science.gov (United States)

    Park, S S; Choi, S H; Hong, J A; Hong, Y H; Jeong, N G; Lee, S Y; Sung, M-W; Hah, J H

    2016-04-01

    The aims of this study were to evaluate the cross-cultural adaptation of the Speech Handicap Index (SHI) for Korean subjects and to determine its reliability and utility in patients with oral cavity cancer. The Korean version of the SHI was administered to 50 healthy subjects and 56 patients with speech problems resulting from treatment for oral cavity cancers. The content and construct validity, internal consistency, and test-retest reliability were examined. Healthy subject and patient group scores were compared, and the Mann-Whitney U-test was used to determine discriminatory ability. The Korean version of the SHI had high internal consistency (Cronbach's alpha=0.99) and test-retest reliability for the total and subscales: total (T) 0.98, speech (S) 0.99, and psychosocial (P) 0.97. Mean scores in the healthy group were 0.5 (T), 0.2 (S), and 0.2 (P), whereas those in the patient group were 34.3 (T), 16.6 (S), and 15.5 (P). The scores differed significantly between the groups (P<0.05). The Korean version of the SHI can be a useful tool to evaluate a patient's self-perception of their speech dysfunction in daily life and to better understand postoperative speech disorders in patients with oral cavity cancer.

  14. Updated concept of validity check when determining the customs value of goods carried in (imported) in the customs territory of Ukraine

    OpenAIRE

    Федотов, О. П.

    2016-01-01

    The article deals with a study of conceptual basics of validity check when determining the customs value of goods carried in (imported) in the customs territory of Ukraine. On the basis of the analysis of the effective legislation of Ukraine related to the state customs procedures the author revealed the issues of concern that arise when determining the «tentative indicators» of the customs value of goods that is used in the risk management system when clearing the goods carried in the custom...

  15. Validity and reliability of a dish-based, semi-quantitative food frequency questionnaire for Korean diet and cancer research.

    Science.gov (United States)

    Park, Min Kyung; Noh, Hwa Young; Song, Na Yeun; Paik, Hee Young; Park, Sohee; Joung, Hyojee; Song, Won O; Kim, Jeongseon

    2012-01-01

    This study evaluated the validity and reliability of applying a newly developed dish-based, semi-quantitative food frequency questionnaire (FFQ) for Korean diet and cancer research. The subjects in the present study were 288 Korean adults over 30 years of age who had completed two FFQs and four 3-day diet records (DRs) from May 2008 to February 2009. Student's t-tests, Chi-square tests, and Spearman's rank correlation coefficients were used to estimate and compare intakes from different dietary assessment tools. Agreement in quintiles was calculated to validate agreement between the results of the second FFQ (FFQ-2) conducted in February 2009 and the DRs. Median Spearman's correlation coefficients between the intake of nutrients and foods assessed by the FFQ-1 and FFQ-2 were 0.59 and 0.57, respectively, and the coefficients between the intake of nutrients and foods assessed by the FFQ-2 and the DRs were 0.31 and 0.29, respectively. The quintile classifications of same or adjacent quintile for intake of nutrients and foods were 64% and 65%, respectively. Misclassification into opposite quintiles occurred in less than 5% for all dietary factors. Thus this newly-developed, Korean dish-based FFQ demonstrated moderate correspondence with the four 3-day DRs. Its reliability and validity are comparable to those reported in other studies.

  16. Data quality at the Bulgarian National Cancer Registry: An overview of comparability, completeness, validity and timeliness.

    Science.gov (United States)

    Dimitrova, Nadya; Parkin, Donald Maxwell

    2015-06-01

    Reporting of neoplasms in Bulgaria has been compulsory since a directive from the Ministry of Health in 1951. The quality of cancer registry data has been estimated rather infrequently in past years. We aimed to provide a comprehensive evaluation of the quality of the data at the Bulgarian National Cancer Registry (BNCR). Quantitative and semi-quantitative methods were applied for cancers diagnosed during the whole period 1993-2010, and also for cases diagnosed in 2006-2010. The methods used include historic data methods, mortality-to-incidence ratios (M:I), capture-recapture and death-certificate methods, proportions of morphologically verified cases (MV%), death-certificate-only cases (DCO%), and cases with missing information (primary site unknown, PSU%; stage unknown, SU%). The BNCR coding and classification systems follow international standards. The overall completeness was estimated at 92.6-94.7% for the period 2006-2010, with variations between cancer sites (86.7-98.5%). During the period 1993-2010, M:I decreased to 0.5 for males and 0.4 for females, MV increased to 87.4%, DCO and SU decreased to 4.8% and 18.8%, respectively, and PSU remained at the same level of about 4% for both sexes together. Sub-analysis revealed differences by site, sex and age groups. The comparison with other registries from the region showed similar incidence rates and directions of trends: M:I, MV% and DCO% that were not significantly different. The underreporting in 2008 and 2009 due to timely publication was estimated at an overall 0.8% and 0.5%, respectively. The present review showed that the BNCR yields internationally comparable data that are reasonably accurate, timely, and close to complete, especially in recent years. This is a prerequisite for the BNCR to expand its role to more areas of cancer control.

  17. Reducing, Maintaining, or Escalating Uncertainty? The Development and Validation of Four Uncertainty Preference Scales Related to Cancer Information Seeking and Avoidance.

    Science.gov (United States)

    Carcioppolo, Nick; Yang, Fan; Yang, Qinghua

    2016-09-01

    Uncertainty is a central characteristic of many aspects of cancer prevention, screening, diagnosis, and treatment. Brashers's (2001) uncertainty management theory details the multifaceted nature of uncertainty and describes situations in which uncertainty can both positively and negatively affect health outcomes. The current study extends theory on uncertainty management by developing four scale measures of uncertainty preferences in the context of cancer. Two national surveys were conducted to validate the scales and assess convergent and concurrent validity. Results support the factor structure of each measure and provide general support across multiple validity assessments. These scales can advance research on uncertainty and cancer communication by providing researchers with measures that address multiple aspects of uncertainty management.

  18. Multifactor Screener in the 2000 National Health Interview Survey Cancer Control Supplement: Validation Results

    Science.gov (United States)

    Risk Factor Assessment Branch (RFAB) staff have assessed the validity of the Multifactor Screener in several studies: NCI's Observing Protein and Energy (OPEN) Study, the Eating at America's Table Study (EATS), and the joint NIH-AARP Diet and Health Study.

  19. Breast carcinoma metastasis suppressor gene 1 (BRMS1): update on its role as the suppressor of cancer metastases.

    Science.gov (United States)

    Kodura, Magdalena Anna; Souchelnytskyi, Serhiy

    2015-12-01

    BRMS1 was discovered over a decade ago as a potential tumor suppressor gene. In this review, we summarize the recent findings about the structure of BRMS1, mechanisms of its action and a role of BRMS1 in the cancer progression. As a suppressor of metastasis, BRMS1 has demonstrated a variety of ways to act on the cell functions, such as cell migration, invasiveness, angiogenesis, cell survival, cytoskeleton rearrangements, cell adhesion, and immune recognition. This variety of effects is a likely reason behind the robustness of anti-metastatic influence of BRMS1. Intracellular signaling mechanisms employed by BRMS1 include regulation of transcription, EGF/HER2 signaling, and expression of NF-kB, fascin, osteopontin, and IL-6. Recently reported clinical studies confirm that BRMS1 can indeed be used as a prognostic marker. Approaches to employ BRMS1 in a development of anti-cancer treatment have also been made. The studies reviewed here with respect to BRMS1 structure, cellular effects, intracellular signaling, and clinical value consolidate the importance of BRMS1 in the development of metastasis.

  20. Serum Protein Expression Profiling for Cancer Detection: Validation of a SELDI-Based Approach for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    William E. Grizzle

    2004-01-01

    Full Text Available Multiple studies have reported that analysis of serum and other bodily fluids using surface enhanced laser desorption/ionization time of flight mass spectroscopy (SELDI-TOF-MS can identify a “fingerprint” or “signature” of spectral peaks that can separate patients with a specific disease from normal control patients. Ultimately, classification by SELDI-TOF-MS relies on spectral differences in position and amplitude of resolved peaks. Since the reproducibility of quantitation, resolution and mass accuracy of the SELDI-TOF-MS, or any high throughput mass spectrometric technique, has never been determined this method has come under some skepticism as to its clinical usefulness. This manuscript describes a detailed design of a three-phase study to validate the clinical usefulness of SELDI-TOF-MS in the identification of patients with prostatic adenocarcinoma (PCA. At the end of this validation study, the usefulness of the general SELDI-TOF-MS approach to identifying patients with PCA will be demonstrated and how it compares with PCA diagnosis by measuring prostate specific antigen.

  1. Nottingham Prognostic Index Plus: Validation of a clinical decision making tool in breast cancer in an independent series.

    Science.gov (United States)

    Green, Andrew R; Soria, Daniele; Stephen, Jacqueline; Powe, Desmond G; Nolan, Christopher C; Kunkler, Ian; Thomas, Jeremy; Kerr, Gillian R; Jack, Wilma; Cameron, David; Piper, Tammy; Ball, Graham R; Garibaldi, Jonathan M; Rakha, Emad A; Bartlett, John Ms; Ellis, Ian O

    2016-01-01

    The Nottingham Prognostic Index Plus (NPI+) is a clinical decision making tool in breast cancer (BC) that aims to provide improved patient outcome stratification superior to the traditional NPI. This study aimed to validate the NPI+ in an independent series of BC. Eight hundred and eighty five primary early stage BC cases from Edinburgh were semi-quantitatively assessed for 10 biomarkers [Estrogen Receptor (ER), Progesterone Receptor (PgR), cytokeratin (CK) 5/6, CK7/8, epidermal growth factor receptor (EGFR), HER2, HER3, HER4, p53, and Mucin 1] using immunohistochemistry and classified into biological classes by fuzzy logic-derived algorithms previously developed in the Nottingham series. Subsequently, NPI+ Prognostic Groups (PGs) were assigned for each class using bespoke NPI-like formulae, previously developed in each NPI+ biological class of the Nottingham series, utilising clinicopathological parameters: number of positive nodes, pathological tumour size, stage, tubule formation, nuclear pleomorphism and mitotic counts. Biological classes and PGs were compared between the Edinburgh and Nottingham series using Cramer's V and their role in patient outcome prediction using Kaplan-Meier curves and tested using Log Rank. The NPI+ biomarker panel classified the Edinburgh series into seven biological classes similar to the Nottingham series (p > 0.01). The biological classes were significantly associated with patient outcome (p  0.01). The good PGs were similarly validated in Luminal B, Basal p53 normal, HER2+/ER- tumours and the poor PG in the Luminal N class (p > 0.01). Due to small patient numbers assigned to the remaining PGs, Luminal N, Luminal B, Basal p53 normal and HER2+/ER- classes could not be validated. This study demonstrates the reproducibility of NPI+ and confirmed its prognostic value in an independent cohort of primary BC. Further validation in large randomised controlled trial material is warranted.

  2. Development of a Novel Anti-HIF-1α Screening System Coupled with Biochemical and Biological Validation for Rapidly Selecting Potent Anti-Cancer Compounds.

    Science.gov (United States)

    Lu, Yi; Madu, Chikezie; Masters, Jordan; Lu, Andrew; Li, Liyuan

    2014-01-01

    Breast cancer (BCa) is the most diagnosed cancer and the second leading cause of cancer death in the American women. Adaptation to the hypoxic environment seen in solid tumors is critical for tumor cell survival and growth. The activation of hypoxia inducible factor-1 alpha (HIF-1α), an important master transcriptional factor that is induced and stabilized by intratumoral hypoxia, stimulates a group of HIF-1α-regulated genes including vascular endothelial growth factor (VEGF), leading tumor cells towards malignant progression. Therefore, a promising therapeutic approach to cancer treatment is to target HIF-1α. The goal of this project was to develop and validate a screening system coupled with secondary screen/validation process that has the capability to screen large numbers of potential anti-cancer small-molecule compounds based on their anti-HIF-1α activities. Breast cancer MDA-231 cells were used as the model to select potent anti-HIF-1α compounds by their abilities to inhibit transactivation of a VEGF promoter fused to a luciferase reporter gene under hypoxia. Positive compounds were then validated by a series of assays that confirm compounds' anti-HIF-1α activities including measurement of HIF-1α downstream VEGF gene expression and angiogenic ability of BCa cells. Results of our pilot screening demonstrate that this prototype screening coupled with validation system can effectively select highly potent anti-HIF-1α agents from the compound library, suggesting that this prototype screen system has the potential to be developed into a high-throughput screen (HTS) coupled with automated validation process for the screening and identification of novel and effective anti-cancer drugs based on anti-HIF-1α mechanism.

  3. Validation of the Memorial Sloan Kettering Cancer Center nomogram for predicting non-sentinel lymph node metastasis in sentinel lymph node-positive breast-cancer patients

    Directory of Open Access Journals (Sweden)

    Bi X

    2015-02-01

    Full Text Available Xiang Bi,1,* Yongsheng Wang,2 Minmin Li,1,* Peng Chen,2 Zhengbo Zhou,2 Yanbing Liu,2 Tong Zhao,2 Zhaopeng Zhang,2 Chunjian Wang,2 Xiao Sun,2 Pengfei Qiu2 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Shandong Cancer Hospital, 2Breast Cancer Center, Shandong Cancer Hospital, Jinan, People’s Republic of China *These authors contributed equally to this study Background: The main purpose of the study reported here was to validate the clinical value of the Memorial Sloan Kettering Cancer Center (MSKCC nomogram that predicts non-sentinel lymph node (SLN metastasis in SLN-positive patients with breast cancer. Methods: Data on 1,576 patients who received sentinel lymph node biopsy (SLNB at the Shandong Cancer Hospital from December 2001 to March 2014 were collected in this study, and data on 509 patients with positive SLN were analyzed to evaluate the risk factors for non-SLN metastasis. The MSKCC nomogram was used to estimate the probability of non-SLN metastasis and was compared with actual probability after grouping into deciles. A receiver-operating characteristic (ROC curve was drawn and predictive accuracy was assessed by calculating the area under the ROC curve. Results: Tumor size, histological grade, lymphovascular invasion, multifocality, number of positive SLNs, and number of negative SLNs were correlated with non-SLN metastasis (P<0.05 by univariate analysis. However, multivariate analysis showed that tumor size (P=0.039, histological grade (P=0.043, lymphovascular invasion (P=0.001, number of positive SLNs (P=0.001, and number of negative SLNs (P=0.000 were identified as independent predictors for non-SLN metastasis. The trend of actual probability in various decile groups was comparable to the predicted probability. The area under the ROC curve was 0.722. Patients with predictive values lower than 10% (97/492, 19.7% had a frequency of non-SLN metastasis of 17.5% (17/97. Conclusion: The

  4. Psychosocial consequences of cancer screening - development and validation of a questionnaire

    DEFF Research Database (Denmark)

    Brodersen, John; Thorsen, H; Kreiner, Svend

    2010-01-01

    , and reliability were established by item analysis, examining the fit between item responses and Rasch models. Results: Eight themes specifically relevant for participants in lung cancer screening results were identified: “self-blame,” “focus on symptoms,” “stigmatization,” “introvert,” “harm of smoking...... experience in lung cancer screening. Part I: “anxiety,” “behavior,” “dejection,” “sleep,” “selfblame,” “focus on airway symptoms,” “stigmatization,” “introvert,” and “harm of smoking.” Part II: “calm/relax,” “social network,” “existential values,” “impulsivity,” “empathy,” and “regretful of still smoking...

  5. Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies

    Directory of Open Access Journals (Sweden)

    Karin Hellner

    2016-08-01

    Full Text Available Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC. The functional and clinical significance of the identified mutations was examined using a combination of population-based whole genome sequencing, targeted deep sequencing, multi-center analysis of protein expression, loss of function experiments in an in-vivo reporter assay and mammalian models, and gain of function experiments in primary cultured fallopian tube epithelial (FTE cells. We identified frequent mutations involving a 40 kb distal repressor region for the key stem cell differentiation gene SOX2. In the apparently normal FTE, the region was also mutated. This was associated with a profound increase in SOX2 expression (p < 2−16, which was not found in patients without cancer (n = 108. Importantly, we show that SOX2 overexpression in FTE is nearly ubiquitous in patients with HGSOCs (n = 100, and common in BRCA1-BRCA2 mutation carriers (n = 71 who underwent prophylactic salpingo-oophorectomy. We propose that the finding of SOX2 overexpression in FTE could be exploited to develop biomarkers for detecting disease at a premalignant stage, which would reduce mortality from this devastating disease.

  6. Validation and Interrogation of Differentially Expressed and Alternatively Spliced Genes in African-American Prostate Cancer

    Science.gov (United States)

    2015-10-01

    research, cancer prevention and control, research, patient care, education and interaction with individuals and organizations outside the University...PIK3CD and MET signaling Overlap: None SPOC approved by Gloria Bass, DCI – 10/12/15 14 Other Support FREEDMAN, JENNIFER A. ACTIVE...MET signaling OVERLAP NONE Spoc approved Gloria Bass, 10.25.15 15 Other Support GEORGE, DANIEL Changes are indicated with an

  7. Neoadjuvant Chemoradiation for Distal Rectal Cancer: 5-Year Updated Results of a Randomized Phase 2 Study of Neoadjuvant Combined Modality Chemoradiation for Distal Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mohiuddin, Mohammed, E-mail: asemuddin@gmail.com [King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Paulus, Rebecca [RTOG Statistical Department, Philadelphia, Pennsylvania (United States); Mitchell, Edith [Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Hanna, Nader [Department of Surgical Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Yuen, Albert [Reading Hospital and Medical Center, Reading, Pennsylvania (United States); Nichols, Romaine [University of Florida Proton Therapy Institute, Jacksonville, Florida (United States); Yalavarthi, Salochna [Ingalls Memorial Hospital, Harvey, Illinois (United States); Hayostek, Cherie [Santa Fe Cancer Center, Santa Fe, New Mexico (United States); Willett, Christopher [Duke University Medical Center, Durham, North Carolina (United States)

    2013-07-01

    Purpose: To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers. Methods and Materials: One hundred six patients with T3/T4 distal rectal cancers were randomized in a phase 2 study. Patients received either continuous venous infusion (CVI) of 5-Fluorouracil (5-FU), 225 mg/m{sup 2} per day, 7 days per week plus pelvic hyperfractionated radiation (HRT), 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers (Arm 1), or CVI of 5-FU, 225 mg/m{sup 2} per day, Monday to Friday, plus irinotecan, 50 mg/m{sup 2} once weekly × 4, plus pelvic radiation therapy (RT), 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers (Arm 2). Surgery was performed 4 to 10 weeks later. Results: All eligible patients (n=103) are included in this analysis; 2 ineligible patients were excluded, and 1 patient withdrew consent. Ninety-eight of 103 patients (95%) underwent resection. Four patients did not undergo surgery for either disease progression or patient refusal, and 1 patient died during induction chemotherapy. The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2. The pathological complete response (pCR) rates were 30% in Arm 1 and 26% in Arm 2. Locoregional recurrence rates were 16% in Arm 1 and 17% in Arm 2. Five-year survival rates were 61% and 75% and Disease-specific survival rates were 78% and 85% for Arm1 and Arm 2, respectively. Five second primaries occurred in patients on Arm 1, and 1 second primary occurred in Arm 2. Conclusions: High rates of disease-specific survival were seen in each arm. Overall survival appears affected by the development of unrelated second cancers. The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival.

  8. [Validity of PSA density of the transition zone in the diagnosis of prostate cancer].

    Science.gov (United States)

    Anastasi, G; Magno, C; Carmignani, A; Inferrera, A; Petrelli, A; Broccio, G

    2000-12-01

    One hundred four patients (mean age 70.6 years) with prostatic specific antigen (PSA) values between 4 and 10 ng/ml (average 7.9 ng/ml), and with no suspects for neoplasia by digital rectal examination (DRE) and transrectal ultrasound (TRUS) were studied. In all patients PSA density for the entire prostate (PSAD) and PSA density for the transition zone (PSAT) were calculated. TRUS was performed using a 5 MHz probe. Prostate and transition zone volumes were obtained by ellipsoid formula. Aim of the study was to evaluate the PSAT predictivity for prostate cancer compared to the PSAD. Sixteen out of 104 patients (15.4%) had histologically confirmed prostate cancer, and 88 (84.6%) had benign prostatic hyperplasia. When cut-off for PSAD was 0.15 ng/ml/cc, specificity and sensitivity were respectively 75% and 68% with positive and negative predictive values of 54% and 17%; when cut-off for PSAT was 0.34% ng/ml/cc, sensitivity and specificity were respectively 100% and 68% with positive and negative predictive values of 60% and 18%. Our results, according to the literature data, suggest that PSAT seems to have a higher predictivity for prostate cancer than PSAD, providing an optimization for the employ of prostatic biopsy, especially for those patients with PSA values between 4 and 10 ng/ml.

  9. Putting evidence into practice: an update of evidence-based interventions for cancer-related fatigue during and following treatment.

    Science.gov (United States)

    Mitchell, Sandra A; Hoffman, Amy J; Clark, Jane C; DeGennaro, Regina M; Poirier, Patricia; Robinson, Carolene B; Weisbrod, Breanna L

    2014-01-01

    Cancer-related fatigue (CRF) has deleterious effects on physical, social, cognitive, and vocational functioning, and causes emotional and spiritual distress for patients and their families; however, it remains under-recognized and undertreated. This article critically reviews and integrates the available empirical evidence supporting the efficacy of pharmacologic and nonpharmacologic treatment approaches to CRF, highlighting new evidence since 2007 and 2009 Putting Evidence Into Practice publications. Interventions that are recommended for practice or likely to be effective in improving fatigue outcomes include exercise; screening for treatable risk factors; management of concurrent symptoms; yoga; structured rehabilitation; Wisconsin ginseng; cognitive-behavioral therapies for insomnia, pain, and depression; mindfulness-based stress reduction; and psychoeducational interventions such as anticipatory guidance, psychosocial support, and energy conservation and activity management. This information can be applied to improve the management of CRF, inform health policy and program development, shape the design of clinical trials of new therapies for CRF, and drive basic and translational research.

  10. Update on taxanes in the first-line treatment of advanced non-small-cell lung cancer.

    Science.gov (United States)

    Socinski, M A

    2014-10-01

    Based on demonstrated favourable risk-benefit profiles, taxanes remain a key component in the first-line standard of care for advanced non-small-cell lung cancer (nsclc) and nsclc subtypes. In 2012, a novel taxane, nab-paclitaxel (Abraxane: Celgene Corporation, Summit, NJ, U.S.A.), was approved, in combination with carboplatin, for the first-line treatment of locally advanced or meta-static nsclc. The approval was granted because of demonstrated improved antitumour activity and tolerability compared with solvent-based paclitaxel-carboplatin in a phase iii trial. This review focuses on the evolution of first-line taxane therapy for advanced nsclc and the new options and advances in taxane therapy that might address unmet needs in advanced nsclc.

  11. Multiparametric MRI of prostate cancer: an update on state-of-the-art techniques and their performance in detecting and localizing prostate cancer.

    Science.gov (United States)

    Hegde, John V; Mulkern, Robert V; Panych, Lawrence P; Fennessy, Fiona M; Fedorov, Andriy; Maier, Stephan E; Tempany, Clare M C

    2013-05-01

    Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided. J. Magn. Reson. Imaging 2013;37:1035-1054. © 2013 Wiley Periodicals, Inc.

  12. Validation of a questionnaire for self-assessment of sexual function and vaginal changes after gynaecological cancer

    DEFF Research Database (Denmark)

    Jensen, Pernille T; Klee, Marianne C; Thranov, Ingrid;

    2004-01-01

    of partner, sexual activity, sexual satisfaction, and body image. Seven additional items assessing current levels of sexual and vaginal problems compared to pre-diagnosis are intended to be used only once in longitudinal studies. The SVQ was validated in two ways: first, the comprehensibility of each item...... of agreement between the patients' and the observer's ratings was high (median overall agreement 0.84, range 0.46-1.00; median kappa: 0.80, range 0.52-1.00). From the 10 items applicable to all patients, three scales were hypothesized: intimacy, sexual interest and global sexual satisfaction. For sexually......The Sexual function-Vaginal changes Questionnaire (SVQ), was developed to investigate sexual and vaginal problems in gynaecological cancer patients. The instrument consists of 20 core items, measuring sexual interest, lubrication, orgasm, dyspareunia, vaginal dimensions, intimacy, sexual problems...

  13. Validation of the University of Washington quality of life questionnaires for head and neck cancer patients in India

    Directory of Open Access Journals (Sweden)

    D′cruz A

    2007-01-01

    Full Text Available Quality of life (QOL is a multidimensional construct capturing the subjective wellbeing of patients in physical, emotional, functional and social domains. Available work on post treatment QOL have only been made in western literature and less in Indian literature. Aims : To translate the UW-QOL into both Hindi and Marathi and psychometrically validate the translation in HandN cancer patients in Indian population. Settings and Design : A prospective study was done at the Tata Memorial Hospital for patients who were treated for H and N cancers. Materials and Methods : 147 patients were enrolled from January to April 2005. The study was carried out in two phases. Patients were given translated versions of the UW-QOL and EORTC QOL questionnaires pre-operatively, 15 days post-operatively and then three months post-operatively. Results : Both the Hindi and Marathi translations had strong internal consistency (Cronbach′s alpha=0.7971 and 0.7839. UW-QOL composite scores correlated well with the global questions on overall QOL in both the Hindi (r=0.69 and Marathi (r=0.66 translations and also with T-stage. QOL scores were worse three months post-operatively than pre-operatively and for patients undergoing surgery that violated the mucosa. A strong correlations was observed (r>0.50 between all similar domains on the UW-QOL and EORTC HandN35 except the saliva item on the Marathi translation, where r< 0.50, but P-values were significant. Conclusions : The Marathi and Hindi versions of the UW-QOL appear to be valid and reliable instruments for assessing the QOL in Indian population and will be a vital tool for achieving greater insight into the short- and the long term QOL.

  14. Updated Results and Patterns of Failure in a Randomized Hypofractionation Trial for High-risk Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Arcangeli, Stefano [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Strigari, Lidia [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Gomellini, Sara; Saracino, Biancamaria; Petrongari, Maria Grazia; Pinnaro, Paola; Pinzi, Valentina [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy); Arcangeli, Giorgio, E-mail: arcangeli.gio@tiscali.it [Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome (Italy)

    2012-12-01

    Purpose: To report long-term results and patterns of failure after conventional and hypofractionated radiation therapy in high-risk prostate cancer. Methods and Materials: This randomized phase III trial compared conventional fractionation (80 Gy at 2 Gy per fraction in 8 weeks) vs hypofractionation (62 Gy at 3.1 Gy per fraction in 5 weeks) in combination with 9-month androgen deprivation therapy in 168 patients with high-risk prostate cancer. Freedom from biochemical failure (FFBF), freedom from local failure (FFLF), and freedom from distant failure (FFDF) were analyzed. Results: In a median follow-up of 70 months, biochemical failure (BF) occurred in 35 of the 168 patients (21%) in the study. Among these 35 patients, local failure (LF) only was detected in 11 (31%), distant failure (DF) only in 16 (46%), and both LF and DF in 6 (17%). In 2 patients (6%) BF has not yet been clinically detected. The risk reduction by hypofractionation was significant in BF (10.3%) but not in LF and DF. We found that hypofractionation, with respect to conventional fractionation, determined only an insignificant increase in the actuarial FFBF but no difference in FFLF and FFDF, when considering the entire group of patients. However, an increase in the 5-year rates in all 3 endpoints-FFBF, FFLF, and FFDF-was observed in the subgroup of patients with a pretreatment prostate-specific antigen (iPSA) level of 20 ng/mL or less. On multivariate analysis, the type of fractionation, iPSA level, Gleason score of 4+3 or higher, and T stage of 2c or higher have been confirmed as independent prognostic factors for BF. High iPSA levels and Gleason score of 4+3 or higher were also significantly associated with an increased risk of DF, whereas T stage of 2c or higher was the only independent variable for LF. Conclusion: Our results confirm the isoeffectiveness of the 2 fractionation schedules used in this study, although a benefit in favor of hypofractionation cannot be excluded in the subgroup of

  15. Validation of cervical cancer screening methods in HIV positive women from Johannesburg South Africa.

    Directory of Open Access Journals (Sweden)

    Cynthia Firnhaber

    Full Text Available BACKGROUND: HIV-infected women are at increased risk for developing cervical cancer. Women living in resource-limited countries are especially at risk due to poor access to cervical cancer screening and treatment. We evaluated three cervical cancer screening methods to detect cervical intraepithelial neoplasia grade 2 and above (CIN 2+ in HIV-infected women in South Africa; Pap smear, visual inspection with 5% acetic acid (VIA and human papillomavirus detection (HPV. METHODS: HIV-infected women aged 18-65 were recruited in Johannesburg. A cross-sectional study evaluating three screening methods for the detection of the histologically-defined gold standard CIN-2 + was performed. Women were screened for cervical abnormalities with the Digene HC2 assay (HPV, Pap smear and VIA. VIA was performed by clinic nurses, digital photographs taken and then later reviewed by specialist physicians. The sensitivity, specificity and predictive valves for CIN-2 + were calculated using maximum likelihood estimators. RESULTS: 1,202 HIV-infected women participated, with a median age of 38 years and CD4 counts of 394 cells/mm(3. One third of women had a high grade lesion on cytology. VIA and HPV were positive in 45% and 61% of women respectively. Estimated sensitivity/specificity for HPV, Pap smear and VIA for CIN 2+ was 92%/51.4%, 75.8%/83.4% and 65.4/68.5% (nurse reading, respectively. Sensitivities were similar, and specificities appeared significantly lower for the HPV test, cytology and VIA among women with CD4 counts ≤200 cells/mm(3 as compared to CD4 counts >350 cells/mm(3. CONCLUSIONS: Although HPV was the most sensitive screening method for detecting CIN 2+, it was less specific than conventional cytology and VIA with digital imaging review. Screening programs may need to be individualized in context of the resources and capacity in each area.

  16. Validation of a Fully Automated HER2 Staining Kit in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Cathy B. Moelans

    2010-01-01

    Full Text Available Background: Testing for HER2 amplification and/or overexpression is currently routine practice to guide Herceptin therapy in invasive breast cancer. At present, HER2 status is most commonly assessed by immunohistochemistry (IHC. Standardization of HER2 IHC assays is of utmost clinical and economical importance. At present, HER2 IHC is most commonly performed with the HercepTest which contains a polyclonal antibody and applies a manual staining procedure. Analytical variability in HER2 IHC testing could be diminished by a fully automatic staining system with a monoclonal antibody.

  17. A comparison between liposomal and nonliposomal formulations of doxorubicin in the treatment of cancer: An updated review

    Directory of Open Access Journals (Sweden)

    Yik Hoe Ngan

    2016-01-01

    Full Text Available Cancer remains a major cause of hospitalization and death every year. From time to time, new formulations of anticancer drugs are available in the market and draw the concern of healthcare professionals in terms of the superiority, toxicology, and cost-effectiveness of the new formulations in comparison to the conventional formulation of the same drugs. Doxorubicin, which is a highly potent chemotherapeutic agent, comes with three formulations (pegylated liposomal, nonpegylated liposomal and nonliposomal conventional formulations. English-language literature in relation to the three formulations has been reviewed to inform the healthcare professionals regarding the differences between these formulations. In terms of efficacy, there is only one study supporting the superiority of liposomal doxorubicin, but there are more data which supports the non-inferiority of liposomal doxorubicin in comparison to conventional non-liposomal doxorubicin. It is emphasized that liposomal doxorubicin promotes better toxicology profile than nonliposomal conventional doxorubicin with an increased cost. The cost-effectiveness of liposomal doxorubicin is not well defined as there are very limited studies in this area. Apart from that, this review highlights the interpatient variability in regards to the clearance and volume of distribution following the administration of liposomal doxorubicin. In conclusion, further studies will be required to better define the superiority of liposomal formulation of doxorubicin regarding the efficacy and dose standardization of liposomal doxorubicin should be sought in the near future.

  18. Initial clinical validation of Health Heritage, a patient-facing tool for personal and family history collection and cancer risk assessment.

    Science.gov (United States)

    Baumgart, Leigh A; Postula, Kristen J Vogel; Knaus, William A

    2016-04-01

    Personal and family health histories remain important independent risk factors for cancer; however they are currently not being well collected or used effectively. Health Heritage was designed to address this need. The purpose of this study was to validate the ability of Health Heritage to identify patients appropriate for further genetic evaluation and to accurately stratify cancer risk. A retrospective chart review was conducted on 100 random patients seen at an adult genetics clinic presenting with concern for an inherited predisposition to cancer. Relevant personal and family history obtained from the patients' medical records was entered into Health Heritage. Recommendations by Health Heritage were compared to national guidelines of eligibility for genetic evaluation. Agreement between Health Heritage referral for genetic evaluation and guideline eligibility for genetic evaluation was 97% (sensitivity 98% and specificity 88%). Risk stratification for cancer was also compared between Health Heritage and those documented by a geneticist. For patients at increased risk for breast, ovarian, or colorectal cancer as determined by the geneticist, risk stratification by Health Heritage agreed 90, 93, and 75%, respectively. Discordances in risk stratification were attributed to both complex situations better handled by the geneticist and Health Heritage's adherence to incorporating all information into its algorithms. Health Heritage is a clinically valid tool to identify patients appropriate for further genetic evaluation and to encourage them to confirm the assessment and management recommendations with cancer genetic experts. Health Heritage also provides an estimate of cancer risk that is complementary to a genetics team.

  19. Fully automated fluorescent in situ hybridization (FISH staining and digital analysis of HER2 in breast cancer: a validation study.

    Directory of Open Access Journals (Sweden)

    Elise M J van der Logt

    Full Text Available HER2 assessment is routinely used to select patients with invasive breast cancer that might benefit from HER2-targeted therapy. The aim of this study was to validate a fully automated in situ hybridization (ISH procedure that combines the automated Leica HER2 fluorescent ISH system for Bond with supervised automated analysis with the Visia imaging D-Sight digital imaging platform. HER2 assessment was performed on 328 formalin-fixed/paraffin-embedded invasive breast cancer tumors on tissue microarrays (TMA and 100 (50 selected IHC 2+ and 50 random IHC scores full-sized slides of resections/biopsies obtained for diagnostic purposes previously. For digital analysis slides were pre-screened at 20x and 100x magnification for all fluorescent signals and supervised-automated scoring was performed on at least two pictures (in total at least 20 nuclei were counted with the D-Sight HER2 FISH analysis module by two observers independently. Results were compared to data obtained previously with the manual Abbott FISH test. The overall agreement with Abbott FISH data among TMA samples and 50 selected IHC 2+ cases was 98.8% (κ = 0.94 and 93.8% (κ = 0.88, respectively. The results of 50 additionally tested unselected IHC cases were concordant with previously obtained IHC and/or FISH data. The combination of the Leica FISH system with the D-Sight digital imaging platform is a feasible method for HER2 assessment in routine clinical practice for patients with invasive breast cancer.

  20. Construct validity and reliability of a real-time multidimensional smartphone app to assess pain in children and adolescents with cancer.

    Science.gov (United States)

    Stinson, Jennifer N; Jibb, Lindsay A; Nguyen, Cynthia; Nathan, Paul C; Maloney, Anne Marie; Dupuis, L Lee; Gerstle, J Ted; Hopyan, Sevan; Alman, Benjamin A; Strahlendorf, Caron; Portwine, Carol; Johnston, Donna L

    2015-12-01

    We evaluated the construct validity (including responsiveness), reliability, and feasibility of the Pain Squad multidimensional smartphone-based pain assessment application (app) in children and adolescents with cancer, using 2 descriptive studies with repeated measures. Participants (8-18 years) undergoing cancer treatment were drawn from 4 pediatric cancer centers. In study 1, 92 participants self-reported their level of pain twice daily for 2 weeks using the Pain Squad app to assess app construct validity and reliability. In study 2, 14 participants recorded their level of pain twice a day for 1 week before and 2 weeks after cancer-related surgery to determine app responsiveness. Participants in both studies completed multiple measures to determine the construct validity and feasibility of the Pain Squad app. Correlations between average weekly pain ratings on the Pain Squad app and recalled least, average, and worst weekly pain were moderate to high (0.43-0.68). Correlations with health-related quality of life and pain coping (measured with PedsQL Inventory 4.0, PedsQL Cancer Module, and Pain Coping Questionnaire) were -0.46 to 0.29. The app showed excellent internal consistency (α = 0.96). Pain ratings changed because of surgery with large effect sizes between baseline and the first week postsurgery (>0.85) and small effect sizes between baseline and the second week postsurgery (0.13-0.32). These findings provide evidence of the construct validity, reliability, and feasibility of the Pain Squad app in children and adolescents with cancer. Use of real-time data capture approaches should be considered in future studies of childhood cancer pain. A video accompanying this abstract is available online as Supplemental Digital Content at http://links.lww.com/PAIN/A169.

  1. Methylenetetrahydrofolate Reductase 677TT Genotype may be Associated with an Increased Lung Cancer Risk in North China: An Updated Meta

    Science.gov (United States)

    Liu, Nan-Bo; Li, Jun; Qi, Jia-Feng; Zhang, Zhen-Zhong; Wu, Xu; Zhang, Jun-Hua

    2014-01-01

    Background Although many epidemiology studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their associations with lung cancer (LC), definite conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of LC, we performed a meta-analysis in Chinese populations. Material/Methods Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) until 16 February 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. Results A total of 11 studies with 2487 LC cases and 3228 controls were included in this meta-analysis. Overall, no significant association was found between MTHFR C677T polymorphism and LC risk when all studies in Chinese populations were pooled into this meta-analysis. In subgroup analyses stratified by geographical location and source of controls, significantly increased risk was found in North China (T vs. C: OR=1.28, 95% CI: 1.14–1.44; TT vs. CC: OR=1.67, 95% CI: 1.33–2.10; TT + CT vs. CC, OR=1.39, 95% CI=1.15–1.69; TT vs. CC + CT: OR=1.46, 95% CI: 1.03–2.06) and in population-based studies (TT vs. CC: OR=1.37, 95% CI: 1.14–1.65; TT vs. CC + CT: OR=1.25, 95% CI: 1.07–1.45). Conclusions This meta-analysis provides evidence that MTHFR C677T polymorphism may contribute to LC development in North China. Studies with larger sample sizes and wider spectrum of populations are warranted to verify this finding. PMID:25544260

  2. Worldwide Incidence of Colorectal Cancer, Leukemia, and Lymphoma in Inflammatory Bowel Disease: An Updated Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Chelle L. Wheat

    2016-01-01

    Full Text Available Background/Aims. Inflammatory bowel disease (IBD is associated with an increased risk of colorectal cancer (CRC. In addition, there may be an association between leukemia and lymphoma and IBD. We conducted a systematic review and meta-analysis of the IBD literature to estimate the incidence of CRC, leukemia, and lymphoma in adult IBD patients. Methods. Studies were identified by a literature search of PubMed, Cochrane Library, Medline, Web of Science, Scopus, EMBASE, and ProQuest Dissertations and Theses. Pooled incidence rates (per 100,000 person-years [py] were calculated through use of a random effects model, unless substantial heterogeneity prevented pooling of estimates. Several stratified analyses and metaregression were performed to explore potential study heterogeneity and bias. Results. Thirty-six articles fulfilled the inclusion criteria. For CRC, the pooled incidence rate in CD was 53.3/100,000 py (95% CI 46.3–60.3/100,000. The incidence of leukemia was 1.5/100,000 py (95% CI −0.06–3.0/100,000 in IBD, 0.3/100,000 py (95% CI −1.0–1.6/100,000 in CD, and 13.0/100,000 py (95% CI 5.8–20.3/100,000 in UC. For lymphoma, the pooled incidence rate in CD was 0.8/100,000 py (95% CI −0.4–2.1/100,000. Substantial heterogeneity prevented the pooling of other incidence estimates. Conclusion. The incidence of CRC, leukemia, and lymphoma in IBD is low.

  3. Research updates of palliative care in cancer patients%肿瘤姑息护理研究进展

    Institute of Scientific and Technical Information of China (English)

    陈凤菊; 张凤玲

    2016-01-01

    By reviewing the latest published papers on palliative care, the article discussed the development and research progress of palliative care for people with advanced cancer, so as to provide reference for the development of palliative care specialty. According to the analysis, it suggested that by means of striving for more government support in both economic and education, raising funds through various channels, perfecting the social insurance system and volunteer′s regimen, promoting group working model, establishing standardized policies and regulations, increasing the publicity of palliative care, palliative care would move forward to a professional and normalized road, so that the people with incurable disease will receive better palliative care to improve the quality of life to the most.%通过文献回顾,了解国内外肿瘤患者姑息护理的发展现状与研究进展,为加速我国姑息护理事业的发展提供参考,提出通过增加政府在姑息护理教育与经济投入、多渠道筹措资金、健全社会保障体系、完善志愿者制度、推广团队服务模式、确立标准化政策和法规、加大姑息护理宣传等建议,促进我国肿瘤姑息护理事业专业化、规范化发展,使得无治愈希望的患者能最大限度地提高生命质量。

  4. Experimental model updating using frequency response functions

    Science.gov (United States)

    Hong, Yu; Liu, Xi; Dong, Xinjun; Wang, Yang; Pu, Qianhui

    2016-04-01

    In order to obtain a finite element (FE) model that can more accurately describe structural behaviors, experimental data measured from the actual structure can be used to update the FE model. The process is known as FE model updating. In this paper, a frequency response function (FRF)-based model updating approach is presented. The approach attempts to minimize the difference between analytical and experimental FRFs, while the experimental FRFs are calculated using simultaneously measured dynamic excitation and corresponding structural responses. In this study, the FRF-based model updating method is validated through laboratory experiments on a four-story shear-frame structure. To obtain the experimental FRFs, shake table tests and impact hammer tests are performed. The FRF-based model updating method is shown to successfully update the stiffness, mass and damping parameters of the four-story structure, so that the analytical and experimental FRFs match well with each other.

  5. Unremarked or Unperformed? Systematic Review on Reporting of Validation Efforts of Health Economic Decision Models in Seasonal Influenza and Early Breast Cancer

    NARCIS (Netherlands)

    de Boer, Pieter T.; Frederix, G.W.J.; Feenstra, Talitha L.; Vemer, Pepijn

    2016-01-01

    BACKGROUND: Transparent reporting of validation efforts of health economic models give stakeholders better insight into the credibility of model outcomes. In this study we reviewed recently published studies on seasonal influenza and early breast cancer in order to gain insight into the reporting of

  6. Unremarked or Unperformed? : Systematic Review on Reporting of Validation Efforts of Health Economic Decision Models in Seasonal Influenza and Early Breast Cancer

    NARCIS (Netherlands)

    de Boer, Pieter T; Frederix, Geert W J; Feenstra, Talitha L; Vemer, Pepijn

    2016-01-01

    BACKGROUND: Transparent reporting of validation efforts of health economic models give stakeholders better insight into the credibility of model outcomes. In this study we reviewed recently published studies on seasonal influenza and early breast cancer in order to gain insight into the reporting of

  7. Unremarked or Unperformed? : Systematic Review on Reporting of Validation Efforts of Health Economic Decision Models in Seasonal Influenza and Early Breast Cancer

    NARCIS (Netherlands)

    de Boer, Pieter T.; Frederix, Geert W. J.; Feenstra, Talitha L.; Vemer, Pepijn

    2016-01-01

    Background Transparent reporting of validation efforts of health economic models give stakeholders better insight into the credibility of model outcomes. In this study we reviewed recently published studies on seasonal influenza and early breast cancer in order to gain insight into the reporting of

  8. The Danish Barriers Questionnaire-II: preliminary validation in cancer pain patients

    DEFF Research Database (Denmark)

    Jacobsen, Ramune; Møldrup, Claus; Christrup, Lona Louring;

    2009-01-01

    of three items addressing the fear of getting tolerant to analgesic effect of pain medicine. Items related to medication side effects were analyzed as separate units. The DBQ-II total had an internal consistency of 0.87. The DBQ-II total score was related to measures of pain relief and anxiety. CONCLUSIONS...... management facilities. Thirty-three patients responded to the DBQ-II, Hospital Anxiety and Depression Scale, and Brief Pain Inventory pain severity scale. RESULTS: A factor analysis of the DBQ-II resulted in six scales. Scale one, Fatalism, consisted of three items addressing fatalistic beliefs regarding...... cancer pain management. Scale two, Immune System, consisted of three items addressing the belief that pain medications harm the immune system. Scale three, Monitor, consisted of three items addressing the fear that pain medicine masks changes in one's body. Scale four, Communication, consisted of five...

  9. The validity of skin care protocols followed by women with breast cancer receiving external radiation.

    Science.gov (United States)

    Aistars, Juli

    2006-08-01

    Skin care in women receiving external radiation to the breast varies among institutions. Studies have been conducted looking at the effect that various skin care products have on the onset and severity of radiation-induced skin reactions in those patients. Results show that no significant difference exists among these products. The practice of avoiding aluminum-based deodorant on the treated side and avoiding use of any skin care products four hours prior to treatment is not evidence based but often is part of skin care protocols for women receiving breast irradiation. A review of the literature since 1996 in the United States, Canada, United Kingdom, and Australia revealed some evidence to refute the practice but no supporting evidence. Because minimal disruption in a woman's normal hygiene routine could mitigate anxiety and improve coping during a time of extreme stress brought on by a cancer diagnosis, further research is warranted to support changing the practice.

  10. MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer

    LENUS (Irish Health Repository)

    Chang, Kah Hoong

    2010-04-29

    Abstract Background Advances in high-throughput technologies and bioinformatics have transformed gene expression profiling methodologies. The results of microarray experiments are often validated using reverse transcription quantitative PCR (RT-qPCR), which is the most sensitive and reproducible method to quantify gene expression. Appropriate normalisation of RT-qPCR data using stably expressed reference genes is critical to ensure accurate and reliable results. Mi(cro)RNA expression profiles have been shown to be more accurate in disease classification than mRNA expression profiles. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in miRNA RT-qPCR studies. Methods We adopt and report a systematic approach to identify the most stable reference genes for miRNA expression studies by RT-qPCR in colorectal cancer (CRC). High-throughput miRNA profiling was performed on ten pairs of CRC and normal tissues. By using the mean expression value of all expressed miRNAs, we identified the most stable candidate reference genes for subsequent validation. As such the stability of a panel of miRNAs was examined on 35 tumour and 39 normal tissues. The effects of normalisers on the relative quantity of established oncogenic (miR-21 and miR-31) and tumour suppressor (miR-143 and miR-145) target miRNAs were assessed. Results In the array experiment, miR-26a, miR-345, miR-425 and miR-454 were identified as having expression profiles closest to the global mean. From a panel of six miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) and two small nucleolar RNA genes (RNU48 and Z30), miR-16 and miR-345 were identified as the most stably expressed reference genes. The combined use of miR-16 and miR-345 to normalise expression data enabled detection of a significant dysregulation of all four target miRNAs between tumour and normal colorectal tissue. Conclusions Our study demonstrates that the top six most

  11. MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer.

    LENUS (Irish Health Repository)

    Chang, Kah Hoong

    2010-01-01

    BACKGROUND: Advances in high-throughput technologies and bioinformatics have transformed gene expression profiling methodologies. The results of microarray experiments are often validated using reverse transcription quantitative PCR (RT-qPCR), which is the most sensitive and reproducible method to quantify gene expression. Appropriate normalisation of RT-qPCR data using stably expressed reference genes is critical to ensure accurate and reliable results. Mi(cro)RNA expression profiles have been shown to be more accurate in disease classification than mRNA expression profiles. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in miRNA RT-qPCR studies. METHODS: We adopt and report a systematic approach to identify the most stable reference genes for miRNA expression studies by RT-qPCR in colorectal cancer (CRC). High-throughput miRNA profiling was performed on ten pairs of CRC and normal tissues. By using the mean expression value of all expressed miRNAs, we identified the most stable candidate reference genes for subsequent validation. As such the stability of a panel of miRNAs was examined on 35 tumour and 39 normal tissues. The effects of normalisers on the relative quantity of established oncogenic (miR-21 and miR-31) and tumour suppressor (miR-143 and miR-145) target miRNAs were assessed. RESULTS: In the array experiment, miR-26a, miR-345, miR-425 and miR-454 were identified as having expression profiles closest to the global mean. From a panel of six miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) and two small nucleolar RNA genes (RNU48 and Z30), miR-16 and miR-345 were identified as the most stably expressed reference genes. The combined use of miR-16 and miR-345 to normalise expression data enabled detection of a significant dysregulation of all four target miRNAs between tumour and normal colorectal tissue. CONCLUSIONS: Our study demonstrates that the top six most

  12. Validity, reliability and understanding of the EORTC-C30 and EORTC-BR23, quality of life questionnaires specific for breast cancer

    Directory of Open Access Journals (Sweden)

    Fernanda Alessandra Silva Michels

    2013-06-01

    Full Text Available Objective: To validate and assess reliability and understanding of the EORTC–C30 quality of life questionnaire and its breast cancer specific module, the EORTC-BR23. Methods: This study was conducted at the AC Camargo Cancer Hospital, São Paulo, Brazil. A total of 100 women diagnosed with breast cancer were interviewed. Internal consistency, confirmatory factorial analysis, convergent validity, construct validity and degree of understanding were examined. Reliability was assessed by comparison of means at times 1 and 2, inter-class coefficient and Bland-Altman graphics. Results: Cronbach’s alpha ranged from 0.72 to 0.86 for the EORTC-C30 and from 0.78 to 0.83 for the EORTC-BR23 questionnaire. Most questions were confirmed in the confirmatory factorial analysis. In the construct validity analysis, the questionnaires were capable of differentiating patients with or without lymphedema, apart from the symptom scales of both questionnaires. Both questionnaires presented a significant correlation in most domains of the SF-36, in the convergent validity analysis. Only a few criticisms were reported concerning questions, and the mean grade of understanding was high (C30 = 4.91 and BR23 = 4.89. The questionnaires presented good rates of reliability, with the exception of the functional scale of the C30 and the symptom scale of the BR23. Conclusions: The EORTC-C30 and EORTC-BR23 quality of life questionnaires were validated, presented good rates of reliability and are easily understood, allowing them to be used in Brazil to assess quality of life among women with breast cancer.

  13. Prediction and experimental validation of novel STAT3 target genes in human cancer cells.

    Directory of Open Access Journals (Sweden)

    Young Min Oh

    Full Text Available The comprehensive identification of functional transcription factor binding sites (TFBSs is an important step in understanding complex transcriptional regulatory networks. This study presents a motif-based comparative approach, STAT-Finder, for identifying functional DNA binding sites of STAT3 transcription factor. STAT-Finder combines STAT-Scanner, which was designed to predict functional STAT TFBSs with improved sensitivity, and a motif-based alignment to minimize false positive prediction rates. Using two reference sets containing promoter sequences of known STAT3 target genes, STAT-Finder identified functional STAT3 TFBSs with enhanced prediction efficiency and sensitivity relative to other conventional TFBS prediction tools. In addition, STAT-Finder identified novel STAT3 target genes among a group of genes that are over-expressed in human cancer cells. The binding of STAT3 to the predicted TFBSs was also experimentally confirmed through chromatin immunoprecipitation. Our proposed method provides a systematic approach to the prediction of functional TFBSs that can be applied to other TFs.

  14. Validation of algorithms to detect distant metastases in men with prostate cancer using routine registry data in Denmark

    Directory of Open Access Journals (Sweden)

    Ehrenstein V

    2015-04-01

    Full Text Available Vera Ehrenstein,1 Rohini K Hernandez,2 Merete Lund Maegbaek,1 Johnny Kahlert,1 Mary Nguyen-Nielsen,1 Mette Nørgaard,1 Alexander Liede2 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Center for Observational Research, Amgen, Thousand Oaks, CA, USA Objective: Among patients with prostate cancer, diagnostic codes for bone metastases in the Danish National Registry of Patients have a sensitivity of 44%. In an attempt to improve the sensitivity of registry-based identification of metastases from prostate cancer, we tested a series of algorithms, combining elevated prostate-specific antigen (PSA levels, use of antiresorptive therapy, and performed bone scintigraphy. Patients and methods: We randomly selected 212 men diagnosed with prostate cancer in 2005–2010 in the Central Denmark Region with prespecified PSA values, antiresorptive therapy, and bone scintigraphy who did not have a registry-based diagnostic code indicating presence of distant metastases. We defined three candidate algorithms for bone metastases: 1 PSA >50 µg/L and bone scintigraphy, 2 PSA >50 µg/L and antiresorptive therapy, and 3 PSA ≤50 µg/L with antiresorptive therapy or bone scintigraphy. An algorithm for distant metastasis site other than bone was defined as PSA >50 µg/L alone. Medical chart review was used as the reference standard to establish the presence or absence of metastases. Validity was expressed as a positive predictive value (PPV or a negative predictive value, based on whether the algorithms correctly classified metastases compared with the reference standard. Results: We identified 113 men with evidence of metastases according to the candidate algorithms, and 99 men without evidence of metastases according to the candidate algorithm. The PPVs of PSA >50 µg/L were 0.10 (95% confidence interval [CI] 0.04–0.19 for bone metastases and 0.14 (95% CI 0.07–0.24 for nonbone metastases, regardless of receipt of antiresorptive

  15. Strain measurement by cardiovascular magnetic resonance in pediatric cancer survivors: validation of feature tracking against harmonic phase imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Jimmy C. [C.S. Mott Children' s Hospital, University of Michigan Congenital Heart Center, Ann Arbor, MI (United States); University of Michigan, Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, Ann Arbor, MI (United States); University of Michigan, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Connelly, James A. [University of Michigan, Department of Pediatrics and Communicable Diseases, Division of Hematology-Oncology, Ann Arbor, MI (United States); Zhao, Lili [University of Michigan, Department of Biostatistics, Ann Arbor, MI (United States); Agarwal, Prachi P. [University of Michigan, Department of Radiology, Division of Cardiothoracic Radiology, Ann Arbor, MI (United States); Dorfman, Adam L. [University of Michigan, Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, Ann Arbor, MI (United States); University of Michigan, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States)

    2014-09-15

    Left ventricular strain may be a more sensitive marker of left ventricular dysfunction than ejection fraction in pediatric cancer survivors after anthracycline therapy, but there is limited validation of strain measurement by feature tracking on cardiovascular magnetic resonance (MR) images. To compare left ventricular circumferential and radial strain by feature tracking vs. harmonic phase imaging analysis (HARP) in pediatric cancer survivors. Twenty-six patients (20.2 ± 5.6 years old) underwent cardiovascular MR at least 5 years after completing anthracycline therapy. Circumferential and radial strain were measured at the base, midventricle and apex from short-axis myocardial tagged images by HARP, and from steady-state free precession images by feature tracking. Left ventricular ejection fraction more closely correlated with global circumferential strain by feature tracking (r = -0.63, P = 0.0005) than by HARP (r = -0.39, P = 0.05). Midventricular circumferential strain did not significantly differ by feature tracking or HARP (-20.8 ± 3.4 vs. -19.5 ± 2.5, P = 0.07), with acceptable limits of agreement. Midventricular circumferential strain by feature tracking strongly correlated with global circumferential strain by feature tracking (r = 0.87, P < 0.0001). Radial strain by feature tracking had poor agreement with HARP, particularly at higher values of radial strain. Intraobserver and interobserver reproducibility was excellent for feature tracking circumferential strain, but reproducibility was poor for feature tracking radial strain. Midventricular circumferential strain by feature tracking is a reliable and reproducible measure of myocardial deformation in patients status post anthracycline therapy, while radial strain measurements are unreliable. Further studies are necessary to evaluate potential relation to long-term outcomes. (orig.)

  16. Identification, validation, and targeting of the mutant p53-PARP-MCM chromatin axis in triple negative breast cancer.

    Science.gov (United States)

    Qiu, Wei-Gang; Polotskaia, Alla; Xiao, Gu; Di, Lia; Zhao, Yuhan; Hu, Wenwei; Philip, John; Hendrickson, Ronald C; Bargonetti, Jill

    2017-01-01

    Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous experiment-based results that poly ADP-ribose polymerase has a positive association with mutant p53 on the chromatin. Here, for the first time we report that the heterohexomeric minichromosome maintenance complex that participates in DNA replication initiation ranked as a high mutant p53-chromatin associated pathway. Enrichment analysis identified the minichromosome maintenance members 2-7. To validate this mutant p53- poly ADP-ribose polymerase-minichromosome maintenance functional axis, we experimentally depleted R273H mutant p53 and found a large reduction of the amount of minichromosome maintenance complex proteins on the chromatin. Furthermore a mutant p53-minichromosome maintenance 2 direct interaction was detected. Overexpressed mutant p53, but not wild type p53, showed a protein-protein interaction with minichromosome maintenance 2 and minichromosome maintenance 4. To target the mutant p53- poly ADP-ribose polymerase-minichromosome maintenance axis we treated cells with the poly ADP-ribose polymerase inhibitor talazoparib and the alkylating agent temozolomide and detected synergistic activation of apoptosis only in the presence of mutant p53. Furthermore when minichromosome maintenance 2-7 activity was inhibited the synergistic activation of apoptosis was blocked

  17. Updated postlicensure surveillance of the meningococcal C conjugate vaccine in England and Wales: effectiveness, validation of serological correlates of protection, and modeling predictions of the duration of herd immunity.

    Science.gov (United States)

    Campbell, Helen; Andrews, Nick; Borrow, Ray; Trotter, Caroline; Miller, Elizabeth

    2010-05-01

    Meningococcal serogroup C conjugate (MCC) vaccines were licensed in the United Kingdom more than 10 years ago based on correlates of protection that had previously been established for serogroup C-containing polysaccharide vaccines by using the serum bactericidal antibody (SBA) assay. These correlates of protection were subsequently validated against postlicensure estimates of observed vaccine effectiveness up to 7 to 9 months after the administration of the MCC vaccine. Vaccine effectiveness was, however, shown to fall significantly more than 1 year after the administration of a 3-dose course in infancy. Despite this finding, the marked impact on serogroup C disease has been sustained, with the lowest recorded incidence (0.02 case per 100,000 population) in the 2008-2009 epidemiological year, mainly due to the indirect herd immunity effect of the vaccine in reducing carriage. Updated estimates of vaccine effectiveness through 30 June 2009 confirmed high short-term protection after vaccination in infancy, at 97% (95% confidence interval [CI], 91% to 99%), falling to 68% (95% CI, -63% to 90%) more than a year after vaccination. The observed vaccine effectiveness more than 12 months postvaccination was consistent with measured declining SBA levels, but confidence intervals were imprecise; vaccine effectiveness estimates were consistent with SBA titers of 1:4 or 1:8 as correlates of long-term protection after a primary course in infants. Modeling suggested that protection against carriage persists for at least 3 years and predicted the stabilization of serogroup C disease at low levels (fewer than 50 cases per year) up to 2015-2016.

  18. Concurrent Reflectance Confocal Microscopy and Laser Doppler Flowmetry to Improve Skin Cancer Imaging: A Monte Carlo Model and Experimental Validation

    Science.gov (United States)

    Mowla, Alireza; Taimre, Thomas; Lim, Yah Leng; Bertling, Karl; Wilson, Stephen J.; Prow, Tarl W.; Soyer, H. Peter; Rakić, Aleksandar D.

    2016-01-01

    Optical interrogation of suspicious skin lesions is standard care in the management of skin cancer worldwide. Morphological and functional markers of malignancy are often combined to improve expert human diagnostic power. We propose the evaluation of the combination of two independent optical biomarkers of skin tumours concurrently. The morphological modality of reflectance confocal microscopy (RCM) is combined with the functional modality of laser Doppler flowmetry, which is capable of quantifying tissue perfusion. To realize the idea, we propose laser feedback interferometry as an implementation of RCM, which is able to detect the Doppler signal in addition to the confocal reflectance signal. Based on the proposed technique, we study numerical models of skin tissue incorporating two optical biomarkers of malignancy: (i) abnormal red blood cell velocities and concentrations and (ii) anomalous optical properties manifested through tissue confocal reflectance, using Monte Carlo simulation. We also conduct a laboratory experiment on a microfluidic channel containing a dynamic turbid medium, to validate the efficacy of the technique. We quantify the performance of the technique by examining a signal to background ratio (SBR) in both the numerical and experimental models, and it is shown that both simulated and experimental SBRs improve consistently using this technique. This work indicates the feasibility of an optical instrument, which may have a role in enhanced imaging of skin malignancies. PMID:27598157

  19. Concurrent Reflectance Confocal Microscopy and Laser Doppler Flowmetry to Improve Skin Cancer Imaging: A Monte Carlo Model and Experimental Validation

    Directory of Open Access Journals (Sweden)

    Alireza Mowla

    2016-09-01

    Full Text Available Optical interrogation of suspicious skin lesions is standard care in the management of skin cancer worldwide. Morphological and functional markers of malignancy are often combined to improve expert human diagnostic power. We propose the evaluation of the combination of two independent optical biomarkers of skin tumours concurrently. The morphological modality of reflectance confocal microscopy (RCM is combined with the functional modality of laser Doppler flowmetry, which is capable of quantifying tissue perfusion. To realize the idea, we propose laser feedback interferometry as an implementation of RCM, which is able to detect the Doppler signal in addition to the confocal reflectance signal. Based on the proposed technique, we study numerical models of skin tissue incorporating two optical biomarkers of malignancy: (i abnormal red blood cell velocities and concentrations and (ii anomalous optical properties manifested through tissue confocal reflectance, using Monte Carlo simulation. We also conduct a laboratory experiment on a microfluidic channel containing a dynamic turbid medium, to validate the efficacy of the technique. We quantify the performance of the technique by examining a signal to background ratio (SBR in both the numerical and experimental models, and it is shown that both simulated and experimental SBRs improve consistently using this technique. This work indicates the feasibility of an optical instrument, which may have a role in enhanced imaging of skin malignancies.

  20. Concurrent Reflectance Confocal Microscopy and Laser Doppler Flowmetry to Improve Skin Cancer Imaging: A Monte Carlo Model and Experimental Validation.

    Science.gov (United States)

    Mowla, Alireza; Taimre, Thomas; Lim, Yah Leng; Bertling, Karl; Wilson, Stephen J; Prow, Tarl W; Soyer, H Peter; Rakić, Aleksandar D

    2016-09-01

    Optical interrogation of suspicious skin lesions is standard care in the management of skin cancer worldwide. Morphological and functional markers of malignancy are often combined to improve expert human diagnostic power. We propose the evaluation of the combination of two independent optical biomarkers of skin tumours concurrently. The morphological modality of reflectance confocal microscopy (RCM) is combined with the functional modality of laser Doppler flowmetry, which is capable of quantifying tissue perfusion. To realize the idea, we propose laser feedback interferometry as an implementation of RCM, which is able to detect the Doppler signal in addition to the confocal reflectance signal. Based on the proposed technique, we study numerical models of skin tissue incorporating two optical biomarkers of malignancy: (i) abnormal red blood cell velocities and concentrations and (ii) anomalous optical properties manifested through tissue confocal reflectance, using Monte Carlo simulation. We also conduct a laboratory experiment on a microfluidic channel containing a dynamic turbid medium, to validate the efficacy of the technique. We quantify the performance of the technique by examining a signal to background ratio (SBR) in both the numerical and experimental models, and it is shown that both simulated and experimental SBRs improve consistently using this technique. This work indicates the feasibility of an optical instrument, which may have a role in enhanced imaging of skin malignancies.

  1. Cytochrome P450 1A1 exon 7 polymorphism and susceptibility to lung cancer in the Chinese population: an updated meta-analysis and review

    Directory of Open Access Journals (Sweden)

    Wei X

    2015-07-01

    Full Text Available Xiu-ping Wei, Jie Hu Respiratory Department, Beijing Tiantan Hospital affiliated to Capital Medical University, Beijing, People’s Republic of China Background: Although many epidemiologic studies have investigated the cytochrome P450 1A1 (CYP1A1 exon 7 gene polymorphism and its association with lung cancer (LC, definitive conclusions cannot be drawn. Objective: To clarify the effects of CYP1A1 exon 7 polymorphism on the risk of LC, an updated meta-analysis was performed in the Chinese population. Methods: Related studies were identified from PubMed, Springer Link, Ovid, the Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI, and the Chinese Biology Medicine (CBM databases until October 2014. Odds ratios (ORs with 95% confidence intervals (CIs were used to assess the strength of the associations.Results: A total of 25 articles including 3,540 LC cases and 5,284 controls were included in this meta-analysis. Overall, significant association was found between CYP1A1 exon 7 polymorphism and LC risk when all studies in the Chinese population were pooled into this meta-analysis (GG versus AA: OR =1.71, 95% CI: 1.46–2.01; GG versus AG: OR =1.41, 95% CI: 1.21–1.64; GG + AG versus AA: OR =1.37, 95% CI: 1.16–1.62; GG versus AA + AG: OR =1.52, 95% CI: 1.32–1.76. In subgroup analyses stratified by ethnicity, source of controls, and geographical locations, significantly increased risk was found in Chinese Han people, in population-based studies, in hospital-based studies, in South China, and in North China.Conclusion: This meta-analysis provides the evidence that CYP1A1 exon 7 polymorphism may contribute to LC development in the Chinese population, and studies with a larger sample size and wider population spectrum are warranted to verify this finding. Keywords: epidemiology, gene, lung neoplasm, CYP1A1 

  2. Cross-validation of three predictive tools for non-sentinel node metastases in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node

    DEFF Research Database (Denmark)

    Tvedskov, T F; Meretoja, T J; Jensen, M B;

    2014-01-01

    BACKGROUND: We cross-validated three existing models for the prediction of non-sentinel node metastases in patients with micrometastases or isolated tumor cells (ITC) in the sentinel node, developed in Danish and Finnish cohorts of breast cancer patients, to find the best model to identify patients...... who might benefit from further axillary treatment. MATERIAL AND METHOD: Based on 484 Finnish breast cancer patients with micrometastases or ITC in sentinel node a model has been developed for the prediction of non-sentinel node metastases. Likewise, two separate models have been developed in 1577...

  3. Risk prediction for breast, endometrial, and ovarian cancer in white women aged 50 y or older: derivation and validation from population-based cohort studies.

    Directory of Open Access Journals (Sweden)

    Ruth M Pfeiffer

    Full Text Available BACKGROUND: Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer. METHODS AND FINDINGS: Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health-AARP Diet and Health Study [NIH-AARP], we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI; the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96-1.04 for breast cancer and 1.08 (95% CI: 0.97-1.19 for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11-1.29. The areas under the receiver operating characteristic curves (AUCs; discriminatory power were 0.58 (95% CI: 0.57-0.59, 0.59 (95% CI: 0.56-0.63, and 0.68 (95% CI: 0.66-0.70 for the breast, ovarian, and endometrial models, respectively. CONCLUSIONS: These models predict absolute risks for breast, endometrial, and ovarian

  4. Measuring health-related quality of life in children with cancer living in mainland China: feasibility, reliability and validity of the Chinese mandarin version of PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module

    Directory of Open Access Journals (Sweden)

    Ji Yi

    2011-11-01

    Full Text Available Abstract Background The Pediatric Quality of Life Inventory (PedsQL is widely used instrument to measure pediatric health-related quality of life (HRQOL for children aged 2 to 18 years. The purpose of the current study was to investigate the feasibility, reliability and validity of the Chinese mandarin version of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in a group of Chinese children with cancer. Methods The PedsQL 4.0 Genetic Core Scales and the PedsQL 3.0 Cancer Module were administered to children with cancer (aged 5-18 years and parents of such children (aged 2-18 years. For comparison, a survey on a demographically group-matched sample of the general population with children (aged 5-18 and parents of children (aged 2-18 years was conducted with the PedsQL 4.0 Genetic Core Scales. Result The minimal mean percentage of missing item responses (except the School Functioning scale supported the feasibility of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module for Chinese children with cancer. Most of the scales showed satisfactory reliability with Cronbach's α of exceeding 0.70, and all scales demonstrated sufficient test-retest reliability. Assessing the clinical validity of the questionnaires, statistically significant difference was found between healthy children and children with cancer, and between children on-treatment versus off-treatment ≥12 months. Positive significant correlations were observed between the scores of the PedsQL 4.0 Generic Core Scale and the PedsQL 3.0 Cancer Module. Exploratory factor analysis demonstrated sufficient factorial validity. Moderate to good agreement was found between child self- and parent proxy-reports. Conclusion The findings support the feasibility, reliability and validity of the Chinese Mandarin version of PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in children with cancer living in mainland China.

  5. Regular database update logics

    NARCIS (Netherlands)

    Spruit, Paul; Wieringa, Roel; Meyer, John-Jules

    2001-01-01

    We study regular first-order update logic (FUL), which is a variant of regular dynamic logic in which updates to function symbols as well as to predicate symbols are possible. We fi1rst study FUL without making assumptions about atomic updates. Second, we look at relational algebra update logic (RAU

  6. Varieties of update

    Directory of Open Access Journals (Sweden)

    Sarah E Murray

    2014-03-01

    Full Text Available This paper discusses three potential varieties of update: updates to the common ground, structuring updates, and updates that introduce discourse referents. These different types of update are used to model different aspects of natural language phenomena. Not-at-issue information directly updates the common ground. The illocutionary mood of a sentence structures the context. Other updates introduce discourse referents of various types, including propositional discourse referents for at-issue information. Distinguishing these types of update allows a unified treatment of a broad range of phenomena, including the grammatical evidentials found in Cheyenne (Algonquian as well as English evidential parentheticals, appositives, and mood marking. An update semantics that can formalize all of these varieties of update is given, integrating the different kinds of semantic contributions into a single representation of meaning. http://dx.doi.org/10.3765/sp.7.2 BibTeX info

  7. Identification, validation, and targeting of the mutant p53-PARP-MCM chromatin axis in triple negative breast cancer

    Science.gov (United States)

    Qiu, Wei-Gang; Polotskaia, Alla; Xiao, Gu; Di, Lia; Zhao, Yuhan; Hu, Wenwei; Philip, John; Hendrickson, Ronald C.; Bargonetti, Jill

    2017-01-01

    Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous experiment-based results that poly ADP-ribose polymerase has a positive association with mutant p53 on the chromatin. Here, for the first time we report that the heterohexomeric minichromosome maintenance complex that participates in DNA replication initiation ranked as a high mutant p53-chromatin associated pathway. Enrichment analysis identified the minichromosome maintenance members 2–7. To validate this mutant p53- poly ADP-ribose polymerase-minichromosome maintenance functional axis, we experimentally depleted R273H mutant p53 and found a large reduction of the amount of minichromosome maintenance complex proteins on the chromatin. Furthermore a mutant p53-minichromosome maintenance 2 direct interaction was detected. Overexpressed mutant p53, but not wild type p53, showed a protein-protein interaction with minichromosome maintenance 2 and minichromosome maintenance 4. To target the mutant p53- poly ADP-ribose polymerase-minichromosome maintenance axis we treated cells with the poly ADP-ribose polymerase inhibitor talazoparib and the alkylating agent temozolomide and detected synergistic activation of apoptosis only in the presence of mutant p53. Furthermore when minichromosome maintenance 2–7 activity was inhibited the synergistic activation of apoptosis was

  8. Validation of Serological Antibody Profiles Against Human Papillomavirus Type 16 Antigens as Markers for Early Detection of Cervical Cancer.

    Science.gov (United States)

    Salazar-Piña, Dolores Azucena; Pedroza-Saavedra, Adolfo; Cruz-Valdez, Aurelio; Ortiz-Panozo, Eduardo; Maldonado-Gama, Minerva; Chihu-Amparan, Lilia; Rodriguez-Ocampo, Angelica Nallelhy; Orozco-Fararoni, Emilia; Esquivel-Guadarrama, Fernando; Gutierrez-Xicotencatl, Lourdes

    2016-02-01

    Cervical cancer (CC) is the second most frequent neoplasia among women worldwide. Cancer prevention programs around the world have used the Papanicolaou (Pap) smear as the primary diagnostic test to reduce the burden of CC. Nevertheless, such programs have not been effective in developing countries, thus leading to research on alternative tests for CC screening. During the virus life cycle and in the process toward malignancy, different human papillomavirus (HPV) proteins are expressed, and they induce a host humoral immune response that can be used as a potential marker for different stages of the disease. We present a new Slot blot assay to detect serum antibodies against HPV16 E4, E7, and VLPs-L1 antigens. The system was validated with sera from a female population (n = 485) aged 18 to 64 years referred to the dysplasia clinic at the General Hospital in Cuautla, Morelos, Mexico. To evaluate the clinical performance of the serological markers, the sensitivity, specificity, positive, and negative predictive values and receiver-operating characteristic curves (for antibodies alone or in combination) were calculated in groups of lesions of increasing severity. The results showed high prevalence of anti-E4 (73%) and anti-E7 (80%) antibodies in the CC group. Seropositivity to 1, 2, or 3 antigens showed associations of increasing magnitude with CC (odds ratio [OR] = 12.6, 19.9, and 58.5, respectively). The highest association with CC was observed when the analysis was restricted to only anti-E4+E7 antibodies (OR = 187.7). The best clinical performance to discriminate CC from cervical intraepithelial neoplasia 2 to 3 was the one for the combination of anti-E4 and/or anti-E7 antibodies, which displayed high sensitivity (93.3%) and moderate specificity (64.1%), followed by anti-E4 and anti-E7 antibodies (73.3% and 80%; 89.6% and 66%, respectively). In addition, the sensitivity of anti-E4 and/or anti-E7 antibodies is high at any time of sexual activity (TSA

  9. Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities

    Science.gov (United States)

    Wang, Bi-Dar; Ceniccola, Kristin; Yang, Qi; Andrawis, Ramez; Patel, Vyomesh; Ji, Youngmi; Rhim, Johng; Olender, Jacqueline; Popratiloff, Anastas; Latham, Patricia; Lai, Yinglei; Patierno, Steven R.; Lee, Norman H

    2015-01-01

    Purpose African Americans (AA) exhibit higher rates of prostate cancer (PCa) incidence and mortality compared to European American (EA) men. In addition to socioeconomic influences, biological factors are believed to play a critical role in PCa disparities. We investigated whether population-specific and -enriched miRNA-mRNA interactions might contribute to PCa disparities. Experimental Design Integrative genomics was employed, combining miRNA and mRNA profiling, miRNA target prediction, pathway analysis and functional validation, to map miRNA-mRNA interactions associated with PCa disparities. Results We identified 22 AA-specific and 18 EA-specific miRNAs in PCa versus patient-matched normal prostate, and 10 ‘AA-enriched/-depleted’ miRNAs in AA PCa versus EA PCa comparisons. Many of these population-specific/-enriched miRNAs could be paired with target mRNAs that exhibited an inverse pattern of differential expression. Pathway analysis revealed epidermal growth factor receptor (EGFR or ERBB) signaling as a critical pathway significantly regulated by AA-specific/-enriched mRNAs and miRNA-mRNA pairings. Novel miRNA-mRNA pairings were validated by qRT-PCR, western blot and/or IHC analyses in PCa specimens. Loss/gain of function assays performed in population-specific PCa cell lines confirmed miR-133a/MCL1, miR-513c/STAT1, miR-96/FOXO3A, miR-145/ITPR2 and miR-34a/PPP2R2A as critical miRNA-mRNA pairings driving oncogenesis. Manipulating the balance of these pairings resulted in decreased proliferation and invasion, and enhanced sensitization to docetaxel-induced cytotoxicity in AA PCa cells. Conclusion Our data suggest that AA-specific/-enriched miRNA-mRNA pairings may play a critical role in the activation of oncogenic pathways in AA PCa. Our findings also suggest that miR-133a/MCL1, miR-513c/STAT1 and miR-96/FOXO3A may have clinical significance in the development of novel strategies for treating aggressive PCa. PMID:26089375

  10. Development and Validation of an Instrument for Measuring Attitudes and Beliefs about Complementary and Alternative Medicine (CAM Use among Cancer Patients

    Directory of Open Access Journals (Sweden)

    Jun J. Mao

    2012-01-01

    Full Text Available Despite cancer patients' extensive use of complementary and alternative medicine (CAM, validated instruments to measure attitudes, and beliefs predictive of CAM use are lacking. We aimed at developing and validating an instrument, attitudes and beliefs about CAM (ABCAM. The 15-item instrument was developed using the theory of planned behavior (TPB as a framework. The literature review, qualitative interviews, expert content review, and cognitive interviews were used to develop the instrument, which was then administered to 317 outpatient oncology patients. The ABCAM was best represented as a 3-factor structure: expected benefits, perceived barriers, and subjective norms related to CAM use by cancer patients. These domains had Eigenvalues of 4.79, 2.37, and 1.43, and together explained over 57.2% of the variance. The 4-item expected benefits, 7-item perceived barriers, and 4-item subjective norms domain scores, each had an acceptable internal consistency (Cronbach's alpha of 0.91, 0.76, and 0.75, respectively. As expected, CAM users had higher expected benefits, lower perceived barriers, and more positive subjective norms (all <0.001 than those who did not use CAM. Our study provides the initial evidence that the ABCAM instrument produced reliable and valid scores that measured attitudes and beliefs related to CAM use among cancer patients.

  11. Sipuleucel-T for therapy of asymptomatic or minimally symptomatic, castrate-refractory prostate cancer: an update and perspective among other treatments

    OpenAIRE

    Gupta SG; Carballido ES; Fishman M

    2011-01-01

    Shilpa Gupta, Estrella Carballido, Mayer FishmanMoffitt Cancer Center and Research Institute, Tampa, FL, USAAbstract: Sipuleucel-T is an autologous cell immunotherapy for castrate-refractory prostate cancer, with US Food and Drug Administration (FDA) approval in asymptomatic or minimally symptomatic prostate cancer. In this review we address the background of prostate cancer incidence and other available therapy onto which sipuleucel-T treatment has been added, with discussion of hormone-ther...

  12. Predicting Overall Survival After Stereotactic Ablative Radiation Therapy in Early-Stage Lung Cancer: Development and External Validation of the Amsterdam Prognostic Model

    Energy Technology Data Exchange (ETDEWEB)

    Louie, Alexander V., E-mail: Dr.alexlouie@gmail.com [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, Massachusetts (United States); Haasbeek, Cornelis J.A. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Mokhles, Sahar [Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam (Netherlands); Rodrigues, George B. [Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Stephans, Kevin L. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Lagerwaard, Frank J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Palma, David A. [Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Videtic, Gregory M.M. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Warner, Andrew [Department of Radiation Oncology, London Regional Cancer Program, University of Western Ontario, London, Ontario (Canada); Takkenberg, Johanna J.M. [Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam (Netherlands); Reddy, Chandana A. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Maat, Alex P.W.M. [Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam (Netherlands); Woody, Neil M. [Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio (United States); Slotman, Ben J.; Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)

    2015-09-01

    Purpose: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). Methods and Materials: A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS. A nomogram for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n=193) and SABR (n=543) datasets. Results: RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r{sup 2}=0.97) and external SABR (r{sup 2}=0.79) and surgical cohorts (r{sup 2}=0.91). Conclusions: The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities.

  13. 3D models of epithelial-mesenchymal transition in breast cancer metastasis: high-throughput screening assay development, validation, and pilot screen.

    Science.gov (United States)

    Li, Qun; Chen, Chaoyu; Kapadia, Amit; Zhou, Qiong; Harper, Mary Kay; Schaack, Jerome; LaBarbera, Daniel V

    2011-02-01

    Despite advancements in therapies developed for the treatment of cancer, patient prognosis and mortality rates have improved minimally, and metastasis remains the primary cause of cancer mortality worldwide. An underlying mechanism promoting metastasis in many types of cancer is epithelial-mesenchymal transition (EMT). Here the authors report a novel 3D model of EMT and metastatic breast cancer suitable for high-throughput screening (HTS) drug discovery. The primary assay incorporates the expression of the prognostic biomarker vimentin, as a luciferase reporter of EMT, in basil-like/triple-negative MDA-MB-231 breast carcinoma spheroids. Using this model, the authors developed a number of known antitumor agents as control modulators of EMT. U0126, PKC412, PF2341066, dasatinib, and axitinib downregulated vimentin expression by 70% to 90% as compared to untreated spheroids. Counterassays were developed to measure spheroid viability and the invasive potential of MDA-MB-231 spheroids after small-molecule treatment and used to confirm hits from primary screening. Finally, the authors conducted a pilot screen to validate this model for HTS using a purified library of marine secondary metabolites. From 230 compounds screened, they obtained a Z' score of 0.64, indicative of an excellent assay, and confirmed 4 hits, including isonaamidine B, papuamine, mycalolide E, and jaspamide. This HTS model demonstrates the potential to identify small-molecule modulators of EMT that could be used to discover novel antimetastatic agents for the treatment of cancer.

  14. Targeted Sequencing for Discovery and Validation of DNA Methylation Markers of Colon Cancer Metastasis — EDRN Public Portal

    Science.gov (United States)

    Colon cancer is the second leading cause of cancer death in the United States. A key issue in treating colon cancer patients is inability to accurately predict tumors that have metastatic potential and require adjuvant chemotherapy. This project will test the model that tumor metastases arise from intra-tumor heterogeneity generated by DNA methylation events, and that detecting these events can provide a predictve signature of tumors with poor outcome

  15. Validation of the Mexican-Spanish version of the EORTC QLQ-C30 and BR23 questionnaires to assess health-related quality of life in Mexican women with breast cancer.

    Science.gov (United States)

    Cerezo, O; Oñate-Ocaña, L F; Arrieta-Joffe, P; González-Lara, F; García-Pasquel, M J; Bargalló-Rocha, E; Vilar-Compte, D

    2012-09-01

    The aim of this study was to validate the Mexican-Spanish version of The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 questionnaire. The translation procedure followed EORTC guidelines. QLQ-C30 and QLQ-BR23 instruments were completed by Mexican women with breast cancer, attending a teaching referral cancer centre from February 2009 to January 2010. Patients were divided in two groups: (1) Patients with early stage of breast cancer; and (2) Patients with locally advanced breast cancer (LABC). Reliability and validity tests were performed, and validity over time (responsiveness) was conducted in a subset of patients. Two hundred and thirty-four women (mean age, 52.3 years) completed both questionnaires. Convergent and divergent validity was adequate. Cronbach's alpha of all multi-item scales showed values ≥0.7 except for Cognitive and Breast symptoms scales (0.52 and 0.65 respectively). Patients with early stages (n= 77) showed better functional scores and lower symptoms scores than patients with LABC (n= 157). Score means variation after responsiveness analysis demonstrated high sensitivity to change after breast cancer surgery. The Mexican-Spanish version of the EORTC QLQ-BR23 questionnaire is a valid and suitable instrument to estimate HRQL in patients with breast cancer.

  16. The development and validation of a CT-based radiomics signature for the preoperative discrimination of stage I-II and stage III-IV colorectal cancer

    Science.gov (United States)

    He, Lan; Chen, Xin; Ma, Zelan; Dong, Di; Tian, Jie; Liang, Changhong; Liu, Zaiyi

    2016-01-01

    Objectives To investigative the predictive ability of radiomics signature for preoperative staging (I-IIvs.III-IV) of primary colorectal cancer (CRC). Methods This study consisted of 494 consecutive patients (training dataset: n=286; validation cohort, n=208) with stage I–IV CRC. A radiomics signature was generated using LASSO logistic regression model. Association between radiomics signature and CRC staging was explored. The classification performance of the radiomics signature was explored with respect to the receiver operating characteristics(ROC) curve. Results The 16-feature-based radiomics signature was an independent predictor for staging of CRC, which could successfully categorize CRC into stage I-II and III-IV (p <0.0001) in training and validation dataset. The median of radiomics signature of stage III-IV was higher than stage I-II in the training and validation dataset. As for the classification performance of the radiomics signature in CRC staging, the AUC was 0.792(95%CI:0.741-0.853) with sensitivity of 0.629 and specificity of 0.874. The signature in the validation dataset obtained an AUC of 0.708(95%CI:0.698-0.718) with sensitivity of 0.611 and specificity of 0.680. Conclusions A radiomics signature was developed and validated to be a significant predictor for discrimination of stage I-II from III-IV CRC, which may serve as a complementary tool for the preoperative tumor staging in CRC. PMID:27120787

  17. The SDF-1 rs1801157 Polymorphism is Associated with Cancer Risk: An Update Pooled Analysis and FPRP Test of 17,876 Participants.

    Science.gov (United States)

    Tong, Xiang; Ma, Yao; Deng, Huajiang; Wang, Xixi; Liu, Sitong; Yan, Zhipeng; Peng, Shifeng; Fan, Hong

    2016-06-06

    The stromal cell derived factor-1 (SDF-1) rs1801157 gene polymorphism has been implicated in susceptibility to cancer, but the results were inconclusive. The current study was to precisely investigate the association between SDF-1 rs1801157 polymorphism and cancer risk using meta-analysis and the false positive report probability (FPRP) test. All 17,876 participants were included in the study. The meta-analysis results indicated a significant association between the SDF-1 rs1801157 polymorphism and cancer risk. By subgroup analyses, the results detected that the SDF-1 rs1801157 polymorphism was associated with cancer susceptibility among Asians and Caucasians. Additionally, we also found significant associations between the SDF-1 rs1801157 polymorphism and susceptibility to different types of cancer. However, to avoid a "false positive report", we further investigated the significant associations observed in the present meta-analysis using the FPRP test. Interestingly, the results of the FPRP test indicated that only 4 gene models were truly associated with cancer risk, especially in Asians. Moreover, we confirmed that the SDF-1 rs1801157 gene polymorphism was only associated with lung and urologic cancer risk. In summary, this study suggested that the SDF-1 rs1801157 polymorphism may serve as a risk factor for cancer development among Asians, especially an increased risk of urologic and lung cancers.

  18. Validation of the euroqol five-dimensions - three-level quality of life instrument in a classical Indian language (Odia and its use to assess quality of life and health status of cancer patients in Eastern India

    Directory of Open Access Journals (Sweden)

    Swagata Tripathy

    2015-01-01

    Conclusions: The Odia version of the EQ5D has good reliability and validity for the measurement of health status in cancer and outpatient department patients. Cancer patients in this part of the country have a poor QOL and may need a closer look at pain management and improved societal support systems.

  19. Quantum-dot-based suspension microarray for multiplex detection of lung cancer markers: preclinical validation and comparison with the Luminex xMAP® system

    Science.gov (United States)

    Bilan, Regina; Ametzazurra, Amagoia; Brazhnik, Kristina; Escorza, Sergio; Fernández, David; Uríbarri, María; Nabiev, Igor; Sukhanova, Alyona

    2017-01-01

    A novel suspension multiplex immunoassay for the simultaneous specific detection of lung cancer markers in bronchoalveolar lavage fluid (BALF) clinical samples based on fluorescent microspheres having different size and spectrally encoded with quantum dots (QDEM) was developed. The designed suspension immunoassay was validated for the quantitative detection of three lung cancer markers in BALF samples from 42 lung cancer patients and 10 control subjects. Tumor markers were detected through simultaneous formation of specific immune complexes consisting of a capture molecule, the target antigen, and biotinylated recognition molecule on the surface of the different QDEM in a mixture. The immune complexes were visualized by fluorescently labeled streptavidin and simultaneously analyzed using a flow cytometer. Preclinical validation of the immunoassay was performed and results were compared with those obtained using an alternative 3-plex immunoassay based on Luminex xMAP® technology, developed on classical organic fluorophores. The comparison showed that the QDEM and xMAP® assays yielded almost identical results, with clear discrimination between control and clinical samples. Thus, developed QDEM technology can become a good alternative to xMAP® assays permitting analysis of multiple protein biomarkers using conventional flow cytometers. PMID:28300171

  20. Quantum-dot-based suspension microarray for multiplex detection of lung cancer markers: preclinical validation and comparison with the Luminex xMAP® system

    Science.gov (United States)

    Bilan, Regina; Ametzazurra, Amagoia; Brazhnik, Kristina; Escorza, Sergio; Fernández, David; Uríbarri, María; Nabiev, Igor; Sukhanova, Alyona

    2017-03-01

    A novel suspension multiplex immunoassay for the simultaneous specific detection of lung cancer markers in bronchoalveolar lavage fluid (BALF) clinical samples based on fluorescent microspheres having different size and spectrally encoded with quantum dots (QDEM) was developed. The designed suspension immunoassay was validated for the quantitative detection of three lung cancer markers in BALF samples from 42 lung cancer patients and 10 control subjects. Tumor markers were detected through simultaneous formation of specific immune complexes consisting of a capture molecule, the target antigen, and biotinylated recognition molecule on the surface of the different QDEM in a mixture. The immune complexes were visualized by fluorescently labeled streptavidin and simultaneously analyzed using a flow cytometer. Preclinical validation of the immunoassay was performed and results were compared with those obtained using an alternative 3-plex immunoassay based on Luminex xMAP® technology, developed on classical organic fluorophores. The comparison showed that the QDEM and xMAP® assays yielded almost identical results, with clear discrimination between control and clinical samples. Thus, developed QDEM technology can become a good alternative to xMAP® assays permitting analysis of multiple protein biomarkers using conventional flow cytometers.

  1. MicroRNA Expression Profiling to Identify and Validate Reference Genes for the Relative Quantification of microRNA in Rectal Cancer

    DEFF Research Database (Denmark)

    Eriksen, Anne Haahr Mellergaard; Andersen, Rikke Fredslund; Pallisgaard, Niels;

    2016-01-01

    management. Real-time quantitative polymerase chain reaction (RT-qPCR) is commonly used, when measuring miRNA expression. Appropriate normalisation of RT-qPCR data is important to ensure reliable results. The aim of the present study was to identify stably expressed miRNAs applicable as normaliser candidates...... expressed miRNAs for subsequent validation. In the first validation experiment, a panel of miRNAs were analysed on 25 pairs of micro dissected rectal cancer tissue and adjacent stroma. Subsequently, the same miRNAs were analysed in 28 pairs of rectal cancer tissue and normal rectal mucosa. RESULTS: From...... the miRNA profiling experiment, miR-645, miR-193a-5p, miR-27a and let-7g were identified as stably expressed, both in malignant and stromal tissue. In addition, NormFinder confirmed high expression stability for the four miRNAs. In the RT-qPCR based validation experiments, no significant difference...

  2. Clinical Practice Guidelines in Breast Cancer by Chinese Anti-Cancer Association (2015 version):interpretation of updates in terms of systemic treatment%2015版《中国抗癌协会乳腺癌诊治指南与规范》:药物治疗策略的解读

    Institute of Scientific and Technical Information of China (English)

    王碧芸; 龚成成; 胡夕春

    2016-01-01

    为推动中国乳腺癌的规范化诊治,中国抗癌协会乳腺癌专业委员会于2007年发布了第1版《中国抗癌协会乳腺癌诊治指南与规范》(简称《指南》),并结合乳腺癌领域最新循证医学进展每2年进行1次更新,指导中国乳腺癌的诊断与治疗。最新公布的2015版《指南》从乳腺癌筛查、影像诊断、病理诊断、手术及全身治疗等方面对乳腺癌临床诊治策略进行了规范。本文从乳腺癌的内分泌治疗、抗HER-2分子靶向治疗、化疗与骨保护治疗的角度出发,对2015版《指南》药物治疗策略的更新内容进行了解读。%In order to standardize the management of breast cancer, Chinese Anti-Cancer Association ( CACA) issued the first edition of Clinical Practice Guidelines in Breast Cancer in 2007 and updates it every other year based on latest evidences. The newly published CACA Clinical Practice Guidelines in Breast Cancer in 2015 covers the overall management of breast cancer including screening, imaging, pathology, surgery and systemic treatment. This article mainly focused on the updates of systemic treatment for breast cancer patients in 2015 version, with regard to endocrine therapy, anti-HER-2 molecular targeted therapy, chemotherapy and bone protection.

  3. [Retinoblastoma update].

    Science.gov (United States)

    Aerts, I; Lumbroso-Le Rouic, L; Gauthier-Villars, M; Brisse, H; Doz, F

    2016-01-01

    Retinoblastoma is the most common intraocular malignancy of infancy with an incidence of 1/15,000 births. Sixty percent of retinoblastomas are unilateral, with a median age at diagnosis of 2 years, and in most cases they are not hereditary. Retinoblastoma is bilateral in 40% of cases, with an earlier median age at diagnosis of 1 year. All bilateral and multifocal unilateral forms are hereditary and are part of a genetic cancer predisposition syndrome. All children with a bilateral or familial form, and 10-15% of children with a unilateral form, constitutionally carry an RB1 gene mutation. The two most frequent symptoms at diagnosis are leukocoria and strabismus. Diagnosis is made by fundoscopy, with ultrasound and magnetic resonance imaging (MRI) contributing both to diagnosis and assessment of the extension of the disease. Treatment of patients with retinoblastoma must take into account the various aspects of the disease (unilateral/bilateral, size, location), the risks for vision, and the possible hereditary nature of the disease. The main prognostic aspects are still early detection and adapted coverage by a multidisciplinary, highly specialized team. Enucleation is still often necessary in unilateral disease; the decision for adjuvant treatment is made according to the histological risk factors. The most important recent therapeutic advances concern conservative treatment, which is proposed for at least one of the two eyes in most bilateral cases: laser alone or in combination with chemotherapy, cryotherapy, or brachytherapy. Recently, the development of new conservative techniques of treatment, such as intra-arterial selective chemotherapy perfusion and intravitreal injections, aims at preserving visual function in these children and decreasing the number of enucleations and the need for external beam radiotherapy. The vital prognosis related to retinoblastoma is now excellent in industrialized countries, but long-term survival is still related to the

  4. Mobile application-based Seoul National University Prostate Cancer Risk Calculator: development, validation, and comparative analysis with two Western risk calculators in Korean men.

    Directory of Open Access Journals (Sweden)

    Chang Wook Jeong

    Full Text Available OBJECTIVES: We developed a mobile application-based Seoul National University Prostate Cancer Risk Calculator (SNUPC-RC that predicts the probability of prostate cancer (PC at the initial prostate biopsy in a Korean cohort. Additionally, the application was validated and subjected to head-to-head comparisons with internet-based Western risk calculators in a validation cohort. Here, we describe its development and validation. PATIENTS AND METHODS: As a retrospective study, consecutive men who underwent initial prostate biopsy with more than 12 cores at a tertiary center were included. In the development stage, 3,482 cases from May 2003 through November 2010 were analyzed. Clinical variables were evaluated, and the final prediction model was developed using the logistic regression model. In the validation stage, 1,112 cases from December 2010 through June 2012 were used. SNUPC-RC was compared with the European Randomized Study of Screening for PC Risk Calculator (ERSPC-RC and the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC. The predictive accuracy was assessed using the area under the receiver operating characteristic curve (AUC. The clinical value was evaluated using decision curve analysis. RESULTS: PC was diagnosed in 1,240 (35.6% and 417 (37.5% men in the development and validation cohorts, respectively. Age, prostate-specific antigen level, prostate size, and abnormality on digital rectal examination or transrectal ultrasonography were significant factors of PC and were included in the final model. The predictive accuracy in the development cohort was 0.786. In the validation cohort, AUC was significantly higher for the SNUPC-RC (0.811 than for ERSPC-RC (0.768, p<0.001 and PCPT-RC (0.704, p<0.001. Decision curve analysis also showed higher net benefits with SNUPC-RC than with the other calculators. CONCLUSIONS: SNUPC-RC has a higher predictive accuracy and clinical benefit than Western risk calculators. Furthermore, it is easy

  5. Using administrative health data to describe colorectal and lung cancer care in New South Wales, Australia: a validation study

    Directory of Open Access Journals (Sweden)

    Goldsbury David E

    2012-11-01

    Full Text Available Abstract Background Monitoring treatment patterns is crucial to improving cancer patient care. Our aim was to determine the accuracy of linked routinely collected administrative health data for monitoring colorectal and lung cancer care in New South Wales (NSW, Australia. Methods Colorectal and lung cancer cases diagnosed in NSW between 2000 and 2002 were identified from the NSW Central Cancer Registry (CCR and linked to their hospital discharge records in the NSW Admitted Patient Data Collection (APDC. These records were then linked to data from two relevant population-based patterns of care surveys. The main outcome measures were the sensitivity and specificity of data from the CCR and APDC for disease staging, investigative procedures, curative surgery, chemotherapy, radiotherapy, and selected comorbidities. Results Data for 2917 colorectal and 1580 lung cancer cases were analysed. Unknown disease stage was more common for lung cancer in the administrative data (18% than in the survey (2%. Colonoscopies were captured reasonably accurately in the administrative data compared with the surveys (82% and 79% respectively; 91% sensitivity, 53% specificity but all other colorectal or lung cancer diagnostic procedures were under-enumerated. Ninety-one percent of colorectal cancer cases had potentially curative surgery recorded in the administrative data compared to 95% in the survey (96% sensitivity, 92% specificity, with similar accuracy for lung cancer (16% and 17%; 92% sensitivity, 99% specificity. Chemotherapy (~40% sensitivity and radiotherapy (sensitivity≤30% were vastly under-enumerated in the administrative data. The only comorbidity that was recorded reasonably accurately in the administrative data was diabetes. Conclusions Linked routinely collected administrative health data provided reasonably accurate information on potentially curative surgical treatment, colonoscopies and comorbidities such as diabetes. Other diagnostic procedures

  6. Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients

    DEFF Research Database (Denmark)

    Győrffy, Balázs; Lánczky, András; Szállási, Zoltán

    2012-01-01

    was set up using gene expression data and survival information of 1287 ovarian cancer patients downloaded from Gene Expression Omnibus and The Cancer Genome Atlas (Affymetrix HG-U133A, HG-U133A 2.0, and HG-U133 Plus 2.0 microarrays). After quality control and normalization, only probes present on all......). A Kaplan–Meier survival plot was generated and significance was computed. The tool can be accessed online at www.kmplot.com/ovar. We used this integrative data analysis tool to validate the prognostic power of 37 biomarkers identified in the literature. Of these, CA125 (MUC16; P=3.7x10–5, hazard ratio (HR...

  7. Validation of an Ion Torrent Sequencing Platform for the Detection of Gene Mutations in Biopsy Specimens from Patients with Non-Small-Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Shiro Fujita

    Full Text Available Treatment for patients with advanced non-small cell lung cancer (NSCLC is often determined by the presence of biomarkers that predict the response to agents targeting specific molecular pathways. Demands for multiplex analysis of the genes involved in the pathogenesis of NSCLC are increasing.We validated the Ion Torrent Personal Genome Machine (PGM system using the Ion AmpliSeq Cancer Hotspot Panel and compared the results with those obtained using the gold standard methods, conventional PCR and Sanger sequencing. The cycleave PCR method was used to verify the results.The Ion Torrent PGM resulted in a similar level of accuracy in identifying multiple genetic mutations in parallel, compared with conventional PCR and Sanger sequencing; however, the Ion Torrent PGM was superior to the other sequencing methods in terms of increased ease of use, even when taking into account the small amount of DNA that was obtained from formalin-fixed paraffin embedded (FFPE biopsy specimens.

  8. Clinical Outcome of Pancreatic Cancer Patients with Diabetes Mellitus: Is Diabetes a Poor Prognostic Factor? Highlights from the "2010 ASCO Annual Meeting". Chicago, IL, USA. June 4-8, 2010

    Directory of Open Access Journals (Sweden)

    Soonmo Peter Kang

    2010-07-01

    Full Text Available Diabetes mellitus and its related factors such as hyperinsulinemia have been linked to various cancer risks and outcomes. Previous research has offered inconsistent results in terms of relationship between diabetes and pancreatic cancers. Establishing clear association between these two entities may guide us in improving clinical outcomes of pancreatic cancer patients. Two abstracts that examined the association between diabetes mellitus and pancreatic cancer are updated in this paper. Herein, the authors report updated information from the 2010 American Society of Clinical Oncology (ASCO Annual Meeting in association between pancreatic cancer and diabetes mellitus. The present paper illustrates insufficient knowledge base to draw a conclusion in this topic. However, validation and understanding of the association could have significant clinical implications with respect to cancer prevention, early detection, and treatment. As such, further investigations are warranted to explore the link diabetes and pancreatic cancers.

  9. Measuring Attitude and Practice of Physician toward Breaking Bad News to the Breast Cancer Patients: Development and Validation of a Questionnaire

    Directory of Open Access Journals (Sweden)

    Somaieh Borjalilu

    2016-06-01

    Full Text Available Background: Breaking bad news to cancer patients is one of the important responsibilities in the oncology setting. The purpose of this study is develop and validate a new theoretically based tool for measurement of attitude and practice of physicians toward breaking bad news.Methods: The psychometric properties of the scale were established by following the guidelines of Clark and Watson. In the first phase, a literature review was performed to create items; then items were assessed for content validity through individual interview (n = 12 and construct validity was assessed by using factor analysis. Reliability was evaluated by Cronbach’s alpha. Research data was gathered from physicians working in breast cancer setting. Results: A total of 12 expert reviews concluded that a large amount of items of attitude and practice questionnaires were important and essential (Content Validity Ratio > 0.73. The exploratory and confirmatory factor analyses for a sample of physicians (n = 200 indicated a 12-item of attitude scale with three factors: full disclosure, non-disclosure and individual disclosure. Cronbach’s Alpha for the factors returned 0.746, 0.834 and 0.795, respectively. The exploratory and confirmatory factor analyses for a sample of physicians (n = 200 indicated a 20-item of practice scale with six factors: preparation, setting of the interaction, communicate well, use of the “cancer” word, patient’s right to know and close the interview, and summarized. Cronbach’s Alpha for the factors returned 0.765, 0.63, 0.65, 0.793, 0.759 and 0.7, respectively.Conclusions: A resultant 12 items of attitude and 20 items of practice questionnaire were developed to assess how physicians are giving bad news to breast cancer patients. The reliability of the new tools needs to be evaluated for further studies. This new questionnaire will provide researchers and clinicians with a thorough and suitable instrument to measure belief and practice

  10. Towards optimised information about clinical trials; identification and validation of key issues in collaboration with cancer patient advocates

    DEFF Research Database (Denmark)

    Dellson, P; Nilbert, M; Bendahl, P-O;

    2011-01-01

    the possibility to discontinue treatment were perceived as the most important issues. Patients' views of the information in clinical trials provide new insights and identify key issues to consider in optimising future written information and may improve recruitment to clinical cancer trials.......Clinical trials are crucial to improve cancer treatment but recruitment is difficult. Optimised patient information has been recognised as a key issue. In line with the increasing focus on patients' perspectives in health care, we aimed to study patients' opinions about the written information used...... in three clinical trials for breast cancer. Primary data collection was done in focus group interviews with breast cancer patient advocates. Content analysis identified three major themes: comprehensibility, emotions and associations, and decision making. Based on the advocates' suggestions...

  11. Validation of a Strategy for Cancer Therapy: Delivering Aminoglycoside Drugs to Mitochondria in HeLa Cells.

    Science.gov (United States)

    Abe, Jiro; Yamada, Yuma; Harashima, Hideyoshi

    2016-02-01

    Mitochondria in human cancer cells have been implicated in cancer cell proliferation, invasion, metastasis, and even drug-resistance mechanisms, making them a potential target organelle for the treatment of human malignancies. Gentamicin (GM), an aminoglycoside drug (AG), is a small molecule that functions as an antibiotic and has ototoxic and nephrotoxic characteristics. Thus, the delivery of GM to mitochondria in cancer cells would be an innovative anticancer therapeutic strategy. In this study, we attempted mitochondrial delivery of GM in HeLa cells derived from a human cervical cancer. For the mitochondrial delivery, we used MITO-Porter, a liposomal nanocarrier for mitochondrial delivery via membrane fusion. We first encapsulated GM in the aqueous phase of the carrier to construct GM-MITO-Porter. Flow cytometry analysis and fluorescent microscopy observations permitted us to confirm that the GM-MITO-Porter was efficiently taken up by HeLa cells and accumulated in mitochondria, whereas naked GM was not taken up by the cells. Moreover, cell viability assays using HeLa cells showed that the GM-MITO-Porter induced strong cytotoxic effects related to mitochondrial disorder. This finding is the first report of the mitochondrial delivery of an AG to cancer cells for cancer therapeutic strategy.

  12. What is the role of sipuleucel-T in the treatment of patients with advanced prostate cancer? An update on the evidence.

    Science.gov (United States)

    Hu, Rachel; George, Daniel J; Zhang, Tian

    2016-08-01

    Prostate cancer is the most common cancer in men and the second most deadly. About one-third of patients with prostate cancer will develop metastatic disease. We discuss the six United States Food and Drug Administration (FDA) approved treatments for metastatic castrate-resistant prostate cancer (mCRPC) with a strong focus on sipuleucel-T. Sipuleucel-T is the first immunotherapy shown to improve survival in asymptomatic or minimally-symptomatic mCRPC. Herein, we discuss the proposed mechanism of sipuleucel-T and its synthesis. We describe in detail the three randomized controlled trials (RTCs) that led to its approval. We also compiled the newest research regarding use of sipuleucel-T with other agents and in different patient populations. Finally, we discuss the current ongoing trials.

  13. Sipuleucel-T for therapy of asymptomatic or minimally symptomatic, castrate-refractory prostate cancer: an update and perspective among other treatments

    Directory of Open Access Journals (Sweden)

    Gupta SG

    2011-06-01

    Full Text Available Shilpa Gupta, Estrella Carballido, Mayer FishmanMoffitt Cancer Center and Research Institute, Tampa, FL, USAAbstract: Sipuleucel-T is an autologous cell immunotherapy for castrate-refractory prostate cancer, with US Food and Drug Administration (FDA approval in asymptomatic or minimally symptomatic prostate cancer. In this review we address the background of prostate cancer incidence and other available therapy onto which sipuleucel-T treatment has been added, with discussion of hormone-therapy, chemotherapy, and other investigational immunotherapies. The sipuleucel-T manufacturing process, toxicity and clinical benefit are reviewed, along with an examination of the issue of clinical benefit to survival, independent of apparent changes of prostate-specific antigen (PSA levels. Sipuleucel-T therapy is appraised from clinician, patient and immunotherapeutic perspectives, with reference to the clinical data from the pivotal trial, the mechanism of action, and the treatment process.Keywords: sipuleucel-T, immunotherapy, vaccine, immunotherapy, dendritic cells

  14. Relationships Among Individual Motivation, Work Environment, and Updating in Engineers. Final Report.

    Science.gov (United States)

    Farr, James L.; And Others

    Reported is a validation study of the Dubin technical updating model, one which identifies variables that may be combined with expectancy theory to predict whether or not engineers will need technical updating. The basic hypothesis is that the likelihood of engaging in updating activities is a function of individual motivation and characteristics…

  15. Identification of valid reference genes for the normalization of RT-qPCR expression studies in human breast cancer cell lines treated with and without transient transfection.

    Directory of Open Access Journals (Sweden)

    Lin-Lin Liu

    Full Text Available Reverse transcription-quantitative polymerase chain reaction (RT-qPCR is a powerful technique for examining gene expression changes during tumorigenesis. Target gene expression is generally normalized by a stably expressed endogenous reference gene; however, reference gene expression may differ among tissues under various circumstances. Because no valid reference genes have been documented for human breast cancer cell lines containing different cancer subtypes treated with transient transfection, we identified appropriate and reliable reference genes from thirteen candidates in a panel of 10 normal and cancerous human breast cell lines under experimental conditions with/without transfection treatments with two transfection reagents. Reference gene expression stability was calculated using four algorithms (geNorm, NormFinder, BestKeeper and comparative delta Ct, and the recommended comprehensive ranking was provided using geometric means of the ranking values using the RefFinder tool. GeNorm analysis revealed that two reference genes should be sufficient for all cases in this study. A stability analysis suggests that 18S rRNA-ACTB is the best reference gene combination across all cell lines; ACTB-GAPDH is best for basal breast cancer cell lines; and HSPCB-ACTB is best for ER+ breast cancer cells. After transfection, the stability ranking of the reference gene fluctuated, especially with Lipofectamine 2000 transfection reagent in two subtypes of basal and ER+ breast cell lines. Comparisons of relative target gene (HER2 expression revealed different expressional patterns depending on the reference genes used for normalization. We suggest that identifying the most stable and suitable reference genes is critical for studying specific cell lines under certain circumstances.

  16. Association between MDM2 SNP309 T>G polymorphism and the risk of bladder cancer: new data in a Chinese population and an updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Xie LG

    2015-12-01

    Full Text Available Linguo Xie,1,2,* Yan Sun,2,* Tao Chen,1,2,* Dawei Tian,1,2 Yujuan Li,3 Yu Zhang,1,2 Na Ding,2 Zhonghua Shen,1,2 Hao Xu,1,2 Xuewu Nian,4 Nan Sha,1,2 Ruifa Han,1,2 Hailong Hu,1,2 Changli Wu1,2 Objective: Human murine double minute 2 protein (MDM2 is mainly a negative regulator of p53 tumor suppressor pathway. We aimed to investigate the association between MDM2 SNP309 polymorphism and bladder cancer risk. Methods: A total of 535 bladder cancer patients and 649 health controls were recruited for our study. MDM2 SNP309 T>G polymorphism was genotyped by polymerase chain reaction-ligase detection reaction method. Logistic regression was used to analyze the relationship between the genotype and susceptibility of bladder cancer. Kaplan–Meier estimates and log-rank test were obtained to analyze the association between the genotype and risk of recrudesce in nonmuscle-invasive bladder cancer patients. A multivariable Cox proportional hazards model was fitted to identify independent prognostic factors. To further investigate the association, we conducted a meta-analysis including six studies. Results: The frequency of the MDM2 SNP309 T>G polymorphism showed no significant difference between cases and controls (all P>0.05. In the stratification analysis, the results showed that G allele carriers were prone to have a significant decrease in risk of low-grade bladder cancer (adjusted odds ratio: 0.613, 95% confidence interval: 0.427–0.881, and G variant was associated with a significantly reduced risk of recurrence in nonmuscle-invasive bladder cancer patients with or without chemotherapy (P<0.05. The results of the meta-analysis showed that G allele and GG genotype of MDM2 SNP309 polymorphism were significantly associated with increased risk of bladder cancer in Caucasians (both P<0.05, and no association was observed in total populations and Asians (P>0.05. Conclusion: MDM2 SNP309 T>G polymorphism has no influence on bladder cancer risk in Asians, but

  17. Validation of a quantitative flow cytometer assay for monitoring HER-2/neu expression level in cell-based cancer immunotherapy products.

    Science.gov (United States)

    Randlev, Britta; Huang, Li-chun; Watatsu, Mitsuko; Marcus, Matthew; Lin, Andy; Shih, Shian-Jiun

    2010-03-01

    GVAX immunotherapy for prostate cancer is comprised of two genetically modified prostate cancer cell lines, CG1940 and CG8711, engineered to secrete granulocyte macrophage-colony-stimulating factor. As part of the matrix of potency assays, CG1940 and CG8711 are tested for the expression level of cell surface HER-2/neu using a quantitative flow cytometer assay. This assay reports the antibody binding capacity value of the cells as a measure of HER-2/neu expression using cells immediately after thawing from cryogenic storage. With optimized cell handling and staining procedure and appropriate system suitability controls, the assay was validated as a quantitative assay. The validation results showed that assay accuracy, specificity, precision, linearity, and range were suitable for the intended use of ensuring lot-to-lot consistency of HER-2/neu expression. Assay robustness was demonstrated using design of experiments that evaluated critical assay parameters. Finally, the assay was successfully transferred to a current good manufacturing practice Quality Control laboratory in a separate facility. Since the overall precision of this assay is better than that of ELISA methods and it can be performed with ease and high throughput, quantitative flow cytometer-based assays may be an appropriate immunological assay platform for Quality Control laboratories for characterization and release of cell-based therapies.

  18. MTHFR gene A1298C polymorphisms are associated with breast cancer risk among Chinese population: evidence based on an updated cumulative meta-analysis

    Science.gov (United States)

    Wang, Yadong; Yang, Haiyan; Duan, Guangcai

    2015-01-01

    Objectives: Published studies on the association between methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphisms and breast cancer risk among Chinese population have yielded conflicting results. The purpose of this study was to clarify the association between MTHFR gene A1298C polymorphisms and breast cancer risk among Chinese population. Methods: Systematic searches were performed through the database of Medline/PubMed, Science Direct, Elsevier, CNKI and Wanfang Medical Online. Results: Overall, a significantly increased risk of breast cancer was observed among the subjects carrying MTHFR gene A1298C AC+CC genotype (odds ratio [OR]=1.05 with 95% confidence interval [CI]: 1.01-1.10) as compared to those carrying AA genotype among total Chinese population. We did not observe any significant association between MTHFR gene A1298C polymorphisms and the risk of breast cancer under the additional genetic models of AC vs. AA, CC vs. AA and C-allele vs. A-allele (OR=1.00 with 95% CI: 0.97-1.02, OR=1.01 with 95% CI: 1.00-1.02 and OR=1.00 with 95% CI: 0.99-1.02, respectively). The cumulative meta-analysis showed similar results. In subgroup analysis, we observed subjects carrying AC+CC genotype had an increased breast cancer risk compared with those carrying AA genotype among the studies of sample size less than 1000. We did not observe any significant association between MTHFR gene A1298C polymorphisms and breast cancer risk in additional subgroup analyses. Conclusions: Our results suggest that MTHFR gene A1298C AC+CC genotype may be a risk factor for the development of breast cancer among Chinese population. Well-designed studies with a large sample size are needed to further confirm our findings. PMID:26884927

  19. OGEE v2: an update of the online gene essentiality database with special focus on differentially essential genes in human cancer cell lines.

    Science.gov (United States)

    Chen, Wei-Hua; Lu, Guanting; Chen, Xiao; Zhao, Xing-Ming; Bork, Peer

    2017-01-04

    OGEE is an Online GEne Essentiality database. To enhance our understanding of the essentiality of genes, in OGEE we collected experimentally tested essential and non-essential genes, as well as associated gene properties known to contribute to gene essentiality. We focus on large-scale experiments, and complement our data with text-mining results. We organized tested genes into data sets according to their sources, and tagged those with variable essentiality statuses across data sets as conditionally essential genes, intending to highlight the complex interplay between gene functions and environments/experimental perturbations. Developments since the last public release include increased numbers of species and gene essentiality data sets, inclusion of non-coding essential sequences and genes with intermediate essentiality statuses. In addition, we included 16 essentiality data sets from cancer cell lines, corresponding to 9 human cancers; with OGEE, users can easily explore the shared and differentially essential genes within and between cancer types. These genes, especially those derived from cell lines that are similar to tumor samples, could reveal the oncogenic drivers, paralogous gene expression pattern and chromosomal structure of the corresponding cancer types, and can be further screened to identify targets for cancer therapy and/or new drug development. OGEE is freely available at http://ogee.medgenius.info.

  20. OGEE v2: an update of the online gene essentiality database with special focus on differentially essential genes in human cancer cell lines

    Science.gov (United States)

    Chen, Wei-Hua; Lu, Guanting; Chen, Xiao; Zhao, Xing-Ming; Bork, Peer

    2017-01-01

    OGEE is an Online GEne Essentiality database. To enhance our understanding of the essentiality of genes, in OGEE we collected experimentally tested essential and non-essential genes, as well as associated gene properties known to contribute to gene essentiality. We focus on large-scale experiments, and complement our data with text-mining results. We organized tested genes into data sets according to their sources, and tagged those with variable essentiality statuses across data sets as conditionally essential genes, intending to highlight the complex interplay between gene functions and environments/experimental perturbations. Developments since the last public release include increased numbers of species and gene essentiality data sets, inclusion of non-coding essential sequences and genes with intermediate essentiality statuses. In addition, we included 16 essentiality data sets from cancer cell lines, corresponding to 9 human cancers; with OGEE, users can easily explore the shared and differentially essential genes within and between cancer types. These genes, especially those derived from cell lines that are similar to tumor samples, could reveal the oncogenic drivers, paralogous gene expression pattern and chromosomal structure of the corresponding cancer types, and can be further screened to identify targets for cancer therapy and/or new drug development. OGEE is freely available at http://ogee.medgenius.info. PMID:27799467

  1. Development and validation of a simple questionnaire for the identification of hereditary breast cancer in primary care

    Directory of Open Access Journals (Sweden)

    Palmero Edenir I

    2009-08-01

    Full Text Available Abstract Background Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult. Methods A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined. Results Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5–26.2 had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65. Conclusion A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at

  2. Reliable categorisation of visual scoring of coronary artery calcification on low-dose CT for lung cancer screening: validation with the standard Agatston score

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Yi-Luan; Wu, Fu-Zong; Wang, Yen-Chi [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung 813 (China); National Yang Ming University, Faculty of Medicine, School of Medicine, Taipei (China); Ju, Yu-Jeng [National Taiwan University, Department of Psychology, Taipei (China); Mar, Guang-Yuan [Kaohsiung Veterans General Hospital, Division of Cardiology, Department of Medicine, Kaohsiung 813 (China); Chuo, Chiung-Chen [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung 813 (China); Lin, Huey-Shyan [Fooyin University, School of Nursing, Kaohsiung (China); Wu, Ming-Ting [Kaohsiung Veterans General Hospital, Department of Radiology, Kaohsiung 813 (China); National Yang Ming University, Faculty of Medicine, School of Medicine, Taipei (China); National Yang Ming University, Institute of Clinical Medicine, Taipei (China)

    2013-05-15

    To validate the reliability of the visual coronary artery calcification score (VCACS) on low-dose CT (LDCT) for concurrent screening of CAC and lung cancer. We enrolled 401 subjects receiving LDCT for lung cancer screening and ECG-gated CT for the Agatston score (AS). LDCT was reconstructed with 3- and 5-mm slice thickness (LDCT-3mm and LDCT-5mm respectively) for VCACS to obtain VCACS-3mm and VCACS-5mm respectively. After a training session comprising 32 cases, two observers performed four-scale VCACS (absent, mild, moderate, severe) of 369 data sets independently, the results were compared with four-scale AS (0, 1-100, 101-400, >400). CACs were present in 39.6 % (146/369) of subjects. The sensitivity of VCACS-3mm was higher than for VCACS-5mm (83.6 % versus 74.0 %). The median of AS of the 24 false-negative cases in VCACS-3mm was 2.3 (range 1.1-21.1). The false-negative rate for detecting AS {>=} 10 on LDCT-3mm was 1.9 %. VCACS-3mm had higher concordance with AS than VCACS-5mm (k = 0.813 versus k = 0.685). An extended test of VCACS-3mm for four junior observers showed high inter-observer reliability (intra-class correlation = 0.90) and good concordance with AS (k = 0.662-0.747). This study validated the reliability of VCACS on LDCT for lung cancer screening and showed that LDCT-3mm was more feasible than LDCT-5mm for CAD risk stratification. (orig.)

  3. Sipuleucel-T for therapy of asymptomatic or minimally symptomatic, castrate-refractory prostate cancer: an update and perspective among other treatments.

    Science.gov (United States)

    Gupta, Shilpa; Carballido, Estrella; Fishman, Mayer

    2011-01-01

    Sipuleucel-T is an autologous cell immunotherapy for castrate-refractory prostate cancer, with US Food and Drug Administration (FDA) approval in asymptomatic or minimally symptomatic prostate cancer. In this review we address the background of prostate cancer incidence and other available therapy onto which sipuleucel-T treatment has been added, with discussion of hormone-therapy, chemotherapy, and other investigational immunotherapies. The sipuleucel-T manufacturing process, toxicity and clinical benefit are reviewed, along with an examination of the issue of clinical benefit to survival, independent of apparent changes of prostate-specific antigen (PSA) levels. Sipuleucel-T therapy is appraised from clinician, patient and immunotherapeutic perspectives, with reference to the clinical data from the pivotal trial, the mechanism of action, and the treatment process.

  4. Potential reduction of contralateral second breast-cancer risks by prophylactic mammary irradiation: validation in a breast-cancer-prone mouse model.

    Directory of Open Access Journals (Sweden)

    Igor Shuryak

    Full Text Available BACKGROUND: Long-term breast-cancer survivors have a highly elevated risk (1 in 6 at 20 years of contralateral second breast cancer. This high risk is associated with the presence of multiple pre-malignant cell clones in the contralateral breast at the time of primary breast cancer diagnosis. Mechanistic analyses suggest that a moderate dose of X-rays to the contralateral breast can kill these pre-malignant clones such that, at an appropriate Prophylactic Mammary Irradiation (PMI dose, the long-term contralateral breast cancer risk in breast cancer survivors would be considerably decreased. AIMS: To test the predicted relationship between PMI dose and cancer risk in mammary glands that have a high risk of developing malignancies. METHODS: We tested the PMI concept using MMTV-PyVT mammary-tumor-prone mice. Mammary glands on one side of each mouse were irradiated with X-rays, while those on the other side were shielded from radiation. The unshielded mammary glands received doses of 0, 4, 8, 12 and 16 Gy in 4-Gy fractions. RESULTS: In high-risk mammary glands exposed to radiation doses designed for PMI (12 and 16 Gy, tumor incidence rates were respectively decreased by a factor of 2.2 (95% CI, 1.1-5.0 at 12 Gy, and a factor of 3.1 (95% CI, 1.3-8.3 at 16 Gy, compared to those in the shielded glands that were exposed to very low radiation doses. The same pattern was seen for PMI-exposed mammary glands relative to zero-dose controls. CONCLUSIONS: The pattern of cancer risk reduction by PMI was consistent with mechanistic predictions. Contralateral breast PMI may thus have promise as a spatially targeted breast-conserving option for reducing the current high risk of contralateral second breast cancers. For estrogen-receptor positive primary tumors, PMI might optimally be used concomitantly with systemically delivered chemopreventive drugs such as tamoxifen or aromatase inhibitors, while for estrogen-receptor negative tumors, PMI might be used alone.

  5. Translation and validation of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4 quality of life instrument into traditional Chinese.

    Science.gov (United States)

    Lau, A K L; Chang, C H; Tai, J W M; Eremenco, S; Liang, R; Lie, A K W; Fong, D Y T; Lau, C M

    2002-01-01

    The need for a culturally sensitive instrument to assess quality of life (QOL) of patients in international oncology clinical trials has been well documented. This study was designed to evaluate the psychometric properties of the traditional Chinese translation (TCHI) of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4. The FACT-BMT consists of the FACT-General and treatment-specific concerns of bone marrow transplantation. The Chinese translation follows the standard Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology. Bilingual teams from the United States and Hong Kong reviewed the translation to develop a provisional TCHI FACT-BMT, which was then pre-tested by interviewing 20 native Chinese-speaking BMT patients in Hong Kong. The pre-test results indicated good content coverage and overall comprehensibility. A refined translation, taking into account patient comments, was validated by 134 BMT patients in Hong Kong. The results indicated the high internal consistency of the TCHI FACT-BMT scales, with Cronbach's alpha coefficients ranging from 0.71 (emotional well-being) to 0.92 (FACT-BMT total). The FACT-BMT also demonstrated good construct validity when correlated with SF-36 Health Survey scales. The QOL of Chinese BMT patients can now be evaluated using a well-validated international QOL instrument in their own language.

  6. Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

    NARCIS (Netherlands)

    Lawrenson, K.; Li, Q.; Kar, S.; Seo, J.H.; Tyrer, J.; Spindler, T.J.; Lee, J. van der; Chen, Y; Karst, A.; Drapkin, R.; Aben, K.K.H.; Anton-Culver, H.; Antonenkova, N.; Baker, H.; Bandera, E.V.; Bean, Y.; Beckmann, M.W.; Berchuck, A.; Bisogna, M.; Bjorge, L.; Bogdanova, N.; Brinton, L.A.; Brooks-Wilson, A.; Bruinsma, F.; Butzow, R.; Campbell, I.G.; Carty, K.; Chang-Claude, J.; Chenevix-Trench, G.; Chen, A; Chen, Z.; Cook, L.S.; Cramer, D.W; Cunningham, J.M.; Cybulski, C.; Dansonka-Mieszkowska, A.; Dennis, J.; Dicks, E.; Doherty, J.A.; Dork, T.; Bois, A. du; Durst, M.; Eccles, D.; Easton, D.T.; Edwards, R.P.; Eilber, U.; Ekici, A.B.; Fasching, P.A.; Fridley, B.L.; Gao, Y.T.; Gentry-Maharaj, A.; Giles, G.G.; Glasspool, R.; Goode, E.L.; Goodman, M.T.; Grownwald, J.; Harrington, P.; Harter, P.; Hasmad, H.N.; Hein, A.; Heitz, F.; Hildebrandt, M.A.; Hillemanns, P.; Hogdall, E.; Hogdall, C.; Hosono, S.; Iversen, E.S.; Jakubowska, A.; James, P.; Jensen, A.; Ji, B.T.; Karlan, B.Y.; Kjaer, S. Kruger; Kelemen, L.E.; Kellar, M.; Kelley, J.L.; Kiemeney, L.A.; Krakstad, C.; Kupryjanczyk, J.; Lambrechts, D.; Lambrechts, S.; Le, N.D.; Lee, A.W.; Lele, S.; Leminen, A.; Lester, J.; Levine, D.A.; Liang, D.; Lissowska, J.; Lu, K.; Lubinski, J.; Lundvall, L.; Massuger, L.F.; Matsuo, K.; McGuire, V.; McLaughlin, J.R.; Nevanlinna, H.; McNeish, I.; Menon, U.; Modugno, F.

    2015-01-01

    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associat

  7. Identifying subgroups among poor prognosis patients with nonseminomatous germ cell cancer by tree modelling: a validation study.

    NARCIS (Netherlands)

    M.R. van Dijk (Merel); E.W. Steyerberg (Ewout); S.P. Stenning; J.D.F. Habbema (Dik)

    2004-01-01

    textabstractBACKGROUND: In order to target intensive treatment strategies for poor prognosis patients with non-seminomatous germ cell cancer, those with the poorest prognosis should be identified. These patients might profit most from more intensive treatment strategies. For this p

  8. Detection of colorectal cancer in symptomatic outpatients without visible rectal bleeding: Validity of the fecal occult blood test

    DEFF Research Database (Denmark)

    Bjerregaard, Niels Christian; Tøttrup, Anders; Sørensen, Henrik Toft

    2009-01-01

    In 2002, a new diagnostic strategy in symptomatic outpatients without known established colorectal cancer risk factors aged 40 years or older was implemented in Denmark. Fecal occult blood test (Hemoccult Sensa®) was a part of that strategy in patients without visible rectal bleeding....

  9. Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study

    Directory of Open Access Journals (Sweden)

    H. Ross-Adams

    2015-09-01

    Interpretation: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

  10. Validation of a questionnaire for self-rating of urological and gynaecological morbidity after treatment of gynaecological cancer

    DEFF Research Database (Denmark)

    Jensen, Pernille Tine; Klee, Marianne Carol; Groenvold, Mogens

    2002-01-01

    of the uro-gynaecological questionnaire (UGQ), a new instrument for patient self-assessment of urological-, genital-, menopausal-, and pain symptomatology in gynaecological cancer patients. MATERIAL AND METHODS: The UGQ was developed after literature review, patient- and expert interviews and pilot testing...

  11. Assessment of stochastically updated finite element models using reliability indicator

    Science.gov (United States)

    Hua, X. G.; Wen, Q.; Ni, Y. Q.; Chen, Z. Q.

    2017-01-01

    Finite element (FE) model updating techniques have been a viable approach to correcting an initial mathematical model based on test data. Validation of the updated FE models is usually conducted by comparing model predictions with independent test data that have not been used for model updating. This approach of model validation cannot be readily applied in the case of a stochastically updated FE model. In recognizing that structural reliability is a major decision factor throughout the lifecycle of a structure, this study investigates the use of structural reliability as a measure for assessing the quality of stochastically updated FE models. A recently developed perturbation method for stochastic FE model updating is first applied to attain the stochastically updated models by using the measured modal parameters with uncertainty. The reliability index and failure probability for predefined limit states are computed for the initial and the stochastically updated models, respectively, and are compared with those obtained from the 'true' model to assess the quality of the two models. Numerical simulation of a truss bridge is provided as an example. The simulated modal parameters involving different uncertainty magnitudes are used to update an initial model of the bridge. It is shown that the reliability index obtained from the updated model is much closer to true reliability index than that obtained from the initial model in the case of small uncertainty magnitude; in the case of large uncertainty magnitude, the reliability index computed from the initial model rather than from the updated model is closer to the true value. The present study confirms the usefulness of measurement-calibrated FE models and at the same time also highlights the importance of the uncertainty reduction in test data for reliable model updating and reliability evaluation.

  12. 2015年V1版《NCCN胃癌临床实践指南》更新解读%Updates of NCCN clinical practice guidelines for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    徐泽宽

    2015-01-01

    In recent years, with the rapid development of diagnosis and treatment of gastric cancer, NCCN gastric cancer clinical practice guidelines also continue to release new versions to follow up the progress of the new frontier. In the new NCCN guideline (Version1.2015), new evidence and standard were introduced, and four major aspects were revised, including:(1)The criteria of unresectability for cure was updated, (2)the principles of genetic risk assessment for gastric cancer, the new risk assessment and genetic consultation were modified, (3) the systemic therapy for locally advanced, locally recurrent or metastatic gastric cancer were modified, (4)the partial contents of radiation therapy were revised. The new guideline has included the latest research achievements, which makes the concept of the treatment of gastric cancer more scientific and standardized. It will provide important guidance for the future clinical practice.%胃癌诊治领域近年来进展迅速,《NCCN胃癌临床实践指南》(《指南》)也不断推出新的版本,以跟进最新的前沿进展。2015年V1版《指南》在原来的基础上引进了新的证据和标准,从四个主要方面进行了修订:(1)更新了“胃癌不可根治性切除的标准”;(2)修改了胃癌的风险分析,新增了“肿瘤风险评估”和“遗传学咨询”;(3)修改了局部进展期、局部复发或转移性胃癌的部分化疗方案;(4)修改了胃癌放疗的部分内容。新版《指南》对胃癌的治疗理念更规范化、科学化,为今后的临床实践提供指导。

  13. Validity of bioelectrical impedance analysis to assess fat-free mass in head and neck cancer patients: an exploratory study

    NARCIS (Netherlands)

    Jager-Wittenaar, Harriët; Dijkstra, Pieter U.; Earthman, Carrie P.; Krijnen, Wim P.; Langendijk, Johannes A.; Laan, Bernard F.A. M. van der; Pruim, Jan; Roodenburg, Jan L.N.

    2013-01-01

    Bioelectrical impedance analysis (BIA) may be used to assess fet free mass (FFM) with reasonable validity based on mean-level comparisons, but differences between BIA and DXA may vary by about 4 kg in an individual patient. These results require confirmation in a larger sample of HNC patients. (Head

  14. The Catechol-O-Methyltransferase Val158Met Polymorphism Contributes to the Risk of Breast Cancer in the Chinese Population: An Updated Meta-Analysis

    Science.gov (United States)

    Wan, Guo-Xing; Cao, Yu-Wen; Li, Wen-Qin; Li, Yu-Cong; Li, Feng

    2014-01-01

    Purpose Catechol-O-methyltransferase (COMT) enzyme plays a central role in estrogen-induced carcinogenesis. Emerging evidence from association studies has revealed that the functional Val158Met polymorphism (rs4680 G>A) of the Catechol-O-methyltransferase gene (COMT) has been implicated in susceptibility to breast cancer in the Chinese population, while results of individual published studies remain inconclusive and inconsistent. To assess this association in the Chinese population, a meta-analysis was performed. Methods Eligible studies were searched on MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, and the Chinese Biomedicine Database. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the association between COMT polymorphisms and the risk of breast cancer using RevMan 5.2 and Stata 12.0 software. Results The meta-analysis included 14 eligible studies, with a total of 4,626 breast cancer cases and 5,637 controls. Overall, the COMT Val158Met polymorphism (rs4680 G>A) was significantly associated with an increased risk of breast cancer in several genetic models (A/A vs. G/G: OR, 1.59, 95% CI, 1.12-2.27; A/A vs. G/A+G/G: OR, 1.62, 95% CI, 1.14-2.29; A vs. G: OR, 1.15, 95% CI, 1.00-1.32), and a subgroup analysis according to menopausal status showed that this association was especially evident among premenopausal Chinese women (A/A vs. G/G: OR, 1.87, 95% CI, 0.99-3.54; A/A vs. G/A+G/G: OR, 1.94, 95% CI, 1.03-3.63). Conclusion The results of this meta-analysis indicated that COMT Val158Met variants contribute to breast cancer susceptibility in the Chinese population, particularly among premenopausal women. PMID:25013436

  15. Helping your child understand a cancer diagnosis

    Science.gov (United States)

    ... patientinstructions/000844.htm Helping your child understand a cancer diagnosis To use the sharing features on this page, ... games. References American Cancer Society. Children Diagnosed With Cancer: Dealing With Diagnosis (Ways to improve coping). Updated October 9, 2014. ...

  16. Update on the role of melatonin in the prevention of cancer tumorigenesis and in the management of cancer correlates, such as sleep-wake and mood disturbances: review and remarks.

    Science.gov (United States)

    Rondanelli, Mariangela; Faliva, Milena Anna; Perna, Simone; Antoniello, Neldo

    2013-10-01

    The aim of this article was to perform a systematic review on the role of melatonin in the prevention of cancer tumorigenesis--in vivo and in vitro--as well as in the management of cancer correlates, such as sleep-wake and mood disturbances. The International Agency for Research on Cancer recently classified "shift-work that involves circadian disruption" as "probably carcinogenic to humans" (Group 2A) based on "limited evidence in humans for the carcinogenicity of shift-work that involves night-work", and "sufficient evidence in experimental animals for the carcinogenicity of light during the daily dark period (biological night)". The clinical implications and the potential uses of melatonin in terms of biologic clock influence (e.g. sleep and mood), immune function, cancer initiation and growth, as well as the correlation between melatonin levels and cancer risk, are hereinafter recorded and summarized. Additionally, this paper includes a description of the newly discovered effects that melatonin has on the management of sleep-wake and mood disturbances as well as with regard to cancer patients' life quality. In cancer patients depression and insomnia are frequent and serious comorbid conditions which definitely require a special attention. The data presented in this review encourage the performance of new clinical trials to investigate the possible use of melatonin in cancer patients suffering from sleep-wake and mood disturbances, also considering that melatonin registered a low toxicity in cancer patients.

  17. Country Update: Israel 2005

    Science.gov (United States)

    Marar, Marianne Maurice

    2005-01-01

    Country Updates is a new section of "Intercultural Education." Starting in "Intercultural Education," Volume 16 No. 5, this column will focus on recent developments during the last two to three years in the field of intercultural education in one particular country. These updates can include recent policy decisions, the main…

  18. Use of indocyanine green for detecting the sentinel lymph node in breast cancer patients: from preclinical evaluation to clinical validation.

    Directory of Open Access Journals (Sweden)

    Chongwei Chi

    Full Text Available Assessment of the sentinel lymph node (SLN in patients with early stage breast cancer is vital in selecting the appropriate surgical approach. However, the existing methods, including methylene blue and nuclides, possess low efficiency and effectiveness in mapping SLNs, and to a certain extent exert side effects during application. Indocyanine green (ICG, as a fluorescent dye, has been proved reliable usage in SLN detection by several other groups. In this paper, we introduce a novel surgical navigation system to detect SLN with ICG. This system contains two charge-coupled devices (CCD to simultaneously capture real-time color and fluorescent video images through two different bands. During surgery, surgeons only need to follow the fluorescence display. In addition, the system saves data automatically during surgery enabling surgeons to find the registration point easily according to image recognition algorithms. To test our system, 5 mice and 10 rabbits were used for the preclinical setting and 22 breast cancer patients were utilized for the clinical evaluation in our experiments. The detection rate was 100% and an average of 2.7 SLNs was found in 22 patients. Our results show that the usage of our surgical navigation system with ICG to detect SLNs in breast cancer patients is technically feasible.

  19. Mechanism of Cancer Growth Suppression of Alpha-Fetoprotein Derived Growth Inhibitory Peptides (GIP): Comparison of GIP-34 versus GIP-8 (AFPep). Updates and Prospects

    Energy Technology Data Exchange (ETDEWEB)

    Mizejewski, Gerald J. [Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States)

    2011-06-20

    The Alpha-fetoprotein (AFP) derived Growth Inhibitory Peptide (GIP) is a 34-amino acid segment of the full-length human AFP molecule that inhibits tumor growth and metastasis. The GIP-34 and its carboxy-terminal 8-mer segment, termed GIP-8, were found to be effective as anti-cancer therapeutic peptides against nine different human cancer types. Following the uptake of GIP-34 and GIP-8 into the cell cytoplasm, each follows slightly different signal transduction cascades en route to inhibitory pathways of tumor cell growth and proliferation. The parallel mechanisms of action of GIP-34 versus GIP-8 are demonstrated to involve interference of signaling transduction cascades that ultimately result in: (1) cell cycle S-phase/G2-phase arrest; (2) prevention of cyclin inhibitor degradation; (3) protection of p53 from inactivation by phosphorylation; and (4) blockage of K{sup +} ion channels opened by estradiol and epidermal growth factor (EGF). The overall mechanisms of action of both peptides are discussed in light of their differing modes of cell attachment and uptake fortified by RNA microarray analysis and electrophysiologic measurements of cell membrane conductance and resistance. As a chemotherapeutic adjunct, the GIPs could potentially aid in alleviating the negative side effects of: (1) tamoxifen resistance, uterine hyperplasia/cancer, and blood clotting; (2) Herceptin antibody resistance and cardiac (arrest) arrhythmias; and (3) doxorubicin's bystander cell toxicity.

  20. Mechanism of Cancer Growth Suppression of Alpha-Fetoprotein Derived Growth Inhibitory Peptides (GIP: Comparison of GIP-34 versus GIP-8 (AFPep. Updates and Prospects

    Directory of Open Access Journals (Sweden)

    Gerald J. Mizejewski

    2011-06-01

    Full Text Available The Alpha-fetoprotein (AFP derived Growth Inhibitory Peptide (GIP is a 34-amino acid segment of the full-length human AFP molecule that inhibits tumor growth and metastasis. The GIP-34 and its carboxy-terminal 8-mer segment, termed GIP-8, were found to be effective as anti-cancer therapeutic peptides against nine different human cancer types. Following the uptake of GIP-34 and GIP-8 into the cell cytoplasm, each follows slightly different signal transduction cascades en route to inhibitory pathways of tumor cell growth and proliferation. The parallel mechanisms of action of GIP-34 versus GIP-8 are demonstrated to involve interference of signaling transduction cascades that ultimately result in: (1 cell cycle S-phase/G2-phase arrest; (2 prevention of cyclin inhibitor degradation; (3 protection of p53 from inactivation by phosphorylation; and (4 blockage of K+ ion channels opened by estradiol and epidermal growth factor (EGF. The overall mechanisms of action of both peptides are discussed in light of their differing modes of cell attachment and uptake fortified by RNA microarray analysis and electrophysiologic measurements of cell membrane conductance and resistance. As a chemotherapeutic adjunct, the GIPs could potentially aid in alleviating the negative side effects of: (1 tamoxifen resistance, uterine hyperplasia/cancer, and blood clotting; (2 Herceptin antibody resistance and cardiac (arrest arrhythmias; and (3 doxorubicin’s bystander cell toxicity.

  1. The association between the TP53 Arg72Pro polymorphism and colorectal cancer: An updated meta-analysis based on 32 studies

    Science.gov (United States)

    Tian, Xin; Dai, Shundong; Sun, Jing; Jiang, Shenyi; Jiang, Youhong

    2017-01-01

    Several previous studies evaluated the association between the Arg72Pro (rs1042522) polymorphism in the TP53 tumor suppressor gene and colorectal cancer (CRC). However, the results are conflicting. This meta-analysis aimed to shed new light on the precise association between TP53 variants and CRC. We analyzed 32 published case-control studies involving 8,586 cases and 10,275 controls using crude odd ratios (ORs) with 95% confidence intervals (CIs). The meta-analysis was performed using a fixed-effect or random-effects model, as appropriate. We found that the TP53 Arg72Pro polymorphism was not significantly associated with CRC risk in the overall population. However, subgroup analysis based on ethnicity revealed an increased risk of CRC among Asians (CC vs. GC+GG: OR=1.22, 95% CI: 1.02-1.45), and similar results were found for rectal cancer (CC vs. GC+GG: OR=1.34, 95% CI: 1.120-1.62). These results suggest that the TP53 Arg72Pro polymorphism CC genotype may contribute to an increased risk of CRC, especially for rectal cancer and among Asians. PMID:27901479

  2. Chemotherapy Plus Cetuximab versus Chemotherapy Alone for Patients with KRAS Wild Type Unresectable Liver-Confined Metastases Colorectal Cancer: An Updated Meta-Analysis of RCTs

    Science.gov (United States)

    Lv, W.; Zhang, G. Q.; Jiao, A.; Zhao, B. C.; Shi, Y.; Chen, B. M.

    2017-01-01

    Purpose. Our study analyses clinical trials and evaluates the efficacy of adding cetuximab in systematic chemotherapy for unresectable colorectal cancer liver-confined metastases patients. Materials and Methods. Search EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials for RCTs comparing chemotherapy plus cetuximab with chemotherapy alone for KRAS wild type patients with colorectal cancer liver metastases (CRLMs). We calculated the relative risks (RRs) with 95% confidence interval and performed meta-analysis of hazard ratios (HRs) for the R0 resection rate, the overall response rate (ORR), the progression-free survival (PFS) and overall survival (OS). Results. 1173 articles were retrieved and 4 RCTs were available for our study. The four studies involved 504 KRAS wild type patients with CRLMs. The addition of cetuximab significantly improved all the 4 outcomes: the R0 resection rate (RR 2.03, p = 0.004), the ORR (RR 1.76, p < 0.00001), PFS (HR 0.63, p < 0.0001), and also OS (HR 0.74, p = 0.04); the last outcome is quite different from the conclusion published before. Conclusions. Although the number of patients analysed was limited, we found that the addition of cetuximab significantly improves the outcomes in KRAS wild type patients with unresectable colorectal cancer liver-confined metastases. Cetuximab combined with systematic chemotherapy perhaps suggests a promising choice for KRAS wild type patients with unresectable liver metastases. PMID:28167959

  3. Bioassays for estrogenic activity: development and validation of estrogen receptor (ERalpha/ERbeta) and breast cancer proliferation bioassays to measure serum estrogenic activity in clinical studies.

    Science.gov (United States)

    Li, J; Lee, L; Gong, Y; Shen, P; Wong, S P; Wise, Stephen D; Yong, E L

    2009-02-01

    Standard estrogenic prodrugs such as estradiol valerate (E2V) and increasingly popular phytoestrogen formulations are commonly prescribed to improve menopausal health. These drugs are metabolized to numerous bioactive compounds, known or unknown, which may exert combinatorial estrogenic effects in vivo. The aim of this study is to develop and validate estrogen receptor (ER) alpha/ERbeta reporter gene and MCF-7 breast cancer cell proliferation bioassays to quantify serum estrogenic activities in a clinical trial setting. We measured changes in serum estrogenicity following ingestion of E2V and compared this to mass spectrometric measurements of its bioactive metabolites, estrone and 17beta-stradiol. ERalpha bioactivity of the 192 serum samples correlated well (R = 79%) with 17beta-estradiol levels, and adding estrone improved R to 0.83 (likelihood ratio test, P estrogenic activity and that these assays suggest that the Epimedium formulation tested is unlikely to exert significant estrogenic effects in humans.

  4. Tyrosine kinase inhibitors for epidermal growth factor receptor gene mutation-positive non-small cell lung cancers: an update for recent advances in therapeutics.

    Science.gov (United States)

    Chung, Clement

    2016-06-01

    The presence of activating gene mutations in the epidermal growth factor receptor of non-small cell lung cancer patients is predictive (improved progression-free survival and improved response rate) when treated with small molecule tyrosine kinase inhibitors such as gefitinib, erlotinib and afatinib. The two most common mutations that account for greater than 85% of all EGFR gene mutations are in-frame deletions in exon 19 (LREA deletions) and substitution in exon 21 (L858R). Exon 18 mutations occur much less frequently at about 4% of all EGFR gene mutations. Together, exon 19 deletion and exon 21 L858R gene substitution are present in about 10% of Caucasian patients and 20-40% of Asian patients with non-small cell lung cancer. T790M gene mutation at exon 20 is associated with acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors. Early studies showed that activating EGFR gene mutations are most common in patients with adenocarcinoma histology, women, never smokers and those of Asian ethnicity. A recent multi-center phase III trial suggested that frontline epidermal growth factor receptor tyrosine kinase inhibitor therapy with afatinib is associated with improved progression-free survival compared to chemotherapy regardless of race. Moreover, guidelines now suggest EGFR gene mutation testing should be conducted in all patients with lung adenocarcinoma or mixed lung cancers with an adenocarcinoma component, regardless of characteristics such as smoking status, gender or race. The success of targeted therapies in non-small cell lung cancer patients has changed the treatment paradigm in metastatic non-small cell lung cancer. However, despite a durable response of greater than a year, resistance to epidermal growth factor receptor tyrosine kinase inhibitors inevitably occurs. This mini-review describes the clinically relevant EGFR gene mutations and the efficacy/toxicity of small molecule epidermal growth factor receptor tyrosine kinase

  5. Role of MTHFR A1298C gene polymorphism in the etiology of prostate cancer: A systematic review and updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Upendra Yadav

    2016-04-01

    Full Text Available Methylenetetrahydrofolate reductase (MTHFR is an important enzyme of folate/homocysteine pathway and is essential for synthesis, repair and methylation of DNA. Various studies have performed to evaluate the role of MTHFR A1298C gene polymorphism to the risk of prostate cancer and the results were inconclusive and inconsistent. A meta-analysis of published case-control studies, up to December 2014, was performed to investigate the association between MTHFR A1298C gene polymorphism and the susceptibility of prostate cancer. PubMed, Science direct, Springer link and Google scholar databases were searched for case-control studies and crude odds ratios (ORs with 95% confidence intervals (CIs were calculated to estimate the strength of association. The analyses were conducted with Open Meta-Analyst and MIX softwares. Total thirteen case-control studies with 4673 prostate cancer patients and 6982 controls were included in this meta-analysis. No associations were observed between MTHFR A1298C gene polymorphism and prostate cancer in any genetic model (allele contrast (C vs. A: OR = 1.01; 95% CI: 0.91–1.13; p = 0.73; dominant model (CC + AC vs. AA: OR = 0.98, 95% CI = 0.91–1.06, p = 0.73; homozygote model (CC vs. AA: OR = 0.96, 95% CI = 0.83–1.10, p = 0.55; co-dominant model (AC vs. AA: OR = 0.98, 95% CI = 0.91–1.07, p = 0.76; and recessive model (CC vs. AC + AA: OR = 0.96, 95% CI = 0.84–1.10, p = 0.61. Moreover, when the data were stratified on the basis of ethnicity no significant associations were observed. The results of the present meta-analysis suggest that the MTHFR A1298C gene polymorphism has no effect on the etiology of prostate cancer.

  6. Immunodiagnosis and molecular validation of Toxoplasma gondii-recombinant dense granular (GRA) 7 protein for the detection of toxoplasmosis in patients with cancer.

    Science.gov (United States)

    Arab-Mazar, Zahra; Fallahi, Shirzad; Koochaki, Ameneh; Haghighi, Ali; Seyyed Tabaei, Seyyed Javad

    2016-02-01

    Serological assays for the diagnosis of toxoplasmosis mostly rely on the tachyzoite specific antigens of Toxoplasma gondii, which are difficult to produce by conventional methods. The aim of this study was to clone and express of GRA7 protein of T. gondii and evaluate its potential for immunodiagnosis of toxoplasmosis in cancer patients. As well as validate the results using a new molecular assay, LAMP technique. The GRA7 gene was successfully cloned, expressed and purified by affinity chromatography and the production was evaluated by SDS PAGE, dot blot and western blot analyses. The rGRA7 was used for developing an ELISA based on the rGRA7 using sera from patients with toxoplasmosis and healthy controls. Furthermore, 50 serum samples from leukemic children infected with toxoplasmosis and 50 seronegative controls were included to evaluate the sensitivity and specificity of rGRA7 based ELISA. Finally, the LAMP technique was used to assess the accuracy and validity of the results obtained by rGRA7 based ELISA. The consistency of the results of two tests was determined by using the Kappa coefficient of agreement. The rGRA7 showed higher and optimum immunoreactivity with 1:100 dilution of serum from Toxoplasma infected patients. The sensitivity and specificity of test were calculated as 92 and 94%, respectively. According to the Kappa coefficient of agreement, there was a significant conformance between the results obtained by ELISA based on the rGRA7 and the results of LAMP technique (≈96%, Ptoxoplasmosis in patients including patients with cancer.

  7. 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 ...

  8. Colorectal cancer biomarker discovery and validation using LC-MS/MS-based proteomics in blood: truth or dare?

    Science.gov (United States)

    Reumer, Ank; Maes, Evelyne; Mertens, Inge; Cho, William C S; Landuyt, Bart; Valkenborg, Dirk; Schoofs, Liliane; Baggerman, Geert

    2014-08-01

    Globally, colorectal cancer (CRC) is the third most common malignant neoplasm. However, highly sensitive, specific, noninvasive tests that allow CRC diagnosis at an early stage are still needed. As circulatory blood reflects the physiological status of an individual and/or the disease status for several disorders, efforts have been undertaken to identify candidate diagnostic CRC markers in plasma and serum. In this review, the challenges, bottlenecks and promising properties of mass spectrometry (MS)-based proteomics in blood are discussed. More specifically, important aspects in clinical design, sample retrieval, sample preparation, and MS analysis are presented. The recent developments in targeted MS approaches in plasma or serum are highlighted as well.

  9. 克罗恩病并发结直肠癌的研究进展%Updates in the research of Crohn's disease complicated by colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    徐骁盟; 任建安

    2014-01-01

    克罗恩病是一种主要累及消化道的自身免疫相关的炎症性疾病.近年来,该病的发病率和患病率在亚洲地区急剧上升,而结直肠癌是其严重的并发症之一.因此,了解克罗恩病癌变的现状与机制,加强对患者的癌症筛查与监测,对于降低克罗恩病患者的癌症病死率具有重要意义.本文对克罗恩病并发结直肠癌的倾向和分子机制,以及目前国际上对克罗恩病患者结直肠癌预防的研究进展进行综述.%Crohn's disease is a relapsing systemic inflammatory disease mainly affecting the gastrointestinal tract.Recently,the incidence and prevalence of Crohn's disease is increasing dramatically in Asia,and colorectal cancer is one of the most fatal complications of Crohn's disease.A thorough understanding of the carcinogenesis of Crohn' s disease and enhance the surveillance of colorectal cancer among Crohn's disease is therefore of significant importance to reduce the mortality.In this review,the tendency and molecular mechanism of carcinogenesis of Crohn's disease were discussed,and the present research on the prevention against colorectal cancer in patients with Crohn's disease was introduced.

  10. Accelerated echo planar J-resolved spectroscopic imaging in prostate cancer: a pilot validation of non-linear reconstruction using total variation and maximum entropy.

    Science.gov (United States)

    Nagarajan, Rajakumar; Iqbal, Zohaib; Burns, Brian; Wilson, Neil E; Sarma, Manoj K; Margolis, Daniel A; Reiter, Robert E; Raman, Steven S; Thomas, M Albert

    2015-11-01

    The overlap of metabolites is a major limitation in one-dimensional (1D) spectral-based single-voxel MRS and multivoxel-based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two-dimensional (2D) J-resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four-dimensional (4D) echo planar J-resolved spectroscopic imaging (EP-JRESI). The goal of the present work was to validate two different non-linear reconstruction methods independently using compressed sensing-based 4D EP-JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty-two patients with PCa with a mean age of 63.8 years (range, 46-79 years) were investigated in this study. A 4D non-uniformly undersampled (NUS) EP-JRESI sequence was implemented on a Siemens 3-T MRI scanner. The NUS data were reconstructed using two non-linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non-cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo-inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP-JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites.

  11. Pathology-based validation of FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schinagl, Dominic A.X. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Radboud University Nijmegen Medical Centre, Department of Radiation Oncology (874), P.O. Box 9101, Nijmegen (Netherlands); Span, Paul N.; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Hoogen, Frank J.A. van den [Radboud University Nijmegen Medical Centre, Department of Otorhinolaryngology, Head and Neck Surgery, Nijmegen (Netherlands); Merkx, Matthias A.W. [Radboud University Nijmegen Medical Centre, Department of Oral and Maxillofacial Surgery, Nijmegen (Netherlands); Slootweg, Piet J. [Radboud University Nijmegen Medical Centre, Department of Pathology, Nijmegen (Netherlands); Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2013-12-15

    FDG PET is increasingly incorporated into radiation treatment planning of head and neck cancer. However, there are only limited data on the accuracy of radiotherapy target volume delineation by FDG PET. The purpose of this study was to validate FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer against the pathological method as the standard. Twelve patients with head and neck cancer and 28 metastatic lymph nodes eligible for therapeutic neck dissection underwent preoperative FDG PET/CT. The metastatic lymph nodes were delineated on CT (Node{sub CT}) and ten PET segmentation tools were used to assess FDG PET-based nodal volumes: interpreting FDG PET visually (PET{sub VIS}), applying an isocontour at a standardized uptake value (SUV) of 2.5 (PET{sub SUV}), two segmentation tools with a fixed threshold of 40 % and 50 %, and two adaptive threshold based methods. The latter four tools were applied with the primary tumour as reference and also with the lymph node itself as reference. Nodal volumes were compared with the true volume as determined by pathological examination. Both Node{sub CT} and PET{sub VIS} showed good correlations with the pathological volume. PET segmentation tools using the metastatic node as reference all performed well but not better than PET{sub VIS}. The tools using the primary tumour as reference correlated poorly with pathology. PET{sub SUV} was unsatisfactory in 35 % of the patients due to merging of the contours of adjacent nodes. FDG PET accurately estimates metastatic lymph node volume, but beyond the detection of lymph node metastases (staging), it has no added value over CT alone for the delineation of routine radiotherapy target volumes. If FDG PET is used in radiotherapy planning, treatment adaptation or response assessment, we recommend an automated segmentation method for purposes of reproducibility and interinstitutional comparison. (orig.)

  12. Cathepsin D Expression in Colorectal Cancer: From Proteomic Discovery through Validation Using Western Blotting, Immunohistochemistry, and Tissue Microarrays

    Directory of Open Access Journals (Sweden)

    Chandra Kirana

    2012-01-01

    Full Text Available Despite recent advances in surgical techniques and therapeutic treatments, survival from colorectal cancer (CRC remains disappointing with some 40–50% of newly diagnosed patients ultimately dying of metastatic disease. Current staging by light microscopy alone is not sufficiently predictive of prognosis and would benefit from additional support from biomarkers in order to stratify patients appropriately for adjuvant therapy. We have identified that cathepsin D expression was significantly greater in cells from invasive front (IF area and liver metastasis (LM than those from main tumour body (MTB. Cathepsin D expression was subsequently examined by immunohistochemistry in tissue microarrays from 119 patients with CRC. Strong expression in tumour cells at the IF did not correlate significantly with any clinico-pathological parameters examined or patient survival. However, cathepsin D expression in cells from the MTB was highly elevated in late stage CRC and showed significant correlation with subsequent distant metastasis and shorter cancer-specific survival. We also found that macrophages surrounding tumour cells stained strongly for cathepsin D but there was no significant correlation found between cathepsin D in macrophages at IF and MTB of CRC patient with the clinic-pathological parameters examined.

  13. Updating verbal and visuospatial working memory: Are the processes parallel?

    Institute of Scientific and Technical Information of China (English)

    YUE ZhenZhu; ZHANG Ming; ZHOU XiaoLin

    2008-01-01

    The current study compared the processes of updating verbal and visuospatial working memory (WM) and examined the roles of central executive and slave systems in working memory updating tasks, by changing the number of items updated simultaneously to manipulate the load on central executive. Ex-periment 1 used the verbal WM updating task, and the results validated the efficiency of the paradigm to manipulate the load on central executive. Experiment 2 employed the verbal WM updating task, with the articulatory suppression task to interfere with the phonological loop. The results supported the study by Morris and Jones, revealing that the central executive system played an important role in the updating component of verbal WM, while the phonological loop was responsible for the serial recall component. Experiment 3 employed the visuospatial WM updating task, with the spatial tapping task to interfere with the visuospatial sketchpad. The results suggested that the visuospatial sketchpad and the central execu-tive together dealt with the updating component, while the visuospatial sketchpad was responsible for the serial recall component by itself. These results are consistent with the findings that visuospatial sketch-pad has close links with central executive, while the phonological loop is separated from the central ex-ecutive. It suggests that updating visuospatial and verbal WM are not two parallel processes.

  14. Non-analgesic effects of opioids: the cognitive effects of opioids in chronic pain of malignant and non-malignant origin. An update.

    Science.gov (United States)

    Højsted, Jette; Kurita, Geana Paula; Kendall, Sally; Lundorff, Lena; de Mattos Pimenta, Cibele Andrucioli; Sjøgren, Per

    2012-01-01

    Opioids constitute the basis for pharmacological treatment of moderate to severe pain in cancer pain and non-cancer pain patients. Their action is mediated by the activation of opioid receptors, which integrates the pain modulation system with other effects in the central nervous system including cognition resulting in complex interactions between pain, opioids and cognition. The literature on this complexity is sparse and information regarding the cognitive effects of opioids in chronic pain patients is substantially lacking. Two previous systematic reviews on cancer pain and non-cancer pain patients only using controlled studies were updated. Fourteen controlled studies on the cognitive effects of opioids in chronic non-cancer pain patients and eleven controlled studies in cancer pain patients were included and analyzed. Opioid treatment involved slightly opposite outcomes in the two patient groups: no effects or worsening of cognitive function in cancer pain patients and no effect or improvements in the chronic non-cancer pain patients, however, due to methodological limitations and a huge variety of designs definite conclusions are difficult to draw from the studies. In studies of higher quality of evidence opioid induced deficits in cognitive functioning were associated with dose increase and the use of supplemental doses of opioids in cancer patients. Future perspectives should comprise the conduction of high quality randomized controlled trials (RCTs) involving relevant control groups and validated neuropsychological assessments tools before and after opioid treatment in order to further explore the complex interaction between pain, opioids and cognition.

  15. Update on study of coagulation and fibrinolysis system in lung cancer patients%肺癌患者凝血纤溶状态的研究进展

    Institute of Scientific and Technical Information of China (English)

    李鸿波; 许启霞

    2011-01-01

    In lung cancer patients, the changes of coagulation and fibrinolysis system have a special influence on the biological characteristics, invasion, metastasis and prognosis of tumer cells. Both pathological hypercoagulability and the effects produced by the urokinase plasminogen activator system through various mechanisms have direct relations with the prognosis in lung cancer patients. Especially,the urokinase plasminogen activator system is expected to be a new breakthrough in theropy and an important prognotic factor.%肺癌患者凝血纤溶系统改变在肿瘤的生物学特性、侵袭、远处转移和预后方面都有独特影响。肺癌患者的病理性高凝状态以及纤溶系统通过各种机制发挥的效应均与肿瘤预后直接相关,尤其是尿激酶型纤溶酶原激活物系统的改变,不仅有望成为肿瘤治疗新的突破点,更是预后的重要影响因素。

  16. Quality of life of head and neck cancer patient: Validation of the European organization for research and treatment of cancer QLQ-C30 and European organization for research and treatment of cancer QLQ-H&N35 in Indian patients

    Directory of Open Access Journals (Sweden)

    Chaukar D

    2005-01-01

    Full Text Available Aims: To present the first cross-culture validation of the European organization for research and treatment of cancer (EORTC quality of life questionnaires, the EORTC-QLQ-C30, and the QLQ-H&N35 in India. Settings and Design: These questionnaires were translated into two vernacular languages and pilot test was done on 15 patients. Two hundred head and neck cancer patients completed the QLQ-C30 and the QLQ-H&N35 at two time points during their treatment. Psychometric evaluation of the structure, reliability, and validity of the questionnaire was undertaken. Results: The data supports the reliability of the scales. Validity was tested by item-scale, scale--scale correlation and by performing known group comparisons. The results demonstrated that the items correlated with their respective scale and no significant correlation was found between scales. The questionnaire was responsive to change over a period of time. Summary: This data suggests that the EORTC QLO-C30 and the QLQ-H&N35 are reliable and valid questionnaires when applied to a sample of head and neck cancer patients in India.

  17. Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures

    NARCIS (Netherlands)

    van den Bogaard, Veerle A B; Ta, Bastiaan D P; van der Schaaf, Arjen; Bouma, Angelique B; Middag, Astrid M H; Bantema-Joppe, Enja J; van Dijk, Lisanne V; van Dijk-Peters, Femke B J; Marteijn, Laurens A W; de Bock, Gertruida H; Burgerhof, Johannes G M; Gietema, Jourik A; Langendijk, Johannes A; Maduro, John H; Crijns, Anne P G

    2017-01-01

    Purpose A relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors f

  18. 2014年第4版日本《胃癌治疗指南》更新要旨%Japanese gastric cancer treatment guidelines-the 4th Edition 2014 update message

    Institute of Scientific and Technical Information of China (English)

    胡祥

    2015-01-01

    2010年第3版日本《胃癌治疗指南》(以下为“指南”)发行以来,对胃癌外科治疗产生了巨大影响,胃癌治疗更为标准化、合理化、规范化。近年来,新的科学研究成果的问世,两次促使“指南”修订、再版。2014年第4版“指南”在原来的基础上,对7个大的问题进行了修订,引进了新的证据和标准(更新胃手术的定义;制定食管胃结合部癌<4 cm时淋巴结清扫的暂行规定和流程图;确定Ⅰ期胃癌腹腔镜下远端胃切除术为常规性治疗;胃镜下治疗的相关标准;化疗方案推荐度;HER2阴性、阳性胃癌的推荐方案、流程图;M1胃癌的手术、化疗问题以及术后随访的相关规定)。第4版“指南”汲取了最新的科学成就,将胃癌治疗的基本原则、概念更为科学化、精准化,为今后的临床实践提供了重要的指导作用。%The launch of Japanese gastric cancer treatment guidelines ( the following as guide)-the 3rd Edition in 2010 has produced a great effect on the surgical treatment of gastric cancer. The treatment of gastric cancer is more standardized, rationalized and normalized. In recent years, new research results made"guide"revised and reedited. In the new"guide"of the 4th Edition 2014, seven major problems were revised on the basis of the previous“guide”. New evidence and standards were introduced (the definition of gastric operation was updated;temporary provisions and flow chart were enacted for the lymph node dissection when the size of esogastric junction adenocarcinoma is smaller than 4cm; laparoscopic distal gastrectomy was considered to be the conventional treatment for stage I gastric cancer; the relevant standards under gastroscope therapy; the recommended degree of chemotherapy ; the recommended scheme and flow chart for HER2-negative and HER2-positive gastric carcinoma; the relevant provisions of the operation, chemotherapy and follow-up for

  19. {sup 177}Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Rajabi, Hossein, E-mail: hrajabi@modares.ac.i [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Babaei, Mohammad Hossein; Daha, Fariba Johari [Department of Radioisotope, Nuclear Science and Technology Research Institute, 14115-331 Tehran (Iran, Islamic Republic of)

    2010-11-15

    Introduction: In the present study, Herceptin was labeled with lutetium-177 via DOTA, and the necessary preclinical quality control tests (in vitro and in vivo) were performed to evaluate its use as a radioimmunotherapy agent. Material and Methods: Herceptin was conjugated to DOTA as a chelator in three different conjugation buffers (ammonium acetate, carbonate and HEPES buffer); each of the resulting conjugates was compared with respect to in vitro characteristics such as number of chelates per antibody, incorporated activity, immunoreactivity and in vitro stability in PBS buffer and blood serum. The biodistribution study and gamma camera imaging were performed in mice bearing breast tumors. To assess the therapeutic effects of {sup 177}Lu-Herceptin, cytotoxicity was investigated for 7 days in a SKBr3 breast cancer cell line. Results: Carbonate buffer was the best conjugation buffer (number of chelates per antibody: 6; incorporated activity: 81%; immunoreactivity: 87%; buffer stability: 86%; serum stability: 81%, after 4 days). The efficient tumor uptake observed in the biodistribution studies was consistent with the gamma camera image results. At a concentration of 4 {mu}g ml{sup -1}, {sup 177}Lu-Herceptin (surviving cells: 5{+-}0.6% of the total cells) of the total cells corresponded to an approximately eightfold increase in cytotoxicity in comparison to unmodified Herceptin (surviving cells: 43{+-}3.9%). Conclusion: The new complex described herein could be considered for further evaluation in animals and potentially in humans as a radiopharmaceutical for use in the radioimmunotherapy of breast cancer. These results may be important for patients who cannot tolerate the therapeutic dosage of Herceptin currently used because of heart problems.

  20. Veterinary medicines update.

    Science.gov (United States)

    2017-03-11

    The following information has been produced for Veterinary Record by the Veterinary Medicines Directorate (VMD) to provide an update for veterinary surgeons on recent changes to marketing authorisations for veterinary medicines in the UK and on other relevant issues.

  1. ACS Updates Environmental Report.

    Science.gov (United States)

    Chemical and Engineering News, 1978

    1978-01-01

    Describes a new publication of a report prepared by the American Chemical Society's Committee on Environmental Improvement. This is a new version that updates a 1969 report and contains additional material and expanded recommendations. (GA)

  2. Updated results of high-dose rate brachytherapy and external beam radiotherapy for locally and locally advanced prostate cancer using the RTOG-ASTRO phoenix definition

    Directory of Open Access Journals (Sweden)

    Antonio C. Pellizzon

    2008-06-01

    Full Text Available PURPOSE: To evaluate the prognostic factors for patients with local or locally advanced prostate cancer treated with external beam radiotherapy (RT and high dose rate brachytherapy (HDR according to the RTOG-ASTRO Phoenix Consensus Conference. MATERIALS AND METHODS: The charts of 209 patients treated between 1997 and 2005 with localized RT and HDR as a boost at the Department of Radiation Oncology, AC Camargo Hospital, Sao Paulo, Brazil were reviewed. Clinical and treatment parameters i.e.: patient's age, Gleason score, clinical stage, initial PSA (iPSA, risk group (RG for biochemical failure, doses of RT and HDR were evaluated. Median age and median follow-up time were 68 and 5.3 years, respectively. Median RT and HDR doses were 45 Gy and 20 Gy. RESULTS: Disease specific survival (DSS at 3.3 year was 94.2%. Regarding RG, for the LR (low risk, IR (intermediate risk and HR (high risk, the DSS rates at 3.3 years were 91.5%, 90.2% and 88.5%, respectively. On univariate analysis prognostic factors related to DSS were RG (p = 0.040, Gleason score ≤ 6 ng/mL (p = 0.002, total dose of HDR ≥ 20 Gy (p < 0.001 On multivariate analysis the only statistical significant predictive factor for biochemical control (bNED was the RG, p < 0.001 (CI - 1.147-3.561. CONCLUSIONS: Although the radiation dose administered to the prostate is an important factor related to bNED, this could not be established with statistical significance in this group of patients. To date , in our own experience, HDR associated to RT could be considered a successful approach in the treatment of prostate cancer.

  3. Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial

    Directory of Open Access Journals (Sweden)

    Shen Kui

    2012-11-01

    Full Text Available Abstract Background The purpose of this study is to assess the predictive accuracy of a multi-gene predictor of response to docetaxel, 5-fluorouracil, epirubicin and cyclophosphamide combination chemotherapy on gene expression data from patients who received these drugs as neoadjuvant treatment. Methods Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC followed by four cycles of docetaxel/capecitabine (TX on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H. The chemotherapy predictor (TFEC-MGP was developed from publicly available gene expression data of 42 breast cancer cell-lines with corresponding in vitro chemotherapy sensitivity results for the four chemotherapy drugs. No predictor was developed for treatment with trastuzumab. The predictive performance of TFEC-MGP in distinguishing cases with pathologic complete response from those with residual disease was evaluated for the FEC/TX and FEC/TX plus H group separately. The area under the receiver-operating characteristic curve (AU-ROC was used as the metric of predictive performance. Genomic predictions were performed blinded to clinical outcome. Results The AU-ROC was 0.70 (95% CI: 0.57-0.82 for the FEC/TX group (n=66 and 0.43 (95% CI: 0.20-0.66 for the FEC/TX plus H group (n=25. Among the patients treated with FEC/TX, the AU-ROC was 0.69 (95% CI: 0.52-0.86 for estrogen receptor (ER-negative (n=28 and it was 0.59 (95% CI: 0.36-0.82 for ER-positive cancers (n=37. ER status was not reported for one patient. Conclusions Our results indicate that the cell line derived 291-probeset genomic predictor of response to FEC/TX combination chemotherapy shows good performance in a blinded validation study, particularly in ER-negative patients.

  4. Factor analysis of the Caregiver Quality of Life Index-Cancer (CQOLC scale for Chinese cancer caregivers: a preliminary reliability and validity study of the CQOLC-Chinese version.

    Directory of Open Access Journals (Sweden)

    Jiaobo Duan

    Full Text Available The English version of the Caregiver Quality of Life Index-Cancer (CQOLC was translated into simplified Chinese (CQOLC-C, following cultural translation, back-translation and pretest steps. Three hundred and sixty one cancer caregivers participated in this study. Cronbach's alpha was used to assess CQOLC-C reliability. Exploratory factor analyses (EFA was used to generate two models of the measure's factor structure, and confirmatory factor analyses (CFA were used to test each model, such that the best model to explain the latent structure of the CQOLC-C was identified. EFA using different factor extraction methods yielded two models including four and eight factors. According to the CFA results, model 2 was better fit for the original study data, based on the RMSEA criterion [0.058(90% CI = 0.051-0.065], χ2 (531 = 853.92, p < 0.0001; CFI (0.96, NNFI (0.96, IFI (0.97, and NFI (0.92. We also examined the effect of removing three items on the CQOLC-C factor structure and discuss the resulting differences from other versions. These results indicate that the CQOLC-C's factor structure does not fully fit the original theorized model. This study provides preliminary support for further use of the CQOLC-C. However, the present work provides only partial support for the relevance and construct validity of the scale for Chinese caregivers.

  5. Gene therapy for gastric cancer: Is it promising?

    Institute of Scientific and Technical Information of China (English)

    Andreas P Sutter; Henry Fechner

    2006-01-01

    Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular alternative in the treatment of gastric cancer,including the replacement of defective tumor suppressor genes, the inactivation of oncogenes, the introduction of suicide genes, genetic immunotherapy, anti-angiogenetic gene therapy, and virotherapy. Improved molecular biological techniques and a better understanding of gastric carcinogenesis have allowed us to validate a variety of genes as molecular targets for gene therapy.This review provides an update of the new developments in cancer gene therapy, new principles, techniques,strategies and vector systems, and shows how they may be applied in the treatment of gastric cancer.

  6. Four-Week Neoadjuvant Intensity-Modulated Radiation Therapy With Concurrent Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer Patients: A Validation Phase II Trial

    Energy Technology Data Exchange (ETDEWEB)

    Arbea, Leire, E-mail: larbea@unav.es [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain); Martinez-Monge, Rafael; Diaz-Gonzalez, Juan A.; Moreno, Marta; Rodriguez, Javier [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain); Hernandez, Jose Luis [Department of General Surgery, Clinica Universidad de Navarra, Navarra (Spain); Sola, Jesus Javier [Department of Pathology, Clinica Universidad de Navarra, Navarra (Spain); Ramos, Luis Isaac [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain); Subtil, Jose Carlos [Department of Gastroenterology, Clinica Universidad de Navarra, Navarra (Spain); Nunez, Jorge [Department of Preventive Medicine and Public Health, Clinica Universidad de Navarra, Navarra (Spain); Chopitea, Ana; Cambeiro, Mauricio; Gaztanaga, Miren; Garcia-Foncillas, Jesus; Aristu, Javier [Department of Oncology, Clinica Universidad de Navarra, Navarra (Spain)

    2012-06-01

    Purpose: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. Methods and Materials: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m{sup 2} b.i.d., Monday to Friday) and oxaliplatin (60 mg/m{sup 2} on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. Results: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. Conclusions: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.

  7. A Validated Prediction Model for Overall Survival From Stage III Non-Small Cell Lung Cancer: Toward Survival Prediction for Individual Patients

    Energy Technology Data Exchange (ETDEWEB)

    Oberije, Cary, E-mail: cary.oberije@maastro.nl [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); De Ruysscher, Dirk [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Universitaire Ziekenhuizen Leuven, KU Leuven (Belgium); Houben, Ruud [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands); Heuvel, Michel van de; Uyterlinde, Wilma [Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Deasy, Joseph O. [Memorial Sloan Kettering Cancer Center, New York (United States); Belderbos, Jose [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Department of Pulmonology, University Hospital Maastricht, Research Institute GROW of Oncology, Maastricht (Netherlands); Rimner, Andreas; Din, Shaun [Memorial Sloan Kettering Cancer Center, New York (United States); Lambin, Philippe [Radiation Oncology, Research Institute GROW of Oncology, Maastricht University Medical Center, Maastricht (Netherlands)

    2015-07-15

    Purpose: Although patients with stage III non-small cell lung cancer (NSCLC) are homogeneous according to the TNM staging system, they form a heterogeneous group, which is reflected in the survival outcome. The increasing amount of information for an individual patient and the growing number of treatment options facilitate personalized treatment, but they also complicate treatment decision making. Decision support systems (DSS), which provide individualized prognostic information, can overcome this but are currently lacking. A DSS for stage III NSCLC requires the development and integration of multiple models. The current study takes the first step in this process by developing and validating a model that can provide physicians with a survival probability for an individual NSCLC patient. Methods and Materials: Data from 548 patients with stage III NSCLC were available to enable the development of a prediction model, using stratified Cox regression. Variables were selected by using a bootstrap procedure. Performance of the model was expressed as the c statistic, assessed internally and on 2 external data sets (n=174 and n=130). Results: The final multivariate model, stratified for treatment, consisted of age, gender, World Health Organization performance status, overall treatment time, equivalent radiation dose, number of positive lymph node stations, and gross tumor volume. The bootstrapped c statistic was 0.62. The model could identify risk groups in external data sets. Nomograms were constructed to predict an individual patient's survival probability ( (www.predictcancer.org)). The data set can be downloaded at (https://www.cancerdata.org/10.1016/j.ijrobp.2015.02.048). Conclusions: The prediction model for overall survival of patients with stage III NSCLC highlights the importance of combining patient, clinical, and treatment variables. Nomograms were developed and validated. This tool could be used as a first building block for a decision support system.

  8. Validating Fiducial Markers for Image-Guided Radiation Therapy for Accelerated Partial Breast Irradiation in Early-Stage Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Catherine K. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Pritz, Jakub [Department of Physics, University of South Florida, Tampa, FL (United States); Zhang, Geoffrey G.; Forster, Kenneth M. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Harris, Eleanor E.R., E-mail: Eleanor.Harris@Moffitt.org [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States)

    2012-03-01

    Purpose: Image-guided radiation therapy (IGRT) may be beneficial for accelerated partial breast irradiation (APBI). The goal was to validate the use of intraparenchymal textured gold fiducials in patients receiving APBI. Methods and Materials: Twenty-six patients were enrolled on this prospective study that had three or four textured gold intraparenchymal fiducials placed at the periphery of the lumpectomy cavity and were treated with three-dimensional (3D) conformal APBI. Free-breathing four-dimensional computed tomography image sets were obtained pre- and posttreatment, as were daily online megavoltage (MV) orthogonal images. Intrafraction motion, variations in respiratory motion, and fiducial marker migration were calculated using the 3D coordinates of individual fiducials and a calculated center of mass (COM) of the fiducials. We also compared the relative position of the fiducial COM with the geometric center of the seroma. Results: There was less than 1 mm of intrafraction respiratory motion, variation in respiratory motion, or fiducial marker migration. The change in seroma position relative to the fiducial COM was 1 mm {+-} 1 mm. The average position of the geometric seroma relative to the fiducial COM pretreatment compared with posttreatment was 1 mm {+-} 1 mm. The largest daily variation in displacement when using bony landmark was in the anteroposterior direction and two standard deviations (SD) of this variation was 10 mm. The average variation in daily separation between the fiducial pairs from daily MV images was 3 mm {+-} 3 mm therefore 2 SD is 6 mm. Conclusion: Fiducial markers are stable throughout the course of APBI. Planning target volume margins when using bony landmarks should be 10 mm and can be reduced to 6 mm if using fiducials.

  9. Safe eating during cancer treatment

    Science.gov (United States)

    ... to 165°F (73.9°C). Warm hot dogs and lunch meats to steaming before you eat ... National Cancer Institute: PDQ Nutrition in cancer care. Bethesda, MD: National Cancer Institute. Updated January 8, 2016. www.cancer. ...

  10. The science behind the 7th edition Tumour, Node, Metastasis staging system for lung cancer.

    Science.gov (United States)

    Marshall, Henry M; Leong, Steven C; Bowman, Rayleen V; Yang, Ian A; Fong, Kwun M

    2012-02-01

    The Tumour, Node, Metastasis (TNM) system for classifying lung cancer is the cornerstone of modern lung cancer treatment and underpins comparative research; yet is continuously evolving through updated revisions. The recently published Union for International Cancer Control 7th Edition TNM Classification for lung cancer addresses many of its predecessor's shortcomings and has been subject to rigorous evidence-based methodology. It is based on a retrospective analysis of over 80 000 lung cancer patients treated between 1990 and 2000 carried out by the International Association for the Study of Lung Cancer. The dataset was truly international and included patients treated by all modalities. Extensive internal and external validation of the findings has ensured that the recommendations are robust and generalizable. For the first time, a single classification system has been shown to be applicable not only to non-small cell lung cancer, but also to be of prognostic significance in small cell lung cancer and bronchopulmonary carcinoid tumours. We review the history of the Union for International Cancer Control TNM staging system, the changes in the most recent 7th edition and the strength of the scientific basis motivating these changes. Limitations of the current staging edition are explored, post-publication independent validation studies are reviewed, and the future of TNM staging for lung cancer is discussed.

  11. Understanding cancer staging

    Science.gov (United States)

    ... Manual and Handbook . 2nd ed. New York, NY: Springer; 2012. National Cancer Institute. Staging. Updated March 9, ... medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- ...

  12. SU-E-J-244: Development and Validation of a Knowledge Based Planning Model for External Beam Radiation Therapy of Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Z; Kennedy, A [Sarah Cannon, Nashville, TN (United States); Larsen, E; Hayes, C; Grow, A [North Florida Cancer Center, Gainesville, FL (United States); Bahamondes, S.; Zheng, Y; Wu, X [JFK Comprehensive Cancer Institute, Lake Worth, FL (United States); Choi, M; Pai, S [Good Samaritan Hospital, Los Gatos, CA (United States); Li, J [Doctors Hospital of Augusta, Augusta, GA (United States); Cranford, K [Trident Medical Center, Charleston, SC (United States)

    2015-06-15

    Purpose: The study aims to develop and validate a knowledge based planning (KBP) model for external beam radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). Methods: RapidPlan™ technology was used to develop a lung KBP model. Plans from 65 patients with LA-NSCLC were used to train the model. 25 patients were treated with VMAT, and the other patients were treated with IMRT. Organs-at-risk (OARs) included right lung, left lung, heart, esophagus, and spinal cord. DVH and geometric distribution DVH were extracted from the treated plans. The model was trained using principal component analysis and step-wise multiple regression. Box plot and regression plot tools were used to identify geometric outliers and dosimetry outliers and help fine-tune the model. The validation was performed by (a) comparing predicted DVH boundaries to actual DVHs of 63 patients and (b) using an independent set of treatment planning data. Results: 63 out of 65 plans were included in the final KBP model with PTV volume ranging from 102.5cc to 1450.2cc. Total treatment dose prescription varied from 50Gy to 70Gy based on institutional guidelines. One patient was excluded due to geometric outlier where 2.18cc of spinal cord was included in PTV. The other patient was excluded due to dosimetric outlier where the dose sparing to spinal cord was heavily enforced in the clinical plan. Target volume, OAR volume, OAR overlap volume percentage to target, and OAR out-of-field volume were included in the trained model. Lungs and heart had two principal component scores of GEDVH, whereas spinal cord and esophagus had three in the final model. Predicted DVH band (mean ±1 standard deviation) represented 66.2±3.6% of all DVHs. Conclusion: A KBP model was developed and validated for radiotherapy of LA-NSCLC in a commercial treatment planning system. The clinical implementation may improve the consistency of IMRT/VMAT planning.

  13. Update of European bioethics

    DEFF Research Database (Denmark)

    Rendtorff, Jacob Dahl

    2015-01-01

    This paper presents an update of the research on European bioethics undertaken by the author together with Professor Peter Kemp since the 1990s, on Basic ethical principles in European bioethics and biolaw. In this European approach to basic ethical principles in bioethics and biolaw, the princip......This paper presents an update of the research on European bioethics undertaken by the author together with Professor Peter Kemp since the 1990s, on Basic ethical principles in European bioethics and biolaw. In this European approach to basic ethical principles in bioethics and biolaw......, the principles of autonomy, dignity, integrity and vulnerability are proposed as the most important ethical principles for respect for the human person in biomedical and biotechnological development. This approach to bioethics and biolaw is presented here in a short updated version that integrates the earlier...

  14. Development and validation of a general approach to predict and quantify the synergism of anti-cancer drugs using experimental design and artificial neural networks.

    Science.gov (United States)

    Pivetta, Tiziana; Isaia, Francesco; Trudu, Federica; Pani, Alessandra; Manca, Matteo; Perra, Daniela; Amato, Filippo; Havel, Josef

    2013-10-15

    The combination of two or more drugs using multidrug mixtures is a trend in the treatment of cancer. The goal is to search for a synergistic effect and thereby reduce the required dose and inhibit the development of resistance. An advanced model-free approach for data exploration and analysis, based on artificial neural networks (ANN) and experimental design is proposed to predict and quantify the synergism of drugs. The proposed method non-linearly correlates the concentrations of drugs with the cytotoxicity of the mixture, providing the possibility of choosing the optimal drug combination that gives the maximum synergism. The use of ANN allows for the prediction of the cytotoxicity of each combination of drugs in the chosen concentration interval. The method was validated by preparing and experimentally testing the combinations with the predicted highest synergistic effect. In all cases, the data predicted by the network were experimentally confirmed. The method was applied to several binary mixtures of cisplatin and [Cu(1,10-orthophenanthroline)2(H2O)](ClO4)2, Cu(1,10-orthophenanthroline)(H2O)2(ClO4)2 or [Cu(1,10-orthophenanthroline)2(imidazolidine-2-thione)](ClO4)2. The cytotoxicity of the two drugs, alone and in combination, was determined against human acute T-lymphoblastic leukemia cells (CCRF-CEM). For all systems, a synergistic effect was found for selected combinations.

  15. MEK Inhibitors Research Update

    Science.gov (United States)

    Drugs that block the MEK protein have shown promise in several cancers. Trametinib has had encouraging results in patients with advanced melanoma, and selumetinib has been tested in patients with advanced thyroid and ovarian cancers.

  16. Multiple Sclerosis: An Update.

    Science.gov (United States)

    Faguy, Kathryn

    2016-05-01

    Multiple sclerosis (MS) is the most common disabling neurologic condition in young adults and imposes high financial and quality of life costs on patients, their families, and society. Yet, developments in the battle against MS include new treatments to slow its progression and updated diagnostic criteria that can accelerate diagnosis and effective treatment. This article offers a review and update on the disease, focusing on risk factors and possible causes, symptoms, forms of MS, diagnostic criteria and tools, and the expanding array of approved treatments. It also reports on the skyrocketing cost of MS drugs, misdiagnosis, and special patient populations with MS.

  17. Agreement for depression diagnosis between DSM-IV-TR criteria, three validated scales, oncologist assessment, and psychiatric clinical interview in elderly patients with advanced ovarian cancer

    Directory of Open Access Journals (Sweden)

    Rhondali W

    2015-07-01

    Anxiety Depression Scale, the distress thermometer, the mood thermometer, and OA. The interview guide for PCI was constructed from three validated scales: the GDS, the Hamilton Depression Rating Scale, and the Montgomery Asberg Depression Rating Scale (MADRS. The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, revised (DSM criteria for depression were used as a gold standard.Results: Out of 109 patients enrolled at 21 centers, 99 (91% completed all the assessments. Patient characteristics were: mean age 78, performance status ≥2: 47 (47%. Thirty six patients (36% were identified as depressed by the PCI versus 15 (15% identified by DSM. We found moderate agreement for depression identification between DSM and GDS (κ=0.508 and PCI (κ=0.431 and high agreement with MADRS (κ=0.663. We found low or no agreement between DSM with the other assessment strategies, including OA (κ=-0.043. Identification according to OA (yes/no resulted in a false-negative rate of 87%. As a screening tool, GDS had the best sensitivity and specificity (94% and 80%, respectively.Conclusion: The use of validated tools, such as GDS, and collaboration between psychologists and oncologists are warranted to better identify emotional disorders in elderly women with AOC. Keywords: depression, elderly, cancer, screening, geriatric assessment

  18. Cancer

    Science.gov (United States)

    ... uses a surgical tool to remove the tumor.Mohs' surgery. Layers of cancer cells are removed one ... usually have not been approved by the U.S. Food and Drug Administration (FDA). The medicine may have ...

  19. Updating the OMERACT filter

    DEFF Research Database (Denmark)

    D'Agostino, Maria-Antonietta; Boers, Maarten; Kirwan, John

    2014-01-01

    OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Filter provides a framework for the validation of outcome measures for use in rheumatology clinical research. However, imaging and biochemical measures may face additional validation challenges because of their technical nature. The Imagin...

  20. Cancer immunotherapy

    DEFF Research Database (Denmark)

    Cairns, Linda; Aspeslagh, Sandrine; Anichini, Andrea

    2016-01-01

    This report covers the Immunotherapy sessions of the 2016 Organisation of European Cancer Institutes (OECI) Oncology Days meeting, which was held on 15th-17th June 2016 in Brussels, Belgium. Immunotherapy is a potential cancer treatment that uses an individual's immune system to fight the tumour....... In recent years significant advances have been made in this field in the treatment of several advanced cancers. Cancer immunotherapies include monoclonal antibodies that are designed to attack a very specific part of the cancer cell and immune checkpoint inhibitors which are molecules that stimulate...... or block the inhibition of the immune system. Other cancer immunotherapies include vaccines and T cell infusions. This report will summarise some of the research that is going on in this field and will give us an update on where we are at present....

  1. Update of telephone exchange

    CERN Multimedia

    2006-01-01

    As part of the upgrade of telephone services, the CERN switching centre will be updated on between Monday 23 October 8.00 p.m. and Tuesday 24 October 2.00 a.m. Telephone services may be disrupted and possibly even interrupted during this operation. We apologise in advance for any inconvenience this may cause. CERN TELECOM Service

  2. Update of telephone exchange

    CERN Multimedia

    2006-01-01

    As part of the upgrade of telephone services, the CERN switching centre will be updated on Monday 3 July between 8.00 p.m. and 3.00 a.m. Telephone services may be disrupted and possibly even interrupted during this operation. We apologise in advance for any inconvenience this may cause. CERN TELECOM Service

  3. Update of telephone exchange

    CERN Multimedia

    2006-01-01

    As part of the upgrade of telephone services, the CERN switching centre will be updated on Wednesday 14 June between 8.00 p.m. and midnight. Telephone services may be disrupted and possibly even interrupted during this operation. We apologise in advance for any inconvenience this may cause. CERN TELECOM Service

  4. Update of telephone exchange

    CERN Multimedia

    2006-01-01

    As part of the upgrade of telephone services, the CERN switching centre will be updated on Monday 3 July between 8.00 p.m. and 3.00 a.m. Telephone services may be disrupted and possibly even interrupted during this operation.We apologise in advance for any inconvenience this may cause. CERN TELECOM Service

  5. XLMR genes: update 2000.

    NARCIS (Netherlands)

    Chiurazzi, P.; Hamel, B.C.J.; Neri, G.

    2001-01-01

    This is the sixth edition of the catalogue of XLMR genes, ie X-linked genes whose malfunctioning causes mental retardation. The cloning era is not yet concluded, actually much remains to be done to account for the 202 XLMR conditions listed in this update. Many of these may eventually prove to be du

  6. Updating Older Fume Hoods.

    Science.gov (United States)

    Saunders, G. Thomas

    1985-01-01

    Provides information on updating older fume hoods. Areas addressed include: (1) adjustment of the hood's back baffle; (2) hood air leakage; (3) light level; (4) hood location in relation to room traffic and room air; and (5) establishing and maintaining hood performance. (JN)

  7. Cohort Profile