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  1. Opportunities for Cancer-relevant Innovative Technologies with Transformative Potential | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.

  2. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

  3. Clinical investigation of TROP-2 as an independent biomarker and potential therapeutic target in colon cancer.

    Science.gov (United States)

    Zhao, Peng; Yu, Hai-Zheng; Cai, Jian-Hui

    2015-09-01

    Colon cancer is associated with a severe demographic and economic burden worldwide. The pathogenesis of colon cancer is highly complex and involves sequential genetic and epigenetic mechanisms. Despite extensive investigation, the pathogenesis of colon cancer remains to be elucidated. As the third most common type of cancer worldwide, the treatment options for colon cancer are currently limited. Human trophoblast cell‑surface marker (TROP‑2), is a cell‑surface transmembrane glycoprotein overexpressed by several types of epithelial carcinoma. In addition, TROP‑2 has been demonstrated to be associated with tumorigenesis and invasiveness in solid types of tumor. The aim of the present study was to investigate the protein expression of TROP‑2 in colon cancer tissues, and further explore the association between the expression of TROP‑2 and clinicopathological features of patients with colon cancer. The expression and localization of the TROP‑2 protein was examined using western blot analysis and immunofluorescence staining. Finally, the expression of TROP‑2 expression was correlated to conventional clinicopathological features of colon cancer using a χ2 test. The results revealed that TROP‑2 protein was expressed at high levels in the colon cancer tissues, which was associated with the development and pathological process of colon cancer. Therefore, TROP‑2 may be used as a biomarker to determine the clinical prognosis, and as a potential therapeutic target in colon cancer.

  4. ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer.

    Science.gov (United States)

    Shi, Yanhua; Wang, Wei; Yang, Baozhi; Tian, Hongge

    2017-10-01

    Cervical cancer is one of the most common cancers among women worldwide. It is highly lethal yet can be treated when found in early stage. Thus, early detection is of significant important for early diagnosis of cervical cancer. Exosomes have been used as biomarkers in clinical diagnosis. It is unknown that whether blood exosomes associated with cervical cancer can be detected and if these exosomes can accurately represent the developmental stage of cervical cancer. Mouse models were made out of a relapsed cervical cancer patient's tumour sample for original and recurrent cervical cancer, and gene analysis in both tumours and exosomes in these mouse models were performed. We found that activating transcription factor 1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary and recurrent cervical cancer mouse model, and they can also be detected in the blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1 and RAS genes were found significantly elevated in tumours of primary and recurrent cervical cancer mouse model, and they were also detected in the blood exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for cervical cancer in the future. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Proton therapy of cancer: Potential clinical advantages and cost-effectiveness

    International Nuclear Information System (INIS)

    Lundkvist, Jonas; Ekman, Mattias; Rehn Ericsson, Suzanne; Glimelius, Bengt; Akademiska sjukhuset, Uppsala

    2005-01-01

    Proton therapy may offer potential clinical advantages compared with conventional radiation therapy for many cancer patients. Due to the large investment costs for building a proton therapy facility, however, the treatment cost with proton radiation is higher than with conventional radiation. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to motivate the higher costs. We assessed the cost-effectiveness of proton therapy in the treatment of four different cancers: left-sided breast cancer, prostate cancer, head and neck cancer, and childhood medulloblastoma. A Markov cohort simulation model was created for each cancer type and used to simulate the life of patients treated with radiation. Cost and quality adjusted life years (QALYs) were used as primary outcome measures. The results indicated that proton therapy was cost-effective if appropriate risk groups were chosen. The average cost per QALY gained for the four types of cancer assessed was about Euro 10,130. If the value of a QALY was set to Euro 55,000, the total yearly net benefit of treating 925 cancer patients with the four types of cancer was about Euro 20.8 million. Investment in a proton facility may thus be cost-effective. The results must be interpreted with caution, since there is a lack of data, and consequently large uncertainties in the assumptions used

  6. Proton therapy for head and neck cancer: Rationale, potential indications, practical considerations, and current clinical evidence

    International Nuclear Information System (INIS)

    Mendenhall, Nancy P.; Malyapa, Robert S.; Su, Zhong; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng

    2011-01-01

    There is a strong rationale for potential benefits from proton therapy (PT) for selected cancers of the head and neck because of the opportunity to improve the therapeutic ratio by improving radiation dose distributions and because of the significant differences in radiation dose distribution achievable with x-ray-based radiation therapy (RT) and PT. Comparisons of dose distributions between x-ray-based and PT plans in selected cases show specific benefits in dose distribution likely to translate into improved clinical outcomes. However, the use of PT in head and neck cancers requires special considerations in the simulation and treatment planning process, and currently available PT technology may not permit realization of the maximum potential benefits of PT. To date, few clinical data are available, but early clinical experiences in sinonasal tumors in particular suggest significant improvements in both disease control and radiation-related toxicity

  7. Proton therapy for head and neck cancer: Rationale, potential indications, practical considerations, and current clinical evidence

    Energy Technology Data Exchange (ETDEWEB)

    Mendenhall, Nancy P.; Malyapa, Robert S.; Su, Zhong; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng (Univ. of Florida Proton Therapy Inst., Jacksonville, Florida (United States)), e-mail: menden@shands.ufl.edu

    2011-08-15

    There is a strong rationale for potential benefits from proton therapy (PT) for selected cancers of the head and neck because of the opportunity to improve the therapeutic ratio by improving radiation dose distributions and because of the significant differences in radiation dose distribution achievable with x-ray-based radiation therapy (RT) and PT. Comparisons of dose distributions between x-ray-based and PT plans in selected cases show specific benefits in dose distribution likely to translate into improved clinical outcomes. However, the use of PT in head and neck cancers requires special considerations in the simulation and treatment planning process, and currently available PT technology may not permit realization of the maximum potential benefits of PT. To date, few clinical data are available, but early clinical experiences in sinonasal tumors in particular suggest significant improvements in both disease control and radiation-related toxicity

  8. High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

    Science.gov (United States)

    Ocak, S; Sos, M L; Thomas, R K; Massion, P P

    2009-08-01

    During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

  9. Emerging treatments for advanced pancreatic cancer: clinical potential of albumin-bound paclitaxel

    Directory of Open Access Journals (Sweden)

    Fontana E

    2014-06-01

    Full Text Available Elisa Fontana, Francesco Sclafani, David Cunningham Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK Abstract: The management of pancreatic cancer has historically represented a major challenge for oncologists. The inherent aggressiveness of this tumor and the fibrotic features of the surrounding stromal tissue have significantly limited the impact of standard chemotherapy. Moreover, the paucity of available tumor tissue has hampered a better understanding of the biology of this disease as well as the development of new treatment strategies. Recently, the therapeutic landscape of metastatic pancreatic cancer has been enriched by two new combination regimens (FOLFIRINOX and gemcitabine-nab-paclitaxel which have been demonstrated to improve the outcome in patients with good performance status. Moreover, the peritumoral stroma has been increasingly recognized as a potential therapeutic target for this disease, and several new agents targeting stromal components are currently under investigation. In this paper, we review the current treatment options for advanced pancreatic cancer, highlight the role of the peritumoral stroma, and discuss the clinical potential of nab-paclitaxel and antistromal treatment strategies. Keywords: pancreatic cancer, nab-paclitaxel, stroma, SPARC

  10. Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

    Directory of Open Access Journals (Sweden)

    Teresa de Souza Fernandez

    2013-01-01

    Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

  11. The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications

    Directory of Open Access Journals (Sweden)

    Juan A Ramos

    2012-01-01

    Full Text Available Prostate cancer is a global public health problem, and it is the most common cancer in American men and the second cause for cancer-related death. Experimental evidence shows that prostate tissue possesses cannabinoid receptors and their stimulation results in anti-androgenic effects. To review currently relevant findings related to effects of cannabinoid receptors in prostate cancer. PubMed search utilizing the terms "cannabis," "cannabinoids," "prostate cancer," and "cancer pain management," giving preference to most recent publications was done. Articles identified were screened for their relevance to the field of prostate cancer and interest to both urologist and pain specialists. Prostate cancer cells possess increased expression of both cannabinoid 1 and 2 receptors, and stimulation of these results in decrease in cell viability, increased apoptosis, and decreased androgen receptor expression and prostate-specific antigen excretion. It would be of interest to conduct clinical studies utilizing cannabinoids for patients with metastatic prostate cancer, taking advantage not only of its beneficial effects on prostate cancer but also of their analgesic properties for bone metastatic cancer pain.

  12. Potential of cancer cell-derived exosomes in clinical application: a review of recent research advances.

    Science.gov (United States)

    Sun, Yu; Liu, Jing

    2014-06-01

    Exosomes are 30- to 100-nm, membrane-bound vesicles that are released by most types of cells, including tumor cells. Exosomes contain a great variety of bioactive molecules, including signal peptides, microRNA, lipids, and DNA. In cancer, tumor cells aberrantly secrete large quantities of exosomes to transport paracrine signals or to contribute to tumor-environment interaction at a distance. The goal of this review was to discuss the recent advances on the mechanism of cancer-derived exosomes in tumor regulation. Pertinent articles and abstracts were identified through searches of PubMed for literature published from 1983 to December 2013. Search terms included exosome, tumor, cancer, diagnosis, and therapy. All of the exposed evidence points to communication between cancer cells and their surroundings, either mediated by cancer cell-derived exosomes or by stromal cell-derived exosomes. This communication probably supports tumor proliferation, motility, invasion, angiogenesis, and premetastatic niche preparation. In addition, recent research implies that cancer cell-derived exosomes play a suppressive role in cancer-directed immune response. The biomarkers detected in bodily fluid-derived exosomes imply a potential for exosomes in cancer diagnosis. Also, exosomes could be used as a vehicle to selectively deliver therapeutic nucleic-acid drugs or conventional drugs for tumor therapy. The tolerability and feasibility of cancer exosomes in diagnosis and therapy need to be further evaluated. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

  13. Potential clinical applications of halichondrins in breast cancer and other neoplasms

    Directory of Open Access Journals (Sweden)

    Ortega V

    2012-02-01

    Full Text Available Vanesa Ortega1, Javier Cortés1,21Department of Oncology, Vall d’Hebrón University Hospital, Barcelona, Spain; 2Vall d’Hebron Institute of Oncology (VHIO, Barcelona, SpainAbstract: Halichondrin B is a large polyether macrolide found in a rare Japanese sponge, Halichondria okadai and has been shown to have anticancer activity. Eribulin mesylate is a completely synthetic analog of halichondrin B with a unique mechanism of action relative to other antimicrotubule agents. This new agent has demonstrated activity in preclinical studies, and it is being developed for the treatment of different tumor types. Eribulin has been approved by the United States Food and Drug Administration and the European Medicines Agency as late-line therapy for metastatic breast cancer patients previously treated with an anthracycline and a taxane. It has demonstrated superiority over other treatments in overall survival (OS (hazard ratio: 0.81, P = 0.041, leading to its regulatory approbation for clinical practice use. Median OS for the eribulin-treated group was 13.1 months versus 10.6 months in the physician’s treatment-of-choice group. Eribulin demonstrated a manageable toxicity profile. Most common adverse events associated with treatment were mild neutropenia and fatigue, mainly of grade 1 or 2. In contrast to other antimicrotubule agents, eribulin has a relatively low incidence of peripheral neuropathy and alopecia. Eribulin has been extensively studied in breast cancer and is currently being developed for treatment of other cancer types. Eribulin has demonstrated activity in Phase II trials in non-small cell lung cancer, pancreatic cancer, urothelial tract cancer, and sarcomas. Further studies in these cancers are ongoing. This article reviews pharmacology, mechanism of action, pharmacokinetics and efficacy of eribulin in breast cancer and other neoplasms.Keywords: halichondrin B, eribulin, antimicrotubule, metastatic breast cancer

  14. Clinical evidence of the efficacy of everolimus and its potential in the treatment of breast cancer

    Directory of Open Access Journals (Sweden)

    Saksena R

    2013-05-01

    Full Text Available Rujuta Saksena, Serena T WongThe Cancer Institute of New Jersey, New Brunswick, NJ, USAAbstract: The PI3K/Akt/mTOR (phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway regulates several key cellular functions and its dysregulation creates an environment that promotes tumorigenesis as well as resistance to therapy. The mTOR inhibitor everolimus has emerged as a promising agent in the treatment of breast cancer and was recently approved in combination with exemestane for advanced hormone receptor–positive disease after progression on a nonsteroidal aromatase inhibitor. Everolimus may also be effective in combination with cytotoxic and human epidermal growth factor receptor-2-directed therapies for the treatment of other subtypes of breast cancer. This paper highlights preclinical and clinical data that have emerged on the role of mTOR inhibition in breast cancer. Although generally well tolerated, everolimus carries a unique side effect profile of which both patients and providers should be made aware. Recommendations related to the administration of everolimus in the clinical setting are also discussed.Keywords: everolimus, breast cancer, mTOR inhibition

  15. Biology and potential clinical implications of tissue inhibitor of metalloproteinases-1 in colorectal cancer treatment

    DEFF Research Database (Denmark)

    Sørensen, Nanna Møller; Sørensen, irene Vejgaard; Würtz, Sidse Ørnbjerg

    2008-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the industrialized world. About half of "curatively" resected patients develop recurrent disease within the next 3-5 years despite the lack of clinical, histological and biochemical evidence of remaining overt disease...... after resection of the primary tumour. Availability of validated biological markers for early detection, selection for adjuvant therapy, prediction of treatment efficacy and monitoring of treatment efficacy would most probably increase survival. Tissue inhibitor of metalloproteinases-1 (TIMP-1) may...... patients, suggesting that TIMP-1 could have a tumour-promoting function. Furthermore, measurement of plasma TIMP-1 has been shown to be useful for disease detection, with a high sensitivity and high specificity for early-stage colon cancer. This review describes some basic information on the current...

  16. The Potential Role of Lycopene for the Prevention and Therapy of Prostate Cancer: From Molecular Mechanisms to Clinical Evidence

    Science.gov (United States)

    Holzapfel, Nina Pauline; Holzapfel, Boris Michael; Champ, Simon; Feldthusen, Jesper; Clements, Judith; Hutmacher, Dietmar Werner

    2013-01-01

    Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. PMID:23857058

  17. Hypnosis in the Perioperative Management of Breast Cancer Surgery: Clinical Benefits and Potential Implications

    Science.gov (United States)

    Roelants, Fabienne; Pospiech, Audrey; Momeni, Mona; Watremez, Christine

    2016-01-01

    The aim of this review is to summarize data published on the use of perioperative hypnosis in patients undergoing breast cancer surgery (BCS). Indeed, the majority of BCS patients experience stress, anxiety, nausea, vomiting, and pain. Correct management of the perioperative period and surgical removal of the primary tumor are clearly essential but can affect patients on different levels and hence have a negative impact on oncological outcomes. This review examines the effect of clinical hypnosis performed during the perioperative period. Thanks to its specific properties and techniques allowing it to be used as complementary treatment preoperatively, hypnosis has an impact most notably on distress and postoperative pain. During surgery, hypnosis may be applied to limit immunosuppression, while, in the postoperative period, it can reduce pain, anxiety, and fatigue and improve wound healing. Moreover, hypnosis is inexpensive, an important consideration given current financial concerns in healthcare. Of course, large randomized prospective studies are now needed to confirm the observed advantages of hypnosis in the field of oncology. PMID:27635132

  18. Potential clinical applications of {sup 18}F-fluorodeoxyglucose position emission tomography/magnetic resonance mammography in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Ihn Ho; Kong, Eun Jung [Dept. of Nuclear Medicine, Yeugnam University Hospital, Daegu (Korea, Republic of)

    2017-09-15

    The whole-body positron emission tomography (PET)/magnetic resonance (MR) scan is a cutting edge technology providing comprehensive structural information from MR imaging and functional features from PET in a single session. Recent research findings and clinical experience have shown that 18F-fluorodeoxyglucose (FDG) whole-body PET/MR imaging has a diagnostic performance comparable with or superior to that of PET/CT in the field of oncology, including for breast cancer. In particular, FDG PET/MR mammography in the prone position with the breast hanging in a pendant manner can provide more comprehensive information about the metabolism, anatomy, and functional features of a breast lesion than a whole-body PET/MR scan. This article reports on current state-of-the-art PET/MR mammography in patients with breast cancer and the prospects for potential application in the future.

  19. Chemoradiation Therapy for Potentially Resectable Gastric Cancer: Clinical Outcomes Among Patients Who Do Not Undergo Planned Surgery

    International Nuclear Information System (INIS)

    Kim, Michelle M.; Mansfield, Paul F.; Das, Prajnan; Janjan, Nora A.; Badgwell, Brian D.; Phan, Alexandria T.; Delclos, Marc E.; Maru, Dipen; Ajani, Jaffer A.; Crane, Christopher H.; Krishnan, Sunil

    2008-01-01

    Purpose: We retrospectively analyzed treatment outcomes among resectable gastric cancer patients treated preoperatively with chemoradiation therapy (CRT) but rendered ineligible for planned surgery because of clinical deterioration or development of overt metastatic disease. Methods and Materials: Between 1996 and 2004, 39 patients with potentially resectable gastric cancer received preoperative CRT but failed to undergo surgery. At baseline clinical staging, 33 (85%) patients had T3-T4 disease, and 27 (69%) patients had nodal involvement. Most patients received 45 Gy of radiotherapy with concurrent 5-fluorouracil-based chemotherapy. Twenty-one patients underwent induction chemotherapy before CRT. Actuarial times to local control (LC), distant control (DC), and overall survival (OS) were calculated by the Kaplan-Meier method. Results: The cause for surgical ineligibility was development of metastatic disease (28 patients, 72%; predominantly peritoneal, 18 patients), poor performance status (5 patients, 13%), patient/physician preference (4 patients, 10%), and treatment-related death (2 patients, 5%). With a median follow-up of 8 months (range, 1-95 months), actuarial 1-year LC, DC, and OS were 46%, 12%, and 36%, respectively. Median LC and OS were 11.0 and 10.1 months, respectively. Conclusions: Patients with potentially resectable gastric cancer treated with preoperative CRT are found to be ineligible for surgery principally because of peritoneal progression. Patients who are unable to undergo planned surgery have outcomes comparable to that of patients with advanced gastric cancer treated with chemotherapy alone. CRT provides durable LC for the majority of the remaining life of these patients

  20. Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications.

    Science.gov (United States)

    Baba, Yoshifumi; Iwatsuki, Masaaki; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

    2017-06-01

    Esophageal cancer ranks among the most aggressive malignant diseases. The limited improvements in treatment outcomes provided by conventional therapies have prompted us to seek innovative strategies for treating this cancer. More than 100 trillion microorganisms inhabit the human intestinal tract and play a crucial role in health and disease conditions, including cancer. The human intestinal microbiome is thought to influence tumor development and progression in the gastrointestinal tract by various mechanisms. For example, Fusobacterium nucleatum , which primarily inhabits the oral cavity and causes periodontal disease, might contribute to aggressive tumor behavior through activation of chemokines such as CCL20 in esophageal cancer tissue. Composition of the intestinal microbiota is influenced by diet, lifestyle, antibiotics, and pro- and prebiotics. Therefore, by better understanding how the bacterial microbiota contributes to esophageal carcinogenesis, we might develop novel cancer prevention and treatment strategies through targeting the gastrointestinal microflora. This review discusses the current knowledge, available data and information on the relationship of microbiota with esophagitis, Barrett's esophagus, esophageal adenocarcinoma and squamous cell carcinoma.

  1. Can reduction of uncertainties in cervix cancer brachytherapy potentially improve clinical outcome?

    DEFF Research Database (Denmark)

    Nesvacil, Nicole; Tanderup, Kari; Lindegaard, Jacob C

    2016-01-01

    AIM: The aim of this study was to quantify the impact of different types and magnitudes of dosimetric uncertainties in cervix cancer brachytherapy (BT) on tumour control probability (TCP) and normal tissue complication probability (NTCP) curves. MATERIALS AND METHODS: A dose-response simulation...

  2. UFT and leucovorin: a review of its clinical development and therapeutic potential in the oral treatment of cancer.

    Science.gov (United States)

    Hoff, P M; Pazdur, R; Benner, S E; Canetta, R

    1998-07-01

    UFT is an oral antineoplastic drug combining uracil and tegafur in a 4:1 molar ratio. Tegafur acts as a prodrug of 5-fluorouracil (5-FU), being slowly metabolized by cytochrome P450 to 5-FU. Uracil competitively inhibits the metabolism of 5-FU, resulting in increased plasma and tumor 5-FU concentrations. At equimolar doses, higher peak plasma 5-FU concentrations are achieved with UFT plus oral leucovorin with similar systemic 5-FU exposure compared with low-dose continuous 5-FU infusions. The elimination half-life of 5-FU following UFT administration is approximately 7 h compared with 0.2 h with i.v. 5-FU. In phase II studies of UFT plus oral leucovorin for the treatment of advanced colorectal cancer, response rates ranged from 25 to 42%. UFT plus oral leucovorin is well tolerated, with manageable diarrhea being the only dose-limiting toxicity; the regimen is not associated with significant myelosuppression, mucositis, hand-foot syndrome or alopecia. UFT, with or without leucovorin, has also been evaluated alone or in combination with other cytotoxic agents for the treatment of advanced lung, breast and gastric cancers. UFT has also been evaluated as adjuvant therapy for colorectal, breast, gastric, head and neck, and superficial bladder cancers. UFT plus leucovorin offers patients an entirely oral cancer treatment, and appears to provide potential advantages over bolus 5-FU regimens with regard to toxicity and convenience of administration. These benefits should be advantageous in the adjuvant setting, as well as in advanced disease settings in which palliation is an important consideration. Ongoing clinical trials will further define the role of this promising oral treatment regimen.

  3. Potential clinical impact of laser-accelerated beams in cancer ion therapy

    Energy Technology Data Exchange (ETDEWEB)

    Obcemea, Ceferino

    2016-09-01

    In this article, I present three advantages of plasma-accelerated ion beams for cancer therapy. I discuss how: 1. low-emittance and well-collimated beams are advantageous in proximal normal tissue-sparing; 2. highly-peaked quasi-monoenergetic beams are ideal for fast energy selection and switching in Pencil Beam Scanning (PBS) as a treatment delivery; 3. high fluence and ultra-short pulse delivery produce collective excitations in the medium and enhance the stopping power. This in turn produces denser ionization track signatures (spurs, blobs, etc.) in target tumors, higher linear energy transfer, higher Bragg peak, and higher radiobiological effectiveness at the micro-level.

  4. Potential clinical predictors of outcome after postoperative radiotherapy of non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Buetof, R. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiation Oncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, OncoRay National Center for Radiation Research in Oncology, Dresden (Germany); Kirchner, K.; Appold, S. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiation Oncology, Dresden (Germany); Loeck, S. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, OncoRay National Center for Radiation Research in Oncology, Dresden (Germany); Rolle, A. [Lungenfachklinik Coswig, Department of Thoracic and Vascular Surgery, Coswig (Germany); Hoeffken, G. [Lungenfachklinik Coswig, Department of Pneumology, Coswig (Germany); Krause, M.; Baumann, M. [Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Department of Radiation Oncology, Dresden (Germany); Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, OncoRay National Center for Radiation Research in Oncology, Dresden (Germany); German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany); Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany)

    2014-03-15

    The aim of this analysis was to investigate the impact of tumour-, treatment- and patient-related cofactors on local control and survival after postoperative adjuvant radiotherapy in patients with non-small cell lung cancer (NSCLC), with special focus on waiting and overall treatment times. For 100 NSCLC patients who had received postoperative radiotherapy, overall, relapse-free and metastases-free survival was retrospectively analysed using Kaplan-Meier methods. The impact of tumour-, treatment- and patient-related cofactors on treatment outcome was evaluated in uni- and multivariate Cox regression analysis. No statistically significant difference between the survival curves of the groups with a short versus a long time interval between surgery and radiotherapy could be shown in uni- or multivariate analysis. Multivariate analysis revealed a significant decrease in overall survival times for patients with prolonged overall radiotherapy treatment times exceeding 42 days (16 vs. 36 months) and for patients with radiation-induced pneumonitis (8 vs. 29 months). Radiation-induced pneumonitis and prolonged radiation treatment times significantly reduced overall survival after adjuvant radiotherapy in NSCLC patients. The negative impact of a longer radiotherapy treatment time could be shown for the first time in an adjuvant setting. The hypothesis of a negative impact of longer waiting times prior to commencement of adjuvant radiotherapy could not be confirmed. (orig.) [German] Das Ziel der vorliegenden Analyse war, den Einfluss von tumor-, patienten- und therapieabhaengigen Kofaktoren auf die lokoregionale Tumorkontrolle und das Ueberleben nach postoperativer adjuvanter Strahlentherapie bei Patienten mit einem nicht-kleinzelligen Bronchialkarzinom (NSCLC) zu untersuchen. Ein spezieller Fokus lag dabei auf der Wartezeit zwischen Operation und Beginn der Strahlentherapie sowie der Gesamtbehandlungszeit der Strahlentherapie. Fuer 100 Patienten, die eine postoperative

  5. Cancer clinical trials

    International Nuclear Information System (INIS)

    Scheurlen, A.; Kay, R.; Baum, M.

    1988-01-01

    This book contains the proceedings on Cancer clinical trials: A critical appraisal. Topics covered include: Scientific fundamentals; Heterogeneous treatment effects; On combining information: Historical controls, overviews, and comprehensive cohort studies; and assessment of quality of life

  6. Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

    Directory of Open Access Journals (Sweden)

    Rothschild SI

    2014-09-01

    Full Text Available Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: The therapeutic landscape in non-small-cell lung cancer (NSCLC is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. Keywords: nintedanib, lung cancer, angiokinase inhibitor, VEGFR, PDGF, FGFR

  7. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

    Science.gov (United States)

    Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A

    2013-11-04

    Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered

  8. MO-C-BRB-05: Translating NIH funding to a [potential] clinical device in breast cancer radiation therapy

    International Nuclear Information System (INIS)

    Yu, C.

    2015-01-01

    Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, and the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration

  9. MO-C-BRB-05: Translating NIH funding to a [potential] clinical device in breast cancer radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yu, C. [Univ Maryland School of Medicine (United States)

    2015-06-15

    Diagnostic radiology and radiation oncology are arguably two of the most technologically advanced specialties in medicine. The imaging and radiation medicine technologies in clinical use today have been continuously improved through new advances made in the commercial and academic research arenas. This symposium explores the translational path from research through clinical implementation. Dr. Pettigrew will start this discussion by sharing his perspectives as director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB). The NIBIB has focused on promoting research that is technological in nature and has high clinical impact. We are in the age of precision medicine, and the technological innovations and quantitative tools developed by engineers and physicists working with physicians are providing innovative tools that increase precision and improve outcomes in health care. NIBIB funded grants lead to a very high patenting rate (per grant dollar), and these patents have higher citation rates by other patents, suggesting greater clinical impact, as well. Two examples of clinical translation resulting from NIH-funded research will be presented, in radiation therapy and diagnostic imaging. Dr. Yu will describe a stereotactic radiotherapy device developed in his laboratory that is designed for treating breast cancer with the patient in the prone position. It uses 36 rotating Cobalt-60 sources positioned in an annular geometry to focus the radiation beam at the system’s isocenter. The radiation dose is delivered throughout the target volume in the breast by constantly moving the patient in a planned trajectory relative to the fixed isocenter. With this technique, the focal spot dynamically paints the dose distribution throughout the target volume in three dimensions. Dr. Jackson will conclude this symposium by describing the RSNA Quantitative Imaging Biomarkers Alliance (QIBA), which is funded in part by NIBIB and is a synergistic collaboration

  10. Clinical Cancer Genetics and Prevention

    Science.gov (United States)

    Olufunmilayo F. Olopade MD, FACP, Professor of Medicine and Human Genetics and Director of the Cancer Risk Clinic Department of Medicine, BSD Section of Hematology/Oncology University of Chicago, presented "Clinical Cancer Genetics and Prevention".

  11. Aberrant expression of PlncRNA-1 and TUG1: potential biomarkers for gastric cancer diagnosis and clinically monitoring cancer progression.

    Science.gov (United States)

    Baratieh, Zohreh; Khalaj, Zahra; Honardoost, Mohammad Amin; Emadi-Baygi, Modjtaba; Khanahmad, Hossein; Salehi, Mansoor; Nikpour, Parvaneh

    2017-12-01

    To evaluate PlncRNA-1, TUG1 and FAM83H-AS1 gene expression and their possible role as a biomarker in gastric cancer (GC) progression. Long noncoding RNA expressions and clinicopathological characteristics were assessed in 70 paired GC tissues. Furthermore, corresponding data from 318 GC patients were downloaded from The Cancer Genome Atlas database. Expression of PlncRNA-1 and TUG1 were significantly upregulated in GC tumoral tissues, and significantly correlated with clinicopathological characters. However, FAM83H-AS1 showed no consistently differential expression. The expression of these three long noncoding RNAs was significantly higher in The Cancer Genome Atlas tumoral tissues. In conclusion, PlncRNA-1 and TUG1 genes may play a critical role in GC progression and may serve as potential diagnostic biomarkers in GC patients.

  12. Peripheral White Blood Cell Subsets in Metastatic Colorectal Cancer Patients Treated with Cetuximab: The Potential Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Ivana Z. Matić

    2018-01-01

    percentages of CD16+, CD56+, and CD16+CD56+ lymphocytes 2 months after treatment in the non-responder group did not differ significantly in comparison with healthy individuals. Considerable alterations of immune cell percentages observed in patients with metastatic colorectal cancer with disease progression indicate that the assessment of peripheral white blood cell architecture before treatment initiation may be clinically relevant.

  13. Pediatric cancer gone viral. Part II: potential clinical application of oncolytic herpes simplex virus-1 in children

    Directory of Open Access Journals (Sweden)

    Gregory K Friedman

    Full Text Available Oncolytic engineered herpes simplex viruses (HSVs possess many biologic and functional attributes that support their use in clinical trials in children with solid tumors. Tumor cells, in an effort to escape regulatory mechanisms that would impair their growth and progression, have removed many mechanisms that would have protected them from virus infection and eventual virus-mediated destruction. Viruses engineered to exploit this weakness, like mutant HSV, can be safely employed as tumor cell killers, since normal cells retain these antiviral strategies. Many preclinical studies and early phase trials in adults demonstrated that oncolytic HSV can be safely used and are highly effective in killing tumor cells that comprise pediatric malignancies, without generating the toxic side effects of nondiscriminatory chemotherapy or radiation therapy. A variety of engineered viruses have been developed and tested in numerous preclinical models of pediatric cancers and initial trials in patients are underway. In Part II of this review series, we examine the preclinical evidence to support the further advancement of oncolytic HSV in the pediatric population. We discuss clinical advances made to date in this emerging era of oncolytic virotherapy.

  14. Therapeutic treatments potentially mediated by melatonin receptors: potential clinical uses in the prevention of osteoporosis, cancer and as an adjuvant therapy.

    Science.gov (United States)

    Witt-Enderby, Paula A; Radio, Nicholas M; Doctor, John S; Davis, Vicki L

    2006-11-01

    Melatonin's therapeutic potential is grossly underestimated because its functional roles are diverse and its mechanism(s) of action are complex and varied. Melatonin produces cellular effects via a variety of mechanisms in a receptor independent and dependent manner. In addition, melatonin is a chronobiotic agent secreted from the pineal gland during the hours of darkness. This diurnal release of melatonin impacts the sensitivity of melatonin receptors throughout a 24-hr period. This changing sensitivity probably contributes to the narrow therapeutic window for use of melatonin in treating sleep disorders, that is, at the light-to-dark (dusk) or dark-to-light (dawn) transition states. In addition to the cyclic changes in melatonin receptors, many genes cycle over the 24-hr period, independent or dependent upon the light/dark cycle. Interestingly, many of these genes support a role for melatonin in modulating metabolic and cardiovascular physiology as well as bone metabolism and immune function and detoxification of chemical agents and cancer reduction. Melatonin also enhances the actions of a variety of drugs or hormones; however, the role of melatonin receptors in modulating these processes is not known. The goal of this review is to summarize the evidence related to the utility of melatonin as a therapeutic agent by focusing on its other potential uses besides sleep disorders. In particular, its use in cancer prevention, osteoporosis and, as an adjuvant to other therapies are discussed. Also, the role that melatonin and, particularly, its receptors play in these processes are highlighted.

  15. PRE-CLINICAL EVALUATION OF EXTRACTS AND ESSENTIAL OILS FROM BETEL-LIKE SCENT PIPER SPECIES IDENTIFIED POTENTIAL CANCER TREATMENT.

    Science.gov (United States)

    Sanubol, Arisa; Chaveerach, Arunrat; Tanee, Tawatchai; Sudmoon, Runglawan

    2017-01-01

    Nine Piper species with betel-like scents are sources of industrial and medicinal aromatic chemicals, but there is lack of information on cytotoxicity and genotoxicity for human safety, including how these plants impact human cervical cancer cell line. Plant leaves were extracted with hexane and hydro-distilled for essential oils. The extracts and oils were pre-clinically studied based on cyto - and genotoxicity using microculture tetrazolium (MTT) and comet assays. The crude extracts showed an IC 50 in leukocytes and HeLa cells of 58.59-97.31 mg/ml and 34.91-101.79 mg/ml, the LD 50 is higher than 5000 mg/kg. With lower values than the crude extracts, the essential oils showed an IC 50 in leukocytes and HeLa cells of 0.023-0.059 μg/ml and 0.025-0.043 μg/ml the LD 50 is less than 50 mg/kg. IC 50 values showed that the essential oils were highly toxic than the crude extracts. At the level of human genetic materials, the crude extracts of two species, including P. betloides and P. crocatum , showed a significant toxicity ( p Piper species showed insignificant toxicity in leukocytes. For HeLa cells, the eight-studied species showed significant toxicity in HeLa cells, whereas only P. submultinerve showed insignificant toxicity. The crude extracts and essential oils should be tested as putative cervical cancer treatments due to less toxicity in human normal cells.

  16. Clinical presentation of thyroid cancer

    International Nuclear Information System (INIS)

    Samuel, A.M.; Shah, D.H.

    1999-01-01

    The clinical manifestation of thyroid cancer (TC) as seen at the Nuclear Medicine Department, where the patients investigated prior to diagnosis of disease are clinically suspected to harbor malignancy and mostly referred for scintigraphic investigations are presented

  17. Integration of Breast Cancer Secretomes with Clinical Data Elucidates Potential Serum Markers for Disease Detection, Diagnosis, and Prognosis.

    Science.gov (United States)

    Ziegler, Yvonne S; Moresco, James J; Yates, John R; Nardulli, Ann M

    2016-01-01

    Cancer cells secrete factors that influence adjacent cell behavior and can lead to enhanced proliferation and metastasis. To better understand the role of these factors in oncogenesis and disease progression, estrogen and progesterone receptor positive MCF-7 cells, triple negative breast cancer MDA-MB-231, DT22, and DT28 cells, and MCF-10A non-transformed mammary epithelial cells were grown in 3D cultures. A special emphasis was placed on triple negative breast cancer since these tumors are highly aggressive and no targeted treatments are currently available. The breast cancer cells secreted factors of variable potency that stimulated proliferation of the relatively quiescent MCF-10A cells. The conditioned medium from each cell line was subjected to mass spectrometry analysis and a variety of secreted proteins were identified including glycolytic enzymes, proteases, protease inhibitors, extracellular matrix proteins, and insulin-like growth factor binding proteins. An investigation of the secretome from each cell line yielded clues about strategies used for breast cancer proliferation and metastasis. Some of the proteins we identified may be useful in the development of a serum-based test for breast cancer detection, diagnosis, prognosis, and monitoring.

  18. Expression of the TPα and TPβ isoforms of the thromboxane prostanoid receptor (TP) in prostate cancer: clinical significance and diagnostic potential.

    Science.gov (United States)

    Mulvaney, Eamon P; Shilling, Christine; Eivers, Sarah B; Perry, Antoinette S; Bjartell, Anders; Kay, Elaine W; Watson, R William; Kinsella, B Therese

    2016-11-08

    The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.

  19. Types of Cancer Clinical Trials

    Science.gov (United States)

    Information about the several types of cancer clinical trials, including treatment trials, prevention trials, screening trials, supportive and palliative care trials. Each type of trial is designed to answer different research questions.

  20. The potential of shark bone powder in breast cancer inhibition (pre-clinical study in DMBA-Induced Sprague Dawly Rats)

    Science.gov (United States)

    Bintari, S. H.; Parman, S.; Dafip, M.

    2018-03-01

    Breast cancer is a malignant disease, which lead to second cause of that after cervical cancer in women. To date, lots of drugs and supplement have been developed and consumed by patients. Shark bone is one of the supplements that might inhibit the proliferation of cancer cells. The application of shark bone powder for supplementation in breast cancer cases still becomes controversy; but until now people are still many who consume as a supplement. This study aimed to prove the potency of shark bone powder in the inhibition of breast cancer proliferation and to propose the possibility of its biological mechanism. The pre-clinical experimental study used a controlled posttest controlled design with 25 white rats strains of DML-induced Sprague-Dawley strains. The cancer markers observed were p53, AgNORs, VEGF, Bcl-2, and Cas-3. The test subjects were divided into 3 groups: control group and 2 treatment groups fed modified with 60% and 90% respectively. A pre-clinical trial of shark bone powder showed that there was significant inhibition for the DMBA-induced anti proliferation and breast cell cancer (p breast cancer proliferation lies in concentration 30mg/BB/day.

  1. Clinical potential of boron neutron capture therapy for locally recurrent inoperable previously irradiated head and neck cancer

    International Nuclear Information System (INIS)

    Lim, Diana; Quah, Daniel SC; Leech, Michelle; Marignol, Laure

    2015-01-01

    This review compares the safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of previously irradiated, inoperable locoregional recurrent HNC patients and compares BNCT against the standard treatment of platinum-based chemotherapy. Our analysis of published clinical trials highlights efficacy of BNCT associated with mild side effects. However, the use of BNCT should be explored in stratified randomised trials. - Highlights: • BNCT can prolong median overall survival. • BNCT can be associated with severe adverse effects. • BNCT may be comparable to chemotherapy-based regimens. • BNCT may be comparable to re-irradiation techniques regimens in patients with low performance status.

  2. Accrual to Cancer Clinical Trials

    LENUS (Irish Health Repository)

    Kelly, C

    2016-07-01

    Accrual to cancer clinical trials (CCT) is imperative to safeguard continued improvement in cancer outcomes. A retrospective chart review was performed of patients (n=140) starting a new anti-cancer agent in a north Dublin cancer centre. This review was performed over a four-month period, beginning in November 2015. Only 29% (n=41) had a CCT option. The overall accrual rate to CCT was 5% (n=7), which is comparable to internationally reported figures. The main reasons for failure to recruit to CCT included the lack of a CCT option for cancer type (n=30, 23%), stage (n=25, 19%), and line of treatment (n=23, 17%). Over the last decade, the rate of accrual to CCTs has in fact doubled and the number of trials open to recruitment has tripled. Ongoing governmental and philanthropic support is necessary to continue this trend to further expand CCT patient options with a target accrual rate of 10%.

  3. Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomised controlled trial

    NARCIS (Netherlands)

    Sharples, L. D.; Jackson, C.; Wheaton, E.; Griffith, G.; Annema, J. T.; Dooms, C.; Tournoy, K. G.; Deschepper, E.; Hughes, V.; Magee, L.; Buxton, M.; Rintoul, R. C.

    2012-01-01

    To assess the clinical effectiveness and cost-effectiveness of endosonography (followed by surgical staging if endosonography was negative), compared with standard surgical staging alone, in patients with non-small cell lung cancer (NSCLC) who are otherwise candidates for surgery with curative

  4. Clinical value and potential pathways of miR-183-5p in bladder cancer: A study based on miRNA-seq data and bioinformatics analysis.

    Science.gov (United States)

    Gao, Jia-Min; Huang, Lin-Zhen; Huang, Zhi-Guang; He, Rong-Quan

    2018-04-01

    The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I-II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919-0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments.

  5. Prostate cancer epigenetics and its clinical implications.

    Science.gov (United States)

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  6. Prostate cancer epigenetics and its clinical implications

    Directory of Open Access Journals (Sweden)

    Srinivasan Yegnasubramanian

    2016-01-01

    Full Text Available Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  7. Potential targets for colorectal cancer prevention.

    Science.gov (United States)

    Temraz, Sally; Mukherji, Deborah; Shamseddine, Ali

    2013-08-22

    The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), survivin and insulin-like growth factor-I (IGF-I). Clinical trials of COX-2 inhibitors have provided the "proof of principle" that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.

  8. Potential Targets for Colorectal Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ali Shamseddine

    2013-08-01

    Full Text Available The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2, nuclear factor kappa B (NF-κB, survivin and insulin-like growth factor-I (IGF-I. Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.

  9. Clinical photoacoustic imaging of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Valluru, Keerthi S.; Willmann, Juergen K. [Dept. of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford (United States)

    2016-08-15

    Photoacoustic imaging is a hybrid technique that shines laser light on tissue and measures optically induced ultrasound signal. There is growing interest in the clinical community over this new technique and its possible clinical applications. One of the most prominent features of photoacoustic imaging is its ability to characterize tissue, leveraging differences in the optical absorption of underlying tissue components such as hemoglobin, lipids, melanin, collagen and water among many others. In this review, the state-of-the-art photoacoustic imaging techniques and some of the key outcomes pertaining to different cancer applications in the clinic are presented.

  10. Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: critical analysis of evidence and potential role in clinical practice.

    Science.gov (United States)

    Taverna, Simona; Giallombardo, Marco; Gil-Bazo, Ignacio; Carreca, Anna Paola; Castiglia, Marta; Chacártegui, Jorge; Araujo, Antonio; Alessandro, Riccardo; Pauwels, Patrick; Peeters, Marc; Rolfo, Christian

    2016-05-10

    Exosomes are nano-sized vesicles of endolysosomal origin, released by several cytotypes in physiological and pathological conditions. Tumor derived exosomes, interacting with other cells of the tumor microenvironment, modulate tumor progression, angiogenic switch, metastasis, and immune escape. Recently, extracellular vesicles were proposed as excellent biomarkers for disease monitoring and prognosis in cancer patients. Non-small cell lung cancer (NSCLC) has a poor 5-year survival rate due to the delay in the detection of the disease. The majority of patients are diagnosed in an advanced disease stage. Exosomes might be promising beneficial tools as biomarker candidates in the scenario of NSCLC, since they contain both, proteins and miRNAs. The clinical case reported in this manuscript is a proof of concept revealing that NSCLC exosomes and sorted miRNAs might constitute, in a near future, novel biomarkers. This review summarizes the role of exosomes in NSCLC, focusing on the importance of exosomal microRNAs in lung cancer diagnosis and prognosis.

  11. Clinically unrecognized pulmonary aspiration during gastrointestinal endoscopy with sedation: A potential pitfall interfering the performance of 18F-FDG PET for cancer screening

    International Nuclear Information System (INIS)

    Hsieh, Te-Chun; Wu, Yu-Chin; Ding, Hueisch-Jy; Wang, Chih-Hsiu; Yen, Kuo-Yang; Sun, Shung-Shung; Yeh, Jun-Jun; Kao, Chia-Hung

    2011-01-01

    Purpose: We found several cases with unexpected pulmonary abnormalities on the 18 F-FDG PET scan after the gastrointestinal endoscopy with sedation during a compact health check-up course, interfering the interpretations of 18 F-FDG PET scan for cancer screening. The current studies aimed to analyze the incidence and the clinical relevance of this pulmonary finding. Materials and methods: From June to December 2009, 127 subjects undergoing the sequential gastrointestinal endoscopy with sedation and 18 F-FDG PET scan within 48 h as part of routine health check-up were retrospectively enrolled in this study. The incidence of abnormal pulmonary findings and their SUV max of FDG were calculated and correlated with the clinical manifestations. Results: Five subjects had abnormal 18 F-FDG PET findings but pulmonary symptoms were only found in 2. The SUV max did not seem to reflect the severity of pulmonary symptoms or the need of intervention. Although the incidence of unrecognized pulmonary aspiration featuring inflammation detected by the 18 F-FDG PET scan was high (3.94%, 5/127), the incidence of events needed intervention remained low (0.79%, 1/127), similar to those previously reported literatures. Conclusions: Although higher incidence of pulmonary aspiration in this study, it probably reflects the better sensitivity of 18 F-FDG PET for inflammation. The low incidence of clinical events needed intervention may still reflect the safety of sedation used for gastrointestinal endoscopy. Proper arrangement of the sequential examinations if subjects need both gastrointestinal endoscopy with sedation and 18 F-FDG PET is important to reduce the interference degrading the performance of 18 F-FDG PET in cancer screening, diagnosis or staging.

  12. Clinical perspectives of cancer stem cell research in radiation oncology

    International Nuclear Information System (INIS)

    Bütof, Rebecca; Baumann, Michael; Dubrovska, Anna

    2013-01-01

    Radiotherapy has a proven potential to eradicate cancer stem cells which is reflected by its curative potential in many cancer types. Considerable progress has been made in identification and biological characterisation of cancer stem cells during the past years. Recent biological findings indicate significant inter- and intratumoural and functional heterogeneity of cancer stem cells and lead to more complex models which have potential implications for radiobiology and radiotherapy. Clinical evidence is emerging that biomarkers of cancer stem cells may be prognostic for the outcome of radiotherapy in some tumour entities. Perspectives of cancer stem cell based research for radiotherapy reviewed here include their radioresistance compared to the mass of non-cancer stem cells which form the bulk of all tumour cells, implications for image- and non-image based predictive bio-assays of the outcome of radiotherapy and a combination of novel systemic treatments with radiotherapy

  13. Clinical survey of prostate cancer

    International Nuclear Information System (INIS)

    Takada, Tsuyoshi; Hatano, Koji; Satoh, Mototaka; Tsujimoto, Yuichi; Honda, Masahito; Matsumiya, Kiyomi; Fujioka, Hideki

    2007-01-01

    Treatment trends and outcomes for prostate cancer in our hospital were reported. A total of 482 patients with prostate cancer treated in our hospital between January, 1990 and December, 2004. The age distribution was from 51 to 99 years-old, with the mean age of 72.9 years-old at onset. The number of prostate cancer patients, especially asymptomatic patients with prostatic specific antigen (PSA) elevation, have increased recently. As for the clinical stage, 92 cases (19.1%), 238 cases (49.4%), 48 cases (10.0%) and 104 cases (21.6%) were stage A, B, C and D, respectively. 425 cases (88.2%) received some form of endocrine therapy. Retropubic prostatectomy or external beam radiation therapy was performed in 77 and 57 cases, respectively all cases. The cause-specific 5-year survival rate of the 482 cases was 79.7%, comprising 100% for stage A1, 96.8% for stage A2, 89.4% for stage B, 79.9% for stage C and 42.9% for stage D. The cause-specific 5-year survival was significantly better in the latter patients (1997-2004) than the former patients (1990-1996) in stage C (p=0.0226), D (p=0.0448). In stage C patients, the retropubic prostatectomy (with endocrine therapy) group, increased in the latter period and showed longer cause-specific 5-year survival than the endocrine therapy group (p=0.0027). In stage D2 patients, chemo-endocrine therapy with etoposide (VP-16), adriamycin (ADM) and cisplatin (CDDP) refractory and cause-specific 5-year survival was longer than endocrine therapy alone (p=0.0467, P=0.0381). Our results suggest that retropubic prostatectomy with endocrine therapy and chemo-endocrine therapy are useful for stage C and D prostate cancer patients, respectively. (author)

  14. Comparative treatment planning study on sequential vs. simultaneous integrated boost in head and neck cancer patients. Differences in dose distributions and potential implications for clinical practice

    Energy Technology Data Exchange (ETDEWEB)

    Stromberger, Carmen; Ghadjar, Pirus; Marnitz, Simone; Thieme, Alexander Henry; Jahn, Ulrich; Karaj-Rossbacher, Evis; Budach, Volker [Charite Universitaetsmedizin Berlin, Department of Radiation Oncology and Radiotherapy, Berlin (Germany); Raguse, Jan D. [Charite Universitaetsmedizin Berlin, Clinic for Oral and Maxillofacial Surgery, Berlin (Germany); Boettcher, Arne [Charite Universitaetsmedizin Berlin, Otorhinolaryngology, Berlin (Germany); Jamil, Basil [Communal Hospital Frankfurt Oder, Department of Radiation Oncology, Frankfurt/Oder (Germany)

    2016-01-15

    The purpose of this work was to compare sequential (SeqB) versus simultaneous integrated boost (SIB) radiotherapy plans delivered with volumetric modulated arc therapy (VMAT) for patients with locally advanced squamous cell cancer of the head and neck (HNSCC). SeqB and SIB plans using VMAT for 10 HNSCC patients given definitive chemoradiation were generated and analysed for differences in dose distribution, coverage, conformity and homogeneity to the planning target volumes (PTV) 1-3 and sparing of organs at risk (OAR). The mean delineated volumes ± standard deviations were 137.7 ± 44.8, 351.3 ± 83.9 and 895.6 ± 120.5 cm{sup 3} for PTV1-3. The mean volumes encompassed by the corresponding 95 % isodoses were 281 (+ 110 %) ± 73.4, 712.2 (+ 115 %) ± 146.4 and 1381.1 (+ 54 %) ± 217.3 cm{sup 3} with SeqB and 138.2 (+ 7 %) ± 40.1, 380.4 (+ 11 %) ± 91.9 and 1057.3 (+ 21 %) ± 161.4 cm{sup 3} with SIB for PTV1-3, respectively. Both strategies achieved excellent PTV coverage. SeqB provided significantly better coverage of PTV1 and 3, worse conformity for PTV1-3 and a higher mean dose than prescribed (111-115 %) to PTV2 and 3 (p ≤ 0.007). Both strategies provided satisfactory OAR sparing. This study showed significant dosimetric differences with potential clinical relevance between two VMAT boost strategies regarding coverage, conformity and dose to the PTVs. SIB might cause less toxicity. A clinical phase III/IV trial endorsed by the German Head and Neck Clinical Trials Group (IAG-KHT) will evaluate differences in acute/late toxicity as well as in locoregional recurrences between the two boost techniques. (orig.) [German] Vergleich von sequentiellem (SeqB) und simultan-integriertem Boost (SIB) mit moderner volumetrischer Arc-Therapie (VMAT) fuer Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region. Fuer 10 Patienten mit Plattenepithelkarzinomen der Kopf-Hals-Region und definitiver Radiochemotherapie erfolgte eine VMAT-Planung als SeqB und SIB fuer die

  15. A Review of Barriers to Minorities' Participation in Cancer Clinical Trials: Implications for Future Cancer Research.

    Science.gov (United States)

    Salman, Ali; Nguyen, Claire; Lee, Yi-Hui; Cooksey-James, Tawna

    2016-04-01

    To enhance nurses' awareness and competencies in practice and research by reporting the common barriers to participation of minorities in cancer clinical trials and discussing facilitators and useful strategies for recruitment. Several databases were searched for articles published in peer reviewed journals. Some of the barriers to minorities' participation in clinical trials were identified within the cultural social-context of cancer patients. The involvement of community networking was suggested as the most effective strategy for the recruitment of minorities in cancer clinical trials. Using culturally sensitive approaches to enhance ethnic minorities' participation is important for advancing cancer care and eliminating health disparities. Awareness of barriers and potential facilitators to the enrollment of ethnic minority cancer patients may contribute to enhancing nurses' competencies of recruiting ethnic minorities in nursing research, playing efficient roles in cancer clinical trials team, and providing culturally competent quality care.

  16. Clinical Trials Management | Division of Cancer Prevention

    Science.gov (United States)

    Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded

  17. Clinical targeting recombinant immunotoxins for cancer therapy

    Directory of Open Access Journals (Sweden)

    Li M

    2017-07-01

    Full Text Available Meng Li,1,* Zeng-Shan Liu,1,* Xi-Lin Liu,1,* Qi Hui,2,* Shi-Ying Lu,1 Lin-Lin Qu,1 Yan-Song Li,1 Yu Zhou,1 Hong-Lin Ren,1 Pan Hu1 1Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, China-Japan Union Hospital, The First Hospital, Jilin University, Changchun, 2School of Pharmacy, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Recombinant immunotoxins (RITs are proteins that contain a toxin fused to an antibody or small molecules and are constructed by the genetic engineering technique. RITs can bind to and be internalized by cells and kill cancerous or non-cancerous cells by inhibiting protein synthesis. A wide variety of RITs have been tested against different cancers in cell culture, xenograft models, and human patients during the past several decades. RITs have shown activity in therapy of several kinds of cancers, but different levels of side effects, mainly related to vascular leak syndrome, were also observed in the treated patients. High immunogenicity of RITs limited their long-term or repeat applications in clinical cases. Recent advances in the design of immunotoxins, such as humanization of antibody fragment, PEGylation, and modification of human B- and T-cell epitopes, are overcoming the above mentioned problems, which predict the use of these immunotoxins as a potential therapeutic method to treat cancer patients. Keywords: targeted therapy, hematologic malignancies, solid tumors, vascular leak syndrome, immunogenicity 

  18. Bilateral breast cancer : mammographic and clinical findings

    International Nuclear Information System (INIS)

    Kim, Eun Kyung; Oh, Ki Keun; Jun, Hwang Yoon; Lee, Byung Chan; Lee, Kyong Sik; Lee, Yong Hee

    1997-01-01

    To evaluate the mammographic and clinical features of bilateral breast cancer. We retrospectively reviewed clinical records(n=23) and mammograms (n=15) of 23 patients with bilateral breast cancer. Patients' age, location of the tumor and pathologic staging were determined from clinical records. Mammographic features were classified as spiculated mass, nonspiculated mass, mass with microcalcification, microcalcification only, asymmetric density, and normal. Of the 23 cases of bilateral breast cancer, 8(34.8%) were synchronous and 15(65.2%) were metachronous. Age at diagnosis of cancer in the first breast was between 27 and 59(mean 43) years ; there was no statistically significant difference in mean age between patients with synchronous and metachronous cancer. The mean interval between the diagnosis of each lesion of the metachronous pairs was 9.1 years. In 11 of 23 cases(48%), tumors were locaated in the same quadrant, and in the other 12 cases(52%), they were in different quadrant. At mammography, five of 15 metachronous cancers(33%) were similar in appearance and 10 pairs(67%) were different. In 4 of 23 cases(17%), cancer in the first breast was at stage 0 and stage 1, and in 13 of 23(57%), cancer in the second breast was at this same stage. In bilateral breast cancer, the two breasts frequently show different mammographic features. Cancer of the second breast was at an early stage; this suggest that regular examination and mammography are important and can allow early detection of contralateral breast cancer

  19. Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions

    NARCIS (Netherlands)

    Breedveld, Pauline; Zelcer, Noam; Pluim, Dick; Sönmezer, Ozgür; Tibben, Matthijs M.; Beijnen, Jos H.; Schinkel, Alfred H.; van Tellingen, Olaf; Borst, Piet; Schellens, Jan H. M.

    2004-01-01

    The antifolate drug methotrexate (MTX) is transported by breast cancer resistance protein (BCRP; ABCG2) and multidrug resistance-associated protein1-4 (MRP1-4; ABCC1-4). In cancer patients, coadministration of benzimidazoles and MTX can result in profound MTX-induced toxicity coinciding with an

  20. Towards Prevention of Breast Cancer: What Are the Clinical Challenges?

    Science.gov (United States)

    Borgquist, Signe; Hall, Per; Lipkus, Isaac; Garber, Judy E

    2018-05-01

    The dramatic increase in breast cancer incidence compels a paradigm shift in our preventive efforts. There are several barriers to overcome before prevention becomes an established part of breast cancer management. The objective of this review is to identify the clinical challenges for improved breast cancer prevention and discuss current knowledge on breast cancer risk assessment methods, risk communication, ethics, and interventional efforts with the aim of covering the aspects relevant for a breast cancer prevention trial. Herein, the following five areas are discussed: (i) Adequate tools for identification of women at high risk of breast cancer suggestively entitled Prevent! Online. (ii) Consensus on the definition of high risk, which is regarded as mandatory for all risk communication and potential prophylactic interventions. (iii) Risk perception and communication regarding risk information. (iv) Potential ethical concerns relevant for future breast cancer prevention programs. (v) Risk-reducing programs involving multileveled prevention depending on identified risk. Taken together, devoted efforts from both policy makers and health care providers are warranted to improve risk assessment and risk counseling in women at risk for breast cancer to optimize the prevention of breast cancer. Cancer Prev Res; 11(5); 255-64. ©2018 AACR . ©2018 American Association for Cancer Research.

  1. Expanding the Playing Field: Immune-Based Therapy Shows Potential for Lung, Other Cancers

    Science.gov (United States)

    Results from two early-phase clinical trials presented at the 2012 American Society of Clinical Oncology annual meeting provide further evidence that priming the immune system to attack tumors has potential as a treatment for certain cancers.

  2. Understanding and potentially reducing second breast cancer

    International Nuclear Information System (INIS)

    Brenner, D.

    2011-01-01

    Full text: Long term survival after breast cancer diagnosis has increased markedly in the last decade: 15-year relative survival after breast cancer diagnosis is now 75% in the US. Associated with these excellent survival prospects, however, long term studies suggest that contralateral second breast cancer rates are in the range from 10 to 15% at 15 years post treatment, and are still higher for BRCA1/2 carriers, as well as for still longer term survivors. These second cancer risks are much higher than those for a comparable healthy woman to develop a first breast cancer. It follows that women with breast cancer are highly prone to develop a second breast cancer. We propose here a new option for reducing the disturbingly high risk of a contralateral second breast cancer. in patients with both estrogen positive and negative primary breast cancer: prophylactic mammary irradiation (PMI) of the contralateral breast. The rationale behind PMI is evidence that standard post-Iumpectomy radiotherapy of the affected (ipsilateral) breast substantially reduces the long-term genetically-based second cancer risk in the ipsilateral breast, by killing the existing premalignant cells in that breast. This suggests that there are relatively few premalignant cells in the breast (hundreds or thousands, not millions), so even a fairly modest radiation cell-kill level across the whole breast would be expected to kill essentially all of them. If this is so, then a modest radiation dose-much lower than that to the affected breast--delivered uniformly to the whole contralateral breast, and typically delivered at the same time as the radiotherapy of the ipsilateral breast, would have the potential to markedly reduce second-cancer risks in the contralateral breast by killing essentially all the pre-malignant cells in that breast while causing only a very low level of radiation-induced sequelae. Therefore we hypothesize that low-dose prophylactic mammary irradiation of the contralateral breast

  3. Vibrational spectroscopy: a clinical tool for cancer diagnostics.

    Science.gov (United States)

    Kendall, Catherine; Isabelle, Martin; Bazant-Hegemark, Florian; Hutchings, Joanne; Orr, Linda; Babrah, Jaspreet; Baker, Rebecca; Stone, Nicholas

    2009-06-01

    Vibrational spectroscopy techniques have demonstrated potential to provide non-destructive, rapid, clinically relevant diagnostic information. Early detection is the most important factor in the prevention of cancer. Raman and infrared spectroscopy enable the biochemical signatures from biological tissues to be extracted and analysed. In conjunction with advanced chemometrics such measurements can contribute to the diagnostic assessment of biological material. This paper also illustrates the complementary advantage of using Raman and FTIR spectroscopy technologies together. Clinical requirements are increasingly met by technological developments which show promise to become a clinical reality. This review summarises recent advances in vibrational spectroscopy and their impact on the diagnosis of cancer.

  4. Lung Cancer Clinical Trials: Advances in Immunotherapy

    Science.gov (United States)

    New treatments for lung cancer and aspects of joining a clinical trial are discussed in this 30-minute Facebook Live event, hosted by NCI’s Dr. Shakun Malik, head of thoracic oncology therapeutics, and Janet Freeman-Daily, lung cancer patient activist and founding member of #LCSM.

  5. International Partnerships for Clinical Cancer Research

    Science.gov (United States)

    CGH co-sponsors the 2015 International Symposium on Cancer Clinical Trials and related meetings held in partnership with the Japanese National Cancer Center (JNCC) and Embassies of France, Korea, United Kingdom (UK), and United States (US) in Tokyo on May 14 - 15, 2015.

  6. Clinical statistics of gynecologic cancers in Japan

    Science.gov (United States)

    Nagase, Satoru

    2017-01-01

    Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve-point six percent of ovarian cancer patients received neoadjuvant chemotherapy. PMID:28198168

  7. CDC25A Protein Stability Represents a Previously Unrecognized Target of HER2 Signaling in Human Breast Cancer: Implication for a Potential Clinical Relevance in Trastuzumab Treatment

    Directory of Open Access Journals (Sweden)

    Emanuela Brunetto

    2013-06-01

    Full Text Available The CDC25A-CDK2 pathway has been proposed as critical for the oncogenic action of human epidermal growth factor receptor 2 (HER2 in mammary epithelial cells. In particular, transgenic expression of CDC25A cooperates with HER2 in promoting mammary tumors, whereas CDC25A hemizygous loss attenuates the HER2-induced tumorigenesis penetrance. On the basis of this evidence of a synergism between HER2 and the cell cycle regulator CDC25A in a mouse model of mammary tumorigenesis, we investigated the role of CDC25A in human HER2-positive breast cancer and its possible implications in therapeutic response. HER2 status and CDC25A expression were assessed in 313 breast cancer patients and we found statistically significant correlation between HER2 and CDC25A (P = .007. Moreover, an HER2-positive breast cancer subgroup with high levels of CDC25A and very aggressive phenotype was identified (P = .005. Importantly, our in vitro studies on breast cancer cell lines showed that the HER2 inhibitor efficacy on cell growth and viability relied also on CDC25A expression and that such inhibition induces CDC25A down-regulation through phosphatidylinositol 3-kinase/protein kinase B pathway and DNA damage response activation. In line with this observation, we found a statistical significant association between CDC25A overexpression and trastuzumab-combined therapy response rate in two different HER2-positive cohorts of trastuzumab-treated patients in either metastatic or neoadjuvant setting (P = .018 for the metastatic cohort and P = .021 for the neoadjuvant cohort. Our findings highlight a link between HER2 and CDC25A that positively modulates HER2- targeted therapy response, suggesting that, in HER2-positive breast cancer patients, CDC25A overexpression affects trastuzumab sensitivity.

  8. Circulating DNA as Potential Biomarker for Cancer Individualized Therapy

    Directory of Open Access Journals (Sweden)

    Shaorong Yu

    2013-09-01

    Full Text Available Cancer individualized therapy often requires for gene mutation analysis of tumor tissue. However, tumor tissue is not always available in clinical practice, particularly from patients with refractory and recurrence disease. Even if patients have sufficient tumor tissue for detection, as development of cancer, the gene status and drug sensitivity of tumor tissues could also change. Hence, screening mutations from primary tumor tissues becomes useless, it’s necessary to find a surrogate tumor tissue for individualized gene screening. Circulating DNA is digested rapidly from blood, which could provide real-time information of the released fragment and make the real-time detection possible. Therefore, it’s expected that circulating DNA could be a potential tumor biomarker for cancer individualized therapy. This review focuses on the biology and clinical utility of circulating DNA mainly on gene mutation detection. Besides, its current status and possible direction in this research area is summarized and discussed objectively.

  9. Immunotherapy in pancreatic cancer: Unleash its potential through novel combinations.

    Science.gov (United States)

    Guo, Songchuan; Contratto, Merly; Miller, George; Leichman, Lawrence; Wu, Jennifer

    2017-06-10

    Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses. However, single checkpoint blockade was ineffective in pancreatic cancer, highlighting the challenges including the poor antigenicity, a dense desmoplastic stroma, and a largely immunosuppressive microenvironment. In this review, we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy, radiotherapy, and targeted therapy. These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.

  10. Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls

    Science.gov (United States)

    Lee, Jihyoun; Chatterjee, Dev Kumar; Lee, Min Hyuk; Krishnan, Sunil

    2014-01-01

    Despite remarkable achievements in the treatment of breast cancer, some obstacles still remain. Gold nanoparticles may prove valuable in addressing these problems owing to their unique characteristics, including their enhanced permeability and retention in tumor tissue, their light absorbance and surface plasmon resonance in near-infrared light, their interaction with radiation to generate secondary electrons, and their ability to be conjugated with drugs or other agents. Herein, we discuss some basic concepts of gold nanoparticles, and early results from studies regarding their use in breast cancer, including toxicity and side effects. We also discuss these particles’ potential clinical applications. PMID:24556077

  11. Recommendations for Obesity Clinical Trials in Cancer Survivors: American Society of Clinical Oncology Statement.

    Science.gov (United States)

    Ligibel, Jennifer A; Alfano, Catherine M; Hershman, Dawn; Ballard, Rachel M; Bruinooge, Suanna S; Courneya, Kerry S; Daniels, Elvan C; Demark-Wahnefried, Wendy; Frank, Elizabeth S; Goodwin, Pamela J; Irwin, Melinda L; Levit, Laura A; McCaskill-Stevens, Worta; Minasian, Lori M; O'Rourke, Mark A; Pierce, John P; Stein, Kevin D; Thomson, Cynthia A; Hudis, Clifford A

    2015-11-20

    Observational evidence has established a relationship between obesity and cancer risk and outcomes. Interventional studies have demonstrated the feasibility and benefits of lifestyle change after cancer diagnosis, and guidelines recommend weight management and regular physical activity in cancer survivors; however, lifestyle interventions are not a routine part of cancer care. The ASCO Research Summit on Advancing Obesity Clinical Trials in Cancer Survivors sought to identify the knowledge gaps that clinical trials addressing energy balance factors in cancer survivors have not answered and to develop a roadmap for the design and implementation of studies with the potential to generate data that could lead to the evidence-based incorporation of weight management and physical activity programs into standard oncology practice. Recommendations highlight the need for large-scale trials evaluating the impact of energy balance interventions on cancer outcomes, as well as the concurrent conduct of studies focused on dissemination and implementation of interventions in diverse populations of cancer survivors, including answering critical questions about the degree of benefit in key subgroups of survivors. Other considerations include the importance of incorporating economic metrics into energy balance intervention trials, the need to establish intermediate biomarkers, and the importance of integrating traditional and nontraditional funding sources. Establishing lifestyle change after cancer diagnosis as a routine part of cancer care will require a multipronged effort to overcome barriers related to study development, funding, and stakeholder engagement. Given the prevalence of obesity and inactivity in cancer survivors in the United States and elsewhere, energy balance interventions hold the potential to reduce cancer morbidity and mortality in millions of patients, and it is essential that we move forward in determining their role in cancer care with the same care and

  12. Radiological and clinical evaluation of colorectal cancer

    International Nuclear Information System (INIS)

    Shin, O. J.; Chin, S. Y.; Lee, K. S.; Park, S. S.

    1982-01-01

    One hundred thirty two cases of the pathologically proven colorectal cancer at Korea Atomic Energy Research Institute Hospital in the period from January 1973 to June 1980 were analyzed radiologically and clinically. The results were as follows: 1. The colorectal cancer was prevalent in rectosigmoid area and in the fourth to seventh decade of life. 2. The clinical pictures were classified into two groups. The one was rectosigmoid cancer with bowel habit changes. The other was one with no specific symptoms or signs. The clinical pictures of the right colon cancer were rather indirected, chronic and systemic than those of the left one. 3. The roentgenological findings were classified into two groups. The one was rectum and left colon cancer with symmetrical annular narrowing and the other showed trumpet-like proximal dilatation. 4. The most frequent complication was intestinal obstruction. 5. The majority of colorectal cancer was adenocarcinoma. The squamous cell carcinoma and atypical cell carcinoma were most prevalent in rectum, but malignantly lymphoma often occurred in right colon. The rarest colorectal cancer was atypical cell carcinoma in rectum

  13. Aptamer nanomedicine for cancer therapeutics: barriers and potential for translation.

    Science.gov (United States)

    Lao, Yeh-Hsing; Phua, Kyle K L; Leong, Kam W

    2015-03-24

    Aptamer nanomedicine, including therapeutic aptamers and aptamer nanocomplexes, is beginning to fulfill its potential in both clinical trials and preclinical studies. Especially in oncology, aptamer nanomedicine may perform better than conventional or antibody-based chemotherapeutics due to specificity compared to the former and stability compared to the latter. Many proof-of-concept studies on applying aptamers to drug delivery, gene therapy, and cancer imaging have shown promising efficacy and impressive safety in vivo toward translation. Yet, there remains ample room for improvement and critical barriers to be addressed. In this review, we will first introduce the recent progress in clinical trials of aptamer nanomedicine, followed by a discussion of the barriers at the design and in vivo application stages. We will then highlight recent advances and engineering strategies proposed to tackle these barriers. Aptamer cancer nanomedicine has the potential to address one of the most important healthcare issues of the society.

  14. Integrating cannabis into clinical cancer care.

    Science.gov (United States)

    Abrams, D I

    2016-03-01

    Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use. For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia. Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects.

  15. Initial Report of a Prospective Dosimetric and Clinical Feasibility Trial Demonstrates the Potential of Protons to Increase the Therapeutic Ratio in Breast Cancer Compared With Photons

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, Julie A., E-mail: jbradley@floridaproton.org; Dagan, Roi; Ho, Meng Wei; Rutenberg, Michael; Morris, Christopher G.; Li, Zuofeng; Mendenhall, Nancy P.

    2016-05-01

    Purpose: To compare dosimetric endpoints between proton therapy (PT) and conventional radiation and determine the feasibility of PT for regional nodal irradiation (RNI) in women with breast cancer. Methods and Materials: From 2012 to 2014, 18 women (stage IIA-IIIB) requiring RNI prospectively enrolled on a pilot study. Median age was 51.8 years (range, 42-73 years). The cohort included breast-conserving therapy (BCT) and mastectomy patients and right- and left-sided cancers. Treatment targets and organs at risk were delineated on computed tomography scans, and PT and conventional plans were developed. Toxicity was prospectively recorded using Common Terminology Criteria for Adverse Events version 4.0. A Wilcoxon signed-rank sum test compared the dose-volume parameters. The primary endpoint was a reduction in cardiac V5. Results: Median follow-up was 20 months (range, 2-31 months). For all patients, the PT plan better met the dosimetric goals and was used for treatment. Proton therapy alone was used for 10 patients (9 postmastectomy, 1 after BCT) and combined proton–photon in 8 (6 BCT, 2 postmastectomy with immediate expander reconstruction). Proton therapy improved coverage of level 2 axilla (P=.0005). Adequate coverage of internal mammary nodes was consistently achieved with PT (median D95, 50.3 Gy; range, 46.6-52.1 Gy) but not with conventional radiation therapy (median D95, 48.2 Gy; range, 40.8-55 Gy; P=.0005). Median cardiac V5 was 0.6% with PT and 16.3% with conventional radiation (P<.0001). Median ipsilateral lung V5 and V20 were improved with PT (median V5 35.3% vs 60.5% [P<.0001]; and median V20, 21.6% vs 35.5% [P<.0001]). Grade 3 dermatitis developed in 4 patients (22%), which was the only grade 3 toxicity. No grade 4+ toxicities developed. Conclusion: Proton therapy for RNI after mastectomy or BCT significantly improves cardiac dose, especially for left-sided patients, and lung V5 and V20 in all patients without excessive acute toxicity

  16. Cancer immunotherapy: potential involvement of mediators

    Directory of Open Access Journals (Sweden)

    S. Ben-Efraim

    1997-01-01

    Full Text Available The description of a cell-free soluble anti-tumour factor by Carswell et al. in 1975 (Proc Natl Acad Sci USA, 72: 3666–3670 was followed by a long series of experimental and clinical investigations into the role of cell-free mediators in cancer immunotherapy. These investigations included research on the effects of macrophage–derived eicosanoids (cycloxygenase and lipoxygenase derivates of arachidonic acid and of monokines such as tumour necrosis factor-α, interleukin-1 and granulocyte–monocyte–macrophage–colony stimulating factor and of lymphocyte products: interleukins and interferons. The investigations yielded information on the effects of various factors on macrophage and T-cell activation in vitro, determination of direct anti-tumour properties on animal and human tumour cells in vitro and on therapeutic effectiveness in tumour-bearing individuals either alone or in combination with other therapeutic factors and their production by tumour cells. During recent years much effort has been dedicated towards the use of the tumour cells transfected with cytokine genes in the preparation of cancer vaccines. Cycloxygenase products (prostaglandins were usually assumed to inhibit expression of anti-tumour activity by macrophages and an increase in their production in cancer patients was considered as a poor prognostic index. Lipoxygenase (leukotrienes products were assumed to exhibit antitumour activity and to induce production of IL-1 by macrophages. Interleukins 2, 4, 6, 7, 12 and the interferons were extensively tested for their therapeutic effectiveness in experimental tumour models and in cancer clinical trials. The general conclusion on the use of cell-free mediators for cancer immunotherapy is that much still has to be done in order to assure effective and reproducible therapeutic effectiveness for routine use in the treatment of human neoplasia.

  17. Change in HER2 (ERBB2) gene status after taxane-based chemotherapy for breast cancer: polyploidization can lead to diagnostic pitfalls with potential impact for clinical management.

    Science.gov (United States)

    Valent, Alexander; Penault-Llorca, Frédérique; Cayre, Anne; Kroemer, Guido

    2013-01-01

    The status of the HER2 (ERBB2) gene in breast cancer is not static and may change among the primary tumor, lymph node metastases, and distant metastases. This status change can be a consequence of the natural evolution of the tumor or can be induced by therapy. The HER2 gene status is, in the majority of cases, established at the moment of diagnosis. After chemotherapy, monitoring HER2 status can be a challenge because of ploidy changes induced by drugs. The cytogeneticist or the pathologist can face real difficulties in distinguishing between a true HER2 amplification and HER2 copy number increase by polyploidization. We performed a HER2 genetic examination by fluorescence in situ hybridization (FISH) of invasive breast cancers before and after taxane treatment. The majority of patients (91%) were HER2-negative both at diagnosis and after treatment. Thirty of 344 patients (9%) whose tumors were initially HER2-negative were found by FISH to have supernumerary HER2 gene copies (up to 15 copies) after neoadjuvant chemotherapy. This HER2 copy increase could not be attributed to true gene amplifications and instead reflected polyploidization events, which presumably affected all chromosomes. Indeed, when we used other FISH probes, we found other gene copy numbers to parallel those of HER2. We recommend careful checking of invasive breast carcinomas by supplementary FISH probes if the copy number of the HER2 gene is >6. This procedure allows the discrimination of specific HER2 gene amplifications and global increases in ploidy. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Optical coherence tomography: potentialities in clinical practice

    Science.gov (United States)

    Zagaynova, Elena; Gladkova, Natalia D.; Shakhov, Andrey; Terentjeva, Anna; Snopova, Ludmila B.; Kuznetzova, Irina A.; Streltzova, Olga; Shakhova, Natalia M.; Kamensky, Vladislav A.; Gelikonov, Grigory V.; Gelikonov, Valentin M.; Kuranov, Roman V.; Myakov, Alex

    2004-08-01

    Clinical studies using OCT involved 2000 patients in various fields of medicine such as gastroenterology, urology, laryngology, gynecology, dermatology, stomatology, etc. Layered high-contrast images were typical for benign epithelial conditions. OCT distinguish in mucosae: epithelium, connective tissue layer, and smooth-muscle layer. Various benign processes occurring in mucosa manifest in OCT images as changes in the epithelial height, scattering properties and the course of the basement membrane. Lack of the layered structural pattern is the main criterion for dysplastic / malignant images. In clinic: OCT data may be critical for choosing a tissue site for excisional biopsy, OCT can detect tumor borders and their linear dimensions, OCT can be used to plan a resection line in operations and to control adequacy of resection, to monitor whether reparative processes are timely and adequate. OCT sensitivity of the uterine cervix, urinary bladder and larynx is 82, 98, 77%, respectively, specificity - 78, 71, 96%, diagnostic accuracy - 81, 85, 87% with significantly good agreement index of clinicians kappa - 0.65, 0.79, 0.83 (confidence intervals: 0.57-0.73; 0.71-0.88; 0.74-0.91). Error in detection of high grade dysplasia and microinvasive cancer is 21.4% in average. Additional modification of OCT (cross-polarisation OCT, OCM), development of the procedure (biotissue compression, application of chemical agents) can improve the specificity and sensitivity of traditional modality.

  19. SU-G-BRC-15: The Potential Clinical Significance of Dose Mapping Error for Intra- Fraction Dose Mapping for Lung Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Sayah, N [Thomas Cancer Center, Richmond, VA (United States); Weiss, E [Virginia Commonwealth University, Richmond, Virginia (United States); Watkins, W [University of Virginia, Charlottesville, VA (United States); Siebers, J [University of Virginia Health System, Charlottesville, VA (United States)

    2016-06-15

    Purpose: To evaluate the dose-mapping error (DME) inherent to conventional dose-mapping algorithms as a function of dose-matrix resolution. Methods: As DME has been reported to be greatest where dose-gradients overlap tissue-density gradients, non-clinical 66 Gy IMRT plans were generated for 11 lung patients with the target edge defined as the maximum 3D density gradient on the 0% (end of inhale) breathing phase. Post-optimization, Beams were copied to 9 breathing phases. Monte Carlo dose computed (with 2*2*2 mm{sup 3} resolution) on all 10 breathing phases was deformably mapped to phase 0% using the Monte Carlo energy-transfer method with congruent mass-mapping (EMCM); an externally implemented tri-linear interpolation method with voxel sub-division; Pinnacle’s internal (tri-linear) method; and a post-processing energy-mass voxel-warping method (dTransform). All methods used the same base displacement-vector-field (or it’s pseudo-inverse as appropriate) for the dose mapping. Mapping was also performed at 4*4*4 mm{sup 3} by merging adjacent dose voxels. Results: Using EMCM as the reference standard, no clinically significant (>1 Gy) DMEs were found for the mean lung dose (MLD), lung V20Gy, or esophagus dose-volume indices, although MLD and V20Gy were statistically different (2*2*2 mm{sup 3}). Pinnacle-to-EMCM target D98% DMEs of 4.4 and 1.2 Gy were observed ( 2*2*2 mm{sup 3}). However dTransform, which like EMCM conserves integral dose, had DME >1 Gy for one case. The root mean square RMS of the DME for the tri-linear-to- EMCM methods was lower for the smaller voxel volume for the tumor 4D-D98%, lung V20Gy, and cord D1%. Conclusion: When tissue gradients overlap with dose gradients, organs-at-risk DME was statistically significant but not clinically significant. Target-D98%-DME was deemed clinically significant for 2/11 patients (2*2*2 mm{sup 3}). Since tri-linear RMS-DME between EMCM and tri-linear was reduced at 2*2*2 mm{sup 3}, use of this resolution is

  20. Clinical application of PET in abdominal cancers

    International Nuclear Information System (INIS)

    Choi, Chang Woon

    2002-01-01

    Clinical application of positron emission tomography (PET) is rapidly increasing for the detection and staging of cancer at whole-body studies performed with the glucose analogue tracer 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FG). Although FDG PET cannot match the anatomic resolution of conventional imaging techniques in the liver and the other abdominal organs, it is particularly useful for identification and characterization of the entire body simultaneously. FDG PET can show foci of metastatic disease that may not be apparent at conventional anatomic imaging and can aid in the characterizing of indeterminate soft-tissue masses. Most abdominal cancer requires surgical management. FGD PET can improve the selection of patients for surgical treatment and thereby reduce the morbidity and mortality associated with inappropriate surgery. FDG PET is also useful for the early detection of recurrence and the monitoring of therapeutic effect. The abdominal cancers, such as gastroesophageal cancer, colorectal cancer, liver cancer and pancreatic cancer, are common malignancies in Korea, and PET is one of the most promising and useful methodologies for the management of abdominal cancers

  1. Fertility preservation during cancer treatment: clinical guidelines

    Science.gov (United States)

    Rodriguez-Wallberg, Kenny A; Oktay, Kutluk

    2014-01-01

    The majority of children, adolescents, and young adults diagnosed with cancer today will become long-term survivors. The threat to fertility that cancer treatments pose to young patients cannot be prevented in many cases, and thus research into methods for fertility preservation is developing, aiming at offering cancer patients the ability to have biologically related children in the future. This paper discusses the current status of fertility preservation methods when infertility risks are related to surgical oncologic treatments, radiation therapy, or chemotherapy. Several scientific groups and societies have developed consensus documents and guidelines for fertility preservation. Decisions about fertility and imminent potentially gonadotoxic therapies must be made rapidly. Timely and complete information on the impact of cancer treatment on fertility and fertility preservation options should be presented to all patients when a cancer treatment is planned. PMID:24623991

  2. Clinical utility of ramucirumab in advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Chan MMK

    2015-09-01

    Full Text Available Matthew MK Chan,1,2 Katrin M Sjoquist,1,3 John R Zalcberg4 1NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia; 2Department of Medical Oncology, Central Coast Cancer Centre, Gosford Hospital, Gosford, NSW, Australia; 3Cancer Care Centre, St George Hospital, Sydney, NSW, Australia; 4School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia Abstract: Gastric cancer is currently the third most common cause of cancer deaths worldwide. Prognosis remains poor with most patients presenting with advanced or metastatic disease. A better understanding of angiogenesis has led to the investigation of drugs that inhibit the vascular endothelial growth factor (VEGF pathway including anti-VEGF antibody therapy (eg, bevacizumab, inhibitors of angiogenic receptor tyrosine kinases (eg, sunitinib, sorafenib, apatinib, regorafenib, and inhibitors of vascular endothelial growth factor receptors (VEGFRs (eg, ramucirumab. Ramucirumab, a VEGFR-2 inhibitor, is the first anti-angiogenic agent approved by the US Food and Drug Administration for use in the treatment of advanced gastric cancers. This review will focus on the clinical utility and potential use of ramucirumab in advanced gastric cancer. Keywords: ramucirumab, IMC-1121B, gastric cancer, vascular endothelial growth factor receptor-2, angiogenesis, targeted therapy

  3. Cetuximab: clinical results in colorectal cancer.

    Science.gov (United States)

    Maiello, E; Giuliani, F; Gebbia, V; Piano, A; Agueli, R; Colucci, G

    2007-06-01

    In recent years, the introduction of targeted therapies into clinical practice seems to offer incremental benefits in the treatment of metastatic colorectal cancer (mCRC), mainly when they are employed in combination with optimal chemotherapy and/or radiotherapy. In this paper, we focus on Cetuximab and its role in the treatment of mCRC.

  4. Research methods to change clinical practice for patients with rare cancers.

    Science.gov (United States)

    Billingham, Lucinda; Malottki, Kinga; Steven, Neil

    2016-02-01

    Rare cancers are a growing group as a result of reclassification of common cancers by molecular markers. There is therefore an increasing need to identify methods to assess interventions that are sufficiently robust to potentially affect clinical practice in this setting. Methods advocated for clinical trials in rare diseases are not necessarily applicable in rare cancers. This Series paper describes research methods that are relevant for rare cancers in relation to the range of incidence levels. Strategies that maximise recruitment, minimise sample size, or maximise the usefulness of the evidence could enable the application of conventional clinical trial design to rare cancer populations. Alternative designs that address specific challenges for rare cancers with the aim of potentially changing clinical practice include Bayesian designs, uncontrolled n-of-1 trials, and umbrella and basket trials. Pragmatic solutions must be sought to enable some level of evidence-based health care for patients with rare cancers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. THERAPEUTIC ANTISENSE OLIGONUCLEOTIDES AGAINST CANCER: HURDLING TO THE CLINIC

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Duarte Moreno

    2014-10-01

    Full Text Available Under clinical development since the early 90’s and with two successfully approved drugs (Fomivirsen and Mipomersen, oligonucleotide-based therapeutics have not yet delivered a clinical drug to the market in the cancer field. Whilst many pre-clinical data has been generated, a lack of understanding still exists on how to efficiently tackle all the different challenges presented for cancer targeting in a clinical setting. Namely, effective drug vectorization, careful choice of target gene or synergistic multi-gene targeting are surely decisive, while caution must be exerted to avoid potential toxic, often misleading off-target-effects. Here a brief overview will be given on the nucleic acid chemistry advances that established oligonucleotide technologies as a promising therapeutic alternative and ongoing cancer related clinical trials. Special attention will be given towards a perspective on the hurdles encountered specifically in the cancer field by this class of therapeutic oligonucleotides and a view on possible avenues for success is presented, with particular focus on the contribution from nanotechnology to the field.

  6. Resveratrol and cancer: Challenges for clinical translation

    Science.gov (United States)

    Singh, Chandra K.; Ndiaye, Mary A.; Ahmad, Nihal

    2014-01-01

    Significant work has been done towards identifying the health-beneficial effects of the grape antioxidant resveratrol in a variety of bioassay- and disease- models, with much research being focused on its possible application to cancer management. Despite the large number of preclinical studies dealing with different aspects of the biological effects of resveratrol, it’s translation to clinics is far from reality due to a variety of challenges. In this review, we discuss the issues and questions associated with resveratrol becoming an effective in vivo anticancer drug, from basic metabolic issues to the problems faced by incomplete understanding of the mechanism(s) of action in the body. We also explore efforts taken by researchers, both public and private, to contend with some of these issues. By examining the published data and previous clinical trials, we have attempted to identify the problems and issues that hinder the clinical translation of resveratrol for cancer management. PMID:25446990

  7. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    Energy Technology Data Exchange (ETDEWEB)

    Liechtenstein, Therese, E-mail: t.liechtenstein.12@ucl.ac.uk [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Perez-Janices, Noemi; Escors, David [University College London, 5 University Street, London, WC1E 6JF (United Kingdom); Navarrabiomed Fundacion Miguel Servet, 3 Irunlarrea St., Hospital Complex of Navarra, 31008 Pamplona, Navarra (Spain)

    2013-07-02

    The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

  8. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    International Nuclear Information System (INIS)

    Liechtenstein, Therese; Perez-Janices, Noemi; Escors, David

    2013-01-01

    The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(γ-)retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and β-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells

  9. Lentiviral Vectors for Cancer Immunotherapy and Clinical Applications

    Directory of Open Access Journals (Sweden)

    David Escors

    2013-07-01

    Full Text Available The success of immunotherapy against infectious diseases has shown us the powerful potential that such a treatment offers, and substantial work has been done to apply this strategy in the fight against cancer. Cancer is however a fiercer opponent than pathogen-caused diseases due to natural tolerance towards tumour associated antigens and tumour-induced immunosuppression. Recent gene therapy clinical trials with viral vectors have shown clinical efficacy in the correction of genetic diseases, HIV and cancer. The first successful gene therapy clinical trials were carried out with onco(g-retroviral vectors but oncogenesis by insertional mutagenesis appeared as a serious complication. Lentiviral vectors have emerged as a potentially safer strategy, and recently the first clinical trial of patients with advanced leukemia using lentiviral vectors has proven successful. Additionally, therapeutic lentivectors have shown clinical efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and b-thalassaemia. This review aims at describing lentivectors and how they can be utilized to boost anti-tumour immune responses by manipulating the effector immune cells.

  10. Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

    Science.gov (United States)

    2016-10-01

    Physics of Cancer Metabolism This application seeks to put together a multidiscipline team of experts in various institutions in USA to assemble and...of this project is to build a research cohort of engaged volunteers that reflects the racial , ethnic, and socioeconomic diversity of New York City...assessed in a randomized, phase III clinical trial. Conflict of interest: Advisory Board: Joe O’Sullivan holds consulting/ advisory roles with Bayer

  11. Potential Effects of Pomegranate Polyphenols in Cancer Prevention and Therapy.

    Science.gov (United States)

    Turrini, Eleonora; Ferruzzi, Lorenzo; Fimognari, Carmela

    2015-01-01

    Cancer is the second leading cause of death and is becoming the leading one in old age. Vegetable and fruit consumption is inversely associated with cancer incidence and mortality. Currently, interest in a number of fruits high in polyphenols has been raised due to their reported chemopreventive and/or chemotherapeutic potential. Pomegranate has been shown to exert anticancer activity, which is generally attributed to its high content of polyphenols. This review provides a comprehensive analysis of known targets and mechanisms along with a critical evaluation of pomegranate polyphenols as future anticancer agents. Pomegranate evokes antiproliferative, anti-invasive, and antimetastatic effects, induces apoptosis through the modulation of Bcl-2 proteins, upregulates p21 and p27, and downregulates cyclin-cdk network. Furthermore, pomegranate blocks the activation of inflammatory pathways including, but not limited to, the NF-κB pathway. The strongest evidence for its anticancer activity comes from studies on prostate cancer. Accordingly, some exploratory clinical studies investigating pomegranate found a trend of efficacy in increasing prostate-specific antigen doubling time in patients with prostate cancer. However, the genotoxicity reported for pomegranate raised certain concerns over its safety and an accurate assessment of the risk/benefit should be performed before suggesting the use of pomegranate or its polyphenols for cancer-related therapeutic purposes.

  12. Potential benefits and risks of clinical xenotransplantation

    Directory of Open Access Journals (Sweden)

    Cooper DKC

    2012-07-01

    Full Text Available David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USAAbstract: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets (for the treatment of diabetes, neuronal cells (for the treatment of Parkinson's disease, and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs

  13. Targeting NK cells for anti-cancer immunotherapy: clinical and pre-clinical approaches

    Directory of Open Access Journals (Sweden)

    Sebastian eCarotta

    2016-04-01

    Full Text Available The recent success of checkpoint blockade has highlighted the potential of immunotherapy approaches for cancer treatment. While the majority of approved immunotherapy drugs target T cell subsets, it is appreciated that other components of the immune system have important roles in tumor immune-surveillance as well and thus represent promising additional targets for immunotherapy. Natural killer cells are the body’s first line of defense against infected or transformed cells as they kill target cells in an antigen-independent manner. Although several studies have clearly demonstrated the active role of NK cells in cancer-immune surveillance, only few clinically approved therapies currently exist that harness their potential. Our increased understanding of NK cell biology over the past few years has renewed the interest in NK cell based anti-cancer therapies, which has lead to a steady increase of NK cell based clinical and pre-clinical trials. Here, the role of NK cells in cancer immunesurveillance is summarized and several novel approaches to enhance NK cell cytotoxicity against cancer are discussed.

  14. Vitamin D and cancer: Clinical aspects

    Science.gov (United States)

    Woloszynska-Read, Anna; Johnson, Candace S.; Trump, Donald L.

    2015-01-01

    There are substantial preclinical and epidemiologic data that suggest that vitamin D plays a role in the prevention and treatment of cancer. Numerous observational studies have shown that low blood levels of 25(OH) vitamin D (cholecalciferol), estimated by geographical location, diet and activity assessment or measured serum levels are associated with a higher risk of cancer and worse cancer-specific survival as well as numerous morbidities to e.g. cardiovascular disease, stroke, infection, autoimmune disease, and neuromuscular dysfunction among large populations. A considerable number of in vitro and in vivo studies indicate that the most active metabolite of vitamin D – 1,25-dihydroxycholecalciferol or calcitriol – has anti-proliferative, pro-apoptotic, pro-differentiating, and anti-angiogenic properties. Combined treatment of calcitriol and many types of cytotoxic agents has synergistic or at least additive effects. However, clinical trials testing these hypotheses have been less encouraging, though a number of methodological, pharmacological, and pharmaceutical issues confound all trials ever conducted. In order to properly assess the clinical value of vitamin D, its metabolites and analogs in cancer prevention and treatment, more studies are needed. PMID:21872802

  15. [Multiple primary colorectal cancer: Clinical aspects].

    Science.gov (United States)

    Soldatkina, N V; Kit, O I; Gevorkyan, Yu A; Milakin, A G

    to define some clinical characteristics of synchronous and metachronous colorectal cancer (CRC). The investigation was concerned with the data of 150 patients with T1-4N0-2M0-1 multiple primary CRC. The clinical, biological, and morphological characteristics of synchronous and metachronous tumors were analyzed. Multiple primary tumors were 6.01% of all the cases of CRC. There was a preponderance of synchronous CRC (63.75%) with the tumor localized in the sigmoid colon and rectum. In women, synchronous colorectal tumors were more often concurrent with breast tumors; metachronous ones were detected after treatment for genital tumors. In men, synchronous colorectal tumors were more frequently concurrent with kidney cancer; metachronous ones were identified after treatment for gastric cancer. The found characteristics of multiple primary colorectal tumors may be taken in account in programs for both primary diagnosis and follow-up after treatment for malignant tumors, which will be able to improve the early detection of cancer patients and their treatment results.

  16. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    Cappello P

    2015-12-01

    Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

  17. Cancer diagnosis in a ''breast clinic''

    International Nuclear Information System (INIS)

    Ghys, R.

    1987-01-01

    Conflicting opinions have been expressed in the world literature over the last 15 years about the value of radiological techniques in breast cancer diagnosis. We reviewed 111 breast cancers which we diagnosed between 1971 and 1985, in unselected patients, by the combined use of palpation, thermography and mammography, complemented, since 1980, by diaphanoscopy. Considerable clinical experience is necessary to interpret both mammograms and thermograms. Each of these approaches, when rated independently, has a very high false negative rate ranging from 41% for clinical examination to 32% for mammography. In cases which are not clinically obvious, diaphanoscopy ''retrieves'' the most cancers, with thermography a close second (definitely malignant in 35% of the cases over the whole age range). Mammography comes third and its efficacy drops to 12.5% in premenopausal women. However, by combining this information with the one derived from anamnesis, the ACDTM scoring system gives us a false negative rate - before biopsy - of 5.5% and a false positive rate of <1%. This approach also drastically reduces the number of unnecessary biopsies

  18. Potential of Epigenetic Therapies in Non-cancerous Conditions

    Directory of Open Access Journals (Sweden)

    Raymond eYung

    2014-12-01

    Full Text Available There has been an explosion of knowledge in the epigenetics field in the past 20 years. The first epigenetic therapies have arrived in the clinic for cancer treatments. In contrast, much of the promise of epigenetic therapies for non-cancerous conditions remains in the laboratories. The current review will focus on the recent progress that has been made in understanding the pathogenic role of epigenetics in immune and inflammatory conditions, and how the knowledge may provide much needed new therapeutic targets for many autoimmune diseases. Dietary factors are increasingly recognized as potential modifiers of epigenetic marks that can influence health and diseases across generations. The current epigenomics revolution will almost certainly complement the explosion of personal genetics medicine to help guide treatment decisions and disease risk stratification.

  19. Frizzled Receptors as Potential Therapeutic Targets in Human Cancers

    Directory of Open Access Journals (Sweden)

    Chui-Mian Zeng

    2018-05-01

    Full Text Available Frizzled receptors (FZDs are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs that serve as receptors for secreted Wingless-type (WNT ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs. We will focus on the development of antibody-based and small molecule inhibitor-based therapeutic strategies by targeting FZDs for human cancers.

  20. Toxicology and clinical potential of nanoparticles

    Science.gov (United States)

    Yildirimer, Lara; Thanh, Nguyen T.K.; Loizidou, Marilena; Seifalian, Alexander M.

    2011-01-01

    Summary In recent years, nanoparticles (NPs) have increasingly found practical applications in technology, research and medicine. The small particle size coupled to their unique chemical and physical properties is thought to underlie their exploitable biomedical activities. Here, we review current toxicity studies of NPs with clinical potential. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge gained from cell-based studies into a human scenario is highlighted. The so-called ‘proof-of-principle’ approach, whereby ultra-high NP concentrations are used to ensure cytotoxicity, is evaluated on the basis of two considerations; firstly, from a scientific perspective, the concentrations used are in no way related to the actual doses required which, in many instances, discourages further vital investigations. Secondly, these inaccurate results cast doubt on the science of nanomedicine and thus, quite dangerously, encourage unnecessary alarm in the public. In this context, the discrepancies between in vitro and in vivo results are described along with the need for a unifying protocol for reliable and realistic toxicity reports. PMID:23293661

  1. Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics.

    Science.gov (United States)

    Timms, John F; Hale, Oliver J; Cramer, Rainer

    2016-06-01

    The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry (MS). Studies using advanced MS have resulted in new insights into cell biology and the etiology of diseases as well as its use in clinical applications. This review discusses recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It also discusses the issues around translating the research findings to the clinic and provides an outline of where the field is moving. Expert commentary: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics.

  2. Enrolling Minority and Underserved Populations in Cancer Clinical Research.

    Science.gov (United States)

    Wallington, Sherrie F; Dash, Chiranjeev; Sheppard, Vanessa B; Goode, Tawara D; Oppong, Bridget A; Dodson, Everett E; Hamilton, Rhonda N; Adams-Campbell, Lucile L

    2016-01-01

    Research suggests that community involvement is integral to solving public health problems, including involvement in clinical trials-a gold standard. Significant racial/ethnic disparities exist in the accrual of participants for clinical trials. Location and cultural aspects of clinical trials influence recruitment and accrual to clinical trials. It is increasingly necessary to be aware of defining characteristics, such as location and culture of the populations from which research participants are enrolled. Little research has examined the effect of location and cultural competency in adapting clinical trial research for minority and underserved communities on accrual for clinical trials. Utilizing embedded community academic sites, the authors applied cultural competency frameworks to adapt clinical trial research in order to increase minority participation in nontherapeutic cancer clinical trials. This strategy resulted in successful accrual of participants to new clinical research trials, specifically targeting participation from minority and underserved communities in metropolitan Washington, DC. From 2012 to 2014, a total of 559 participants enrolled across six nontherapeutic clinical trials, representing a 62% increase in the enrollment of blacks in clinical research. Embedding cancer prevention programs and research in the community was shown to be yet another important strategy in the arsenal of approaches that can potentially enhance clinical research enrollment and capacity. The analyses showed that the capacity to acquire cultural knowledge about patients-their physical locales, cultural values, and environments in which they live-is essential to recruiting culturally and ethnically diverse population samples. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Clinical practice guidelines in breast cancer

    Science.gov (United States)

    Tyagi, N. Kumar; Dhesy-Thind, S.

    2018-01-01

    Background A number of clinical practice guidelines (cpgs) concerning breast cancer (bca) screening and management are available. Here, we review the strengths and weaknesses of cpgs from various professional organizations and consensus groups with respect to their methodologic quality, recommendations, and implementability. Methods Guidelines from four groups were reviewed with respect to two clinical scenarios: adjuvant ovarian function suppression (ofs) in premenopausal women with early-stage estrogen receptor–positive bca, and use of sentinel lymph node biopsy (slnb) after neoadjuvant chemotherapy (nac) for locally advanced bca. Guidelines from the American Society of Clinical Oncology (asco); Cancer Care Ontario’s Program in Evidence Based Care (cco’s pebc); the U.S. National Comprehensive Cancer Network (nccn); and the St. Gallen International Breast Cancer Consensus Conference were reviewed by two independent assessors. Guideline methodology and applicability were evaluated using the agree ii tool. Results The quality of the cpgs was greatest for the guidelines developed by asco and cco’s pebc. The nccn and St. Gallen guidelines were found to have lower scores for methodologic rigour. All guidelines scored poorly for applicability. The recommendations for ofs were similar in three guidelines. Recommendations by the various organizations for the use of slnb after nac were contradictory. Conclusions Our review demonstrated that cpgs can be heterogeneous in methodologic quality. Low-quality cpg implementation strategies contribute to low uptake of, and adherence to, bca cpgs. Further research examining the barriers to recommendations—such as intrinsic guideline characteristics and the needs of end users—is required. The use of bca cpgs can improve the knowledge-to-practice gap and patient outcomes.

  4. Nonpalpable breast cancer : mammographic and clinical findings

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Jae Seung; Kim, Eun Kyung; Oh, Ki Keun; Cheon, Young Jik; Lee, Byung Chan [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    1998-08-01

    To evaluate the mammographic and clinical findings of nonpalpable breast cancer. Materials and Methods : In 28 of 607 breast cancer patients examined between January 1994 and April 1997, lesions were nonpalpable. We retrospectively analyzed the mammographic, clinical and pathologic features of 25 patients (28 lesions) whose mammograms we obtained. Results : Among these 25 patients (28 lesions) screening was abnormal in 22; other symptoms were bloody nipple discharge(n=4), and nipple eczema(n=2). The patients were 34-62 (mean 52)years old. Invasive ductal carcinoma(n=13), DCIS(ductal carcinoma in situ, n-12), Paget's disease (n=2), and LCIS(lobular carcinoma in situ, n=1) were found during surgery. Six of 28 lesions(21%) showed evidence of axillary nodal metastasis;the majority arose from the upper outer quadrant of the breast (n=21). The mammographic findings were mass (50%), (and mass with microcalcification, 11%); microcalcification(29%); asymmetrical density(14%); and normal (7%). According to the mammographic density of breast parenchyma, the major finding in the low density group(N1+P1) was mass(9/9), and in the high density group(P2+DY) was microcalcification (12/19). Conclusion : The most common mammographic findings of nonpalpable breast cancer were mass (50%) and microcalcification(29%). Its features varied according to the mammographic density of breast parenchyma;mass was the main finding in the low density group and microcalcification in the high density group.

  5. Nonpalpable breast cancer : mammographic and clinical findings

    International Nuclear Information System (INIS)

    Seo, Jae Seung; Kim, Eun Kyung; Oh, Ki Keun; Cheon, Young Jik; Lee, Byung Chan

    1998-01-01

    To evaluate the mammographic and clinical findings of nonpalpable breast cancer. Materials and Methods : In 28 of 607 breast cancer patients examined between January 1994 and April 1997, lesions were nonpalpable. We retrospectively analyzed the mammographic, clinical and pathologic features of 25 patients (28 lesions) whose mammograms we obtained. Results : Among these 25 patients (28 lesions) screening was abnormal in 22; other symptoms were bloody nipple discharge(n=4), and nipple eczema(n=2). The patients were 34-62 (mean 52)years old. Invasive ductal carcinoma(n=13), DCIS(ductal carcinoma in situ, n-12), Paget's disease (n=2), and LCIS(lobular carcinoma in situ, n=1) were found during surgery. Six of 28 lesions(21%) showed evidence of axillary nodal metastasis;the majority arose from the upper outer quadrant of the breast (n=21). The mammographic findings were mass (50%), (and mass with microcalcification, 11%); microcalcification(29%); asymmetrical density(14%); and normal (7%). According to the mammographic density of breast parenchyma, the major finding in the low density group(N1+P1) was mass(9/9), and in the high density group(P2+DY) was microcalcification (12/19). Conclusion : The most common mammographic findings of nonpalpable breast cancer were mass (50%) and microcalcification(29%). Its features varied according to the mammographic density of breast parenchyma;mass was the main finding in the low density group and microcalcification in the high density group

  6. When fear of cancer recurrence becomes a clinical issue: a qualitative analysis of features associated with clinical fear of cancer recurrence.

    Science.gov (United States)

    Mutsaers, Brittany; Jones, Georden; Rutkowski, Nicole; Tomei, Christina; Séguin Leclair, Caroline; Petricone-Westwood, Danielle; Simard, Sébastien; Lebel, Sophie

    2016-10-01

    Fear of cancer recurrence (FCR) is a common experience for cancer survivors. However, it remains unclear what characteristics differentiate non-clinical from clinical levels of FCR. The goal of this study was to investigate the potential hallmarks of clinical FCR. A convenience sample of 40 participants (n = 19 female) was drawn from another study (Lebel et al. in Qual Life Res 25:311-321. doi: 10.1007/s11136-015-1088-2 , 2016). The semi-structured interview for fear of cancer recurrence (Simard and Savard in J Cancer Surviv 9:481-491. doi: 10.1007/s11764-015-0424-4 , 2015) was used to identify participants with non-clinical and clinical FCR and qualitative analysis of these interviews was performed. Individuals with clinical FCR reported the following features: death-related thoughts, feeling alone, belief that the cancer would return, experiencing intolerance of uncertainty, having cancer-related thoughts and imagery that were difficult to control, daily and recurrent, lasted 30 minutes or more, increased over time, caused distress and impacted their daily life. Triggers of FCR and coping strategies did not appear to be features of clinical FCR as they were reported by participants with a range of FCR scores. While features of clinical FCR found in this analysis such as intrusive thoughts, distress and impact on functioning confirmed previous FCR research, other features spontaneously emerged from the interviews including "death-related thoughts," "feeling alone," and "belief that the cancer will return." The participants' descriptions of cancer-specific fear and worry suggest that FCR is a distinct phenomenon related to cancer survivorship, despite similarities with psychological disorders (e.g., Anxiety Disorders). Future research investigating the construct of FCR, and the distinguishing features of clinical FCR across a range of cancer types and gender is required.

  7. Hereditary Nonpolyposis Colorectal Cancer and Cancer Syndromes: Recent Basic and Clinical Discoveries

    Directory of Open Access Journals (Sweden)

    Erbao Chen

    2018-01-01

    Full Text Available Approximately one-third of individuals diagnosed with colorectal cancer have a family history of cancer, suggesting that CRCs may result from a heritable component. Despite the availability of current gene-identification techniques, only 5% of all CRCs emerge from well-identifiable inherited causes for predisposition, including polyposis and nonpolyposis syndromes. Hereditary nonpolyposis colorectal cancer represents a large proportion of cases, and robustly affected patients are at increased risk for early onset, synchronous, and metachronous colorectal malignancies and extracolonic malignancies. HNPCC encompasses several cancer syndromes, such as Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X, which have remarkable clinical presentations and overlapping genetic profiles that make clinical diagnosis a challenging task. Therefore, distinguishing between the HNPCC disorders is crucial for physicians as an approach to tailor different recommendations for patients and their at-risk family members according to the risks for colonic and extracolonic cancer associated with each syndrome. Identification of these potential patients through epidemiological characteristics and new genetic testing can estimate the individual risk, which informs appropriate cancer screening, surveillance, and/or treatment strategies. In the past three years, many appealing and important advances have been made in our understanding of the relationship between HNPCC and CRC-associated syndromes. The knowledge from the genetic profile of cancer syndromes and unique genotype-phenotype profiles in the different syndromes has changed our cognition. Therefore, this review presents and discusses HNPCC and several common nonpolyposis syndromes with respect to molecular phenotype, histopathologic features, and clinical presentation.

  8. Peculiarities of clinical course of children skin cancer

    International Nuclear Information System (INIS)

    Zikiryakhodjaev, D.Z.; Sanginov, D.R.

    2001-01-01

    In this chapter of book authors investigated the peculiarities of clinical course of children skin cancer. They noted that comprehensive studying of peculiarities of clinical course of children skin cancer proved that they depend not only from age, but from morphologic structure, previous skin illness which was cause of skin cancer

  9. Training Needs of Clinical and Research Professionals to Optimize Minority Recruitment and Retention in Cancer Clinical Trials.

    Science.gov (United States)

    Niranjan, Soumya J; Durant, Raegan W; Wenzel, Jennifer A; Cook, Elise D; Fouad, Mona N; Vickers, Selwyn M; Konety, Badrinath R; Rutland, Sarah B; Simoni, Zachary R; Martin, Michelle Y

    2017-08-03

    The study of disparities in minority recruitment to cancer clinical trials has focused primarily on inquiries among minority patient populations. However, clinical trial recruitment is complex and requires a broader appreciation of the multiple factors that influence minority participation. One area that has received little attention is minority recruitment training for professionals who assume various roles in the clinical trial recruitment process. Therefore, we assessed the perspectives of cancer center clinical and research personnel on their training and education needs toward minority recruitment for cancer clinical trials. Ninety-one qualitative interviews were conducted at five U.S. cancer centers among four stakeholder groups: cancer center leaders, principal investigators, referring clinicians, and research staff. Interviews were recorded and transcribed. Qualitative analyses focused on response data related to training for minority recruitment for cancer clinical trials. Four prominent themes were identified: (1) Research personnel are not currently being trained to focus on recruitment and retention of minority populations; (2) Training for minority recruitment and retention provides for a specific focus on factors influencing minority research participation; (3) Training on cultural awareness may help to bridge cultural gaps between potential minority participants and research professionals; (4) Views differ regarding the importance of research personnel training designed to focus on recruitment of minority populations. There is a lack of systematic training for minority recruitment. Many stakeholders acknowledged the benefits of minority recruitment training and welcomed training that focuses on increasing cultural awareness to increase the participation of minorities in cancer clinical trials.

  10. Evaluating the effect of clinical care pathways on quality of cancer care: analysis of breast, colon and rectal cancer pathways.

    Science.gov (United States)

    Bao, Han; Yang, Fengjuan; Su, Shaofei; Wang, Xinyu; Zhang, Meiqi; Xiao, Yaming; Jiang, Hao; Wang, Jiaying; Liu, Meina

    2016-05-01

    Substantial gaps exist between clinical practice and evidence-based cancer care, potentially leading to adverse clinical outcomes and decreased quality of life for cancer patients. This study aimed to evaluate the usefulness of clinical pathways as a tool for improving quality of cancer care, using breast, colon, and rectal cancer pathways as demonstrations. Newly diagnosed patients with invasive breast, colon, and rectal cancer were enrolled as pre-pathway groups, while patients with the same diagnoses treated according to clinical pathways were recruited for post-pathway groups. Compliance with preoperative core biopsy or fine-needle aspiration, utilization of sentinel lymph node biopsy, and proportion of patients whose tumor hormone receptor status was stated in pathology report were significantly increased after implementation of clinical pathway for breast cancer. For colon cancer, compliance with two care processes was significantly improved: surgical resection with anastomosis and resection of at least 12 lymph nodes. Regarding rectal cancer, there was a significant increase in compliance with preoperative evaluation of depth of tumor invasion, total mesorectal excision treatment of middle- or low-position rectal cancer, and proportion of patients who had undergone rectal cancer surgery whose pathology report included margin status. Moreover, total length of hospital stay was decreased remarkably for all three cancer types, and postoperative complications remained unchanged following implementation of the clinical pathways. Clinical pathways can improve compliance with standard care by implementing evidence-based quality indicators in daily practice, which could serve as a useful tool for narrowing the gap between clinical practice and evidence-based care.

  11. The Clinical Proteomic Technologies for Cancer | Antibody Portal

    Science.gov (United States)

    An objective of the Reagents and Resources component of NCI's Clinical Proteomic Technologies for Cancer Initiative is to generate highly characterized monoclonal antibodies to human proteins associated with cancer.

  12. Main clinical epidemiological features of lung cancer

    International Nuclear Information System (INIS)

    Costa Montane, Daniel Marino; Prado Lage, Yulien; Lozano Salazar; Jorge Luis

    2011-01-01

    A descriptive and cross-sectional study of 95 patients with lung cancer, discharged from Neumology Service at 'Dr Juan Bruno Zayas Alfonso' General Hospital in Santiago de Cuba, was carried out from January, 2008 to December, 2008 in order to identify the main clinical epidemiological features of the aforementioned disease. A malignancy predominance among men aged between 56 and 65 years old, belonging to urban areas and being heavy smoker (out of 30 cigarettes per day over 30 years ), was found. Those affected without a confirmed histological type and IV clinical stage epidermoid carcinoma were predominant. Most of them had the opportunity to be treated. Increasing and intensifying health promotion and disease prevention campaigns were recommended so as to achieve the population to avoid or quit the smoking habit. (author)

  13. Multiparametric MRI in the detection of clinically significant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Futterer, Jurgen J. [Dept. of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen (Netherlands)

    2017-08-01

    Prostate cancer is the most common cancer among men aged 50 years and older in developed countries and the third leading cause of cancer-related death in men. Multiparametric prostate MR imaging is currently the most accurate imaging modality to detect, localize, and stage prostate cancer. The role of multi-parametric MR imaging in the detection of clinically significant prostate cancer are discussed. In addition, insights are provided in imaging techniques, protocol, and interpretation.

  14. [The Functional Role of Exosomes in Cancer Biology and Their Potential as Biomarkers and Therapeutic Targets of Cancer].

    Science.gov (United States)

    Naito, Yutaka; Yoshioka, Yusuke; Ochiya, Takahiro

    2015-06-01

    Intercellular communication plays an important role in the regulation of various cellular events. In particular, cancer cells and the surrounding cells communicate with each other, and this intercellular communication triggers cancer initiation and progression through the secretion of molecules, including growth factors and cytokines. Recent advances in cancer biology have indicated that small membrane vesicles, termed exosomes, also serve as regulatory agents in intercellular communications. Exosomes contain functional cellular components, including proteins and microRNAs (miRNAs), and they transfer these components to recipient cells. This exosome-mediated intercellular communication leads to increased growth, invasion, and metastasis of cancer. Thus, researchers regard exosomes as important cues to understanding the molecular mechanisms of cancer biology. Indeed, several lines of evidence have demonstrated that exosomes can explain multiple aspects of cancer biology. In addition, increasing evidence suggests that exosomes and their specific molecules are also attractive for use as biomarkers and therapeutic targets in cancer. Recent reports showed the efficacy of a novel diagnosis by detecting component molecules of cancer-derived exosomes, including miRNAs and membrane proteins. Furthermore, clinical trials that test the application of exosomes for cancer therapy have already been reported. From these points of view, we will summarize experimental data that support the role of exosomes in cancer progression and the potential of exosomes for use in novel diagnostic and therapeutic approaches for cancer.

  15. Positron Emission Tomography (PET) and breast cancer in clinical practice

    International Nuclear Information System (INIS)

    Lavayssiere, Robert; Cabee, Anne-Elizabeth; Filmont, Jean-Emmanuel

    2009-01-01

    The landscape of oncologic practice has changed deeply during the past few years and there is now a need, through a multidisciplinary approach, for imaging to provide accurate evaluation of morphology and function and to guide treatment (Image Guided Therapy). Increasing emphasis has been put on Position Emission Tomography (PET) role in various cancers among clinicians and patients despite a general context of healthcare expenditure limitation. Positron Emission Tomography has currently a limited role in breast cancer, but also general radiologists and specialists should be aware of these indications, especially when staging aggressive cancers and looking for recurrence. Currently, the hybrid systems associating PET and Computed Tomography (CT) and in the same device [Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology 2004;231:305-32; Blodgett TM, Meltzer CM, Townsend DW. PET/CT: form and function. Radiology 2007;242:360-85; von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and futures directions. Radiology 2006;238(2):405-22], or PET-CT, are more commonly used and the two techniques are adding their potentialities. Other techniques, MRI in particular, may also compete with PET in some instance and as far as ionizing radiations dose limitation is considered, some breast cancers becoming some form of a chronic disease. Breast cancer is a very complex, non-uniform, disease and molecular imaging at large may contribute to a better knowledge and to new drugs development. Ongoing research, Positron Emission Mammography (PEM) and new tracers, are likely to bring improvements in patient care [Kelloff GJ, Hoffman JM, Johnson B, et al. Progress and promise of FDG-PET Imaging for cancer patient management and oncologic drug development. Clin Cancer Res 2005;1(April (8)): 2005

  16. Positron Emission Tomography (PET) and breast cancer in clinical practice

    Energy Technology Data Exchange (ETDEWEB)

    Lavayssiere, Robert [Centre d' Imagerie Paris-Nord, 1, avenue Charles Peguy, 95200 Sarcelles (France); Institut du Sein Henri Hartmann (ISHH), 1, rue des Dames Augustines, 92200 Neuilly sur Seine (France)], E-mail: cab.lav@wanadoo.fr; Cabee, Anne-Elizabeth [Centre d' Imagerie Paris-Nord, 1, avenue Charles Peguy, 95200 Sarcelles (France); Institut du Sein Henri Hartmann (ISHH), 1, rue des Dames Augustines, 92200 Neuilly sur Seine (France); Centre RMX, 80, avenue Felix Faure, 75105 Paris (France); Filmont, Jean-Emmanuel [Institut du Sein Henri Hartmann (ISHH), 1, rue des Dames Augustines, 92200 Neuilly sur Seine (France); American Hospital of Paris, Nuclear Medicine, 63, boulevard Victor Hugo - BP 109, 92202 Neuilly sur Seine Cedex (France)

    2009-01-15

    The landscape of oncologic practice has changed deeply during the past few years and there is now a need, through a multidisciplinary approach, for imaging to provide accurate evaluation of morphology and function and to guide treatment (Image Guided Therapy). Increasing emphasis has been put on Position Emission Tomography (PET) role in various cancers among clinicians and patients despite a general context of healthcare expenditure limitation. Positron Emission Tomography has currently a limited role in breast cancer, but also general radiologists and specialists should be aware of these indications, especially when staging aggressive cancers and looking for recurrence. Currently, the hybrid systems associating PET and Computed Tomography (CT) and in the same device [Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology 2004;231:305-32; Blodgett TM, Meltzer CM, Townsend DW. PET/CT: form and function. Radiology 2007;242:360-85; von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and futures directions. Radiology 2006;238(2):405-22], or PET-CT, are more commonly used and the two techniques are adding their potentialities. Other techniques, MRI in particular, may also compete with PET in some instance and as far as ionizing radiations dose limitation is considered, some breast cancers becoming some form of a chronic disease. Breast cancer is a very complex, non-uniform, disease and molecular imaging at large may contribute to a better knowledge and to new drugs development. Ongoing research, Positron Emission Mammography (PEM) and new tracers, are likely to bring improvements in patient care [Kelloff GJ, Hoffman JM, Johnson B, et al. Progress and promise of FDG-PET Imaging for cancer patient management and oncologic drug development. Clin Cancer Res 2005;1(April (8)): 2005].

  17. Single-cell proteomics: potential implications for cancer diagnostics.

    Science.gov (United States)

    Gavasso, Sonia; Gullaksen, Stein-Erik; Skavland, Jørn; Gjertsen, Bjørn T

    2016-01-01

    Single-cell proteomics in cancer is evolving and promises to provide more accurate diagnoses based on detailed molecular features of cells within tumors. This review focuses on technologies that allow for collection of complex data from single cells, but also highlights methods that are adaptable to routine cancer diagnostics. Current diagnostics rely on histopathological analysis, complemented by mutational detection and clinical imaging. Though crucial, the information gained is often not directly transferable to defined therapeutic strategies, and predicting therapy response in a patient is difficult. In cancer, cellular states revealed through perturbed intracellular signaling pathways can identify functional mutations recurrent in cancer subsets. Single-cell proteomics remains to be validated in clinical trials where serial samples before and during treatment can reveal excessive clonal evolution and therapy failure; its use in clinical trials is anticipated to ignite a diagnostic revolution that will better align diagnostics with the current biological understanding of cancer.

  18. Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

    Science.gov (United States)

    2017-10-01

    prostate cancer . Cancer Res 70: 7992-8002, 2010 8. Nelson PS: Molecular states underlying an- drogen receptor activation: A framework for thera- peutics...targeting androgen signaling in prostate cancer . J Clin Oncol 30:644-646, 2012 9. Thadani-Mulero M, Nanus DM, Giannakakou P: Androgen receptor on the... prostate cancer . Clin Cancer Res 21:795-807, 2015 17. van Soest RJ, de Morrée ES, Kweldam CF, et al: Targeting the androgen receptor confers in vivo

  19. Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal Effect for Advanced Cancers

    Directory of Open Access Journals (Sweden)

    Joe Abdo

    2018-03-01

    Full Text Available Since the 1920s the gold standard for treating cancer has been surgery, which is typically preceded or followed with chemotherapy and/or radiation, a process that perhaps contributes to the destruction of a patient’s immune defense system. Cryosurgery ablation of a solid tumor is mechanistically similar to a vaccination where hundreds of unique antigens from a heterogeneous population of tumor cells derived from the invading cancer are released. However, releasing tumor-derived self-antigens into circulation may not be sufficient enough to overcome the checkpoint escape mechanisms some cancers have evolved to avoid immune responses. The potentiated immune response caused by blocking tumor checkpoints designed to prevent programmed cell death may be the optimal treatment method for the immune system to recognize these new circulating cryoablated self-antigens. Preclinical and clinical evidence exists for the complementary roles for Cytotoxic T-lymphocyte-associated protein (CTLA-4 and PD-1 antagonists in regulating adaptive immunity, demonstrating that combination immunotherapy followed by cryosurgery provides a more targeted immune response to distant lesions, a phenomenon known as the abscopal effect. We propose that when the host’s immune system has been “primed” with combined anti-CTLA-4 and anti-PD-1 adjuvants prior to cryosurgery, the preserved cryoablated tumor antigens will be presented and processed by the host’s immune system resulting in a robust cytotoxic CD8+ T-cell response. Based on recent investigations and well-described biochemical mechanisms presented herein, a polyvalent autoinoculation of many tumor-specific antigens, derived from a heterogeneous population of tumor cancer cells, would present to an unhindered yet pre-sensitized immune system yielding a superior advantage in locating, recognizing, and destroying tumor cells throughout the body.

  20. Plasma YKL-40: a potential new cancer biomarker?

    DEFF Research Database (Denmark)

    Johansen, Julia S; Schultz, Nicolai A; Jensen, Benny V

    2009-01-01

    tissue remodeling. Plasma levels of YKL-40 are elevated in a subgroup of patients with primary or advanced cancer compared with age-matched healthy subjects, but also in patients with many different diseases characterized by inflammation. Elevated plasma YKL-40 levels are an independent prognostic...... by inflammation. Large prospective, longitudinal clinical cancer studies are needed to determine if plasma YKL-40 is a new cancer biomarker, or is mainly a biomarker of inflammation....

  1. Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer.

    Science.gov (United States)

    Yang, Wanli; Ma, Jiaojiao; Zhou, Wei; Cao, Bo; Zhou, Xin; Yang, Zhiping; Zhang, Hongwei; Zhao, Qingchuan; Fan, Daiming; Hong, Liu

    2017-11-01

    Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.

  2. Fulfilling the potential of cancer prevention and early detection

    National Research Council Canada - National Science Library

    Curry, Susan J; Byers, Tim; Hewitt, Maria Elizabeth

    2003-01-01

    ... competences and with regard for appropriate balance. Support for this project was provided by the National Cancer Institute; the Centers for Disease Control and Prevention; the American Cancer Society; Abbott Laboratories; the American Society of Clinical Oncology; Amgen, Inc.; Aventis; and the United Health Care Foundation. The views pre...

  3. Checkpoint inhibitors in endometrial cancer: preclinical rationale and clinical activity.

    Science.gov (United States)

    Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Aglietta, Massimo; Genta, Sofia; Valabrega, Giorgio

    2017-10-27

    Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors. We analyzed all available evidence supporting the role of tumor microenvironment (TME) in EC development and the therapeutic implications offered by immune checkpoint inhibitors in this setting. We performed a review on Pubmed with Mesh keywords 'endometrial cancer' and the name of each checkpoint inhibitor discussed in the article. The same search was operated on clinicaltrial.gov to identify ongoing clinical trials exploring PD-1/PD-L1 and CTLA-4 axis in EC, particularly focusing on POLE-ultra-muted and MSI-H cancer types. POLE-ultra-mutated and MSI-H ECs showed an active TME expressing high number of neo-antigens and an elevated amount of tumor infiltrating lymphocytes (TILs). Preliminary results from a phase-1 clinical trial (KEYNOTE-028) demonstrated antitumor activity of Pembrolizumab in EC. Moreover, both Pembrolizumab and Nivolumab reported durable clinical responses in POLE-ultra-mutated patients. Immune checkpoint inhibitors are an attractive option in POLE-ultra-mutated and MSI-H ECs. Future investigations in these subgroups include combinations of checkpoints inhibitors with chemotherapy and small tyrosine kinase inhibitors (TKIs) to enhance a more robust intra-tumoral immune response.

  4. Clinical Characteristics of Patients with Sporadic Colorectal Cancer and Primary Cancers of Other Organs

    Directory of Open Access Journals (Sweden)

    Jung-Yu Kan

    2006-11-01

    Full Text Available Most cancer patients often neglect the possibility of secondary cancer. Colorectal cancer (CRC is the third leading cause of cancer death in Taiwan. It is important to be aware of the clinical characteristics of double cancer in CRC patients for early diagnosis and treatment. We retrospectively analyzed 1,031 CRC patients who underwent surgical treatment at the Department of Surgery of Kaohsiung Medical University Hospital between January 1998 and December 2004. Among these patients, CRC was accompanied by cancer of other organs in 17 patients (1.65%, either synchronously or metachronously. Therefore, we describe our experience regarding the location of CRC, the clinical symptoms and signs of these patients, the TNM stage, histology, phase, association with other malignancies, interval between cancers and clinical outcomes. Of the 17 patients in whom CRC was accompanied by primary cancer of other organs, there were four synchronous and 13 metachronous multiple cancer patients. Our patient group comprised six men and 11 women with ages ranging from 47 to 88 years (median age, 66 years. The most common location of CRC was the sigmoid colon. Six gastric cancers (35.2% and six breast cancers (35.2% were associated with primary CRC. The remaining six second primary cancers were one lung cancer, one thyroid cancer, one cervical cancer, one ovarian cancer, one skin cancer, and one urinary bladder cancer. Of the 13 metachronous multiple cancer patients, eight patients developed subsequent CRC after primary cancers of other organs, whereas two patients developed a subsequent second primary cancer after CRC. The intervals between the development of metachronous multiple cancers ranged from 2 to 19 years. In this retrospective analysis, breast and gastric cancer patients were at increased risk of developing subsequent secondary CRC. Careful attention should always be paid to the possibility of secondary CRC in treating these cancer patients. Cancer

  5. AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer.

    Science.gov (United States)

    Shigeyasu, Kunitoshi; Okugawa, Yoshinaga; Toden, Shusuke; Miyoshi, Jinsei; Toiyama, Yuji; Nagasaka, Takeshi; Takahashi, Naoki; Kusunoki, Masato; Takayama, Tetsuji; Yamada, Yasuhide; Fujiwara, Toshiyoshi; Chen, Leilei; Goel, Ajay

    2018-06-21

    Adenosine-to-inosine (A-to-I) RNA editing, a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family, is a recently discovered epigenetic modification dysregulated in human cancers. However, the clinical significance and the functional role of RNA editing in colorectal cancer (CRC) remain unclear. We have systematically and comprehensively investigated the significance of the expression status of ADAR1 and of the RNA editing levels of antizyme inhibitor 1 (AZIN1), one of the most frequently edited genes in cancers, in 392 colorectal tissues from multiple independent CRC patient cohorts. Both ADAR1 expression and AZIN1 RNA editing levels were significantly elevated in CRC tissues when compared with corresponding normal mucosa. High levels of AZIN1 RNA editing emerged as a prognostic factor for overall survival and disease-free survival and were an independent risk factor for lymph node and distant metastasis. Furthermore, elevated AZIN1 editing identified high-risk stage II CRC patients. Mechanistically, edited AZIN1 enhances stemness and appears to drive the metastatic processes. We have demonstrated that edited AZIN1 functions as an oncogene and a potential therapeutic target in CRC. Moreover, AZIN1 RNA editing status could be used as a clinically relevant prognostic indicator in CRC patients.

  6. Metachronous Lung Cancer: Clinical Characteristics and Effects of Surgical Treatment.

    Science.gov (United States)

    Rzechonek, Adam; Błasiak, Piotr; Muszczyńska-Bernhard, Beata; Pawełczyk, Konrad; Pniewski, Grzegorz; Ornat, Maciej; Grzegrzółka, Jędrzej; Brzecka, Anna

    2018-01-01

    The occurrence of a second lung tumor after surgical removal of lung cancer usually indicates a lung cancer metastasis, but sometimes a new lesion proves to be a new primary lung cancer, i.e., metachronous lung cancer. The goal of the present study was to conduct a clinical evaluation of patients with metachronous lung cancer and lung cancer metastasis, and to compare the early and distant outcomes of surgical treatment in both cancer types. There were 26 age-matched patients with lung cancer metastases and 23 patients with metachronous lung cancers, who underwent a second lung cancer resection. We evaluated the histological type of a resected cancer, the extent of thoracosurgery, the frequency of early postoperative complications, and the probability of 5-year survival after the second operation. The findings were that metachronous lung cancer was adenocarcinoma in 52% of patients, with a different histopathological pattern from that of the primary lung cancer in 74% of patients. In both cancer groups, mechanical resections were the most common surgery type (76% of all cases), with anatomical resections such as segmentectomy, lobectomy, or pneumectomy being much rarer conducted. The incidence of early postoperative complications in metachronous lung cancer and lung cancer metastasis (30% vs. 31%, respectively) and the probability of 5-year survival after resection of either cancer tumor (60.7% vs. 50.9%, respectively) were comparable. In conclusion, patients undergoing primary lung cancer surgery require a long-term follow-up due to the risk of metastatic or metachronous lung cancer. The likelihood of metachronous lung cancer and pulmonary lung cancer metastases, the incidence of postoperative complications, and the probability of 5-year survival after resection of metachronous lung cancer or lung cancer metastasis are similar.

  7. Monitoring cancer stem cells: insights into clinical oncology

    Directory of Open Access Journals (Sweden)

    Lin SC

    2016-02-01

    Full Text Available ShuChen Lin,1,* YingChun Xu,2,* ZhiHua Gan,1 Kun Han,1 HaiYan Hu,3 Yang Yao,3 MingZhu Huang,4 DaLiu Min1 1Department of Oncology, Shanghai Sixth People’s Hospital East Campus, Shanghai Jiao Tong University, 2Department of Oncology, Renji Hospital, Shanghai Jiao Tong University, 3Department of Oncology, The Sixth People’s Hospital, Shanghai Jiao Tong University, 4Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Cancer stem cells (CSCs are a small, characteristically distinctive subset of tumor cells responsible for tumor initiation and progression. Several treatment modalities, such as surgery, glycolytic inhibition, driving CSC proliferation, immunotherapy, and hypofractionated radiotherapy, may have the potential to eradicate CSCs. We propose that monitoring CSCs is important in clinical oncology as CSC populations may reflect true treatment response and assist with managing treatment strategies, such as defining optimal chemotherapy cycles, permitting pretreatment cancer surveillance, conducting a comprehensive treatment plan, modifying radiation treatment, and deploying rechallenge chemotherapy. Then, we describe methods for monitoring CSCs. Keywords: cancer stem cells, glycolytic inhibition, watchful waiting, rechallenge, immunotherapy

  8. Computational Omics Funding Opportunity | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the NVIDIA Foundation are pleased to announce funding opportunities in the fight against cancer. Each organization has launched a request for proposals (RFP) that will collectively fund up to $2 million to help to develop a new generation of data-intensive scientific tools to find new ways to treat cancer.

  9. Anticancer potential of Hericium erinaceus extracts against human gastrointestinal cancers.

    Science.gov (United States)

    Li, Guang; Yu, Kai; Li, Fushuang; Xu, Kangping; Li, Jing; He, Shujin; Cao, Shousong; Tan, Guishan

    2014-04-28

    indole, pyrimidines, amino acids and derivative, three flavones, one anthraquinone, and six small aromatic compounds. HTJ5 and HTJ5A exhibited concentration-dependent cytotoxicity in vitro against liver cancer HepG2 and Huh-7, colon cancer HT-29, and gastric cancer NCI-87 cells with the IC50 in 2.50±0.25 and 2.00±0.25, 0.80±0.08 and 1.50±0.28, 1.25±0.06 and 1.25±0.05, and 5.00±0.22 and 4.50±0.14 mg/ml; respectively. For in vivo tumor xenograft studies, HTJ5 and HTJ5A showed significantly antitumor efficacy against all four xenograft models of HepG2, Huh-7, HT-29 and NCI-87 without toxicity to the host. Furthermore, HTJ5 and HTJ5A are more effective than that of 5-FU against the four tumors with less toxicity. HE extracts (HTJ5 and HTJ5A) are active against liver cancer HepG2 and Huh-7, colon cancer HT-29 and gastric cancer NCI-87 cells in vitro and tumor xenografts bearing in SCID mice in vivo. They are more effective and less toxic compared to 5-FU in all four in vivo tumor models. The compounds have the potential for development into anticancer agents for the treatment of gastrointestinal cancer used alone and/or in combination with clinical used chemotherapeutic drugs. However, further studies are required to find out the active chemical constituents and understand the mechanism of action associated with the super in vivo anticancer efficacy. In addition, future studies are needed to confirm our preliminary results of in vivo synergistic antitumor efficacy in animal models of tumor xenografts with the combination of HE extracts and clinical used anticancer drugs such as 5-FU, cisplatin and doxurubicin for the treatment of gastrointestinal cancers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Nutraceuticals as potential therapeutic agents for colon cancer: a review.

    Science.gov (United States)

    Kuppusamy, Palaniselvam; Yusoff, Mashitah M; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

    2014-06-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

  11. Nutraceuticals as potential therapeutic agents for colon cancer: a review

    Directory of Open Access Journals (Sweden)

    Palaniselvam Kuppusamy

    2014-06-01

    Full Text Available Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis.

  12. Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

    Science.gov (United States)

    Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

    2016-01-01

    Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

  13. Clinical Relevance of KRAS in Human Cancers

    Directory of Open Access Journals (Sweden)

    Sylwia Jančík

    2010-01-01

    Full Text Available The KRAS gene (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog is an oncogene that encodes a small GTPase transductor protein called KRAS. KRAS is involved in the regulation of cell division as a result of its ability to relay external signals to the cell nucleus. Activating mutations in the KRAS gene impair the ability of the KRAS protein to switch between active and inactive states, leading to cell transformation and increased resistance to chemotherapy and biological therapies targeting epidermal growth factor receptors. This review highlights some of the features of the KRAS gene and the KRAS protein and summarizes current knowledge of the mechanism of KRAS gene regulation. It also underlines the importance of activating mutations in the KRAS gene in relation to carcinogenesis and their importance as diagnostic biomarkers, providing clues regarding human cancer patients' prognosis and indicating potential therapeutic approaches.

  14. Efficiency of clinical and combined diagnosis of breast cancer

    International Nuclear Information System (INIS)

    Solov'ev, I.E.

    1986-01-01

    Problems on clinical, instrumental, laboratory diagnosis of mammary glands cancer are described. Efficiency of clinical examination, mammography, cytological examination, ultrasonic, radioisotopic diagnosis, some biochemical tests are estimated. The conclusion concerning advisability of complex diagnosis of mammary glands cancer especially its early forms is made. Perspectivity of application of polyamine test in diagnosis of primary cancer of the mammary gland is mark to estimate efficiency of its treatment

  15. EGFR signaling in colorectal cancer: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Saletti P

    2015-01-01

    Full Text Available Piercarlo Saletti,1 Francesca Molinari,2 Sara De Dosso,1 Milo Frattini2 1Oncology Institute of Southern Switzerland, Bellinzona, 2Laboratory of Molecular Pathology, Institute of Pathology, Locarno, Switzerland Abstract: Colorectal cancer (CRC remains a formidable health burden worldwide, with up to 50% of patients developing metastases during the course of their disease. This group of CRC patients, characterized by the worst prognosis, has been extensively investigated to improve their life expectancy. Main efforts, focused on the epidermal growth-factor receptor (EGFR, which plays a pivotal role in CRC pathogenesis, have led to the development and introduction in clinical practice of specific targeted therapies (ie, monoclonal antibodies. Subsequently, the scientific community has tried to identify molecular predictors of the efficacy of such therapies. However, it has become clear that EGFR alterations occurring in CRC are difficult to investigate, and therefore their predictive role is unclear. In contrast, the clinical role of two downstream members (KRAS and NRAS has been clearly demonstrated. Currently, EGFR-targeted therapies can be administered only to patients with wild-type KRAS and NRAS genes. Our review addresses the medical management of metastatic CRC. Specifically, we describe in detail the molecular biology of metastatic CRC, focusing on the EGFR signaling pathway, and we discuss the role of current and emerging related biomarkers and therapies in this field. We also summarize the clinical evidence regarding anti-EGFR monoclonal antibodies and examine potential future perspectives. Keywords: colorectal cancer, EGFR, gene mutations, cetuximab, panitumumab

  16. Inclusion of Minority Patients in Breast Cancer Clinical Trials: The Role of the Clinical Trial Environment

    National Research Council Canada - National Science Library

    Kaplan, Celia P

    2007-01-01

    .... While inroads to increasing minority inclusion in breast cancer clinical trials have been made, recent reports continue to demonstrate lower enrollment among African Americans, Asian Americans...

  17. TCGA bladder cancer study reveals potential drug targets

    Science.gov (United States)

    Investigators with TCGA have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bla

  18. Managing Potentially Resectable Metastatic Colon Cancer

    OpenAIRE

    Marshall, John L.

    2008-01-01

    For patients with metastatic colon cancer, management has evolved from resecting a single liver metastasis and having only one chemotherapy medicine, to resecting multiple metastases including those outside the liver as well as using combination chemotherapy (based on recent supportive trials) to improve outcomes. This success has also raised many questions, including the role of adjuvant chemotherapy to downstage borderline resectable tumors, whether patients who receive preoperative chemoth...

  19. Clinical Pharmacology of Chemotherapy Agents in Older People with Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoye He

    2011-01-01

    Full Text Available Populations around the world are aging, and the associated increase in cancer incidence has led to the recognition of the importance of geriatric oncology. Chronological age is a poor determinant of pharmacological response to cancer chemotherapy agents. Age-associated changes in physiology and organ function have a significant impact on the clinical pharmacology of cancer chemotherapy agents used in cancer treatment. Altered response to medicines in older people is a consequence of changes in body composition, organ function, concomitant pathophysiology, multiple medications, genetic determinants of drug response, and patient's clinical status. These issues highlight the need to individualize the management of cancer in the older people with consideration of age-related changes in the clinical pharmacology of cancer drugs, analgesics, and adjunctive therapies.

  20. Clinical and endorectal ultrasound staging of circumferential rectal cancers

    International Nuclear Information System (INIS)

    Smith, A.; Farmer, K.C.; Chapple, K.

    2008-01-01

    Full text: Circumferential rectal cancers present at a more advanced stage than those located in a single quadrant. Although accurate staging is an important aspect of the preoperative management of the patient with a rectal cancer, the clinical and radiological staging of this subgroup of rectal cancer patients has been poorly studied. All patients with a rectal cancer were assessed clinically (by digital rectal examination and rigid sigmoidoscopy) before the radiological assessment by endorectal ultrasound (ERUS). Data collected included tumour height (distance from anal verge in centimetre) and tumour type (circumferential or non-circumferential). Radiological tumour staging was with the TNM system. Fifty-nine subjects (33 men, 26 women; median age 65 years (range 38-86 years)) were identified with a circumferential rectal cancer. Mean height of the cancer was 8 - 0.4 cm (standard error of the mean; range 2-13 cm). Forty-two cancers were palpable, and 17 cancers were impalpable. All cancers assessed clinically as circumferential were confirmed as circumferential on ERUS scanning. Tumour stage as assessed by ERUS was either T3 (n = 57) or T4 (n = 2). Nodal status was NO (n = 29) and N1 (n = 30). All rectal cancers assessed as circumferential on clinical examination have an ERUS stage of T3 or greater.

  1. Clinical Trial Design for Testing the Stem Cell Model for the Prevention and Treatment of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, Rishindra M., E-mail: reddyrm@med.umich.edu [Medical Center, University of Michigan, 1500 E. Medical Center Drive, 2120 Taubman Center, Ann Arbor, MI 48109 (United States); Kakarala, Madhuri; Wicha, Max S. [Comprehensive Cancer Center, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109 (United States)

    2011-06-20

    The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples.

  2. Clinical Trial Design for Testing the Stem Cell Model for the Prevention and Treatment of Cancer

    International Nuclear Information System (INIS)

    Reddy, Rishindra M.; Kakarala, Madhuri; Wicha, Max S.

    2011-01-01

    The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples

  3. Molecular Biomarkers in the Clinical Management of Prostate Cancer.

    Science.gov (United States)

    Udager, Aaron M; Tomlins, Scott A

    2018-01-08

    Prostate cancer, one of the most common noncutaneous malignancies in men, is a heterogeneous disease with variable clinical outcome. Although the majority of patients harbor indolent tumors that are essentially cured by local therapy, subsets of patients present with aggressive disease or recur/progress after primary treatment. With this in mind, modern clinical approaches to prostate cancer emphasize the need to reduce overdiagnosis and overtreatment via personalized medicine. Advances in our understanding of prostate cancer pathogenesis, coupled with recent technologic innovations, have facilitated the development and validation of numerous molecular biomarkers, representing a range of macromolecules assayed from a variety of patient sample types, to help guide the clinical management of prostate cancer, including early detection, diagnosis, prognostication, and targeted therapeutic selection. Herein, we review the current state of the art regarding prostate cancer molecular biomarkers, emphasizing those with demonstrated utility in clinical practice. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  4. Clinically Relevant Physical Benefits of Exercise Interventions in Breast Cancer Survivors.

    Science.gov (United States)

    Kirkham, Amy A; Bland, Kelcey A; Sayyari, Sarah; Campbell, Kristin L; Davis, Margot K

    2016-02-01

    Evidence is currently limited for the effect of exercise on breast cancer clinical outcomes. However, several of the reported physical benefits of exercise, including peak oxygen consumption, functional capacity, muscle strength and lean mass, cardiovascular risk factors, and bone health, have established associations with disability, cardiovascular disease risk, morbidity, and mortality. This review will summarize the clinically relevant physical benefits of exercise interventions in breast cancer survivors and discuss recommendations for achieving these benefits. It will also describe potential differences in intervention delivery that may impact outcomes and, lastly, describe current physical activity guidelines for cancer survivors.

  5. Epigenetic Modifications: Therapeutic Potential in Cancer

    Directory of Open Access Journals (Sweden)

    Manisha Sachan

    2015-08-01

    Full Text Available Epigenetic modifications and alterations in chromatin structure and function contribute to the cumulative changes observed as normal cells undergo malignant transformation. These modifications and enzymes (DNA methyltransferases, histone deacetylases, histone methyltransferases, and demethylases related to them have been deeply studied to develop new drugs, epigenome-targeted therapies and new diagnostic tools. Epigenetic modifiers aim to restore normal epigenetic modification patterns through the inhibition of epigenetic modifier enzymes. Four of them (azacitidine, decitabine, vorinostat and romidepsin are approved by the U.S. Food and Drug Administration. This article provides an overview about the known functional roles of epigenetic enzymes in cancer development.

  6. [A web-based integrated clinical database for laryngeal cancer].

    Science.gov (United States)

    E, Qimin; Liu, Jialin; Li, Yong; Liang, Chuanyu

    2014-08-01

    To establish an integrated database for laryngeal cancer, and to provide an information platform for laryngeal cancer in clinical and fundamental researches. This database also meet the needs of clinical and scientific use. Under the guidance of clinical expert, we have constructed a web-based integrated clinical database for laryngeal carcinoma on the basis of clinical data standards, Apache+PHP+MySQL technology, laryngeal cancer specialist characteristics and tumor genetic information. A Web-based integrated clinical database for laryngeal carcinoma had been developed. This database had a user-friendly interface and the data could be entered and queried conveniently. In addition, this system utilized the clinical data standards and exchanged information with existing electronic medical records system to avoid the Information Silo. Furthermore, the forms of database was integrated with laryngeal cancer specialist characteristics and tumor genetic information. The Web-based integrated clinical database for laryngeal carcinoma has comprehensive specialist information, strong expandability, high feasibility of technique and conforms to the clinical characteristics of laryngeal cancer specialties. Using the clinical data standards and structured handling clinical data, the database can be able to meet the needs of scientific research better and facilitate information exchange, and the information collected and input about the tumor sufferers are very informative. In addition, the user can utilize the Internet to realize the convenient, swift visit and manipulation on the database.

  7. Patient-Centered Care in Breast Cancer Genetic Clinics

    Directory of Open Access Journals (Sweden)

    Anne Brédart

    2018-02-01

    Full Text Available With advances in breast cancer (BC gene panel testing, risk counseling has become increasingly complex, potentially leading to unmet psychosocial needs. We assessed psychosocial needs and correlates in women initiating testing for high genetic BC risk in clinics in France and Germany, and compared these results with data from a literature review. Among the 442 counselees consecutively approached, 212 (83% in France and 180 (97% in Germany, mostly BC patients (81% and 92%, respectively, returned the ‘Psychosocial Assessment in Hereditary Cancer’ questionnaire. Based on the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA BC risk estimation model, the mean BC lifetime risk estimates were 19% and 18% in France and Germany, respectively. In both countries, the most prevalent needs clustered around the “living with cancer” and “children-related issues” domains. In multivariate analyses, a higher number of psychosocial needs were significantly associated with younger age (b = −0.05, higher anxiety (b = 0.78, and having children (b = 1.51, but not with country, educational level, marital status, depression, or loss of a family member due to hereditary cancer. These results are in line with the literature review data. However, this review identified only seven studies that quantitatively addressed psychosocial needs in the BC genetic counseling setting. Current data lack understandings of how cancer risk counseling affects psychosocial needs, and improves patient-centered care in that setting.

  8. Potential Impact on Clinical Decision Making via a Genome-Wide Expression Profiling: A Case Report

    Directory of Open Access Journals (Sweden)

    Hyun Kim

    2016-11-01

    Full Text Available Management of men with prostate cancer is fraught with uncertainty as physicians and patients balance efficacy with potential toxicity and diminished quality of life. Utilization of genomics as a prognostic biomarker has improved the informed decision-making process by enabling more rationale treatment choices. Recently investigations have begun to determine whether genomic information from tumor transcriptome data can be used to impact clinical decision-making beyond prognosis. Here we discuss the potential of genomics to alter management of a patient who presented with high-risk prostate adenocarcinoma. We suggest that this information help selecting patients for advanced imaging, chemotherapies, or clinical trial.

  9. A prospective three-dimensional analysis about the impact of differences in the clinical target volume in prostate cancer irradiation on normal-tissue exposure. A potential for increasing the benefit/risk ratio

    International Nuclear Information System (INIS)

    Hille, A.; Toews, N.; Schmidberger, H.; Hess, C.F.

    2005-01-01

    Background and purpose: rectal toxicity following external-beam irradiation of prostate cancer correlates with the exposed percentage of rectal volume. Recently, it has been recommended to reduce the volume of the seminal vesicles that should be included in the clinical target volume (CTV). The purpose of this study was to quantitatively assess the impact of this CTV reduction on the expected rectal and bladder dose sparing. Patients and methods: 14 patients with localized prostate cancer undergoing external-beam radiotherapy were investigated. The prostate, the prostate + entire seminal vesicles, or the prostate + proximal seminal vesicles were delineated as CTV. Treatment plans were generated and compared concerning rectum and bladder dose-volume histograms (DVHs). Results: the exposure of rectum and bladder volume was significantly lower in case of irradiation of the prostate only compared to inclusion of the proximal or entire seminal vesicles into the CTV. The reduction of the CTV from prostate + entire seminal vesicles to prostate + proximal seminal vesicles led to a significant reduction of the rectal and bladder dose exposure. Conclusion: reduction of the CTV to the prostate only, or to the prostate + proximal seminal vesicles led to significant rectal and bladder dose sparing compared to irradiation of the prostate + entire seminal vesicles. In patients with a higher risk for seminal vesicles involvement, irradiation of the prostate + proximal seminal vesicles should be preferred. In case of a need for irradiation of the entire seminal vesicles, patients should be informed about a higher risk for chronic rectal toxicity and, possibly, for bladder complications. (orig.)

  10. Cancer clinical trials in persons with HIV infection.

    Science.gov (United States)

    Little, Richard F

    2017-01-01

    The era of modern HIV therapeutics is well underway. The cancer and infectious disease epidemiology of HIV disease has markedly altered as populations are availed to the benefits of antiretroviral therapy (ARV). The types of cancers occurring among those with HIV infection has broadened but the case burden in absolute numbers is very low relative to the background population. There are fewer incident cases of the AIDS-defining cancers (aggressive B-cell lymphomas, Kaposi's sarcoma, and cervical cancer). There is an increased risk for certain non-AIDS-defining cancers, but these occur somewhat sporadically relative to clinical trial enrollment. The changing epidemiology of cancer in HIV poses challenges as well as opportunities for participation of persons with HIV in cancer therapy clinical trials. There are excellent examples of cancer trials that inform cancer therapy for patients with HIV infection. Examples include those from HIV-specific trials and from trials mainly focused on the background population that included patients with HIV infection. Interpretation of clinical trials to guide therapy for those with HIV infection and cancer largely depends on data that does not include HIV-infected patients. The ability to extend clinical trial findings to populations not included in clinical trials remains problematic for a variety of populations, including those with HIV or AIDS. Careful prioritization of studies designed to bridge this gap is needed. However, there are published studies that serve as excellent examples bridging these gaps and the portfolio of cancer therapy trials underway will inform HIV and cancer better than at any time in the past.

  11. Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

    Science.gov (United States)

    Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

    2016-08-15

    A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

  12. Au/TiO2 nanobelt heterostructures for the detection of cancer cells and anticancer drug activity by potential sensing

    International Nuclear Information System (INIS)

    Cui, Jingjie; Xu, Ping; Li, Hong; Chen, Jing; Chen, Shaowei; Gao, Li

    2016-01-01

    Cancer is a cell dysfunction disease. The detection of cancer cells is extremely important for early diagnosis and clinical treatments. At present, the pretreatment for the detection of cancer cells is costly, complicated and time-consuming. As different species of the analytes may give rise to specific voltammetric signals at distinctly different potentials, simple potential sensing has the specificity to detect different cellular species. By taking advantage of the different electrochemical characteristics of normal cells, cancer cells and biointeractions between anticancer drugs and cancer cells, we develop a specific, sensitive, direct, cost-effective and rapid method for the detection of cancer cells by electrochemical potential sensing based on Au/TiO 2 nanobelt heterostructure electrodes that will be of significance in early cancer diagnosis, in vitro screening of anticancer drugs  and molecular biology research. (paper)

  13. Prostate cancer metastasis-driving genes: hurdles and potential approaches in their identification

    Directory of Open Access Journals (Sweden)

    Yan Ting Chiang

    2014-08-01

    Full Text Available Metastatic prostate cancer is currently incurable. Metastasis is thought to result from changes in the expression of specific metastasis-driving genes in nonmetastatic prostate cancer tissue, leading to a cascade of activated downstream genes that set the metastatic process in motion. Such genes could potentially serve as effective therapeutic targets for improved management of the disease. They could be identified by comparative analysis of gene expression profiles of patient-derived metastatic and nonmetastatic prostate cancer tissues to pinpoint genes showing altered expression, followed by determining whether silencing of such genes can lead to inhibition of metastatic properties. Various hurdles encountered in this approach are discussed, including (i the need for clinically relevant, nonmetastatic and metastatic prostate cancer tissues such as xenografts of patients' prostate cancers developed via subrenal capsule grafting technology and (ii limitations in the currently available methodology for identification of master regulatory genes.

  14. Mammography - recent technical developments and their clinical potential

    Energy Technology Data Exchange (ETDEWEB)

    Hemdal, Bengt; Mattsson, Soeren [Malmoe Univ. Hospital (Sweden). Dept. of Radiation Physics; Andersson, Ingvar [Malmoe Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Thilander Klang, Anne [Sahlgrenska Univ. Hospital, Goeteborg (Sweden). Dept. of Medical Physics and Biomedical Engineering; Bengtsson, Gert; Jarlman, O. [Lund Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Leitz, Wolfram [Swedish Radiation Protection Authority, Stockholm (Sweden); Bjurstam, Nils [Univ. of North Norway, Troms (Norway). Dept. of Radiology

    2002-05-01

    The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography

  15. Mammography - recent technical developments and their clinical potential

    International Nuclear Information System (INIS)

    Hemdal, Bengt; Mattsson, Soeren; Bjurstam, Nils

    2002-05-01

    The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography

  16. Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer

    Science.gov (United States)

    Banerji, Christopher R. S.; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E.

    2015-01-01

    The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

  17. Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.

    Directory of Open Access Journals (Sweden)

    Christopher R S Banerji

    2015-03-01

    Full Text Available The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample's genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers.

  18. Clinical study of early laryngeal cancer

    International Nuclear Information System (INIS)

    Nagatani, Gunji; Mori, Takanori; Udaka, Tsuyoshi; Shiomori, Teruo; Ohbuchi, Toyoaki; Suzuki, Hideaki

    2007-01-01

    We retrospectively analyzed 71 consecutive cases of early laryngeal cancer (stage I or II) that had undergone primary treatment in our department between 1999 and 2004. There were 68 males and 3 females, and their ages ranged from 40 to 85 years of age (average; 67.7 years). Eight patients had the supraglottic type, 61 had the glottic type, and 2 had the subglottic type. Chemoradiotherapy was performed as the primary treatment except in the patients with glottic T1a cancer, who received radiotherapy alone. The 5-year survival rates was 91.1% for glottic cancer (T1a: 100%, T1b: 92.3%, T2: 85.8%) and 75.0% for supraglottic cancer. The local control rate of glottic cancer was 79.6% (T1a: 80.0%, T1b: 74.0%, T2: 85.2%), and significantly higher than that of supraglottic cancer (56.2%, p<0.05). The laryngeal preservation rate was 84.4% in glottic cancer (T1a: 100%, T1b: 76.9%, T2: 77.5%) and 58.3% in supraglottic cancer, and the difference between T1a and T2 glottic cancer was significant (p<0.05). Local recurrence and cervical lymph node metastasis were seen in 9 patients and 6 patients, respectively. Distant metastasis occurred in 4 patients, all of whom had the glottic type. Four patients died of their disease, and distant metastasis was the major cause of death in 3 of them. These results indicate that additional treatment should be performed in cases in which radiotherapy/chemoradiotherapy is ineffective and that both in the early stages glottic and supraglottic cancers can be successfully treated by radiotherapy/chemoradiotherapy. The results also suggested that the survival of patients with early laryngeal cancer depends on whether they develop distant metastasis. Introduction of adjuvant chemotherapy to improve their prognosis remains to be assessed. (author)

  19. CAsubtype: An R Package to Identify Gene Sets Predictive of Cancer Subtypes and Clinical Outcomes.

    Science.gov (United States)

    Kong, Hualei; Tong, Pan; Zhao, Xiaodong; Sun, Jielin; Li, Hua

    2018-03-01

    In the past decade, molecular classification of cancer has gained high popularity owing to its high predictive power on clinical outcomes as compared with traditional methods commonly used in clinical practice. In particular, using gene expression profiles, recent studies have successfully identified a number of gene sets for the delineation of cancer subtypes that are associated with distinct prognosis. However, identification of such gene sets remains a laborious task due to the lack of tools with flexibility, integration and ease of use. To reduce the burden, we have developed an R package, CAsubtype, to efficiently identify gene sets predictive of cancer subtypes and clinical outcomes. By integrating more than 13,000 annotated gene sets, CAsubtype provides a comprehensive repertoire of candidates for new cancer subtype identification. For easy data access, CAsubtype further includes the gene expression and clinical data of more than 2000 cancer patients from TCGA. CAsubtype first employs principal component analysis to identify gene sets (from user-provided or package-integrated ones) with robust principal components representing significantly large variation between cancer samples. Based on these principal components, CAsubtype visualizes the sample distribution in low-dimensional space for better understanding of the distinction between samples and classifies samples into subgroups with prevalent clustering algorithms. Finally, CAsubtype performs survival analysis to compare the clinical outcomes between the identified subgroups, assessing their clinical value as potentially novel cancer subtypes. In conclusion, CAsubtype is a flexible and well-integrated tool in the R environment to identify gene sets for cancer subtype identification and clinical outcome prediction. Its simple R commands and comprehensive data sets enable efficient examination of the clinical value of any given gene set, thus facilitating hypothesis generating and testing in biological and

  20. Knowledge and skills of cancer clinical trials nurses in Australia.

    Science.gov (United States)

    Scott, Kathleen; White, Kate; Johnson, Catherine; Roydhouse, Jessica K

    2012-05-01

      This paper is a report of the development and testing of a questionnaire measuring knowledge and skills of cancer clinical trials nurse in Australia.   The role of cancer clinical trials nurse, widely acknowledged as an integral member of the clinical research team, has evolved in recent years. Elements of the clinical trials nurse role in cancer have previously been described. To evaluate specific cancer clinical trials nurse educational and training needs, the development of a valid and reliable tool is required.   In 2009, a study was conducted in three stages. Stage I: questionnaire development and pilot testing; stage II: focus group; stage III: national survey. Internal consistency reliability testing and multi-trait analysis of item convergent/divergent validity were employed. Regression analysis was used to identify predictors of clinical trials nurse knowledge and skills.   The national survey was a 48-item questionnaire, measuring six clinical trial knowledge and seven skills sub-scales. Of 61 respondents, 90% were women, with mean age 43 years, 19 years as a Registered Nurse and 5 years as a cancer clinical trials nurse. Self-reported knowledge and skills were satisfactory to good. Internal consistency reliability was high (Cronbach's alpha: knowledge = 0·98; skills = 0·90). Criteria for item convergent/divergent validity were met. Number of years as cancer clinical trials nurse was positively related to self-reported knowledge and skills.   Preliminary data suggest that the national survey is reliable and valid. Data have contributed to better understanding the knowledge and skills of cancer clinical trials nurse in Australia and development of a postgraduate course in clinical trials. © 2011 Blackwell Publishing Ltd.

  1. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

    Science.gov (United States)

    Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

    2015-01-01

    Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect

  2. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper.

    Science.gov (United States)

    Herzog, Thomas J; Armstrong, Deborah K; Brady, Mark F; Coleman, Robert L; Einstein, Mark H; Monk, Bradley J; Mannel, Robert S; Thigpen, J Tate; Umpierre, Sharee A; Villella, Jeannine A; Alvarez, Ronald D

    2014-01-01

    To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect from active post-progression therapies

  3. Therapeutic potential of snake venom in cancer therapy: current perspectives

    Science.gov (United States)

    Vyas, Vivek Kumar; Brahmbhatt, Keyur; Bhatt, Hardik; Parmar, Utsav

    2013-01-01

    Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer. Snake venom toxins contributed significantly to the treatment of many medical conditions. There are many published studies describing and elucidating the anti-cancer potential of snake venom. Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species. Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes, affecting the migration and proliferation of these cells. Some of substances found in the snake venom present a great potential as anti-tumor agent. In this review, we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity. PMID:23593597

  4. Clinical Outcomes of Colorectal Cancer in Kenya

    African Journals Online (AJOL)

    treatment and follow up were included. Patient ... and recurrence and the associated patient and disease ... The incidence of colorectal cancer (CRC) in the devel- ... therapy, disease stage and curative intent (table 3). ... through genetic and family analyses (4,6). ... Polite BN, Dignam JJ: A colorectal cancer model of health.

  5. Cancer-specific Therapeutic Potential of Resveratrol: Metabolic Approach against Hallmarks of Cancer

    Directory of Open Access Journals (Sweden)

    Dong Hoon Suh

    2013-08-01

    Full Text Available ABSTRACTCancer hallmarks include evading apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis. Cancer cells undergo metabolic reprogramming and inevitably take advantage of glycolysis to meet the increased metabolic demand: rapid energy generation and macromolecular synthesis. Resveratrol, a polyphenolic phytoalexin, is known to exhibit pleiotropic anti-cancer effects most of which are linked to metabolic reprogramming in cancer cells. This review summarizes various anti-cancer effects of resveratrol in the context of cancer hallmarks in relation to metabolic reprogramming.

  6. Pancreatic cancer clinical trials and accrual in the United States.

    Science.gov (United States)

    Hoos, William A; James, Porsha M; Rahib, Lola; Talley, Anitra W; Fleshman, Julie M; Matrisian, Lynn M

    2013-09-20

    Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer. Pancreatic cancer-specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors. The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual. Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.

  7. Protein mislocalization: mechanisms, functions and clinical applications in cancer

    Science.gov (United States)

    Wang, Xiaohong; Li, Shulin

    2014-01-01

    The changes from normal cells to cancer cells are primarily regulated by genome instability, which foster hallmark functions of cancer through multiple mechanisms including protein mislocalization. Mislocalization of these proteins, including oncoproteins, tumor suppressors, and other cancer-related proteins, can interfere with normal cellular function and cooperatively drive tumor development and metastasis. This review describes the cancer-related effects of protein subcellular mislocalization, the related mislocalization mechanisms, and the potential application of this knowledge to cancer diagnosis, prognosis, and therapy. PMID:24709009

  8. Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

    Directory of Open Access Journals (Sweden)

    José Manuel Calderón-Montaño

    2014-01-01

    Full Text Available Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na+/K+-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studies.

  9. US-LA CRN Clinical Cancer Research in Latin America

    Science.gov (United States)

    The United States – Latin America Cancer Research Network (US-LA CRN) convened its Annual Meeting, in coordination with the Ministry of Health of Chile to discuss the Network’s first multilateral clinical research study: Molecular Profiling of Breast Cancer (MPBC).

  10. Clinical confrontation results of diagnostics and treatment of skin cancer

    International Nuclear Information System (INIS)

    Zikiryakhodjaev, D.Z.; Sanginov, D.R.

    2001-01-01

    In this chapter of book authors investigated the clinical confrontation results of diagnostics and treatment of skin cancer. They noted that diagnostic of skin cancer have to foresee the determination morphologic implements and degree of malignancy tumorous process why in general depend prognosis of illness

  11. Clinical Outcomes of Colorectal Cancer in Kenya | Saidi | Annals of ...

    African Journals Online (AJOL)

    Background The incidence of colorectal cancer in Africa is increasing. True data on clinical outcomes of the disease is hampered by follow up challenges. Method Follow up data of 233 patients treated for colorectal cancer between 2005 and 2010 at various Nairobi hospitals were evaluated. The primary outcome was ...

  12. Pre-operative diagnosis of thyroid cancer: Clinical, radiological and ...

    African Journals Online (AJOL)

    The diagnosis or exclusion of cancer in the thyroid nodule remains a clinical dilemma for general surgeons and endocrinologists. Nodular disease of the thyroid is very common, while cancer is rare; a definite diagnosis of either is difficult to make. The general prevalence of thyroid nodules is very high. They are detectable ...

  13. Clinical impact of molecular analysis on thyroid cancer management

    NARCIS (Netherlands)

    Wreesmann, Volkert B.; Singh, Bhuvanesh

    2008-01-01

    Thyroid cancer constitutes a progressive continuum of disease ranging from indolent well-differentiated carcinomas to aggressive poorly differentiated carcinomas and universally fatal anaplastic carcinomas. The wide divergence in clinical behavior is poorly predicted for by current

  14. Magnetic resonance imaging for clinical management of rectal cancer

    DEFF Research Database (Denmark)

    Beets-Tan, Regina G H; Lambregts, Doenja M J; Maas, Monique

    2018-01-01

    OBJECTIVES: To update the 2012 ESGAR consensus guidelines on the acquisition, interpretation and reporting of magnetic resonance imaging (MRI) for clinical staging and restaging of rectal cancer. METHODS: Fourteen abdominal imaging experts from the European Society of Gastrointestinal and Abdomin...

  15. Epidemiological, clinical and therapeutic profile of cervical cancer in ...

    African Journals Online (AJOL)

    MJP

    2015-08-21

    Aug 21, 2015 ... Results: The incidence of cervical cancer in Butembo was 0.97% with a peak in 2011 .... bleeding, vaginal discharge, pelvic pain, Schiller. Test, clinical ..... female students and staff in a tertiary institution in the Niger Delta.

  16. Bilateral male breast cancer with male potential hypogonadism

    Directory of Open Access Journals (Sweden)

    Kurokawa Yasushi

    2007-06-01

    Full Text Available Abstract Background Male breast cancer is a comparatively rare disease, and simultaneous bilateral male breast cancer is considered to be an extremely rare event. Risk factors are said to be genetic factors and hormonal abnormalities due to obesity or testicular diseases. Case presentation The patient was a 47-year-old Japanese male. His family had no history of female breast cancer. This patient also had hypospadias and hormonal examination indicated the presence of primary testicular potential hypogonadism, and these hormonal abnormalities seemed to be present since childhood or the fetal period. The bilateral breast cancer developed in this man at a comparatively young age, and histopathological studies of multiple sections showed that there was almost no normal epithelial cell in the ducts, while the ducts were almost completely filled with breast cancer cells. Conclusion It is thought that male breast cancer is caused by an imbalance between estrogen and testosterone. We cannot rule out the possibility that the breast cancer developed due to the effect of the slight elevation of estrogen over a long period of time, but the actual causative factors in this patient were unable to be definitively identified. In the future, we hope to further elucidate the causes of male breast cancer.

  17. Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives

    Directory of Open Access Journals (Sweden)

    Yoon Young Choi

    2016-01-01

    Full Text Available Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

  18. Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives.

    Science.gov (United States)

    Choi, Yoon Young; Noh, Sung Hoon; Cheong, Jae-Ho

    2016-01-01

    Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

  19. Endocrine therapy for breast cancer prevention in high-risk women: clinical and economic considerations.

    Science.gov (United States)

    Groom, Amy G; Younis, Tallal

    2016-01-01

    The global burden of breast cancer highlights the need for primary prevention strategies that demonstrate both favorable clinical benefit/risk profile and good value for money. Endocrine therapy with selective estrogen-receptor modulators (SERMs) or aromatase inhibitors (AIs) has been associated with a favorable clinical benefit/risk profile in the prevention of breast cancer in women at high risk of developing the disease. The available endocrine therapy strategies differ in terms of their relative reductions of breast cancer risk, potential side effects, and upfront drug acquisition costs, among others. This review highlights the clinical trials of SERMs and AIs for the primary prevention of breast cancer, and the cost-effectiveness /cost-utility studies that have examined their "value for money" in various health care jurisdictions.

  20. Fertility Preservation for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

    Science.gov (United States)

    Loren, Alison W.; Mangu, Pamela B.; Beck, Lindsay Nohr; Brennan, Lawrence; Magdalinski, Anthony J.; Partridge, Ann H.; Quinn, Gwendolyn; Wallace, W. Hamish; Oktay, Kutluk

    2013-01-01

    Purpose To update guidance for health care providers about fertility preservation for adults and children with cancer. Methods A systematic review of the literature published from March 2006 through January 2013 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Panel reviewed the evidence and updated the recommendation language. Results There were 222 new publications that met inclusion criteria. A majority were observational studies, cohort studies, and case series or reports, with few randomized clinical trials. After review of the new evidence, the Update Panel concluded that no major, substantive revisions to the 2006 American Society of Clinical Oncology recommendations were warranted, but clarifications were added. Recommendations As part of education and informed consent before cancer therapy, health care providers (including medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, and surgeons) should address the possibility of infertility with patients treated during their reproductive years (or with parents or guardians of children) and be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, the Update Panel encourages providers to advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm and embryo cryopreservation as well as oocyte cryopreservation are considered standard practice and are widely available. Other fertility preservation methods should be considered investigational and should be performed by providers with the necessary expertise. PMID:23715580

  1. Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance

    Directory of Open Access Journals (Sweden)

    Claire Jackson

    2013-01-01

    Full Text Available Overexpression of human epidermal growth factor receptor (HER-2 occurs in 20–30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant 16HER-2 (results from exon 16 skipping increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention and p100 (results from intron 15 retention inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. “Individualised” strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

  2. Major Clinical Impact of Platinum-Based Chemotherapy in a Patient with a Borderline Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jian Chen

    2009-09-01

    Full Text Available A patient with extensive and painful chest wall involvement from a metastatic borderline cancer of the ovary was treated with a carboplatin plus paclitaxel chemotherapy regimen. She achieved a rather dramatic improvement of pain control, a significant biochemical response with 75% reduction of the CA-125 antigen level, but only limited radiographic tumor regression. This experience emphasizes the potential clinical utility of platinum-based cytotoxic chemotherapy in the setting of symptomatic advanced borderline ovarian cancer.

  3. Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yung-Lin Chu

    2013-07-01

    Full Text Available Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic 大 蒜 Dà Suàn; Allium sativum, is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.

  4. Minimal residual disease in breast cancer. Clinical significance

    International Nuclear Information System (INIS)

    Kvalheim, G.

    2004-01-01

    compared to other defined prognostic factors of the primary tumor. A bone marrow ITC change at time of diagnosis and at six months post-treatment is associated with prognosis (RF S: p=0.006, Bcs: p=0.006) and is an independent predictor of survival. Those who have consistent none ITC in bone marrow constitute a group of patients with good prognosis. Based on these data and similar findings in other in-house studies a new clinical trial has been initiated. Breast cancer patients given adjuvant chemotherapy (FEC) with I CT in bone marrow 6 months following therapy are stratified for further therapy with 6 cycles of Docetaxel. Whether such an approach will benefit the patients remain to be seen. In conclusion detection of minimal residual disease in bone marrow is a potential useful surrogate marker in breast cancer and in other solid tumors such as prostate cancer

  5. Design of clinical trials for therapeutic cancer vaccines development.

    Science.gov (United States)

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

  6. Clinical Activity in General Practice and Cancer

    DEFF Research Database (Denmark)

    Hjertholm, Peter

    2015-01-01

    , and to analyse how a suspicion influenced the demand for health care services and predicted a future diagnosis of serious disease - to investigate whether variation in GPs’ diagnostic activity influences cancer patients’ prognosis in relation to prostate-specific antigen (PSA) testing and prostate cancer....... In the future, we need to learn to differentiate between indolent and aggressive prostate cancers. This may, again, leave room for PSA testing as a screening tool. Our findings do indicate a small positive effect of more lower endoscopies, which could be investigated in an intervention study where some GPs...... are randomised to a more liberal access to lower endoscopies. Alongside this, we need to keep on exploring alternative approaches including the use of iFOBT in symptomatic patients. Overall, this thesis indicates that the role of GPs in the diagnosis of cancer should be strengthened through easy access...

  7. Inhibiting TRK Proteins in Clinical Cancer Therapy

    OpenAIRE

    Allison M. Lange; Hui-Wen Lo

    2018-01-01

    Gene rearrangements resulting in the aberrant activity of tyrosine kinases have been identified as drivers of oncogenesis in a variety of cancers. The tropomyosin receptor kinase (TRK) family of tyrosine receptor kinases is emerging as an important target for cancer therapeutics. The TRK family contains three members, TRKA, TRKB, and TRKC, and these proteins are encoded by the genes NTRK1, NTRK2, and NTRK3, respectively. To activate TRK receptors, neurotrophins bind to the extracellular regio...

  8. Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic

    Directory of Open Access Journals (Sweden)

    Samantha B. Foley

    2015-01-01

    Full Text Available Despite the potential of whole-genome sequencing (WGS to improve patient diagnosis and care, the empirical value of WGS in the cancer genetics clinic is unknown. We performed WGS on members of two cohorts of cancer genetics patients: those with BRCA1/2 mutations (n = 176 and those without (n = 82. Initial analysis of potentially pathogenic variants (PPVs, defined as nonsynonymous variants with allele frequency < 1% in ESP6500 in 163 clinically-relevant genes suggested that WGS will provide useful clinical results. This is despite the fact that a majority of PPVs were novel missense variants likely to be classified as variants of unknown significance (VUS. Furthermore, previously reported pathogenic missense variants did not always associate with their predicted diseases in our patients. This suggests that the clinical use of WGS will require large-scale efforts to consolidate WGS and patient data to improve accuracy of interpretation of rare variants. While loss-of-function (LoF variants represented only a small fraction of PPVs, WGS identified additional cancer risk LoF PPVs in patients with known BRCA1/2 mutations and led to cancer risk diagnoses in 21% of non-BRCA cancer genetics patients after expanding our analysis to 3209 ClinVar genes. These data illustrate how WGS can be used to improve our ability to discover patients' cancer genetic risks.

  9. Guide to clinical PET in oncology: Improving clinical management of cancer patients

    International Nuclear Information System (INIS)

    2008-10-01

    Positron emission tomography (PET) has an approximately 50 year-history. It was developed as a tool of medical science to quantitatively measure metabolic rates of bio-substances in vivo and in particular the number of receptors in neuroscience. Until the late 1990s PET was, in most cases, research oriented activity. In 2001, positron emission tomography/X ray computed tomography (PET/CT) hybrid imaging system became commercially available. An era of clinical PET then emerged, in which PET images were utilized for clinical practice in the treatment and diagnosis of cancer patients. PET imaging could recognize areas of abnormal metabolic behaviour of cancers in vivo, and the addition of CT imaging underlines the site of malignancy. More accurate and precise interpretation of cancer lesions can therefore be performed by PET/CT imaging than PET or CT imaging alone. Clinical PET, in particular with fluorine-18-fluorodeoxyglucose ( 18 F-FDG), has already proven itself to have considerable value in oncology. The indications include malignant lymphoma and melanoma, head and neck cancers, oesophageal cancer, breast cancer, lung cancer and colorectal cancer, and it is still being expanded. The roles of clinical PET could be for 1) preoperative staging of cancers, 2) differentiation between residual tumour and scarring, 3) demonstration of suspected recurrences, 4) monitoring response to therapy, 5) prognosis and 6) radiotherapy treatment planning. Clinical PET can be used to illustrate exactly which treatment should be applied for a cancer patient as well as where surgeons should operate and where radiation oncologists should target radiation therapy. An almost exponential rise in the introduction of clinical PET, as well as the installation of PET/CT has been seen throughout the world. Clinical PET is currently viewed as the most powerful diagnostic tool in its field. This IAEA-TECDOC presents an overview of clinical PET for cancer patients and a relevant source of

  10. Clinical and Biological Features of Interval Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Yu Mi Lee

    2017-05-01

    Full Text Available Interval colorectal cancer (I-CRC is defined as a CRC diagnosed within 60 months after a negative colonoscopy, taking into account that 5 years is the “mean sojourn time.” It is important to prevent the development of interval cancer. The development of interval colon cancer is associated with female sex, old age, family history of CRC, comorbidities, diverticulosis, and the skill of the endoscopist. During carcinogenesis, sessile serrated adenomas/polyps (SSA/Ps share many genomic and colonic site characteristics with I-CRCs. The clinical and biological features of I-CRC should be elucidated to prevent the development of interval colon cancer.

  11. Obesity Paradox in Lung Cancer Prognosis: Evolving Biological Insights and Clinical Implications.

    Science.gov (United States)

    Zhang, Xueli; Liu, Yamin; Shao, Hua; Zheng, Xiao

    2017-10-01

    The survival rate of lung cancer remains low despite the progress of surgery and chemotherapy. With the increasing comorbidity of obesity in patients with lung cancer, new challenges are emerging in the management of this patient population. A key issue of interest is the prognostic effect of obesity on surgical and chemotherapeutic outcomes in patients with lung cancer, which is fueled by the growing observation of survival benefits in overweight or obese patients. This unexpected inverse relationship between obesity and lung cancer mortality, called the obesity paradox, remains poorly understood. The evolving insights into the heterogeneity of obesity phenotypes and associated biological connections with lung cancer progression in recent years may help explain some of the seemingly paradoxical relationship, and well-designed clinical studies looking at the causal role of obesity-associated molecules are expected. Here, we examine potential biological mechanisms behind the protective effects of obesity in lung cancer. We highlight the need to clarify the clinical implications of this relationship toward an updated intervention strategy in the clinical care of patients with lung cancer and obesity. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  12. Estimation of T2 relaxation time of breast cancer: Correlation with clinical, imaging and pathological features

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Mirinae; Sohn, Yu Mee [Dept. of Radiology, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Ryu, Jung Kyu; Jahng, Geon Ho; Rhee, Sun Jung; Oh, Jang Hoon; Won, Kyu Yeoun [Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul (Korea, Republic of)

    2017-01-15

    The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer.

  13. Eph receptor A10 has a potential as a target for a prostate cancer therapy

    International Nuclear Information System (INIS)

    Nagano, Kazuya; Yamashita, Takuya; Inoue, Masaki; Higashisaka, Kazuma; Yoshioka, Yasuo; Abe, Yasuhiro; Mukai, Yohei; Kamada, Haruhiko

    2014-01-01

    Highlights: • EphA10 mRNA is overexpressed in breast, prostate and colon cancer cell lines. • EphA10 is overexpressed in clinical prostate tumors at mRNA and protein levels. • Anti-EphA10 antibodies were cytotoxic on EphA10-positive prostate cancer cells. - Abstract: We recently identified Eph receptor A10 (EphA10) as a novel breast cancer-specific protein. Moreover, we also showed that an in-house developed anti-EphA10 monoclonal antibody (mAb) significantly inhibited proliferation of breast cancer cells, suggesting EphA10 as a promising target for breast cancer therapy. However, the only other known report for EphA10 was its expression in the testis at the mRNA level. Therefore, the potency of EphA10 as a drug target against cancers other than the breast is not known. The expression of EphA10 in a wide variety of cancer cells was studied and the potential of EphA10 as a drug target was evaluated. Screening of EphA10 mRNA expression showed that EphA10 was overexpressed in breast cancer cell lines as well as in prostate and colon cancer cell lines. Thus, we focused on prostate cancers in which EphA10 expression was equivalent to that in breast cancers. As a result, EphA10 expression was clearly shown in clinical prostate tumor tissues as well as in cell lines at the mRNA and protein levels. In order to evaluate the potential of EphA10 as a drug target, we analyzed complement-dependent cytotoxicity effects of anti-EphA10 mAb and found that significant cytotoxicity was mediated by the expression of EphA10. Therefore, the idea was conceived that the overexpression of EphA10 in prostate cancers might have a potential as a target for prostate cancer therapy, and formed the basis for the studies reported here

  14. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

    Directory of Open Access Journals (Sweden)

    Milosz Wilczynski

    Full Text Available Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034. These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

  15. Nanotechnology Strategies To Advance Outcomes in Clinical Cancer Care.

    Science.gov (United States)

    Hartshorn, Christopher M; Bradbury, Michelle S; Lanza, Gregory M; Nel, Andre E; Rao, Jianghong; Wang, Andrew Z; Wiesner, Ulrich B; Yang, Lily; Grodzinski, Piotr

    2018-01-23

    Ongoing research into the application of nanotechnology for cancer treatment and diagnosis has demonstrated its advantages within contemporary oncology as well as its intrinsic limitations. The National Cancer Institute publishes the Cancer Nanotechnology Plan every 5 years since 2005. The most recent iteration helped codify the ongoing basic and translational efforts of the field and displayed its breadth with several evolving areas. From merely a technological perspective, this field has seen tremendous growth and success. However, an incomplete understanding of human cancer biology persists relative to the application of nanoscale materials within contemporary oncology. As such, this review presents several evolving areas in cancer nanotechnology in order to identify key clinical and biological challenges that need to be addressed to improve patient outcomes. From this clinical perspective, a sampling of the nano-enabled solutions attempting to overcome barriers faced by traditional therapeutics and diagnostics in the clinical setting are discussed. Finally, a strategic outlook of the future is discussed to highlight the need for next-generation cancer nanotechnology tools designed to address critical gaps in clinical cancer care.

  16. Functional Assay of Cancer Cell Invasion Potential Based on Mechanotransduction of Focused Ultrasound

    Directory of Open Access Journals (Sweden)

    Andrew C. Weitz

    2017-08-01

    Full Text Available Cancer cells undergo a number of biophysical changes as they transform from an indolent to an aggressive state. These changes, which include altered mechanical and electrical properties, can reveal important diagnostic information about disease status. Here, we introduce a high-throughput, functional technique for assessing cancer cell invasion potential, which works by probing for the mechanically excitable phenotype exhibited by invasive cancer cells. Cells are labeled with fluorescent calcium dye and imaged during stimulation with low-intensity focused ultrasound, a non-contact mechanical stimulus. We show that cells located at the focus of the stimulus exhibit calcium elevation for invasive prostate (PC-3 and DU-145 and bladder (T24/83 cancer cell lines, but not for non-invasive cell lines (BPH-1, PNT1A, and RT112/84. In invasive cells, ultrasound stimulation initiates a calcium wave that propagates from the cells at the transducer focus to other cells, over distances greater than 1 mm. We demonstrate that this wave is mediated by extracellular signaling molecules and can be abolished through inhibition of transient receptor potential channels and inositol trisphosphate receptors, implicating these proteins in the mechanotransduction process. If validated clinically, our technology could provide a means to assess tumor invasion potential in cytology specimens, which is not currently possible. It may therefore have applications in diseases such as bladder cancer, where cytologic diagnosis of tumor invasion could improve clinical decision-making.

  17. Clinical analysis of lung cancer complicated by pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Sugino, Keishi; Homma, Sakae; Miyamoto, Atsushi; Takaya, Hisashi; Sakamoto, Susumu; Kawabata, Masateru; Kishi, Kazuma; Tsuboi, Eiyasu; Yoshimura, Kunihiko

    2007-01-01

    The aim of this study was to assess the characteristic clinical features of lung cancer associated with pulmonary tuberculosis. Among 1,028 patients with pulmonary tuberculosis admitted in our hospital between 1985 and 2005, 17 (15 men, 2 women; mean age 73±8) were diagnosed as having lung cancer. Patient characteristics, clinical features, radiographic images, treatment and prognosis were evaluated retrospectively. Patients were classified into 2 groups: group A (n=5), lung cancer complicated by active tuberculosis, and group B (n=12), lung cancer with tuberculosis sequelae. All patients in group A and 8 patients (33%) in group B had either stage III or IV lung cancer, whereas 4 patients in group B had stage I lung cancer. Coexistence of lung cancer and pulmonary tuberculosis in the same segment or lobe was seen in 80% (n=4) or 60% (n=3) of group A cases, respectively, and in 67% (n=8) or 8% (n=1) respectively, in group B. Mean survival in group A and group B was 9.2 months and 26.8 months, respectively. More attention should be paid to the possibility of development of lung cancer in individuals with a history of pulmonary tuberculosis or who have had tuberculosis sequelae revealed by chest radiography. Also, the possible coexistence of lung cancer must be carefully examined in patients with active pulmonary tuberculosis. (author)

  18. Potentialities of computed tomography and ultrasonography in colonic cancer

    International Nuclear Information System (INIS)

    Gorshkov, A.N.

    2001-01-01

    Data of examination of 59 patients with colonic cancer were used to consider the potentialities of transabdominal, transrectal ultrasonography and X-ay compound tomography and to assess their value in diagnosing colonic cancer, including its minor forms. Ultrasound and computed tomographic semiotics of colonic cancer and determines a place of the above techniques in the algorithm of radiation and instrumental studies are described. Inclusion of these techniques into the diagnostic algorithm may solve a range of differentially diagnostic problems and allows a preliminary analysis to be made in a tumor lesion according to the International TNM classification. Ultrasonography and X-ray computed tomography should be included into a range of basic methods for diagnosis of colonic cancer [ru

  19. Present-day potentialities of radiodiagnosis of stomach cancer

    International Nuclear Information System (INIS)

    Portnoj, L.M.; Simavonyan, K.V.; Turovskij, B.M.; Kaluzhskij, A.A.

    1986-01-01

    Present-day potentialities of radiodiagnosis of stomach cancer were studied using the results of clinicoradiological examination of 209 patients, mainly with endophytic and small forms of stomach cancer and 28 with stomach polypus. It was shown that to achieve the most complete and objective estimation of tumor changes in the stomach a combination of X-ray methods including routine examination with barium suspension and double contrast should be used. One of the most promising trends in radiodiagnosis of stomach cancer is fluorographic mass screening for stomach cancer in persons at high risk with subsequent selective endoscopic examination ( according to indications ). Double contrast remains the major and most informative part of standardized technique of gastrofluorographic examination

  20. Clinical Trials of Precision Medicine through Molecular Profiling: Focus on Breast Cancer.

    Science.gov (United States)

    Zardavas, Dimitrios; Piccart-Gebhart, Martine

    2015-01-01

    High-throughput technologies of molecular profiling in cancer, such as gene-expression profiling and next-generation sequencing, are expanding our knowledge of the molecular landscapes of several cancer types. This increasing knowledge coupled with the development of several molecularly targeted agents hold the promise for personalized cancer medicine to be fully realized. Moreover, an expanding armamentarium of targeted agents has been approved for the treatment of specific molecular cancer subgroups in different diagnoses. According to this paradigm, treatment selection should be dictated by the specific molecular aberrations found in each patient's tumor. The classical clinical trials paradigm of patients' eligibility being based on clinicopathologic parameters is being abandoned, with current clinical trials enrolling patients on the basis of specific molecular aberrations. New, innovative trial designs have been generated to better tackle the multiple challenges induced by the increasing molecular fragmentation of cancer, namely: (1) longitudinal cohort studies with or without downstream trials, (2) studies assessing the clinical utility of molecular profiling, (3) master or umbrella trials, (4) basket trials, (5) N-of-1 trials, and (6) adaptive design trials. This article provides an overview of the challenges for clinical trials in the era of molecular profiling of cancer. Subsequently, innovative trial designs with respective examples and their potential to expedite efficient clinical development of targeted anticancer agents is discussed.

  1. Breast cancer and depression: issues in clinical care

    Directory of Open Access Journals (Sweden)

    Thingbaijam B. Singh

    2012-11-01

    Full Text Available Many of breast-cancer patients experience distress and most of them experience depression which may lead to amplification of physical symptoms, increased functional impairment, and poor treatment adherence. We did a review on available literature from PubMed about prevalence, distress magnitudes, coping styles, and treatment methods of major depression in women with breast cancer from 1978 to 2010. Diagnosis and treatment of depressive episodes in women with breast cancer is challenging because of overlapping symptoms and co-morbid conditions. Major depression is often under-recognized and undertreated among breast cancer patients. This review highlighted the issues on identifying and managing depression in breast cancer patients in clinical settings. (Med J Indones. 2012;21:240-6Keywords: Breast cancer, coping, depression, distress

  2. Clinical application and research of tumor markers in colorectal cancer

    International Nuclear Information System (INIS)

    Chen Yumei

    2005-01-01

    Colorectal cancer is one of the most common malignant tumors. There are many tumor markers for detecting colorectal cancer, some of which have been widely used in clinical area. However, still lack an ideal tumor marker of colorectal cancer. In this review, we simply characterized some common tumor markers including carcinoembryonic antigen, CA19-9, CA50, CA242 etc and their dignostic value. And here we discussed some combined detecting procedures which improve diagnostic accuracy of colorectal cancer. In addition, with the development of the biomoleculer technique, some newly discovered tumor markers and genetic marekers have gained great progress in the research of colorectal cancer, and will become a promissing technique in the diagnosis of colorectal cancer. (authors)

  3. Clinical multi-omics strategies for the effective cancer management.

    Science.gov (United States)

    Yoo, Byong Chul; Kim, Kyung-Hee; Woo, Sang Myung; Myung, Jae Kyung

    2017-08-15

    Cancer is a global health issue as a multi-factorial complex disease, and early detection and novel therapeutic strategies are required for more effective cancer management. With the development of systemic analytical -omics strategies, the therapeutic approach and study of the molecular mechanisms of carcinogenesis and cancer progression have moved from hypothesis-driven targeted investigations to data-driven untargeted investigations focusing on the integrated diagnosis, treatment, and prevention of cancer in individual patients. Predictive, preventive, and personalized medicine (PPPM) is a promising new approach to reduce the burden of cancer and facilitate more accurate prognosis, diagnosis, as well as effective treatment. Here we review the fundamentals of, and new developments in, -omics technologies, together with the key role of a variety of practical -omics strategies in PPPM for cancer treatment and diagnosis. In this review, a comprehensive and critical overview of the systematic strategy for predictive, preventive, and personalized medicine (PPPM) for cancer disease was described in a view of cancer prognostic prediction, diagnostics, and prevention as well as cancer therapy and drug responses. We have discussed multi-dimensional data obtained from various resources and integration of multisciplinary -omics strategies with computational method which could contribute the more effective PPPM for cancer. This review has provided the novel insights of the current applications of each and combined -omics technologies, which showed their powerful potential for the establishment of PPPM for cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Clinical implications of epigenetic regulation in oral cancer.

    Science.gov (United States)

    D'Souza, Wendy; Saranath, Dhananjaya

    2015-12-01

    Oral cancer is a high incidence cancer which is of major public health concern in India being the most common cancer in males and fifth most common cancer in females in India, contributing to 26% of the global oral cancer burden. The major risk factors of oral cancer are tobacco, alcohol and high risk Human Papilloma Virus type 16/18. However, only 3-12% of the high risk individuals with dysplasia develop oral cancer. Thus, individual genomic variants representing the genomic constitution and epigenetic alterations play a critical role in the development of oral cancer. Extensive epigenetic studies on the molecular lesions including oncogenes, tumor suppressor genes, genes associated with apoptosis, DNA damage repair have been reported. The current review highlights epigenetic regulation with a focus on molecular biomarkers and epidrug therapy in oral cancer. Epigenetic regulation by hypermethylation, histone modifications and specific microRNAs are often associated with early events and advanced stages in oral cancer, and thus indicate epidrug therapy for intervention. The presence of epigenetic marks in oral lesions, cancers and tumor associated mucosa emphasizes indications as biomarkers and epidrugs with therapeutic potential for better patient management. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Active surveillance for clinically localized prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Brasso, Klaus; Klotz, Laurence H

    2014-01-01

    Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection for the AS stra......Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection...

  6. Clinical treatment planning in gynecologic cancer

    International Nuclear Information System (INIS)

    Brady, L.W.; Markoe, A.M.; Micaily, B.; Damsker, J.I.; Karlsson, U.L.; Amendola, B.E.

    1987-01-01

    Treatment planning in gynecologic cancer is a complicated and difficult procedure. It requires an adequate preoperative assessment of the true extent of the patient's disease process and oftentimes this can be achieved not only by conventional studies but must employ surgical exploratory techniques in order to truly define the extent of the disease. However, with contemporary sophisticated treatment planning techniques that are now available in most contemporary departments of radiation oncology, radiation therapy is reemerging as an important and major treatment technique in the management of patients with gynecologic cancer

  7. Clinical application of dendritic cells in cancer vaccination therapy

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Soot, Mette Line; Buus, Søren

    2003-01-01

    During the last decade use of dendritic cells (DC) has moved from murine and in vitro studies to clinical trials as adjuvant in cancer immunotherapy. Here they function as delivery vehicles for exogenous tumor antigens, promoting an efficient antigen presentation. The development of protocols...... for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity...

  8. Does access to private healthcare influence potential lung cancer ...

    African Journals Online (AJOL)

    remains the most common cause of cancer-related death, resulting in >1.59 million ... have an inferior potential cure rate at presentation when compared ... is a primary referral centre serving approximately three million people. .... negative counterparts. .... Brewster DH, Thomson CS, Hole DJ, Black RJ, Stroner PL, Gillis CR.

  9. VEGF in nuclear medicine : Clinical application in cancer and future perspectives (Review)

    NARCIS (Netherlands)

    Taurone, Samanta; Galli, Filippo; Signore, Alberto; Agostinelli, Enzo; Dierckx, Rudi A. J. O.; Minni, Antonio; Pucci, Marcella; Artico, Marco

    Clinical trials using antiangiogenic drugs revealed their potential against cancer. Unfortunately, a large percentage of patients does not yet benefit from this therapeutic approach highlighting the need of diagnostic tools to non-invasively evaluate and monitor response to therapy. It would also

  10. Clinical experience of integrative cancer immunotherapy with GcMAF.

    Science.gov (United States)

    Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Mette, Martin; Uto, Yoshihiro; Hori, Hitoshi; Sakamoto, Norihiro

    2013-07-01

    Immunotherapy has become an attractive new strategy in the treatment of cancer. The laboratory and clinical study of cancer immunotherapy is rapidly advancing. However, in the clinical setting, the results of cancer immunotherapy are mixed. We therefore contend that cancer immunotherapy should be customized to each patient individually based on their immune status and propose an integrative immunotherapy approach with second-generation group-specific component macrophage activating factor (GcMAF)-containing human serum. The standard protocol of our integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily. By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy was remarkably effective. The results of our integrative immunotherapy seem hopeful. We also plan to conduct a comparative clinical study.>

  11. Clinical adenoviral gene therapy for prostate cancer

    Czech Academy of Sciences Publication Activity Database

    Schenk, E.; Essand, M.; Bangma, Ch. H.; Barber, Ch.; Behr, J.-P.; Briggs, S.; Carlisle, R.; Cheng, W.-S.; Danielsson, A.; Dautzenberg, I. J. C.; Dzojic, H.; Erbacher, P.; Fisher, K.; Frazier, A.; Georgopoulos, L. J.; Hoeben, R.; Kochanek, S.; Koppers-Lalic, D.; Kraaij, R.; Kreppel, F.; Lindholm, L.; Magnusson, M.; Maitland, N.; Neuberg, P.; Nilsson, B.; Ogris, M.; Remy, J.-S.; Scaife, M.; Schooten, E.; Seymour, L.; Totterman, T.; Uil, T. G.; Ulbrich, Karel; Veldhoven-Zweistra, J. L. M.; de Vrij, J.; van Weerden, W.; Wagner, E.; Willemsen, R.

    2010-01-01

    Roč. 21, č. 7 (2010), s. 807-813 ISSN 1043-0342 EU Projects: European Commission(XE) 512087 - GIANT Keywords : adenovirus * gene delivery * prostate cancer Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.829, year: 2010

  12. Breast cancer screening: An outpatient clinic study

    Directory of Open Access Journals (Sweden)

    Mustafa Girgin

    2017-03-01

    Conclusion: A multidisciplinary cancer screening program should be maintained. With such a process, the aim is to reduce the morbidity and mortality of the disease without adversely affecting the health conditions of asymptomatic individuals based on the screening. Success is brought about by the combination of individual features. [Arch Clin Exp Surg 2017; 6(1.000: 23-27

  13. Drug resistance in the mouse cancer clinic

    NARCIS (Netherlands)

    Rottenberg, Sven; Borst, Piet

    2012-01-01

    Drug resistance is one of the most pressing problems in treating cancer patients today. Local and regional disease can usually be adequately treated, but patients eventually die from distant metastases that have become resistant to all available chemotherapy. Although work on cultured tumor cell

  14. Mutational analysis and clinical correlation of metastatic colorectal cancer.

    Science.gov (United States)

    Russo, Andrea L; Borger, Darrell R; Szymonifka, Jackie; Ryan, David P; Wo, Jennifer Y; Blaszkowsky, Lawrence S; Kwak, Eunice L; Allen, Jill N; Wadlow, Raymond C; Zhu, Andrew X; Murphy, Janet E; Faris, Jason E; Dias-Santagata, Dora; Haigis, Kevin M; Ellisen, Leif W; Iafrate, Anthony J; Hong, Theodore S

    2014-05-15

    Early identification of mutations may guide patients with metastatic colorectal cancer toward targeted therapies that may be life prolonging. The authors assessed tumor genotype correlations with clinical characteristics to determine whether mutational profiling can account for clinical similarities, differences, and outcomes. Under Institutional Review Board approval, 222 patients with metastatic colon adenocarcinoma (n = 158) and rectal adenocarcinoma (n = 64) who underwent clinical tumor genotyping were reviewed. Multiplexed tumor genotyping screened for >150 mutations across 15 commonly mutated cancer genes. The chi-square test was used to assess genotype frequency by tumor site and additional clinical characteristics. Cox multivariate analysis was used to assess the impact of genotype on overall survival. Broad-based tumor genotyping revealed clinical and anatomic differences that could be linked to gene mutations. NRAS mutations were associated with rectal cancer versus colon cancer (12.5% vs 0.6%; P colon cancer (13% vs 3%; P = .024) and older age (15.8% vs 4.6%; P = .006). TP53 mutations were associated with rectal cancer (30% vs 18%; P = .048), younger age (14% vs 28.7%; P = .007), and men (26.4% vs 14%; P = .03). Lung metastases were associated with PIK3CA mutations (23% vs 8.7%; P = .004). Only mutations in BRAF were independently associated with decreased overall survival (hazard ratio, 2.4; 95% confidence interval, 1.09-5.27; P = .029). The current study suggests that underlying molecular profiles can differ between colon and rectal cancers. Further investigation is warranted to assess whether the differences identified are important in determining the optimal treatment course for these patients. © 2014 American Cancer Society.

  15. Tumor Volume and Metabolism of Prostate Cancer Determined by Proton Magnetic Resonance Spectroscopic Imaging at 3T Without Endorectal Coil Reveal Potential Clinical Implications in the Context of Radiation Oncology

    International Nuclear Information System (INIS)

    Crehange, Gilles; Parfait, Sebastien; Liegard, Melanie; Maingon, Philippe; Ben Salem, Douraied; Cochet, Alexandre; Funes de la Vega, Mathilde; Cormier, Luc; Bonnetain, Franck; Mirjolet, Celine; Brunotte, Francois; Walker, Paul M.

    2011-01-01

    Purpose: To determine whether a relationship exists between the tumor volume (TV) or relative choline content determined using magnetic resonance spectroscopy imaging (MRSI) at 3T and the clinical prognostic parameters for patients with localized prostate cancer (PCa). Methods and Materials: A total of 72 men (mean age, 67.8 ± 6.2 years) were stratified as having low-risk (n = 26), intermediate-risk (n = 24), or high-risk (n = 22) PCa. MRSI was performed at 3T using a phased-array coil. Spectra are expressed as the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamines plus creatine/citrate ratios. The mean ratio of the most pathologic voxels and the MRSI-based TV were also determined. Results: The mean values of the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamine plus creatine/citrate ratios were greater for Stage T2b or greater tumors vs. Stage T2a or less tumors: 7.53 ± 13.60 vs. 2.31 ± 5.65 (p = .018), 8.98 ± 14.58 vs. 2.56 ± 5.70 (p = .016), and 10.32 ± 15.47 vs. 3.55 ± 6.16 (p = .014), respectively. The mean MRSI-based TV for Stage T2b or greater and Stage T2a or less tumors was significantly different (2.23 ± 2.62 cm 3 vs. 1.26 ± 2.06 cm 3 , respectively; p = .030). This TV correlated with increased prostate-specific antigen levels (odds ratio, 1.293; p = .012). Patients with high-risk PCa had a larger TV than did the patients with intermediate-risk PCa. A similar result was found for the intermediate-risk group compared with the low-risk group (odds ratio, 1.225; p = .041). Conclusion: Biomarkers expressing the relative choline content and TV were significant parameters for the localization of PCa and could be helpful for determining the prognosis more accurately.

  16. Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.

    Science.gov (United States)

    Heymach, John; Krilov, Lada; Alberg, Anthony; Baxter, Nancy; Chang, Susan Marina; Corcoran, Ryan; Dale, William; DeMichele, Angela; Magid Diefenbach, Catherine S; Dreicer, Robert; Epstein, Andrew S; Gillison, Maura L; Graham, David L; Jones, Joshua; Ko, Andrew H; Lopez, Ana Maria; Maki, Robert G; Rodriguez-Galindo, Carlos; Schilsky, Richard L; Sznol, Mario; Westin, Shannon Neville; Burstein, Harold

    2018-04-01

    A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors' genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients' own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy-a type of adoptive cell immunotherapy-has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation's support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal

  17. The MCT4 Gene: A Novel, Potential Target for Therapy of Advanced Prostate Cancer.

    Science.gov (United States)

    Choi, Stephen Yiu Chuen; Xue, Hui; Wu, Rebecca; Fazli, Ladan; Lin, Dong; Collins, Colin C; Gleave, Martin E; Gout, Peter W; Wang, Yuzhuo

    2016-06-01

    The management of castration-resistant prostate cancer (CRPC) is a major challenge in the clinic. Androgen receptor signaling-directed strategies are not curative in CRPC therapy, and new strategies targeting alternative, key cancer properties are needed. Using reprogrammed glucose metabolism (aerobic glycolysis), cancer cells typically secrete excessive amounts of lactic acid into their microenvironment, promoting cancer development, survival, and progression. Cellular lactic acid secretion is thought to be predominantly mediated by MCT4, a plasma membrane transporter protein. As such, the MCT4 gene provides a unique, potential therapeutic target for cancer. A tissue microarray of various Gleason grade human prostate cancers was stained for MCT4 protein. Specific, MCT4-targeting antisense oligonucleotides (MCT4 ASO) were designed and candidate MCT4 ASOs checked for effects on (i) MCT4 expression, lactic acid secretion/content, glucose consumption, glycolytic gene expression, and proliferation of human CRPC cells and (ii) growth of PC-3 tumors in nude mice. Elevated MCT4 expression was associated with human CRPC and an earlier time to relapse. The treatment of PC-3, DU145, and C4-2 CRPC cultures with candidate MCT4 ASOs led to marked inhibition of MCT4 expression, lactic acid secretion, to increased intracellular lactic acid levels, and markedly reduced aerobic glycolysis and cell proliferation. Treatment of PC-3 tumor-bearing nude mice with the MCT4 ASOs markedly inhibited tumor growth without inducing major host toxicity. MCT4-targeting ASOs that inhibit lactic acid secretion may be useful for therapy of CRPC and other cancers, as they can interfere with reprogrammed energy metabolism of cancers, an emerging hallmark of cancer. Clin Cancer Res; 22(11); 2721-33. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Novel drugs that target the estrogen-related receptor alpha: their therapeutic potential in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    May, Felicity EB, E-mail: F.E.B.May@ncl.ac.uk [Northern Institute for Cancer Research and Department of Pathology, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne (United Kingdom)

    2014-05-23

    The incidence of breast cancer continues to rise: 1.7 million women were diagnosed with and 521,000 women died from breast cancer in 2012. This review considers first current treatment options: surgery; radiotherapy; and systemic endocrine, anti-biological, and cytotoxic therapies. Clinical management includes prevention, early detection by screening, treatment with curative intent, management of chronic disease, and palliative control of advanced breast cancer. Next, the potential of novel drugs that target DNA repair, growth factor dependence, intracellular and intercellular signal transduction, and cell cycle are considered. Estrogen-related receptor alpha has attracted attention as a therapeutic target in triple-negative breast cancers with de novo resistance to, and in breast cancers with acquired resistance to, endocrine therapies such as antiestrogens and aromatase inhibitors. Estrogen-related receptor alpha is an orphan receptor and transcription factor. Its activity is regulated by coregulator proteins and posttranslational modification. It is an energy sensor that controls adaptation to energy demand and may facilitate glycolytic metabolism and mitochondrial oxidative respiration in breast cancer cells. Estrogen-related receptor alpha increases breast cancer cell migration, proliferation, and tumor development. It is expressed at high levels in estrogen receptor-negative tumors, and is proposed to activate estrogen-responsive genes in endocrine-resistant tumors. The structures and functions of the ligand-binding domains of estrogen receptor alpha and estrogen-related receptor alpha, their ability to bind estrogens, phytoestrogens, and synthetic ligands, and the effects of ligand agonists, antagonists, and inverse agonists on biological activity, are evaluated. Synthetic ligands of estrogen-related receptor alpha have activity in preclinical models of metabolic disorders, diabetes, osteoporosis, and oncology. The clinical settings in which these novel

  19. Novel drugs that target the estrogen-related receptor alpha: their therapeutic potential in breast cancer

    International Nuclear Information System (INIS)

    May, Felicity EB

    2014-01-01

    The incidence of breast cancer continues to rise: 1.7 million women were diagnosed with and 521,000 women died from breast cancer in 2012. This review considers first current treatment options: surgery; radiotherapy; and systemic endocrine, anti-biological, and cytotoxic therapies. Clinical management includes prevention, early detection by screening, treatment with curative intent, management of chronic disease, and palliative control of advanced breast cancer. Next, the potential of novel drugs that target DNA repair, growth factor dependence, intracellular and intercellular signal transduction, and cell cycle are considered. Estrogen-related receptor alpha has attracted attention as a therapeutic target in triple-negative breast cancers with de novo resistance to, and in breast cancers with acquired resistance to, endocrine therapies such as antiestrogens and aromatase inhibitors. Estrogen-related receptor alpha is an orphan receptor and transcription factor. Its activity is regulated by coregulator proteins and posttranslational modification. It is an energy sensor that controls adaptation to energy demand and may facilitate glycolytic metabolism and mitochondrial oxidative respiration in breast cancer cells. Estrogen-related receptor alpha increases breast cancer cell migration, proliferation, and tumor development. It is expressed at high levels in estrogen receptor-negative tumors, and is proposed to activate estrogen-responsive genes in endocrine-resistant tumors. The structures and functions of the ligand-binding domains of estrogen receptor alpha and estrogen-related receptor alpha, their ability to bind estrogens, phytoestrogens, and synthetic ligands, and the effects of ligand agonists, antagonists, and inverse agonists on biological activity, are evaluated. Synthetic ligands of estrogen-related receptor alpha have activity in preclinical models of metabolic disorders, diabetes, osteoporosis, and oncology. The clinical settings in which these novel

  20. Establishing a family risk assessment clinic for breast cancer.

    LENUS (Irish Health Repository)

    Mulsow, Jurgen

    2012-02-01

    Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15-20% of women who develop breast cancer have a family history and 5-10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score >or=16. BRCA1\\/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management.

  1. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Söletormos, Georg; Duffy, Michael J; Othman Abu Hassan, Suher

    2016-01-01

    OBJECTIVE: To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer. METHODS: Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. RESULTS: Because of its low s...

  2. Exosomes are fingerprints of originating cells: potential biomarkers for ovarian cancer

    Directory of Open Access Journals (Sweden)

    Kobayashi M

    2015-03-01

    Full Text Available Miharu Kobayashi, Gregory E Rice, Jorge Tapia, Murray D Mitchell, Carlos Salomon Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. Abstract: The past decade has seen an extraordinary explosion of research in the field of extracellular vesicles, especially in a specific type of extracellular vesicles originating from endosomal compartments, called exosomes. Exosomes are a specific subtype of secreted vesicles that are defined as small (~30–120 nm but very stable membrane vesicles that are released from a wide range of cells, including normal and cancer cells. As the content of exosomes is cell type specific, it is believed that they are a "fingerprint" of the releasing cell and its metabolic status. We hypothesized that the exosomes and their specific exosomal content (eg, microribonucleic acid represent a precious biomedical tool and may be used as biomarkers for the diagnosis and prognosis of malignant tumors. In addition, exosomes may modify the phenotype of the parent and/or target cell by transferring pro-oncogenic molecules to induce cancerous phenotype of recipient cells and contribute to the formation of the premetastatic niche. The mechanism involved in these phenomena remains unclear; however, inclusion of signaling mediators into exosomes or exosome release may reduce their intracellular bioavailability in the parent cell, thereby altering cell phenotype and their metastatic potential. The aim of this review therefore is to analyze the biogenesis and role of exosomes from tumor cells, focusing primarily on ovarian cancer. Ovarian cancer is the most lethal gynecologic cancer, and an effective early diagnosis has the potential to improve patient survival. Ovarian cancer currently lacks a reliable method for early detection, however, exosomes have received great attention as potential biomarkers and mediators

  3. Epigenetics in prostate cancer: biologic and clinical relevance.

    Science.gov (United States)

    Jerónimo, Carmen; Bastian, Patrick J; Bjartell, Anders; Carbone, Giuseppina M; Catto, James W F; Clark, Susan J; Henrique, Rui; Nelson, William G; Shariat, Shahrokh F

    2011-10-01

    Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence. To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge. PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications. Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance. Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  4. Hyaluronic acid-modified zirconium phosphate nanoparticles for potential lung cancer therapy.

    Science.gov (United States)

    Li, Ranwei; Liu, Tiecheng; Wang, Ke

    2017-02-01

    Novel tumor-targeting zirconium phosphate (ZP) nanoparticles modified with hyaluronic acid (HA) were developed (HA-ZP), with the aim of combining the drug-loading property of ZP and the tumor-targeting ability of HA to construct a tumor-targeting paclitaxel (PTX) delivery system for potential lung cancer therapy. The experimental results indicated that PTX loading into the HA-ZP nanoparticles was as high as 20.36%±4.37%, which is favorable for cancer therapy. PTX-loaded HA-ZP nanoparticles increased the accumulation of PTX in A549 lung cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo anticancer efficacy assay revealed that HA-ZP nanoparticles possessed preferable anticancer abilities, which exhibited minimized toxic side effects of PTX and strong tumor-suppression potential in clinical application.

  5. Bisphosphonates as potential adjuvants for patients with cancers of the digestive system.

    Science.gov (United States)

    Ang, Celina; Doyle, Erin; Branch, Andrea

    2016-01-21

    Best known for their anti-resorptive activity in bone, bisphosphonates (BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor (HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.

  6. Improving the clinical impact of biomaterials in cancer immunotherapy

    Science.gov (United States)

    Gammon, Joshua M.; Dold, Neil M.; Jewell, Christopher M.

    2016-01-01

    Immunotherapies for cancer have progressed enormously over the past few decades, and hold great promise for the future. The successes of these therapies, with some patients showing durable and complete remission, demonstrate the power of harnessing the immune system to eradicate tumors. However, the effectiveness of current immunotherapies is limited by hurdles ranging from immunosuppressive strategies employed by tumors, to inadequate specificity of existing therapies, to heterogeneity of disease. Further, the vast majority of approved immunotherapies employ systemic delivery of immunomodulators or cells that make addressing some of these challenges more difficult. Natural and synthetic biomaterials–such as biocompatible polymers, self-assembled lipid particles, and implantable biodegradable devices–offer unique potential to address these hurdles by harnessing the benefits of therapeutic targeting, tissue engineering, co-delivery, controlled release, and sensing. However, despite the enormous investment in new materials and nanotechnology, translation of these ideas to the clinic is still an uncommon outcome. Here we review the major challenges facing immunotherapies and discuss how the newest biomaterials and nanotechnologies could help overcome these challenges to create new clinical options for patients. PMID:26871948

  7. Bone metastases from gastric cancer. Clinical evaluation on bone scintigram

    Energy Technology Data Exchange (ETDEWEB)

    Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi [Kanazawa Univ. (Japan). School of Medicine

    1983-07-01

    We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N/sub 0/ or N/sub 1/ regional lymph node metastases, highly differentiated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone metastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer.

  8. Immunomodulatory nutraceuticals with potential clinical use for dogs and cats

    Directory of Open Access Journals (Sweden)

    Leandro Zaine

    2014-09-01

    Full Text Available The use of nutraceuticals in veterinary medicine is growing and is assumed that they could aid in clinical treatment. This review aims to describe some nutraceuticals that act on the immunity of dogs and cats and show the possible benefits as an adjuvant treatment for some diseases. The action of some yeast derivates as immunomodulators, especially the beta-glucan fraction, was already proved to occur in dogs and cats, being beneficial as an adjuvant therapy in many clinical conditions. Omega-3 polyunsatured fatty acids, possibly the mostly used nutraceuticals, can improve the condition in some diseases, such as hypertension, renal, cardiac, gastrointestinal and autoimmune diseases, arthritis and cancer. Vitamin E has antioxidant and immunomodulatory action and can aid in the treatment of dermatologic and hepatobiliar conditions. The use of carotenoids, which have similar action to vitamin E, can be of interest for being potent antioxidants and might be helpful for enhancing immune response against microorganisms and also act preventing tumors. Despite it are still needed clinical trials to better understand the real benefits of nutraceuticals supplementation in each specific disease, the comprehension of the mechanisms by which they act indicates they are promising for clinical use.

  9. Selectively starving cancer cells through dietary manipulation: methods and clinical implications.

    Science.gov (United States)

    Simone, Brittany A; Champ, Colin E; Rosenberg, Anne L; Berger, Adam C; Monti, Daniel A; Dicker, Adam P; Simone, Nicole L

    2013-07-01

    As the link between obesity and metabolic syndrome and cancer becomes clearer, the need to determine the optimal way to incorporate dietary manipulation in the treatment of cancer patients becomes increasingly important. Metabolic-based therapies, such as caloric restriction, intermittent fasting and a ketogenic diet, have the ability to decrease the incidence of spontaneous tumors and slow the growth of primary tumors, and may have an effect on distant metastases in animal models. Despite the abundance of preclinical data demonstrating the benefit of dietary modification for cancer, to date there are few clinical trials targeting diet as an intervention for cancer patients. We hypothesize that this may be due, in part, to the fact that several different types of diet modification exist with no clear recommendations regarding the optimal method. This article will delineate three commonly used methods of dietary manipulation to assess the potential of each as a regimen for cancer therapy.

  10. Roles of Ubiquitination and SUMOylation on Prostate Cancer: Mechanisms and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Zhenbang Chen

    2015-02-01

    Full Text Available The initiation and progression of human prostate cancer are highly associated with aberrant dysregulations of tumor suppressors and proto-oncogenes. Despite that deletions and mutations of tumor suppressors and aberrant elevations of oncogenes at the genetic level are reported to cause cancers, emerging evidence has revealed that cancer progression is largely regulated by posttranslational modifications (PTMs and epigenetic alterations. PTMs play critical roles in gene regulation, cellular functions, tissue development, diseases, malignant progression and drug resistance. Recent discoveries demonstrate that ubiquitination and SUMOylation are complicated but highly-regulated PTMs, and make essential contributions to diseases and cancers by regulation of key factors and signaling pathways. Ubiquitination and SUMOylation pathways can be differentially modulated under various stimuli or stresses in order to produce the sustained oncogenic potentials. In this review, we discuss some new insights about molecular mechanisms on ubiquitination and SUMOylation, their associations with diseases, oncogenic impact on prostate cancer (PCa and clinical implications for PCa treatment.

  11. Progastrin: a potential predictive marker of liver metastasis in colorectal cancer.

    Science.gov (United States)

    Westwood, David A; Patel, Oneel; Christophi, Christopher; Shulkes, Arthur; Baldwin, Graham S

    2017-07-01

    Staging of colorectal cancer often fails to discriminate outcomes of patients with morphologically similar tumours that exhibit different clinical behaviours. Data from several studies suggest that the gastrin family of growth factors potentiates colorectal cancer tumourigenesis. The aim of this study was to investigate whether progastrin expression may predict clinical outcome in colorectal cancer. Patients with colorectal adenocarcinoma of identical depth of invasion who had not received neoadjuvant therapy were included. The patients either had stage IIa disease with greater than 3-year disease-free survival without adjuvant therapy or stage IV disease with liver metastases on staging CT. Progastrin expression in tumour sections was scored with reference to the intensity and area of immunohistochemical staining. Progastrin expression by stage IV tumours was significantly greater than stage IIa tumours with mean progastrin immunopositivity scores of 2.1 ± 0.2 versus 0.5 ± 0.2, respectively (P colorectal cancer and supports its clinical relevance and potential use as a biomarker.

  12. Clinical target volume for rectal cancer. Preoperative radiotherapy

    International Nuclear Information System (INIS)

    Lorchel, F.; Bossel, J.F.; Baron, M.H.; Goubard, O.; Bartholomot, B.; Mantion, G.; Pelissier, E.P.; Maingon, P.

    2001-01-01

    The total meso-rectal excision allows the marked increase of the local control rate in rectal cancer. Therefore, the meso-rectal space is the usual field for the spread of rectal cancer cells. It could therefore be considered as the clinical target volume in the preoperative plan by the radiation oncologist. We propose to identify the mesorectum on anatomical structures of a treatment-position CT scan. (authors)

  13. Rad51 expression levels predict synthetic lethality and metastatic potential in high grade breast cancers

    International Nuclear Information System (INIS)

    Wiegmans, A.P.; Al-Ejeh, F.; Khanna, K.K.

    2012-01-01

    Among women with breast cancer, 30-40% will develop metastatic disease and only achieve an overall survival of less than 5 years. Despite new-targeted therapy, breast tumors that harbour similar histology or molecular phenotype differ in their response to treatment. To uncover potential new therapeutic targets and improve outcome, we performed data mining of cancer micro array databases. We found that high expression of the homologous recombination protein, RAD51, was significantly associated with high-grade breast cancer, aggressive subtypes and increased risk of metastasis. We confirmed using immunohistochemistry that RAD5 1 was highly expressed in metastatic tumours and high-grade triple negative, HER2+ and luminal-B tumours. This provided a rationale for targeting RAD5 1 in high-grade, therapy-resistant breast cancers. Here, we report for the first time preclinical evaluation of RAD5 1 as a therapeutic target. We found that, in-vitro high RAD5 expressing cell lines were resistant to PARP inhibitor while knockdown reversed this resistance. In-vivo, knockdown of RAD5 1 inhibited metastatic progression using a syngeneic breast cancer model and the seeding of human xenografts to distant sites, including brain and lung. Concurrent PARP inhibition reduced primary tumor growth and delayed metastasis supporting synthetic lethality in-vivo. Together these insights provide pre-clinical data demonstrating RAD5 1 as a new biomarker and potential therapeutic target against aggressive metastatic breast cancer. (author)

  14. A Semantic Web-based System for Mining Genetic Mutations in Cancer Clinical Trials.

    Science.gov (United States)

    Priya, Sambhawa; Jiang, Guoqian; Dasari, Surendra; Zimmermann, Michael T; Wang, Chen; Heflin, Jeff; Chute, Christopher G

    2015-01-01

    Textual eligibility criteria in clinical trial protocols contain important information about potential clinically relevant pharmacogenomic events. Manual curation for harvesting this evidence is intractable as it is error prone and time consuming. In this paper, we develop and evaluate a Semantic Web-based system that captures and manages mutation evidences and related contextual information from cancer clinical trials. The system has 2 main components: an NLP-based annotator and a Semantic Web ontology-based annotation manager. We evaluated the performance of the annotator in terms of precision and recall. We demonstrated the usefulness of the system by conducting case studies in retrieving relevant clinical trials using a collection of mutations identified from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology and Haematology. In conclusion, our system using Semantic Web technologies provides an effective framework for extraction, annotation, standardization and management of genetic mutations in cancer clinical trials.

  15. Predicting reattendance at a high-risk breast cancer clinic.

    Science.gov (United States)

    Ormseth, Sarah R; Wellisch, David K; Aréchiga, Adam E; Draper, Taylor L

    2015-10-01

    The research about follow-up patterns of women attending high-risk breast-cancer clinics is sparse. This study sought to profile daughters of breast-cancer patients who are likely to return versus those unlikely to return for follow-up care in a high-risk clinic. Our investigation included 131 patients attending the UCLA Revlon Breast Center High Risk Clinic. Predictor variables included age, computed breast-cancer risk, participants' perceived personal risk, clinically significant depressive symptomatology (CES-D score ≥ 16), current level of anxiety (State-Trait Anxiety Inventory), and survival status of participants' mothers (survived or passed away from breast cancer). A greater likelihood of reattendance was associated with older age (adjusted odds ratio [AOR] = 1.07, p = 0.004), computed breast-cancer risk (AOR = 1.10, p = 0.017), absence of depressive symptomatology (AOR = 0.25, p = 0.009), past psychiatric diagnosis (AOR = 3.14, p = 0.029), and maternal loss to breast cancer (AOR = 2.59, p = 0.034). Also, an interaction was found between mother's survival and perceived risk (p = 0.019), such that reattendance was associated with higher perceived risk among participants whose mothers survived (AOR = 1.04, p = 0.002), but not those whose mothers died (AOR = 0.99, p = 0.685). Furthermore, a nonlinear inverted "U" relationship was observed between state anxiety and reattendance (p = 0.037); participants with moderate anxiety were more likely to reattend than those with low or high anxiety levels. Demographic, medical, and psychosocial factors were found to be independently associated with reattendance to a high-risk breast-cancer clinic. Explication of the profiles of women who may or may not reattend may serve to inform the development and implementation of interventions to increase the likelihood of follow-up care.

  16. MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

    International Nuclear Information System (INIS)

    Pal, Manish K.; Jaiswar, Shyam P.; Dwivedi, Vinaya N.; Tripathi, Amit K.; Dwivedi, Ashish; Sankhwar, Pushplata

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers (mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as microRNAs (miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish miRNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers

  17. Preclinical and Clinical Effects of Mistletoe against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mohsen Marvibaigi

    2014-01-01

    Full Text Available Breast cancer is among the most frequent types of cancer in women worldwide. Current conventional treatment options are accompanied by side effects. Mistletoe is amongst the important herbal medicines traditionally used as complementary remedies. An increasing number of studies have reported anticancer activity of mistletoe extracts on breast cancer cells and animal models. Some recent evidence suggests that cytotoxic activity of mistletoe may be mediated through different mechanisms. These findings provide a good base for clinical trials. Various studies on mistletoe therapy for breast cancer patients revealed similar findings concerning possible benefits on survival time, health-related quality of life (HRQoL, remission rate, and alleviating adverse reactions to conventional therapy. This review provides an overview of the recent findings on preclinical experiments and clinical trials of mistletoe for its cytotoxic and antitumor activity and its effect on HRQoL in breast cancer patients. Moreover, studies investigating molecular and cellular mechanisms underlying antitumor activity of mistletoe are discussed in this paper. The analyzed trials provided evidence that there might be a combination of pharmacological and motivational aspects mediated by the mistletoe extract application which may contribute to the clinical benefit and positive outcome such as improved HRQoL and self-regulation in breast cancer patients.

  18. Clinical management of gastric cancer: results of a multicentre survey

    International Nuclear Information System (INIS)

    Zhang, Xiaolong; Wen, Feng; Jiang, Yu; Xu, Feng; Feng, Hong; Bi, Feng; Li, Qiu; Li, Nanjing; Wei, Wen; Yao, Wenxiu; Xie, Ke; Hu, Jiankun; Shen, Lida; Ji, Weizheng; Lu, You

    2011-01-01

    The National Comprehensive Cancer Network clinical practice guidelines in oncology-gastric cancer guidelines have been widely used to provide appropriate recommendations for the treatment of patients with gastric cancer. The aim of this study was to examine the adherence of surgical oncologists, medical oncologists, and radiation oncologists' to the recommended guidelines. A questionnaire asking the treatment options for gastric cancer cases was sent to 394 Chinese oncology specialists, including surgical oncologists, medical oncologists, and radiation oncologists working in hospitals joined in The Western Cooperative Gastrointestinal Oncology Group of China. The questionnaire involved a series of clinical scenarios regarding the interpretation of surgery, neoadjuvant, adjuvant, and advanced treatment planning of gastric cancer. Analysis of 358 respondents (91%) showed variations between each specialization and from the recommended guidelines in the management approaches to specific clinical scenarios. The majority of specialists admitted that less than 50% of patients received multidisciplinary evaluation before treatment. The participants gave different responses to questions involving adjuvant, neoadjuvant, and advanced settings, compared to the recommended guidelines. These results highlight the heterogeneity of the treatment of gastric cancer. Surgical oncologists, medical oncologists, and radiation oncologists are not adhering to the recommended guidelines

  19. Prostate cancer - epidemiology, etiology, diagnostics, clinical symptoms, screening

    International Nuclear Information System (INIS)

    Ondrus, D.

    2006-01-01

    Prostate cancer presents a real important medical and social problem at present. It is one of the most common malignancy in males. In global point of view it means permanent incidence increase of this disease. Despite improvement of prostate cancer diagnosis and complex treatment mortality does not decreased significantly. Knowledge of etiological factors are relatively limited. Important factors are: genetic disposition, age, life style, race, positive familial history, circulated androgens. Diagnostics is well known, based on routine clinical methods: digital rectal examination, measurement of PSA a transrectal ultrasound. Benefit of prostate cancer screening is until now unclear, controversial. (author)

  20. Preclinical Murine Models for Lung Cancer: Clinical Trial Applications

    Directory of Open Access Journals (Sweden)

    Amelia Kellar

    2015-01-01

    Full Text Available Murine models for the study of lung cancer have historically been the backbone of preliminary preclinical data to support early human clinical trials. However, the availability of multiple experimental systems leads to debate concerning which model, if any, is best suited for a particular therapeutic strategy. It is imperative that these models accurately predict clinical benefit of therapy. This review provides an overview of the current murine models used to study lung cancer and the advantages and limitations of each model, as well as a retrospective evaluation of the uses of each model with respect to accuracy in predicting clinical benefit of therapy. A better understanding of murine models and their uses, as well as their limitations may aid future research concerning the development and implementation of new targeted therapies and chemotherapeutic agents for lung cancer.

  1. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.

    Science.gov (United States)

    Wicki, Andreas; Witzigmann, Dominik; Balasubramanian, Vimalkumar; Huwyler, Jörg

    2015-02-28

    Cancer is a leading cause of death worldwide. Currently available therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology towards the development of nanomedicine products holds great promise to improve therapeutic strategies against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multi-functionality. They can improve the pharmacokinetic and pharmacodynamic profiles of conventional therapeutics and may thus optimize the efficacy of existing anti-cancer compounds. In this review, we discuss state-of-the-art nanoparticles and targeted systems that have been investigated in clinical studies. We emphasize the challenges faced in using nanomedicine products and translating them from a preclinical level to the clinical setting. Additionally, we cover aspects of nanocarrier engineering that may open up new opportunities for nanomedicine products in the clinic. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Cancer stem cells and drug resistance: the potential of nanomedicine

    Science.gov (United States)

    Vinogradov, Serguei; Wei, Xin

    2012-01-01

    Properties of the small group of cancer cells called tumor-initiating or cancer stem cells (CSCs) involved in drug resistance, metastasis and relapse of cancers can significantly affect tumor therapy. Importantly, tumor drug resistance seems to be closely related to many intrinsic or acquired properties of CSCs, such as quiescence, specific morphology, DNA repair ability and overexpression of antiapoptotic proteins, drug efflux transporters and detoxifying enzymes. The specific microenvironment (niche) and hypoxic stability provide additional protection against anticancer therapy for CSCs. Thus, CSC-focused therapy is destined to form the core of any effective anticancer strategy. Nanomedicine has great potential in the development of CSC-targeting drugs, controlled drug delivery and release, and the design of novel gene-specific drugs and diagnostic modalities. This review is focused on tumor drug resistance-related properties of CSCs and describes current nanomedicine approaches, which could form the basis of novel combination therapies for eliminating metastatic and CSCs. PMID:22471722

  3. Clinical advances of nanocarrier-based cancer therapy and diagnostics.

    Science.gov (United States)

    Luque-Michel, Edurne; Imbuluzqueta, Edurne; Sebastián, Víctor; Blanco-Prieto, María J

    2017-01-01

    Cancer is a leading cause of death worldwide and efficient new strategies are urgently needed to combat its high mortality and morbidity statistics. Fortunately, over the years, nanotechnology has evolved as a frontrunner in the areas of imaging, diagnostics and therapy, giving the possibility of monitoring, evaluating and individualizing cancer treatments in real-time. Areas covered: Polymer-based nanocarriers have been extensively studied to maximize cancer treatment efficacy and minimize the adverse effects of standard therapeutics. Regarding diagnosis, nanomaterials like quantum dots, iron oxide nanoparticles or gold nanoparticles have been developed to provide rapid, sensitive detection of cancer and, therefore, facilitate early treatment and monitoring of the disease. Therefore, multifunctional nanosystems with both imaging and therapy functionalities bring us a step closer to delivering precision/personalized medicine in the cancer setting. Expert opinion: There are multiple barriers for these new nanosystems to enter the clinic, but it is expected that in the near future, nanocarriers, together with new 'targeted drugs', could replace our current treatments and cancer could become a nonfatal disease with good recovery rates. Joint efforts between scientists, clinicians, the pharmaceutical industry and legislative bodies are needed to bring to fruition the application of nanosystems in the clinical management of cancer.

  4. Overcoming Age Limits in Cancer Clinical Trials

    Science.gov (United States)

    Adolescents, young adults, and the elderly lag far behind other age groups when it comes to enrolling in clinical trials. Their participation is critical to advancing effective therapies for these age groups.

  5. Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer

    International Nuclear Information System (INIS)

    Dayan, Dan; Salo, Tuula; Salo, Sirpa; Nyberg, Pia; Nurmenniemi, Sini; Costea, Daniela Elena; Vered, Marilena

    2012-01-01

    We characterized tumor microenvironment (TME) components of mobile tongue (MT) cancer patients in terms of overall inflammatory infiltrate, focusing on the protumorigenic/anti-inflammatory phenotypes and on cancer-associated fibroblasts (CAFs) in order to determine their interrelations and associations with clinical outcomes. In addition, by culturing tongue carcinoma cells (HSC-3) on a three-dimensional myoma organotypic model that mimics TME, we attempted to investigate the possible existence of a molecular crosstalk between cancer cells and TME components. Analysis of 64 cases of MT cancer patients revealed that the overall density of the inflammatory infiltrate was inversely correlated to the density of CAFs (P = 0.01), but that the cumulative density of the protumorigenic/anti-inflammatory phenotypes, including regulatory T cells (Tregs, Foxp3+), tumor-associated macrophages (TAM2, CD163+), and potentially Tregs-inducing immune cells (CD80+), was directly correlated with the density of CAFs (P = 0.01). The hazard ratio (HR) for recurrence in a TME rich in CD163+ Foxp3+ CD80+ was 2.9 (95% CI 1.03–8.6, P = 0.043 compared with low in CD163+ Foxp3+ CD80+). The HR for recurrence in a TME rich in CAFs was 4.1 (95% confidence interval [CI] 1.3–12.8, P = 0.012 compared with low in CAFs). In vitro studies showed cancer-derived exosomes, epithelial–mesenchymal transition process, fibroblast-to-CAF-like cell transdifferentiation, and reciprocal interrelations between different cytokines suggesting the presence of molecular crosstalk between cancer cells and TME components. Collectively, these results highlighted the emerging need of new therapies targeting this crosstalk between the cancer cells and TME components in MT cancer

  6. Intraoperative radiotherapy in early stage breast cancer: potential indications and evidence to date

    Science.gov (United States)

    Kirby, A M

    2015-01-01

    Following early results of recent studies of intraoperative radiotherapy (IORT) in the adjuvant treatment of patients with early breast cancer, the clinical utility of IORT is a subject of much recent debate within the breast oncology community. This review describes the intraoperative techniques available, the potential indications and the evidence to date pertaining to local control and toxicity. We also discuss any implications for current practice and future research. PMID:25734489

  7. The role of hypoxia in oral cancer and potentially malignant disorders: a review.

    Science.gov (United States)

    Kujan, Omar; Shearston, Kate; Farah, Camile S

    2017-04-01

    Oral and oropharyngeal cancer are major health problems globally with over 500 000 new cases diagnosed annually. Despite the fact that oral cancer is a preventable disease and has the potential for early detection, the overall survival rate remains at around 50%. Most oral cancer cases are preceded by a group of clinical lesions designated 'potentially malignant disorders'. It is difficult to predict if and when these lesions may transform to malignancy, and in turn it is difficult to agree on appropriate management strategies. Understanding underlying molecular pathways would help in predicting the malignant transformation of oral potentially malignant disorders and ultimately identifying effective methods for early detection and prevention of oral cancer. Reprogramming energy metabolism is an emerging hallmark of cancer that is predominantly controlled by hypoxia-induced genes regulating angiogenesis, tumour vascularization, invasion, drug resistance and metastasis. This review aims to highlight the role of hypoxia in oral carcinogenesis and to suggest future research implications in this arena. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Review of Natural Compounds for Potential Skin Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tawona N. Chinembiri

    2014-08-01

    Full Text Available Most anti-cancer drugs are derived from natural resources such as marine, microbial and botanical sources. Cutaneous malignant melanoma is the most aggressive form of skin cancer, with a high mortality rate. Various treatments for malignant melanoma are available, but due to the development of multi-drug resistance, current or emerging chemotherapies have a relatively low success rates. This emphasizes the importance of discovering new compounds that are both safe and effective against melanoma. In vitro testing of melanoma cell lines and murine melanoma models offers the opportunity for identifying mechanisms of action of plant derived compounds and extracts. Common anti-melanoma effects of natural compounds include potentiating apoptosis, inhibiting cell proliferation and inhibiting metastasis. There are different mechanisms and pathways responsible for anti-melanoma actions of medicinal compounds such as promotion of caspase activity, inhibition of angiogenesis and inhibition of the effects of tumor promoting proteins such as PI3-K, Bcl-2, STAT3 and MMPs. This review thus aims at providing an overview of anti-cancer compounds, derived from natural sources, that are currently used in cancer chemotherapies, or that have been reported to show anti-melanoma, or anti-skin cancer activities. Phytochemicals that are discussed in this review include flavonoids, carotenoids, terpenoids, vitamins, sulforaphane, some polyphenols and crude plant extracts.

  9. Phase II cancer clinical trials for biomarker-guided treatments.

    Science.gov (United States)

    Jung, Sin-Ho

    2018-01-01

    The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

  10. Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

    Energy Technology Data Exchange (ETDEWEB)

    Giantsoudi, Drosoula, E-mail: dgiantsoudi@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)

    2013-09-01

    Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

  11. Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

    International Nuclear Information System (INIS)

    Giantsoudi, Drosoula; Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald

    2013-01-01

    Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

  12. A clinical analysis of maxillary sinus cancer

    International Nuclear Information System (INIS)

    Yasumatsu, Ryuji; Nakashima, Torahiko; Ayada, Toranoshin; Shiratsuchi, Hideki; Toh, Satoshi; Komune, Shizuo

    2009-01-01

    Thirty-two patients (23 males, 9 females) with maxillary sinus cancer were treated at Kyushu University Hospital during 2000-2008. They were classified by T classification as 5 cases with T2, 13 with T3, 12 with T4a, and 2 with T4b. Between 2000 and 2003, 16 patients were given irradiation, intra-arterial 5-fluorouracil (5-FU) infusion chemotherapy, maxillectomy and postoperative irradiation. After 2004, two patients with T4b maxillary sinus cancer were treated by superselective intra-arterial chemotherapy with Cisplatin (CDDP) and Docetaxel (DOC) and irradiation. Other patients were given irradiation and chemotherapy with S-1 and intra-arterial infusion of 5-FU. The 3-year survival rate was 68.3% for all patients. The 3-year survival rate was 74.6% for patients treated after 2004, whereas it was 62.5% for patients treated between 2000 and 2003. Chemotherapy with S-1 or superselective intra-arterial chemotherapy with CDDP and DOC improved cause-specific survival rates. (author)

  13. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline.

    Science.gov (United States)

    Runowicz, Carolyn D; Leach, Corinne R; Henry, N Lynn; Henry, Karen S; Mackey, Heather T; Cowens-Alvarado, Rebecca L; Cannady, Rachel S; Pratt-Chapman, Mandi L; Edge, Stephen B; Jacobs, Linda A; Hurria, Arti; Marks, Lawrence B; LaMonte, Samuel J; Warner, Ellen; Lyman, Gary H; Ganz, Patricia A

    2016-02-20

    The purpose of the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline is to provide recommendations to assist primary care and other clinicians in the care of female adult survivors of breast cancer. A systematic review of the literature was conducted using PubMed through April 2015. A multidisciplinary expert workgroup with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology, and nursing was formed and tasked with drafting the Breast Cancer Survivorship Care Guideline. A total of 1,073 articles met inclusion criteria; and, after full text review, 237 were included as the evidence base. Patients should undergo regular surveillance for breast cancer recurrence, including evaluation with a cancer-related history and physical examination, and should be screened for new primary breast cancer. Data do not support performing routine laboratory tests or imaging tests in asymptomatic patients to evaluate for breast cancer recurrence. Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy. Recommendations provided in this guideline are based on current evidence in the literature and expert consensus opinion. Most of the evidence is not sufficient to warrant a strong evidence-based recommendation. Recommendations on surveillance for breast cancer recurrence, screening for second primary cancers, assessment and management of physical and psychosocial long-term and late effects of breast cancer and its treatment, health promotion, and care coordination/practice implications are made.This guideline was developed through a collaboration between the American Cancer Society and the American Society of Clinical Oncology and has been published jointly by invitation and consent in both CA: A Cancer Journal for

  14. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

    Science.gov (United States)

    Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

  15. Asian Americans and Cancer Clinical Trials: A Mixed-Methods Approach to Understanding Awareness and Experience

    Science.gov (United States)

    Paterniti, Debora A.; Chen, Moon S.; Chiechi, Christine; Beckett, Laurel A.; Horan, Nora; Turrell, Corinne; Smith, Ligaya; Morain, Claudia; Montell, Lisa; Gonzalez, Jose Luis; Davis, Sharon; Lara, Primo N.

    2006-01-01

    Cancer clinical trials have been based on low accrual rates. Barriers to recruitment of minority populations affect the generalizability and impact of trial findings for those populations. The authors undertook a mixed-methods approach to understanding levels of awareness and experiences with cancer clinical trials. A survey was administered to new cancer patients and their caretakers (family, close friends, or other social support) at outpatient oncology clinics. Field observations of the trial accrual process also were conducted by employing the grounded theory approach in qualitative methods. Comparison of survey results for Asian-American respondents and non-Asian respondents indicated that Asians were less likely to have heard the term “clinical trial” and were more likely to define a clinical trial as “an experiment” or “a test procedure in a clinic” than non-Asians. Asians were more likely to have employer-based insurance and to report understanding issues related to cost reimbursement. Asians were less likely to have been involved in or to know someone in a trial and reported less willingness than white respondents to consider trial participation. Qualitative observations suggested that Asians who presented for a potential trial were interested in the availability of a novel cancer therapy but were not eligible for available trials. Multiple strategies will be necessary to enhance awareness of and experience with accrual to cancer clinical trials for Asians, including richer understanding and increased involvement of Asians in cancer clinical trials and greater attention to the location and diversity of the Asian population in structuring study centers and evaluating trial results. PMID:16247795

  16. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

    Science.gov (United States)

    Cha, Eugene K; Eastham, James A

    2015-05-01

    Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Potential use of custirsen to treat prostate cancer

    Directory of Open Access Journals (Sweden)

    Higano CS

    2013-06-01

    Full Text Available Celestia S Higano Department of Medicine, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, WA, USA Abstract: Over the last few years, five agents have demonstrated a survival benefit over a comparator treatment or placebo in the treatment of metastatic castration-resistant prostate cancer and have been approved by the US Food and Drug Administration: sipuleucel-T (a dendritic cell immunotherapy; cabazitaxel; abiraterone acetate and enzalutamide (both hormonal agents; and radium 223 (an alpha emitter. The development of these agents pivoted on whether patients had been treated with docetaxel, which remains the first-line chemotherapy of choice. To date, no combination of docetaxel and another active agent has demonstrated superiority to docetaxel alone despite numerous Phase III trials. Clusterin is a cytoprotective chaperone protein that is upregulated in response to various anticancer therapies. When overexpressed, clusterin interferes with apoptotic signaling, thereby promoting cell survival and conferring broad-spectrum resistance in cancer cell lines. Custirsen (OGX-011 is a second-generation 2´-methoxyethyl modified phosphorothioate antisense oligonucleotide that inhibits expression of clusterin. This review presents the preclinical and clinical data that provided the rationale for the combination of custirsen with chemotherapy in ongoing Phase III trials. Keywords: castration-resistant prostate cancer, clusterin, custirsen, OGX-011, antisense, OGX-427, apoptosis

  18. A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens.

    Science.gov (United States)

    Jacobson, Rebecca S; Becich, Michael J; Bollag, Roni J; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayurapriyan; Tseytlin, Eugene; Weaver, JoEllen

    2015-12-15

    Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that are de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies, and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network. ©2015 American Association for Cancer Research.

  19. Association of Metronidazole with Cancer: A Potential Risk Factor or Inconsistent Deductions?

    Science.gov (United States)

    Adil, Muhammad; Iqbal, Waheed; Adnan, Fazal; Wazir, Shabnam; Khan, Imran; Khayam, Mohammad Umar; Kamal, Mohammad Amjad; Ahmad, Shafiq; Ahmad, Jawad; Khan, Ishaq N

    2018-03-29

    Metronidazole is a synthetic derivative of nitroimidazole that has been widely used for the treatment of several bacterial and protozoal parasitic infections including trichomoniasis, amoebiasis, giardiasis, liver abscess, acute ulcerative gingivitis, syphilis and tropical phagedena. In addition to its toxicity in the gastrointestinal tract and central/peripheral nervous system, metronidazole has been reported to cause mucosal imbalance by affecting the expression of mucin (Muc2 gene), which is responsible to form an insoluble mucous barrier that protects the gut lumen from microbial colonization. Since metronidazole is a nitro-group containing compound and used significantly for therapeutic purposes, scientists evaluated its carcinogenicity in different preclinical in-vitro and in-vivo studies. In addition to the preclinical in-vitro validation of DNA damage, metronidazole has been reported to induce cancer in the variety of animal models including lung cancer, malignant lymphomas, breast cancer, hepatocellular carcinoma, pituitary tumors, testicular neoplasms and uterine cancer. Several retrospective cohort studies have reported metronidazole as a potential risk factor for lung cancer (n = 771), cervical cancer (n = 2500), breast cancer (n = 2), cholangiocarcinoma (n = 1), and neuroblastoma (n = 28). So far, all the reported data have confirmed metronidazole carcinogenicity in animals; however, it is still controversial in humans. Based on previous observations, the oxidative metabolites from metronidazole metabolism are shown to have more carcinogenic effects than the parent drug itself. Since ~40% of drug metabolism is reliant on cytochromes, the inter-patient' differences in metronidazole metabolism potentially indicate the individual susceptibility to developing cancer. Due to these potent carcinogenic behaviors, use of metronidazole for animals treatment and its uses in animal food products are barred in the USA and European countries; however, its clinical

  20. Exosomal microRNAs as potential circulating biomarkers in gastrointestinal tract cancers: a systematic review protocol

    Directory of Open Access Journals (Sweden)

    Elmira Gheytanchi

    2017-11-01

    Full Text Available Abstract Background Metastasis is the most frequent type of recurrence in gastrointestinal (GI cancers, and there is an emerging potential for new diagnostic and therapeutic approaches, especially in the cases of metastatic GI carcinomas. The expression profiles of circulating exosomal microRNAs are of particular interest as novel non-invasive diagnostic and prognostic biomarkers for improved detection of GI cancers in body fluids, especially in the serum of patients with recurrent cancers. The aim of this study is to systematically review primary studies and identify the miRNA profiles of serum exosomes of GI cancers. Methods and design This systematic review will be reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA guidance. Relevant studies will be identified through a comprehensive search of the following main electronic databases: PubMed, Web of Science, Embase, Scopus, and Google Scholar, with no language restrictions (up to July 2017. Full copies of articles will be identified by a defined search strategy and will be considered for inclusion against pre-defined criteria. The quality assessment of the included studies will be performed by the Newcastle-Ottawa Scale (NOS. Data will be analyzed using Stata software V.12. Publication bias will be assessed by funnel plots, Beggs’ and Eggers’ tests. The levels of evidence for primary outcomes will be evaluated using the GRADE criteria. Discussion The analysis of circulating exosomal miRNA profiles provides attractive screening and non-invasive diagnostic tools for the majority of solid tumors including GI cancers. There is limited information regarding the relationship between serum exosomal miRNA profiles and the pathological condition of patients with different GI cancers. Since there is no specific biomarker for GI cancers, we aim to suggest a number of circulating exosomal miRNA candidates as potential multifaceted GI cancer biomarkers

  1. Ionizing radiation-induced cancers. Experimental and clinical data

    International Nuclear Information System (INIS)

    Joveniaux, Alain.

    1978-03-01

    This work attempts to give an idea of radiocarcinogenesis, both experimental and clinical. Experimentally the possibility of radio-induced cancer formation has considerable doctrinal importance since it proves without question the carcinogenetic effect of radiations, and also yields basis information on the essential constants implicated in its occurrence: need for a latency time varying with the animal species and technique used, but quite long in relation to the specific lifetime of each species; importance of a massive irradiation, more conducive to cancerisation as long as it produces no necroses liable to stop the formation of any subsequent neoplasia; finally, rarity of is occurrence. Clinically although the cause and effect relationship between treatment and cancer is sometimes difficult to establish categorically, the fact is that hundreds of particularly disturbing observations remain and from their number often emerges under well-defined circumstances, an undeniable clinical certainty. Most importantly these observation fix the criteria necessary for the possibility of a radioinduced cancer to arise, i.e: the notion of a prior irradiation; the appearance of a cancer in the irradiation area; serious tissue damage in relation with an excessive radiation dose; a long latency period between irradition and appearance of the cancer [fr

  2. Patient representatives? views on patient information in clinical cancer trials

    OpenAIRE

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-01-01

    Background Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives? views and perceptions on the written trial information used in clinical cancer trials. Methods Written patient information leaflet...

  3. Prognostic and predictive potential molecular biomarkers in colon cancer.

    Science.gov (United States)

    Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

    2011-01-01

    An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

  4. Potential of radiosensitizing agents in cancer chemo-radiotherapy

    Directory of Open Access Journals (Sweden)

    Girdhani S

    2005-01-01

    Full Text Available Potential of herbs and other plant-based formulations have been increasingly recognized in prevention and treatment of human diseases including cancer. There exist enormous prospect for screening and evaluation of herbal/plant products for developing effective radiosensitization and radioprotection relevant to nuclear research program. Investigations in our laboratory have focused on the mechanism of activity of variety of anticancer and antioxidant agents, namely, Eugenol, (EU, Ellagic acid (EA, Triphala (TPL, Tocopherol Succinate (TOS and Arachidonic acid on normal and cancer cells with view to design effective protocols in practical radioprotection and cancer radiotherapy. This paper is mainly focused on studies on cytotoxic effects on cancer cell lines. Results have shown that these agents produced radiosensitizing action involving oxidative damage, membrane alteration and damage to nucleic acid in various human cell lines. Studies were performed employing fluorescence probes and electron spin resonance methods and gel electrophoresis protocols. It has been found that cytotoxic effect was induced by initiating membrane oxidative damage and by triggering intracellular generation of reactive oxygen species (ROS by gamma radiation in combination with phytochemicals like TPL, EA and TOS in tumor cell line Ehrlich Ascites (EAC, Human cervical (HeLa and breast (MCF-7 cells. Membrane damage and ROS generation was measured by DPH and DCF-FDA fluorescent probes respectively after exposure to low to moderate doses of gamma radiation. This talk will present the cytotoxic effects of phytochemicals in combination with ionizing radiation. It is emphasized that modulation of membrane peroxidative damage and intra cellular ROS may help achieve efficient killing of cancer cells which may provide a new approach to developing effective treatment of cancer.

  5. Exogenous near-infrared fluorophores and their applications in cancer diagnosis: biological and clinical perspectives.

    Science.gov (United States)

    Zhang, Hua; Uselman, Ryan R; Yee, Douglas

    2011-05-01

    Near-infrared fluorescent (NIRF) imaging is a rapidly growing research field which has the potential to be an important imaging modality in cancer diagnosis. Various exogenous NIR fluorophores have been developed for the technique, including small molecule fluorophores and nanoparticles. NIRF imaging has been used in animal models for the detection of cancer overthe last twenty years and has in recent years been used in human clinical trials. This article describes the types and characteristics of exogenous fluorophores available for in vivo fluorescent cancer imaging. The article also discusses the progression of NIRF cancer imaging over recent years and its future challenges, from both a biological and clinical perspective. in The review also looks at its application for lymph node mapping, tumor targeting and characterization, and tumor margin definition for surgical guidance. NIRF imaging is not in routine clinical cancer practice; yet, the authors predict that techniques using NIR fluorophores for tumor margin definition and lymph node mapping will enter clinical practice in the near future. The authors also anticipate that NIRF imaging research will lead to the development of flurophores with 'high brightness' that will overcome the limited penetration of this modality and be better suited for non invasive tumor targeting.

  6. Primary Patient-Derived Cancer Cells and Their Potential for Personalized Cancer Patient Care

    Directory of Open Access Journals (Sweden)

    David P. Kodack

    2017-12-01

    Full Text Available Personalized cancer therapy is based on a patient’s tumor lineage, histopathology, expression analyses, and/or tumor DNA or RNA analysis. Here, we aim to develop an in vitro functional assay of a patient’s living cancer cells that could complement these approaches. We present methods for developing cell cultures from tumor biopsies and identify the types of samples and culture conditions associated with higher efficiency of model establishment. Toward the application of patient-derived cell cultures for personalized care, we established an immunofluorescence-based functional assay that quantifies cancer cell responses to targeted therapy in mixed cell cultures. Assaying patient-derived lung cancer cultures with this method showed promise in modeling patient response for diagnostic use. This platform should allow for the development of co-clinical trial studies to prospectively test the value of drug profiling on tumor-biopsy-derived cultures to direct patient care.

  7. Rectal prolapse as initial clinical manifestation of colon cancer.

    Science.gov (United States)

    Chen, C-W; Hsiao, C-W; Wu, C-C; Jao, S-W

    2008-04-01

    Rectal prolapse as the initial clinical manifestation of colorectal cancer is uncommon. We describe the case of a 75-year-old woman who was diagnosed as having adenocarcinoma of the sigmoid colon after presenting with complete rectal prolapse. The tumor caused rectosigmoid intussusception and then it prolapsed out through the anus. She underwent rectosigmoidectomy and rectopexy. The postoperative course was uneventful. The relationship between colorectal cancer and rectal prolapse has not been clearly established. This case report describes an unusual presentation of colorectal cancer. It suggests that rectal prolapse can present as the initial symptom of colorectal cancer and may also be a presenting feature of the occult intra-abdominal pathology. The importance of adequate investigation such as colonoscopy should be emphasized in patients who develop a new onset of rectal prolapse.

  8. Clinical significance of lymph node metastasis in gastric cancer

    Science.gov (United States)

    Deng, Jing-Yu; Liang, Han

    2014-01-01

    Gastric cancer, one of the most common malignancies in the world, frequently reveals lymph node, peritoneum, and liver metastases. Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection, which results in poor prognosis. Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer. Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials, it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year follow-up study. Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide, but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis. It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer. Besides, the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer. PMID:24744586

  9. Accuracy of family history of cancer : clinical genetic implications

    NARCIS (Netherlands)

    Sijmons, RH; Boonstra, AE; Reefhuis, J; Hordijk-Hos, JM; de Walle, HEK; Oosterwijk, JC; Cornel, MC

    Family medical history is the cornerstone of clinical genetic diagnosis and management in cases of familial cancer. The soundness of medical decisions can be compromised if reports by the family on affected relatives are inaccurate. Although very time consuming, family medical histories are

  10. B metastases in breast cancer. Clinical, diagnostic and therapeutic aspects

    International Nuclear Information System (INIS)

    Ferrigno, R.; Petitto, J.V.

    1989-01-01

    Osseous metastases are the most frequent sites of dissemination in breast cancer and diminish the quality of patients life, being one of the most serious problems of the disease. The authors discuss the clinical, diagnosis and therapeutic aspects, based on their own experience and data from the literature. (author)

  11. Cancer of unknown primitive metastatic. About two clinical cases

    International Nuclear Information System (INIS)

    Cawen, L; Cordoba, A.

    2010-01-01

    This work is about the two clinical cases about the unknown primitive metastatic cancer. The main techniques used for the diagnosis, treatment and monitoring of different s carcinomas are: Electronic microscope, molecular biology and genetics, especially histopathological study, topographic survey, ultrasound, radiography, chemotherapy, radiotherapy

  12. Viruses cancer - an overview | Buhari | African Journal of Clinical ...

    African Journals Online (AJOL)

    ... by the immune system. The mechanism o f transformation o f a normal cell into a neoplastic cell can either be direct or indirect. Better understanding o f the role o f viruses in human cancer will have therapeutic implication as control can be instituted. African Journal of Clinical and Experimental Microbiology Vol. 7(2) 2006: ...

  13. Cancer Cell Adhesion and Metastasis: Selectins, Integrins, and the Inhibitory Potential of Heparins

    Directory of Open Access Journals (Sweden)

    Gerd Bendas

    2012-01-01

    Full Text Available Cell adhesion molecules play a significant role in cancer progression and metastasis. Cell-cell interactions of cancer cells with endothelium determine the metastatic spread. In addition, direct tumor cell interactions with platelets, leukocytes, and soluble components significantly contribute to cancer cell adhesion, extravasation, and the establishment of metastatic lesions. Clinical evidence indicates that heparin, commonly used for treatment of thromboembolic events in cancer patients, is beneficial for their survival. Preclinical studies confirm that heparin possesses antimetastatic activities that lead to attenuation of metastasis in various animal models. Heparin contains several biological activities that may affect several steps in metastatic cascade. Here we focus on the role of cellular adhesion receptors in the metastatic cascade and discuss evidence for heparin as an inhibitor of cell adhesion. While P- and L-selectin facilitation of cellular contacts during hematogenous metastasis is being accepted as a potential target of heparin, here we propose that heparin may also interfere with integrin activity and thereby affect cancer progression. This review summarizes recent findings about potential mechanisms of tumor cell interactions in the vasculature and antimetastatic activities of heparin.

  14. Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma.

    Science.gov (United States)

    Karagonlar, Zeynep F; Korhan, Peyda; Atabey, Neşe

    2015-11-01

    Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. © 2015 Wiley Periodicals, Inc.

  15. The Swedish Family-Cancer Database: Update, Application to Colorectal Cancer and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Hemminki Kari

    2005-01-01

    Full Text Available Abstract The Swedish Family-Cancer Database has been used for almost 10 years in the study of familial risks at all common sites. In the present paper we describe some main features of version VI of this Database, assembled in 2004. This update included all Swedes born in 1932 and later (offspring with their biological parents, a total of 10.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from 1958-2002, including over 1.2 million first and multiple primary cancers and in situ tumours. Compared to previous versions, only 6.0% of deceased offspring with a cancer diagnosis lack any parental information. We show one application of the Database in the study of familial risks in colorectal adenocarcinoma, with defined age-group and anatomic site specific analyses. Familial standardized incidence ratios (SIRs were determined for offspring when parents or sibling were diagnosed with colon or rectal cancer. As a novel finding it was shown that risks for siblings were higher than those for offspring of affected parents. The excess risk was limited to colon cancer and particularly to right-sided colon cancer. The SIRs for colon cancer in age matched populations were 2.58 when parents were probands and 3.81 when siblings were probands; for right-sided colon cancer the SIRs were 3.66 and 7.53, respectively. Thus the familial excess (SIR-1.00 was more than two fold higher for right-sided colon cancer. Colon and rectal cancers appeared to be distinguished between high-penetrant and recessive conditions that only affect the colon, whereas low-penetrant familial effects are shared by the two sites. Epidemiological studies can be used to generate clinical estimates for familial risk, conditioned on numbers of affected family members and their ages of onset. Useful risk estimates have been developed for familial breast and prostate cancers. Reliable risk estimates for other cancers should also be seriously considered for

  16. Salmonella-mediated cancer therapy: Roles and potential

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Vu Hong [Dept. of Experimental TherapeuticsBeckman Research Institute of City of Hope, Duarte (United States); Min, Jung Joon [Dept. of Nuclear MedicineChonnam National University Medical School, Gwangju (Korea, Republic of)

    2017-06-15

    The use of bacteria for cancer therapy, which was proposed many years ago, was not recognized as a potential therapeutic strategy until recently. Technological advances and updated knowledge have enabled the genetic engineering of bacteria for their safe and effective application in the treatment of cancer. The efficacy of radiotherapy depends mainly on tissue oxygen levels, and low oxygen concentrations in necrotic and hypoxic regions are a common cause of treatment failure. In addition, the distribution of a drug is important for the therapeutic effect of chemotherapy, and the poor vasculature in tumors impairs drug delivery, limiting the efficacy of a drug, especially in necrotic and hypoxic regions. Bacteria-mediated cancer therapy (BMCT) relies on facultative anaerobes that can survive in well or poorly oxygenated regions, and it therefore improves the therapeutic efficacy drug distribution throughout the tumor mass. Since the mid-1990s, the number of published bacterial therapy papers has increased rapidly, with a doubling time of 2.5 years in which the use of Salmonella increased significantly. BMCT is being reevaluated to overcome some of the drawbacks of conventional therapies. This review focuses on Salmonella-mediated cancer therapy as the most widely used type of BMCT.{sub 2}.

  17. Re: Engineered Nanoparticles Induce Cell Apoptosis: Potential for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Fehmi Narter

    2016-09-01

    Full Text Available Engineered nanoparticles (ENPs have been widely applied in industry, biology and medicine recently (i.e. clothes, sunscreens, cosmetics, foods, diagnostic medicine, imaging and drug delivery. There are many kinds of manufactured nanomaterial products including TiO2, ZnO, CeO2, Fe2O3, and CuO (as metal oxide nanoparticles as well as gold, silver, platinum and palladium (as metal nanoparticles, and other carbon-based ENP’s such as carbon nanotububes and quantum dots. ENPs with their sizes no larger than 100 nm are able to enter the human body and accumulate in organs and cause toxic effects. In many researches, ENP effects on the cancer cells of different organs with related cell apoptosis were noted (AgNP, nano-Cr2O3, Au-Fe2O3 NPs, nano-TiO2, nano-HAP, nano-Se, MoO3 nanoplate, Realgar nanoparticles. ENPs, with their unique properties, such as surface charge, particle size, composition and surface modification with tissue recognition ligands or antibodies, has been increasingly explored as a tool to carry small molecular weight drugs as well as macromolecules for cancer therapy, thus generating the new concept “nanocarrier”. Direct induction of cell apoptosis by ENPs provides an opportunity for cancer treatment. In the century of nanomedicine that depends on development of the nanotechnology, ENPs have a great potential for application in cancer treatment with minimal side effects.

  18. Salmonella-mediated cancer therapy: Roles and potential

    International Nuclear Information System (INIS)

    Nguyen, Vu Hong; Min, Jung Joon

    2017-01-01

    The use of bacteria for cancer therapy, which was proposed many years ago, was not recognized as a potential therapeutic strategy until recently. Technological advances and updated knowledge have enabled the genetic engineering of bacteria for their safe and effective application in the treatment of cancer. The efficacy of radiotherapy depends mainly on tissue oxygen levels, and low oxygen concentrations in necrotic and hypoxic regions are a common cause of treatment failure. In addition, the distribution of a drug is important for the therapeutic effect of chemotherapy, and the poor vasculature in tumors impairs drug delivery, limiting the efficacy of a drug, especially in necrotic and hypoxic regions. Bacteria-mediated cancer therapy (BMCT) relies on facultative anaerobes that can survive in well or poorly oxygenated regions, and it therefore improves the therapeutic efficacy drug distribution throughout the tumor mass. Since the mid-1990s, the number of published bacterial therapy papers has increased rapidly, with a doubling time of 2.5 years in which the use of Salmonella increased significantly. BMCT is being reevaluated to overcome some of the drawbacks of conventional therapies. This review focuses on Salmonella-mediated cancer therapy as the most widely used type of BMCT._2

  19. Cancer chemopreventive potential of apples, apple juice, and apple components.

    Science.gov (United States)

    Gerhauser, Clarissa

    2008-10-01

    Apples ( MALUS sp., Rosaceae) are a rich source of nutrient as well as non-nutrient components and contain high levels of polyphenols and other phytochemicals. Main structural classes of apple constituents include hydroxycinnamic acids, dihydrochalcones, flavonols (quercetin glycosides), catechins and oligomeric procyanidins, as well as triterpenoids in apple peel and anthocyanins in red apples. Several lines of evidence suggest that apples and apple products possess a wide range of biological activities which may contribute to health beneficial effects against cardiovascular disease, asthma and pulmonary dysfunction, diabetes, obesity, and cancer (reviewed by Boyer and Liu, Nutr J 2004). The present review will summarize the current knowledge on potential cancer preventive effects of apples, apple juice and apple extracts (jointly designated as apple products). In brief, apple extracts and components, especially oligomeric procyanidins, have been shown to influence multiple mechanisms relevant for cancer prevention in IN VITRO studies. These include antimutagenic activity, modulation of carcinogen metabolism, antioxidant activity, anti-inflammatory mechanisms, modulation of signal transduction pathways, antiproliferative and apoptosis-inducing activity, as well as novel mechanisms on epigenetic events and innate immunity. Apple products have been shown to prevent skin, mammary and colon carcinogenesis in animal models. Epidemiological observations indicate that regular consumption of one or more apples a day may reduce the risk for lung and colon cancer.

  20. Clinical proteomics: Applications for prostate cancer biomarker discovery and detection.

    Science.gov (United States)

    Petricoin, Emanuel F; Ornstein, David K; Liotta, Lance A

    2004-01-01

    The science of proteomics comprises much more than simply generating lists of proteins that change in expression as a cause of or consequence of pathophysiology. The goal of proteomics should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. Serum proteomic pattern diagnostics is a new type of proteomic concept in which patterns of ion signatures generated from high dimensional mass spectrometry data are used as diagnostic classifiers. This recent approach has exciting potential for clinical utility of diagnostic patterns because low molecular weight metabolites, peptides, and protein fragments may have higher accuracy than traditional biomarkers of cancer detection. Intriguingly, we now have discovered that this diagnostic information exists in a bound state, complexed with circulating highly abundant carrier proteins. These diagnostic fragments may one day be harvested by circulating nanoparticles, designed to absorb, enrich, and amplify the repertoire of diagnostic biomarkers generated-even at the critical, initial stages of carcinogenesis. Copyright 2004 Elsevier Inc.

  1. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    International Nuclear Information System (INIS)

    Rizwani, Wasia; Allen, Amanda E.; Trevino, Jose G.

    2015-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer

  2. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    Energy Technology Data Exchange (ETDEWEB)

    Rizwani, Wasia [Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007 (India); Allen, Amanda E.; Trevino, Jose G., E-mail: Jose.Trevino@surgery.ufl.edu [Department of Surgery, University of Florida, 1600 SW Archer Rd, Rm 6175, P.O. Box 100109, Gainesville, FL 32610 (United States)

    2015-09-03

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF), the sole ligand for c-MET (mesenchymal-epithelial transition), an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.

  3. Hepatocyte Growth Factor from a Clinical Perspective: A Pancreatic Cancer Challenge

    Directory of Open Access Journals (Sweden)

    Wasia Rizwani

    2015-09-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and incidence rates are rising. Both detection and treatment options for pancreatic cancer are limited, providing a less than 5% five-year survival advantage. The need for new biomarkers for early detection and treatment of pancreatic cancer demands the efficient translation of bench knowledge to provide clinical benefit. One source of therapeutic resistance is the pancreatic tumor microenvironment, which is characterized by desmoplasia and hypoxia making it less conducive to current therapies. A major factor regulating desmoplasia and subsequently promoting chemoresistance in pancreatic cancer is hepatocyte growth factor (HGF, the sole ligand for c-MET (mesenchymal-epithelial transition, an epithelial tyrosine kinase receptor. Binding of HGF to c-MET leads to receptor dimerization and autophosphorylation resulting in the activation of multiple cellular processes that support cancer progression. Inhibiting activation of c-MET in cancer cells, in combination with other approaches for reducing desmoplasia in the tumor microenvironment, might significantly improve the success of chemotherapy. Therefore, HGF makes a potent novel target for developing therapeutic strategies in combination with existing drugs for treating pancreatic adenocarcinoma. This review provides a comprehensive analysis of HGF and its promising potential as a chemotherapeutic target for pancreatic cancer.

  4. Pre-Clinical and Clinical Investigation of the Impact of Obesity on Ovarian Cancer Pathogenesis

    Science.gov (United States)

    2015-12-01

    clinical cancer drug discovery , including 10 years as a Research Assistant Professor in the Department of Surgery at Duke University Medical Center...cancer therapy. Nature chemical biology . 2015;11(1):9-15. Epub 2014/12/18. doi: 10.1038/nchembio.1712. PubMed PMID: 25517383; PubMed Central PMCID...Assistant Professor of Nutrition, a member of the Nutrition Obesity Research Center, Center for Gastrointestinal Biology and Disease, McCallister Heart

  5. Serum Testosterone Kinetics After Brachytherapy for Clinically Localized Prostate Cancer

    International Nuclear Information System (INIS)

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan H.; Allen, Zachariah A.; Wallner, Kent E.

    2012-01-01

    Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase ≥25%, 23% of men experienced a decrease ≥25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response

  6. Serum Testosterone Kinetics After Brachytherapy for Clinically Localized Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Taira, Al V. [Western Radiation Oncology, Mountain View, CA (United States); Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, WV (United States); Galbreath, Robert W.; Butler, Wayne M.; Lief, Jonathan H.; Allen, Zachariah A. [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, WV (United States); Wallner, Kent E. [Puget Sound Healthcare Corporation Group Health Cooperative, University of Washington, Seattle, WA (United States)

    2012-01-01

    Purpose: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. Methods and Materials: Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike. Results: There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase {>=}25%, 23% of men experienced a decrease {>=}25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p < 0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21). Conclusion: Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response

  7. Multidrug Resistance in Breast Cancer: From In Vitro Models to Clinical Studies

    International Nuclear Information System (INIS)

    Wind, N.S.; Holen, I.

    2011-01-01

    The development of multidrug resistance (MDR) and subsequent relapse on therapy is a widespread problem in breast cancer, but our understanding of the underlying molecular mechanisms is incomplete. Numerous studies have aimed to establish the role of drug transporter pumps in MDR and to link their expression to response to chemotherapy. The ATP-binding cassette (ABC) transporters are central to breast cancer MDR, and increases in ABC expression levels have been shown to correlate with decreases in response to various chemotherapy drugs and a reduction in overall survival. But as there is a large degree of redundancy between different ABC transporters, this correlation has not been seen in all studies. This paper provides an introduction to the key molecules associated with breast cancer MDR and summarises evidence of their potential roles reported from model systems and clinical studies. We provide possible explanations for why despite several decades of research, the precise role of ABC transporters in breast cancer MDR remains elusive

  8. The biology, function and clinical implications of exosomes in lung cancer.

    Science.gov (United States)

    Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong

    2017-10-28

    Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The role of pancreatic cancer-derived exosomes in cancer progress and their potential application as biomarkers.

    Science.gov (United States)

    Jin, H; Wu, Y; Tan, X

    2017-08-01

    Pancreatic cancer is one of the most deadly cancers, with dismal prognosis due to its poor early detection rate and high metastatic rate. Thus, elucidation of the molecular mechanisms accounting for its metastasis and discovery of competent biomarkers is required. Exosomes are multivesicular body-derived small extracellular vesicles released by various cell types that serve as important message carriers during intercellular communication. They are also known to play critical roles during cancer-genesis, cancer-related immune reactions, and metastasis. They also possess promising potential as novel biomarkers for cancer early detection. Therefore, extensive studies on pancreatic cancer-derived exosomes are currently being performed because they hold the promising potential of elevating the overall survival rate of patients with pancreatic cancer. In the present review, we focus on the role of exosomes in pancreatic cancer-related immune reactions, metastasis, and complications, and on their potential application as pancreatic cancer biomarkers.

  10. A clinical analysis of maxillary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Haruhiko; Amatsu, Mutsuo [Kobe Univ. (Japan). School of Medicine

    2001-03-01

    Forty-five patients with maxillary cancer were treated at Kobe University Hospital during the years 1990-1999. We analyzed 35 of there cases that had undergone curative treatment. They were classified by T the classification (UICC, 1997) as two cases with T1, seven with T2, eight with T3, and 18 with T4. The two patients with T1 were treated with radiation alone, and four of the other patients were treated with surgery alone. Eight patients were given irradiation, intra-arterial infusion chemotherapy, and curettage of necotic tumor (combined therapy group); 10 received preoperative intra-arterial infusion chemotherapy, irradiation, and maxillectomy or extended maxillectomy (preoperative treatment group), and 11 underwent extended surgery and postoperative chemotherapy and/or irradiation (postoperative treatment group). The five-year survival rates were 65.1% for all patients, 83.3% for T3 cases, and 41.6% for T4 cases. The five-year survival rates were 48.6% for the combined therapy group, 80% for the preoperative treatment group, and 54.6% for the postoperative treatment group. Although the four cases with T2 who underwent combined therapy all remained disease-free, all three cases with T3 and T4 died of the disease. On the other hand, six of the seven patients with T3 and T4 in the preoperative treatment group remained disease-free. Based on these results, we believe that maxillectomy or extended maxillectomy following intra-arterial chemotherapy and irradiation is the most effective treatment modality for T3 and T4 cases. (author)

  11. A clinical analysis of maxillary cancer

    International Nuclear Information System (INIS)

    Ishida, Haruhiko; Amatsu, Mutsuo

    2001-01-01

    Forty-five patients with maxillary cancer were treated at Kobe University Hospital during the years 1990-1999. We analyzed 35 of there cases that had undergone curative treatment. They were classified by T the classification (UICC, 1997) as two cases with T1, seven with T2, eight with T3, and 18 with T4. The two patients with T1 were treated with radiation alone, and four of the other patients were treated with surgery alone. Eight patients were given irradiation, intra-arterial infusion chemotherapy, and curettage of necotic tumor (combined therapy group); 10 received preoperative intra-arterial infusion chemotherapy, irradiation, and maxillectomy or extended maxillectomy (preoperative treatment group), and 11 underwent extended surgery and postoperative chemotherapy and/or irradiation (postoperative treatment group). The five-year survival rates were 65.1% for all patients, 83.3% for T3 cases, and 41.6% for T4 cases. The five-year survival rates were 48.6% for the combined therapy group, 80% for the preoperative treatment group, and 54.6% for the postoperative treatment group. Although the four cases with T2 who underwent combined therapy all remained disease-free, all three cases with T3 and T4 died of the disease. On the other hand, six of the seven patients with T3 and T4 in the preoperative treatment group remained disease-free. Based on these results, we believe that maxillectomy or extended maxillectomy following intra-arterial chemotherapy and irradiation is the most effective treatment modality for T3 and T4 cases. (author)

  12. Increased gut permeability in cancer cachexia: mechanisms and clinical relevance.

    Science.gov (United States)

    Bindels, Laure B; Neyrinck, Audrey M; Loumaye, Audrey; Catry, Emilie; Walgrave, Hannah; Cherbuy, Claire; Leclercq, Sophie; Van Hul, Matthias; Plovier, Hubert; Pachikian, Barbara; Bermúdez-Humarán, Luis G; Langella, Philippe; Cani, Patrice D; Thissen, Jean-Paul; Delzenne, Nathalie M

    2018-04-06

    Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium ( Faecalibacterium prausnitzii ) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients. Altogether, our data highlight profound alterations of the intestinal homeostasis in cancer cachexia occurring independently of any chemotherapy and food intake reduction, with potential relevance in humans. In addition, we point out the lipopolysaccharide-binding protein as a new biomarker of cancer cachexia related to gut dysbiosis.

  13. 7T: Physics, safety, and potential clinical applications.

    Science.gov (United States)

    Kraff, Oliver; Quick, Harald H

    2017-12-01

    With more than 60 installed magnetic resonance imaging (MRI) systems worldwide operating at a magnetic field strength of 7T or higher, ultrahigh-field (UHF) MRI has been established as a platform for clinically oriented research in recent years. Profound technical and methodological developments have helped overcome the inherent physical challenges of UHF radiofrequency (RF) signal homogenization in the human body. The ongoing development of dedicated RF coil arrays was pivotal in realizing UHF body MRI, beyond mere brain imaging applications. Another precondition to clinical application of 7T MRI is the safety testing of implants and the establishment of safety concepts. Against this backdrop, 7T MRI and MR spectroscopy (MRS) recently have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. This article provides an overview of the immanent physical challenges of 7T UHF MRI and discusses recent technical solutions and safety concepts. Furthermore, recent clinically oriented studies are highlighted that span a broad application spectrum from 7T UHF brain to body MRI. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1573-1589. © 2017 International Society for Magnetic Resonance in Medicine.

  14. Nano medicine in Action: An Overview of Cancer Nano medicine on the Market and in Clinical Trials

    International Nuclear Information System (INIS)

    Wang, R.; Billone, P.S.; Mullett, W.M.

    2013-01-01

    Nano medicine, defined as the application of nano technology in the medical field, has the potential to significantly change the course of diagnostics and treatment of life-threatening diseases, such as cancer. In comparison with traditional cancer diagnostics and therapy, cancer nano medicine provides sensitive cancer detection and/or enhances treatment efficacy with significantly minimized adverse effects associated with standard therapeutics. Cancer nano medicine has been increasingly applied in areas including nano drug delivery systems, nano pharmaceuticals, and nano analytical contrast reagents in laboratory and animal model research. In recent years, the successful introduction of several novel nano medicine products into clinical trials and even onto the commercial market has shown successful outcomes of fundamental research into clinics. This paper is intended to examine several nano medicines for cancer therapeutics and/or diagnostics-related applications, to analyze the trend of nano medicine development, future opportunities, and challenges of this fast-growing area.

  15. Patient representatives' views on patient information in clinical cancer trials

    DEFF Research Database (Denmark)

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-01-01

    of future simplified and more attractive informed consent forms. CONCLUSIONS: The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language......BACKGROUND: Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed...... consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. METHODS: Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I...

  16. Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations

    Science.gov (United States)

    Tosoian, Jeffrey J.; Gorin, Michael A.; Ross, Ashley E.; Pienta, Kenneth J.; Tran, Phuoc T.; Schaeffer, Edward M.

    2018-01-01

    The oligometastatic state has been proposed as an intermediate stage of cancer spread between localized disease and widespread metastases. With improvements in diagnostic modalities such as functional imaging, oligometastatic prostate cancer is being diagnosed with greater frequency than ever before. Furthermore, the paradigm for treatment of advanced prostate cancers is shifting toward a more aggressive approach. Many questions surround the understanding of the process and consequences of oligometastasis, meaning that the contemporary literature offers a wide variety of definitions of oligometastatic prostate cancer. Until genomic data exist to provide a biological component to the definition of oligometastatic disease, a clinical diagnosis made on the basis of up to five extrapelvic lesions is reasonable for use. Retrospective studies suggest that interventions such as radical prostatectomy and local or metastasis-directed radiotherapy can be performed in the metastatic setting with minimal risk of toxic effects. These therapies seem to decrease the need for subsequent palliative interventions, but insufficient data are available to draw reliable conclusions regarding their effect on survival. Thus, a protocol for clinicians to manage the patient presenting with oligometastatic prostate cancer would be a useful clinical tool. PMID:27725639

  17. Black tea: Phytochemicals, cancer chemoprevention, and clinical studies.

    Science.gov (United States)

    Singh, Brahma N; Rawat, A K S; Bhagat, R M; Singh, B R

    2017-05-03

    Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-κB, Bcl-xL, caspases, p53, FOXO1, TNFα, PARP, and MAPK, which may be the basis of how dose of black tea prevents and cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea to reveal its anti-cancer effect.

  18. Emerging therapeutic potential of graviola and its constituents in cancers.

    Science.gov (United States)

    Qazi, Asif Khurshid; Siddiqui, Jawed A; Jahan, Rahat; Chaudhary, Sanjib; Walker, Larry A; Sayed, Zafar; Jones, Dwight T; Batra, Surinder K; Macha, Muzafar A

    2018-04-05

    Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.

  19. Thymoquinone as a Potential Adjuvant Therapy for Cancer Treatment: Evidence from Preclinical Studies

    Directory of Open Access Journals (Sweden)

    A.G.M. Mostofa

    2017-06-01

    Full Text Available Thymoquinone (TQ, the main bioactive component of Nigella sativa, has been found to exhibit anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteracts carcinogenesis, malignant growth, invasion, migration, and angiogenesis. Moreover, TQ can specifically sensitize tumor cells toward conventional cancer treatments (e.g., radiotherapy, chemotherapy, and immunotherapy and simultaneously minimize therapy-associated toxic effects in normal cells. In this review, we summarized the adjuvant potential of TQ as observed in various in vitro and in vivo animal models and discussed the pharmacological properties of TQ to rationalize its supplementary role in potentiating the efficacy of standard therapeutic modalities namely surgery, radiotherapy, chemotherapy, and immunotherapy. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical levels to delineate its implied utility as a novel complementary adjuvant therapy for cancer treatment.

  20. Epigenome engineering in cancer: fairytale or a realistic path to the clinic?

    Directory of Open Access Journals (Sweden)

    Fahimeh eFalahi

    2015-02-01

    Full Text Available Epigenetic modifications such as histone post-transcriptional modifications and DNA methylation organize the DNA in the nucleus of eukaryotic cells and are critical for the spatio-temporal regulation of gene expression. These epigenetic modifications are reversible and precisely regulated by epigenetic enzymes. In addition to genetic mutations, epigenetic modifications are highly disrupted in cancer relative to normal tissues. Many epigenetic alterations (epi-mutations are associated with aberrations in the expression and/or activity of epigenetic enzymes. Thus, epigenetic regulators have emerged as prime targets for cancer therapy. Currently, several inhibitors of epigenetic enzymes (epi-drugs have been approved for use in the clinic to treat cancer patients with hematological malignancies. However, one potential disadvantage of epi-drugs is their lack of locus-selective specificity, which may result in the over-expression of undesirable parts of the genome. The emerging and rapidly growing field of epigenome engineering has opened new grounds for improving epigenetic therapy in view of reducing the genome-wide off-target effects of the treatment. In the current review, we will first describe the language of epigenetic modifications and their involvement in cancer. Next, we will overview the current strategies for engineering of artificial DNA binding domains in order to manipulate and ultimately normalize the aberrant landscape of the cancer epigenome (epigenome engineering. Lastly, the potential clinical applications of these emerging genome-engineering approaches will be discussed.

  1. Midwives at youth clinics attitude to HPV vaccination and their role in cervical cancer prevention.

    Science.gov (United States)

    Oscarsson, Marie G; Dahlberg, Annica; Tydén, Tanja

    2011-11-01

    To explore youth clinic midwives role in cervical cancer prevention and their attitude to HPV vaccination. Individual interviews with 13 midwives working at youth clinics in Sweden. The interviews were recorded, transcribed, and analysed by qualitative content analysis. Three themes were identified in the qualitative content analysis: "Cervical cancer prevention not a prioritised area", "Ambivalence to the HPV vaccine", and "Gender and socioeconomic controversies". Few midwives talked spontaneously about cervical cancer prevention. The responsibility for providing information about HPV vaccination was considered as primarily that of school health nurses and parents. Midwives were positive about the HPV vaccination, but recognised certain risks, such as its potential negative impact on cervical cancer screening and increased sexual risk taking. The midwives expressed concerns with medical risks, such as side effects and unknown long-term effects of the HPV vaccine. The midwives in the study had ethical concerns that boys were not included in the program and not all families had the financial resources to vaccinate their children. Thus, weak socioeconomic groups might be excluded. The midwives considered cervical cancer prevention as important, but did not integrate information on the HPV vaccine into their routine work, mainly because young people visiting youth clinics had had their sexual debut and they were concerned about the medical risks and that the vaccine was too expensive. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations.

    Science.gov (United States)

    Tamborero, David; Rubio-Perez, Carlota; Deu-Pons, Jordi; Schroeder, Michael P; Vivancos, Ana; Rovira, Ana; Tusquets, Ignasi; Albanell, Joan; Rodon, Jordi; Tabernero, Josep; de Torres, Carmen; Dienstmann, Rodrigo; Gonzalez-Perez, Abel; Lopez-Bigas, Nuria

    2018-03-28

    While tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Here we present the Cancer Genome Interpreter, a versatile platform that automates the interpretation of newly sequenced cancer genomes, annotating the potential of alterations detected in tumors to act as drivers and their possible effect on treatment response. The results are organized in different levels of evidence according to current knowledge, which we envision can support a broad range of oncology use cases. The resource is publicly available at http://www.cancergenomeinterpreter.org .

  3. Clinical librarian support for rapid review of clinical utility of cancer molecular biomarkers.

    Science.gov (United States)

    Geng, Yimin; Fowler, Clara S; Fulton, Stephanie

    2015-01-01

    The clinical librarian used a restricted literature searching and quality-filtering approach to provide relevant clinical evidence for the use of cancer molecular biomarkers by institutional policy makers and clinicians in the rapid review process. The librarian-provided evidence was compared with the cited references in the institutional molecular biomarker algorithm. The overall incorporation rate of the librarian-provided references into the algorithm was above 80%. This study suggests the usefulness of clinical librarian expertise for clinical practice. The searching and filtering methods for high-level evidence can be adopted by information professionals who are involved in the rapid literature review.

  4. Plasma membrane proteomics of human breast cancer cell lines identifies potential targets for breast cancer diagnosis and treatment.

    Directory of Open Access Journals (Sweden)

    Yvonne S Ziegler

    Full Text Available The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.

  5. VIDEO: Dr. Henry Rodriguez - Proteogenomics in Cancer Medicine | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Dr. Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research (OCCPR) at NCI, speaks with ecancer television at WIN 2017 about the translation of the proteins expressed in a patient's tumor into a map for druggable targets. By combining genomic and proteomic information (proteogenomics), leading scientists are gaining new insights into ways to detect and treat cancer due to a more complete and unified understanding of complex biological processes.

  6. Breath acetone as a potential marker in clinical practice.

    Science.gov (United States)

    Ruzsányi, Veronika; Péter Kalapos, Miklós

    2017-06-01

    In recent decades, two facts have changed the opinion of researchers about the function of acetone in humans. Firstly, it has turned out that acetone cannot be regarded as simply a waste product of metabolism, because there are several pathways in which acetone is produced or broken down. Secondly, methods have emerged making possible its detection in exhaled breath, thereby offering an attractive alternative to investigation of blood and urine samples. From a clinical point of view the measurement of breath acetone levels is important, but there are limitations to its wide application. These limitations can be divided into two classes, technical and biological limits. The technical limits include the storage of samples, detection threshold, standardization of clinical settings, and the price of instruments. When considering the biological ranges of acetone, personal factors such as race, age, gender, weight, food consumption, medication, illicit drugs, and even profession/class have to be taken into account to use concentration information for disorders. In some diseases such as diabetes mellitus and lung cancer, as well as in nutrition-related behavior such as starvation and ketogenic diet, breath acetone has been extensively examined. At the same time, there is a lack of investigations in other cases in which ketosis is also evident, such as in alcoholism or an inborn error of metabolism. In summary, the detection of acetone in exhaled breath is a useful and promising tool for diagnosis and it can be used as a marker to follow the effectiveness of treatments in some disorders. However, further endeavors are needed for clarification of the exact distribution of acetone in different body compartments and evaluation of its complex role in humans, especially in those cases in which a ketotic state also occurs.

  7. Evaluation of eligibility and recruitment in breast cancer clinical trials.

    Science.gov (United States)

    Lemieux, Julie; Forget, Geneviève; Brochu, Olyvia; Provencher, Louise; Cantin, Guy; Desbiens, Christine; Doyle, Catherine; Poirier, Brigitte; Camden, Stéphanie; Durocher, Martin

    2014-08-01

    Objectives of the study were to measure recruitment rates in clinical trials and to identify patients, physicians or trials characteristics associated with higher recruitment rates. Among patients who had a clinical trial available for their cancer, 83.5% (345/413) met the eligibility criteria to at least one clinical trial. At least one trial was proposed to 33.1% (113/341) of the eligible patients and 19.7% (68/345) were recruited. Overall recruitment was 16.5% (68/413). In multivariate analyses, trial proposal and enrollment were lower for elderly patients and higher in high cancer stages. Trials from pharmaceutical industry had higher recruitment rates and trials testing hormonal therapy enrolled more patients. Breast cancer patients' accrual to a clinical trial could be improved by trying to systematically identify all eligible patients and propose a trial to those eligible and to whom the treatment is planned to be equivalent to the standard arm of the trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Macrophage migration inhibitory factor as a potential prognostic factor in gastric cancer

    Science.gov (United States)

    He, Long-Jun; Xie, Dan; Hu, Pin-Jin; Liao, Yi-Ji; Deng, Hai-Xia; Kung, Hsiang-Fu; Zhu, Sen-Lin

    2015-01-01

    AIM: To investigate macrophage migration inhibitory factor (MIF) expression and its clinical relevance in gastric cancer, and effects of MIF knockdown on proliferation of gastric cancer cells. METHODS: Tissue microarray containing 117 samples of gastric cancer and adjacent non-cancer normal tissues was studied for MIF expression by immunohistochemistry (IHC) semiquantitatively, and the association of MIF expression with clinical parameters was analyzed. MIF expression in gastric cancer cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Two pairs of siRNA targeting the MIF gene (MIF si-1 and MIF si-2) and one pair of scrambled siRNA as a negative control (NC) were designed and chemically synthesized. All siRNAs were transiently transfected in AGS cells with OligofectamineTM to knock down the MIF expression, with the NC group and mock group (OligofectamineTM alone) as controls. At 24, 48, and 72 h after transfection, MIF mRNA was analyzed by RT-PCR, and MIF and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot. The proliferative rate of AGS cells was assessed by methylthiazolyl tetrazolium (MTT) assay and colony forming assay. RESULTS: The tissue microarray was informative for IHC staining, in which the MIF expression in gastric cancer tissues was higher than that in adjacent non-cancer normal tissues (P < 0.001), and high level of MIF was related to poor tumor differentiation, advanced T stage, advanced tumor stage, lymph node metastasis, and poor patient survival (P < 0.05 for all). After siRNA transfection, MIF mRNA was measured by real-time PCR, and MIF protein and PCNA were assessed by Western blot analysis. We found that compared to the NC group and mock group, MIF expression was knocked down successfully in gastric cancer cells, and PCNA expression was downregulated with MIF knockdown as well. The cell counts and the doubling times were assayed by MTT 4 d after transfection, and

  9. Potentially malignant disorders of the oral cavity: a clinical study.

    Science.gov (United States)

    Shukla, Anirudh

    2014-01-01

    Oral cancers in India, unlike in the West are the most common cancers encountered, be it a primary or a tertiary referral practice. This makes the study and management of these cancers an important issue especially for the otolaryngologist. It is well known that the most common variant of oral cancers is the squamous cell carcinoma. Also the etiology is well established; with tobacco use in both smoking and smokeless forms, alcohol, betel nut and recently the Human Papilloma virus infection being implicated. Certain conditions which definitely increase the probability of getting oral cancers are known and this study aims in revisiting these aspects of pre-malignancy. The progression from a pre-cancerous lesion/condition to frank cancer is well established across many studies and many specialties. Also timely recognizing these pre-cancerous conditions and administration of proper treatment will greatly help in reducing the morbidity and mortality from subsequent much advanced and dangerous oral cancer. Keeping these facts in mind this study was planned to study the established pre-cancerous lesions which are known to progress to oral cancers.

  10. Conducting qualitative research within Clinical Trials Units: avoiding potential pitfalls.

    Science.gov (United States)

    Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy

    2014-07-01

    The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.

  11. Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

    Science.gov (United States)

    Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

    2016-12-01

    Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

  12. Early diagnostic potential of APC hypermethylation in esophageal cancer

    Directory of Open Access Journals (Sweden)

    Wang B

    2018-02-01

    Full Text Available Bujiang Wang,1 Haojun Song,1 Haizhong Jiang,1 Yangbo Fu,1 Xiaoyun Ding,1 Chongchang Zhou2 1Department of Gastroenterology, Laboratory of Digestive Diseases, Ningbo First Hospital, Ningbo, 2Department of Otorhinolaryngology Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China Background: The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC. However, the association between APC methylation and the initiation and progression of EC is poorly understood. Purpose and methods: The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett’s esophagus (BE, and 782 controls. Results: Our results showed higher methylation of APC in EC (OR = 23.33, P < 0.001 and BE (OR = 9.34, P < 0.001 than in normal controls. Whereas APC methylation in EC was similar to that in BE (P = 0.052, it was not associated with tumor stage (P = 0.204. Additionally, APC methylation was not significantly associated with overall survival (OS and relapse-free survival (RFS in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Conclusion: Our results imply that APC methylation detection is a potential diagnostic biomarker for EC and BE. Keywords: esophageal cancer, Barrett’s esophagus, methylation, APC

  13. Enrollment of Patients With Lung and Colorectal Cancers Onto Clinical Trials

    OpenAIRE

    Fouad, Mona N.; Lee, Jeannette Y.; Catalano, Paul J.; Vogt, Thomas M.; Zafar, Syed Yousuf; West, Dee W.; Simon, Christian; Klabunde, Carrie N.; Kahn, Katherine L.; Weeks, Jane C.; Kiefe, Catarina I.

    2012-01-01

    Both practice environment and patient clinical and demographic characteristics are associated with cancer clinical trial enrollment; simultaneous intervention may be required when trying to increase enrollment rates.

  14. The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui; Shi, Tujin; Qian, Wei-Jun; Liu, Tao; Kagan, Jacob; Srivastava, Sudhir; Smith, Richard D.; Rodland, Karin D.; Camp, David G.

    2015-12-04

    Mass spectrometry-based proteomics has become an indispensable tool in biomedical research with broad applications ranging from fundamental biology, systems biology, and biomarker discovery. Recent advances in LC-MS have made it become a major technology in clinical applications, especially in cancer biomarker discovery and verification. To overcome the challenges associated with the analysis of clinical samples, such as extremely wide dynamic range of protein concentrations in biofluids and the need to perform high throughput and accurate quantification, significant efforts have been devoted to improve the overall performance of LC-MS bases clinical proteomics. In this review, we summarize the recent advances in LC-MS in the aspect of cancer biomarker discovery and quantification, and discuss its potentials, limitations, and future perspectives.

  15. Yoga & Cancer Interventions: A Review of the Clinical Significance of Patient Reported Outcomes for Cancer Survivors

    Directory of Open Access Journals (Sweden)

    S. Nicole Culos-Reed

    2012-01-01

    Full Text Available Limited research suggests yoga may be a viable gentle physical activity option with a variety of health-related quality of life, psychosocial and symptom management benefits. The purpose of this review was to determine the clinical significance of patient-reported outcomes from yoga interventions conducted with cancer survivors. A total of 25 published yoga intervention studies for cancer survivors from 2004–2011 had patient-reported outcomes, including quality of life, psychosocial or symptom measures. Thirteen of these studies met the necessary criteria to assess clinical significance. Clinical significance for each of the outcomes of interest was examined based on 1 standard error of the measurement, 0.5 standard deviation, and relative comparative effect sizes and their respective confidence intervals. This review describes in detail these patient-reported outcomes, how they were obtained, their relative clinical significance and implications for both clinical and research settings. Overall, clinically significant changes in patient-reported outcomes suggest that yoga interventions hold promise for improving cancer survivors' well-being. This research overview provides new directions for examining how clinical significance can provide a unique context for describing changes in patient-reported outcomes from yoga interventions. Researchers are encouraged to employ indices of clinical significance in the interpretation and discussion of results from yoga studies.

  16. Oral mucosal color changes as a clinical biomarker for cancer detection.

    Science.gov (United States)

    Latini, Giuseppe; De Felice, Claudio; Barducci, Alessandro; Chitano, Giovanna; Pignatelli, Antonietta; Grimaldi, Luca; Tramacere, Francesco; Laurini, Ricardo; Andreassi, Maria Grazia; Portaluri, Maurizio

    2012-07-01

    Screening is a key tool for early cancer detection/prevention and potentially saves lives. Oral mucosal vascular aberrations and color changes have been reported in hereditary nonpolyposis colorectal cancer patients, possibly reflecting a subclinical extracellular matrix abnormality implicated in the general process of cancer development. Reasoning that physicochemical changes of a tissue should affect its optical properties, we investigated the diagnostic ability of oral mucosal color to identify patients with several types of cancer. A total of 67 patients with several histologically proven malignancies at different stages were enrolled along with a group of 60 healthy controls of comparable age and sex ratio. Oral mucosal color was measured in selected areas, and then univariate, cluster, and principal component analyses were carried out. Lower red and green and higher blue values were significantly associated with evidence of cancer (all Pgreen coordinates. Likewise, the second principal component coordinate of the red-green clusters discriminated patients from controls with 98.2% sensitivity and 95% specificity (cut-off criterion≤0.4547; P=0.0001). The scatterplots of the chrominances revealed the formation of two well separated clusters, separating cancer patients from controls with a 99.4% probability of correct classification. These findings highlight the ability of oral color to encode clinically relevant biophysical information. In the near future, this low-cost and noninvasive method may become a useful tool for early cancer detection.

  17. Evolution of Clinical Proteomics and its Role in Medicine | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    NCI's Office of Cancer Clinical Proteomics Research authored a review of the current state of clinical proteomics in the peer-reviewed Journal of Proteome Research. The review highlights outcomes from the CPTC program and also provides a thorough overview of the different technologies that have pushed the field forward. Additionally, the review provides a vision for moving the field forward through linking advances in genomic and proteomic analysis to develop new, molecularly targeted interventions.

  18. Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer

    DEFF Research Database (Denmark)

    Havelund, Birgitte Mayland; Spindler, Karen-Lise Garm; Sørensen, Flemming Brandt

    2010-01-01

    Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer  Birgitte Mayland Havelund1,4 MD, Karen-Lise Garm Spindler1,4 MD, PhD, Flemming Brandt Sørensen2,4 MD, DMSc, Ivan Brandslund3 MD, DMSc, Anders Jakobsen1,4 MD, DMSc.1Department of Oncology, 2Pathology and 3Biochemistry, Vejle...... Hospital, Vejle, Denmark4Institute of Regional Health Services Research, University of Southern Denmark, Odense DenmarkBackgroundPrognostic and predictive markers are needed for individualizing the treatment of colorectal cancer. Hypoxia-inducible factor 1α (HIF-1α) is a transcription-inducing factor which...... the predictive and prognostic value of HIF-1α in colorectal cancer.Materials and MethodsThe project is divided into 3 substudies:1. Biological and methodological aspects. The expression of HIF-1α measured by immunohistochemistry in paraffin embedded tissue is related to single nucleotide polymorphism (SNP...

  19. Preventive and therapeutic potential of peptides from cereals against cancer.

    Science.gov (United States)

    Ortiz-Martinez, Margarita; Winkler, Robert; García-Lara, Silverio

    2014-12-05

    Epidemiological studies have shown that regular consumption of food based on whole-grain cereals and their products is associated with reduced risks of various types of degenerative chronic diseases. Food proteins are considered an important source of nutraceutical peptides and amino acids that can exert biological functions to promote health and prevent disease, including cancer. There have been several reports on peptides with anti-tumour activity in recent years. Plant-derived peptides, such as rapeseed, amaranth and soybean lunasin have received main attention. In this review, we extend this vision to analyse the evidence of current advances in peptides in cereals such as wheat, maize, rice, barley, rye and pseudocereals compared with soybean. We also show evidence of several mechanisms through which bioactive peptide exerts anti-tumour activity. Finally, we report the current status of major strategies for the fractionation, isolation and characterisation of bioactive peptides in cereals. In recent reports, it has been shown that peptides are an interesting alternative in the search for new treatments for cancer. One of the most studied sources of these peptides is food proteins; however, a review that includes more recent findings for cereals as a potential source of bioactive peptides in the treatment of cancer, the techniques for their isolation and characterisation and the assays used to prove their bioactivity is not available. This review can be used as a tool in the search for new sources of anti-cancer peptides. The authors have no conflicts of interest, financial or otherwise. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Identification and Pathogenic Potential of Clinical Bacillus and Paenibacillus Isolates.

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    Francesco Celandroni

    Full Text Available The soil-related Bacillus and Paenibacillus species have increasingly been implicated in various human diseases. Nevertheless, their identification still poses problems in the clinical microbiology laboratory and, with the exception of Bacillus anthracis and Bacillus cereus, little is known on their pathogenicity for humans. In this study, we evaluated the use of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS in the identification of clinical isolates of these genera and conducted genotypic and phenotypic analyses to highlight specific virulence properties. Seventy-five clinical isolates were subjected to biochemical and MALDI-TOF MS identification. 16S rDNA sequencing and supplemental tests were used to solve any discrepancies or failures in the identification results. MALDI-TOF MS significantly outperformed classical biochemical testing for correct species identification and no misidentification was obtained. One third of the collected strains belonged to the B. cereus species, but also Bacillus pumilus and Bacillus subtilis were isolated at high rate. Antimicrobial susceptibility testing showed that all the B. cereus, B. licheniformis, B. simplex, B. mycoides, Paenibacillus glucanolyticus and Paenibacillus lautus isolates are resistant to penicillin. The evaluation of toxin/enzyme secretion, toxin-encoding genes, motility, and biofilm formation revealed that B. cereus displays the highest virulence potential. However, although generally considered nonpathogenic, most of the other species were shown to swim, swarm, produce biofilms, and secrete proteases that can have a role in bacterial virulence. In conclusion, MALDI-TOF MS appears useful for fast and accurate identification of Bacillus and Paenibacillus strains whose virulence properties make them of increasing clinical relevance.

  1. The clinical value of MR elastography in the diagnosis of prostate cancer

    International Nuclear Information System (INIS)

    Chen Min; Li Saying; Wang Wenchao; Zhao Weifeng; Yang Zhenghan; Liu Ming; Zhou Cheng

    2010-01-01

    Objective: To investigate the clinical value of MR elastography in the diagnosis of prostate cancer at 3.0 T, and to assess the elasticity and viscosity of prostate cancer and benign prostatic diseases. Methods: Eight patients (63±7 years old) with 12 foci of prostate cancer and 10 patients (59±3 years old) with 14 foci of prostatitis in the peripheral zone were evaluated by MR elastography. MR elastography was performed by transmitting low-frequency longitudinal mechanical waves of 100 Hz into prostate with a transducer placed above the pubic bones. The phase images were reconstructed to acquire viscoelastic mapping. t test was used to compare the mean elasticity and viscosity of prostate cancer and prostatitis. The correlation of elasticity and Gleason scores between prostate cancer and prostatitis were also retrospectively analyzed with Pearson Correlation. Results: The mean elasticity and viscosity were significantly higher in prostate cancer [(6.55±0.47) kPa, (6.56±0.99) Pa·s, respectively] than in prostatitis [(1.99±0.66) kPa, (2.13±0.21) Pa·s, respectively], and the difference was statistically significant (t=19.392, 16.372; P<0.01). In 8 patients with prostate cancer, the Gleason scores were 5 (2 cases), 6 (3 cases), 7 (2 cases) and 8 (1 case), respectively. The mean elasticity for the cases with different Gleason scores was 5.83, 6.02, 7.45 and 8.05 kPa, respectively. There was a positive correlation between Gleason scores and elasticity of the prostate cancer(r=0.913, P<0.01) in this study. Conclusion: MR elastography can be used to visualize the difference in stiffness between prostate cancer and benign prostatic disease, it is a new imaging method with great potential in grading of prostate cancer. (authors)

  2. Claudin-Low Breast Cancer; Clinical & Pathological Characteristics.

    Directory of Open Access Journals (Sweden)

    Kay Dias

    Full Text Available Claudin-low breast cancer is a molecular type of breast cancer originally identified by gene expression profiling and reportedly associated with poor survival. Claudin-low tumors have been recognised to preferentially display a triple-negative phenotype, however only a minority of triple-negative breast cancers are claudin-low. We sought to identify an immunohistochemical profile for claudin-low tumors that could facilitate their identification in formalin fixed paraffin embedded tumor material. First, an in silico collection of ~1600 human breast cancer expression profiles was assembled and all claudin-low tumors identified. Second, genes differentially expressed between claudin-low tumors and all other molecular subtypes of breast cancer were identified. Third, a number of these top differentially expressed genes were tested using immunohistochemistry for expression in a diverse panel of breast cancer cell lines to determine their specificity for claudin-low tumors. Finally, the immunohistochemical panel found to be most characteristic of claudin-low tumors was examined in a cohort of 942 formalin fixed paraffin embedded human breast cancers with >10 years clinical follow-up to evaluate the clinico-pathologic and survival characteristics of this tumor subtype. Using this approach we determined that claudin-low breast cancer is typically negative for ER, PR, HER2, claudin 3, claudin 4, claudin 7 and E-cadherin. Claudin-low tumors identified with this immunohistochemical panel, were associated with young age of onset, higher tumor grade, larger tumor size, extensive lymphocytic infiltrate and a circumscribed tumor margin. Patients with claudin-low tumors had a worse overall survival when compared to patients with luminal A type breast cancer. Interestingly, claudin-low tumors were associated with a low local recurrence rate following breast conserving therapy. In conclusion, a limited panel of antibodies can facilitate the identification of

  3. Burden of HPV-caused cancers in Denmark and the potential effect of HPV-vaccination

    DEFF Research Database (Denmark)

    Skorstengaard, Malene; Thamsborg, Lise Holst; Lynge, Elsebeth

    2017-01-01

    -caused cancers in women and men, and to evaluate the potential of HPV-vaccination in cancer control. Methods: Data were retrieved from the literature on population prevalence of high risk (HR) HPV, on HR HPV-prevalence and genotypes in HPV-related cancers, and on number of cytology samples in cervical screening...... were preventable with HPV vaccination. However, including screening prevented cervical cancers, the burden of cancers caused by HPV-infection would be 1300–2000 in women as compared to 234 in men. Conclusion: Taking screening prevented cervical cancers into account, the cancer control potential of HPV...

  4. An apple oligogalactan potentiates the growth inhibitory effect of celecoxib on colorectal cancer.

    Science.gov (United States)

    Li, Yuhua; Niu, Yinbo; Sun, Yang; Mei, Lin; Zhang, Bangle; Li, Qian; Liu, Li; Zhang, Rong; Chen, Jianfa; Mei, Qibing

    2014-01-01

    Multiple studies have indicated that selective cyclooxygenase-2 (COX-2) inhibitors possess clinically chemopreventive and preclinically anticancer activities. Their long-term use, however, may be limited by the cardiovascular toxicity. This study tried to investigate whether an apple oligogalactan (AOG) could enhance the growth inhibitory effect of celecoxib on colorectal cancer. Caco-2 and HT-29 cell lines were exposed to different concentrations of AOG (0-1 g/L), celecoxib (0-25 μmol/L), and their combination. COX-2 levels were assessed by reverse transcription PCR and Western blot. COX-2 activity was evaluated by measuring prostaglandin E2 concentration. A colitis-associated colorectal cancer (CACC) mouse model was used to determine the effect of the combination in vivo. AOG (0.1-0.5 g/L) could potentiate the inhibitory effect of physiologic doses of celecoxib (5 μmol/L) on cell growth and decrease COX-2 expressions both at RNA and protein levels. In vivo, the combination (2.5% AOG plus 0.04% celecoxib, w/w) prevented against CACC in mice effectively. Our data indicate that AOG could potentiate the growth inhibitory effect of celecoxib on colorectal cancer both in vitro and in vivo through influencing the expression and function of COX-2 and phosphorylation of MAPKs, which suggests a new possible combinatorial strategy in colorectal cancer therapy.

  5. Potential role of estrogen receptor beta as a tumor suppressor of epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Carine Bossard

    Full Text Available Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb, phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients.

  6. Potential Role of Estrogen Receptor Beta as a Tumor Suppressor of Epithelial Ovarian Cancer

    Science.gov (United States)

    Gaudin, Françoise; Machelon, Véronique; Brigitte, Madly; Jacquard, Carine; Pillon, Arnaud; Balaguer, Patrick; Balabanian, Karl; Lazennec, Gwendal

    2012-01-01

    Ovarian cancer is the gynecological cancer exhibiting the highest morbidity and improvement of treatments is still required. Previous studies have shown that Estrogen-receptor beta (ERβ) levels decreased along with ovarian carcinogenesis. Here, we present evidence that reintroduction of ERβ in BG-1 epithelial ovarian cancer cells, which express ERα, leads in vitro to a decrease of basal and estradiol-promoted cell proliferation. ERβ reduced the frequency of cells in S phase and increased the one of cells in G2/M phase. At the molecular level, we found that ERβ downregulated total retinoblastoma (Rb), phosphorylated Rb and phospho-AKT cellular content as well as cyclins D1 and A2. In addition, ERβ had a direct effect on ERα, by strongly inhibiting its expression and activity, which could explain part of the anti-proliferative action of ERβ. By developing a novel preclinical model of ovarian cancer based on a luminescent orthotopic xenograft in athymic Nude mice, we further revealed that ERβ expression reduces tumor growth and the presence of tumor cells in sites of metastasis, hence resulting in improved survival of mice. Altogether, these findings unveil a potential tumor-suppressor role of ERβ in ovarian carcinogenesis, which could be of potential clinical relevance for the selection of the most appropriate treatment for patients. PMID:22970307

  7. Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer.

    Science.gov (United States)

    Clermont, Pier-Luc; Crea, Francesco; Chiang, Yan Ting; Lin, Dong; Zhang, Amy; Wang, James Z L; Parolia, Abhijit; Wu, Rebecca; Xue, Hui; Wang, Yuwei; Ding, Jiarui; Thu, Kelsie L; Lam, Wan L; Shah, Sohrab P; Collins, Colin C; Wang, Yuzhuo; Helgason, Cheryl D

    2016-01-01

    While localized prostate cancer (PCa) can be effectively cured, metastatic disease inevitably progresses to a lethal state called castration-resistant prostate cancer (CRPC). Emerging evidence suggests that aberrant epigenetic repression by the polycomb group (PcG) complexes fuels PCa progression, providing novel therapeutic opportunities. In the search for potential epigenetic drivers of CRPC, we analyzed the molecular profile of PcG members in patient-derived xenografts and clinical samples. Overall, our results identify the PcG protein and methyl-lysine reader CBX2 as a potential therapeutic target in advanced PCa. We report that CBX2 was recurrently up-regulated in metastatic CRPC and that elevated CBX2 expression was correlated with poor clinical outcome in PCa cohorts. Furthermore, CBX2 depletion abrogated cell viability and induced caspase 3-mediated apoptosis in metastatic PCa cell lines. Mechanistically explaining this phenotype, microarray analysis in CBX2-depleted cells revealed that CBX2 controls the expression of many key regulators of cell proliferation and metastasis. Taken together, this study provides the first evidence that CBX2 inhibition induces cancer cell death, positioning CBX2 as an attractive drug target in lethal CRPC.

  8. EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe?

    Directory of Open Access Journals (Sweden)

    Ke-Sin Yan

    2017-05-01

    Full Text Available Enhancer of zeste homolog 2 (EZH2, a histone methyltransferase, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3 to regulate gene expression through epigenetic machinery. EZH2 functions as a double-facet molecule in regulation of gene expression via repression or activation mechanisms, depending on the different cellular contexts. EZH2 interacts with both histone and non-histone proteins to modulate diverse physiological functions including cancer progression and malignancy. In this review article, we focused on the updated information regarding microRNAs (miRNAs and long non coding RNAs (lncRNAs in regulation of EZH2, the oncogenic and tumor suppressive roles of EZH2 in cancer progression and malignancy, as well as current pre-clinical and clinical trials of EZH2 inhibitors.

  9. Model Comparison for Breast Cancer Prognosis Based on Clinical Data.

    Directory of Open Access Journals (Sweden)

    Sabri Boughorbel

    Full Text Available We compared the performance of several prediction techniques for breast cancer prognosis, based on AU-ROC performance (Area Under ROC for different prognosis periods. The analyzed dataset contained 1,981 patients and from an initial 25 variables, the 11 most common clinical predictors were retained. We compared eight models from a wide spectrum of predictive models, namely; Generalized Linear Model (GLM, GLM-Net, Partial Least Square (PLS, Support Vector Machines (SVM, Random Forests (RF, Neural Networks, k-Nearest Neighbors (k-NN and Boosted Trees. In order to compare these models, paired t-test was applied on the model performance differences obtained from data resampling. Random Forests, Boosted Trees, Partial Least Square and GLMNet have superior overall performance, however they are only slightly higher than the other models. The comparative analysis also allowed us to define a relative variable importance as the average of variable importance from the different models. Two sets of variables are identified from this analysis. The first includes number of positive lymph nodes, tumor size, cancer grade and estrogen receptor, all has an important influence on model predictability. The second set incudes variables related to histological parameters and treatment types. The short term vs long term contribution of the clinical variables are also analyzed from the comparative models. From the various cancer treatment plans, the combination of Chemo/Radio therapy leads to the largest impact on cancer prognosis.

  10. Vitamin D and colorectal cancer: molecular, epidemiological and clinical evidence.

    Science.gov (United States)

    Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L; Manson, JoAnn E; Qian, Zhi Rong; Ogino, Shuji

    2016-05-01

    In many cells throughout the body, vitamin D is converted into its active form calcitriol and binds to the vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D-metabolising enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating the effects of vitamin D. Preclinical and epidemiological studies have provided evidence for anti-cancer effects of vitamin D (particularly against colorectal cancer), although clinical trials have yet to prove its benefit. In addition, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses and clinical trials on vitamin D efficacy in colorectal cancer patients. In this study, we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies and discuss the links and controversies within and between the two parts of evidence.

  11. Clinical usefulness of 111In transferrin scintigraphy in colorectal cancer

    International Nuclear Information System (INIS)

    Hirano, Morihisa; Naruki, Yukihiko; Urita, Yosihisa; Nakatani, Naoto; Otsuka, Sachio; Noguchi, Masahiro; Takano, Masaaki; Maruyama, Yuuzou.

    1993-01-01

    As assessment was made regarding the clinical value of 111 In transferrin in scintigraphy on 28 lesions in 26 cases of colorectal cancer. The positive rate of colorectal cancer was high: 21 lesions out of the 28 (75%) were found to be positive. As for the location of cancer, there was a tendency for the positive rate to be high in the ascending and transverse colon. There was no obvious trend regarding Borrmann's classification, histological type, or macroscopic depth of invasion. There was a trend for cases in which the maximum diameter of the tumor was large and depth of invasion was in progress to be positive. Ten cases in which a specimen was resected were all shown to be positive by scintigraphy. Radioactivity in the tumorous regions was 4.41±2.96 times that of the non-tumorous regions. Moreover, tumorous tissue was strongly stained by the immuno-histological staining with anti-Tf-receptor antibody. From the above findings, it was considered that 111 In transferrin is clinically useful in scintigraphy, since it is evident that it accumulates in the tissue of colorectal cancer. (author)

  12. 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

    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...... to appraise the validity. For validity assessment 100 cases were randomly selected from the DATHYRCA database; medical records were used as a reference. RESULT: The database held 1934 cases of thyroid carcinoma and completeness of case ascertainment was estimated to 90.9%. Completeness of registration......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...

  13. Photodynamic therapy potentiates the paracrine endothelial stimulation by colorectal cancer

    Science.gov (United States)

    Lamberti, María Julia; Florencia Pansa, María; Emanuel Vera, Renzo; Belén Rumie Vittar, Natalia; Rivarola, Viviana Alicia

    2014-11-01

    Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death worldwide. Recurrence is a major problem and is often the ultimate cause of death. In this context, the tumor microenvironment influences tumor progression and is considered as a new essential feature that clearly impacts on treatment outcome, and must therefore be taken into consideration. Photodynamic therapy (PDT), oxygen, light and drug-dependent, is a novel treatment modality when CRC patients are inoperable. Tumor vasculature and parenchyma cells are both potential targets of PDT damage modulating tumor-stroma interactions. In biological activity assessment in photodynamic research, three-dimensional (3D) cultures are essential to integrate biomechanical, biochemical, and biophysical properties that better predict the outcome of oxygen- and drug-dependent medical therapies. Therefore, the objective of this study was to investigate the antitumor effect of methyl 5-aminolevulinic acid-PDT using a light emitting diode for the treatment of CRC cells in a scenario that mimics targeted tissue complexity, providing a potential bridge for the gap between 2D cultures and animal models. Since photodynamic intervention of the tumor microenvironment can effectively modulate the tumor-stroma interaction, it was proposed to characterize the endothelial response to CRC paracrine communication, if one of these two populations is photosensitized. In conclusion, we demonstrated that the dialogue between endothelial and tumor populations when subjected to lethal PDT conditions induces an increase in angiogenic phenotype, and we think that it should be carefully considered for the development of PDT therapeutic protocols.

  14. Organization and Running of the First Comprehensive Hereditary Cancer Clinic in India

    Directory of Open Access Journals (Sweden)

    Rajkumar T

    2005-11-01

    Full Text Available Abstract Hereditary cancers are thought to account for around 5% of cancers, particularly breast/ovarian and colorectal cancers. In India there is a paucity of data on hereditary cancers and the mutations in some of the common genes linked to hereditary cancers, such as BRCA1, BRCA2, hMSH2 and hMLH1. The country's first comprehensive hereditary cancer clinic was established in February 2002. The article describes the organization and running of the Clinic. It also discusses some of the social issues relevant to the given population in running the Hereditary Cancer Clinic.

  15. Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells

    International Nuclear Information System (INIS)

    Sasaki, Kazuhito; Hiyoshi, Masaya; Kaneko, Manabu; Kitayama, Joji; Takahashi, Koki; Nagawa, Hirokazu; Tsuno, Nelson H; Sunami, Eiji; Tsurita, Giichiro; Kawai, Kazushige; Okaji, Yurai; Nishikawa, Takeshi; Shuno, Yasutaka; Hongo, Kumiko

    2010-01-01

    Chloroquine (CQ), the worldwide used anti-malarial drug, has recently being focused as a potential anti-cancer agent as well as a chemosensitizer when used in combination with anti-cancer drugs. It has been shown to inhibit cell growth and/or to induce cell death in various types of cancer. 5-Fluorouracil (5-FU) is the chemotherapeutic agent of first choice in colorectal cancer, but in most cases, resistance to 5-FU develops through various mechanisms. Here, we focused on the combination of CQ as a mechanism to potentiate the inhibitory effect of 5-FU on human colon cancer cells. HT-29 cells were treated with CQ and/or 5-FU, and their proliferative ability, apoptosis and autophagy induction effects, and the affection of the cell cycle were evaluated. The proliferative ability of HT-29 was analyzed by the MTS assay. Apoptosis was quantified by flow-cytometry after double-staining of the cells with AnnexinV/PI. The cell cycle was evaluated by flow-cytometry after staining of cells with PI. Autophagy was quantified by flow-cytometry and Western blot analysis. Finally, to evaluate the fate of the cells treated with CQ and/or 5-FU, the colony formation assay was performed. 5-FU inhibited the proliferative activity of HT-29 cells, which was mostly dependent on the arrest of the cells to the G0/G1-phase but also partially on apoptosis induction, and the effect was potentiated by CQ pre-treatment. The potentiation of the inhibitory effect of 5-FU by CQ was dependent on the increase of p21 Cip1 and p27 Kip1 and the decrease of CDK2. Since CQ is reported to inhibit autophagy, the catabolic process necessary for cell survival under conditions of cell starvation or stress, which is induced by cancer cells as a protective mechanism against chemotherapeutic agents, we also analyzed the induction of autophagy in HT-29. HT-29 induced autophagy in response to 5-FU, and CQ inhibited this induction, a possible mechanism of the potentiation of the anti-cancer effect of 5-FU. Our

  16. DIAGNOSIS AND TREATMENT OF METACHRONOUS TESTICULAR CANCER: A CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    A. S. Kalpinsky

    2013-01-01

    Full Text Available The incidence of bilateral testicular cancer is 5% in the total cohort of patients. Synchronous and metachronous testicular cancers are detected in 1-2 and 3% of cases, respectively. The standard treatment for testicular cancer is orchifuniculectomy and that for synchronous or metachronous cancer is organ-saving treatment, testectomy.The paper describes a clinical case of multiple primary metachronous testicular cancer. A 24-year-old patient underwent surgery (orchifuniculectomy and received 4 courses of BEP polychemotherapy for embryonal carcinoma of the left testicle at the P.A. Herzen Moscow Oncology Research Institute. After 55 months, a dynamic control examination diagnosed a 9-mm tumor in his single right testis that was thereafter resected. Its histological examination revealed embryonal carcinoma with solitary structures in the immature teratoma. Following 22 months, a control examination showed a recurrence of the disease, for which orchifuniculectomy of the single right testis, followed by hormone replacement therapy, was performed. The follow-up period was 80 months; no recurrence is now observed.

  17. Use of crowdsourcing for cancer clinical trial development.

    Science.gov (United States)

    Leiter, Amanda; Sablinski, Tomasz; Diefenbach, Michael; Foster, Marc; Greenberg, Alex; Holland, John; Oh, William K; Galsky, Matthew D

    2014-10-01

    Patient and physician awareness and acceptance of trials and patient ineligibility are major cancer clinical trial accrual barriers. Yet, trials are typically conceived and designed by small teams of researchers with limited patient input. We hypothesized that through crowdsourcing, the intellectual and creative capacity of a large number of researchers, clinicians, and patients could be harnessed to improve the clinical trial design process. In this study, we evaluated the feasibility and utility of using an internet-based crowdsourcing platform to inform the design of a clinical trial exploring an antidiabetic drug, metformin, in prostate cancer. Over a six-week period, crowd-sourced input was collected from 60 physicians/researchers and 42 patients/advocates leading to several major (eg, eligibility) and minor modifications to the clinical trial protocol as originally designed. Crowdsourcing clinical trial design is feasible, adds value to the protocol development process, and may ultimately improve the efficiency of trial conduct. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Clinical Implications of Hedgehog Pathway Signaling in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Daniel L. Suzman

    2015-09-01

    Full Text Available Activity in the Hedgehog pathway, which regulates GLI-mediated transcription, is important in organogenesis and stem cell regulation in self-renewing organs, but is pathologically elevated in many human malignancies. Mutations leading to constitutive activation of the pathway have been implicated in medulloblastoma and basal cell carcinoma, and inhibition of the pathway has demonstrated clinical responses leading to the approval of the Smoothened inhibitor, vismodegib, for the treatment of advanced basal cell carcinoma. Aberrant Hedgehog pathway signaling has also been noted in prostate cancer with evidence suggesting that it may render prostate epithelial cells tumorigenic, drive the epithelial-to-mesenchymal transition, and contribute towards the development of castration-resistance through autocrine and paracrine signaling within the tumor microenvironment and cross-talk with the androgen pathway. In addition, there are emerging clinical data suggesting that inhibition of the Hedgehog pathway may be effective in the treatment of recurrent and metastatic prostate cancer. Here we will review these data and highlight areas of active clinical research as they relate to Hedgehog pathway inhibition in prostate cancer.

  19. BAX protein expression and clinical outcome in epithelial ovarian cancer.

    Science.gov (United States)

    Tai, Y T; Lee, S; Niloff, E; Weisman, C; Strobel, T; Cannistra, S A

    1998-08-01

    Expression of the pro-apoptotic protein BAX sensitizes ovarian cancer cell lines to paclitaxel in vitro by enhancing the pathway of programmed cell death. The present study was performed to determine the relationship between BAX expression and clinical outcome in 45 patients with newly diagnosed ovarian cancer. BAX protein expression was analyzed by immunohistochemistry, and its relationship with clinical outcome was determined. Assessment of BAX mRNA transcript levels and mutational analysis of the BAX coding region were also performed. BAX protein was expressed at high levels (defined as > or = 50% of tumor cells positive) in tumor tissue from 60% of newly diagnosed patients. All patients whose tumors expressed high levels of BAX achieved a complete response (CR) to first-line chemotherapy that contained paclitaxel plus a platinum analogue, compared with 57% of patients in the low-BAX group (P = .036). After a median follow-up of 1.9 years, the median disease-free survival (DFS) of patients in the high-BAX group has not been reached, compared with a median DFS of 1.1 years for low-BAX expressors (P = .0061). BAX retained independent prognostic significance in multivariate analysis when corrected for stage and histology. BAX mRNA transcripts were easily detected in samples with low BAX protein expression, and no BAX mutations were identified. The correlation between high BAX levels and improved clinical outcome suggests that an intact apoptotic pathway is an important determinant of chemoresponsiveness in ovarian cancer patients who receive paclitaxel.

  20. Cancer diagnosis in a ''breast clinic''. A 15 years retrospection

    Energy Technology Data Exchange (ETDEWEB)

    Ghys, R

    1987-01-01

    Conflicting opinions have been expressed in the world literature over the last 15 years about the value of radiological techniques in breast cancer diagnosis. We reviewed 111 breast cancers which we diagnosed between 1971 and 1985, in unselected patients, by the combined use of palpation, thermography and mammography, complemented, since 1980, by diaphanoscopy. Considerable clinical experience is necessary to interpret both mammograms and thermograms. Each of these approaches, when rated independently, has a very high false negative rate ranging from 41% for clinical examination to 32% for mammography. In cases which are not clinically obvious, diaphanoscopy ''retrieves'' the most cancers, with thermography a close second (definitely malignant in 35% of the cases over the whole age range). Mammography comes third and its efficacy drops to 12.5% in premenopausal women. However, by combining this information with the one derived from anamnesis, the ACDTM scoring system gives us a false negative rate - before biopsy - of 5.5% and a false positive rate of <1%. This approach also drastically reduces the number of unnecessary biopsies.

  1. Biomarkers in prostate cancer - Current clinical utility and future perspectives.

    Science.gov (United States)

    Kretschmer, Alexander; Tilki, Derya

    2017-12-01

    Current tendencies in the treatment course of prostate cancer patients increase the need for reliable biomarkers that help in decision-making in a challenging clinical setting. Within the last decade, several novel biomarkers have been introduced. In the following comprehensive review article, we focus on diagnostic (PHI ® , 4K score, SelectMDx ® , ConfirmMDx ® , PCA3, MiPS, ExoDX ® , mpMRI) and prognostic (OncotypeDX GPS ® , Prolaris ® , ProMark ® , DNA-ploidy, Decipher ® ) biomarkers that are in widespread clinical use and are supported by evidence. Hereby, we focus on multiple clinical situations in which innovative biomarkers may guide decision-making in prostate cancer therapy. In addition, we describe novel liquid biopsy approaches (circulating tumor cells, cell-free DNA) that have been described as predictive biomarkers in metastatic castration-resistant prostate cancer and might support an individual patient-centred oncological approach in the nearer future. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data.

    Science.gov (United States)

    Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor-McCourt, Maureen

    2015-02-01

    specific patterns and tissue-specificity, which are driven by aging and other cancer-inducing agents. This framework represents the logics of complex cancer biology as a myriad of phenotypic complexities governed by a limited set of underlying organizing principles. It therefore adds to our understanding of tumor evolution and tumorigenesis, and moreover, potential usefulness of predicting tumors' evolutionary paths and clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for cancer patients, as well as cancer risks for healthy individuals are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial impact on timely diagnosis, personalized treatment and personalized prevention of cancer. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  3. Mesenchymal stem cells: biological characteristics and potential clinical applications

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2004-01-01

    are among the first stem cell types to be introduced in the clinic. Several studies have demonstrated the possible use of MSC in systemic transplantation for systemic diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues...... and organs in tissue engineering protocols. Before their widespread use in therapy, methods allowing the generation of large number of cells without affecting their differentiation potential as well as technologies that overcome immunological rejection (in case allogenic transplantation) must be developed.......Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal...

  4. [Genetic, epidemiologic and clinical study of familial prostate cancer].

    Science.gov (United States)

    Valéri, Antoine

    2002-01-01

    Prostate cancer (CaP) is the most frequent cancer among men over 50 and its frequency increases with age. It has become a significant public health problem due to the ageing population. Epidemiologists report familial aggregation in 15 to 25% of cases and inherited susceptibility with autosomal dominant or X-linked model in 5 to 10% of cases. Clinical and biological features of familial CaP remain controversial. To perform: (1) Genetic study of familial Cap (mapping of susceptibility genes), (2) epidemiologic study (prevalence, associated cancers in the genealogy, model of transmission), and clinical study of familial CaP. (I) conducting a nationwide family collection (ProGène study) with 2+ CaP we have performed a genomewide linkage analysis and identified a predisposing locus on 1q42.2-43 named PCaP (Predisposing to Cancer of the Prostate); (II) conducting a systematic genealogic analysis of 691 CaP followed up in 3 University departments of urology (Hospitals of Brest, Paris St Louis and Nancy) we have observed: (1) 14.2% of familial and 3.6% of hereditary CaP, (2) a higher risk of breast cancer in first degree relatives of probands (CaP+) in familial CaP than in sporadic CaP and in early onset CaP (< 55 years) when compared with late onset CaP ([dG]75 years), (3) an autosomal dominant model with brother-brother dependance), (4) the lack of specific clinical or biological feature (except for early onset) in hereditary CaP when compared with sporadic CaP. (1) The mapping of a susceptibility locus will permit the cloning of a predisposing gene on 1q42.2-43, offer the possibility of genetic screening in families at risk and permit genotype/phenotype correlation studies; (2) the transmission model will improve parameteric linkage studies; (3) the lack of distinct specific clinical patterns suggest diagnostic and follow up modalities for familial and hereditary CaP similar to sporadic cancer while encouraging early screening of families at risk, given the earlier

  5. Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

    Science.gov (United States)

    Sdrulla, Andrei D; Guan, Yun; Raja, Srinivasa N

    2018-03-11

    Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy. © 2018 World Institute of Pain.

  6. Clinical diagnostic potentials of thyroid ultrasonography and scintigraphy; An evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Torizuka, Tatsuo; Kasagi, Kanji; Hatabu, Hiroto; Misaki, Takashi; Iida, Yasuhiro; Konishi, Junji (Kyoto Univ. (Japan). Hospital); Endo, Keigo

    1993-06-01

    This prospective study was designed to evaluate the potential contributions of high resolution ultrasonography (US) and Tc-99m scintigraphy in the routine diagnosis of thyroid disease. The diagnostic impacts of US and Tc-99m scintigraphy results in 177 patients visiting our thyroid clinic were assessed and scored according to the following criteria: when the information provided by either test supported, confirmed or changed the initial clinical diagnosis, they received scores of 2, 3 and 4 respectively, while score 1 was given when the test itself was useless for the differential diagnosis. US identified focal lesions that both palpation and scintigraphy had failed to detect in 14 (12.1%) of 116 patients with diffuse thyroid diseases, suggesting the necessity of Hashimoto's thyroiditis, adenoma, adenocarcinoma and adenomatous goiter, and vice versa in the diagnosis of hyperthyroid and euthyroid Graves's diseases. Thus, the advantages of US over scintigraphy for morphological evaluation were confirmed. US was particularly useful for the differential diagnosis of adenomatous goiter from Hashimoto's thyroiditis or a single nodular disease. In contrast, scintigraphy gave functional images, being especially helpful for the differential diagnosis of thyrotoxicosis. (author).

  7. Long noncoding RNA MALAT1 as a potential novel biomarker in digestive system cancers: a meta-analysis.

    Science.gov (United States)

    Song, Wei; Zhang, Run J; Zou, Shu B

    2016-08-01

    Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a newly discovered long non-coding RNA (lncRNA), has been reported to be overexpressed in various cancers. However, the clinical value of MALAT1 in digestive system cancers is unclear. This study was designed to investigate the potential value of MALAT1 as a prognostic biomarker in digestive system cancers. We searched the Medline, Embase and Cochrane Library databases. All studies that explored the correlation between lncRNA MALAT1 expression and survival in digestive system tumors were selected. A quantitative meta-analysis was performed for the correlation between lncRNA MALAT1 expression and survival in digestive system tumors. Five studies were eligible for analysis, which included 547 patients. Meta-analysis showed that high expression of MALAT1 could predict poor overall survival (OS) in digestive system cancers (pooled HR: 1.85, 95% CI: 1.41-2.43, Pdigestive system cancers.

  8. Population-Attributable Risk Proportion of Clinical Risk Factors for Breast Cancer.

    Science.gov (United States)

    Engmann, Natalie J; Golmakani, Marzieh K; Miglioretti, Diana L; Sprague, Brian L; Kerlikowske, Karla

    2017-09-01

    Many established breast cancer risk factors are used in clinical risk prediction models, although the proportion of breast cancers explained by these factors is unknown. To determine the population-attributable risk proportion (PARP) for breast cancer associated with clinical breast cancer risk factors among premenopausal and postmenopausal women. Case-control study with 1:10 matching on age, year of risk factor assessment, and Breast Cancer Surveillance Consortium (BCSC) registry. Risk factor data were collected prospectively from January 1, 1996, through October 31, 2012, from BCSC community-based breast imaging facilities. A total of 18 437 women with invasive breast cancer or ductal carcinoma in situ were enrolled as cases and matched to 184 309 women without breast cancer, with a total of 58 146 premenopausal and 144 600 postmenopausal women enrolled in the study. Breast Imaging Reporting and Data System (BI-RADS) breast density (heterogeneously or extremely dense vs scattered fibroglandular densities), first-degree family history of breast cancer, body mass index (>25 vs 18.5-25), history of benign breast biopsy, and nulliparity or age at first birth (≥30 years vs breast cancer. Of the 18 437 women with breast cancer, the mean (SD) age was 46.3 (3.7) years among premenopausal women and 61.7 (7.2) years among the postmenopausal women. Overall, 4747 (89.8%) premenopausal and 12 502 (95.1%) postmenopausal women with breast cancer had at least 1 breast cancer risk factor. The combined PARP of all risk factors was 52.7% (95% CI, 49.1%-56.3%) among premenopausal women and 54.7% (95% CI, 46.5%-54.7%) among postmenopausal women. Breast density was the most prevalent risk factor for both premenopausal and postmenopausal women and had the largest effect on the PARP; 39.3% (95% CI, 36.6%-42.0%) of premenopausal and 26.2% (95% CI, 24.4%-28.0%) of postmenopausal breast cancers could potentially be averted if all women with heterogeneously or extremely dense

  9. Predictive genomics: A cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data

    OpenAIRE

    Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor, Maureen

    2014-01-01

    We discuss a cancer hallmark network framework for modelling genome-sequencing data to predict cancer clonal evolution and associated clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for a cancer patient, as well as cancer risks for a healthy individual are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial i...

  10. Evaluating the cancer detection and grading potential of prostatic-zinc imaging: a simulation study

    International Nuclear Information System (INIS)

    Cortesi, M; Chechik, R; Breskin, A; Vartsky, D; Ramon, J; Raviv, G; Volkov, A; Fridman, E

    2009-01-01

    The present work deals with the analysis of prostatic-zinc-concentration images. The goal is to evaluate potential clinically relevant information that can be extracted from such images. In the absence of experimental images, synthetic ones are produced from clinically measured zinc-concentration distributions in certified benign and cancerous tissue samples, classified by the lesion grade. We describe the method for producing the images and model the effect of counting statistics noise. We present in detail the image analysis, which is based on a combination of standard image processing and segmentation tools, optimized for this particular application. The information on lowest zinc value obtained from the image analysis is translated to clinical data such as tumour presence, location, size and grade. Their confidence is evaluated with the help of standard statistical tools such as receiver operating characteristic analysis. The present work predicts a potential for detecting small prostate-cancer lesions, of grade (4+3) and above, with very good specificity and sensitivity. The present analysis further provides data on the pixel size and image counting statistics requested from the trans-rectal probe that will record in vivo prostatic-zinc maps in patients.

  11. Older cancer patients in cancer clinical trials are underrepresented. Systematic literature review of almost 5000 meta- and pooled analyses of phase III randomized trials of survival from breast, prostate and lung cancer.

    Science.gov (United States)

    Dunn, Cita; Wilson, Andrew; Sitas, Freddy

    2017-12-01

    Older people represent increasing proportions of the population with cancer. To understand the representivity of cancer treatments in older people, we performed a systematic literature review using PRISMA guidelines of the age distribution of clinical trial participants for three leading cancer types, namely breast, prostate, and lung. We used PubMed to identify articles detailing meta or pooled-analyses of phase III, randomised controlled trials (RCTs) of survival for breast, prostate and lung cancer, published ≤5 years from 2016. We compared the age distribution of participants to that of these cancers for "More developed regions". 4993 potential papers were identified, but only three papers on breast cancer, three on lung cancer, and none on prostate cancer presented the age distribution of their participants. Except for one paper of breast cancer, participants ≥70 years in all other papers were underrepresented. We recommend the age distribution of patients be clearly reported in all clinical trials, as per guidelines. Clinical trials ought to be more representative of the populations most affected by the disease for which treatments are being tested. This should lead to better knowledge of effectiveness of treatments and better translation of trial results to optimal care of older cancer patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The potential of proton beam radiation therapy in lung cancer (including mesothelioma)

    Energy Technology Data Exchange (ETDEWEB)

    Bjelkengren, Goeran [Univ. Hospital, Malmoe (Sweden). Dept. of Oncology; Glimelius, Bengt [Karolinska Inst., Stockholm (Sweden). Dept. of Oncology and Pathology; Akademiska sjukhuset, Uppsala (Sweden). Dept. of Oncology, Radiology and Clinical Immunology

    2005-12-01

    A Swedish group of oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. It is estimated that about 350 patients with lung cancer and about 20 patients with mesothelioma annually may benefit from proton beam therapy.

  13. Preclinical studies and clinical trial of targeted alpha therapy for cancer

    International Nuclear Information System (INIS)

    Allen, B.J.

    2002-01-01

    Full text: Targeted Alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukemia, colorectal, breast and prostate cancers. Materials and Methods: The alpha-emitting radioisotope is Bi-213, which is produced by the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (eg plasmmogen activator inhibitor PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukemia (WM60 mab), colorectal (C30.6 mab), breast (PAI2) and prostate (PAI2, J591 mab) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. Results: In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than nonspecific ACs, specific beta emitting conjugates or free isotope. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can also completely regress advanced sc melanomas but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Conclusions: These results point to the application of local and systemic TAT in the management of secondary cancer. A phase 1 and 2 clinical trial of TAT of subcutaneous, secondary melanoma has commenced at St George Hospital, and 10/30 subjects have been treated by intralesional injection

  14. Syndecans as modulators and potential pharmacological targets in cancer progression

    Directory of Open Access Journals (Sweden)

    Despoina eBarbouri

    2014-02-01

    Full Text Available Extracellular matrix (ECM components form a dynamic network of key importance for cell function and properties. Key macromolecules in this interplay are syndecans (SDCs, a family of transmembrane heparan sulfate proteoglycans (HSPGs. Specifically, heparan sulfate (HS chains with their different sulfation pattern have the ability to interact with growth factors and their receptors in tumor microenvironment, promoting the activation of different signaling cascades that regulate tumor cell behavior. The affinity of HS chains with ligands is altered during malignant conditions because of the modification of chain sequence/sulfation pattern. Furthermore, matrix degradation enzymes derived from the tumor itself or the tumor microenvironment, like heparanase and matrix metalloproteinases (MMPs, ADAM as well as ADΑMTS are involved in the cleavage of SDCs ectodomain at the HS and protein core level, respectively. Such released soluble syndecans shed syndecans in the extracellular matrix interact in an autocrine or paracrine manner with the tumor or/and stromal cells. Shed syndecans, upon binding to several matrix effectors, such as growth factors, chemokines and cytokines, have the ability to act as competitive inhibitors for membrane PGs, and modulate the inflammatory microenvironment of cancer cells. It is notable that syndecans and their soluble counterparts may affect either the behavior of cancer cells and/or their microenvironment during cancer progression. The importance of these molecules has been highlighted since HSPGs have been proposed as prognostic markers of solid tumors and hematopoietic malignancies. Going a step further down the line, the multi-actions of syndecans in many levels make them appealing as potential pharmacological targets, either by targeting directly the tumor or indirectly the adjacent stroma.

  15. Patient representatives' views on patient information in clinical cancer trials.

    Science.gov (United States)

    Dellson, Pia; Nilbert, Mef; Carlsson, Christina

    2016-02-01

    Patient enrolment into clinical trials is based on oral information and informed consent, which includes an information sheet and a consent certificate. The written information should be complete, but at the same time risks being so complex that it may be questioned if a fully informed consent is possible to provide. We explored patient representatives' views and perceptions on the written trial information used in clinical cancer trials. Written patient information leaflets used in four clinical trials for colorectal cancer were used for the study. The trials included phase I-III trials, randomized and non-randomized trials that evaluated chemotherapy/targeted therapy in the neoadjuvant, adjuvant and palliative settings. Data were collected through focus groups and were analysed using inductive content analysis. Two major themes emerged: emotional responses and cognitive responses. Subthemes related to the former included individual preferences and perceptions of effect, while subthemes related to the latter were comprehensibility and layout. Based on these observations the patient representatives provided suggestions for improvement, which largely included development of future simplified and more attractive informed consent forms. The emotional and cognitive responses to written patient information reported by patient representatives provides a basis for revised formats in future trials and add to the body of information that support use of plain language, structured text and illustrations to improve the informed consent process and thereby patient enrolment into clinical trials.

  16. Incidental pulmonary embolism in cancer patients: clinical characteristics and outcome – a comprehensive cancer center experience

    Directory of Open Access Journals (Sweden)

    Abdel-Razeq H

    2011-03-01

    Full Text Available Hikmat N Abdel-Razeq1, Asem H Mansour2, Yousef M Ismael11Department of Internal Medicine, 2Department of Radiology, King Hussein Cancer Center, Amman, JordanBackground and objectives: Cancer patients undergo routine imaging studies much more than others. The widespread use of the recently introduced multi-detector CT scanners has resulted in an increasing number of incidentally diagnosed pulmonary embolism (PE in asymptomatic cancer patients. The significance and clinical outcome of such incidental PE is described.Methods: Both radiology department and hospital databases were searched for all cancer patients with a diagnosis of incidental PE. CT scans were performed using a 64-slice scanner with a 5.0 mm slice thickness.Results: During the study period, 34 patients with incidental PE were identified. The mean age (±SD was 57.7 (±12.4 years. All patients had active cancer, gastric, lung, colorectal, and lymphomas being the most frequent. Most patients had advanced-stage disease at the time of PE diagnosis; 26 (77% patients had stage IV, whereas only 3 patients had stages I or II disease. Twenty-seven (79% patients had their PE while undergoing active treatment with chemotherapy (68% or radiotherapy (12%; none, however, were on hormonal therapy. Most (74% patients had their PE diagnosed without history of recent hospital admission. Except for 5 (15%, all other patients were anticoagulated. With follow-up, 2 patients developed recurrent PE, 2 others had clinical and echocardiographic evidence of pulmonary hypertension, and 9 (26% died suddenly within 30 days of the diagnosis of incidental PE; 2 of these where among the 5 patients who were not anticoagulated.Conclusion: Incidental PE in cancer patients is increasingly encountered. Similar to symptomatic PE, many were diagnosed in patients with advanced stage disease and while undergoing active anti-cancer therapy. A significant percentage of patients had recurrent emboli, pulmonary hypertension

  17. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2016-12-01

    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  18. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

    International Nuclear Information System (INIS)

    Martirosyan, Anna; Clendening, James W; Goard, Carolyn A; Penn, Linda Z

    2010-01-01

    Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage) and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a mevalonate-dependent mechanism. Moreover, we also show lovastatin synergizes

  19. Early diagnostic potential of APC hypermethylation in esophageal cancer.

    Science.gov (United States)

    Wang, Bujiang; Song, Haojun; Jiang, Haizhong; Fu, Yangbo; Ding, Xiaoyun; Zhou, Chongchang

    2018-01-01

    The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC). However, the association between APC methylation and the initiation and progression of EC is poorly understood. The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett's esophagus (BE), and 782 controls. Our results showed higher methylation of APC in EC (OR = 23.33, P APC methylation in EC was similar to that in BE ( P = 0.052), it was not associated with tumor stage ( P = 0.204). Additionally, APC methylation was not significantly associated with overall survival (OS) and relapse-free survival (RFS) in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Our results imply that APC methylation detection is a potential diagnostic biomarker for EC and BE.

  20. Colorectal cancer chemoprevention: the potential of a selective approach.

    Science.gov (United States)

    Ben-Amotz, Oded; Arber, Nadir; Kraus, Sarah

    2010-10-01

    Colorectal cancer (CRC) is a leading cause of cancer death, and therefore demands special attention. Novel recent approaches for the chemoprevention of CRC focus on selective targeting of key pathways. We review the study by Zhang and colleagues, evaluating a selective approach targeting APC-deficient premalignant cells using retinoid-based therapy and TNF-related apoptosis-inducing ligand (TRAIL). This study demonstrates that induction of TRAIL-mediated death signaling contributes to the chemopreventive value of all-trans-retinyl acetate (RAc) by sensitizing premalignant adenoma cells for apoptosis without affecting normal cells. We discuss these important findings, raise few points that deserve consideration, and may further contribute to the development of RAc-based combination therapies with improved efficacy. The authors clearly demonstrate a synergistic interaction between TRAIL, RAc and APC, which leads to the specific cell death of premalignant target cells. The study adds to the growing body of literature related to CRC chemoprevention, and provides solid data supporting a potentially selective approach for preventing CRC using RAc and TRAIL.

  1. Patient perspectives: Kundalini yoga meditation techniques for psycho-oncology and as potential therapies for cancer.

    Science.gov (United States)

    Shannahoff-Khalsa, David S

    2005-03-01

    The ancient system of Kundalini Yoga (KY) includes a vast array of meditation techniques. Some were discovered to be specific for treating psychiatric disorders and others are supposedly beneficial for treating cancers. To date, 2 clinical trials have been conducted for treating obsessive-compulsive disorder (OCD). The first was an open uncontrolled trial and the second a single-blinded randomized controlled trial (RCT) comparing a KY protocol against the Relaxation Response and Mindfulness Meditation (RRMM) techniques combined. Both trials showed efficacy on all psychological scales using the KY protocol; however, the RCT showed no efficacy on any scale with the RRMM control group. The KY protocol employed an OCD-specific meditation technique combined with other techniques that are individually specific for anxiety, low energy, fear, anger, meeting mental challenges, and turning negative thoughts into positive thoughts. In addition to OCD symptoms, other symptoms, including anxiety and depression, were also significantly reduced. Elements of the KY protocol other than the OCD-specific technique also may have applications for psycho-oncology patients and are described here. Two depression-specific KY techniques are described that also help combat mental fatigue and low energy. A 7-part protocol is described that would be used in KY practice to affect the full spectrum of emotions and distress that complicate a cancer diagnosis. In addition, there are KY techniques that practitioners have used in treating cancer. These techniques have not yet been subjected to formal clinical trials but are described here as potential adjunctive therapies. A case history demonstrating rapid onset of acute relief of intense fear in a terminal breast cancer patient using a KY technique specific for fear is presented. A second case history is reported for a surviving male diagnosed in 1988 with terminal prostate cancer who has used KY therapy long term as part of a self

  2. Intratumoral heterogeneity: Role of differentiation in a potentially lethal phenotype of testicular cancer.

    Science.gov (United States)

    Tu, Shi-Ming; Bilen, Mehmet Asim; Hess, Kenneth R; Broaddus, Russell R; Kopetz, Scott; Wei, Chongjuan; Pagliaro, Lance C; Karam, Jose A; Ward, John F; Wood, Christopher G; Rao, Priya; Tu, Zachary H; General, Rosale; Chen, Adrienne H; Nieto, Yago L; Yeung, Sai-Ching J; Lin, Sue-Hwa; Logothetis, Christopher J; Pisters, Louis L

    2016-06-15

    Intratumoral heterogeneity presents a major obstacle to the widespread implementation of precision medicine. The authors assessed the origin of intratumoral heterogeneity in nonseminomatous germ cell tumor of the testis (NSGCT) and identified distinct tumor subtypes and a potentially lethal phenotype. In this retrospective study, all consecutive patients who had been diagnosed with an NSGCT between January 2000 and December 2010 were evaluated. The histologic makeup of primary tumors and the clinical course of disease were determined for each patient. A Fine and Gray proportional hazards regression analysis was used to determine the prognostic risk factors, and the Gray test was used to detect differences in the cumulative incidence of cancer death. In a separate prospective study, next-generation sequencing was performed on tumor samples from 9 patients to identify any actionable mutations. Six hundred fifteen patients were included in this study. Multivariate analysis revealed that the presence of yolk sac tumor in the primary tumor (P = .0003) was associated with an unfavorable prognosis. NSGCT could be divided into 5 subgroups. Patients in the yolk sac-seminoma subgroup had the poorest clinical outcome (P = .0015). These tumors tended to undergo somatic transformation (P Cancer 2016;122:1836-43. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2016 American Cancer Society.

  3. Generation dependent cancer targeting potential of poly(propyleneimine) dendrimer.

    Science.gov (United States)

    Kesharwani, Prashant; Tekade, Rakesh K; Jain, Narendra K

    2014-07-01

    Dendrimer-mediated delivery of bioactive is a successful and widely explored concept. This paper desribes comparative data pertaining to generation dependent cancer targeting propensity of Poly(propyleneimine) (PPI) dendrimers. This debut report reportsthe drug targeting and antciancer potential of different dendrimer generations. PPI dendrimers of different generations (3.0G, 4.0G and 5.0G) were synthesized and loaded with Melphalan. Results from loading, hemolysis, hematologic, cytotoxicty and flow cytometry assay depicted that as the generation of dendrimer increased from fourth to fifth, the only parameter i.e. toxicty is increased exponentionally. However, others parameters, i.e. loading, sustained release behavior, and targeting efficacy increased negligibly. Kaplan-Meier survival curves clearly depicted comparable therapeutic potential of PPI4M with PPI5M. In vivo investigations in Balb/c mice again favored 4.0G PPI dendrimer to be preferable nanocarrier for anticancer drug delivery owing to analogous anticancer potential. The outcomes of the investigation evidently projects 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer in respect of its drug delivery benefit as well as superior biocompatibility. Thus, much against the common belief, 4.0G PPI dendrimers may be considered to be optimum in respect of drug delivery precluding the use of much more toxic 5.0G PPI dendrimer, which offers no benefit over 4.0G. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. A Clinical Decision Support System for Breast Cancer Patients

    Science.gov (United States)

    Fernandes, Ana S.; Alves, Pedro; Jarman, Ian H.; Etchells, Terence A.; Fonseca, José M.; Lisboa, Paulo J. G.

    This paper proposes a Web clinical decision support system for clinical oncologists and for breast cancer patients making prognostic assessments, using the particular characteristics of the individual patient. This system comprises three different prognostic modelling methodologies: the clinically widely used Nottingham prognostic index (NPI); the Cox regression modelling and a partial logistic artificial neural network with automatic relevance determination (PLANN-ARD). All three models yield a different prognostic index that can be analysed together in order to obtain a more accurate prognostic assessment of the patient. Missing data is incorporated in the mentioned models, a common issue in medical data that was overcome using multiple imputation techniques. Risk group assignments are also provided through a methodology based on regression trees, where Boolean rules can be obtained expressed with patient characteristics.

  5. Clinical advance in radionuclide imaging of pulmonary cancer

    International Nuclear Information System (INIS)

    Deng Zhiyong; Yang Lichun

    2008-01-01

    Radionuclide imaging of pulmonary cancer develops very rapidly in recent years. Its important value on the diagnosis, staging, monitoring recur and metastasis after treatment, and judging the curative effect and prognosis has been demonstrated. Clinicians pay more attention to it than before. This present article introduces the imaging principle, clinical use, good and bad points, progress situation of 67 Ga, 201 Tl, 99 Tc m , 18 F and their labelled compounds, which are more commonly used in clinical. And introduces the clinical progress of radionuclide imaging of pulmonary neoplasm concerning 99 Tc m -sestamibi ( 99 Tc m -MIBI), 99 Tc m -HL91 and 18 F-fluorodeoxyglucose ( 18 F-FDG) with emphasis. (authors)

  6. Ovarian cancer: the clinical role of US, CT, and MRI

    International Nuclear Information System (INIS)

    Togashi, K.

    2003-01-01

    This article presents an overview of ovarian cancer, which addresses the clinical roles of imaging studies, including US, CT, and MR imaging in the course of diagnosis and treatment of this important disease. US is the modality of choice in the evaluation of patients with suspected adnexal masses. Although its accuracy is not sufficient to avert surgery, morphological analysis of adnexal masses with US helps narrow the differential diagnosis, determining the degree of suspicion for malignancy, usually in concert with a serum CA-125 level. Combined morphological and vascular imaging obtained by US appear to further improve the preoperative assessment of adnexal masses. For uncertain or problematic cases, MR imaging helps to distinguish benign from malignant, with an overall accuracy for the diagnosis of malignancy of 93%. The accuracy of MR imaging in the confident diagnosis of mature cystic teratoma, endometrial cysts, and leiomayomas is very high. CT is not indicated for differential diagnosis of adnexal masses because of poor soft tissue discrimination, except for fatty tissue and for calcification, and the disadvantages of irradiation. In the staging of ovarian cancer, CT, US, and MR imaging all have a similarly high accuracy. Although it is difficult to suggest a simple algorithm for evaluating the state of women with adnexal masses, the correct preoperative diagnosis and staging of ovarian cancer with the use of any of these imaging studies will lead to an appropriate referral to a specialist in gynecologic oncology and offer a significant survival advantage for patients with ovarian cancer. (orig.)

  7. Clinical Characteristics in Patients with Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Janet Yeh

    2017-01-01

    Full Text Available Purpose. The purpose of this study was to compare and contrast the clinical characteristics of the triple negative breast cancer (TNBC and non-TNBC patients, with a particular focus on genetic susceptibility and risk factors prior to diagnosis. Methods. Our institutional database was queried for all patients diagnosed with invasive breast cancer between January 2010 and May 2016. Results. Out of a total of 1964 patients, 190 (10% patients had TNBC. The median age for both TNBC and non-TNBC was 59 years. There was a significantly higher proportion of African American and Asian patients with TNBC (p=0.0003 compared to patients with non-TNBC. BRCA1 and BRCA2 were significantly associated with TNBC (p<0.0001, p=0.0007. A prior history of breast cancer was significantly associated with TNBC (p=0.0003. There was no relationship observed between TNBC and a history of chemoprevention or patients who had a history of AH or LCIS. Conclusions. We found that having Asian ancestry, a prior history of breast cancer, and a BRCA1 or BRCA2 mutation all appear to be positively associated with TNBC. In order to develop more effective treatments, better surveillance, and improved prevention strategies, it is necessary to improve our understanding of the population at risk for TNBC.

  8. The Clinical Application of Raman Spectroscopy for Breast Cancer Detection

    Directory of Open Access Journals (Sweden)

    Pin Gao

    2017-01-01

    Full Text Available Raman spectroscopy has been widely used as an important clinical tool for real-time in vivo cancer diagnosis. Raman information can be obtained from whole organisms and tissues, at the cellular level and at the biomolecular level. The aim of this paper is to review the newest developments of Raman spectroscopy in the field of breast cancer diagnosis and treatment. Raman spectroscopy can distinguish malignant tissues from noncancerous/normal tissues and can assess tumor margins or sentinel lymph nodes during an operation. At the cellular level, Raman spectra can be used to monitor the intracellular processes occurring in blood circulation. At the biomolecular level, surface-enhanced Raman spectroscopy techniques may help detect the biomarker on the tumor surface as well as evaluate the efficacy of anticancer drugs. Furthermore, Raman images reveal an inhomogeneous distribution of different compounds, especially proteins, lipids, microcalcifications, and their metabolic products, in cancerous breast tissues. Information about these compounds may further our understanding of the mechanisms of breast cancer.

  9. Clinical and molecular characterization of BRCA-associated breast cancer

    DEFF Research Database (Denmark)

    Soenderstrup, I. M.H.; Laenkholm, A. V.; Jensen, M. B.

    2018-01-01

    Background: In breast cancer (BC) patients a cancer predisposing BRCA1/2 mutation is associated with adverse tumor characteristics, risk assessment and treatment allocation. We aimed to estimate overall- (OS) and disease-free survival (DFS) according to tumor characteristics and treatment among...... women who within two years of definitive surgery for primary BC were shown to carry a mutation in BRCA1/2 . Material and methods: From the clinical database of the Danish Breast Cancer Group we included 141 BRCA1 and 96 BRCA2 BC patients. Estrogen receptor and HER2 status were centrally reviewed......–81). Ten-year OS and DFS for BRCA2 BC were 88% (95% CI 78–94) and 84% (95% CI 74–91). BRCA1 BC patients as compared to BRCA2 BC patients had a higher risk of BC relapse or non-breast cancer within ten years of follow-up, independent of ER status (adjusted HR 2.78 95% CI 1.28–6.05, p = .01), but BRCA...

  10. Adjuvant Chemotherapy for Stage II Colon Cancer: A Clinical Dilemma.

    Science.gov (United States)

    Kannarkatt, Joseph; Joseph, Joe; Kurniali, Peter C; Al-Janadi, Anas; Hrinczenko, Borys

    2017-04-01

    The decision to treat a patient with stage II colon cancer with adjuvant chemotherapy can be challenging. Although the benefit of treatment is clear in most patients with stage III disease, the decision to provide chemotherapy after surgical resection in stage II disease must be made on an individual basis. Several trials have demonstrated the small but absolute benefits of receiving adjuvant chemotherapy for stage II colon cancer for disease-free survival and overall survival. In an attempt to better understand the role of chemotherapy, several studies were performed that identified high-risk characteristics that can be used prognostically and predictively to aid in the clinical decision making process. ASCO, the National Comprehensive Cancer Network, and the European Society of Medical Oncology have published guidelines describing these high-risk characteristics. Since then, several other molecular markers have emerged that may offer more information on a given patient's risk for recurrence. The decision to treat a patient with stage II colon cancer must be made on an individual basis, considering the risks and benefits of treatment. In this short review, we will present the available evidence and offer possible directions for future study.

  11. Vitamin D and Colorectal Cancer: Molecular, Epidemiological, and Clinical Evidence

    Science.gov (United States)

    Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L.; Manson, JoAnn E.; Qian, Zhi Rong; Ogino, Shuji

    2016-01-01

    In many cells throughout the body, vitamin D is converted into its active form calcitriol, and binds to vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D metabolizing enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating effects of vitamin D. Preclinical and epidemiological studies provide evidence for anticancer effects of vitamin D (in particular, against colorectal cancer), though clinical trials have yet to prove its benefit. Additionally, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses, and clinical trials on vitamin D efficacy in colorectal cancer patients. Here we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies, and discuss the links and controversies within and between the two parts of evidence. PMID:27245104

  12. HN125: A Novel Immunoadhesin Targeting MUC16 with Potential for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Xinran Xiang, Mingqian Feng, Mildred Felder, Joseph P. Connor, Yan-gao Man, Manish S. Patankar, Mitchell Ho

    2011-01-01

    Full Text Available Background: The mucin MUC16 expresses the repeating peptide epitope CA125 that has been known for decades to be a well-validated cancer marker that is overexpressed on the cell surface of ovarian cancers and other malignant tumors. In spite of recent efforts to make mouse monoclonal antibodies to MUC16 to treat ovarian cancer, a human monoclonal antibody against this mucin has not been described. MUC16 interacts with mesothelin, a protein that mediates heterotypic cancer cell adhesion, indicating that MUC16 and mesothelin play an important role in the peritoneal implantation and metastasis of ovarian tumors. Therefore, a suitable candidate for therapeutic targeting of MUC16 would functionally block the interaction of MUC16 and mesothelin.Methodology/Principal Findings: Here we report the generation of a novel immunoadhesin, HN125, against MUC16 that consists of a functional MUC16 binding domain of mesothelin (IAB and the Fc portion of a human antibody IgG1. The yield for purified HN125 proteins is over 100 µg/mL of HEK-293 culture supernatant. We show that HN125 has high and specific affinity for MUC16-expressing cancer cells by flow cytometry and immunohistochemistry. HN125 has the ability to disrupt the heterotypic cancer cell adhesion mediated by the MUC16-mesothelin interaction. Moreover, it elicits strong antibody-dependent cell mediated cytotoxicity against MUC16-positive cancer cells in vitro.Conclusion/Significance: This report describes a novel human immunotherapeutic agent highly specific for MUC16 with potential for treating ovarian cancer and other MUC16-expressing tumors. Because of its lower immunogenicity in patients, a fully human protein is the most desirable format for clinical applications. We believe that the methods developed here may apply to the generation of other tumor-targeting immunoadhesins when it is difficult to obtain a human monoclonal antibody to a given antigen for clinical applications. The resultant

  13. Circulating tumor cells and their relationship with clinical and morphological characteristics of colorectal cancer

    Directory of Open Access Journals (Sweden)

    O I Kit

    2018-02-01

    Full Text Available Aim. To investigate the dependence of the number of circulating tumor cells in peripheral blood of colorectal cancer patients on the clinical and morphological characteristics of underlying disease. Methods. 91 patients with verified metastatic colorectal cancer Т3-4N1-2М1 were included in the study. The average age of the patients was 61.5±1.7 years. The patients were divided into the study group (laparoscopic surgical treatment, n=44 and control group (open surgical intervention, n=47. The number of circulating tumor cells was determined in CellSearch™ system in the peripheral blood drawn before the intervention. The study of the association of attributes by constructing contingency tables consisted in calculating Pearson’s contingency coefficient c2 with Mantel-Haenszel correction for likelihood (nonparametric correction, estimating statistical significance of contingency and analyzing the tightness of the association by A. Chuprov’s mutual contingency coefficient. Results. We found contingency of the number of circulating tumor cells with clinical and morphological parameters of patients with colorectal cancer. The relationship between potential risk factors and increase of the number of circulating tumor cells in the peripheral blood was observed in all colorectal cancer patients, regardless of the surgical intervention method. The most pronounced association of the number of circulating tumor cells in the peripheral blood of metastatic colorectal cancer patients before surgery according to the mutual contingency coefficient (K was shown to be with present distant metastases (status M1b; K=0.63, p=0.0001 and stage T4 (K=0.56, p=0.0009. Conclusion. The obtained results emphasize the important predictive significance of the circulating tumor cells level in peripheral blood for assessment of the potential for colorectal cancer progression.

  14. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yun, Chae-Ok [Department of Bioengineering, College of Engineering, Hanyang University, Seoul (Korea, Republic of); Han, Deok-Jong [Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Young, E-mail: choieun@ulsan.ac.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2015-12-04

    Overexpression of the Del-1 gene potentiates proliferation and invasion of lung carcinoma cells. • Del-1 may be used as a diagnostic or prognostic marker for lung cancer progression.

  15. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon; Yun, Chae-Ok; Han, Deok-Jong; Choi, Eun Young

    2015-01-01

    Overexpression of the Del-1 gene potentiates proliferation and invasion of lung carcinoma cells. • Del-1 may be used as a diagnostic or prognostic marker for lung cancer progression.

  16. American Society of Clinical Oncology guidance statement: the cost of cancer care.

    Science.gov (United States)

    Meropol, Neal J; Schrag, Deborah; Smith, Thomas J; Mulvey, Therese M; Langdon, Robert M; Blum, Diane; Ubel, Peter A; Schnipper, Lowell E

    2009-08-10

    Advances in early detection, prevention, and treatment have resulted in consistently falling cancer death rates in the United States. In parallel with these advances have come significant increases in the cost of cancer care. It is well established that the cost of health care (including cancer care) in the United States is growing more rapidly than the overall economy. In part, this is a result of the prices and rapid uptake of new agents and other technologies, including advances in imaging and therapeutic radiology. Conventional understanding suggests that high prices may reflect the costs and risks associated with the development, production, and marketing of new drugs and technologies, many of which are valued highly by physicians, patients, and payers. The increasing cost of cancer care impacts many stakeholders who play a role in a complex health care system. Our patients are the most vulnerable because they often experience uneven insurance coverage, leading to financial strain or even ruin. Other key groups include pharmaceutical manufacturers that pass along research, development, and marketing costs to the consumer; providers of cancer care who dispense increasingly expensive drugs and technologies; and the insurance industry, which ultimately passes costs to consumers. Increasingly, the economic burden of health care in general, and high-quality cancer care in particular, will be less and less affordable for an increasing number of Americans unless steps are taken to curb current trends. The American Society of Clinical Oncology (ASCO) is committed to improving cancer prevention, diagnosis, and treatment and eliminating disparities in cancer care through support of evidence-based and cost-effective practices. To address this goal, ASCO established a Cost of Care Task Force, which has developed this Guidance Statement on the Cost of Cancer Care. This Guidance Statement provides a concise overview of the economic issues facing stakeholders in the cancer

  17. The potential contribution of dietary factors to breast cancer prevention.

    Science.gov (United States)

    Shapira, Niva

    2017-09-01

    Breast cancer (BC), the leading cancer in women, is increasing in prevalence worldwide, concurrent with western metabolic epidemics, that is, obesity, metabolic syndrome, and diabetes, and shares major risk factors with these diseases. The corresponding potential for nutritional contributions toward BC prevention is reviewed and related to critical stages in the life cycle and their implications for carcinogenic and pathometabolic trajectories. BC initiation potentially involves diet-related pro-oxidative, inflammatory, and procarcinogenic processes, that interact through combined lipid/fatty acid peroxidation, estrogen metabolism, and related DNA-adduct/depurination/mutation formation. The pathometabolic trajectory is affected by high estrogen, insulin, and growth factor cascades and resultant accelerated proliferation/progression. Anthropometric risk factors - high birth weight, adult tallness, adiposity/BMI, and weight gain - are often reflective of these trends. A sex-based nutritional approach targets women's specific risk in western obesogenic environments, associated with increasing fatness, estrogen metabolism, n-6 : n-3 polyunsaturated fatty acid ratio, and n-6 polyunsaturated fatty acid conversion to proinflammatory/carcinogenic eicosanoids, and effects of timing of life events, for example, ages at menarche, full-term pregnancy, and menopause. Recent large-scale studies have confirmed the effectiveness of the evidence-based recommendations against BC risk, emphasizing low-energy density diets, highly nutritious plant-based regimes, physical activity, and body/abdominal adiposity management. Better understanding of dietary inter-relationships with BC, as applied to food intake, selection, combination, and processing/preparation, and recommended patterns, for example, Mediterranean, DASH, plant-based, low energy density, and low glycemic load, with high nutrient/phytonutrient density, would increase public motivation and authoritative support for early

  18. Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors.

    Directory of Open Access Journals (Sweden)

    Hector Hernandez-Vargas

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions. METHODS AND FINDINGS: We characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption. Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy. CONCLUSION: Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis.

  19. Clinical utility of exemestane in the treatment of breast cancer 

    Directory of Open Access Journals (Sweden)

    Zucchini G

    2015-05-01

    Full Text Available Giorgia Zucchini,1 Elena Geuna,1 Andrea Milani,1 Caterina Aversa,2 Rossella Martinello,2 Filippo Montemurro1 1Investigative Clinical Oncology, Fondazione del Piemonte per l’Oncologia-Candiolo Cancer Institute (IRCCs, Candiolo, 2University of Turin Medical School, Turin, Italy Abstract: Breast cancer is the most prevalent cancer in women, causing a significant mortality worldwide. Different endocrine strategies are available for the treatment of hormone-sensitive breast cancer, including antiestrogen tamoxifen and fulvestrant, as well as third-generation aromatase inhibitors (AIs, such as letrozole, anastrozole, and exemestane. In this review, we will focus on exemestane, its clinical use, and its side effects. Exemestane is a steroidal third-generation AI now used in all treatment settings for breast cancer. In the metastatic disease, it has been extensively investigated as the first-, second-, and further-line treatment and it is now registered for the treatment of postmenopausal women with advanced estrogen-receptor-positive breast cancer whose disease has progressed following antiestrogen therapy. A potential lack of cross-resistance with nonsteroidal AIs has been described, giving additional therapeutic opportunities in sequences of endocrine agents. Exemestane is also approved for the adjuvant treatment of postmenopausal early breast cancer, either as upfront monotherapy for 5 years, as a switch following 2–3 years of tamoxifen, or as extended therapy beyond 5 years of adjuvant treatment. New promising data also showed a beneficial effect in young premenopausal early breast cancer patients, when administered together with ovarian suppression. Interesting results have also emerged when exemestane has been investigated as neodjuvant treatment as well as preventive agent in healthy women at high risk for breast cancer. Exemestane is generally well tolerated, with a side effect profile similar to that of other AIs, including menopausal

  20. [Willingness of potential service suppliers to provide cancer screening in urban China].

    Science.gov (United States)

    Mao, A Y; Shi, J F; Qiu, W Q; Dong, P; Sun, Z X; Huang, H Y; Sun, X J; Liu, G X; Wang, D B; Bai, Y N; Liao, X Z; Ren, J S; Guo, L W; Lan, L; Zhou, Q; Zhou, J Y; Yang, L; Wang, J L; Qin, M F; Zhang, Y Z; Song, B B; Xing, X J; Zhu, L; Mai, L; Du, L B; Liu, Y Q; Lou, P A; Cai, B; Sun, X H; Wu, S L; Qi, X; Zhang, K; He, J; Dai, M

    2018-02-10

    Objective: Based on the investment for potential suppliers of cancer screening services, we assessed the reasons that affecting their participation motivation related to the long-term sustainability of cancer screening in China. Methods: Hospitals that had never been involved in any national level cancer screening project were selected by using the convenient sampling method within the 16 project cities of Cancer Screening Program in Urban China (CanSPUC) with 1 or 2 hospitals for each city. All the managers from the institutional/department level and professional staff working and providing screening services in these hospitals, were interviewed by paper-based questionnaire. SAS 9.4 was used for logical verification and data analysis. Results: A total of 31 hospitals (18 hospitals at the third level and, 13 hospitals at the second level) and 2 201 staff (508 hospital and clinic unit managers, 1 693 professional staff) completed the interview. All the hospitals guaranteed their potential capacity in service providing. 92.5% hospital managers showed strong willingness in providing cancer screening services, while 68.3% of them declared that the project fund-raising function was the responsibility of the government. For professional staff, their prospect gains from providing screening service would include development on professional skills (72.4%) and material rewards (46.8%). Their main worries would include extra work for CanSPUC might interfere their routine work (42.1%) plus inadequate compensation (41.8%). Medians of the prospect compensation for extra work ran between 20 to 90 Chinese Yuan per screening item respectively. For all the screening items, workers from the third-level hospitals expected their compensation to be twice as much of those working at the second level hospitals. Conclusion: Professional capacity building and feasible material incentive seemed to be the two key factors that influenced the sustainability and development of the programs.

  1. The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Shunfei Yan

    2017-01-01

    Full Text Available Overall survival for patients with ovarian cancer (OC has shown little improvement for decades meaning new therapeutic options are critical. OC comprises multiple histological subtypes, of which the most common and aggressive subtype is high-grade serous ovarian cancer (HGSOC. HGSOC is characterized by genomic structural variations with relatively few recurrent somatic mutations or dominantly acting oncogenes that can be targeted for the development of novel therapies. However, deregulation of pathways controlling homologous recombination (HR and ribosome biogenesis has been observed in a high proportion of HGSOC, raising the possibility that targeting these basic cellular processes may provide improved patient outcomes. The poly (ADP-ribose polymerase (PARP inhibitor olaparib has been approved to treat women with defects in HR due to germline BRCA mutations. Recent evidence demonstrated the efficacy of targeting ribosome biogenesis with the specific inhibitor of ribosomal RNA synthesis, CX-5461 in v-myc avian myelocytomatosis viral oncogene homolog (MYC-driven haematological and prostate cancers. CX-5461 has now progressed to a phase I clinical trial in patients with haematological malignancies and phase I/II trial in breast cancer. Here we review the currently available targeted therapies for HGSOC and discuss the potential of targeting ribosome biogenesis as a novel therapeutic approach against HGSOC.

  2. 99mTc-Glucarate as a potential novel tracer of lung cancer lesions

    International Nuclear Information System (INIS)

    Gambini, Juan P; Cabral, Pablo; Santander, Gianeya; Canepa, Jorge; Andruskevicius, Patricia; Piuma, Lourdes; Savio, Eduardo; Delgado, Lucia; Quagliata, Adriana; Alonso, Omar

    2006-01-01

    Lung cancer is the leading cause of cancer-related mortality in the world. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung malignant tumors and it usually presents at the moment of diagnosis as a locally advanced or metastatic disease. Surgery is not indicated in two thirds of them, being chemotherapy (QT) the accepted therapeutic approach. Only 30% of those patients respond to treatment whereas the remaining group will receive antineoplasic drugs without any therapeutic benefit but suffering their adverse effects. In this situation, it would be of clinical relevance to have a functional scintigraphic technique with the potential to evaluate in an early-phase the response to therapy. Our group has developed a clinical protocol to investigate if 99m Tc-Glucarate can be used to predict the response to QT in this group of patients. In order to accomplish this objective, we have to previously demonstrate that primary and secondary lesions of NSCLC can accumulate the radiotracer. The present case report describes for the first time in the indexed literature the use of 99m Tc-Glucarate as a functional marker of primary and secondary lesions of NSCLC (au)

  3. [THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

    Science.gov (United States)

    Mikhailenko, D S; Kushlinskii, N E

    2016-02-01

    All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

  4. Virtual simulation. First clinical results in patients with prostate cancer

    International Nuclear Information System (INIS)

    Buchali, A.; Dinges, S.; Koswig, S.; Rosenthal, P.; Salk, S.; Harder, C.; Schlenger, L.; Budach, V.

    1998-01-01

    Investigation of options of virtual simulation in patients with localized prostate cancer. Twenty-four patients suffering from prostate cancer were virtual simulated. The clinical target volume was contoured and the planning target volume was defined after CT scan. The isocenter of the planning target volume was determined and marked at patient's skin. The precision of patients marking was controlled with conventional simulation after physical radiation treatment planning. Mean differences of the patient's mark revealed between the 2 simulations in all room axes around 1 mm. The organs at risk were visualized in the digital reconstructed radiographs. The precise patient's mark of the isocentre by virtual simulation allows to skip the conventional simulation. The visualisation of organs at risk leeds to an unnecessarity of an application of contrast medium and to a further relieve of the patient. The personal requirement is not higher in virtual simulation than in conventional CT based radiation treatment planning. (orig./MG) [de

  5. Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer

    DEFF Research Database (Denmark)

    Havelund, Birgitte Mayland; Spindler, Karen-Lise Garm; Sørensen, Flemming Brandt

    Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer  Birgitte Mayland Havelund1,4 MD, Karen-Lise Garm Spindler1,4 MD, PhD, Flemming Brandt Sørensen2,4 MD, DMSc, Ivan Brandslund3 MD, DMSc, Anders Jakobsen1,4 MD, DMSc.1Department of Oncology, 2Pathology and 3Biochemistry, Vejle...... activates transcription of numerous genes associated with angiogenesis, ATP-metabolism, cell-proliferation, glycolysis and apoptosis. HIF-1α is over expressed in many malignant tumors and is reported to play an important role in tumor invasion and progression. The aim of this Ph.D. project is to investigate...... the predictive and prognostic value of HIF-1α in colorectal cancer.Materials and MethodsThe project is divided into 3 substudies:1. Biological and methodological aspects. The expression of HIF-1α measured by immunohistochemistry in paraffin embedded tissue is related to single nucleotide polymorphism (SNP...

  6. Metformin and breast cancer: basic knowledge in clinical context.

    Science.gov (United States)

    Pizzuti, Laura; Vici, Patrizia; Di Lauro, Luigi; Sergi, Domenico; Della Giulia, Marina; Marchetti, Paolo; Maugeri-Saccà, Marcello; Giordano, Antonio; Barba, Maddalena

    2015-05-01

    Although preclinical work is vital in unraveling the molecular tenets which apply to metformin action in breast cancer, it is by nature unable to capture the host's response to metformin in terms of insulin-mediated effects and related changes in the hormonal and metabolic asset at the systemic level. The latter might sound seemingly paradoxical when considering the inveterate use of metformin in dysmetabolisms and pathologic conditions with underlying hormonal disruption. Bridging the gap between the molecular target and characteristics of breast cancer patients may help lab-based experiments and clinical work converge into one or more well characterized sub-populations instead of a sub optimally selected one. An appropriate patient selection is the main key to the most suitable outcome interpretation and amelioration, in an attempt to meet our patients needs midway between overestimation of benefits and efficacy dilution for any given intervention and/or co-intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. [Molecular characterization of breast cancer in clinical practice].

    Science.gov (United States)

    Zemmouri, Y; De Croze, D; Vincent Salomon, A; Rouzier, R; Bonneau, C

    2016-05-01

    Breast cancer involves various types of tumors. The objective of this review was to provide a summary of the main methods currently available in clinical practice to characterize breast cancers at a molecular level and to discuss their prognostic and predictive values. Hormonal receptors expression and the HER2 status are prognostic markers and can also predict the response to targeted therapies. Their analysis through immunohistochemistry is systematical. Ki67 is an effective prognostic marker, but its reliability is debated because of its low reproducibility between laboratories and between pathologists. Commercial genomic signatures are all considered valid prognostic tools and may guide physicians to make therapeutic choices. These signatures are costly and should therefore be restricted to situations in which the use of chemotherapy remains equivocal. Copyright © 2016. Published by Elsevier SAS.

  8. Pharmacogenetics: progress, pitfalls and clinical potential for coronary heart disease.

    Science.gov (United States)

    Humphries, Steve E; Hingorani, Aroon

    2006-02-01

    Much has been written about the potential of pharmacogenetic testing to inform therapy based on an individual's genetic makeup, and to decide the most effective choice of available drugs, or to avoid dangerous side effects. Currently, there is little hard data for either in the field of cardiovascular disease. The usual approach has been opportunistic use of drug trials in unrelated patients, and to look for differences in response or outcome by "candidate gene" genotype, for example genes coding for drug metabolising enzymes (activators and metabolisers), and enzymes and receptors involved in lipid metabolism, adrenergic response, etc. As with all association studies, initially promising results have often failed the test of replication in larger studies, and the relationship between the CETP Taq-I variant and response to statins has now been disproved. The strongest data to date is the report [Chasman, D.I., Posada, D., Subrahmanyan, L., Cook, N.R., Stanton Jr., V.P., Ridker, P.M., 2004. Pharmacogenetic study of statin therapy and cholesterol reduction. J. Am. Med. Assoc. 291, 2821-2827] of a poorer cholesterol-lowering response to Pravastatin in the 7% of patients carrying a certain haplotype of the HMG CoA reductase gene (14% fall versus 19%), but if this is overcome simply by a higher dose, it is of little clinical relevance. Currently, the best example of avoiding side effects is determining genotype at the CYP2C9 locus with respect of warfarin treatment, since carriers for functional variants (>20% of the population) require lower doses for optimal anticoagulation, and homozygotes, although rare, may well experience serious bleeding if given a usual dose. The full potential of this field will only be realised with much further work.

  9. Province wide clinical governance network for clinical audit for quality improvement in endometrial cancer management.

    Science.gov (United States)

    Mandato, Vincenzo Dario; Formisano, Debora; Pirillo, Debora; Ciarlini, Gino; Cerami, Lillo Bruno; Ventura, Alessandro; Spreafico, Lorenzo; Palmieri, Tamara; La Sala, Giovanni Battista; Abrate, Martino

    2012-01-01

    According to the hub-and-spoke model introduced in the Provincial Healthcare System of Reggio Emilia, early endometrial cancer is treated in peripheral low-volume hospitals (spokes) by general gynecologist, whereas more complex cancers are treated by gynecological oncologists at the main hospital (hub). To guarantee a uniformly high standard of care to all patients with endometrial cancer treated in hub and spoke hospitals of Reggio Emilia Province. The specialists of the 5 hospitals of Reggio Emilia Province instituted an inter hospital and multidisciplinary oncology group to write common and shared guidelines based on evidence-based medicine through the use of clinical audit. They valued the process indicators before and after guidelines introduction identifying the site of improvement and verifying the standard achievement. Diagnostic hysteroscopy use increased significantly from preguideline period, 53%, to postguideline period, 74%. Magnetic resonance use and accuracy increased significantly from preguideline to postguideline periods: 8.1% to 35.3% and 37.3% to 74.7%, respectively. Laparoscopy use increased from 1.6% (preguideline) to 18.6 (postguideline). Early surgical complications decreased from 16% (preguideline) to 9% (postguideline). Radiotherapy use increased from 14.% (preguideline) to 32.3% (postguideline). It is possible for a provincial oncology group to build an oncology network providing an improvement in the assistance of patients with endometrial cancer through the use of clinical audit. Clinical audit made it possible to obtain the full attendance of specialists of various disciplines involved in the treatment of endometrial cancer to optimize response time schematizing process.

  10. [Role and management of cancer clinical database in the application of gastric cancer precision medicine].

    Science.gov (United States)

    Li, Yuanfang; Zhou, Zhiwei

    2016-02-01

    Precision medicine is a new medical concept and medical model, which is based on personalized medicine, rapid progress of genome sequencing technology and cross application of biological information and big data science. Precision medicine improves the diagnosis and treatment of gastric cancer to provide more convenience through more profound analyses of characteristics, pathogenesis and other core issues in gastric cancer. Cancer clinical database is important to promote the development of precision medicine. Therefore, it is necessary to pay close attention to the construction and management of the database. The clinical database of Sun Yat-sen University Cancer Center is composed of medical record database, blood specimen bank, tissue bank and medical imaging database. In order to ensure the good quality of the database, the design and management of the database should follow the strict standard operation procedure(SOP) model. Data sharing is an important way to improve medical research in the era of medical big data. The construction and management of clinical database must also be strengthened and innovated.

  11. Synthesis maps: visual knowledge translation for the CanIMPACT clinical system and patient cancer journeys.

    Science.gov (United States)

    Jones, P H; Shakdher, S; Singh, P

    2017-04-01

    Salient findings and interpretations from the canimpact clinical cancer research study are visually represented in two synthesis maps for the purpose of communicating an integrated presentation of the study to clinical cancer researchers and policymakers. Synthesis maps integrate evidence and expertise into a visual narrative for knowledge translation and communication. A clinical system synthesis map represents the current Canadian primary care and cancer practice systems, proposed as a visual knowledge translation from the mixed-methods canimpact study to inform Canadian clinical research, policy, and practice discourses. Two synthesis maps, drawn together from multiple canimpact investigations and sources, were required to articulate critical differences between the clinical system and patient perspectives. The synthesis map of Canada-wide clinical cancer systems illustrates the relationships between primary care and the full cancer continuum. A patient-centred map was developed to represent the cancer (and primary care) journeys as experienced by breast and colorectal cancer patients.

  12. Clinical Potential of Hyperbaric Pressure-Treated Whey Protein

    Science.gov (United States)

    Piccolomini, André F.; Kubow, Stan; Lands, Larry C.

    2015-01-01

    Whey protein (WP) from cow’s milk is a rich source of essential and branched chain amino acids. Whey protein isolates (WPI) has been demonstrated to support muscle accretion, antioxidant activity, and immune modulation. However, whey is not readily digestible due to its tight conformational structure. Treatment of WPI with hyperbaric pressure results in protein unfolding. This enhances protein digestion, and results in an altered spectrum of released peptides, and greater release of essential and branched chain amino acids. Pressurized whey protein isolates (pWPI), through a series of cell culture, animal models and clinical studies, have been demonstrated to enhance muscle accretion, reduce inflammation, improve immunity, and decrease fatigue. It is also conceivable that pWPI would be more accessible to digestive enzymes, which would allow for a more rapid proteolysis of the proteins and an increased or altered release of small bioactive peptides. The altered profile of peptides released from WP digestion could thus play a role in the modulation of the immune response and tissue glutathione (GSH) concentrations. The research to date presents potentially interesting applications for the development of new functional foods based on hyperbaric treatment of WPI to produce products with more potent nutritional and nutraceutical properties. PMID:27417773

  13. Understanding Cancer Worry Among Patients in a Community Clinic-Based Colorectal Cancer Screening Intervention Study.

    Science.gov (United States)

    Christy, Shannon M; Schmidt, Alyssa; Wang, Hsiao-Lan; Sutton, Steven K; Davis, Stacy N; Chavarria, Enmanuel; Abdulla, Rania; Quinn, Gwendolyn P; Vadaparampil, Susan T; Schultz, Ida; Roetzheim, Richard; Shibata, David; Meade, Cathy D; Gwede, Clement K

    2018-06-04

    To reduce colorectal cancer (CRC) screening disparities, it is important to understand correlates of different types of cancer worry among ethnically diverse individuals. The current study examined the prevalence of three types of cancer worry (i.e., general cancer worry, CRC-specific worry, and worry about CRC test results) as well as sociodemographic and health-related predictors for each type of cancer worry. Participants were aged 50-75, at average CRC risk, nonadherent to CRC screening guidelines, and enrolled in a randomized controlled trial to increase CRC screening. Participants completed a baseline questionnaire assessing sociodemographics, health beliefs, healthcare experiences, and three cancer worry measures. Associations between study variables were examined with separate univariate and multivariable logistic regression models. Responses from a total of 416 participants were used. Of these, 47% reported experiencing moderate-to-high levels of general cancer worry. Predictors of general cancer worry were salience and coherence (aOR = 1.1, 95% CI [1.0, 1.3]), perceived susceptibility (aOR = 1.2, 95% CI [1.1, 1.3), and social influence (aOR = 1.1, 95% CI [1.0, 0.1]). Fewer (23%) reported moderate-to-high levels of CRC-specific worry or CRC test worry (35%). Predictors of CRC worry were perceived susceptibility (aOR = 1.4, 95% CI [1.3, 1.6]) and social influence (aOR = 1.1, 95% CI [1.0, 1.2]); predictors of CRC test result worry were perceived susceptibility (aOR = 1.2, 95% CI [1.1, 1.3) and marital status (aOR = 2.0, 95% CI [1.1, 3.7] for married/partnered vs. single and aOR = 2.3, 95% CI [1.3, 4.1] for divorced/widowed vs. single). Perceived susceptibility consistently predicted the three types of cancer worry, whereas other predictors varied between cancer worry types and in magnitude of association. The three types of cancer worry were generally predicted by health beliefs, suggesting potential malleability. Future research should include multiple

  14. A Preclinical Evaluation of Antimycin A as a Potential Antilung Cancer Stem Cell Agent

    Directory of Open Access Journals (Sweden)

    Chi-Tai Yeh

    2013-01-01

    Full Text Available Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs as the major contributor to these clinical challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs, was used to identify potential anti-CSC agents. An antibiotic, antimycin A (AMA, was identified as a top candidate. SP A549 cells exhibited an elevated stemness profile, including Nanog, β-catenin, Sox2, and CD133, and increased self-renewal ability. AMA treatment was found to suppress β-catenin signaling components and tumor sphere formation. Furthermore, AMA treatment decreased the proliferation of gefitinib-resistant PC-9/GR cells and percentage of SP population. AMA demonstrated synergistic suppression of PC-9/GR cell viability when combined with gefitinib. Finally, AMA treatment suppressed tumorigenesis in mice inoculated with A549 SP cells. Collectively, we have identified AMA using CMAP as a novel antilung CSC agent, which acts to downregulate β-catenin signaling. The combination of AMA and targeted therapeutic agents could be considered for overcoming drug resistance and relapse in lung cancer patients.

  15. National Cancer Patient Registry--a patient registry/clinical database to evaluate the health outcomes of patients undergoing treatment for cancers in Malaysia.

    Science.gov (United States)

    Lim, G C C; Azura, D

    2008-09-01

    Cancer burden in Malaysia is increasing. Although there have been improvements in cancer treatment, these new therapies may potentially cause an exponential increase in the cost of cancer treatment. Therefore, justification for the use of these treatments is mandated. Availability of local data will enable us to evaluate and compare the outcome of our patients. This will help to support our clinical decision making and local policy, improve access to treatment and improve the provision and delivery of oncology services in Malaysia. The National Cancer Patient Registry was proposed as a database for cancer patients who seek treatment in Malaysia. It will be a valuable tool to provide timely and robust data on the actual setting in oncology practice, safety and cost effectiveness of treatment and most importantly the outcome of these patients.

  16. Fulfilling the potential of cancer prevention and early detection

    National Research Council Canada - National Science Library

    Curry, Susan J; Byers, Tim; Hewitt, Maria Elizabeth

    2003-01-01

    .... The National Cancer Policy Board, part of the Institute of Medicine, outlines a national strategy to realize the promise of cancer prevention and early detection, including specific and wide-ranging recommendations...

  17. American Society of Clinical Oncology Policy Statement: The Role of the Oncologist in Cancer Prevention and Risk Assessment

    Science.gov (United States)

    Zon, Robin T.; Goss, Elizabeth; Vogel, Victor G.; Chlebowski, Rowan T.; Jatoi, Ismail; Robson, Mark E.; Wollins, Dana S.; Garber, Judy E.; Brown, Powel; Kramer, Barnett S.

    2009-01-01

    Oncologists have a critical opportunity to utilize risk assessment and cancer prevention strategies to interrupt the initiation or progression of cancer in cancer survivors and individuals at high risk of developing cancer. Expanding knowledge about the natural history and prognosis of cancers positions oncologists to advise patients regarding the risk of second malignancies and treatment-related cancers. In addition, as recognized experts in the full spectrum of cancer care, oncologists are afforded opportunities for involvement in community-based cancer prevention activities. Although oncologists are currently providing many cancer prevention and risk assessment services to their patients, economic barriers exist, including inadequate or lack of insurance, that may compromise uniform patient access to these services. Additionally, insufficient reimbursement for existing and developing interventions may discourage patient access to these services. The American Society of Clinical Oncology (ASCO), the medical society representing cancer specialists involved in patient care and clinical research, is committed to supporting oncologists in their wide-ranging involvement in cancer prevention. This statement on risk assessment and prevention counseling, although not intended to be a comprehensive overview of cancer prevention describes the current role of oncologists in risk assessment and prevention; provides examples of risk assessment and prevention activities that should be offered by oncologists; identifies potential opportunities for coordination between oncologists and primary care physicians in prevention education and coordination of care for cancer survivors; describes ASCO's involvement in education and training of oncologists regarding prevention; and proposes improvement in the payment environment to encourage patient access to these services. PMID:19075281

  18. Potential clinical efficacy of intensity-modulated conformal therapy

    International Nuclear Information System (INIS)

    Meeks, Sanford L.; Buatti, John M.; Bova, Francis J.; Friedman, William A.; Mendenhall, William M.; Zlotecki, Robert A.

    1998-01-01

    Purpose: The purpose of this study was to examine the potential benefit of using intensity-modulated conformal therapy for a variety of lesions currently treated with stereotactic radiosurgery or conventional radiotherapy. Methods and Materials: Intensity-modulated conformal treatment plans were generated for small intracranial lesions, as well as head and neck, lung, breast, and prostate cases, using the Peacock Plan[reg] treatment-planning system (Nomos Corporation). For small intracranial lesions, intensity-modulated conformal treatment plans were compared with stereotactic radiosurgery treatment plans generated for patient treatment at the University of Florida Shands Cancer Center. For other sites (head and neck, lung, breast, and prostate), plans generated using the Peacock Plan[reg] were compared with conventional treatment plans, as well as beam's-eye-view conformal treatment plans. Plan comparisons were accomplished through conventional qualitative review of two-dimensional (2D) dose distributions in conjunction with quantitative techniques, such as dose-volume histograms, dosimetric statistics, normal tissue complication probabilities, tumor control probabilities, and objective numerical scoring. Results: For small intracranial lesions, there is little difference between intensity-modulated conformal treatment planning and radiosurgery treatment planning in the conformation of high isodose lines with the target volume. However, stereotactic treatment planning provides a steeper dose gradient outside the target volume and, hence, a lower normal tissue toxicity index. For extracranial sites, objective numerical scores for beam's-eye-view and intensity-modulated conformal planning techniques are superior to scores for conventional treatment plans. The beam's-eye-view planning technique prevents geographic target misses and better excludes healthy tissues from the treatment portal. Compared with scores for the beam's-eye-view planning technique, scores for

  19. Nutraceuticals as potential therapeutic agents for colon cancer: a review

    OpenAIRE

    Kuppusamy, Palaniselvam; Yusoff, Mashitah M.; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

    2014-01-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment o...

  20. Therapeutic potential of bryophytes and derived compounds against cancer

    Directory of Open Access Journals (Sweden)

    Abhijit Dey

    2015-08-01

    Full Text Available Bryophytes, taxonomically placed between the algae and the pteridophytes, are divided into three classes such as Liverworts, Hornworts and Mosses. Indigenous use involves this small group of plants to treat various diseases. Bryophytes have been investigated pharmacologically for active biomolecules. Several constituents with therapeutic potential have been isolated, characterized and investigated for antibacterial, antifungal, antiviral, antioxidative, antiinflamatory and anticancerous efficacy. The present review deals with the literature covering the anticancerous potential of bryophytes. Apart from the examples of the compounds and the containing bryophyte genera, the authors have tried to include the examples of cancer cell lines on which the efficacy have been tested and the mode of action of certain cytotoxic agents. Crude extracts and isolated compounds from bryophytes were found to possess potent cytotoxic properties. Different types of terpenoids and bibenzyls have been reported among the most potent cytotoxic compounds. Most of these compounds were found to induce apoptosis by activating a number of genes and enzymes. Biochemical markers such as DNA fragmentation, nuclear condensation, proteolysis of poly (ADP-ribose polymerase, activation of caspases, inhibition of antiapoptotic nuclear transcriptional factor-kappaB, activation of p38 mitogen-activated protein kinase etc. have been found to be associated with apoptotic and necrotic response. This review summarizes recent scientific findings and suggests further investigations to evaluate the cytotoxic efficacy of bryophytes.

  1. Concanavalin A: A potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics

    International Nuclear Information System (INIS)

    Li, Wen-wen; Yu, Jia-ying; Xu, Huai-long; Bao, Jin-ku

    2011-01-01

    Highlights: → ConA induces cancer cell death targeting apoptosis and autophagy. → ConA inhibits cancer cell angiogenesis. → ConA is utilized in pre-clinical and clinical trials. -- Abstract: Concanavalin A (ConA), a Ca 2+ /Mn 2+ -dependent and mannose/glucose-binding legume lectin, has drawn a rising attention for its remarkable anti-proliferative and anti-tumor activities to a variety of cancer cells. ConA induces programmed cell death via mitochondria-mediated, P73-Foxo1a-Bim apoptosis and BNIP3-mediated mitochondrial autophagy. Through IKK-NF-κB-COX-2, SHP-2-MEK-1-ERK, and SHP-2-Ras-ERK anti-angiogenic pathways, ConA would inhibit cancer cell survival. In addition, ConA stimulates cell immunity and generates an immune memory, resisting to the same genotypic tumor. These biological findings shed light on new perspectives of ConA as a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis in pre-clinical or clinical trials for cancer therapeutics.

  2. Clinical studies on radiosensitization of cervical cancer by cisplatinum

    International Nuclear Information System (INIS)

    Yu Shiying; Chen Yuan; Xu Zhiqiang

    1993-01-01

    A prospective randomized clinical trial on the radiosensitizing effect of cisplatinum was carried out in 60 patients with cervical cancer, of whom 30 were given cisplatinum in combination with radiotherapy (radiosensitizing group) and the remaining 30 radiotherapy alone (control group). The results showed that the length of time of immediate CR and PR was shorter in the radiosensitizing group than in the control group. The sensitive enhancement ratio was 1.846. No toxicity was observed in the radiosensitizing group, and the treatment was well tolerated by the patients

  3. Surgical treatment for progressive prostate cancer: A clinical case

    Directory of Open Access Journals (Sweden)

    E. I. Veliev

    2014-01-01

    Full Text Available In spite of its existing standards, the treatment of patients with progressive prostate cancer (PC remains a matter of debate. Ensuring that the patients have good quality of life is also relevant. The paper describes a clinical case of a patient with progressive PC after hormone therapy, brachytherapy, salvage prostatectomy, enucleation of the testicular parenchyma, and salvage lymphadenectomy. A phallic prosthesis and an artificial urinary sphincter have been implanted to improve quality of life. The results of preoperative examination and the technological features of surgical interventions are given.

  4. [Clinical impact of social marketing strategy on breast cancer detection].

    Science.gov (United States)

    Quintana-Vidaurri, Adriana Guadalupe; Santana-Chávez, Luis Alejandro; González-Villalobos, Cynthia Guadalupe

    2013-01-01

    to prove the impact of social marketing strategies in breast cancer detection, taking as a parameter the number of mammographies performed. quasi-experimental research, before and after. Sixty-nine physicians in charge of medical consultation and fourteen nurses were studied for a period of seven months, applying social marketing strategies. The total of mammographies were analyzed using Wilcoxon rank-sum test (p marketing proved to be an adequate strategy, which has an impact on the clinical practice of both physicians and nurses.

  5. Biomarkers Associated with Cognitive Impairment in Treated Cancer Patients: Potential Predisposition and Risk Factors

    Science.gov (United States)

    Castel, Hélène; Denouel, Angeline; Lange, Marie; Tonon, Marie-Christine; Dubois, Martine; Joly, Florence

    2017-01-01

    Purpose: Cognitive impairment in cancer patients induced, at least in part, by treatment are frequently observed and likely have negative impacts on patient quality of life. Such cognitive dysfunctions can affect attention, executive functions, and memory and processing speed, can persist after treatment, and their exact causes remain unclear. The aim of this review was to create an inventory and analysis of clinical studies evaluating biological markers and risk factors for cognitive decline in cancer patients before, during, or after therapy. The ultimate objectives were to identify robust markers and to determine what further research is required to develop original biological markers to enable prevention or adapted treatment management of patients at risk. Method: This review was guided by the PRISMA statement and included a search strategy focused on three components: “cognition disorders,” “predictive factors”/“biological markers,” and “neoplasms,” searched in PubMed since 2005, with exclusion criteria concerning brain tumors, brain therapy, and imaging or animal studies. Results: Twenty-three studies meeting the criteria were analyzed. Potential associations/correlations were identified between cognitive impairments and specific circulating factors, cerebral spinal fluid constituents, and genetic polymorphisms at baseline, during, and at the end of treatment in cancer populations. The most significant results were associations between cognitive dysfunctions and genetic polymorphisms, including APOE-4 and COMT-Val; increased plasma levels of the pro-inflammatory cytokine, IL-6; anemia; and hemoglobin levels during chemotherapy. Plasma levels of specific hormones of the hypothalamo-pituitary-adrenal axis are also modified by treatment. Discussion: It is recognized in the field of cancer cognition that cancer and comorbidities, as well as chemotherapy and hormone therapy, can cause persistent cognitive dysfunction. A number of biological

  6. Promoting early presentation of breast cancer in older women: sustained effect of an intervention to promote breast cancer awareness in routine clinical practice.

    Science.gov (United States)

    Dodd, Rachael H; Forster, Alice S; Sellars, Sarah; Patnick, Julietta; Ramirez, Amanda J; Forbes, Lindsay J L

    2017-06-05

    Older women have poorer survival from breast cancer, which may be at least partly due to poor breast cancer awareness leading to delayed presentation and more advanced stage at diagnosis. In a randomised trial, an intervention to promote early presentation of breast cancer in older women increased breast cancer awareness at 1 year compared with usual care (24 versus 4%). We examined its effectiveness in routine clinical practice. We piloted the intervention delivered by practising health professionals to women aged about 70 in four breast screening services. We measured the effect on breast cancer awareness at 1 year compared with comparison services, where women did not receive the intervention. At 1 year, 25% of women in pilot services were breast cancer aware compared with 4% in comparison services (p = 0.001). The components of breast cancer awareness were knowledge of breast cancer non-lump symptoms (pilot: 63% vs comparison: 82% at 1 year; OR = 2.56, 95% CI 1.92-3.42), knowledge of age related risk (pilot: 8% vs comparison: 36% at 1 year; OR = 5.56, 95% CI 4.0-7.74) and reported breast checking (pilot: 70% vs comparison: 78% at 1 year; OR = 1.49, 95% CI 1.13-1.96). The intervention may be as effective in routine clinical practice as in a randomised controlled trial. This intervention has the potential to reduce patient delay in the diagnosis of breast cancer in older women. The PEP trial was registered with the International Standard Registered Clinical/soCial sTudy Number (ISRCTN) as a clinical trial ( ISRCTN31994827 ) on 3rd October 2007.

  7. Receptor tyrosine kinase (c-Kit inhibitors: a potential therapeutic target in cancer cells

    Directory of Open Access Journals (Sweden)

    Abbaspour Babaei M

    2016-08-01

    Full Text Available Maryam Abbaspour Babaei,1 Behnam Kamalidehghan,2,3 Mohammad Saleem,4–6 Hasniza Zaman Huri,1,7 Fatemeh Ahmadipour1 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB, Shahrak-e Pajoohesh, 3Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Urology, 5Department of Laboratory Medicine and Pathology, Masonic Cancer Center, University of Minnesota, 6Section of Molecular Therapeutics & Cancer Health Disparity, The Hormel Institute, Austin, MN, USA; 7Clinical Investigation Centre, University Malaya Medical Centre, Lembah Pantai, Kuala Lumpur, Malaysia Abstract: c-Kit, a receptor tyrosine kinase, is involved in intracellular signaling, and the mutated form of c-Kit plays a crucial role in occurrence of some cancers. The function of c-Kit has led to the concept that inhibiting c-Kit kinase activity can be a target for cancer therapy. The promising results of inhibition of c-Kit for treatment of cancers have been observed in some cancers such as gastrointestinal stromal tumor, acute myeloid leukemia, melanoma, and other tumors, and these results have encouraged attempts toward improvement of using c-Kit as a capable target for cancer therapy. This paper presents the findings of previous studies regarding c-Kit as a receptor tyrosine kinase and an oncogene, as well as its gene targets and signaling pathways in normal and cancer cells. The c-Kit gene location, protein structure, and the role of c-Kit in normal cell have been discussed. Comprehending the molecular mechanism underlying c-Kit-mediated tumorogenesis is consequently essential and may lead to the identification of future novel drug targets. The potential mechanisms by which c-Kit induces cellular transformation have been described. This study aims to elucidate the function of c

  8. Innovating information-delivery for potential clinical trials participants. What do patients want from multi-media resources?

    Science.gov (United States)

    Shneerson, Catherine; Windle, Richard; Cox, Karen

    2013-01-01

    To discover whether the provision of clinical trials information via a multi-media platform could better meet the needs, preferences and practices of potential cancer trial participants. A mixed qualitative and quantitative questionnaire was delivered to 72 participants from cancer support groups to elicit views on the provision and design features of multimedia resources in delivering clinical trials information. Perceived lack of information is an expressed barrier to clinical trials participation. Multimedia resources were viewed positively as a way to address this barrier by most potential clinical trials participants; in particular by helping to align information to individual needs, promote active engagement with information, and by allowing more control of the learning experience. Whilst text remained the most valued attribute of any resource, other highly rated attributes included the resource being simple to use, easily accessible, having a clear focus, incorporating examples and visual aids, and being interactive. Provision of support for the learning resource was also rated highly. As in other areas, such as education, multimedia resources may enhance the delivery and acceptance of information regarding clinical trials. Better alignment of information may have a positive impact on recruitment and retention into clinical trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte

    2015-01-01

    Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic...... and predictive significance in CRC patients. This review provides an overview of the intestinal stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), B cell–specific Moloney murine leukemia virus insertion site 1 (BMI1), Musashi1 (MSI1), and sex-determining region y-box 9 (SOX9......) and their implications in human CRC. The exact roles of the intestinal stem cell markers in CRC development and progression remain unclear; however, high expression of these stem cell markers have a potential prognostic significance and might be implicated in chemotherapy resistance...

  10. Proton and neutron radiation in cancer treatment: clinical and economic outcomes

    International Nuclear Information System (INIS)

    Fleurette, F.; Charvet-Protat, S.

    1996-01-01

    The French National Agency for Medical Evaluation (ANDEM) was requested to assess the effectiveness of proton and neutron beam therapy in cancer treatment compared to conventional radiotherapy. This task was accomplished by a critical appraisal of the clinical and economic literature. According to the published economic literature and the capital and staffing cost analysis, it appears that the costs of proton therapy are likely to be two or three times greater than those conformal therapy. According to the published clinical literature, proton beam therapy should be proposed as a routine treatment only for uveal melanoma and skull base cancers. Neutron beam therapy should be proposed as a routine treatment for inoperable salivary gland tumors; its use may be also discussed in cases of stage C-D1 prostate cancers and soft tissue sarcomas. Based on the current scientific evidence and given the incidence rate of these tumors, the time and material requirements, the current French proton/neutron beam facilities are able to meet the current demand. FOr other cancers the medical and economic potential of proton therapy is still an open question. (author)

  11. The detection rates and tumor clinical/pathological stages of whole-body FDG-PET cancer screening

    International Nuclear Information System (INIS)

    Ono, Ken; Omagari, Junichi; Ochiai, Reiji; Yoshida, Tsuyoshi; Kitagawa, Mami; Kobayashi, Hisashi; Yamashita, Yasuyuki

    2007-01-01

    Fluorodeoxyglucose (FDG)-positron emission tomography (PET) has been used for cancer screening, mainly in East-Asia, and cancers are found not infrequently. However, their stages have not been clarified. We examined the detection rates of various cancers using whole-body PET for the screening of cancers in asymptomatic individuals, focusing on their clinical and pathological stages. Whole-body PET was obtained as a part of our cancer screening program among 3,426 healthy subjects. All subjects participated in a course of PET examination in conjunction with conventional examinations including a medical questionnaire, tumor markers, immunological fecal occult blood test, neck and abdominal ultrasonography and whole body computed tomography. A diagnosis and staging was obtained by an analysis of the pathological findings or by an analysis of the clinical follow-up data. Malignant tumors were discovered in 65 lesions found in 3,426 participants (1.90%). The PET findings were true-positive in 46 of the 65 cancer cases. The cancers were found in the following organs: the colon 14; thyroid gland 10; stomach 7; lung 5; liver 3; breast 2; and one each in the kidney, gallbladder, esophagus, pancreas and retroperitoneum. The stages were as follows: stage 0 5, stage I 17, stage II 10, stage III 7, and stage IV 6. One was an unknown primary. There were 19 false-negative findings (0.6%) on PET. Six cancers (0.18%) were missed in our screening program. PET imaging has the potential to detect a wide variety of cancers at potentially curative stages. Most PET-negative cancers are early stage cancers, and thus can be detected using other conventional examinations such as endoscopy. (author)

  12. Galectin-3 expression in colorectal cancer and its correlation with clinical pathological characteristics and prognosis

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2017-07-01

    Full Text Available To explore the expression levels of galectin-3 in colorectal cancer and the association between galectin-3 and its clinical pathological parameters, as well as the prognosis of colorectal cancer patients.

  13. Clinical utility of circulating cell-free DNA in advanced colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Allan A Lima Pereira

    Full Text Available Circulating cell-free DNA (cfDNA isolated from the plasma of cancer patients (pts has been shown to reflect the genomic mutation profile of the tumor. However, physician and patient assessment of clinical utility of these assays in patients with metastatic colorectal cancer (mCRC has not been previously described.Patients were prospectively consented to a prospective genomic matching protocol (Assessment of Targeted Therapies Against Colorectal Cancer [ATTACC], with collection of blood for cfDNA extraction and sequencing of a 54-gene panel in a CLIA-certified lab. Formalin-fixed, paraffin-embedded (FFPE tissue from prior resections or biopsies underwent 50-gene sequencing. Results from both assays were returned to the treating physicians for patient care and clinical trial selection. Follow-up surveys of treating physicians and chart reviews assessed clinical utility.128 mCRC pts were enrolled between 6/2014 and 1/2015. Results were returned in median of 13 and 26 days for cfDNA and FFPE sequencing, respectively. With cfDNA sequencing, 78% (100/128 of samples had a detectable somatic genomic alteration. 50% of cfDNA cases had potentially actionable alterations, and 60% of these could be genomically matched to at least one clinical trial in our institution. 50% (15/30 of these pts enrolled onto an identified matched trial. Physicians reported that the cfDNA testing improved the quality of care they could provide in 73% of the cases, and that 89% of pts reported greater satisfaction with the efforts to personalize experimental therapeutic agents.cfDNA sequencing can provide timely information on potentially actionable mutations and amplifications, thereby facilitating clinical trial enrollment and improving the perceived quality of care.

  14. TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy.

    Science.gov (United States)

    Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F; Tang, Jen-Yang; Chang, Hsueh-Wei

    2017-07-14

    Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer.

  15. TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy

    Science.gov (United States)

    Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F.; Tang, Jen-Yang

    2017-01-01

    Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer. PMID:28708091

  16. Examination of skin lesions for cancer : Which clinical decision aids and tools are available in general practice?

    NARCIS (Netherlands)

    Koelink, Cecile J. L.; Jonkman, Marcel F.; Van der Meer, Klaas; Van der Heide, Wouter K.

    2014-01-01

    Background While skin cancer incidence is rising throughout Europe, general practitioners (GP) feel unsure about their ability to diagnose skin malignancies. Objectives To evaluate whether the GP has sufficient validated clinical decision aids and tools for the examination of potentially malignant

  17. Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

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    Cymbaluk-Ploska A

    2017-06-01

    Full Text Available Aneta Cymbaluk-Płoska,1 Anita Chudecka-Głaz,1 Ewa Pius-Sadowska,2 Agnieszka Sompolska-Rzechuła,3 Bogusław Machaliński,2 Anna Surowiec,1 Janusz Menkiszak1 1Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, 2Department of General Pathology, Pomeranian Medical University, 3Department of Statistics, West Pomeranian University of Technology, Szczecin, Poland Introduction: Endometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer.Aim: To explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer.Materials and methods: Included in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012–2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA. MMP2 concentrations were quantified in the serum using multiplex immunoassays.Results: We observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium (P=0.002/0.003. The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV vs low (FIGO I and II clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3 on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre

  18. Potential Diagnostic, Prognostic and Therapeutic Targets of MicroRNAs in Human Gastric Cancer

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    Ming-Ming Tsai

    2016-06-01

    Full Text Available Human gastric cancer (GC is characterized by a high incidence and mortality rate, largely because it is normally not identified until a relatively advanced stage owing to a lack of early diagnostic biomarkers. Gastroscopy with biopsy is the routine method for screening, and gastrectomy is the major therapeutic strategy for GC. However, in more than 30% of GC surgical patients, cancer has progressed too far for effective medical resection. Thus, useful biomarkers for early screening or detection of GC are essential for improving patients’ survival rate. MicroRNAs (miRNAs play an important role in tumorigenesis. They contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors. Because of their stability in tissues, serum/plasma and other body fluids, miRNAs have been suggested as novel tumor biomarkers with suitable clinical potential. Recently, aberrantly expressed miRNAs have been identified and tested for clinical application in the management of GC. Aberrant miRNA expression profiles determined with miRNA microarrays, quantitative reverse transcription-polymerase chain reaction and next-generation sequencing approaches could be used to establish sample specificity and to identify tumor type. Here, we provide an up-to-date summary of tissue-based GC-associated miRNAs, describing their involvement and that of their downstream targets in tumorigenic and biological processes. We examine correlations among significant clinical parameters and prognostic indicators, and discuss recurrence monitoring and therapeutic options in GC. We also review plasma/serum-based, GC-associated, circulating miRNAs and their clinical applications, focusing especially on early diagnosis. By providing insights into the mechanisms of miRNA-related tumor progression, this review will hopefully aid in the identification of novel potential therapeutic targets.

  19. Molecular diagnostics of lung cancer in the clinic.

    Science.gov (United States)

    Sholl, Lynette

    2017-10-01

    According to current practice guidelines, all patients with advanced non-small cell lung cancer (NSCLC) should undergo predictive biomarker testing. For squamous cell carcinoma patients, PD-L1 immunohistochemistry is indicated to select patients for immunotherapy in the first line. For lung adenocarcinoma, all patients with advanced disease should undergo testing for epidermal growth factor receptor ( EGFR ) mutations, ALK and ROS1 rearrangements, and PD-L1 expression to predict response to EGFR, ALK, or ROS1 targeted inhibitors or immunotherapy, respectively. Besides these, a number of other biomarkers are under clinical investigation as predictors of response to targeted therapies, including BRAF , ERBB2 , MET splice mutations and amplification, and RET rearrangements. Successful testing for this complex array of molecular targets demands careful coordination between proceduralists, pathologists and molecular laboratories to ensure proper tumor tissue handling following biopsy as well as judicious use of diagnostic immunohistochemistry. Even so, sample failure rates due to inadequate tumor tissue are high in practice, particularly when using sequential testing methods. Use of next generation sequencing (NGS) in clinical practice can enable detection of multiple targets and multiple alteration types (mutation, gene copy change, and rearrangement) simultaneously even with small amounts of input nucleic acids, thus increasing molecular testing success rates. In patients with an established lung cancer diagnosis but with prohibitively limited amounts of tumor tissue or who are experiencing relapse, analyses of circulating tumor DNA (ctDNA) from the plasma can serve as an alternate testing substrate, however the more limited clinical sensitivity of this approach must be taken into account. This review will explore the indications for and pitfalls of routine NGS and plasma genotyping in the clinic, including the intersection of these technologies.

  20. Immunohistochemical expression of Fascin-1 in colorectal cancer in relation to clinical and pathological parameters.

    Science.gov (United States)

    Piskor, Barbara M; Pryczynicz, Anna; Lubowicka, Emilia; Miniewska, Katarzyna; Zinczuk, Justyna; Zareba, Konrad; Guzinska-Ustymowicz, Katarzyna

    2018-06-11

    Fascins are a group of proteins taking part in the maintenance of a proper structure of the cellular cytoskeleton. Fascin-1 is an actin-bundling protein present in neurons, fibroblasts, endothelial, smooth muscle, dendritic and mesenchymal cells whereas lack of its expression is characteristic of epithelial cells. Fascin-1 overexpression can be observed in neoplastic cells. Therefore, the aim of this study was to assess the expression of Fascin-1 protein in patients with colorectal cancer (CRC) and to analyze associations between Fascin-1 expression and clinical-pathological parameters. The study material included postoperative samples (tumor and unchanged colon tissue) obtained from 51 CRC patients. Fascin-1 expression was assessed in the paraffin sections by immunohistochemistry. A statistically significant correlation was found between the histological type of cancer and the expression of Fascin-1 (p = 0.012). Increased expression of Fascin-1 in CRC was more frequent in adenocarcinoma type without the mucosal component with a better prognosis and decreased expression of this protein correlated with infiltration of cancer cells to blood and lymphatic vessels (p = 0.038). Our findings indicate a potential role of Fascin-1 in the pathogenesis of colon cancer; however, further studies will show whether this protein plays a role in the infiltration of colorectal cancer cells.

  1. MicroRNA-10b expression in breast cancer and its clinical association.

    Directory of Open Access Journals (Sweden)

    Jianhui Zhang

    Full Text Available MicroRNAs (miRNAs are short non-coding RNA molecules that play a significant role in many types of cancers including breast cancer. In the current study, we evaluated the expression levels of microR-10b (miR-10b in 115 breast cancer patients from Sichuan Cancer Center. Real time reverse transcription-PCR was used to assess miR-10b expression. Clinical data including disease stage, survival status, age, ER/PR/HER2 status, molecular subtypes, tumor size, lymph node status and Ki-67 expression levels were correlated with miR-10b expression levels. Our data showed that the miR-10b expression is correlated with disease stage, living status and tumor sizes. We also found that miR-10b expression levels are higher in the lymph node positive group and the Ki-67 higher scoring group (score > 20. No statistically significant differences were observed based on age or molecular sub-type grouping. In conclusion, miR-10b may be a biomarker for breast cancer and is a potential treatment target.

  2. Chinese herbal medicine for cancer-related fatigue: a systematic review of randomized clinical trials.

    Science.gov (United States)

    Su, Chun-Xiang; Wang, Li-Qiong; Grant, Suzanne J; Liu, Jian-Ping

    2014-06-01

    To assess the effectiveness and safety of Chinese herbal medicine for the treatment of cancer-related fatigue. We systematically searched seven electronic databases and two trial registries for randomized clinical trials of Chinese herbal medicine for cancer-related fatigue. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool. Data were synthesized using RevMan 5.2 software. A total of 10 trials involving 751 participants with cancer-related fatigue were identified and the methodological quality of the included trials was generally poor. Chinese herbal medicine used alone or in combination with chemotherapy or supportive care showed significant relief in cancer-related fatigue compared to placebo, chemotherapy or supportive care based on single trials. Chinese herbal medicine plus chemotherapy or supportive care was superior to chemotherapy or supportive care in improving quality of life. Data from one trial demonstrated Chinese herbal medicine exerted a greater beneficial effect on relieving anxiety but no difference in alleviating depression. Seven trials reported adverse events and no severe adverse effects were found in Chinese herbal medicine groups. The findings from limited number of trials suggest that Chinese herbal medicine seems to be effective and safe in the treatment of cancer-related fatigue. However, the current evidence is insufficient to draw a confirmative conclusion due to the poor methodological quality of included trials. Thus, conducting rigorously designed trials on potential Chinese herbal medicine is warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Expression analysis and clinical utility of L-Dopa decarboxylase (DDC) in prostate cancer.

    Science.gov (United States)

    Avgeris, Margaritis; Koutalellis, Georgios; Fragoulis, Emmanuel G; Scorilas, Andreas

    2008-10-01

    L-Dopa decarboxylase (DDC) is a pyridoxal 5'-phosphate-dependent enzyme that was found to be involved in many malignancies. The aim of this study was to investigate the mRNA expression levels of DDC in prostate tissues and to evaluate its clinical utility in prostate cancer (CaP). Total RNA was isolated from 118 tissue specimens from benign prostate hyperplasia (BPH) and CaP patients and a highly sensitive quantitative real-time RT-PCR (qRT-PCR) method for DDC mRNA quantification has been developed using the SYBR Green chemistry. LNCaP prostate cancer cell line was used as a calibrator and GAPDH as a housekeeping gene. DDC was found to be overexpressed, at the mRNA level, in the specimens from prostate cancer patients, in comparison to those from benign prostate hyperplasia patients (pDDC expression has significant discriminatory value between CaP and BPH (pDDC expression status was compared with other established prognostic factors, in prostate cancer. High expression levels of DDC were found more frequently in high Gleason's score tumors (p=0.022) as well as in advanced stage patients (p=0.032). Our data reveal the potential of DDC expression, at the mRNA level, as a novel biomarker in prostate cancer.

  4. Perspectives on barriers and facilitators to minority recruitment for clinical trials among cancer center leaders, investigators, research staff, and referring clinicians: enhancing minority participation in clinical trials (EMPaCT).

    Science.gov (United States)

    Durant, Raegan W; Wenzel, Jennifer A; Scarinci, Isabel C; Paterniti, Debora A; Fouad, Mona N; Hurd, Thelma C; Martin, Michelle Y

    2014-04-01

    The study of disparities in minority recruitment to cancer clinical trials has focused primarily on inquiries among minority populations. Yet very little is known about the perceptions of individuals actively involved in minority recruitment to clinical trials within cancer centers. Therefore, the authors assessed the perspectives of cancer center clinical and research personnel on barriers and facilitators to minority recruitment. In total, 91 qualitative interviews were conducted at 5 US cancer centers among 4 stakeholder groups: cancer center leaders, principal investigators, research staff, and referring clinicians. All interviews were recorded and transcribed. Qualitative analyses of response data was focused on identifying prominent themes related to barriers and facilitators to minority recruitment. The perspectives of the 4 stakeholder groups were largely overlapping with some variations based on their unique roles in minority recruitment. Four prominent themes were identified: 1) racial and ethnic minorities are influenced by varying degrees of skepticism related to trial participation, 2) potential minority participants often face multilevel barriers that preclude them from being offered an opportunity to participate in a clinical trial, 3) facilitators at both the institutional and participant level potentially encourage minority recruitment, and 4) variation between internal and external trial referral procedures may limit clinical trial opportunities for racial and ethnic minorities. Multilevel approaches are needed to address barriers and optimize facilitators within cancer centers to enhance minority recruitment for cancer clinical trials. © 2014 American Cancer Society.

  5. Epidemiology of HPV 16 and cervical cancer in Finland and the potential impact of vaccination: mathematical modelling analyses.

    Directory of Open Access Journals (Sweden)

    Ruanne V Barnabas

    2006-05-01

    Full Text Available BACKGROUND: Candidate human papillomavirus (HPV vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question. METHODS AND FINDINGS: We developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation and high (90% in a national immunisation programme coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16 cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention. CONCLUSIONS: HPV vaccination has the potential to

  6. Identification of Cell Surface Proteins as Potential Immunotherapy Targets in 12 Pediatric Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Orentas, Rimas J. [Immunology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Yang, James J. [Immunology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Oncogenomics Section, Advanced Technology Center, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Gaithersburg, MD (United States); Wen, Xinyu; Wei, Jun S. [Oncogenomics Section, Advanced Technology Center, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Gaithersburg, MD (United States); Mackall, Crystal L. [Immunology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Khan, Javed, E-mail: rimas.orentas@nih.gov [Oncogenomics Section, Advanced Technology Center, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Gaithersburg, MD (United States)

    2012-12-17

    Technological advances now allow us to rapidly produce CARs and other antibody-derived therapeutics targeting cell surface receptors. To maximize the potential of these new technologies, relevant extracellular targets must be identified. The Pediatric Oncology Branch of the NCI curates a freely accessible database of gene expression data for both pediatric cancers and normal tissues, through which we have defined discrete sets of over-expressed transcripts in 12 pediatric cancer subtypes as compared to normal tissues. We coupled gene expression profiles to current annotation databases (i.e., Affymetrix, Gene Ontology, Entrez Gene), in order to categorize transcripts by their sub-cellular location. In this manner we generated a list of potential immune targets expressed on the cell surface, ranked by their difference from normal tissue. Global differences from normal between each of the pediatric tumor types studied varied, indicating that some malignancies expressed transcript sets that were more highly diverged from normal tissues than others. The validity of our approach is seen by our findings for pre-B cell ALL, where targets currently in clinical trials were top-ranked hits (CD19, CD22). For some cancers, reagents already in development could potentially be applied to a new disease class, as exemplified by CD30 expression on sarcomas. Moreover, several potential new targets shared among several pediatric solid tumors are herein identified, such as MCAM (MUC18), metadherin (MTDH), and glypican-2 (GPC2). These targets have been identified at the mRNA level and are yet to be validated at the protein level. The safety of targeting these antigens has yet to be demonstrated and therefore the identified transcripts should be considered preliminary candidates for new CAR and therapeutic antibody targets. Prospective candidate targets will be evaluated by proteomic analysis including Westerns and immunohistochemistry of normal and tumor tissues.

  7. Therapeutic vaccines for cancer: an overview of clinical trials

    NARCIS (Netherlands)

    Melero, I.; Gaudernack, G.; Gerritsen, W.R.; Huber, C.; Parmiani, G.; Scholl, S.; Thatcher, N.; Wagstaff, J.; Zielinski, C.; Faulkner, I.; Mellstedt, H.

    2014-01-01

    The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are entering clinical practice. Antitumour immunization is a complex, multi-component task, and the

  8. Clinical and prognostic significance of plasma fibrinogen in lung cancer

    Directory of Open Access Journals (Sweden)

    Chen YS

    2014-01-01

    Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

  9. Clinical applications of textural analysis in non-small cell lung cancer.

    Science.gov (United States)

    Phillips, Iain; Ajaz, Mazhar; Ezhil, Veni; Prakash, Vineet; Alobaidli, Sheaka; McQuaid, Sarah J; South, Christopher; Scuffham, James; Nisbet, Andrew; Evans, Philip

    2018-01-01

    Lung cancer is the leading cause of cancer mortality worldwide. Treatment pathways include regular cross-sectional imaging, generating large data sets which present intriguing possibilities for exploitation beyond standard visual interpretation. This additional data mining has been termed "radiomics" and includes semantic and agnostic approaches. Textural analysis (TA) is an example of the latter, and uses a range of mathematically derived features to describe an image or region of an image. Often TA is used to describe a suspected or known tumour. TA is an attractive tool as large existing image sets can be submitted to diverse techniques for data processing, presentation, interpretation and hypothesis testing with annotated clinical outcomes. There is a growing anthology of published data using different TA techniques to differentiate between benign and malignant lung nodules, differentiate tissue subtypes of lung cancer, prognosticate and predict outcome and treatment response, as well as predict treatment side effects and potentially aid radiotherapy planning. The aim of this systematic review is to summarize the current published data and understand the potential future role of TA in managing lung cancer.

  10. Clinical Significance of CK19 Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Nobuyuki Arima

    2012-12-01

    Full Text Available Analysis of sentinel lymph nodes (SLNs by means of One-Step Nucleic Acid Amplification (OSNA is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19 which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

  11. Clinical Significance of CK19 Negative Breast Cancer

    International Nuclear Information System (INIS)

    Fujisue, Mamiko; Nishimura, Reiki; Okumura, Yasuhiro; Tashima, Rumiko; Nishiyama, Yasuyuki; Osako, Tomofumi; Toyozumi, Yasuo; Arima, Nobuyuki

    2012-01-01

    Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis

  12. Management of advanced pancreatic cancer in daily clinical practice.

    Science.gov (United States)

    Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

    2016-01-01

    The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

  13. Clinical Significance of CK19 Negative Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Fujisue, Mamiko, E-mail: nishimura.reiki@cityhosp-kumamoto.jp; Nishimura, Reiki; Okumura, Yasuhiro [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Tashima, Rumiko [Department of Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Nishiyama, Yasuyuki; Osako, Tomofumi [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Toyozumi, Yasuo; Arima, Nobuyuki [Department of Pathology, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan)

    2012-12-21

    Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

  14. Heavy particle beam cancer treatment apparatus, HIMAC, and clinical trial

    International Nuclear Information System (INIS)

    Soga, Fuminori

    1994-01-01

    The clinical trial was begun in June, 1994, on the treatment of cancer patients using heavy particle beam for the first time in Japan in National Institute of Radiological Sciences. It is the result of promoting the construction of Heavy Ion Medical Accelerator in Chiba (HIMAC) with the first period construction cost of 32.6 billion yen as a part of the 10 year general strategy against cancer. This is only one facility of this kind in the world. The features of heavy particle beam as radiation therapy are the excellent concentration of dose distribution, biological effect and so on. The nuclides to be used are those having the atomic number from helium to argon. The acceleration energy of ions was set at 800 MeV per nucleon so as to reach 30 cm in human bodies. The beam intensity is 5 Gy/min to finish irradiation within 1 min. The maximum irradiation field is 22 cm in diameter. The specification of the HIMAC accelerator is summarized. The Penning Ionization Gauge and the electron cyclotron resonance ion sources were installed for the reliability. The radio frequency quadrupole linear accelerator is suitable to accelerate low velocity, high intensity beam. Two synchrotrons of 41 m mean diameter are installed. High energy beam transport system, irradiation equipment, and the clinical trial are reported. (K.I.)

  15. Clinical potential of meningioma genomic insights: a practical review for neurosurgeons.

    Science.gov (United States)

    Karsy, Michael; Azab, Mohammed A; Abou-Al-Shaar, Hussam; Guan, Jian; Eli, Ilyas; Jensen, Randy L; Ormond, D Ryan

    2018-06-01

    Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.

  16. Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Keller-von Amsberg G

    2013-03-01

    Full Text Available Gunhild Keller-von Amsberg,1 Steffen Koschmieder21Department of Hematology and Oncology, University Cancer Center Hamburg, University Hospital Hamburg Eppendorf, 2Department of Medicine (Hematology, Oncology, and Stem Cell Transplantation, University Medical Center of Aachen and RWTH Aachen University, Aachen, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML. Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML.Keywords: bosutinib, chronic myeloid leukemia, BCR-ABL, Src/Abl kinase inhibitor, point mutation, imatinib resistance

  17. RET is a potential tumor suppressor gene in colorectal cancer

    Science.gov (United States)

    Luo, Yanxin; Tsuchiya, Karen D.; Park, Dong Il; Fausel, Rebecca; Kanngurn, Samornmas; Welcsh, Piri; Dzieciatkowski, Slavomir; Wang, Jianping; Grady, William M.

    2012-01-01

    Cancer arises as the consequence of mutations and epigenetic alterations that activate oncogenes and inactivate tumor suppressor genes. Through a genome-wide screen for methylated genes in colon neoplasms, we identified aberrantly methylated RET in colorectal cancer. RET, a transmembrane receptor tyrosine kinase and a receptor for the GDNF-family ligands, was one of the first oncogenes to be identified and has been shown to be an oncogene in thyroid cancer and pheochromocytoma. However, unexpectedly, we found RET is methylated in 27% of colon adenomas and in 63% of colorectal cancers, and now provide evidence that RET has tumor suppressor activity in colon cancer. The aberrant methylation of RET correlates with decreased RET expression, whereas the restoration of RET in colorectal cancer cell lines results in apoptosis. Furthermore, in support of a tumor suppressor function of RET, mutant RET has also been found in primary colorectal cancer. We now show that these mutations inactivate RET, which is consistent with RET being a tumor suppressor gene in the colon. These findings suggest that the aberrant methylation of RET and the mutational inactivation of RET promote colorectal cancer formation and that RET can serve as a tumor suppressor gene in the colon. Moreover, the increased frequency of methylated RET in colon cancers compared to adenomas suggests RET inactivation is involved in the progression of colon adenomas to cancer. PMID:22751117

  18. Evaluation of clinical, laboratory and morphologic prognostic factors in colon cancer

    Science.gov (United States)

    Grande, Michele; Milito, Giovanni; Attinà, Grazia Maria; Cadeddu, Federica; Muzi, Marco Gallinella; Nigro, Casimiro; Rulli, Francesco; Farinon, Attilio Maria

    2008-01-01

    Background The long-term prognosis of patients with colon cancer is dependent on many factors. To investigate the influence of a series of clinical, laboratory and morphological variables on prognosis of colon carcinoma we conducted a retrospective analysis of our data. Methods Ninety-two patients with colon cancer, who underwent surgical resection between January 1999 and December 2001, were analyzed. On survival analysis, demographics, clinical, laboratory and pathomorphological parameters were tested for their potential prognostic value. Furthermore, univariate and multivariate analysis of the above mentioned data were performed considering the depth of tumour invasion into the bowel wall as independent variable. Results On survival analysis we found that depth of tumour invasion (P anismus, hematocrit, WBC count, fibrinogen value and CT scanning were significantly related to the degree of mural invasion of the cancer. On the multivariate analysis, fibrinogen value was the most statistically significant variable (P < 0.001) with the highest F-ratio (F-ratio 5.86). Finally, in the present study, the tumour site was significantly related neither to the survival nor to the mural invasion of the tumour. Conclusion The various clinical, laboratory and patho-morphological parameters showed different prognostic value for colon carcinoma. In the future, preoperative prognostic markers will probably gain relevance in order to make a proper choice between surgery, chemotherapy and radiotherapy. Nevertheless, current data do not provide sufficient evidence for preoperative stratification of high and low risk patients. Further assessments in prospective large studies are warranted. PMID:18778464

  19. Searching for cures: Inner-city and rural patients' awareness and perceptions of cancer clinical trials

    Directory of Open Access Journals (Sweden)

    Mugur Geana

    2017-03-01

    Full Text Available Fewer than 5% of cancer patients participate in clinical trials, making it challenging to test new therapies or interventions for cancer. Even within that small number, patients living in inner-city and rural areas are underrepresented in clinical trials. This study explores cancer patients' awareness and perceptions of cancer clinical trials, as well as their perceptions of patient-provider interactions related to discussing cancer clinical trials in order to improve accrual in cancer clinical trials. Interviews with 66 former and current in inner-city and rural cancer patients revealed a lack of awareness and understanding about clinical trials, as well as misconceptions about what clinical trials entail. Findings also revealed that commercials and television shows play a prominent role in forming inner-city and rural patients' attitudes and/or misconceptions about clinical trials. However, rural patients were more likely to hold unfavorable views about clinical trials than inner-city patients. Patient-provider discussions emerged as being crucial for increasing awareness of clinical trials among patients and recruiting them to trials. Findings from this study will inform communication strategies to enhance recruitment to cancer clinical trials by increasing awareness and countering misconceptions about clinical trials.

  20. Vulvar cancer: epidemiology, clinical presentation, and management options

    Directory of Open Access Journals (Sweden)

    Alkatout I

    2015-03-01

    Full Text Available Ibrahim Alkatout,1 Melanie Schubert,1 Nele Garbrecht,2 Marion Tina Weigel,1 Walter Jonat,1 Christoph Mundhenke,1 Veronika Günther1 1Department of Gynecology and Obstetrics, 2Institute for Pathology, University Hospitals Schleswig-Holstein, Campus Kiel, Kiel, Germany Epidemiology: Vulvar cancer can be classified into two groups according to predisposing factors: the first type correlates with a HPV infection and occurs mostly in younger patients. The second group is not HPV associated and occurs often in elderly women without neoplastic epithelial disorders. Histology: Squamous cell carcinoma (SCC is the most common malignant tumor of the vulva (95%. Clinical features: Pruritus is the most common and long-lasting reported symptom of vulvar cancer, followed by vulvar bleeding, discharge, dysuria, and pain. Therapy: The gold standard for even a small invasive carcinoma of the vulva was historically radical vulvectomy with removal of the tumor with a wide margin followed by an en bloc resection of the inguinal and often the pelvic lymph nodes. Currently, a more individualized and less radical treatment is suggested: a radical wide local excision is possible in the case of localized lesions (T1. A sentinel lymph node (SLN biopsy may be performed to reduce wound complications and lymphedema. Prognosis: The survival of patients with vulvar cancer is good when convenient therapy is arranged quickly after initial diagnosis. Inguinal and/or femoral node involvement is the most significant prognostic factor for survival. Keywords: vulvar cancer, HPV infection, radical vulvectomy, groin dissection, sentinel lymph node biopsy, overall survival

  1. Prostate atypia: does repeat biopsy detect clinically significant prostate cancer?

    Science.gov (United States)

    Dorin, Ryan P; Wiener, Scott; Harris, Cory D; Wagner, Joseph R

    2015-05-01

    While the treatment pathway in response to benign or malignant prostate biopsies is well established, there is uncertainty regarding the risk of subsequently diagnosing prostate cancer when an initial diagnosis of prostate atypia is made. As such, we investigated the likelihood of a repeat biopsy diagnosing prostate cancer (PCa) in patients in which an initial biopsy diagnosed prostate atypia. We reviewed our prospectively maintained prostate biopsy database to identify patients who underwent a repeat prostate biopsy within one year of atypia (atypical small acinar proliferation; ASAP) diagnosis between November 1987 and March 2011. Patients with a history of PCa were excluded. Chart review identified patients who underwent radical prostatectomy (RP), radiotherapy (RT), or active surveillance (AS). For some analyses, patients were divided into two subgroups based on their date of service. Ten thousand seven hundred and twenty patients underwent 13,595 biopsies during November 1987-March 2011. Five hundred and sixty seven patients (5.3%) had ASAP on initial biopsy, and 287 (50.1%) of these patients underwent a repeat biopsy within one year. Of these, 122 (42.5%) were negative, 44 (15.3%) had atypia, 19 (6.6%) had prostatic intraepithelial neoplasia, and 102 (35.6%) contained PCa. Using modified Epstein's criteria, 27/53 (51%) patients with PCa on repeat biopsy were determined to have clinically significant tumors. 37 (36.3%) proceeded to RP, 25 (24.5%) underwent RT, and 40 (39.2%) received no immediate treatment. In patients who underwent surgery, Gleason grade on final pathology was upgraded in 11 (35.5%), and downgraded 1 (3.2%) patient. ASAP on initial biopsy was associated with a significant risk of PCa on repeat biopsy in patients who subsequently underwent definitive local therapy. Patients with ASAP should be counseled on the probability of harboring both clinically significant and insignificant prostate cancer. © 2015 Wiley Periodicals, Inc.

  2. Galectin-3 expression in colorectal cancer and its correlation with clinical pathological characteristics and prognosis

    OpenAIRE

    Tao Liu; Jin Li; Dechun Li; Hongqiang Yang; Changhua Kou; Guijun Lei

    2017-01-01

    Abstract Objective To explore the expression levels of galectin-3 in colorectal cancer and the association between galectin-3 and its clinical pathological parameters, as well as the prognosis of colorectal cancer patients. Methods An immunohistochemistry assay was used to test the expression levels of galectin-3 in cancer tissues of 61 colorectal cancer cases and in normal intestinal tissues adjacent to the cancer tissues of 23 cases. The associations between protein expression levels of gal...

  3. Safety of bevacizumab in clinical practice for recurrent ovarian cancer: A retrospective cohort study

    Science.gov (United States)

    SELLE, FRÉDÉRIC; EMILE, GEORGE; PAUTIER, PATRICIA; ASMANE, IRÈNE; SOARES, DANIELE G.; KHALIL, AHMED; ALEXANDRE, JEROME; LHOMMÉ, CATHERINE; RAY-COQUARD, ISABELLE; LOTZ, JEAN-PIERRE; GOLDWASSER, FRANÇOIS; TAZI, YOUSSEF; HEUDEL, PIERRE; PUJADE-LAURAINE, ERIC; GOUY, SÉBASTIEN; TREDAN, OLIVIER; BARBAZA, MARIE O.; ADY-VAGO, NORA; DUBOT, CORALINE

    2016-01-01

    The poor outcome of patients with recurrent ovarian cancer constitutes a continuous challenge for decision-making in clinical practice. In this setting, molecular targets have recently been identified, and novel compounds are now available. Bevacizumab has been introduced for the treatment of patients with ovarian cancer and is, to date, the most extensively investigated targeted therapy in this setting. However, potential toxicities are associated with the use of this monoclonal antibody. These toxicities have been reported in clinical trials, and can also be observed outside of trials. As limited data is currently available regarding the safety of bevacizumab treatment in daily clinical practice, the current retrospective study was designed to evaluate this. Data from 156 patients with recurrent ovarian cancer who had received bevacizumab treatment between January 2006 and June 2009 were retrospectively identified from the institutional records of five French centers. In contrast to clinical trials, the patients in the present study were not selected and had a heterogeneous profile according to their prior medical history, lines of treatment prior to bevacizumab introduction and number of relapses. The results first confirm the effect of heavy pretreatment on the occurrence of serious and fatal adverse events in clinical practice, as previously reported for clinical trials and for other retrospective cohort studies. Importantly, the data also demonstrates, for the first time, that medical history of hypertension is an independent predictive risk factor for the development of high-grade hypertension during bevacizumab treatment. These results thus suggest that treating physicians must consider all risk factors for managing bevacizumab toxicity prior to its introduction. Such risk factors include the time of bevacizumab introduction, a patient's history of hypertension and a low incidence of pre-existing obstructive disease. PMID:26998090

  4. Unanticipated potential cancer risk near metal recycling facilities

    Energy Technology Data Exchange (ETDEWEB)

    Raun, Loren, E-mail: raun@rice.edu [Department of Statistics, MS 138, Rice University, P.O. Box 1892, Houston, TX 77251-1892 (United States); Pepple, Karl, E-mail: pepple.karl@epa.gov [State and Local Programs Group, Air Quality Policy Division, Office of Air Quality Planning and Standards, Policy, Analysis, and Communications Staff, Mail Drop C404-03, U.S. EPA, Research Triangle Park, NC 27711 (United States); Hoyt, Daniel, E-mail: hoyt.daniel@epa.gov [Air Surveillance Section, US EPA, Region 6, 6EN-AS, 1445 Ross Avenue, Dallas, TX 75202-2733 (United States); Richner, Donald, E-mail: Donald.Richner@houstontx.gov [Houston Department of Health and Human Services, Bureau of Pollution Control and Prevention, 7411 Park Place Blvd., Houston, TX 77087 (United States); Blanco, Arturo, E-mail: arturo.blanco@houstontx.gov [Pollution Control and Prevention, Environmental Health Division, Houston Department of Health and Human Services, 7411 Park Place Blvd., Houston, TX 77087 (United States); Li, Jiao, E-mail: jiao.li@rice.edu [Wiess School of Natural Science, Rice University, 6100 Main St., Houston, TX 77005 (United States)

    2013-07-15

    and the number of shifts that could operate a year. Further study is warranted to better understand the metal air pollution levels in the community and if necessary, to evaluate the feasibility of emission controls and identify operational improvements and best management practices for this industry. This research adds two new aspects to the literature: identification of types and magnitude of metal particulate matter air pollutants associated with a previously unrecognized area source, metal recyclers and their potential risk to health. -- Highlights: • Air monitoring study in response to community complaints found metal contamination. • Metal recyclers found to potentially pose cancer from metal particulates • Chromium, nickel, cobalt and cadmium samples were detected in five metal recyclers. • These metals were not detected in background air samples. • Estimated increased cancer risk ranges from 1 in 1,000,000 to 8 in 10,000.

  5. Unanticipated potential cancer risk near metal recycling facilities

    International Nuclear Information System (INIS)

    Raun, Loren; Pepple, Karl; Hoyt, Daniel; Richner, Donald; Blanco, Arturo; Li, Jiao

    2013-01-01

    and the number of shifts that could operate a year. Further study is warranted to better understand the metal air pollution levels in the community and if necessary, to evaluate the feasibility of emission controls and identify operational improvements and best management practices for this industry. This research adds two new aspects to the literature: identification of types and magnitude of metal particulate matter air pollutants associated with a previously unrecognized area source, metal recyclers and their potential risk to health. -- Highlights: • Air monitoring study in response to community complaints found metal contamination. • Metal recyclers found to potentially pose cancer from metal particulates • Chromium, nickel, cobalt and cadmium samples were detected in five metal recyclers. • These metals were not detected in background air samples. • Estimated increased cancer risk ranges from 1 in 1,000,000 to 8 in 10,000

  6. Expression of tumor necrosis factor receptor-associated protein 1 and its clinical significance in kidney cancer.

    Science.gov (United States)

    Si, Tong; Yang, Guosheng; Qiu, Xiaofu; Luo, Youhua; Liu, Baichuan; Wang, Bingwei

    2015-01-01

    To investigate the expression and clinical significance of TRAP1 (tumor necrosis factor receptor-associated protein 1) in kidney cancer. TRAP1 expression was detected in kidney cancer and normal kidney tissues by qRT-PCR and immunohistochemistry (IHC), respectively. Then, the correlation of TRAP1 expression with clinicopathological characters and patients' prognosis was evaluated in kidney cancer. IHC results revealed that the high-expression rates of TRAP1 in kidney cancer tissues and normal kidney tissues were 51.3% (41/80), 23.3% (7/30), and the difference was statistically significant (P=0.01). Also, TRAP1 mRNA level in kidney cancer was found to be significantly greater compared with those in normal kidney by qRT-PCR. In addition, TRAP1 expression in kidney cancer significantly correlated with lymph node metastasis and clinical stage (Pkidney cancer and correlates with patients prognosis, which may be served as a potential marker for the diagnosis and treatment of kidney cancer.

  7. Why providers participate in clinical trials: considering the National Cancer Institute's Community Clinical Oncology Program.

    Science.gov (United States)

    McAlearney, Ann Scheck; Song, Paula H; Reiter, Kristin L

    2012-11-01

    The translation of research evidence into practice is facilitated by clinical trials such as those sponsored by the National Cancer Institute's Community Clinical Oncology Program (CCOP) that help disseminate cancer care innovations to community-based physicians and provider organizations. However, CCOP participation involves unsubsidized costs and organizational challenges that raise concerns about sustained provider participation in clinical trials. This study was designed to improve our understanding of why providers participate in the CCOP in order to inform the decision-making process of administrators, clinicians, organizations, and policy-makers considering CCOP participation. We conducted a multi-site qualitative study of five provider organizations engaged with the CCOP. We interviewed 41 administrative and clinician key informants, asking about what motivated CCOP participation, and what benefits they associated with involvement. We deductively and inductively analyzed verbatim interview transcripts, and explored themes that emerged. Interviewees expressed both "altruistic" and "self-interested" motives for CCOP participation. Altruistic reasons included a desire to increase access to clinical trials and feeling an obligation to patients. Self-interested reasons included the desire to enhance reputation, and a need to integrate disparate cancer care activities. Perceived benefits largely matched expressed motives for CCOP participation, and included internal and external benefits to the organization, and quality of care benefits for both patients and participating physicians. The motives and benefits providers attributed to CCOP participation are consistent with translational research goals, offering evidence that participation can contribute value to providers by expanding access to innovative medical care for patients in need. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Layers in sorting practices: Sorting out patients with potential cancer

    DEFF Research Database (Denmark)

    Møller, Naja Holten; Bjørn, Pernille

    2011-01-01

    for a particular patient. Due to the limited resources within the Danish healthcare system, initiating cancer pathways for all patients with a remote suspicion of cancer would crash the system, as it would be impossible for healthcare professionals to commit to the prescribed schedules and times defined...... they show that sorting patients before initiating a standardized cancer pathway is not a simple process of deciding on a predefined category that will stipulate particular dates and times. Instead, these informal sorting mechanisms show that the process of sorting patients prior to diagnosis......In the last couple of years, widespread use of standardized cancer pathways has been seen across a range of countries, including Denmark, to improve prognosis of cancer patients. In Denmark, standardized cancer pathways take the form of guidelines prescribing well-defined sequences where steps...

  9. Smoking cessation results in a clinical lung cancer screening program.

    Science.gov (United States)

    Borondy Kitts, Andrea K; McKee, Andrea B; Regis, Shawn M; Wald, Christoph; Flacke, Sebastian; McKee, Brady J

    2016-07-01

    Lung cancer screening may provide a "teachable moment" for promoting smoking cessation. This study assessed smoking cessation and relapse rates among individuals undergoing follow-up low-dose chest computed tomography (CT) in a clinical CT lung screening program and assessed the influence of initial screening results on smoking behavior. Self-reported smoking status for individuals enrolled in a clinical CT lung screening program undergoing a follow-up CT lung screening exam between 1st February, 2014 and 31st March, 2015 was retrospectively reviewed and compared to self-reported smoking status using a standardized questionnaire at program entry. Point prevalence smoking cessation and relapse rates were calculated across the entire population and compared with exam results. All individuals undergoing screening fulfilled the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Lung Cancer Screening v1.2012(®) high-risk criteria and had an order for CT lung screening. A total of 1,483 individuals underwent a follow-up CT lung screening exam during the study interval. Smoking status at time of follow-up exam was available for 1,461/1,483 (98.5%). A total of 46% (678/1,461) were active smokers at program entry. The overall point prevalence smoking cessation and relapse rates were 20.8% and 9.3%, respectively. Prior positive screening exam results were not predictive of smoking cessation (OR 1.092; 95% CI, 0.715-1.693) but were predictive of reduced relapse among former smokers who had stopped smoking for 2 years or less (OR 0.330; 95% CI, 0.143-0.710). Duration of program enrollment was predictive of smoking cessation (OR 0.647; 95% CI, 0.477-0.877). Smoking cessation and relapse rates in a clinical CT lung screening program rates are more favorable than those observed in the general population. Duration of participation in the screening program correlated with increased smoking cessation rates. A positive exam result correlated with reduced

  10. Real-time Raman spectroscopy for in vivo, online gastric cancer diagnosis during clinical endoscopic examination

    Science.gov (United States)

    Duraipandian, Shiyamala; Sylvest Bergholt, Mads; Zheng, Wei; Yu Ho, Khek; Teh, Ming; Guan Yeoh, Khay; Bok Yan So, Jimmy; Shabbir, Asim; Huang, Zhiwei

    2012-08-01

    Optical spectroscopic techniques including reflectance, fluorescence and Raman spectroscopy have shown promising potential for in vivo precancer and cancer diagnostics in a variety of organs. However, data-analysis has mostly been limited to post-processing and off-line algorithm development. In this work, we develop a fully automated on-line Raman spectral diagnostics framework integrated with a multimodal image-guided Raman technique for real-time in vivo cancer detection at endoscopy. A total of 2748 in vivo gastric tissue spectra (2465 normal and 283 cancer) were acquired from 305 patients recruited to construct a spectral database for diagnostic algorithms development. The novel diagnostic scheme developed implements on-line preprocessing, outlier detection based on principal component analysis statistics (i.e., Hotelling's T2 and Q-residuals) for tissue Raman spectra verification as well as for organ specific probabilistic diagnostics using different diagnostic algorithms. Free-running optical diagnosis and processing time of based on the randomly resampled training database (80% for learning and 20% for testing) provide the diagnostic accuracy of 85.6% [95% confidence interval (CI): 82.9% to 88.2%] [sensitivity of 80.5% (95% CI: 71.4% to 89.6%) and specificity of 86.2% (95% CI: 83.6% to 88.7%)] for the detection of gastric cancer. The PLS-DA algorithms are further applied prospectively on 10 gastric patients at gastroscopy, achieving the predictive accuracy of 80.0% (60/75) [sensitivity of 90.0% (27/30) and specificity of 73.3% (33/45)] for in vivo diagnosis of gastric cancer. The receiver operating characteristics curves further confirmed the efficacy of Raman endoscopy together with PLS-DA algorithms for in vivo prospective diagnosis of gastric cancer. This work successfully moves biomedical Raman spectroscopic technique into real-time, on-line clinical cancer diagnosis, especially in routine endoscopic diagnostic applications.

  11. CYberinfrastructure for COmparative effectiveness REsearch (CYCORE): improving data from cancer clinical trials.

    Science.gov (United States)

    Patrick, Kevin; Wolszon, Laura; Basen-Engquist, Karen M; Demark-Wahnefried, Wendy; Prokhorov, Alex V; Barrera, Stephanie; Baru, Chaitan; Farcas, Emilia; Krueger, Ingolf; Palmer, Doug; Raab, Fred; Rios, Phil; Ziftci, Celal; Peterson, Susan

    2011-03-01

    Improved approaches and methodologies are needed to conduct comparative effectiveness research (CER) in oncology. While cancer therapies continue to emerge at a rapid pace, the review, synthesis, and dissemination of evidence-based interventions across clinical trials lag in comparison. Rigorous and systematic testing of competing therapies has been clouded by age-old problems: poor patient adherence, inability to objectively measure the environmental influences on health, lack of knowledge about patients' lifestyle behaviors that may affect cancer's progression and recurrence, and limited ability to compile and interpret the wide range of variables that must be considered in the cancer treatment. This lack of data integration limits the potential for patients and clinicians to engage in fully informed decision-making regarding cancer prevention, treatment, and survivorship care, and the translation of research results into mainstream medical care. Particularly important, as noted in a 2009 report on CER to the President and Congress, the limited focus on health behavior-change interventions was a major hindrance in this research landscape (DHHS 2009). This paper describes an initiative to improve CER for cancer by addressing several of these limitations. The Cyberinfrastructure for Comparative Effectiveness Research (CYCORE) project, informed by the National Science Foundation's 2007 report "Cyberinfrastructure Vision for 21(st) Century Discovery" has, as its central aim, the creation of a prototype for a user-friendly, open-source cyberinfrastructure (CI) that supports acquisition, storage, visualization, analysis, and sharing of data important for cancer-related CER. Although still under development, the process of gathering requirements for CYCORE has revealed new ways in which CI design can significantly improve the collection and analysis of a wide variety of data types, and has resulted in new and important partnerships among cancer researchers engaged in

  12. Birth weight, breast cancer and the potential mediating hormonal environment.

    Directory of Open Access Journals (Sweden)

    Radek Bukowski

    Full Text Available Previous studies have shown that woman's risk of breast cancer in later life is associated with her infants birth weights. The objective of this study was to determine if this association is independent of breast cancer risk factors, mother's own birth weight and to evaluate association between infants birth weight and hormonal environment during pregnancy. Independent association would have implications for understanding the mechanism, but also for prediction and prevention of breast cancer.Risk of breast cancer in relation to a first infant's birth weight, mother's own birth weight and breast cancer risk factors were evaluated in a prospective cohort of 410 women in the Framingham Study. Serum concentrations of estriol (E3, anti-estrogen alpha-fetoprotein (AFP, and pregnancy-associated plasma protein-A (PAPP-A were measured in 23,824 pregnant women from a separate prospective cohort, the FASTER trial. During follow-up (median, 14 years 31 women (7.6% were diagnosed with breast cancer. Women with large birth weight infants (in the top quintile had a higher breast cancer risk compared to other women (hazard ratio (HR, 2.5; 95% confidence interval (CI, 1.2-5.2; P = 0.012. The finding was not affected by adjustment for birth weight of the mother and traditional breast cancer risk factors (adjusted HR, 2.5; 95% CI, 1.2-5.6; P = 0.021. An infant's birth weight had a strong positive relationship with the mother's serum E3/AFP ratio and PAPP-A concentration during pregnancy. Adjustment for breast cancer risk factors did not have a material effect on these relationships.Giving birth to an infant with high birth weight was associated with increased breast cancer risk in later life, independently of mother's own birth weight and breast cancer risk factors and was also associated with a hormonal environment during pregnancy favoring future breast cancer development and progression.

  13. Birth weight, breast cancer and the potential mediating hormonal environment.

    LENUS (Irish Health Repository)

    Bukowski, Radek

    2012-01-01

    Previous studies have shown that woman\\'s risk of breast cancer in later life is associated with her infants birth weights. The objective of this study was to determine if this association is independent of breast cancer risk factors, mother\\'s own birth weight and to evaluate association between infants birth weight and hormonal environment during pregnancy. Independent association would have implications for understanding the mechanism, but also for prediction and prevention of breast cancer.

  14. Potential Therapeutic Roles of Tanshinone IIA in Human Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sheng-Chun Chiu

    2014-09-01

    Full Text Available Tanshinone IIA (Tan-IIA, one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae, has been found to exhibit anticancer activity in various cancer cells. We have demonstrated that Tan-IIA induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. Here we explored the anticancer effect of Tan-IIA in human bladder cancer cell lines. Our results showed that Tan-IIA caused bladder cancer cell death in a time- and dose-dependent manner. Tan-IIA induced apoptosis through the mitochondria-dependent pathway in these bladder cancer cells. Tan-IIA also suppressed the migration of bladder cancer cells as revealed by the wound healing and transwell assays. Finally, combination therapy of Tan-IIA with a lower dose of cisplatin successfully killed bladder cancer cells, suggesting that Tan-IIA can serve as a potential anti-cancer agent in bladder cancer.

  15. Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging?

    Science.gov (United States)

    Pallis, Athanasios G; Hatse, Sigrid; Brouwers, Barbara; Pawelec, Graham; Falandry, Claire; Wedding, Ulrich; Lago, Lissandra Dal; Repetto, Lazzaro; Ring, Alistair; Wildiers, Hans

    2014-04-01

    Aging of an individual entails a progressive decline of functional reserves and loss of homeostasis that eventually lead to mortality. This process is highly individualized and is influenced by multiple genetic, epigenetic and environmental factors. This individualization and the diversity of factors influencing aging result in a significant heterogeneity among people with the same chronological age, representing a major challenge in daily oncology practice. Thus, many factors other than mere chronological age will contribute to treatment tolerance and outcome in the older patients with cancer. Clinical/comprehensive geriatric assessment can provide information on the general health status of individuals, but is far from perfect as a prognostic/predictive tool for individual patients. On the other hand, aging can also be assessed in terms of biological changes in certain tissues like the blood compartment which result from adaptive alterations due to past history of exposures, as well as intrinsic aging processes. There are major signs of 'aging' in lymphocytes (e.g. lymphocyte subset distribution, telomere length, p16INK4A expression), and also in (inflammatory) cytokine expression and gene expression patterns. These result from a combination of the above two processes, overlaying genetic predispositions which contribute significantly to the aging phenotype. These potential "aging biomarkers" might provide additional prognostic/predictive information supplementing clinical evaluation. The purpose of the current paper is to describe the most relevant potential "aging biomarkers" (markers that indicate the biological functional age of patients) which focus on the biological background, the (limited) available clinical data, and technical challenges. Despite their great potential interest, there is a need for much more (validated) clinical data before these biomarkers could be used in a routine clinical setting. This manuscript tries to provide a guideline on how

  16. Synthesis maps: visual knowledge translation for the CanIMPACT clinical system and patient cancer journeys

    OpenAIRE

    Jones, P.H.; Shakdher, S.; Singh, P.

    2017-01-01

    Salient findings and interpretations from the canimpact clinical cancer research study are visually represented in two synthesis maps for the purpose of communicating an integrated presentation of the study to clinical cancer researchers and policymakers. Synthesis maps integrate evidence and expertise into a visual narrative for knowledge translation and communication. A clinical system synthesis map represents the current Canadian primary care and cancer practice systems, proposed as a visu...

  17. Potential Protective Effects of Probiotics and Prebiotics Against Colorectal Cancer

    Science.gov (United States)

    Allsopp, Philip; Rowland, Ian

    Colorectal cancer (CRC) is the fourth most frequent cause of cancer related mortality in the world. Approximately 944,000 new cases were diagnosed globally in 2000 and this accounts for 9.2% of all new cancer cases (IARC, 2000). In Western societies namely Europe, North America and Australasia, it is the second most prevalent cancer after lung/breast (Boyle and Langman, 2000). About 363,000 new cases were reported in Europe in 2000 and it affects 6% of men and women by age 75, in almost equal proportion.

  18. Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

    Science.gov (United States)

    Terlikowska, Katarzyna M.; Witkowska, Anna M.; Zujko, Malgorzata E.; Dobrzycka, Bozena; Terlikowski, Slawomir J.

    2014-01-01

    Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies. PMID:25429431