Variation in Breast Cancer-Risk Factor Associations by Method of Detection: Results From a Series of Case-Control Studies.

PubMed

Sprague, Brian L; Gangnon, Ronald E; Hampton, John M; Egan, Kathleen M; Titus, Linda J; Kerlikowske, Karla; Remington, Patrick L; Newcomb, Polly A; Trentham-Dietz, Amy

2015-06-15

Concerns about breast cancer overdiagnosis have increased the need to understand how cancers detected through screening mammography differ from those first detected by a woman or her clinician. We investigated risk factor associations for invasive breast cancer by method of detection within a series of case-control studies (1992-2007) carried out in Wisconsin, Massachusetts, and New Hampshire (n=15,648 invasive breast cancer patients and 17,602 controls aged 40-79 years). Approximately half of case women reported that their cancer had been detected by mammographic screening and half that they or their clinician had detected it. In polytomous logistic regression models, parity and age at first birth were more strongly associated with risk of mammography-detected breast cancer than with risk of woman/clinician-detected breast cancer (P≤0.01; adjusted for mammography utilization). Among postmenopausal women, estrogen-progestin hormone use was predominantly associated with risk of woman/clinician-detected breast cancer (odds ratio (OR)=1.49, 95% confidence interval (CI): 1.29, 1.72), whereas obesity was predominantly associated with risk of mammography-detected breast cancer (OR=1.72, 95% CI: 1.54, 1.92). Among regularly screened premenopausal women, obesity was not associated with increased risk of mammography-detected breast cancer (OR=0.99, 95% CI: 0.83, 1.18), but it was associated with reduced risk of woman/clinician-detected breast cancer (OR=0.53, 95% CI: 0.43, 0.64). These findings indicate important differences in breast cancer risk factors according to method of detection. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prostate Cancer and Bone: The Elective Affinities

PubMed Central

2014-01-01

The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients. PMID:24971315

Transcriptional master regulator analysis in breast cancer genetic networks.

PubMed

Tovar, Hugo; García-Herrera, Rodrigo; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

2015-12-01

Gene regulatory networks account for the delicate mechanisms that control gene expression. Under certain circumstances, gene regulatory programs may give rise to amplification cascades. Such transcriptional cascades are events in which activation of key-responsive transcription factors called master regulators trigger a series of gene expression events. The action of transcriptional master regulators is then important for the establishment of certain programs like cell development and differentiation. However, such cascades have also been related with the onset and maintenance of cancer phenotypes. Here we present a systematic implementation of a series of algorithms aimed at the inference of a gene regulatory network and analysis of transcriptional master regulators in the context of primary breast cancer cells. Such studies were performed in a highly curated database of 880 microarray gene expression experiments on biopsy-captured tissue corresponding to primary breast cancer and healthy controls. Biological function and biochemical pathway enrichment analyses were also performed to study the role that the processes controlled - at the transcriptional level - by such master regulators may have in relation to primary breast cancer. We found that transcription factors such as AGTR2, ZNF132, TFDP3 and others are master regulators in this gene regulatory network. Sets of genes controlled by these regulators are involved in processes that are well-known hallmarks of cancer. This kind of analyses may help to understand the most upstream events in the development of phenotypes, in particular, those regarding cancer biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Health and cancer prevention: implications of the knowledge and beliefs of 15-16 year old school pupils in South Africa.

PubMed

Walker, A R; Walker, B F; Jerling, J; Rossouw, K; Lelake, A

1999-06-01

The objective was to collect information from African and white pupils aged 15-16 years on their knowledge of and attitudes towards cancer, and their understanding of health-related behaviours in relation to their future experience. Questionnaires were completed by a series of 338 African and 378 white pupils in suburban secondary schools. African and white pupils knew most about lung cancer, and had some knowledge of skin and breast cancers. Smoking was seen by most as the chief cause of the disease. Half of both groups perceived a high intake of vegetables and fruit as protective. Television and printed media were the most important sources of information. The children in both groups were more anxious about unemployment and violence, and also, among African children, about AIDS, than about future ill-health. Thus, health was not perceived by many as the most important goal in life. Discussion indicates that white adolescents and also white adults, with more advanced understanding of cancer causation, make very limited use of their knowledge, dietary and non-dietary, to avoid the disease. In brief, level of cancer knowledge has very limited implications. Although young Africans in the course of their transition are very unlikely to seek to diminish their risk of cancer, there must be no lessening of urgent warnings and advice through the media on the avoidance of the disease.

[Pulmonary embolism in patients with cancer: foundations of the EPIPHANY study].

PubMed

Font, Carme; Carmona-Bayonas, Alberto; Plasencia, Juana M; Calvo-Temprano, David; Sánchez, Marcelo; Jiménez-Fonseca, Paula; Beato, Carmen; Biosca, Mercè; Vicente, Vicente; Otero, Remedios

2015-01-01

Pulmonary thromboembolism (PE) is a common cause of morbidity and mortality in patients with cancer. Having cancer is an independent risk factor for death in the general series of patients with PE and is included as a variable in the prognostic scales of acute symptomatic PE. This fact limits the discriminatory power of these general scales for patients with cancer and has prompted the development of specific prognostic tools: POMPE-C and a scale derived from the RIETE registry. Whether the increased risk of death by PE in patients with cancer is due to complications related to the neoplasm or to a greater severity of the thromboembolic episode in this population has not been well studied. Moreover, the introduction of computed multidetector tomography in recent years has led to a growing diagnosis of incidental PE, which currently represents up to half of pulmonary embolisms in patients with cancer. The EPIPHANY study attempts to further the understanding of the characteristics of pulmonary embolisms in patients with cancer by including incidental and symptomatic events. Its primary objectives are a) to understand the clinical and epidemiological patterns of pulmonary embolism associated with cancer and b) to develop and validate a specific prognosis model for PE in this population. The registry includes variables of interest to oncology (cancer type and extent, oncospecific treatments, patient's functional condition, cancer progression), radiological variables (thrombotic burden, signs of ventricular overload and other findings), location of treatment (hospital or outpatient), acute complications and causes of death in patients with PE associated with cancer. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

All the World's a Stage: Facilitating Discovery Science and Improved Cancer Care through the Global Alliance for Genomics and Health.

PubMed

Lawler, Mark; Siu, Lillian L; Rehm, Heidi L; Chanock, Stephen J; Alterovitz, Gil; Burn, John; Calvo, Fabien; Lacombe, Denis; Teh, Bin Tean; North, Kathryn N; Sawyers, Charles L

2015-11-01

The recent explosion of genetic and clinical data generated from tumor genome analysis presents an unparalleled opportunity to enhance our understanding of cancer, but this opportunity is compromised by the reluctance of many in the scientific community to share datasets and the lack of interoperability between different data platforms. The Global Alliance for Genomics and Health is addressing these barriers and challenges through a cooperative framework that encourages "team science" and responsible data sharing, complemented by the development of a series of application program interfaces that link different data platforms, thus breaking down traditional silos and liberating the data to enable new discoveries and ultimately benefit patients. ©2015 American Association for Cancer Research.

Infectious Agents and Cancer Epidemiology Research Webinar Series

Cancer.gov

Infectious Agents and Cancer Epidemiology Research Webinar Series highlights emerging and cutting-edge research related to infection-associated cancers, shares scientific knowledge about technologies and methods, and fosters cross-disciplinary discussions on infectious agents and cancer epidemiology.

Genes, dreams, and cancer.

PubMed Central

Sikora, K.

1994-01-01

There have been tremendous advances in our understanding of cancer from the application of molecular biology over the past decade. The disease is caused by a series of defects in the genes that accelerate growth--oncogenes--and those that slow down cellular turnover--tumour suppressor genes. The proteins they encode provide a promising hunting ground in which to design and test new anticancer drugs. Several treatment strategies are now under clinical trial entailing direct gene transfer. These include the use of gene marking to detect minimal residual disease, the production of novel cancer vaccines by the insertion of genes which uncloak cancer cells so making them visible to the host's immune system, the isolation and coupling of cancer specific molecular switches upstream of drug activating genes, and the correction of aberrant oncogenes or tumour suppressor genes. The issues in these approaches are likely to have a profound impact on the management of cancer patients as we enter the next century. Images p1221-a PMID:8180542

Online patient education and risk assessment: project OPERA from Cancerbackup. Putting inherited breast cancer risk information into context using argumentation theory.

PubMed

Mackay, James; Schulz, Peter; Rubinelli, Sara; Pithers, Andrea

2007-08-01

Many people are concerned about their family history of breast cancer, and are anxious about the possibility of developing breast cancer themselves. The majority of these people are likely not to be at significantly increased risk of developing inherited breast cancer. All women are at risk of developing sporadic breast cancer, and this risk increases with age. This project aims to aid people's understanding of these issues using an interactive online computer programme. The UK National Institute of Health and Clinical Excellence has published guidance for the National Health Service on the management of familial breast cancer. That guidance lays down clear criteria for categorising risk level and the appropriate management options. We have developed a user-friendly computer programme named OPERA (online patient education and risk assessment) which captures the individuality of the user's situation in a comprehensive way, and then produces personalised information packages, building on the theoretical framework of argumentation developed by Toulmin [Toulmin S. The uses of argument. Cambridge, MA: Cambridge University Press; 1958]. We will test this programme in a series of pilot studies commencing in 2007. This paper describes the progress of this project to date and focuses on the design of the programme. It is possible to construct a user friendly programme which delivers a personalised information package to individuals who are concerned about their risk of developing breast cancer. This user friendly programme needs to be tested within a series of carefully thought out pilot studies before it is ready for general release and use by the public.

Stars in Nutrition and Cancer Lecture Series | Division of Cancer Prevention

Cancer.gov

This lecture series features extraordinary contributors or "stars" in the field of cancer and nutrition research. Speakers highlight the important role that nutrition plays in modifying cancer development. Past lectures are videotaped and available for viewing. |

The curative management of synchronous rectal and prostate cancer

PubMed Central

Kavanagh, Dara O; Martin, Joseph; Small, Cormac; Joyce, Myles R; Faul, Clare M; Kelly, Paul J; O'Riordain, Michael; Gillham, Charles M; Armstrong, John G; Salib, Osama; McNamara, Deborah A; McVey, Gerard; O'Neill, Brian D P

2016-01-01

Objective: Neoadjuvant “long-course” chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45–50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2–6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45–50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. Advances in knowledge: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients. PMID:26539631

Infections and cancer: debate about using vaccines as a cancer control tool.

PubMed

Mbulaiteye, Sam M; Buonaguro, Franco M

2013-05-04

In 2012, Infectious Agents and Cancer commissioned a thematic series collection of articles on Prevention of HPV related cancer. The articles have attracted wide interest and stimulated debate, including about the utility of vaccines in cancer control. The application of vaccines to cancer control fulfills a promise envisioned at the turn of the 20th century when remarkable experiments showed that some cancers were caused by infections. This suggested the possibility of applying infection-control strategies to cancer control. Vaccines represent the most practical cost-effective technology to prevent wide human suffering and death from many acute infectious diseases, such as small pox or polio. Hitherto applied to control of acute fatal infections, vaccines, if developed, might provide a potent way to control cancer. The articles in the HPV thematic series show success in developing and applying a vaccine against human papilloma virus (HPV). A vaccine is also available against hepatitis B virus (HBV), which causes liver cancer. These vaccines augment the tools available to control the associated cancers. Scientific endeavor continues for six other cancer-associated infections, mostly viruses. Not surprisingly, debate about the safety of vaccines targeting cancer has been triggered in the scientific community. Questions about safety have been raised for those populations where other means to control these cancers may be available. Although it is difficult to quantify risk from vaccines in individuals where other cancer control services exist, it is likely to be low. Vaccines are much safer today than before. Technological advancement in vaccine development and manufacture and improved regulatory review and efficient distribution have minimized substantially the risk for harm from vaccines. Formal and informal debate about the pros and cons of applying vaccines as a cancer control tools is ongoing in scientific journals and on the web. Infectious Agents and Cancer encourages evidence-based discussion to clarify understanding of the role of vaccines in cancer control. In a similar vein, the journal will not consider anecdotal reports and rhetorical arguments because they are unlikely to inform policy, regulation, or the public.

Colorectal cancer development and advances in screening.

PubMed

Simon, Karen

2016-01-01

Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective.

Colorectal cancer development and advances in screening

PubMed Central

Simon, Karen

2016-01-01

Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective. PMID:27486317

A 3D Hydrodynamic Model for Cytokinesis of Eukaryotic Cells

DTIC Science & Technology

2014-08-01

goes wrong may lead to a catastrophe or failure, which may lead to an unwelcome outcome for instance cancer . Thus, a detailed understanding on... biofilm - drug interaction. Discrete and Continuous Dynamical Systems Series B, 15:417–456, March 2011. 13 [17] Brandon Lindley, Qi Wang, and Tianyu Zhang...Multicomponent hydrodynamic model for heterogeneous biofilms : Two-dimensional numerical simulations of growth and in- teraction with flows. Physical

Penile rehabilitation following prostate cancer treatment: review of current literature

PubMed Central

Clavell-Hernandez, Jonathan; Wang, Run

2015-01-01

Radical prostatectomy (RP) and radiotherapy (RT) are highly effective in improving prostate cancer survival. However, both have a detrimental effect on erectile function (EF). Penile rehabilitation consists of understanding the mechanisms that cause erectile dysfunction (ED) and utilizing pharmacologic agents, devices or interventions to promote male sexual function. For the past decade, many researchers have pursued to define effective treatment modalities to improve ED after prostate cancer treatment. Despite the understanding of the mechanisms and well-established rationale for postprostate treatment penile rehabilitation, there is still no consensus regarding effective rehabilitation programs. This article reviews a contemporary series of trials that assess penile rehabilitation and explore treatment modalities that might play a role in the future. Published data and trials related to penile rehabilitation after RP and RT were reviewed and presented. Although recent trials have shown that most therapies are well-tolerated and aid in some degree on EF recovery, we currently do not have tangible evidence to recommend an irrefutable penile rehabilitation algorithm. However, advancements in research and technology will ultimately create and refine management options for penile rehabilitation. PMID:25851656

Understanding resistance to EGFR inhibitors—impact on future treatment strategies

PubMed Central

Wheeler, Deric L.; Dunn, Emily F.; Harari, Paul M.

2010-01-01

EGFR is a tyrosine kinase that participates in the regulation of cellular homeostasis. Following ligand binding, EGFR stimulates downstream cell signaling cascades that influence cell proliferation, apoptosis, migration, survival and complex processes, including angiogenesis and tumorigenesis. EGFR has been strongly implicated in the biology of human epithelial malignancies, with therapeutic applications in cancers of the colon, head and neck, lung, and pancreas. Accordingly, targeting EGFR has been intensely pursued, with the development of a series of promising molecular inhibitors for use in clinical oncology. As is common in cancer therapy, challenges with respect to treatment resistance emerge over time. This situation is certainly true of EGFR inhibitor therapies, where intrinsic and acquired resistance is now well recognized. In this Review, we provide a brief overview regarding the biology of EGFR biology, preclinical and clinical development of EGFR inhibitors, and molecular mechanisms that underlie the development of treatment resistance. A greater understanding of the mechanisms that lead to EGFR resistance may provide valuable insights to help design new strategies that will enhance the impact of this promising class of inhibitors for the treatment of cancer. PMID:20551942

Navigating the cancer information environment: The reciprocal relationship between patient-clinician information engagement and information seeking from nonmedical sources.

PubMed

Moldovan-Johnson, Mihaela; Tan, Andy S L; Hornik, Robert C

2014-01-01

Prior theory has argued and empirical studies have shown that cancer patients rely on information from their health care providers as well as lay sources to understand and make decisions about their disease. However, research on the dynamic and interdependent nature of cancer patients' engagement with different information sources is lacking. This study tested the hypotheses that patient-clinician information engagement and information seeking from nonmedical sources influence one another longitudinally among a representative cohort of 1,293 cancer survivors in Pennsylvania. The study hypotheses were supported in a series of lagged multiple regression analyses. Baseline seeking information from nonmedical sources positively predicted subsequent patient-clinician information engagement at 1-year follow-up. The reverse relationship was also statistically significant; baseline patient-clinician information engagement positively predicted information seeking from nonmedical sources at follow-up. These findings suggest that cancer survivors move between nonmedical and clinician sources in a dynamic way to learn about their disease.

Navigating the cancer information environment: The reciprocal relationship between patient-clinician information engagement and information seeking from nonmedical sources

PubMed Central

Moldovan-Johnson, Mihaela; Tan, Andy SL; Hornik, Robert C

2014-01-01

Prior theory has argued and empirical studies have shown that cancer patients rely on information from their health care providers as well as lay sources to understand and make decisions about their disease. However, research on the dynamic and interdependent nature of cancer patients’ engagement with different information sources is lacking. This study tested the hypotheses that patient-clinician information engagement and information seeking from nonmedical sources influence one another longitudinally among a representative cohort of 1,293 cancer survivors in Pennsylvania. The study hypotheses were supported in a series of lagged multiple regression analyses. Baseline seeking information from nonmedical sources positively predicted subsequent patient-clinician information engagement at one-year follow-up. The reverse relationship was also statistically significant; baseline patient-clinician information engagement positively predicted information seeking from nonmedical sources at follow-up. These findings suggest that cancer survivors move between nonmedical to clinician sources in a dynamic way to learn about their disease. PMID:24359259

AACR precision medicine series: Highlights of the integrating clinical genomics and cancer therapy meeting.

PubMed

Maggi, Elaine; Montagna, Cristina

2015-12-01

The American Association for Cancer Research (AACR) Precision Medicine Series "Integrating Clinical Genomics and Cancer Therapy" took place June 13-16, 2015 in Salt Lake City, Utah. The conference was co-chaired by Charles L. Sawyers form Memorial Sloan Kettering Cancer Center in New York, Elaine R. Mardis form Washington University School of Medicine in St. Louis, and Arul M. Chinnaiyan from University of Michigan in Ann Arbor. About 500 clinicians, basic science investigators, bioinformaticians, and postdoctoral fellows joined together to discuss the current state of Clinical Genomics and the advances and challenges of integrating Next Generation Sequencing (NGS) technologies into clinical practice. The plenary sessions and panel discussions covered current platforms and sequencing approaches adopted for NGS assays of cancer genome at several national and international institutions, different approaches used to map and classify targetable sequence variants, and how information acquired with the sequencing of the cancer genome is used to guide treatment options. While challenges still exist from a technological perspective, it emerged that there exists considerable need for the development of tools to aid the identification of the therapy most suitable based on the mutational profile of the somatic cancer genome. The process to match patients to ongoing clinical trials is still complex. In addition, the need for centralized data repositories, preferably linked to well annotated clinical records, that aid sharing of sequencing information is central to begin understanding the contribution of variants of unknown significance to tumor etiology and response to therapy. Here we summarize the highlights of this stimulating four-day conference with a major emphasis on the open problems that the clinical genomics community is currently facing and the tools most needed for advancing this field. Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Understanding and Targeting Epigenetic Alterations in Acquired Bone Marrow Failure

DTIC Science & Technology

2016-07-01

should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT...modifiers may specifically impact DNA methylation and/or histone post -translational modifications in a manner that is therapeutically targetable, and (c) if...2016 Tisch Cancer Institute Seminar Series, Icahn School of Medicine at Mount Sinai, New York, NY 2016 11th CML & MPN Post -ASH Workshop, La Jolla

Improving Cancer-Related Outcomes with Connected Health - Acknowledgements

Cancer.gov

The President’s Cancer Panel is grateful to all participants who invested their time to take part in the series of workshops on connected health and cancer. A complete list of participants is in Series Information. The Panel is especially appreciative to the series co-chairs who graciously contributed their time and knowledge on this topic, providing valuable guidance during workshop planning and extensive input on this report.

Sequencing Strategies for Population and Cancer Epidemiology Studies (SeqSPACE) Webinar Series

Cancer.gov

The Sequencing Strategies for Population and Cancer Epidemiology Studies (SeqSPACE) Webinar Series provides an opportunity for our grantees and other interested individuals to share lessons learned and practical information regarding the application of next generation sequencing to cancer epidemiology studies.

Comment from the Editor to the Special Issue: “Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis”

PubMed Central

Spaggiari, Lorenzo

2018-01-01

With this Editorial we want to present the Special Issue “Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis” to the scientific community, which aims to gather experts on the early detection of lung cancer in order to implement common efforts in the fight against cancer. PMID:29425180

Research Strategies for Nutritional and Physical Activity Epidemiology and Cancer Prevention

Cancer.gov

In response to a series of controversial articles about nutritional epidemiology and cancer published in 2014, staff from the Environmental Epidemiology Branch initiated a series of meetings to refine programmatic priorities for human nutrition/physical activity and cancer etiology research in the near term.

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties.

PubMed

Godlewska, Marlena; Arczewska, Katarzyna D; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław; Czarnocka, Barbara

2017-01-01

Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.

An integrated approach of network-based systems biology, molecular docking, and molecular dynamics approach to unravel the role of existing antiviral molecules against AIDS-associated cancer.

PubMed

Omer, Ankur; Singh, Poonam

2017-05-01

A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.

Profile of e-patients: analysis of their cancer information-seeking from a national survey.

PubMed

Kim, Kyunghye; Kwon, Nahyun

2010-10-01

Researchers have yet to fully understand how competent e-patients are in selecting and using health information sources, or, more importantly, who e-patients are. This study attempted to uncover how cancer e-patients differ from other cancer information seekers in terms of their sociodemographic background, social networks, information competence, and selection of cancer information sources. We analyzed data from the National Cancer Institute's 2005 Health Information National Trends Survey, and a series of chi-square tests showed that factors that distinguished cancer e-patients from other cancer information seekers were age, gender, education, employment status, health insurance, and membership in online support groups. They were not different in the other factors measured by the survey. Our logistic regression analysis revealed that the e-patients were older and talked about their health issues with friends or family more frequently compared with online health information seekers without cancer. While preferring information from their doctors over the Internet, e-patients used the Internet as their primary source. In contrast to previous literature, we found little evidence that e-patients were savvy health information consumers who could make informed decisions on their own health. The findings of this study addressed a need for a better design and delivery of health information literacy programs for cancer e-patients.

Review: the Contribution of both Nature and Nurture to Carcinogenesis and Progression in Solid Tumours.

PubMed

Hyndman, Iain Joseph

2016-04-01

Cancer is a leading cause of mortality worldwide. Cancer arises due to a series of somatic mutations that accumulate within the nucleus of a cell which enable the cell to proliferate in an unregulated manner. These mutations arise as a result of both endogenous and exogenous factors. Genes that are commonly mutated in cancer cells are involved in cell cycle regulation, growth and proliferation. It is known that both nature and nurture play important roles in cancer development through complex gene-environment interactions; however, the exact mechanism of these interactions in carcinogenesis is presently unclear. Key environmental factors that play a role in carcinogenesis include smoking, UV light and oncoviruses. Angiogenesis, inflammation and altered cell metabolism are important factors in carcinogenesis and are influenced by both genetic and environmental factors. Although the exact mechanism of nature-nurture interactions in solid tumour formation are not yet fully understood, it is evident that neither nature nor nurture can be considered in isolation. By understanding more about gene-environment interactions, it is possible that cancer mortality could be reduced.

Social representations of human papillomavirus in Bogotá, Colombia.

PubMed

Wiesner, Carolina; Acosta, Jesús; Díaz Del Castillo, Adriana; Tovar, Sandra

2012-01-01

Identifying DNA of Human papillomavirus (HPV) has been proposed as a new screening method for cervical cancer control. Conventionally, health education for screening programs is based on scientific information without considering any community cognitive processes. We examine HPV social representations of 124 men and women from diverse educational status living in Bogotá, Colombia. The social representation of HPV involves a series of figurative nuclei derived from meanings linked to scientific information. While women focused on symbols associated to contagion, men focused on its venereal character. Figurative nuclei also included long-term uncertainty, need or urgent treatment, and feelings of imminent death associated with cancer and chronic sexually transmitted infections. The social representation of HPV impeded many participants from clearly understanding written information about HPV transmission, clearance, and cancer risk; they are built into a framework of values, which must be deconstructed to allow women full participation in HPV screening programs.

[Update of breast cancer in Primary Care (II/V)].

PubMed

Brusint, B; Vich, P; Ávarez-Hernández, C; Cuadrado-Rouco, C; Díaz-García, N; Redondo-Margüello, E

2014-10-01

Breast cancer is a prevalent disease affecting all areas of patients' lives. Therefore, family doctors need to thoroughly understand this disease in order to optimize the health care services for these patients, making the best use of available resources. A series of 5 articles on breast cancer is presented below. It is based on a review of the scientific literature over the last 10 years. The second one deals with population screening and its controversies, screening in high-risk women, and the current recommendations. This summary report aims to provide a current and practical review about this problem, providing answers to family doctors, and helping them to be able to care for their patients for their benefit throughout their illness. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

[Update of breast cancer in primary care (IV/V)].

PubMed

Álvarez-Hernández, C; Brusint, B; Vich, P; Díaz-García, N; Cuadrado-Rouco, C; Hernández-García, M

2015-01-01

Breast cancer is a prevalent disease affecting all areas of patients' lives. Therefore, family physicians must thoroughly understand this pathology in order to optimize the health care services and make the best use of available resources, for these patients. A series of 5 articles on breast cancer is presented below. It is based on a review of the scientific literature over the last 10 years. This fourth article deals with the treatment of the disease, the role of the primary care physician, and management of major complications. This summary report aims to provide a current and practical review about this problem, providing answers to family doctors and helping them to support their patients and care for them throughout their illness. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Development of km23-Based Diagnostics and Therapeutics

DTIC Science & Technology

2004-05-01

Publishers, Cancer Treatment and Research Book Series. Chap . 15, 315-327, 2004. Abstracts: Jin Q, MD, Ding W, MD, PhD, Staub CM, Gao G, MD, Mulder KM, PhD...Kluwer Academic Publishers, Cancer Treatment and Research Book Series. Chap . 15, 315-327, 2004. Ilangovan U, Ding W, Zuniga J, Wilson, CL, Hinck AP...Academic Publishers, Cancer Treatment and Research Book Series. Chap . 15, 315-327, 2004. 2. Manuscript Submitted: Jin Q. Ding W, Staub CM, Gao G, Tang Q

Cancer incidence in atomic bomb survivors. Part IV: Comparison of cancer incidence and mortality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ron, E.; Preston, D.L.; Mabuchi, Kiyohiko

1994-02-01

This report compares cancer incidence and mortality among atomic bomb survivors in the Radiation Effects Research Foundation Life Span Study (LSS) cohort. Because the incidence data are derived from the Hiroshima and Nagasaki tumor registries, case ascertainment is limited to the time (1958-1987) and geographic restrictions (Hiroshima and Nagasaki) of the registries, whereas mortality data are available from 1950-1987 anywhere in Japan. With these conditions, there were 9,014 first primary incident cancer cases identified among LSS cohort members compared with 7,308 deaths for which cancer was listed as the underlying cause of death on death certificates. When deaths were limitedmore » to those occurring between 1958-1987 in Hiroshima or Nagasaki, there were 3,155 more incident cancer cases overall, and 1,262 more cancers of the digestive system. For cancers of the oral cavity and pharynx, skin, breast, female and male genital organs, urinary system and thyroid, the incidence series was at least twice as large as the comparable mortality series. Although the incidence and mortality data are dissimilar in many ways, the overall conclusions regarding which solid cancers provide evidence of a significant dose response generally confirm the mortality findings. When either incidence or mortality data are evaluated, significant excess risks are observed for all solid cancers, stomach, colon, liver (when it is defined as primary liver cancer or liver cancer not otherwise specified on the death certificate), lung, breast, ovary and urinary bladder. No significant radiation effect is seen for cancers of the pharynx, rectum, gallbladder, pancreas, nose, larynx, uterus, prostate or kidney in either series. There is evidence of a significant excess of nonmelanoma skin cancer in the incidence data, but not in the mortality series. 19 refs., 2 figs., 10 tabs.« less

Cervical and female breast cancers in the Americas: current situation and opportunities for action.

PubMed

Luciani, Silvana; Cabanes, Anna; Prieto-Lara, Elisa; Gawryszewski, Vilma

2013-09-01

To understand better the current regional situation and public health response to cervical cancer and female breast cancer in the Americas. Data on cervical cancer and female breast cancers in 33 countries, for the period from 2000 to the last year with available data, were extracted from the Pan American Health Organization (PAHO) Regional Mortality Database and analysed. Changes in mortality rates over the study period - in all countries except those with small populations and large fluctuations in time-series mortality data - were calculated using Poisson regression models. Information from the PAHO Country Capacity Survey on noncommunicable diseases was also analysed. The Bahamas, Trinidad and Tobago and Uruguay showed relatively high rates of death from breast cancer, whereas the three highest rates of death from cervical cancer were observed in El Salvador, Nicaragua and Paraguay. Several countries - particularly Paraguay and Venezuela - have high rates of death from both types of cancer. Although mortality from cervical cancer has generally been decreasing in the Americas, decreases in mortality from breast cancer have only been observed in a few countries in the Region of the Americas. All but one of the 25 countries in the Americas included in the PAHO Country Capacity Survey reported having public health services for the screening and treatment of breast and cervical cancers. Most countries in the Americas have the public health capacity needed to screen for - and treat - breast and cervical cancers and, therefore, the potential to reduce the burden posed by these cancers.

LuCaP Prostate Cancer Patient-Derived Xenografts Reflect the Molecular Heterogeneity of Advanced Disease an--d Serve as Models for Evaluating Cancer Therapeutics.

PubMed

Nguyen, Holly M; Vessella, Robert L; Morrissey, Colm; Brown, Lisha G; Coleman, Ilsa M; Higano, Celestia S; Mostaghel, Elahe A; Zhang, Xiaotun; True, Lawrence D; Lam, Hung-Ming; Roudier, Martine; Lange, Paul H; Nelson, Peter S; Corey, Eva

2017-05-01

Metastatic prostate cancer is a common and lethal disease for which there are no therapies that produce cures or long-term durable remissions. Clinically relevant preclinical models are needed to increase our understanding of biology of this malignancy and to evaluate new agents that might provide effective treatment. Our objective was to establish and characterize patient-derived xenografts (PDXs) from advanced prostate cancer (PC) for investigation of biology and evaluation of new treatment modalities. Samples of advanced PC obtained from primary prostate cancer obtained at surgery or from metastases collected at time of death were implanted into immunocompromised mice to establish PDXs. Established PDXs were propagated in vivo. Genomic, transcriptomic, and STR profiles were generated. Responses to androgen deprivation and docetaxel in vivo were characterized. We established multiple PDXs (LuCaP series), which represent the major genomic and phenotypic features of the disease in humans, including amplification of androgen receptor, PTEN deletion, TP53 deletion and mutation, RB1 loss, TMPRSS2-ERG rearrangements, SPOP mutation, hypermutation due to MSH2/MSH6 genomic aberrations, and BRCA2 loss. The PDX models also exhibit variation in intra-tumoral androgen levels. Our in vivo results show heterogeneity of response to androgen deprivation and docetaxel, standard therapies for advanced PC, similar to the responses of patients to these treatments. The LuCaP PDX series reflects the diverse molecular composition of human castration-resistant PC and allows for hypothesis-driven cause-and-effect studies of mechanisms underlying treatment response and resistance. Prostate 77: 654-671, 2017. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc. © 2017 The Authors. The Prostate Published by Wiley Periodicals, Inc.

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties

PubMed Central

Godlewska, Marlena; Arczewska, Katarzyna D.; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław

2017-01-01

Background Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. Methods In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. Results We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Conclusions Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism. PMID:28575127

A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions

NASA Astrophysics Data System (ADS)

Zhu, Wei; Castro, Nathan J.; Cui, Haitao; Zhou, Xuan; Boualam, Benchaa; McGrane, Robert; Glazer, Robert I.; Zhang, Lijie Grace

2016-08-01

Bone metastasis is one of the most prevalent complications of late-stage breast cancer, in which the native bone matrix components, including osteoblasts, are intimately involved in tumor progression. The development of a successful in vitro model would greatly facilitate understanding the underlying mechanism of breast cancer bone invasion as well as provide a tool for effective discovery of novel therapeutic strategies. In the current study, we fabricated a series of in vitro bone matrices composed of a polyethylene glycol hydrogel and nanocrystalline hydroxyapatite of varying concentrations to mimic the native bone microenvironment for the investigation of breast cancer bone metastasis. A stereolithography-based three-dimensional (3D) printer was used to fabricate the bone matrices with precisely controlled architecture. The interaction between breast cancer cells and osteoblasts was investigated in the optimized bone matrix. Using a Transwell® system to separate the two cell lines, breast cancer cells inhibited osteoblast proliferation, while osteoblasts stimulated breast cancer cell growth, whereas, both cell lines increased IL-8 secretion. Breast cancer cells co-cultured with osteoblasts within the 3D bone matrix formed multi-cellular spheroids in comparison to two-dimensional monolayers. These findings validate the use of our 3D printed bone matrices as an in vitro metastasis model, and highlights their potential for investigating breast cancer bone metastasis.

Proceedings of the third international molecular pathological epidemiology (MPE) meeting.

PubMed

Campbell, Peter T; Rebbeck, Timothy R; Nishihara, Reiko; Beck, Andrew H; Begg, Colin B; Bogdanov, Alexei A; Cao, Yin; Coleman, Helen G; Freeman, Gordon J; Heng, Yujing J; Huttenhower, Curtis; Irizarry, Rafael A; Kip, N Sertac; Michor, Franziska; Nevo, Daniel; Peters, Ulrike; Phipps, Amanda I; Poole, Elizabeth M; Qian, Zhi Rong; Quackenbush, John; Robins, Harlan; Rogan, Peter K; Slattery, Martha L; Smith-Warner, Stephanie A; Song, Mingyang; VanderWeele, Tyler J; Xia, Daniel; Zabor, Emily C; Zhang, Xuehong; Wang, Molin; Ogino, Shuji

2017-02-01

Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods, and resources from epidemiology, pathology, biostatistics, bioinformatics, and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: (1) the development of new statistical methods to address etiologic heterogeneity; (2) the enhancement of causal inference; (3) the identification of previously unknown exposure-subtype disease associations; and (4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields.

Proceedings of the Third International Molecular Pathological Epidemiology (MPE) Meeting

PubMed Central

Campbell, Peter T.; Rebbeck, Timothy R.; Nishihara, Reiko; Beck, Andrew H.; Begg, Colin B.; Bogdanov, Alexei A.; Cao, Yin; Coleman, Helen G.; Freeman, Gordon J.; Heng, Yujing J.; Huttenhower, Curtis; Irizarry, Rafael A.; Kip, N. Sertac; Michor, Franziska; Nevo, Daniel; Peters, Ulrike; Phipps, Amanda I.; Poole, Elizabeth M.; Qian, Zhi Rong; Quackenbush, John; Robins, Harlan; Rogan, Peter K.; Slattery, Martha L.; Smith-Warner, Stephanie A.; Song, Mingyang; VanderWeele, Tyler J.; Xia, Daniel; Zabor, Emily C.; Zhang, Xuehong; Wang, Molin; Ogino, Shuji

2016-01-01

Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods and resources from epidemiology, pathology, biostatistics, bioinformatics and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: 1) the development of new statistical methods to address etiologic heterogeneity; 2) the enhancement of causal inference; 3) the identification of previously unknown exposure-subtype disease associations; and 4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields. PMID:28097472

The solid-state signaling pathway from extracellular matrix to nuclear matrix: The critical role of three-dimensional architecture for functional differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lelievre, S.; Bissell, M.J.

Breast cells are useful experimental subjects for cell biologists because the mammary gland is one of the few tissues that undergoes dramatic changes in form and function after adulthood. Recently, the study in our laboratory of a human breast tumor progression series has allowed for the analysis of changes in cellular architecture (including nuclear architecture) when phenotypically normal cells become tumorigenic. This research aims to participate in the battle against breast cancer by helping to understand tumor progression and to identify new therapeutic markers for cancer treatment. This article explores the advantages and challenges of using high resolution X-ray computedmore » microtomography for the study of 3-dimensional organization of breast tissue architecture.« less

Use of a Shared Mental Model by a Team Composed of Oncology, Palliative Care, and Supportive Care Clinicians to Facilitate Shared Decision Making in a Patient With Advanced Cancer.

PubMed

D'Ambruoso, Sarah F; Coscarelli, Anne; Hurvitz, Sara; Wenger, Neil; Coniglio, David; Donaldson, Dusty; Pietras, Christopher; Walling, Anne M

2016-11-01

Our case describes the efforts of team members drawn from oncology, palliative care, supportive care, and primary care to assist a woman with advanced cancer in accepting care for her psychosocial distress, integrating prognostic information so that she could share in decisions about treatment planning, involving family in her care, and ultimately transitioning to hospice. Team members in our setting included a medical oncologist, oncology nurse practitioner, palliative care nurse practitioner, oncology social worker, and primary care physician. The core members were the patient and her sister. Our team grew organically as a result of patient need and, in doing so, operationalized an explicitly shared understanding of care priorities. We refer to this shared understanding as a shared mental model for care delivery, which enabled our team to jointly set priorities for care through a series of warm handoffs enabled by the team's close proximity within the same clinic. When care providers outside our integrated team became involved in the case, significant communication gaps exposed the difficulty in extending our shared mental model outside the integrated team framework, leading to inefficiencies in care. Integration of this shared understanding for care and close proximity of team members proved to be key components in facilitating treatment of our patient's burdensome cancer-related distress so that she could more effectively participate in treatment decision making that reflected her goals of care.

Detecting discordance enrichment among a series of two-sample genome-wide expression data sets.

PubMed

Lai, Yinglei; Zhang, Fanni; Nayak, Tapan K; Modarres, Reza; Lee, Norman H; McCaffrey, Timothy A

2017-01-25

With the current microarray and RNA-seq technologies, two-sample genome-wide expression data have been widely collected in biological and medical studies. The related differential expression analysis and gene set enrichment analysis have been frequently conducted. Integrative analysis can be conducted when multiple data sets are available. In practice, discordant molecular behaviors among a series of data sets can be of biological and clinical interest. In this study, a statistical method is proposed for detecting discordance gene set enrichment. Our method is based on a two-level multivariate normal mixture model. It is statistically efficient with linearly increased parameter space when the number of data sets is increased. The model-based probability of discordance enrichment can be calculated for gene set detection. We apply our method to a microarray expression data set collected from forty-five matched tumor/non-tumor pairs of tissues for studying pancreatic cancer. We divided the data set into a series of non-overlapping subsets according to the tumor/non-tumor paired expression ratio of gene PNLIP (pancreatic lipase, recently shown it association with pancreatic cancer). The log-ratio ranges from a negative value (e.g. more expressed in non-tumor tissue) to a positive value (e.g. more expressed in tumor tissue). Our purpose is to understand whether any gene sets are enriched in discordant behaviors among these subsets (when the log-ratio is increased from negative to positive). We focus on KEGG pathways. The detected pathways will be useful for our further understanding of the role of gene PNLIP in pancreatic cancer research. Among the top list of detected pathways, the neuroactive ligand receptor interaction and olfactory transduction pathways are the most significant two. Then, we consider gene TP53 that is well-known for its role as tumor suppressor in cancer research. The log-ratio also ranges from a negative value (e.g. more expressed in non-tumor tissue) to a positive value (e.g. more expressed in tumor tissue). We divided the microarray data set again according to the expression ratio of gene TP53. After the discordance enrichment analysis, we observed overall similar results and the above two pathways are still the most significant detections. More interestingly, only these two pathways have been identified for their association with pancreatic cancer in a pathway analysis of genome-wide association study (GWAS) data. This study illustrates that some disease-related pathways can be enriched in discordant molecular behaviors when an important disease-related gene changes its expression. Our proposed statistical method is useful in the detection of these pathways. Furthermore, our method can also be applied to genome-wide expression data collected by the recent RNA-seq technology.

Cervical and female breast cancers in the Americas: current situation and opportunities for action

PubMed Central

Cabanes, Anna; Prieto-Lara, Elisa; Gawryszewski, Vilma

2013-01-01

Abstract Objective To understand better the current regional situation and public health response to cervical cancer and female breast cancer in the Americas. Methods Data on cervical cancer and female breast cancers in 33 countries, for the period from 2000 to the last year with available data, were extracted from the Pan American Health Organization (PAHO) Regional Mortality Database and analysed. Changes in mortality rates over the study period – in all countries except those with small populations and large fluctuations in time–series mortality data – were calculated using Poisson regression models. Information from the PAHO Country Capacity Survey on noncommunicable diseases was also analysed. Findings The Bahamas, Trinidad and Tobago and Uruguay showed relatively high rates of death from breast cancer, whereas the three highest rates of death from cervical cancer were observed in El Salvador, Nicaragua and Paraguay. Several countries – particularly Paraguay and Venezuela – have high rates of death from both types of cancer. Although mortality from cervical cancer has generally been decreasing in the Americas, decreases in mortality from breast cancer have only been observed in a few countries in the Region of the Americas. All but one of the 25 countries in the Americas included in the PAHO Country Capacity Survey reported having public health services for the screening and treatment of breast and cervical cancers. Conclusion Most countries in the Americas have the public health capacity needed to screen for – and treat – breast and cervical cancers and, therefore, the potential to reduce the burden posed by these cancers. PMID:24101780

Genome-wide association study in discordant sibships identifies multiple inherited susceptibility alleles linked to lung cancer.

PubMed

Galvan, Antonella; Falvella, Felicia S; Frullanti, Elisa; Spinola, Monica; Incarbone, Matteo; Nosotti, Mario; Santambrogio, Luigi; Conti, Barbara; Pastorino, Ugo; Gonzalez-Neira, Anna; Dragani, Tommaso A

2010-03-01

We analyzed a series of young (median age = 52 years) non-smoker lung cancer patients and their unaffected siblings as controls, using a genome-wide 620 901 single-nucleotide polymorphism (SNP) array analysis and a case-control DNA pooling approach. We identified 82 putatively associated SNPs that were retested by individual genotyping followed by use of the sib transmission disequilibrium test, pointing to 36 SNPs associated with lung cancer risk in the discordant sibs series. Analysis of these 36 SNPs in a polygenic model characterized by additive and interchangeable effects of rare alleles revealed a highly statistically significant dosage-dependent association between risk allele carrier status and proportion of cancer cases. Replication of the same 36 SNPs in a population-based series confirmed the association with lung cancer for three SNPs, suggesting that phenocopies and genetic heterogeneity can play a major role in the complex genetics of lung cancer risk in the general population.

The intersection of cancer, cancer stem cells, and the immune system: therapeutic opportunities.

PubMed

Silver, Daniel J; Sinyuk, Maksim; Vogelbaum, Michael A; Ahluwalia, Manmeet S; Lathia, Justin D

2016-02-01

During brain neoplasia, malignant cells subjugate the immune system to provide an environment that favors tumor growth. These mechanisms capitalize on tumor-promoting functions of various immune cell types and typically result in suppression of tumor immune rejection. Immunotherapy efforts are underway to disrupt these mechanisms and turn the immune system against developing tumors. While many of these therapies are already in early-stage clinical trials, understanding how these therapies impact various tumor cell populations, including self-renewing cancer stem cells, may help to predict their efficacy and clarify their mechanisms of action. Moreover, interrogating the biology of glioma cell, cancer stem cell, and immune cell interactions may provide additional therapeutic targets to leverage against disease progression. In this review, we begin by highlighting a series of investigations into immune cell-mediated tumor promotion that do not parse the tumor into stem and non-stem components. We then take a closer look at the immune-suppressive mechanisms derived specifically from cancer stem cell interactions with the immune system and end with an update on immunotherapy and cancer stem cell-directed clinical trials in glioblastoma. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Periostin: a putative mediator involved in tumour resistance to anti-angiogenic therapy?

PubMed

Wang, Wei; Ma, Jin-Liang; Jia, Wei-Dong; Xu, Ge-Liang

2011-11-01

Despite advances in the development of anti-angiogenic agents for cancer treatment, the increase in the survival duration of cancer patients is still rather modest. One major obstacle in anti-angiogenic therapy is the emergence of drug resistance. Understanding the molecular mechanisms that enable a tumour to evade anti-angiogenic treatment is valuable to improve therapeutic efficacy. Targeting blood supply usually causes hypoxic responses of tumours that trigger a series of adaptive changes leading to a resistant phenotype. Periostin, a secreted ECM (extracellular matrix) protein, is mainly produced by CAFs (cancer-associated fibroblasts) on hypoxic stress. As CAFs have been casually linked to tumour resistance to angiogenesis blockade and periostin can influence many aspects of tumour biology, we hypothesized that periostin might be a crucial mediator involved anti-angiogenic resistance in cancer treatment. This hypothesis is indirectly supported by the following facts: (a) high levels of periostin promote tumour angiogenesis; (b) periostin improves cancer cell survival under hypoxic conditions; and (c) genetic modulation of periostin induces EMT (epithelial-mesenchymal transition) and enhances cancer cell invasion and metastasis, which represents an escape mechanism from anticancer treatment. Testing and confirmation of this hypothesis will give more insight into the resistance mechanisms and provide the rationale for improvement of therapeutic outcome of anti-angiogenic therapy.

Understanding how prostate cancer patients value the current treatment options for metastatic castration resistant prostate cancer.

PubMed

Benidir, Tarik; Hersey, Karen; Finelli, Antonio; Hamilton, Rob; Joshua, Anthony M; Kulkarni, Girish; Zlotta, Alexandre; Fleshner, Neil

2018-05-01

Several new compounds are now available for castration resistant prostate cancer (CRPC). Individual costs range between $40,000 and $93,000 with mean survival extensions from 2.4 to 4.8 months. Currently, it remains unclear how patients with prostate cancer (PCa) value the effect of these therapies in the setting of CRPC. To assess patient understanding of core cancer concepts, opinions on the cost and overall benefit of CRPC drugs, whether out-of-pocket costs would change opinions and whether patients would ultimately opt out of CRPC drug treatment for an end-of-life (EOL) premium. We conducted a qualitative survey among patients with various PCa states ranging from active surveillance to CRPC and from various familial, financial and educational demographics. Through a series of hypothetical scenarios, we extrapolated opinions on CRPC drug value, efficacy and monetary worth. We assessed patient willingness to accept an EOL ($50,000) premium in lieu of CRPC drug treatment. Statistically, chi-squared analysis and Fisher's exact test were used when appropriate. In total, 103 patients completed the questionnaire, one-half of whom did not understand "advanced PCa" state and more than one-third of the concept of palliative care despite multiple meetings with Urologists. Patients willingness-to-pay and proposed drug value was higher than that accepted by government when government funded, with costs exceeding $250,000 per person, but lower than that accepted by government when self-funded. A majority (60%) would accept/consider the EOL premium in the setting of CRPC. Patients with higher education were more skeptical about CRPC drug value and more likely to accept the EOL premium (P = 0.003.) CONCLUSION: Patients have an incomplete understanding of their own disease prognosis and its therapeutic options. This ultimately influences patient decision-making. Education, income and out-of-pocket costs diminished opinion of CRPC drugs considerably. As such, an EOL premium should be considered in subsets of patients. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

AHNS Series: Do you know your guidelines? Principles of surgery for head and neck cancer: A review of the National Comprehensive Cancer Network guidelines.

PubMed

Miller, Matthew C; Goldenberg, David

2017-04-01

This article continues a series developed by the American Head and Neck Society's Education Committee entitled "Do you know your guidelines?" It is hoped that these features will increase awareness of and adherence to current best practices in head and neck cancer care. In this installment, the National Comprehensive Cancer Network (NCCN) guidelines for surgical therapy are reviewed. © 2016 Wiley Periodicals, Inc. Head Neck 39: 791-796, 2017. © 2016 Wiley Periodicals, Inc.

Staging of Lung Cancer

MedlinePlus

... LUNG CANCER MINI-SERIES #2 Staging of Lung Cancer Once your lung cancer is diagnosed, staging tells you and your health care provider about ... at it under a microscope. The stages of lung cancer are listed as I, II, III, and IV ...

AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective

PubMed Central

Talmadge, James E; Fidler, Isaiah J

2014-01-01

Metastases resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His “seed and soil” hypothesis was substantiated a century later with experimental studies and numerous reports have confirmed these seminal observations. Inarguably, an improved understanding of the metastatic process and the attributes of the cells selected by this process are critical to the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, such that metastasis prevention may not be relevant, and treatment of systemic disease, as well as the identity of patients with early disease, should be our goal. During the last three decades, revitalized research has focused on new discoveries in the biology of metastasis. While our understanding of the molecular events that regulate metastasis has improved; nonetheless, the relevant contributions and timing of molecular lesion(s) potentially involved in its pathogenesis remain unclear. The history of pioneering observations and discussion of current controversies should help investigators understand the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and allow for the design of successful therapy. PMID:20610625

Pathological characterisation of male breast cancer: Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.

PubMed

Vermeulen, Marijn A; Slaets, Leen; Cardoso, Fatima; Giordano, Sharon H; Tryfonidis, Konstantinos; van Diest, Paul J; Dijkstra, Nizet H; Schröder, Carolien P; van Asperen, Christi J; Linderholm, Barbro; Benstead, Kim; Foekens, Renee; Martens, John W M; Bartlett, John M S; van Deurzen, Carolien H M

2017-09-01

Several prognostic histological features have been established in female breast cancer (BC), but it is unknown whether these can be extrapolated to male BC patients. The aim of this study was to evaluate the prognostic value of several histological features in a large series of male BC. Central pathology review was performed for 1483 male BCs collected through part 1 of the European Organisation for Research and Treatment of Cancer (EORTC) International Male BC Program. Pathology review included histological subtype, grade, mitotic activity index (MAI), presence of a fibrotic focus and density of tumour-infiltrating lymphocytes (TILs). These features were correlated with clinical outcome. The relationship between these features and surrogate molecular subtypes using immunohistochemistry was also assessed. Median follow-up for overall survival (OS) was 7.1 years. Overall histological grade was not significantly associated with OS (p = 0.129). MAI, the presence of a fibrotic focus and a low TIL density however were correlated with unfavourable OS (p = 0.023, p = 0.004 and p = 0.011, respectively). BC subtype correlated with TIL density (p = 0.015), as we observed a higher density for human epidermal growth factor receptor type 2 (HER2) positive BC compared to luminal HER2-negative subtype. No association was observed between subtype and fibrotic focus. Histologic grade was not significantly correlated with clinical outcome in this series, unlike what is seen in female patients. These results contribute to our understanding of male BC and indicate the importance of further research on the optimisation of risk stratification and treatment decisions for male BC patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multiclass classification for skin cancer profiling based on the integration of heterogeneous gene expression series.

PubMed

Gálvez, Juan Manuel; Castillo, Daniel; Herrera, Luis Javier; San Román, Belén; Valenzuela, Olga; Ortuño, Francisco Manuel; Rojas, Ignacio

2018-01-01

Most of the research studies developed applying microarray technology to the characterization of different pathological states of any disease may fail in reaching statistically significant results. This is largely due to the small repertoire of analysed samples, and to the limitation in the number of states or pathologies usually addressed. Moreover, the influence of potential deviations on the gene expression quantification is usually disregarded. In spite of the continuous changes in omic sciences, reflected for instance in the emergence of new Next-Generation Sequencing-related technologies, the existing availability of a vast amount of gene expression microarray datasets should be properly exploited. Therefore, this work proposes a novel methodological approach involving the integration of several heterogeneous skin cancer series, and a later multiclass classifier design. This approach is thus a way to provide the clinicians with an intelligent diagnosis support tool based on the use of a robust set of selected biomarkers, which simultaneously distinguishes among different cancer-related skin states. To achieve this, a multi-platform combination of microarray datasets from Affymetrix and Illumina manufacturers was carried out. This integration is expected to strengthen the statistical robustness of the study as well as the finding of highly-reliable skin cancer biomarkers. Specifically, the designed operation pipeline has allowed the identification of a small subset of 17 differentially expressed genes (DEGs) from which to distinguish among 7 involved skin states. These genes were obtained from the assessment of a number of potential batch effects on the gene expression data. The biological interpretation of these genes was inspected in the specific literature to understand their underlying information in relation to skin cancer. Finally, in order to assess their possible effectiveness in cancer diagnosis, a cross-validation Support Vector Machines (SVM)-based classification including feature ranking was performed. The accuracy attained exceeded the 92% in overall recognition of the 7 different cancer-related skin states. The proposed integration scheme is expected to allow the co-integration with other state-of-the-art technologies such as RNA-seq.

Targeting Programmed Cell Death Using Small-Molecule Compounds to Improve Potential Cancer Therapy.

PubMed

Ke, Bowen; Tian, Mao; Li, Jingjing; Liu, Bo; He, Gu

2016-11-01

Evasion of cell death is one of the hallmarks of cancer cells, beginning with long-established apoptosis and extending to other new forms of cell death. An elaboration of cell death pathways thus will contribute to a better understanding of cancer pathogenesis and therapeutics. With the recent substantial biochemical and genetic explorations of cell death subroutines, their classification has switched from primarily morphological to more molecular definitions. According to their measurable biochemical features and intricate mechanisms, cell death subroutines can be divided into apoptosis, autophagic cell death, mitotic catastrophe, necroptosis, parthanatos, ferroptosis, pyroptosis, pyronecrosis, anoikis, cornification, entosis, and NETosis. Supportive evidence has gradually revealed the prime molecular mechanisms of each subroutine and thus providing series of possible targets in cancer therapy, while the intricate relationships between different cell death subroutines still remain to be clarified. Over the past decades, cancer drug discovery has significantly benefited from the use of small-molecule compounds to target classical modalities of cell death such as apoptosis, while newly identified cell death subroutines has also emerging their potential for cancer drug discovery in recent years. In this review, we comprehensively focus on summarizing 12 cell death subroutines and discussing their corresponding small-molecule compounds in potential cancer therapy. Together, these inspiring findings may provide more evidence to fill in the gaps between cell death subroutines and small-molecule compounds to better develop novel cancer therapeutic strategies. © 2016 Wiley Periodicals, Inc.

Dynamics of biological systems: role of systems biology in medical research.

PubMed

Assmus, Heike E; Herwig, Ralf; Cho, Kwang-Hyun; Wolkenhauer, Olaf

2006-11-01

Cellular systems are networks of interacting components that change with time in response to external and internal events. Studying the dynamic behavior of these networks is the basis for an understanding of cellular functions and disease mechanisms. Quantitative time-series data leading to meaningful models can improve our knowledge of human physiology in health and disease, and aid the search for earlier diagnoses, better therapies and a healthier life. The advent of systems biology is about to take the leap into clinical research and medical applications. This review emphasizes the importance of a dynamic view and understanding of cell function. We discuss the potential for computer-aided mathematical modeling of biological systems in medical research with examples from some of the major therapeutic areas: cancer, cardiovascular, diabetic and neurodegenerative medicine.

AHNS Series: Do you know your guidelines?Principles of radiation therapy for head and neck cancer: A review of the National Comprehensive Cancer Network guidelines.

PubMed

Gooi, Zhen; Fakhry, Carole; Goldenberg, David; Richmon, Jeremy; Kiess, Ana P

2016-07-01

This article is a continuation of the "Do You Know Your Guidelines" series, an initiative of the American Head and Neck Society's Education Committee to increase awareness of current best practices pertaining to head and neck cancer. The National Comprehensive Cancer Network guidelines for radiotherapy in the treatment for head and neck cancers are reviewed here in a systematic fashion according to site and stage. These guidelines outline indications for primary and adjuvant treatment, as well as general principles of radiotherapy. © 2016 Wiley Periodicals, Inc. Head Neck 38: 987-992, 2016. © 2016 Wiley Periodicals, Inc.

Central nervous system tumours profile at a referral center in the Brazilian Amazon region, 1997–2014

PubMed Central

Semblano, Aluízio Augusto Pereira; Moreira, Matheus Acácio; de Lemos, Manuela Nascimento; de Mello, Vanessa Jóia; Hamoy, Moisés; Nazareth Junior, Mario Hermes; Paschoal Junior, Fernando Mendes; Adami, Fernando

2017-01-01

Tumours of the Central Nervous System (CNS) are an important cause of mortality from cancer. Epidemiological data on neoplams affecting the CNS are scarce in Brazil, especially in the Amazon region. The study aims at describing the histopathological profile of CNS tumours cases at a high-complexity referral cancer center. This study has described a 17-year-series profile of CNS tumours, registered at a high-complexity referral cancer center in Pará state, from January 1997 until July 2014 in the Brazilian Amazon Region. Data was gathered from histopathology reports kept in the hospital’s cancer registry and 949 cases of CNS tumours were analyzed. The most common histopathology were neuroepithelial tumours (approx. 40%) and meningioma was the most frequent especific tumor histologic subtype (22.2%). Neuroepithelial tumours were more frequent in patients with ages ranging from less than a year to 19 years, whereas metastatic tumours were prevalent in patients over 40 years of age. It was not found temporal trends during the studied period. The knowledge of these tumours profile is valuable for the understanding of cancer epidemiology in the region, since its prevalence is currently underreported and more awareness on the disease is needed. PMID:28369089

Primary focal prostate radiotherapy: Do all patients really need whole-prostate irradiation?

PubMed

Jereczek-Fossa, Barbara Alicja; Ciardo, Delia; Petralia, Giuseppe; Bellomi, Massimo; De Bari, Berardino; De Cobelli, Ottavio; Orecchia, Roberto

2016-09-01

To review the available data about focal primary partial prostate irradiation (focal radiotherapy, FRT) for early prostate cancer. Medline search for English language full paper on primary FRT for early prostate cancer including review articles, planning studies or patient series (clinical outcome available) published before May 31, 2015. 22 papers have been found: 11 review articles, 4 planning studies and 7 patient series. Eleven review articles were dedicated to all types of focal therapy including FRT and 2 to FRT only. All planning studies included brachytherapy and showed excellent organ-at-risk sparing. Patient series included together 715 patients (99% treated with brachytherapy) and showed promising tumour control in low-risk cancer. In intermediate-risk tumours, FRT might be suboptimal. Primary FRT is feasible in early prostate cancer. As any other focal therapy, FRT remains investigational until numerous questions are answered. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Addressing cancer disparities through community engagement: improving breast health among Haitian women.

PubMed

Meade, Cathy D; Menard, Janelle; Thervil, Claudine; Rivera, Marlene

2009-11-01

To describe processes for fostering community engagement among Haitian women to facilitate breast health education and outreach that are consonant with Haitians' cultural values, literacy, and linguistic skills. Existing breast cancer education and outreach efforts for Haitian immigrant communities were reviewed. Local community partners were the primary source of information and guided efforts to create a series of health-promoting activities. The resultant partnership continues to be linked to a larger communitywide effort to reduce cancer disparities led by the Tampa Bay Community Cancer Network. A systematic framework known as the CLEAN (Culture, Literacy, Education, Assessment, and Networking) Look Checklist guided efforts for improved communications. Community engagement forms the foundation for the development and adaptation of sustainable breast education and outreach. Understanding and considering aspects of Haitian culture are important to the provision of competent and meaningful care. Nurses should expand their skills, knowledge, and competencies to better address the changing demographics of their communities. Nurses also can play a critical role in the development of outreach programs that are relevant to the culture and literacy of Haitian women by forming mutually beneficial partnerships that can decrease health disparities in communities.

Survival Benefit of Japanese Extended Lymphadenectomy for Clinically Node-Negative and Node-Positive Colorectal Cancers.

PubMed

Ouchi, Akira; Komori, Koji; Kimura, Kenya; Kinoshita, Takashi; Shimizu, Yasuhiro; Nagino, Masato

2018-02-01

The impact of extended lymphadenectomy for colorectal cancer is still not sufficiently clear. The aim of the present study was to evaluate the survival benefit of extended lymphadenectomy compared with nonextended lymphadenectomy for clinically node-negative and node-positive colorectal cancers. The present study was a retrospective cohort study that used prospectively collected data and a propensity score matching method. The present study was conducted at a single specialized colorectal surgery department. Of the 1314 patients who underwent radical resection with nonextended or extended lymphadenectomy between 1988 and 2007, we included 711 and 603 patients in the cN0 and cN1/2 series. Propensity score matching was applied, and 141 and 63 pairs were extracted from the cN0 and cN1/2 series. Disease-free survival, cancer-specific survival, and overall survival of the 2 groups were calculated and compared. In the cN0 series, no differences were observed in the long-term outcomes between the nonextended and extended groups. In the cN1/2 series, the disease-free survival, cancer-specific survival and overall survival were significantly higher (log rank, p = 0.04, p = 0.02, and p = 0.01, respectively), and the frequency of local recurrence was significantly lower (p = 0.04) in the extended group. The present study was limited by its nonrandomized retrospective design. Extended lymphadenectomy demonstrated a good inhibitory effect on the local recurrence rate and led to improved disease-free survival, cancer-specific survival, and overall survival of patients in the cN1/2 series. See Video Abstract at http://links.lww.com/DCR/A517.

Special Section: Preventing, Detecting, and Treating Colorectal Cancer

MedlinePlus

... long series to promote colon and rectal (colorectal) cancer awareness and screening. Following that, research showed that the ... has helped to raise millions of dollars for cancer research and awareness programs. Fast Facts Cancers of the colon and ...

Facing Forward Series: Life After Cancer Treatment

MedlinePlus

... Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors ... Levels of Evidence: Integrative Therapies Fact Sheets NCI Dictionaries NCI Dictionary of Cancer Terms NCI Drug Dictionary ...

Overview of players and information in the cancer epidemiology and control world in Asia.

PubMed

Moore, Malcolm A; Yoo, Keun-Young; Tuncer, Murat; Sobue, Tomotaka

2010-01-01

Cancer and related lifestyle diseases are on the increase across Asia and already account for over half the disease-associated mortality in the vast majority of the included countries. An understanding of the epidemiology is therefore of paramount importance. In addition, given the immensity of the problem, cooperation among all the interested parties is of the essence. The present series of reviews were complied with the aim of promoting better comprehension and interaction, focusing on cancer prevalence and the underlying risk and preventive factors in Asia. Data from Cancer Incidence in Five Continents and Globocan 2002, published by the International Agency for Research on Cancer, as well as various other cancer registry sources, were thus married with research information in the public domain, accessible through PubMed. It is hoped that the comprehensive approach adopted for the different regions will help bring together all of the Asian community of individuals involved in cancer epidemiology and control and contribute to establishment of Asian networks for collaborative research. The major players and the overall picture for cancer control are covered in the present overview. Further details are then provided in seven separate regional reviews: for North-Western and Central Asia; South-West Asia; South Asia; Mainland South-East Asia; Peninsular and Island South-East Asia, the Pacific; and North-East Asia. The final section covers possible organ-based strategies for cancer control and, lastly, an Appendix has been included listing research institutes and staff in Asia to facilitate contacts between interested individuals.

Did You Know? Video Series - SEER Cancer Statistics

Cancer.gov

Videos that explain cancer statistics. Choose from topics including survival, statistics overview, survivorship, disparities, and specific cancer types including breast, lung, colorectal, prostate, melanoma of the skin, and others.

Children's understanding of maternal breast cancer: A qualitative study.

PubMed

Huang, Xiaoyan; O'Connor, Margaret; Hu, Yan; Gao, Hongyun; Lee, Susan

2018-06-01

To explore how children understand their mother's diagnosis of and treatment for breast cancer. Interpretive description was adopted as the methodology in this study. Eight children aged 8-18 years old, whose mother has been diagnosed with non-terminal breast cancer, were interviewed individually and six of them drew a picture to express their understanding of maternal breast cancer. Four themes were identified in this study: "the cancer word is scary" - children's understanding of cancer; "scars and tubes" - children's understanding of surgery; "hair loss" - children's understanding of chemotherapy, and "I can't explain it" - children's understanding of other treatments. Children's understanding of maternal breast cancer and its treatment was relatively realistic, although sometimes inaccurate. Individual evaluation and appropriate explanation is significant to further children's understanding of their mother's illness. Future studies with larger sample size are needed to explore the understanding for children of different ages, in order to provide specific help for these children. Copyright © 2018 Elsevier Ltd. All rights reserved.

A guide to help children understand cancer

MedlinePlus

... approach will depend on your child's age and maturity. Here is a general guide. CHILDREN AGES 0 ... child understands cancer. www.cancer.net/coping-and-emotions/communicating-loved-ones/how-child-understands-cancer . Updated ...

Resolution of Novel Pancreatic Ductal Adenocarcinoma Subtypes by Global Phosphotyrosine Profiling*

PubMed Central

Humphrey, Emily S.; Su, Shih-Ping; Nagrial, Adnan M.; Hochgräfe, Falko; Pajic, Marina; Lehrbach, Gillian M.; Parton, Robert G.; Yap, Alpha S.; Horvath, Lisa G.; Chang, David K.; Biankin, Andrew V.; Wu, Jianmin; Daly, Roger J.

2016-01-01

Comprehensive characterization of signaling in pancreatic ductal adenocarcinoma (PDAC) promises to enhance our understanding of the molecular aberrations driving this devastating disease, and may identify novel therapeutic targets as well as biomarkers that enable stratification of patients for optimal therapy. Here, we use immunoaffinity-coupled high-resolution mass spectrometry to characterize global tyrosine phosphorylation patterns across two large panels of human PDAC cell lines: the ATCC series (19 cell lines) and TKCC series (17 cell lines). This resulted in the identification and quantification of over 1800 class 1 tyrosine phosphorylation sites and the consistent segregation of both PDAC cell line series into three subtypes with distinct tyrosine phosphorylation profiles. Subtype-selective signaling networks were characterized by identification of subtype-enriched phosphosites together with pathway and network analyses. This revealed that the three subtypes characteristic of the ATCC series were associated with perturbations in signaling networks associated with cell-cell adhesion and epithelial-mesenchyme transition, mRNA metabolism, and receptor tyrosine kinase (RTK) signaling, respectively. Specifically, the third subtype exhibited enhanced tyrosine phosphorylation of multiple RTKs including the EGFR, ERBB3 and MET. Interestingly, a similar RTK-enriched subtype was identified in the TKCC series, and 'classifier' sites for each series identified using Random Forest models were able to predict the subtypes of the alternate series with high accuracy, highlighting the conservation of the three subtypes across the two series. Finally, RTK-enriched cell lines from both series exhibited enhanced sensitivity to the small molecule EGFR inhibitor erlotinib, indicating that their phosphosignature may provide a predictive biomarker for response to this targeted therapy. These studies highlight how resolution of subtype-selective signaling networks can provide a novel taxonomy for particular cancers, and provide insights into PDAC biology that can be exploited for improved patient management. PMID:27259358

Lung Cancer Precision Medicine Trials

Cancer.gov

Patients with lung cancer are benefiting from the boom in targeted and immune-based therapies. With a series of precision medicine trials, NCI is keeping pace with the rapidly changing treatment landscape for lung cancer.

A cancer genetics education campaign: delivering parallel messages to clinicians and the public.

PubMed

Piniewski-Bond, Joanne; Celestino, Paul B; Mahoney, Martin C; Farrell, Carolyn D; Bauer, Joseph E; Hastrup, Janice L; Cummings, K Michael

2003-01-01

Up to 10% of all cancers are thought to have a familial basis through complex interactions between genes and environment. A community-wide education campaign was conducted that included several elements: a five part television news series; an educational newsletter; web site pages and links to educational materials; a Continuing Medical Education (CME) program for professionals; and an evaluation survey. Survey estimates revealed that 39000 households recalled seeing the series; 14800 households changed their views about the risks of hereditary cancers; and about 9900 households were made more aware/informed about cancer and hereditary risk. This awareness campaign broadened public knowledge about the myths and realities associated with genetic factors and cancer risk. It reinforced the importance of early screening for persons at high risk of cancer due to hereditary factors.

Failure to Confirm the Macrophage Electrophoretic Mobility Test in Cancer

PubMed Central

Forrester, J. A.; Dando, P. M.; Smith, W. J.; Turberville, C.

1977-01-01

A series of patients with a variety of histopathologically confirmed cancers have been examined using the MOD-MEM test as described by Pritchard et al. (1973). Despite the closest possible adherence to the experimental protocols recommended by these authors, no positive reactions to the test were observed in this series: neither were we able to demonstrate the release of a “macrophage-slowing factor” by a panel of normal donors when challenged with tubercle PPD. We conclude that the test has no present application to the diagnosis of cancer.

Implementing a user-driven online quality improvement toolkit for cancer care.

PubMed

Luck, Jeff; York, Laura S; Bowman, Candice; Gale, Randall C; Smith, Nina; Asch, Steven M

2015-05-01

Peer-to-peer collaboration within integrated health systems requires a mechanism for sharing quality improvement lessons. The Veterans Health Administration (VA) developed online compendia of tools linked to specific cancer quality indicators. We evaluated awareness and use of the toolkits, variation across facilities, impact of social marketing, and factors influencing toolkit use. A diffusion of innovations conceptual framework guided the collection of user activity data from the Toolkit Series SharePoint site and an online survey of potential Lung Cancer Care Toolkit users. The VA Toolkit Series site had 5,088 unique visitors in its first 22 months; 5% of users accounted for 40% of page views. Social marketing communications were correlated with site usage. Of survey respondents (n = 355), 54% had visited the site, of whom 24% downloaded at least one tool. Respondents' awareness of the lung cancer quality performance of their facility, and facility participation in quality improvement collaboratives, were positively associated with Toolkit Series site use. Facility-level lung cancer tool implementation varied widely across tool types. The VA Toolkit Series achieved widespread use and a high degree of user engagement, although use varied widely across facilities. The most active users were aware of and active in cancer care quality improvement. Toolkit use seemed to be reinforced by other quality improvement activities. A combination of user-driven tool creation and centralized toolkit development seemed to be effective for leveraging health information technology to spread disease-specific quality improvement tools within an integrated health care system. Copyright © 2015 by American Society of Clinical Oncology.

International cancer seminars: a focus on esophageal squamous cell carcinoma.

PubMed

Murphy, G; McCormack, V; Abedi-Ardekani, B; Arnold, M; Camargo, M C; Dar, N A; Dawsey, S M; Etemadi, A; Fitzgerald, R C; Fleischer, D E; Freedman, N D; Goldstein, A M; Gopal, S; Hashemian, M; Hu, N; Hyland, P L; Kaimila, B; Kamangar, F; Malekzadeh, R; Mathew, C G; Menya, D; Mulima, G; Mwachiro, M M; Mwasamwaja, A; Pritchett, N; Qiao, Y-L; Ribeiro-Pinto, L F; Ricciardone, M; Schüz, J; Sitas, F; Taylor, P R; Van Loon, K; Wang, S-M; Wei, W-Q; Wild, C P; Wu, C; Abnet, C C; Chanock, S J; Brennan, P

2017-09-01

The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts. Published by Oxford University Press on behalf of the European Society for Medical Oncology 2017. This work is written by US Government employees and is in the public domain in the US.

Pharmacological Inhibitors of NAD Biosynthesis as Potential An ticancer Agents.

PubMed

Lucas, Stephanie; Soave, Claire; Nabil, Ghazal; Ahmed, Zainab Sabry Othman; Chen, Guohua; El-Banna, Hossny Awad; Dou, Q Ping; Wang, Jian

2017-01-01

Alteration of cellular metabolism is a hallmark of cancer, which underlies exciting opportunities to develop effective, anti-cancer therapeutics through inhibition of cancer metabolism. Nicotinamide Adenine Dinucleotide (NAD+), an essential coenzyme of energy metabolism and a signaling molecule linking cellular energy status to a spectrum of molecular regulation, has been shown to be in high demand in a variety of cancer cells. Depletion of NAD+ by inhibition of its key biosynthetic enzymes has become an attractive strategy to target cancer. The main objective of this article is to review the recent patents which develop and implicate the chemical inhibitors of the key NAD+ biosynthetic enzymes for cancer treatment. We first discuss the biological principles of NAD+ metabolism in normal and malignant cells, with a focus on the feasibility of selectively targeting cancer cells by pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT) and indoleamine/tryptophan 2,3-dioxygenases (IDO/TDO), the rate-limiting salvage and de novo NAD+ biosynthetic enzymes, respectively. We then analyze a series of recent patents on development and optimization of chemical scaffolds for inhibiting NAMPT or IDO/TDO enzymes as potential anticancer drugs. Conclusion and Results: We have reviewed 16 relevant patents published since 2015, and summarized the chemical properties, mechanisms of action and proposed applications of the patented compounds. Without a better understanding of the properties of these compounds, their utility for further optimization and clinical use is unknown. For the compounds that have been tested using cell and mouse models of cancer, results look promising and clinical trials are currently ongoing to see if these results translate to improved cancer treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.

PubMed

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

PubMed Central

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib. PMID:28744140

Dr. Dinah Singer: Increasing Diversity in Cancer Research: One Lab at a Time

Cancer.gov

As part of the series “Increasing Diversity in Cancer Research,” CRCHD spoke with Dr. Dinah Singer, Director of NCI’s Division of Cancer Biology, about training and mentorship, and the role it plays in attracting and retaining students and investigators underrepresented in cancer research.

Bladder perivascular epithelioid cell tumor (PEComa): a case report and literature review.

PubMed

Sarti, Alessandra; Rubilotta, Emanuele; Balzarro, Matteo; Cerruto, Maria Angela; Brunelli, Matteo; Artibani, Walter

2015-01-01

Perivascular epithelioid cell tumors (PEComa) are a very uncommon mesenchymal cancer with uncertain malignant potential. A computerized research on Pub Med was performed regarding bladder PEComa. We evaluated the literature cases and described a case of bladder PEComa. PEComa of the bladder is a very rare neoplasm and only 15 cases have been reported so far. Bladder PEComa involves young subjects of both genders, mostly under 40 years of age. Surgical treatment (partial or radical cystectomy) is the most common management.A long-term follow-up and larger series are required to better understand the best clinical approach to bladder PEComa.

Clinicopathologic and prognostic characteristics of alpha-fetoprotein–producing gastric cancer

PubMed Central

Dong, Xuqiang; Wang, Yao; Zhang, Weiming; Shen, Lizong; Zhang, Zhihong

2017-01-01

Alpha-fetoprotein–producing gastric cancer (AFPGC) accounts for 1.5%–7.1% of all gastric cancer cases. Compared with other types of gastric cancer, AFPGC is more aggressive and prone to liver and lymph node (LN) metastasis, with extremely poor prognosis. To improve understanding of AFPGC we reviewed a consecutive series of 82 AFPGC patients and investigated the prognostic factors. The incidence of AFPGC among our gastric cancer patients was 1.95%, and 29.27% of AFPGCs were diagnosed with metastasis at the time of presentation, mainly liver metastasis. The serum AFP level of patients with AFPGC was significantly associated with tumor differentiation. Histologically, these AFPGC patients were composed of 34.55% hapatiod type, 58.18% fetal gastrointestinal type, 9.09% yolk sac tumor-like type, and 14.55% mixed type. Patient gender, tumor differentiation, Lauren classification, and number of metastatic lymph nodes showed significant differences among these four subtypes. The overall survival time was 42.02 months and the 3-year cumulative survival rate was 53.13%. Age, American Joint Committee on Cancer (AJCC) TNM staging classification (TNM stage), serum AFP level, and surgery were prognostic factors for overall survival; however, TNM stage was the only independent risk factor for prognosis of AFPGC. In short, AFPGC is a rare, unique, and heterogeneous entity, and its proper identification and treatment remain a challenge. More attention should be paid to AFPGC to improve patient care and the dismal prognosis. PMID:28423604

Clinicopathologic and prognostic characteristics of alpha-fetoprotein-producing gastric cancer.

PubMed

He, Ruji; Yang, Qinyi; Dong, Xuqiang; Wang, Yao; Zhang, Weiming; Shen, Lizong; Zhang, Zhihong

2017-04-04

Alpha-fetoprotein-producing gastric cancer (AFPGC) accounts for 1.5%-7.1% of all gastric cancer cases. Compared with other types of gastric cancer, AFPGC is more aggressive and prone to liver and lymph node (LN) metastasis, with extremely poor prognosis. To improve understanding of AFPGC we reviewed a consecutive series of 82 AFPGC patients and investigated the prognostic factors. The incidence of AFPGC among our gastric cancer patients was 1.95%, and 29.27% of AFPGCs were diagnosed with metastasis at the time of presentation, mainly liver metastasis. The serum AFP level of patients with AFPGC was significantly associated with tumor differentiation. Histologically, these AFPGC patients were composed of 34.55% hapatiod type, 58.18% fetal gastrointestinal type, 9.09% yolk sac tumor-like type, and 14.55% mixed type. Patient gender, tumor differentiation, Lauren classification, and number of metastatic lymph nodes showed significant differences among these four subtypes. The overall survival time was 42.02 months and the 3-year cumulative survival rate was 53.13%. Age, American Joint Committee on Cancer (AJCC) TNM staging classification (TNM stage), serum AFP level, and surgery were prognostic factors for overall survival; however, TNM stage was the only independent risk factor for prognosis of AFPGC. In short, AFPGC is a rare, unique, and heterogeneous entity, and its proper identification and treatment remain a challenge. More attention should be paid to AFPGC to improve patient care and the dismal prognosis.

Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin.

PubMed

Raju, Jayadev; Mehta, Rekha

2009-01-01

Cancer chemoprevention is a strategy taken to retard, regress, or resist the multistep process of carcinogenesis, including the blockage of its vital morphogenetic milestones viz. normal-preneoplasia-neoplasia-metastasis. For several reasons, including safety, minimal (or no) toxicity and side-effects, and better availability, alternatives such as naturally occurring phytochemicals that are found in foods are becoming increasingly popular over synthetic drugs. Food saponins have been used in complimentary and traditional medicine against a variety of diseases including several cancers. Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a well-known precursor of various synthetic steroidal drugs that are extensively used in the pharmaceutical industry. Over the past decade, a series of preclinical and mechanistic studies have been conducted to understand the role of diosgenin as a chemopreventive/therapeutic agent against several cancers. This review highlights the biological activity of diosgenin that contributes to cancer chemoprevention and control. The anticancer mode of action of diosgenin has been demonstrated via modulation of multiple cell signaling events involving critical molecular candidates associated with growth, differentiation, apoptosis, and oncogenesis. Altogether, these preclinical and mechanistic findings strongly implicate the use of diosgenin as a novel, multitarget-based chemopreventive or therapeutic agent against several cancer types. Future research in this field will help to establish not only whether diosgenin is safe and efficacious as a chemopreventive agent against several human cancers, but also to develop and evaluate standards of evidence for health claims for diosgenin-containing foods as they become increasingly popular and enter the marketplace labeled as functional foods and nutraceuticals.

Fatalistic Beliefs and Completion of the HPV Vaccination Series Among a Sample of Young Appalachian Kentucky Women

PubMed Central

Vanderpool, Robin C.; Van Meter Dressler, Emily; Stradtman, Lindsay R.; Crosby, Richard A.

2016-01-01

Purpose Uptake and completion of the 3-dose human papillomavirus (HPV) vaccine is important for the primary prevention of cervical cancer. However, HPV vaccination rates among adolescent females and young women remain low in certain geographic areas of the United States, including Appalachia. Although greater fatalistic beliefs have been previously associated with lower rates of preventive cancer behaviors among adults, little research exists on the impact of fatalism on HPV vaccination behaviors, especially among younger individuals. Therefore, the purpose of this study was to examine the association between fatalistic beliefs and completion of the full HPV vaccine series among young women, ages 18–26, in Appalachian Kentucky. Results Data from this study were from a baseline survey completed by 344 women randomized into a communication intervention trial focused on increasing adherence to the 3-dose HPV vaccine series. Principal components analysis was used to construct 2 fatalism-related subscales from 8 survey questions. Findings In a controlled analysis, 1 subscale—“lack of control over cancer”— was significantly associated with not completing the full HPV vaccine series. In a rural area that experiences higher rates of cervical cancer, poverty, limited access to health care, and negative cancer-related attitudes and experiences, fatalism may be common, even among young people. Conclusion Future educational and interventional research addressing fatalistic beliefs in a culturally sensitive manner may be warranted to improve HPV vaccination behaviors and impact cancer disparities among Appalachian women. PMID:25640763

NOVEL POLYPHENOLS THAT INHIBIT COLON CANCER CELL GROWTH AFFECTING CANCER CELL METABOLISM.

PubMed

Gomez de Cedron, Marta; Vargas, Teodoro; Madrona, Andres; Jimenez, Aranza; Perez Perez, Maria Jesus; Quintela, Jose Carlos; Reglero, Guillermo; San-Felix, Ana Rosa; Ramirez de Molina, Ana

2018-06-05

New series of polyphenols with a hydrophilic galloyl based "head" and a hydrophobic N-acyl "tail", linked through a serinol moiety, have been synthesized and tested against colon cancer cell growth. Our structure activity relationship studies revealed that galloyl moieties are essential for growth inhibition. Moreover, the length of the N-acyl chain is crucial for the activity. Introduction of a (Z) double bond in the acyl chain increased the anti-cancer properties. Our findings demonstrate that 16, the most potent compound within this series, has inhibitory effects on colon cancer cell growth and metabolism (glycolysis and mitochondrial respiration) at the same time that activates AMPK and induces apoptotic cell death. Based on these results we propose that 16 might reprogram colon cancer cell metabolism through AMPK activation. This might lead to alterations on cancer cell bioenergy compromising cancer cell viability. Importantly, these anti-proliferative and pro-apoptotic effects are selective for cancer cells. Accordingly, these results indicate that 16, with an unsaturated C18 chain, might be a useful prototype for the development of novel colon cancer cell growth inhibitors affecting cell metabolism. The American Society for Pharmacology and Experimental Therapeutics.

Time series analyses of breathing patterns of lung cancer patients using nonlinear dynamical system theory.

PubMed

Tewatia, D K; Tolakanahalli, R P; Paliwal, B R; Tomé, W A

2011-04-07

The underlying requirements for successful implementation of any efficient tumour motion management strategy are regularity and reproducibility of a patient's breathing pattern. The physiological act of breathing is controlled by multiple nonlinear feedback and feed-forward couplings. It would therefore be appropriate to analyse the breathing pattern of lung cancer patients in the light of nonlinear dynamical system theory. The purpose of this paper is to analyse the one-dimensional respiratory time series of lung cancer patients based on nonlinear dynamics and delay coordinate state space embedding. It is very important to select a suitable pair of embedding dimension 'm' and time delay 'τ' when performing a state space reconstruction. Appropriate time delay and embedding dimension were obtained using well-established methods, namely mutual information and the false nearest neighbour method, respectively. Establishing stationarity and determinism in a given scalar time series is a prerequisite to demonstrating that the nonlinear dynamical system that gave rise to the scalar time series exhibits a sensitive dependence on initial conditions, i.e. is chaotic. Hence, once an appropriate state space embedding of the dynamical system has been reconstructed, we show that the time series of the nonlinear dynamical systems under study are both stationary and deterministic in nature. Once both criteria are established, we proceed to calculate the largest Lyapunov exponent (LLE), which is an invariant quantity under time delay embedding. The LLE for all 16 patients is positive, which along with stationarity and determinism establishes the fact that the time series of a lung cancer patient's breathing pattern is not random or irregular, but rather it is deterministic in nature albeit chaotic. These results indicate that chaotic characteristics exist in the respiratory waveform and techniques based on state space dynamics should be employed for tumour motion management.

Online Series presents Cancer Prevention Through Immunomodulation. Does Diet Play a Role? | Division of Cancer Prevention

Cancer.gov

Scientists are increasingly harnessing the power of the immune system to prevent cancer. Nutrition provides an opportunity for a generalized immune activation and reduction of cancer risk in certain populations. Research on several foods and bioactive food components as immunologic modulators is showing promising results. |

How information about overdetection changes breast cancer screening decisions: a mediation analysis within a randomised controlled trial.

PubMed

Hersch, Jolyn; McGeechan, Kevin; Barratt, Alexandra; Jansen, Jesse; Irwig, Les; Jacklyn, Gemma; Houssami, Nehmat; Dhillon, Haryana; McCaffery, Kirsten

2017-10-06

In a randomised controlled trial, we found that informing women about overdetection changed their breast screening decisions. We now present a mediation analysis exploring the psychological pathways through which study participants who received the intervention processed information about overdetection and how this influenced their decision-making. We examined a series of potential mediators in the causal chain between exposure to overdetection information and women's subsequently reported breast screening intentions. Serial multiple mediation analysis within a randomised controlled trial. New South Wales, Australia. 811 women aged 48-50 years with no personal history of breast cancer. Two versions of a decision aid giving women information about breast cancer deaths averted and false positives from mammography screening, either with (intervention) or without (control) information on overdetection. Intentions to undergo breast cancer screening in the next 2-3 years. Knowledge about overdetection, worry about breast cancer, attitudes towards breast screening and anticipated regret. The effect of information about overdetection on women's breast screening intentions was mediated through multiple cognitive and affective processes. In particular, the information led to substantial improvements in women's understanding of overdetection, and it influenced-both directly and indirectly via its effect on knowledge-their attitudes towards having screening. Mediation analysis showed that the mechanisms involving knowledge and attitudes were particularly important in determining women's intentions about screening participation. Even in this emotive context, new information influenced women's decision-making by changing their understanding of possible consequences of screening and their attitudes towards undergoing it. These findings emphasise the need to provide good-quality information on screening outcomes and to communicate this information effectively, so that women can make well-informed decisions. This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613001035718) on 17 September 2013. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Advances in Understanding of Penile Carcinogenesis: The Search for Actionable Targets

PubMed Central

Chaing, Sharon; Azizi, Mounsif; Kidd, Laura C.; Kim, Patricia; Spiess, Philippe E.

2017-01-01

Penile cancer (PeCa) is a rare malignancy with potentially devastating effects. Squamous cell carcinoma is the most common variant with distinct precancerous lesions before development into invasive disease. Involvement of the inguinal lymph nodes is the most important prognostic factor in PeCa, and once disease is present outside the groin, prognosis is poor. Metastatic PeCa is challenging to treat and often requires multidisciplinary approaches in management. Due to its rarity, molecular understanding of the disease continues to be limited with most studies based on small, single center series. Thus far, it appears PeCa has diverse mechanisms of carcinogenesis affecting similar molecular pathways. In this review, we evaluate the current landscape of the molecular carcinogenesis of PeCa and explore ongoing research on potential actionable targets of therapy. The emergence of anti-epidermal growth factor receptor (EGFR) and other immunotherapeutic strategies may improve outcomes for PeCa patients. PMID:28813024

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

PubMed Central

Anderson, Grant; Forrest, Douglas; Galton, Valerie Anne; Gereben, Balázs; Kim, Brian W.; Kopp, Peter A.; Liao, Xiao Hui; Obregon, Maria Jesus; Peeters, Robin P.; Refetoff, Samuel; Sharlin, David S.; Simonides, Warner S.; Weiss, Roy E.; Williams, Graham R.

2014-01-01

Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment approaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothyroidism, hyperthyroidism, or thyroid cancer are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a series of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes. PMID:24001133

A Younger Man With Localized Prostate Cancer Asks, "Which Type of Radiation Is Right for Me?"

PubMed

Bekelman, Justin E

2018-06-20

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 61-year-old man presents with stage II prostate cancer after a period of active surveillance. Work-up reveals T1cN0M0 carcinoma, a prostate-specific antigen (PSA) level of 4.8 ng/mL, and Grade Group II (highest Gleason 3+4) in three cores of 12 taken, at the right mid-gland and right apex. The patient has been on active surveillance for the past 16 months. He was originally diagnosed after biopsy for an elevated PSA with stage I prostate cancer, T1cN0M0; PSA, 4.5 ng/mL; Grade Group 1 (Gleason 3+3) in one core of 12 taken, also at the right mid-gland. A multiparametric magnetic resonance imaging scan showed a heterogeneous peripheral zone without a dominant lesion and a calculated prostate volume of 28 mL. His medical history includes hypercholesterolemia, for which he takes atorvastatin. He is otherwise healthy and has no other significant medical or surgical history. His father had prostate cancer in his 70s and died of other causes at 89 years of age. The patient reports 2- to 3-hour urinary frequency and 0 to 1 nocturia, and has no difficulty obtaining or maintaining an erection. After meeting with his urologist, he sees a radiation oncologist.

Next-generation sequencing for cancer drug development: the present and visions for the future.

PubMed

Kahn, Scott M

2014-03-01

NGS for Cancer Drug Development 24-26 September 2013, Boston, MA, USA Many of us who, prior to the -omics revolution, staunchly pursued the molecular basis of disease causation recognized the fundamental importance that biomarkers held for the eventuality of personalized medicine, more accurate diagnostics and targeted drug discovery. With slab sequencing apparatuses now mere memories relegated to the dusty reaches of old laboratory cabinets, we are fervently unraveling the complexities of many diseases through newer, more powerful innovative technologies. Quicker than ever before, we are achieving a deeper understanding of causative genetic lesions, perturbed pathways and the functions of altered networks. This has opened the door to a golden age of data generation that shows promise as a vital key to the successful treatment of human diseases. Hanson Wade recently organized a series of three related symposia that highlighted advances in industry and academic research in the areas of drug development, companion diagnostics and disease profiling: 'NGS for Cancer Drug Development' conference in Boston on 24-26 September 2013, the 'NGS Data Analysis' conference in San Francisco on 15-17 October 2013 and the 'World CDx' conference in Boston on 12-15 November 2013. These meetings provided forums for leaders to present advancements in personalized medicine, strategies for drug development, and innovations in diagnostics and other important areas. Their highly interactive nature also provided opportunities for industry and academic attendees to identify common hurdles that stand in the way of progress, (e.g., biomarker validation, analytical software limitations, data sharing, sample handling, regulatory and reimbursement restrictions), and to propose strategies for independent and community approaches toward overcoming such hurdles. In the interest of space, this review will be limited to the first in this series, the NGS for Cancer Drug Development conference, and its six major areas of focus.

ETS Gene Fusions as Predictive Biomarkers of Resistance to Radiation Therapy for Prostate Cancer

DTIC Science & Technology

2012-08-01

proposal included a series of regular meetings with mentors, research seminars, journal clubs, and workshops, all of which are intended to help Dr. Feng...accomplished as a result of this grant resulted in two publications in very high- impact journals , four national presentations, and three grants (two...for prostate cancer. The training goals of this grant proposal included a series of regular meetings with mentors, research seminars, journal clubs

Online CME Series Can Nutrition Simultaneously Affect Cancer and Aging? | Division of Cancer Prevention

Cancer.gov

Aging is considered by some scientists to be a normal physiological process, while others believe it is a disease. Increased cancer risk in the elderly raises the question regarding the common pathways for cancer and aging. Undeniably, nutrition plays an important role in both cases and this webinar will explore whether nutrition can simultaneously affect cancer and aging. |

Concurrent Chemotherapy and Radiation Therapy for Inoperable Locally Advanced Non-Small-Cell Lung Cancer.

PubMed

Rosenzweig, Kenneth E; Gomez, Jorge E

2017-01-01

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 72-year-old man with a 40-pack-year tobacco history developed a cough and decreased exercise tolerance. A chest x-ray demonstrated a right-upper-lobe opacity. Chest computed tomography (CT) scan revealed a 2.5-cm mass in the right upper lobe with multiple mediastinal lymph node disease ( Fig 1 ). A positron emission tomography (PET) scan confirmed the lung lesion and the mediastinal lymphadenopathy without distant metastases. Brain magnetic resonance imaging results were negative. The biopsy specimen revealed adenocarcinoma with no actionable mutations present. Cervical mediastinoscopy was positive for carcinoma in level 2, 3, 4R, and 7 lymph nodes; level 4L was negative. The patient's stage was T1bN2M0, stage IIIA. His medical history was significant for hyperlipidemia and hypothyroidism. He had smoked one pack a day for 40 years and had quit 15 years earlier. Physical examination was unrevealing, and the patient had an Eastern Cooperative Oncology Group performance status of 0. Because of the extent of lung cancer in the mediastinum, the patient's cancer was deemed inoperable, and he was referred for consideration of concurrent chemotherapy and radiation.

Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas: Mutational signature associated with MUTYH deficiency in cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pilati, Camilla; Shinde, Jayendra; Alexandrov, Ludmil B.

Germline alterations in DNA repair genes are implicated in cancer predisposition and can result in characteristic mutational signatures. However, specific mutational signatures associated with base excision repair (BER) defects remain to be characterized. Here, by analysing a series of colorectal cancers (CRCs) using exome sequencing, we identified a particular spectrum of somatic mutations characterized by an enrichment of C > A transversions in NpCpA or NpCpT contexts in three tumours from a MUTYH-associated polyposis (MAP) patient and in two cases harbouring pathogenic germline MUTYH mutations. In two series of adrenocortical carcinomas (ACCs), we identified four tumours with a similar signaturemore » also presenting germline MUTYH mutations. Altogether, these findings demonstrate that MUTYH inactivation results in a particular mutational signature, which may serve as a useful marker of BER-related genomic instability in new cancer types.« less

Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas: Mutational signature associated with MUTYH deficiency in cancers

DOE PAGES

Pilati, Camilla; Shinde, Jayendra; Alexandrov, Ludmil B.; ...

2017-03-29

Germline alterations in DNA repair genes are implicated in cancer predisposition and can result in characteristic mutational signatures. However, specific mutational signatures associated with base excision repair (BER) defects remain to be characterized. Here, by analysing a series of colorectal cancers (CRCs) using exome sequencing, we identified a particular spectrum of somatic mutations characterized by an enrichment of C > A transversions in NpCpA or NpCpT contexts in three tumours from a MUTYH-associated polyposis (MAP) patient and in two cases harbouring pathogenic germline MUTYH mutations. In two series of adrenocortical carcinomas (ACCs), we identified four tumours with a similar signaturemore » also presenting germline MUTYH mutations. Altogether, these findings demonstrate that MUTYH inactivation results in a particular mutational signature, which may serve as a useful marker of BER-related genomic instability in new cancer types.« less

Design and multi-step synthesis of chalcone-polyamine conjugates as potent antiproliferative agents.

PubMed

Rioux, Benjamin; Pouget, Christelle; Fidanzi-Dugas, Chloë; Gamond, Aurélie; Laurent, Aurélie; Semaan, Josiane; Pinon, Aline; Champavier, Yves; Léger, David Y; Liagre, Bertrand; Duroux, Jean-Luc; Fagnère, Catherine; Sol, Vincent

2017-09-15

The aim of this study is to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. 3-hydroxy-3',4,4',5'-tetramethoxychalcone (1) and 3',4,4',5'-tetramethoxychalcone (2) were selected as parent chalcones since they were found to be efficient anti-proliferative agents on various cancer cells. A series of ten chalcone-polyamine conjugates was obtained by reacting carboxychalcones with different polyamine tails. Chalcones 1 and 2 showed a strong cytotoxic activity against two prostatic cancer (PC-3 and DU-145) and two colorectal cancer (HT-29 and HCT-116) cell lines. Then, chalcone-spermine conjugates 7d and 8d were shown to be the most active of the series and could be considered as promising compounds for colon and prostatic cancer adjuvant therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Viruses in case series of tumors: Consistent presence in different cancers in the same subject

PubMed Central

Arroyo Mühr, Laila Sara; Hortlund, Maria; Bzhalava, Zurab; Nordqvist Kleppe, Sara; Bzhalava, Davit; Dillner, Joakim

2017-01-01

Studies investigating presence of viruses in cancer often analyze case series of cancers, resulting in detection of many viruses that are not etiologically linked to the tumors where they are found. The incidence of virus-associated cancers is greatly increased in immunocompromised individuals. Non-melanoma skin cancer (NMSC) is also greatly increased and a variety of viruses have been detected in NMSC. As immunosuppressed patients often develop multiple independent NMSCs, we reasoned that viruses consistently present in independent tumors might be more likely to be involved in tumorigenesis. We sequenced 8 different NMSCs from 1 patient in comparison to 8 different NMSCs from 8 different patients. Among the latter, 12 different virus sequences were detected, but none in more than 1 tumor each. In contrast, the patient with multiple NMSCs had human papillomavirus type 15 and type 38 present in 6 out of 8 NMSCs. PMID:28257474

Discovering the route from inflammation to pancreatic cancer

PubMed Central

MOMI, N.; KAUR, S.; KRISHN, S. R.; BATRA, S. K.

2013-01-01

Pancreatic cancer (PC) remains a complex malignancy with the worst prognosis, lack of early diagnostic symptoms and resistance to conventional chemo- and radiotherapies. A better understanding of the etiology and early developmental events of PC requires profound attention. The evolution of fully blown PC from initial pancreatic injury is a multi-factorial phenomenon with a series of sequential events. The initial acute infection or tissue damage triggers inflammation that, in conjunction with innate immunity, establishes a state of homeostasis to limit harm to the body. Recurrent pancreatic injuries due to genetic susceptibility, smoking, unhealthy diet, and alcohol abuse induces a pro-inflammatory milieu, consisting of various types of immune cells, cytokines, chemokines, growth factors and restructured extracellular matrix, leading to prolonged inflammatory/chronic conditions. Cells having sustained DNA damage and/or mutagenic assault take advantage of this prolonged inflammatory response and aid in the initiation and development of neoplastic/fibrotic events. Eventually, many tumor-stromal interactions result in a chaotic environment accompanied by a loss of immune surveillance and repair response, thereby leading to PC. A better understanding of the inflammatory markers defining this “injury-inflammation-cancer” pathway would help to identify novel molecular targets for early screening and therapeutic intervention for this lethal malignancy. PMID:23207606

Understanding your cancer prognosis

MedlinePlus

... about: Treatment Palliative care Personal matters such as finances Knowing what to expect may make it easier ... treatment. www.cancer.net/navigating-cancer-care/cancer-basics/understanding-statistics-used-guide-prognosis-and-evaluate-treatment . ...

Risk determination and prevention of breast cancer.

PubMed

Howell, Anthony; Anderson, Annie S; Clarke, Robert B; Duffy, Stephen W; Evans, D Gareth; Garcia-Closas, Montserat; Gescher, Andy J; Key, Timothy J; Saxton, John M; Harvie, Michelle N

2014-09-28

Breast cancer is an increasing public health problem. Substantial advances have been made in the treatment of breast cancer, but the introduction of methods to predict women at elevated risk and prevent the disease has been less successful. Here, we summarize recent data on newer approaches to risk prediction, available approaches to prevention, how new approaches may be made, and the difficult problem of using what we already know to prevent breast cancer in populations. During 2012, the Breast Cancer Campaign facilitated a series of workshops, each covering a specialty area of breast cancer to identify gaps in our knowledge. The risk-and-prevention panel involved in this exercise was asked to expand and update its report and review recent relevant peer-reviewed literature. The enlarged position paper presented here highlights the key gaps in risk-and-prevention research that were identified, together with recommendations for action. The panel estimated from the relevant literature that potentially 50% of breast cancer could be prevented in the subgroup of women at high and moderate risk of breast cancer by using current chemoprevention (tamoxifen, raloxifene, exemestane, and anastrozole) and that, in all women, lifestyle measures, including weight control, exercise, and moderating alcohol intake, could reduce breast cancer risk by about 30%. Risk may be estimated by standard models potentially with the addition of, for example, mammographic density and appropriate single-nucleotide polymorphisms. This review expands on four areas: (a) the prediction of breast cancer risk, (b) the evidence for the effectiveness of preventive therapy and lifestyle approaches to prevention, (c) how understanding the biology of the breast may lead to new targets for prevention, and (d) a summary of published guidelines for preventive approaches and measures required for their implementation. We hope that efforts to fill these and other gaps will lead to considerable advances in our efforts to predict risk and prevent breast cancer over the next 10 years.

Providing a molecular mechanism for P-glycoprotein; why would I bother?

PubMed Central

Callaghan, Richard

2015-01-01

It is almost 40 years since the drug efflux pump P-glycoprotein (permeability glycoprotein or P-gp) was shown to confer multi-drug resistance in cancer cells. This protein has been one of the most extensively investigated transport proteins due to its intriguing mechanism and its affect in oncology. P-gp is known to interact with over 300 compounds and the ability to achieve this has not yet been revealed. Following the binding of substrate and nucleotide, a complex series of conformational changes in the membrane and cytosolic domains translocates substrate across the membrane. Despite over 30 years of biochemical investigation, the availability of structural data and a plethora of chemical tools to modulate its function, the molecular mechanism remains a mystery. In addition, overcoming its activity in resistant cancer cells has not been achieved in the clinic, thereby garnering some degree of pessimism in the field. This review highlights the progress that has been achieved in understanding this complex protein and the value of undertaking molecular studies. PMID:26517914

Cell- and Tissue-based Proteome Profiling and Dual Imaging of Apoptosis Markers with Probes Derived from Venetoclax and Idasanutlin.

PubMed

Li, Zhengqiu; Zhu, Dongsheng; Guo, Haijun; Chang, Yu; Ni, Yun; Li, Lin; Hao, Piliang; Xu, Yong; Ding, Ke

2018-05-16

Venetoclax (ABT-199) and idasanutlin (RG7388) are efficient anticancer drugs targeting two essential apoptosis markers, Bcl2 and MDM2, respectively. Recent studies have shown that the combination of these two drugs leads to remarkable enhancement of anticancer efficacy, both in vitro and in vivo. In an attempt to understand the mechanism of this synergistic effect, competitive affinity-based proteome profiling coupled with bioimaging was employed to characterize their protein targets in the same cancer cell line and tumor tissue. A series of protein hits, including ITPR1, GSR, RER1, PDIA3, Apoa1 and Tnfrsf17 were simultaneously identified by pull-down/LC-MS/MS with the two sets of affinity-based probes. Dual imaging was successfully carried out, simultaneously detecting Bcl2 and MDM2 expression in various cancer cells. This could facilitate the novel diagnostic and therapeutic strategies of dual targeting of Bcl2/MDM2. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systematic review of FDG-PET prediction of complete pathological response and survival in rectal cancer.

PubMed

Memon, Sameer; Lynch, A Craig; Akhurst, Timothy; Ngan, Samuel Y; Warrier, Satish K; Michael, Michael; Heriot, Alexander G

2014-10-01

Advances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of (18)F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. A search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. Seventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). SUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.

Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy.

PubMed

Kaliff, Malin; Sorbe, Bengt; Mordhorst, Louise Bohr; Helenius, Gisela; Karlsson, Mats G; Lillsunde-Larsson, Gabriella

2018-04-10

Cervical cancer (CC) is one of the most common cancers in women and virtually all cases of CC are a result of a persistent infection of human papillomavirus (HPV). For disease detected in early stages there is curing treatment but when diagnosed late with recurring disease and metastasis there are limited possibilities. Here we evaluate HPV impact on treatment resistance and metastatic disease progression. Prevalence and distribution of HPV genotypes and HPV16 variants in a Swedish CC patient cohort (n=209) was evaluated, as well as HPV influence on patient prognosis. Tumor samples suitable for analysis (n=204) were genotyped using two different real-time PCR methods. HPV16 variant analysis was made using pyrosequencing. Results showed that HPV prevalence in the total series was 93%. Of the HPV-positive samples, 13% contained multiple infections, typically with two high-risk HPV together. Primary cure rate for the complete series was 95%. Recurrence rate of the complete series was 28% and distant recurrences were most frequent (20%). Patients with tumors containing multiple HPV-strains and particularly HPV genotypes belonging to the alpha 7 and 9 species together had a significantly higher rate of distant tumor recurrences and worse cancer-specific survival rate.

BMC Obesity - expanding the BMC series into an important area of research.

PubMed

Horne, Genevieve; McTernan, Philip; Visscher, Tommy; Peeters, Anna

2014-01-01

This Editorial marks the launch of an important new journal to join the BMC series portfolio - BMC Obesity. BMC Obesity joins BMC Cancer as the second journal within the series to focus on a particular condition in the human body and the factors that contribute towards it.

Alpha fetoprotein - series (image)

MedlinePlus

... normal levels of AFP may be due to: Cancer in testes, ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer Malignant teratoma Recovery from hepatitis Problems during pregnancy ...

Dr. Stefan Ambs: Increasing Diversity in Cancer Research: One Lab at a Time

Cancer.gov

As part of the series “Increasing Diversity in Cancer Research,” CRCHD interviewed Dr. Stefan Ambs, an investigator at NCI’s Center for Cancer Research, who is using novel approaches to discover gene differences in the tumors of African American patients.

Understanding the Needs of Young Women Regarding Breast Cancer Risk Assessment and Genetic Testing: Convergence and Divergence among Patient-Counselor Perceptions and the Promise of Peer Support.

PubMed

Evans, Chalanda; Hamilton, Rebekah J; Tercyak, Kenneth P; Peshkin, Beth N; Rabemananjara, Kantoniony; Isaacs, Claudine; O'Neill, Suzanne C

2016-06-28

Young women from hereditary breast and ovarian cancer (HBOC) families face a series of medical decisions regarding their cancer risk management and integrating this information into their life planning. This presents unique medical and psychosocial challenges that exist without comprehensive intervention. To help lay the groundwork for intervention, we conducted a qualitative study among young women from HBOC families (N = 12; Mean age = 22) and cancer genetic counselors (N = 12) to explicate domains most critical to caring for this population. Women and counselors were interviewed by telephone. The predominant interview themes included preventative care planning and risk management, decision making around the pros and cons of cancer risk assessment, medical management, and psychosocial stresses experienced. Young women endorsed psychosocial stress significantly more frequently than did counselors. Both groups noted the short- and long-term decision making challenges and the support and conflict engendered among familial relationships. Our results suggest young women value the support they receive from their families and their genetic counselors, but additional, external supports are needed to facilitate adaptation to HBOC risk. In feedback interviews focused on intervention planning with a subset of these young women (N = 9), they endorsed the predominant interview themes discovered as important intervention content, a structure that would balance discussion of medical information and psychosocial skill-building that could be tailored to the young women's needs, and delivery by trained peers familiar with HBOC risk.

Understanding the Needs of Young Women Regarding Breast Cancer Risk Assessment and Genetic Testing: Convergence and Divergence among Patient-Counselor Perceptions and the Promise of Peer Support

PubMed Central

Evans, Chalanda; Hamilton, Rebekah J.; Tercyak, Kenneth P.; Peshkin, Beth N.; Rabemananjara, Kantoniony; Isaacs, Claudine; O’Neill, Suzanne C.

2016-01-01

Young women from hereditary breast and ovarian cancer (HBOC) families face a series of medical decisions regarding their cancer risk management and integrating this information into their life planning. This presents unique medical and psychosocial challenges that exist without comprehensive intervention. To help lay the groundwork for intervention, we conducted a qualitative study among young women from HBOC families (N = 12; Mean age = 22) and cancer genetic counselors (N = 12) to explicate domains most critical to caring for this population. Women and counselors were interviewed by telephone. The predominant interview themes included preventative care planning and risk management, decision making around the pros and cons of cancer risk assessment, medical management, and psychosocial stresses experienced. Young women endorsed psychosocial stress significantly more frequently than did counselors. Both groups noted the short- and long-term decision making challenges and the support and conflict engendered among familial relationships. Our results suggest young women value the support they receive from their families and their genetic counselors, but additional, external supports are needed to facilitate adaptation to HBOC risk. In feedback interviews focused on intervention planning with a subset of these young women (N = 9), they endorsed the predominant interview themes discovered as important intervention content, a structure that would balance discussion of medical information and psychosocial skill-building that could be tailored to the young women’s needs, and delivery by trained peers familiar with HBOC risk. PMID:27417623

[COMPARISON OF REPAIR EFFECT BETWEEN CHIMERIC ANTEROLATERAL THIGH FLAP AND SERIES-WOUND FLAPS FOR DEFECT AFTER RESECTION OF ORAL AND MAXILLOFACIAL CANCER].

PubMed

Yang, Heping; Zhang, Hongwu; Chen, Haidi; Yang, Shuxiong; Wang, Jun; Hu, Dawang

2016-04-01

To compare the effectiveness of complex defects repair between using chimeric anterolateral thigh flap and series-wound flaps after resection of oral and maxillofacial cancer. After resection of oral and maxillofacial cancer, defect was repaired with chimeric anterolateral thigh flap in 39 patients between January 2011 and July 2014 (chimeric anterolateral thigh flap group); and defect was repaired with series-wound flaps in 35 patients between January 2009 and December 2010 (series-wound flaps group). There was no significant difference in gender, age, duration of disease, tumor type, tumor staging, defect location, and defect area between 2 groups (P > 0.05). The operation time, flap harvesting and microvascular anastomosis time, stomach tube extraction time, and oral feeding time were recorded and compared between 2 groups, and postoperative complications were observed; the effectiveness was evaluated according to clinical efficacy evaluation table of bone and soft tissue defects reconstruction surgery in oral and maxillofacial region. Vascular crisis occurred in 2 cases of chimeric anterolateral thigh flap group, and 4 cases of series-wound flaps group. Partial necrosis appeared at distal end of a series-wound flaps, and oral fistula and infection developed in 3 series-wound flaps. The other flaps and the grafted skin at donor site survived; wounds at recipient site healed by first intention. The operation time, stomach tube extraction time, and oral feeding time of chimeric anterolateral thigh flap group were significantly shorter than those of series-wound flaps group (P < 0.05), while the flap harvesting and microvascular anastomosis time was significantly longer than that of series-wound flaps group (P < 0.05). The patients were followed up 1-5 years (mean, 2.5 years). At 3 months after operation, the appearance, patients' satisfaction, working conditions, oral closure function, chew, language performance, and swallowing scores of the chimeric anterolateral thigh-flap group were significantly better than those of the series-wound flaps group (P < 0.05), while there was no significant difference in diet, mouth opening degree, oral cavity holding water test, and occlusion scores between the 2 groups (P > 0.05). Using chimeric anterolateral thigh flap for defect repair after resection of oral and maxillofacial cancer can significantly shorten the operation time, accelerate postoperative rehabilitation, and help the functional recovery of oral closure, chewing, language performance, swallowing function when compared with the series-wound flaps.

Nanoparticle-triggered in situ catalytic chemical reactions for tumour-specific therapy.

PubMed

Lin, Han; Chen, Yu; Shi, Jianlin

2018-03-21

Tumour chemotherapy employs highly cytotoxic chemodrugs, which kill both cancer and normal cells by cellular apoptosis or necrosis non-selectively. Catalysing/triggering the specific chemical reactions only inside tumour tissues can generate abundant and special chemicals and products locally to initiate a series of unique biological and pathologic effects, which may enable tumour-specific theranostic effects to combat cancer without bringing about significant side effects on normal tissues. Nevertheless, chemical reaction-initiated selective tumour therapy strongly depends on the advances in chemistry, materials science, nanotechnology and biomedicine. This emerging cross-disciplinary research area is substantially different from conventional cancer-theranostic modalities in clinics. In response to the fast developments in cancer theranostics based on intratumoural catalytic chemical reactions, this tutorial review summarizes the very-recent research progress in the design and synthesis of representative nanoplatforms with intriguing nanostructures, compositions, physiochemical properties and biological behaviours for versatile catalytic chemical reaction-enabled cancer treatments, mainly by either endogenous tumour microenvironment (TME) triggering or exogenous physical irradiation. These unique intratumoural chemical reactions can be used in tumour-starving therapy, chemodynamic therapy, gas therapy, alleviation of tumour hypoxia, TME-responsive diagnostic imaging and stimuli-responsive drug release, and even externally triggered versatile therapeutics. In particular, the challenges and future developments of such a novel type of cancer-theranostic modality are discussed in detail to understand the future developments and prospects in this research area as far as possible. It is highly expected that this kind of unique tumour-specific therapeutics by triggering specific in situ catalytic chemical reactions inside tumours would provide a novel but efficient methodology for benefiting personalized biomedicine in combating cancer.

Acta Oncologica Lecture. Gastrointestinal consequences of cancer treatment and the wider context: a bad gut feeling.

PubMed

Muls, Ann Cecile

2014-03-01

The percentage of people living with a diagnosis of cancer is rising globally. Between 20% and 25% of people treated for cancer experience a consequence of cancer which has an adverse impact on the quality of their life. Gastrointestinal (GI) symptoms are the most common of all consequences of cancer treatment and have the greatest impact on daily activity. PATHOPHYSIOLOGY OF LONG-TERM BOWEL DAMAGE AFTER PELVIC RADIOTHERAPY: Long-term damage to the bowel after radiotherapy is mediated by ischaemic changes and fibrosis. Each fraction of radiotherapy causes a series of repetitive injuries to the intestinal tissue resulting in an altered healing process, which affects the integrity of the repair and changes the architecture of the bowel wall. THE NATURE OF GI SYMPTOMS THAT DEVELOP: Patient-reported outcome measures show that diarrhoea, urgency, increased bowel frequency, tenesmus and flatulence are the five most prevalent GI symptoms with a moderate or severe impact on patients' daily lives after treatment with pelvic radiotherapy. Many patients also experience fatigue, urinary problems and have sexual concerns. SYSTEMATIC ASSESSMENT AND MANAGEMENT: The complex nature of those symptoms warrants systematic assessment and management. The use of a tested algorithm can assist in achieving this. The most common contributing factors to ongoing bowel problems after pelvic radiotherapy are small intestinal bacterial overgrowth, bile acid malabsorption, pancreatic insufficiency, rectal bleeding and its impact on bone health. Symptom burden, socio-psychosocial impact, memory and cognitive function, fatigue, urinary problems and sexual concerns need to be taken into account when thinking about consequences of cancer treatment. As our understanding of consequences of cancer treatments continues to emerge and encompass a wide variety of specialties, a holistic, multifaceted and multidisciplinary approach is required to manage those consequences long-term.

Thrombospondin 1 Wages a Double Hit Against Cancer | Center for Cancer Research

Cancer.gov

Cancer is the result of a complex series of molecular steps that promote uncontrolled growth and erode the body’s ability to fight the resulting tumor. Generating a more complete picture of these molecular events should help identify strategies to prevent and treat the disease.

Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study.

PubMed

Yao, Song; Sucheston, Lara E; Millen, Amy E; Johnson, Candace S; Trump, Donald L; Nesline, Mary K; Davis, Warren; Hong, Chi-Chen; McCann, Susan E; Hwang, Helena; Kulkarni, Swati; Edge, Stephen B; O'Connor, Tracey L; Ambrosone, Christine B

2011-02-28

Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08-0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22-0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women.

Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

PubMed Central

Yao, Song; Sucheston, Lara E.; Millen, Amy E.; Johnson, Candace S.; Trump, Donald L.; Nesline, Mary K.; Davis, Warren; Hong, Chi-Chen; McCann, Susan E.; Hwang, Helena; Kulkarni, Swati; Edge, Stephen B.; O'Connor, Tracey L.; Ambrosone, Christine B.

2011-01-01

Background Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. Methods and Findings In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. Conclusion In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women. PMID:21386992

Molecular understanding of lung cancers-A review

PubMed Central

Singh, Chinnappan Ravinder; Kathiresan, Kandasamy

2014-01-01

Lung cancer is considered to be the most common cancer in the world. The purpose of this paper is to review scientific evidence, particularly epidemiologic evidence of overall lung cancer burden in the world. And molecular understanding of lung cancer at various levels by dominant and suppressor oncogenes. PMID:25183110

Considerations of Culture and Social Class for Families Facing Cancer: The Need for a New Model for Health Promotion and Psychosocial Intervention

PubMed Central

Marshall, Catherine A.; Larkey, Linda K.; Curran, Melissa A.; Weihs, Karen L.; Badger, Terry A.; Armin, Julie; García, Francisco

2012-01-01

Cancer is a family experience, and family members often have as much, or more, difficulty in coping with cancer as does the person diagnosed with cancer. Using both family systems and sociocultural frameworks, we call for a new model of health promotion and psychosocial intervention that builds on the current understanding that family members, as well as the individuals diagnosed with cancer, are themselves survivors of cancer. We argue that considering culture, or the values, beliefs, and customs of the family, including their choice of language, is necessary to understand fully a family’s response to cancer. Likewise, acknowledging social class is necessary to understand how access to, and understanding of, otherwise available interventions for families facing cancer can be limited. Components of the model as conceptualized are discussed and provide guidance for psychosocial cancer health disparities research and the development of family-focused, strength-based, interventions. PMID:21688902

Use of Cancer Stem Cells to Investigate the Pathogenesis of Colitis-associated Cancer

PubMed Central

Davies, Julie M.; Santaolalla, Rebeca

2016-01-01

Abstract: Colitis-associated cancer (CAC) can develop in patients with inflammatory bowel disease with long-term uncontrolled inflammation. The mutational history and tumor microenvironment observed in CAC patients is distinct from that observed in sporadic colon cancer and suggests a different etiology. Recently, much attention has been focused on understanding the cellular origin of cancer and the cancer stem cells, which is key to growth and progression. Cancer stem cells are often chemo-resistant making them attractive targets for improving patient outcomes. New techniques have rapidly been evolving allowing for a better understanding of the normal intestinal stem cell function and behavior in the niche. Use of these new technologies will be crucial to understanding cancer stem cells in both sporadic and CAC. In this review, we will explore emerging methods related to the study of normal and cancer stem cells in the intestine, and examine potential avenues of investigation and application to understanding the pathogenesis of CAC. PMID:26963566

A comprehensive experiment for molecular biology: Determination of single nucleotide polymorphism in human REV3 gene using PCR-RFLP.

PubMed

Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

2017-07-08

Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of DNA polymerase ζ and SNPs in this gene are associated with altered susceptibility to cancer. This newly designed experiment is composed of three parts, including genomic DNA extraction, gene amplification by PCR, and genotyping by RFLP. By combining these activities, the students are not only able to learn a series of biotechniques in molecular biology, but also acquire the ability to link the learned knowledge with practical applications. This comprehensive experiment will help the medical students improve the conceptual understanding of SNP and the technical understanding of SNP detection. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(4):299-304, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

Cancer biology and implications for practice.

PubMed

Rieger, Paula Trahan

2006-08-01

The media seem to announce a new scientific discovery related to cancer daily. Oncology nurses are challenged to keep up with the explosion of new knowledge and to understand how it ultimately relates to the care of patients with cancer. A framework for classifying new knowledge can be useful as nurses seek to understand the biology of cancer and its related implications for practice. To understand the molecular roots of cancer, healthcare practitioners specializing in cancer care require insight into genes, their messages, and the proteins produced from those messages, as well as the new tools of molecular biology.

Management of Infection and Febrile Neutropenia in Patients with Solid Cancer.

PubMed

Aguado, José María; Cruz, Juan Jesús; Virizuela, Juan Antonio; Aguilar, Manuela; Carmona, Alberto; Cassinello, Javier; Gudiol, Carlota; Jiménez Fonseca, Paula; Lizasoain, Manuel; Marco, Francesc; Ruiz, Isabel; Ruiz, Maribel; Salavert, Miguel; Vicente, David; Carratalà, Jordi

A group of experts from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Medical Oncology (SEOM) have reviewed in this paper the main aspects to be considered in the evaluation of patients with solid cancer and infectious diseases. They have established a series of recommendations on the prevention of the most prevalent infections in these patients, the use of vaccines, the control measures of vascular catheter infection and prevention of infections before certain surgical procedures. Also the criteria for management of febrile neutropenia and the use of colony-stimulating factors were revised. Finally they provide a series of recommendations for the treatment of cancer patients with severe infection. The document is completed with a series of measures for the control of hospital infection. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

In vitro study on effect of germinated wheat on human breast cancer cells

USDA-ARS?s Scientific Manuscript database

This research investigated the possible anti-cancer effects of germinated wheat flours (GWF) on cell growth and apoptosis of human breast cancer cells. In a series of in vitro experiments, estrogen receptor-positive (MCF-7) and negative (MDA-MB-231) cells were cultured and treated with GWF that wer...

The Psychosocial Problems of Cancer Patients: A Prospective Study.

ERIC Educational Resources Information Center

Gordon, Wayne; And Others

The course of psychosocial adjustment to cancer was examined in 105 adults with cancer of the lung, breast and skin. Half of the patients received a program of systematic psychosocial rehabilitation plus evaluation, and the other half received only an evaluation, consisting of a series of psychometric instruments and a problem-oriented structured…

Development of a Targeted Smoking Relapse-Prevention Intervention for Cancer Patients.

PubMed

Meltzer, Lauren R; Meade, Cathy D; Diaz, Diana B; Carrington, Monica S; Brandon, Thomas H; Jacobsen, Paul B; McCaffrey, Judith C; Haura, Eric B; Simmons, Vani N

2018-04-01

We describe the series of iterative steps used to develop a smoking relapse-prevention intervention customized to the needs of cancer patients. Informed by relevant literature and a series of preliminary studies, an educational tool (DVD) was developed to target the unique smoking relapse risk factors among cancer patients. Learner verification interviews were conducted with 10 cancer patients who recently quit smoking to elicit feedback and inform the development of the DVD. The DVD was then refined using iterative processes and feedback from the learner verification interviews. Major changes focused on visual appeal, and the inclusion of additional testimonials and graphics to increase comprehension of key points and further emphasize the message that the patient is in control of their ability to maintain their smoking abstinence. Together, these steps resulted in the creation of a DVD titled Surviving Smokefree®, which represents the first smoking relapse-prevention intervention for cancer patients. If found effective, the Surviving Smokefree® DVD is an easily disseminable and low-cost portable intervention which can assist cancer patients in maintaining smoking abstinence.

AHNS series: Do you know your guidelines? Management of head and neck cancer in the era of human papillomavirus: Educating our patients on human papillomavirus.

PubMed

Guo, Theresa; Goldenberg, David; Fakhry, Carole

2017-05-01

Human papillomavirus (HPV) has changed the face of head and neck cancer over the past 2 decades. No longer is this solely a disease of older patients with a history of heavy tobacco and alcohol use. Patients with HPV-related head and neck cancers tend to be younger, healthier, and have an improved prognosis, compared with those with HPV-negative tumors. As more patients are diagnosed with HPV-related head and neck cancer, physicians have important topics to consider. These include prevalence, transmission, and natural history of HPV, the role of screening, vaccines, and HPV testing in head and neck cancer. This article continues a series developed by the American Head and Neck Society's Education Committee entitled "Do you know your guidelines?" and is intended to provide guidance for navigating common questions and concerns patients may have about HPV infection and HPV-related head and neck cancer. © 2017 Wiley Periodicals, Inc. Head Neck 39: 833-839, 2017. © 2017 Wiley Periodicals, Inc.

Cancer understanding among Japanese students based on a nationwide survey.

PubMed

Sugisaki, Koshu; Ueda, Seiji; Monobe, Hirofumi; Yako-Suketomo, Hiroko; Eto, Takashi; Watanabe, Masaki; Mori, Ryoichi

2014-11-01

The objective of this study was to determine cancer understanding among Japanese primary and secondary school students. The study design was a cross-sectional nationwide survey using a self-administered questionnaire. The prefecture with the lowest student population was set to 1, and that with the highest student population was set to 18 for elementary schools and 19 for junior high and high schools based on the ratio of the student population. In this way, 213 elementary schools, 222 junior high schools, and 208 high schools were selected from all 47 prefectures in Japan, and questionnaires were sent to each school. The questionnaire listed the names of 15 cancers and asked respondents to choose one answer from three: "Never heard of," "Heard of/Don't understand," or "Heard of/Understand." Response rates for schools were 44.1 % (n = 94) for elementary schools, 46.4 % (n = 103) for junior high schools, and 55.8 % (n = 116) for high schools. A total of 8,876 questionnaires were used for the analysis. Our survey suggests that the most commonly understood types of cancer differed by grade, with lung cancer the most commonly understood in elementary school, leukemia in junior high schools, and breast cancer in high schools. Girls tended to demonstrate greater cancer understanding than boys, with particularly large differences by gender in rates of understanding of breast and uterine cancer at each assessed grade level. Here, we examined Japanese primary and secondary school students. Marked differences in cancer recognition by grade and gender suggest that educational efforts are needed at various grade levels and gender-specific cancer education. Further, more than 50 % of students at any school level were not familiar with most cancers. It suggests that cancer education is deficient.

Children's cancer camps: a way to understand grief differently.

PubMed

Laing, Catherine M; Moules, Nancy J

2015-01-01

A philosophical hermeneutic study was conducted as part of the first author's doctoral research to understand the meaning of children's cancer camps for the child with cancer and the family. Twenty family members from six families were interviewed in order to bring understanding to this topic. This article will detail the finding related to the experience of grief that often accompanies a cancer diagnosis, and how camp seems to allow children and families to understand their grief differently. The interesting thing about this particular cancer camp is that families of children who have died continue to attend the camp yearly, and there are events to memorialize the many children known to all the campers who no longer attend camp. This is not a grief camp but a cancer camp where grief is allowed presence as it necessarily has to in the world of childhood cancer.

Quantitative assessment of effect of preanalytic cold ischemic time on protein expression in breast cancer tissues.

PubMed

Neumeister, Veronique M; Anagnostou, Valsamo; Siddiqui, Summar; England, Allison Michal; Zarrella, Elizabeth R; Vassilakopoulou, Maria; Parisi, Fabio; Kluger, Yuval; Hicks, David G; Rimm, David L

2012-12-05

Companion diagnostic tests can depend on accurate measurement of protein expression in tissues. Preanalytic variables, especially cold ischemic time (time from tissue removal to fixation in formalin) can affect the measurement and may cause false-negative results. We examined 23 proteins, including four commonly used breast cancer biomarker proteins, to quantify their sensitivity to cold ischemia in breast cancer tissues. A series of 93 breast cancer specimens with known time-to-fixation represented in a tissue microarray and a second series of 25 matched pairs of core needle biopsies and breast cancer resections were used to evaluate changes in antigenicity as a function of cold ischemic time. Estrogen receptor (ER), progesterone receptor (PgR), HER2 or Ki67, and 19 other antigens were tested. Each antigen was measured using the AQUA method of quantitative immunofluorescence on at least one series. All statistical tests were two-sided. We found no evidence for loss of antigenicity with time-to-fixation for ER, PgR, HER2, or Ki67 in a 4-hour time window. However, with a bootstrapping analysis, we observed a trend toward loss for ER and PgR, a statistically significant loss of antigenicity for phosphorylated tyrosine (P = .0048), and trends toward loss for other proteins. There was evidence of increased antigenicity in acetylated lysine, AKAP13 (P = .009), and HIF1A (P = .046), which are proteins known to be expressed in conditions of hypoxia. The loss of antigenicity for phosphorylated tyrosine and increase in expression of AKAP13, and HIF1A were confirmed in the biopsy/resection series. Key breast cancer biomarkers show no evidence of loss of antigenicity, although this dataset assesses the relatively short time beyond the 1-hour limit in recent guidelines. Other proteins show changes in antigenicity in both directions. Future studies that extend the time range and normalize for heterogeneity will provide more comprehensive information on preanalytic variation due to cold ischemic time.

Highlights from the Inaugural International Cancer Microbiome Consortium Meeting (ICMC), 5-6 September 2017, London, UK.

PubMed

Scott, Alasdair J; Merrifield, Claire A; Alexander, James L; Marchesi, Julian R; Kinross, James M

2017-01-01

The International Cancer Microbiome Consortium (ICMC) is a recently launched collaborative between academics and academic-clinicians that aims to promote microbiome research within the field of oncology, establish expert consensus and deliver education for academics and clinicians. The inaugural two-day meeting was held at the Royal Society of Medicine (RSM), London, UK, 5-6 September 2017. Microbiome and cancer experts from around the world first delivered a series of talks during an educational day and then sat for a day of roundtable discussion to debate key topics in microbiome-cancer research. Talks delivered during the educational day covered a broad range of microbiome-related topics. The potential role of the microbiome in the pathogenesis of colorectal cancer was discussed and debated in detail with experts highlighting the latest data in animal models and humans and addressing the question of causation versus association. The impact of the microbiota on other cancers-such as lung and urogenital tract-was also discussed. The microbiome represents a novel target for therapeutic manipulation in cancer and a number of talks explored how this might be realised through diet, faecal microbiota transplant and chemotherapeutics. On the second day, experts debated pre-agreed topics with the aim of producing a consensus statement with a focus on the current state of our knowledge and key gaps for further development. The panel debated the notion of a 'healthy' microbiome and, in turn, the concept of dysbiosis in cancer. The mechanisms of microbiota-induced carcinogenesis were discussed in detail and our current conceptual models were assessed. Experts also considered co-factors in microbiome-induced carcinogenesis to conclude that the tripartite 'interactome' between genetically vulnerable host, environment and the microbiome is central to our current understanding. To conclude, the roundtable discussed how the microbiome may be exploited for therapeutic benefit in cancer and the safety implications of performing such research in oncology patients.

[Development of the Oral Assessment Scale for Post-Operational Patients With Oral Cancer].

PubMed

Lee, Yi-Chen; Hsu, Ya-Chuan; Chiang, Hui-Ying

2017-04-01

Current oral assessment scales are designed to assess the severity of oral health in cancer patients who have undergone radiotherapy or chemotherapy. Currently, no scale is available that assesses the overall oral health situation of patients. However, this type of scale is critical for guiding nursing staff to understand the oral status of postoperative patients and for facilitating the development of patient-centered oral nursing treatments. To develop the oral assessment scale for post-operational patients with oral cancer (OASPOCa) and establish its psychometric properties. The ten associated items of the OASPOCa were determined using a series of five professional council meetings and two verifications of content validity by 5 experts in the field of oral cancer care. A pilot study was conducted on 30 participants and a formal study was conducted on 100 participants at the ICU and the oral and maxillofacial surgery ward at a medical center in southern Taiwan. All of the participants were oral cancer patients who had been admitted to excise tumors of oral cancer. None of the participants had been treated previously for oral cancer using chemotherapy or radiotherapy. The intraclass correlation coefficient (ICC), internal consistency reliability, and concurrent validity of the OASPOCa were evaluated. A content validity of 1.0 was obtained. The inter-rater reliability assessment in the pilot study yielded ICCs of .97 for two assessment items ("lips" and "tongue") and 1.0 for the remaining eight items. The Cronbach's α coefficient was .72 for the OASPOCa. Further, a statistically significant negative relationship was found between overall oral status and oral comfort level (r = -.93, p < .001). The oral assessment scale for post-operational patients with oral cancer was found to have good reliability and validity. This scale is a reliable tool for assessing the oral status of postoperative oral cancer patients.

Nuclear grade and DNA ploidy in stage IV breast cancer with only visceral metastases at initial diagnosis.

PubMed

De Lena, M; Barletta, A; Marzullo, F; Rabinovich, M; Leone, B; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriguez, R; Schittulli, F; Paradisco, A

1996-01-01

The presence of early metastases to distant sites in breast cancer patients is an infrequent event whose mechanisms are still not clear. The aim of this study was to evaluate the biologic and clinical role of DNA ploidy and cell nuclear grade of primary tumors in the metastatic process of a series of stage IV previously untreated breast cancer patients with only visceral metastases. DNA flow cytometry analysis on paraffin-embedded material and cell nuclear grading of primary tumors was performed on a series of 50 breast cancer patients with only visceral metastases at the time of initial diagnosis. Aneuploidy was found in 28/46 (61%) of evaluable cases and was independent of site of involvement, clinical response, time of progression and overall survival of patients. Of the 46 cases evaluable for nuclear grade, 5 (11%), 16 (35%) and 25 (54%) were classified as G1 (well-differentiated) G2 and G3, respectively. Nuclear grade also was unrelated to response to therapy and overall survival, whereas time to progression was significantly longer in G1-2 than G3 tumors with the logrank test (P < 0.03) and multivariate analysis. Our results seem to stress the difficulty to individualize different prognostic subsets from a series of breast cancer patients with only visceral metastases at initial diagnosis according to DNA flow cytometry and nuclear grade.

Molecular Testing for Targeted Therapy in Advanced Non-Small Cell Lung Cancer: Suitability of Endobronchial Ultrasound Transbronchial Needle Aspiration.

PubMed

Casadio, Chiara; Guarize, Juliana; Donghi, Stefano; Di Tonno, Clementina; Fumagalli, Caterina; Vacirca, Davide; Dell'Orto, Patrizia; De Marinis, Filippo; Spaggiari, Lorenzo; Viale, Giuseppe; Barberis, Massimo

2015-10-01

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has revolutionized the diagnosis and staging of lung cancer. The goal of the present study was to investigate the yield and applicability of molecular testing in the specimens obtained by EBUS-TBNA from patients with advanced non-small cell lung cancer (NSCLC), comparing the results with a series of patients who underwent diagnostic surgical procedures in the same institution. The study followed 306 consecutive patients with clinically diagnosed primary lung cancer who had the EBUS-TBNA procedure. EGFR and KRAS mutations were evaluated on cytologic specimens by Sanger sequencing and Cobas real-time polymerase chain reaction, whereas ALK rearrangement was tested by fluorescence in situ hybridization. The results were compared with those obtained from a series of 1,000 NSCLC surgical samples routinely analyzed. Molecular testing was possible in 96.9% of the samples obtained by EBUS-TBNA. EGFR (exons 18-21) mutations were found in 16.9%, KRAS mutation (exons 2-3) in 31.6%, and ALK rearrangement in 3.9% of the cases. In the surgical series, the mutations' distribution were 14.8%, 29.0%, and 3.4%, respectively. There were no statistical differences between the two series. Our study demonstrates that EBUS-TBNA can be effectively used not just for diagnosis but also for complete mutational testing. Copyright© by the American Society for Clinical Pathology.

Predicting disease progression from short biomarker series using expert advice algorithm

NASA Astrophysics Data System (ADS)

Morino, Kai; Hirata, Yoshito; Tomioka, Ryota; Kashima, Hisashi; Yamanishi, Kenji; Hayashi, Norihiro; Egawa, Shin; Aihara, Kazuyuki

2015-05-01

Well-trained clinicians may be able to provide diagnosis and prognosis from very short biomarker series using information and experience gained from previous patients. Although mathematical methods can potentially help clinicians to predict the progression of diseases, there is no method so far that estimates the patient state from very short time-series of a biomarker for making diagnosis and/or prognosis by employing the information of previous patients. Here, we propose a mathematical framework for integrating other patients' datasets to infer and predict the state of the disease in the current patient based on their short history. We extend a machine-learning framework of ``prediction with expert advice'' to deal with unstable dynamics. We construct this mathematical framework by combining expert advice with a mathematical model of prostate cancer. Our model predicted well the individual biomarker series of patients with prostate cancer that are used as clinical samples.

Discovery of estrogen receptor α modulators from natural compounds in Si-Wu-Tang series decoctions using estrogen-responsive MCF-7 breast cancer cells.

PubMed

Liu, Li; Ma, Hongyue; Tang, Yuping; Chen, Wenxing; Lu, Yin; Guo, Jianming; Duan, Jin-Ao

2012-01-01

The binding between the estrogen receptor α (ER-α) and a variety of compounds in traditional Chinese formulae, Si-Wu-Tang (SWT) series decoctions, was studied using a stably-transfected human breast cancer cell line (MVLN). In 38 compounds tested from SWT series decoctions, the estrogen-like activity of 22 compounds was above 60% in 20 μg mL(-1). Furthermore, theoretical affinity of these compounds was certificated using the functional virtual screen of ER-α modulators by FlexX-Pharm. The accuracy of functional virtual screening of ER-α modulators could reach to 77.27%. The results showed that some compounds, such as organic acids and flavones in SWT series decoctions could be used as selective estrogen receptor modulators (SERMs) and could be selected for further development as potential agents for estrogen related diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

Predicting disease progression from short biomarker series using expert advice algorithm.

PubMed

Morino, Kai; Hirata, Yoshito; Tomioka, Ryota; Kashima, Hisashi; Yamanishi, Kenji; Hayashi, Norihiro; Egawa, Shin; Aihara, Kazuyuki

2015-05-20

Well-trained clinicians may be able to provide diagnosis and prognosis from very short biomarker series using information and experience gained from previous patients. Although mathematical methods can potentially help clinicians to predict the progression of diseases, there is no method so far that estimates the patient state from very short time-series of a biomarker for making diagnosis and/or prognosis by employing the information of previous patients. Here, we propose a mathematical framework for integrating other patients' datasets to infer and predict the state of the disease in the current patient based on their short history. We extend a machine-learning framework of "prediction with expert advice" to deal with unstable dynamics. We construct this mathematical framework by combining expert advice with a mathematical model of prostate cancer. Our model predicted well the individual biomarker series of patients with prostate cancer that are used as clinical samples.

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... and Musculoskeletal and Skin Diseases) Also in Spanish Acute Lymphocytic Leukemia Understanding Chemotherapy (National Cancer Institute) - PDF ... Therapy (National Cancer Institute) - PDF Also in Spanish Acute Myeloid Leukemia Understanding Chemotherapy (National Cancer Institute) - PDF ...

Working to Increase Vaccination for Human Papillomavirus: A Survey of Wisconsin Stakeholders, 2015.

PubMed

Mroz, Sarah; Zhang, Xiao; Williams, Mercedes; Conlon, Amy; LoConte, Noelle K

2017-09-28

Infection with human papillomavirus (HPV) is common and can progress to various types of cancer. HPV infection can be prevented through vaccination; however, vaccination rates among adolescents are low. The objective of this study was to assess efforts among Wisconsin stakeholders in HPV vaccination and organizational capacity for future collaborative work. We conducted a cross-sectional online survey of 277 stakeholders in HPV vaccination activities, from April 30, 2015, through June 30, 2015. Stakeholders were public health professionals, health care providers, educators, quality improvement professionals, researchers, and advocates identified as engaged in HPV vaccination work. Of the 277 invited stakeholders, 117 (42%) responded to the survey. Findings showed that most current HPV vaccination activities targeted 3 groups: adolescents and parents, clinical and health professionals, and communities and health systems. The main activities directed at these groups were providing printed educational materials, professional education, and media campaigns to raise awareness. Common barriers reported were lack of understanding about the link between HPV and cancer, requests to delay vaccination, difficulty completing the 3-dose vaccine series, and reluctance to discuss sexuality. HPV vaccination rates are far below those of other vaccinations administered to adolescents in Wisconsin. Our study showed that various local efforts were being made to increase HPV vaccination uptake; however, many barriers exist to initiation and completion of the vaccine series. Future interventions should address barriers and employ evidence-based strategies for increasing HPV vaccination rates.

Ketamine for cancer pain: what is the evidence?

PubMed

Jonkman, Kelly; van de Donk, Tine; Dahan, Albert

2017-06-01

In this review, we assess the benefit of ketamine in the treatment of terminal cancer pain that is refractory to opioid treatment and/or complicated by neuropathy. While randomized controlled trials consistently show lack of clinical efficacy of ketamine in treating cancer pain, a large number of open-label studies and case series show benefit. Ketamine is an N-methyl-D-aspartate receptor antagonist that at low-dose has effective analgesic properties. In cancer pain, ketamine is usually prescribed as adjuvant to opioid therapy when pain becomes opioid resistant or when neuropathic pain symptoms dominate the clinical picture. A literature search revealed four randomized controlled trials that examined the benefit of oral, subcutaneous or intravenous ketamine in opioid refractory cancer pain. None showed clinically relevant benefit in relieving pain or reducing opioid consumption. This suggests absence of evidence of benefit for ketamine as adjuvant analgesic in cancer pain. These findings contrast the benefit from ketamine observed in a large number of open-label studies and (retrospective) case series. We relate the opposite outcomes to methodological issues. The complete picture is such that there is still insufficient evidence to state with certainty that ketamine is not effective in cancer pain.

Early Detection of Pancreatic Cancer: The Role of Industry in the Development of Biomarkers.

PubMed

Kenner, Barbara J; Go, Vay Liang W; Chari, Suresh T; Goldberg, Ann E; Rothschild, Laura J

A diagnosis of pancreatic cancer is devastating owing to its poor prognosis, with a 5-year survival rate of only 9%. Currently, most individuals are diagnosed at a late stage when treatment options are limited. Early detection of pancreatic cancer provides the greatest hope for making substantial improvements in survival. The Kenner Family Research Fund in partnership with the American Pancreatic Association has sponsored a series of fora to stimulate discussion and collaboration on early detection of pancreatic cancer. At the first forum in 2014, "Early Detection of Sporadic Pancreatic Cancer Summit Conference," a strategic plan was set forth by an international group of interdisciplinary scientific representatives and subsequently The Strategic Map for Innovation was generated. The current conference report is the third forum in the series, "Early Detection of Pancreatic Cancer: The Role of Industry in the Development of Biomarkers," which was held in Boston, Massachusetts, on October 27, 2016. This report provides an overview of examples of innovative initiatives by industry and confirms the critical need for collaboration among industry, government, research institutions, and advocacy groups in order to make pancreatic cancer more easily detectable in its earlier stages, when it is more treatable.

Update on Sporadic Colorectal Cancer Genetics.

PubMed

Hardiman, Karin M

2018-05-01

Our understanding of the genetics of colorectal cancer has changed dramatically over recent years. Colorectal cancer can be classified in multiple different ways. Along with the advent of whole-exome sequencing, we have gained an understanding of the scale of the genetic changes found in sporadic colorectal cancer. We now know that there are multiple pathways that are commonly involved in the evolution of colorectal cancer including Wnt/β-catenin, RAS, EGFR, and PIK3 kinase. Another recent leap in our understanding of colorectal cancer genetics is the recognition that many, if not all tumors, are actually genetically heterogeneous within individual tumors and also between tumors. Recent research has revealed the prognostic and possibly therapeutic implications of various specific mutations, including specific mutations in BRAF and KRAS . There is increasing interest in the use of mutation testing for screening and surveillance through stool and circulating DNA testing. Recent advances in translational research in colorectal cancer genetics are dramatically changing our understanding of colorectal cancer and will likely change therapy and surveillance in the near future.

Prostatic cancers: understanding their molecular pathology and the 2016 WHO classification

PubMed Central

Inamura, Kentaro

2018-01-01

Accumulating evidence suggests that prostatic cancers represent a group of histologically and molecularly heterogeneous diseases with variable clinical courses. In accordance with the increased knowledge of their clinicopathologies and genetics, the World Health Organization (WHO) classification of prostatic cancers has been revised. Additionally, recent data on their comprehensive molecular characterization have increased our understanding of the genomic basis of prostatic cancers and enabled us to classify them into subtypes with distinct molecular pathologies and clinical features. Our increased understanding of the molecular pathologies of prostatic cancers has permitted their evolution from a poorly understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes that allow the implementation of personalized therapies and better patient management. This review provides perspectives on the new 2016 WHO classification of prostatic cancers as well as recent knowledge of their molecular pathologies. The WHO classification of prostatic cancers will require additional revisions to allow for reliable and clinically meaningful cancer diagnoses as a better understanding of their molecular characteristics is obtained. PMID:29581876

When Someone in Your Family Has Cancer.

ERIC Educational Resources Information Center

National Cancer Inst. (NIH), Bethesda, MD.

This booklet was written for children who have a parent or sibling with cancer. It is intended to help readers understand more about cancer, how it is treated, and changes that may be happening in the family's life because of cancer. In addition, it is intended to help readers understand and deal with their feelings about cancer and about the…

Learning curve in robotic rectal cancer surgery: current state of affairs.

PubMed

Jiménez-Rodríguez, Rosa M; Rubio-Dorado-Manzanares, Mercedes; Díaz-Pavón, José Manuel; Reyes-Díaz, M Luisa; Vazquez-Monchul, Jorge Manuel; Garcia-Cabrera, Ana M; Padillo, Javier; De la Portilla, Fernando

2016-12-01

Robotic-assisted rectal cancer surgery offers multiple advantages for surgeons, and it seems to yield the same clinical outcomes as regards the short-time follow-up of patients compared to conventional laparoscopy. This surgical approach emerges as a technique aiming at overcoming the limitations posed by rectal cancer and other surgical fields of difficult access, in order to obtain better outcomes and a shorter learning curve. A systematic review of the literature of robot-assisted rectal surgery was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted in October 2015 in PubMed, MEDLINE and the Cochrane Central Register of Controlled Trials, for articles published in the last 10 years and pertaining the learning curve of robotic surgery for colorectal cancer. It consisted of the following key words: "rectal cancer/learning curve/robotic-assisted laparoscopic surgery". A total of 34 references were identified, but only 9 full texts specifically addressed the analysis of the learning curve in robot-assisted rectal cancer surgery, 7 were case series and 2 were non-randomised case-comparison series. Eight papers used the cumulative sum (CUSUM) method, and only one author divided the series into two groups to compare both. The mean number of cases for phase I of the learning curve was calculated to be 29.7 patients; phase II corresponds to a mean number 37.4 patients. The mean number of cases required for the surgeon to be classed as an expert in robotic surgery was calculated to be 39 patients. Robotic advantages could have an impact on learning curve for rectal cancer and lower the number of cases that are necessary for rectal resections.

Online Series presents The Impact of Obesity on Cancer Risk | Division of Cancer Prevention

Cancer.gov

Obesity is a critical public health problem which is worsening over time. According to the Centers for Disease Control and Prevention, more than one third (34.9% or 78.6 million) of U.S. adults are obese. Growing obesity incidence is associated with detrimental health consequences including cancer. Experts in the field of nutrition and cancer will present the latest data and

Programs | Office of Cancer Genomics

Cancer.gov

OCG facilitates cancer genomics research through a series of highly-focused programs. These programs generate and disseminate genomic data for use by the cancer research community. OCG programs also promote advances in technology-based infrastructure and create valuable experimental reagents and tools. OCG programs encourage collaboration by interconnecting with other genomics and cancer projects in order to accelerate translation of findings into the clinic. Below are OCG’s current, completed, and initiated programs:

Diet and Cancer Are Cooked Meats Involved

ScienceCinema

LLNL - University of California Television

2017-12-09

Diet has been associated with differences in cancer rates in human populations for many years. Mark Knize presents the latest research on cancer causes including work performed at Lawrence Livermore National Laboratory investigating some interesting chemical products created when meat is cooked and how to reduce them. Series: Science on Saturday [10/2006] [Health and Medicine] [Science] [Show ID: 11542

Internalization of subcellular-scale microfabricated chips by healthy and cancer cells

PubMed Central

Wong, H.-S. Philip

2018-01-01

Continuous monitoring of physiological parameters inside a living cell will lead to major advances in our understanding of biology and complex diseases, such as cancer. It also enables the development of new medical diagnostics and therapeutics. Progress in nanofabrication and wireless communication has opened up the potential of making a wireless chip small enough that it can be wholly inserted into a living cell. To investigate how such chips could be internalized into various types of living single cells and how this process might affect cells’ physiology, we designed and fabricated a series of multilayered micron-scale tag structures with different sizes as potential RFID (Radio Frequency IDentification) cell trackers. While the present structures are test structures that do not resonate, the tags that do resonate have similar structure from device fabrication, material properties, and device size point of view. The structures are in four different sizes, the largest with the lateral dimension of 9 μm × 21 μm. The thickness for these structures is kept constant at 1.5 μm. We demonstrate successful delivery of our fabricated chips into various types of living cells, such as melanoma skin cancer, breast cancer, colon cancer and healthy/normal fibroblast skin cells. To our surprise, we observed a remarkable internalization rate difference between each cell type; the uptake rate was faster for more aggressive cancer cells than the normal/healthy cells. Cell viability before and after tag cellular internalization and persistence of the internalized tags have also been recorded over the course of five days of incubation. These results establish the foundations of the possibility of long term, wireless, intracellular physiological signal monitoring. PMID:29601607

Fatty Acid Synthesis Gene Variants and Breast Cancer Risk: A Study within the European Prospective Investigation into Cancer and Nutrition

DTIC Science & Technology

2005-02-01

refined carbohydrates, is associated with high incidence of breast cancer in women. Excess energy intake causes elevated blood levels of glucose and...confer increased breast cancer susceptibility. In a series of 46 breast cancer cases, we are systematically searching the coding and regulatory regions of...of excess energy in the form of triglycerides , produced either from the diet fatty acids or from those synthesized de novo. Excess energy intake and

Dual functions of silver nanoparticles in F9 teratocarcinoma stem cells, a suitable model for evaluating cytotoxicity- and differentiation-mediated cancer therapy.

PubMed

Han, Jae Woong; Gurunathan, Sangiliyandi; Choi, Yun-Jung; Kim, Jin-Hoi

2017-01-01

Silver nanoparticles (AgNPs) exhibit strong antibacterial and anticancer activity owing to their large surface-to-volume ratios and crystallographic surface structure. Owing to their various applications, understanding the mechanisms of action, biological interactions, potential toxicity, and beneficial effects of AgNPs is important. Here, we investigated the toxicity and differentiation-inducing effects of AgNPs in teratocarcinoma stem cells. AgNPs were synthesized and characterized using various analytical techniques such as UV-visible spectroscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. The cellular responses of AgNPs were analyzed by a series of cellular and biochemical assays. Gene and protein expressions were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The AgNPs showed typical crystalline structures and spherical shapes (average size =20 nm). High concentration of AgNPs induced cytotoxicity in a dose-dependent manner by increasing lactate dehydrogenase leakage and reactive oxygen species. Furthermore, AgNPs caused mitochondrial dysfunction, DNA fragmentation, increased expression of apoptotic genes, and decreased expression of antiapoptotic genes. Lower concentrations of AgNPs induced neuronal differentiation by increasing the expression of differentiation markers and decreasing the expression of stem cell markers. Cisplatin reduced the viability of F9 cells that underwent AgNPs-induced differentiation. The results showed that AgNPs caused differentially regulated cytotoxicity and induced neuronal differentiation of F9 cells in a concentration-dependent manner. Therefore, AgNPs can be used for differentiation therapy, along with chemotherapeutic agents, for improving cancer treatment by targeting specific chemotherapy-resistant cells within a tumor. Furthermore, understanding the molecular mechanisms of apoptosis and differentiation in stem cells could also help in developing new strategies for cancer stem cell (CSC) therapies. The findings of this study could significantly contribute to the nanomedicine because this study is the first of its kind, and our results will lead to new strategies for cancer and CSC therapies.

[Diagnosis and treatment of depression in the advanced stage of cancer].

PubMed

Ronson, A

2002-10-01

The diagnosis of depression in patients with advanced cancer is a particularly complex task. The lack of diagnostic tools specifically developed for this patient population, the difficulty of interpreting neurovegetative symptoms of depression--which can result from the neoplastic disease--and the "normal and understandable" nature of many symptoms or signs of psychological distress are among the main obstacles to a clear-cut diagnosis of depression. Things go even more complex when it comes about to discuss whether one should treat patients displaying psychological distress that does not meet established criteria for the diagnosis of a depressive illness. When the indication to treat is finally acknowledged, the choice of the optimal antidepressant will depend upon a series of parameters including survival expectancy, tolerance profile and drug interactions. Though we currently lack prospective data about the efficacy and safety of antidepressants in depressed patients with advanced cancer, extrapolation of data available from other patient populations with severe medical conditions and clinical experience allow to draw guidelines aimed at helping healthcare professionals faced with those problems to improve the quality of life of their patients. These elements are presented and discussed in this paper in the light of the recent developments resulting from the growing interest of the medical community to the care to patients with terminal illness.

Light-at-night, circadian disruption and breast cancer: assessment of existing evidence.

PubMed

Stevens, Richard G

2009-08-01

Breast cancer incidence is increasing globally for largely unknown reasons. The possibility that a portion of the breast cancer burden might be explained by the introduction and increasing use of electricity to light the night was suggested >20 years ago. The theory is based on nocturnal light-induced disruption of circadian rhythms, notably reduction of melatonin synthesis. It has formed the basis for a series of predictions including that non-day shift work would increase risk, blind women would be at lower risk, long sleep duration would lower risk and community nighttime light level would co-distribute with breast cancer incidence on the population level. Accumulation of epidemiological evidence has accelerated in recent years, reflected in an International Agency for Research on Cancer (IARC) classification of shift work as a probable human carcinogen (2A). There is also a strong rodent model in support of the light-at-night (LAN) idea. If a consensus eventually emerges that LAN does increase risk, then the mechanisms for the effect are important to elucidate for intervention and mitigation. The basic understanding of phototransduction for the circadian system, and of the molecular genetics of circadian rhythm generation are both advancing rapidly, and will provide for the development of lighting technologies at home and at work that minimize circadian disruption, while maintaining visual efficiency and aesthetics. In the interim, there are strategies now available to reduce the potential for circadian disruption, which include extending the daily dark period, appreciate nocturnal awakening in the dark, using dim red light for nighttime necessities, and unless recommended by a physician, not taking melatonin tablets.

Inspiring Examples in Rearrangements of Infinite Series

ERIC Educational Resources Information Center

Ramasinghe, W.

2002-01-01

Simple examples are really encouraging in the understanding of rearrangements of infinite series, since many texts and teachers provide only existence theorems. In the absence of examples, an existence theorem is just a statement and lends little confidence to understanding. Iterated sums of double series seem to have a similar spirit of…

Epidemiological Trends of GI Cancers in Patients Visiting a Tertiary Care Hospital in Chandigarh, North India.

PubMed

Sharma, Munesh K; Singh, Tarundeep; Pandey, Avdesh K; Kankaria, Ankita

2015-01-01

Cancer has become an epidemic disease. Nearly ten million new cancer cases are diagnosed annually in the world and out of these about half are from the developing world. To appropriately plan for treatment, management and prevention of the disease, it becomes necessary to study the trends about morbidity caused by cancers. Data for patients diagnosed with any form of gastrointestinal (GI) cancers was extracted from records maintained in the outpatient department registers of the Oncology Department of Government Medical College and Hospital in Chandigarh from 1999 to 2012. Trends were analysed for different categories of GI cancers for the period of 12 years. In present study GI cancers accounted for 23 % of all registered cases (n-9603) of carcinomas. Males predominated for all GI cancers except in the gall bladder. Gastrointestinal cancers as a proportion of total cancers increased from 21% in 1999 to 25.9% in 2012 with a significant increasing trend in our series (χ2 for linear trend=9.36, p<0.003). Cancers of the tonsil, oral cavity and pharynx taken together showed an increasing trend over the years (χ2 for trend=55.2, p<0.001) whereas cancers of the lower GI (χ2=19.6, p<0.0001) and gall bladder (χ2=19.5, p<0.0001) showed a declining trend in our series. GI cancers form a significant proportion of all cancers reporting to our data. In depth studies to ascertain the reasons for the changing trends are required to design intervention programs. Further information is necessary from cancer registries and from the hospital records of oncology departments.

Ascribing emotion to reasonable use in accelerated cancer services.

PubMed

Obling, Anne Roelsgaard

2013-01-01

A recurrent theme in medical sociology has been the juxtaposition of emotion with scientific rationality in the delivery of health care services. However, apart from addressing this juxtaposition very little is said about the complex intertwinement of "emotional" and "rational" practices which makes up professionals' own day-to-day work experiences - and how these experiences are influenced by present ways of organising health care. This paper aims to explore the ways that hospital doctors relate emotions to their understanding of professional medical work and how they respond to recent organisational changes within the field. Drawing upon a small series of semi-structured interviews (n = 14) with doctors from a public teaching hospital in Denmark, the paper adopts a constructivist framework to analyse personal biographies of health professionals' working lives. The doctors represented rich accounts of professional medical work, which includes an understanding of what a doctor should feel and how he/she should make him/herself emotionally available to others. However, the impetus for making this appearance was not left unaffected by recent new public management reforms and attempts to accelerate the delivery of services. The organisation of cancer services into a work system, which consists of a set of tasks broken down into narrow jobs, underestimates the emotional components of patient-doctor encounters. This makes the creation and maintenance of a genuine patient-doctor relationship difficult and the result is feelings of a failed encounter on behalf of the doctor. The paper suggests that recent rearrangements of cancer services complicate doctors' ability to incorporate emotion into a stream of medical care in a "rational" way. This is shown to challenge their professional ethos and the forms emotional engagement takes in medical practice.

Objectives | Office of Cancer Clinical Proteomics Research

Cancer.gov

The overall objective of CPTAC is to systematically identify proteins that derive from alterations in cancer genomes and related biological processes, in order to understand the molecular basis of cancer that is not fully elucidated or not possible through genomics and to accelerate the translation of molecular findings into the clinic.  This is to be achieved through enhancing our understanding of cancer genome biology by adding a complementary functional layer of protein biology (a “proteogenome” approach) that refines/prioritizes driver genes, enhances understanding of pathogenesis

Highlights from the Inaugural International Cancer Microbiome Consortium Meeting (ICMC), 5–6 September 2017, London, UK

PubMed Central

Scott, Alasdair J; Merrifield, Claire A; Alexander, James L; Marchesi, Julian R; Kinross, James M

2017-01-01

The International Cancer Microbiome Consortium (ICMC) is a recently launched collaborative between academics and academic-clinicians that aims to promote microbiome research within the field of oncology, establish expert consensus and deliver education for academics and clinicians. The inaugural two-day meeting was held at the Royal Society of Medicine (RSM), London, UK, 5–6 September 2017. Microbiome and cancer experts from around the world first delivered a series of talks during an educational day and then sat for a day of roundtable discussion to debate key topics in microbiome-cancer research. Talks delivered during the educational day covered a broad range of microbiome-related topics. The potential role of the microbiome in the pathogenesis of colorectal cancer was discussed and debated in detail with experts highlighting the latest data in animal models and humans and addressing the question of causation versus association. The impact of the microbiota on other cancers—such as lung and urogenital tract—was also discussed. The microbiome represents a novel target for therapeutic manipulation in cancer and a number of talks explored how this might be realised through diet, faecal microbiota transplant and chemotherapeutics. On the second day, experts debated pre-agreed topics with the aim of producing a consensus statement with a focus on the current state of our knowledge and key gaps for further development. The panel debated the notion of a ‘healthy’ microbiome and, in turn, the concept of dysbiosis in cancer. The mechanisms of microbiota-induced carcinogenesis were discussed in detail and our current conceptual models were assessed. Experts also considered co-factors in microbiome-induced carcinogenesis to conclude that the tripartite ‘interactome’ between genetically vulnerable host, environment and the microbiome is central to our current understanding. To conclude, the roundtable discussed how the microbiome may be exploited for therapeutic benefit in cancer and the safety implications of performing such research in oncology patients. PMID:29290760

TCGA and Its Vital Role in Understanding the Landscape of Somatic Alterations in Cancer - TCGA

Cancer.gov

Dr. Stephen Chanock, M.D., Director of the Division of Cancer Epidemiology & Genetics at the NCI, discusses how TCGA provides a strong foundation for understanding key biological alterations in cancer.

Prostatic cancer. Treated at a categorical center, 1980-1983.

PubMed

Slack, N H; Lane, W W; Priore, R L; Murphy, G P

1986-03-01

This report covers the experience from 537 patients with prostatic cancer seen at Roswell Park Memorial Institute (RPMI) from 1980 through 1983. This is a look at experiences in the early 1980s and is a continuation of the series covering the decades of the 1950s, 1960s, and 1970s. Referrals continue to dominate the series (85% of cases) but are now only slightly younger (65 years) than in-house diagnoses (66 years), of which one third were diagnosed at autopsy. Survival rates in this series, although limited in follow-up, were similar at two years to those in the 1970s and in the extensive series collected by the survey of the American College of Surgeons. Multiple primary tumors were observed in 22 per cent of this series, most frequently involving the bladder in addition to the prostate. Treatments continue to involve chemotherapy earlier in the course of disease as part of a succession of therapeutic modalities that include transurethral resection of prostate (TURP) or prostatectomy, lymph node dissection, external irradiation, castration, and hormones.

The lived experience of men diagnosed with prostate cancer.

PubMed

Krumwiede, Kelly A; Krumwiede, Norma

2012-09-01

To investigate the lived experience of prostate cancer from a patient perspective. Descriptive, qualitative. Community setting. 10 men with prostate cancer aged 62-70 years. A hermeneutic phenomenologic method using semistructured, open-ended questions addressing the lived experience. Phenomenology of praxis proposed by van Manen guided the data analysis and transformed personal experiences into disciplinary understanding. The use of van Manen's method of inquiry and analysis has contributed to the findings of the study by providing a way to explore the meaning of the lived experiences in an attempt to understand living with prostate cancer. Several themes were identified: living in the unknown, yearning to understand and know, struggling with unreliability of body, bearing the diagnosis of cancer, shifting priorities in the gap, and feeling comfort in the presence of others. Oncology nurses can use van Manen's four fundamental existentials-lived space (spatiality), lived body (corporeality), lived time (temporality), and lived other (relationality)-to understand the lived experience of prostate cancer. Nurses have many opportunities to impact the lives of men diagnosed with prostate cancer, including diagnosis, management of physical integrity, management of psychosocial integrity, and providing education. Nurses may encourage men to describe their diagnosis story and illness experience to better understand the meaning of the prostate cancer experience and to provide appropriate nursing care.

LDR vs. HDR brachytherapy for localized prostate cancer: the view from radiobiological models.

PubMed

King, Christopher R

2002-01-01

Permanent LDR brachytherapy and temporary HDR brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never be conducted comparing these two forms of brachytherapy, a comparative radiobiological modeling analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. Radiobiological models based upon the linear quadratic equations are presented for fractionated external beam, fractionated (192)Ir HDR brachytherapy, and (125)I and (103)Pd LDR brachytherapy. These models incorporate the dose heterogeneities present in brachytherapy based upon patient-derived dose volume histograms (DVH) as well as tumor doubling times and repair kinetics. Radiobiological parameters are normalized to correspond to three accepted clinical risk factors based upon T-stage, PSA, and Gleason score to compare models with clinical series. Tumor control probabilities (TCP) for LDR and HDR brachytherapy (as monotherapy or combined with external beam) are compared with clinical bNED survival rates. Predictions are made for dose escalation with HDR brachytherapy regimens. Model predictions for dose escalation with external beam agree with clinical data and validate the models and their underlying assumptions. Both LDR and HDR brachytherapy achieve superior tumor control when compared with external beam at conventional doses (<70 Gy), but similar to results from dose escalation series. LDR brachytherapy as boost achieves superior tumor control than when used as monotherapy. Stage for stage, both LDR and current HDR regimens achieve similar tumor control rates, in agreement with current clinical data. HDR monotherapy with large-dose fraction sizes might achieve superior tumor control compared with LDR, especially if prostate cancer possesses a high sensitivity to dose fractionation (i.e., if the alpha/beta ratio is low). Radiobiological models support the current clinical evidence for equivalent outcomes in localized prostate cancer with either LDR or HDR brachytherapy using current dose regimens. However, HDR brachytherapy dose escalation regimens might be able to achieve higher biologically effective doses of irradiation in comparison to LDR, and hence improved outcomes. This advantage over LDR would be amplified should prostate cancer possess a high sensitivity to dose fractionation (i.e., a low alpha/beta ratio) as the current evidence suggests.

Pancreatic cancer stromal biology and therapy

PubMed Central

Xie, Dacheng; Xie, Keping

2015-01-01

Pancreatic cancer is one of the most lethal malignancies. Significant progresses have been made in understanding of pancreatic cancer pathogenesis, including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia (PanINs), description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior. However, the currently used therapeutic strategies targeting tumor epithelial cells, which are potent in cell culture and animal models, have not been successful in the clinic. Presumably, therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis, which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression. Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies. This review focuses on the origination, evolution and disruption of stromal molecular and cellular components in pancreatic cancer, and their biological effects on pancreatic cancer pathogenesis. PMID:26114155

Eco-friendly synthesis of novel cyanopyridine derivatives and their anticancer and PIM-1 kinase inhibitory activities.

PubMed

Abouzid, Khaled A M; Al-Ansary, Ghada H; El-Naggar, Abeer M

2017-07-07

Targeting Pim-1 kinase recently proved to be profitable for conquering cancer proliferation. In the current study, we report the design, synthesis and biological evaluation of two novel series of 2-amino cyanopyridine series (5a-g) and 2-oxocyanopyridine series (6a-g) targeting Pim-1 kinase. All of the newly synthesized compounds were evaluated for their in vitro anticancer activity against a panel of three cell lines, namely, the liver cancer cell line (HepG2), the colon cancer cell line (HCT-116) and the breast cancer cell line (MCF-7). Most of the compounds showed good to moderate anti-proliferative activity against HepG2 and HCT-116 cell lines while only few compounds showed significant cytotoxic activity against MCF-7 cell line. Further, the Pim-1 kinase inhibitory activity for the two series was evaluated where most of the tested compounds showed marked Pim-1 kinase inhibitory activity (26%-89%). Moreover, determination of the IC 50 values unraveled very potent molecules in the submicromolar range where compound 6c possessed an IC 50 value of 0.94 μM. Moreover, apoptosis studies were conducted on the most potent compound 6c to evaluate the proapoptotic potential of our compounds. Interestingly, it induced the level of active caspase 3 and boosted the Bax/Bcl2 ratio 22704 folds in comparison to the control. Finally, a molecular docking study was conducted to reveal the probable interaction with the Pim-1 kinase active site. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Synchronous Adenocarcinoma and Mantle Cell Lymphoma of the Stomach

PubMed Central

Koo, Min Young

2007-01-01

Synchronous occurrence of mantle cell lymphoma (MCL) and gastric cancer in the same patient has not yet been reported in the English literature. MCL comprises 2.5 - 7% of non-Hodgkin's lymphomas and is characterized by a poor prognosis with a median survival probability of 3 - 4 years in most series. A 62-year-old man was referred to our hospital for evaluation of an abnormal gastric lesion. The endoscopic finding was compatible with type IIc early gastric cancer (EGC) in the middle third of the stomach, and a biopsy of the lesion proved to be carcinoma. Radical total gastrectomy with splenectomy and Roux-en-Y esophagojejunostomy were performed. The resected specimen revealed two grossly separated lesions. Postoperative histological examination reported both adenocarcinoma and MCL. Immunohistochemical staining showed positivity for CD5, CD20, and cyclin D1 in the infiltrated lymphoid cells. MCL is an aggressive non-Hodgkin's lymphoma, and the current treatment approach is still unsatisfactory. Further advancements in the understanding of the synchronous occurrence of both diseases, and more efforts on investigations of treatment are needed. PMID:18159604

Synthesis facilitates an understanding of the structural basis for translation inhibition by the lissoclimides

NASA Astrophysics Data System (ADS)

Könst, Zef A.; Szklarski, Anne R.; Pellegrino, Simone; Michalak, Sharon E.; Meyer, Mélanie; Zanette, Camila; Cencic, Regina; Nam, Sangkil; Voora, Vamsee K.; Horne, David A.; Pelletier, Jerry; Mobley, David L.; Yusupova, Gulnara; Yusupov, Marat; Vanderwal, Christopher D.

2017-11-01

The lissoclimides are unusual succinimide-containing labdane diterpenoids that were reported to be potent cytotoxins. Our short semisynthesis and analogue-oriented synthesis approaches provide a series of lissoclimide natural products and analogues that expand the structure-activity relationships (SARs) in this family. The semisynthesis approach yielded significant quantities of chlorolissoclimide (CL) to permit an evaluation against the National Cancer Institute's 60-cell line panel and allowed us to obtain an X-ray co-crystal structure of the synthetic secondary metabolite with the eukaryotic 80S ribosome. Although it shares a binding site with other imide-based natural product translation inhibitors, CL engages in a particularly interesting and novel face-on halogen-π interaction between the ligand's alkyl chloride and a guanine residue. Our analogue-oriented synthesis provides many more lissoclimide compounds, which were tested against aggressive human cancer cell lines and for protein synthesis inhibitory activity. Finally, computational modelling was used to explain the SARs of certain key compounds and set the stage for the structure-guided design of better translation inhibitors.

Genomic analysis and selected molecular pathways in rare cancers

NASA Astrophysics Data System (ADS)

Liu, Stephen V.; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J.; Eng, Cathy; Ramanathan, Ramesh K.; Von Hoff, Daniel D.; Barrett, Michael T.

2012-12-01

It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

Genomic analysis and selected molecular pathways in rare cancers.

PubMed

Liu, Stephen V; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J; Eng, Cathy; Ramanathan, Ramesh K; Von Hoff, Daniel D; Barrett, Michael T

2012-12-01

It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

Atomic Fuel, Understanding the Atom Series. Revised.

ERIC Educational Resources Information Center

Hogerton, John F.

This publication is part of the "Understanding the Atom" series. Complete sets of the series are available free to teachers, schools, and public librarians who can make them available for reference or use by groups. Among the topics discussed are: What Atomic Fuel Is; The Odyssey of Uranium; Production of Uranium; Fabrication of Reactor…

Determining the sensitivity of transrectal ultrasonography on a consecutive series of prostate cancers in a clinical and screening setting.

PubMed

Ciatto, Stefano; Bonardi, Rita; Lombardi, Claudio; Zappa, Marco; Gervasi, Ginetta

2002-01-01

To evaluate the sensitivity at transrectal ultrasonography (TRUS) for prostate cancer. A consecutive series of 170 prostate cancers identified by matching local cancer registry and TRUS archives at the Centro per lo Studio e la Prevenzione Oncologica of Florence. TRUS sensitivity was determined as the ratio of TRUS positive to total prostate cancers occurring at different intervals from TRUS date. Univariate and multivariate analyses of sensitivity determinants were performed. Sensitivity at 6 months, 1, 2 and 3 years after the test was 94.1% (95% CI, 90-98), 89.8% (95% CI, 85-95), 80.4% (95% CI, 74-87) and 74.1% (95% CI, 68-81%), respectively. A higher sensitivity (statistically significant) of TRUS was observed only if digital rectal examination was suspicious, whereas no association to sensitivity was observed for age, prostate-specific antigen or prostate-specific antigen density. The study provided a reliable estimate of TRUS sensitivity, particularly reliable being checked against a cancer registry: observed sensitivity was high, at least of the same magnitude of other cancer screening tests. TRUS, which is known to allow for considerable diagnostic anticipation and is more specific than prostate-specific antigen, might still be considered for its contribution to a screening approach.

The 150 most important questions in cancer research and clinical oncology series: questions 40-49.

PubMed

2017-07-13

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 10 more questions are presented as followed. Question 40. Why do mice being used as tumorigenesis models raised in different places or different conditions possess different tumor formation rate? Question 41. How could we generate more effective anti-metastasis drugs? Question 42. What is the molecular mechanism underlying heterogeneity of cancer cachexia in patients with the same pathologic type? Question 43. Will patients with oligo-metastatic disease be curable by immunotherapy plus stereotactic body radiotherapy? Question 44. Can the Warburg effect regulation be targeted for cancer treatment? Question 45. Why do adenocarcinomas seldom occur in the small intestine? Question 46. Is Epstein-Barr virus infection a causal factor for nasal natural killer/T cell lymphoma formation? Question 47. Why will not all but very few human papillomavirus-infected patients eventually develop cervical cancer? Question 48. Why do cervical carcinomas induced by human papilloma virus have a low mutation rate in tumor suppressor genes? Question 49. Can viral infection trigger lung cancer relapse?

Onco-Golgi: Is Fragmentation a Gate to Cancer Progression?

PubMed Central

Petrosyan, Armen

2015-01-01

The Golgi apparatus-complex is a highly dynamic organelle which is considered the “heart” of intracellular transportation. Since its discovery by Camillo Golgi in 1873, who described it as the “black reaction,” and despite the enormous volume of publications about Golgi, this apparatus remains one of the most enigmatic of the cytoplasmic organelles. A typical mammalian Golgi consists of a parallel series of flattened, disk-shaped cisternae which align into stacks. The tremendous volume of Golgi-related incoming and outgoing traffic is mediated by different motor proteins, including members of the dynein, kinesin, and myosin families. Yet in spite of the strenuous work it performs, Golgi contrives to maintain its monolithic morphology and orchestration of matrix and residential proteins. However, in response to stress, alcohol, and treatment with many pharmacological drugs over time, Golgi undergoes a kind of disorganization which ranges from mild enlargement to critical scattering. While fragmentation of the Golgi was confirmed in cancer by electron microscopy almost fifty years ago, it is only in recent years that we have begun to understand the significance of Golgi fragmentation in the biology of tumors. Below author would like to focus on how Golgi fragmentation opens the doors for cascades of fatal pathways which may facilitate cancer progression and metastasis. Among the issues addressed will be the most important cancer-specific hallmarks of Golgi fragmentation, including aberrant glycosylation, abnormal expression of the Ras GTPases, dysregulation of kinases, and hyperactivity of myosin motor proteins. PMID:27064441

Semi-automated delineation of breast cancer tumors and subsequent materialization using three-dimensional printing (rapid prototyping).

PubMed

Schulz-Wendtland, Rüdiger; Harz, Markus; Meier-Meitinger, Martina; Brehm, Barbara; Wacker, Till; Hahn, Horst K; Wagner, Florian; Wittenberg, Thomas; Beckmann, Matthias W; Uder, Michael; Fasching, Peter A; Emons, Julius

2017-03-01

Three-dimensional (3D) printing has become widely available, and a few cases of its use in clinical practice have been described. The aim of this study was to explore facilities for the semi-automated delineation of breast cancer tumors and to assess the feasibility of 3D printing of breast cancer tumors. In a case series of five patients, different 3D imaging methods-magnetic resonance imaging (MRI), digital breast tomosynthesis (DBT), and 3D ultrasound-were used to capture 3D data for breast cancer tumors. The volumes of the breast tumors were calculated to assess the comparability of the breast tumor models, and the MRI information was used to render models on a commercially available 3D printer to materialize the tumors. The tumor volumes calculated from the different 3D methods appeared to be comparable. Tumor models with volumes between 325 mm 3 and 7,770 mm 3 were printed and compared with the models rendered from MRI. The materialization of the tumors reflected the computer models of them. 3D printing (rapid prototyping) appears to be feasible. Scenarios for the clinical use of the technology might include presenting the model to the surgeon to provide a better understanding of the tumor's spatial characteristics in the breast, in order to improve decision-making in relation to neoadjuvant chemotherapy or surgical approaches. J. Surg. Oncol. 2017;115:238-242. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Synthesis of novel ring-contracted artemisinin dimers with potent anticancer activities.

PubMed

Zhang, Ning; Yu, Zhimei; Yang, Xiaohong; Hu, Ping; He, Yun

2018-04-25

Artemisinin is a potential anticancer agent with an interesting trioxane sesquiterpene structure. In order to improve the biological activity and metabolic stability of artemisinin, a series of novel ring-contracted artemisinin dimers were synthesized. These dimers were evaluated by MTT assay against six cancer cell lines. Most of the dimmers exhibited improved antiproliferative activities over artemisinin. Especially, compound 8b showed the most pronounced anti-cancer activity for PC12 cancer cells with an IC 50 value of 1.56 μM. Thus, PC12 cancer cells were used to further investigate the mechanism of antiproliferation for this series of compounds. Compound 8b arrested cell cycle at G1 phase and induced cell apoptosis via up-regulation of Bad, Bax, caspase-3 and caspase-9 protein expressions while inhibiting the expression of Bcl-xL. The present studies are the first to synthesize the ring-contracted artemisinin as dimers and show that these dimers have potent anti-tumor activities against several cancer cell lines. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Expression of Proteins Involved in Epithelial-Mesenchymal Transition as Predictors of Metastasis and Survival in Breast Cancer Patients

DTIC Science & Technology

2012-11-01

at Roswell Park Cancer Institute (RPCI), works-in-progress meetings, weekly Institute-wide seminar series, and monthly Breast Disease Site Research...status to the tumor size-lymph node metastasis relationship. This analysis included 805 women diagnosed with primary, incident breast cancer enrolled...to the NJ Department of Health and Senior Services. Collection of NJ cancer incidence data is supported by SEER under contract N01-PC-95001-20. The

POLE Proofreading Mutations Elicit an Antitumor Immune Response in Endometrial Cancer.

PubMed

van Gool, Inge C; Eggink, Florine A; Freeman-Mills, Luke; Stelloo, Ellen; Marchi, Emanuele; de Bruyn, Marco; Palles, Claire; Nout, Remi A; de Kroon, Cor D; Osse, Elisabeth M; Klenerman, Paul; Creutzberg, Carien L; Tomlinson, Ian Pm; Smit, Vincent Thbm; Nijman, Hans W; Bosse, Tjalling; Church, David N

2015-07-15

Recent studies have shown that 7% to 12% of endometrial cancers are ultramutated due to somatic mutation in the proofreading exonuclease domain of the DNA replicase POLE. Interestingly, these tumors have an excellent prognosis. In view of the emerging data linking mutation burden, immune response, and clinical outcome in cancer, we investigated whether POLE-mutant endometrial cancers showed evidence of increased immunogenicity. We examined immune infiltration and activation according to tumor POLE proofreading mutation in a molecularly defined endometrial cancer cohort including 47 POLE-mutant tumors. We sought to confirm our results by analysis of RNAseq data from the TCGA endometrial cancer series and used the same series to examine whether differences in immune infiltration could be explained by an enrichment of immunogenic neoepitopes in POLE-mutant endometrial cancers. Compared with other endometrial cancers, POLE mutants displayed an enhanced cytotoxic T-cell response, evidenced by increased numbers of CD8(+) tumor-infiltrating lymphocytes and CD8A expression, enrichment for a tumor-infiltrating T-cell gene signature, and strong upregulation of the T-cell cytotoxic differentiation and effector markers T-bet, Eomes, IFNG, PRF, and granzyme B. This was accompanied by upregulation of T-cell exhaustion markers, consistent with chronic antigen exposure. In silico analysis confirmed that POLE-mutant cancers are predicted to display more antigenic neoepitopes than other endometrial cancers, providing a potential explanation for our findings. Ultramutated POLE proofreading-mutant endometrial cancers are characterized by a robust intratumoral T-cell response, which correlates with, and may be caused by an enrichment of antigenic neopeptides. Our study provides a plausible mechanism for the excellent prognosis of these cancers. ©2015 American Association for Cancer Research.

Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital.

PubMed

Rubio-Briones, J; Ramírez-Backhaus, M; Gómez-Ferrer, A; Mir, C; Domínguez-Escrig, J; Collado, A; Iborra, I; Casanova, J; Solsona, E; Mascarós, J M; Calatrava, A

2018-04-06

To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P 25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

PubMed

Furet, Elise; El Bouchtaoui, Morad; Feugeas, Jean-Paul; Miquel, Catherine; Leboeuf, Christophe; Beytout, Clémentine; Bertheau, Philippe; Le Rhun, Emilie; Bonneterre, Jacques; Janin, Anne; Bousquet, Guilhem

2017-06-06

Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases. Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series. The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.

Lasers, Understanding the Atom Series.

ERIC Educational Resources Information Center

Hellman, Hal

This booklet is one of the booklets in the "Understanding the Atom Series" published by the U. S. Atomic Energy Commission for high school science teachers and their students. Basic information for understanding the laser is provided including discussion of the electromagnetic spectrum, radio waves, light and the atom, coherent light, controlled…

New insights into pancreatic cancer biology.

PubMed

Hidalgo, M

2012-09-01

Pancreatic cancer remains a devastating disease. Over the last few years, there have been important advances in the molecular and biological understanding of pancreatic cancer. This included understanding of the genomic complexity of the disease, the role of pancreatic cancer stem cells, the relevance of the tumor microenvironment, and the unique metabolic adaptation of pancreas cancer cells to obtain nutrients under hypoxic environment. In this paper, we review the most salient developments in these few areas.

GPER-targeted, 99mTc-labeled, nonsteroidal ligands demonstrate selective tumor imaging and in vivo estrogen binding.

PubMed

Nayak, Tapan K; Ramesh, Chinnasamy; Hathaway, Helen J; Norenberg, Jeffrey P; Arterburn, Jeffrey B; Prossnitz, Eric R

2014-11-01

Our understanding of estrogen (17β-estradiol, E2) receptor biology has evolved in recent years with the discovery and characterization of a 7-transmembrane-spanning G protein-coupled estrogen receptor (GPER/GPR30) and the development of GPER-selective functional chemical probes. GPER is highly expressed in certain breast, endometrial, and ovarian cancers, establishing the importance of noninvasive methods to evaluate GPER expression in vivo. Here, we developed (99m)Tc-labeled GPER ligands to demonstrate the in vivo status of GPER as an estrogen receptor (ER) and for GPER visualization in whole animals. A series of (99m)Tc(I)-labeled nonsteroidal tetrahydro-3H-cyclopenta[c]quinolone derivatives was synthesized utilizing pyridin-2-yl hydrazine and picolylamine chelates. Radioligand receptor binding studies revealed binding affinities in the 10 to 30 nmol/L range. Cell signaling assays previously demonstrated that derivatives retaining a ketone functionality displayed agonist properties, whereas those lacking such a hydrogen bond acceptor were antagonists. In vivo biodistribution and imaging studies performed on mice bearing human endometrial and breast cancer cell xenografts yielded significant tumor uptake (0.4-1.1%ID/g). Blocking studies revealed specific uptake in multiple organs (adrenals, uterus, and mammary tissue), as well as tumor uptake with similar levels of competition by E2 and G-1, a GPER-selective agonist. In conclusion, we synthesized and evaluated a series of first-generation (99m)Tc-labeled GPER-specific radioligands, demonstrating GPER as an estrogen-binding receptor for the first time in vivo using competitive binding principles, and establishing the utility of such ligands as tumor imaging agents. These results warrant further investigation into the role of GPER in estrogen-mediated carcinogenesis and as a target for diagnostic/therapeutic/image-guided drug delivery. These studies provide a molecular basis to evaluate GPER expression and function as an ER through in vivo imaging. ©2014 American Association for Cancer Research.

Quantitative Assessment of Effect of Preanalytic Cold Ischemic Time on Protein Expression in Breast Cancer Tissues

PubMed Central

2012-01-01

Background Companion diagnostic tests can depend on accurate measurement of protein expression in tissues. Preanalytic variables, especially cold ischemic time (time from tissue removal to fixation in formalin) can affect the measurement and may cause false-negative results. We examined 23 proteins, including four commonly used breast cancer biomarker proteins, to quantify their sensitivity to cold ischemia in breast cancer tissues. Methods A series of 93 breast cancer specimens with known time-to-fixation represented in a tissue microarray and a second series of 25 matched pairs of core needle biopsies and breast cancer resections were used to evaluate changes in antigenicity as a function of cold ischemic time. Estrogen receptor (ER), progesterone receptor (PgR), HER2 or Ki67, and 19 other antigens were tested. Each antigen was measured using the AQUA method of quantitative immunofluorescence on at least one series. All statistical tests were two-sided. Results We found no evidence for loss of antigenicity with time-to-fixation for ER, PgR, HER2, or Ki67 in a 4-hour time window. However, with a bootstrapping analysis, we observed a trend toward loss for ER and PgR, a statistically significant loss of antigenicity for phosphorylated tyrosine (P = .0048), and trends toward loss for other proteins. There was evidence of increased antigenicity in acetylated lysine, AKAP13 (P = .009), and HIF1A (P = .046), which are proteins known to be expressed in conditions of hypoxia. The loss of antigenicity for phosphorylated tyrosine and increase in expression of AKAP13, and HIF1A were confirmed in the biopsy/resection series. Conclusions Key breast cancer biomarkers show no evidence of loss of antigenicity, although this dataset assesses the relatively short time beyond the 1-hour limit in recent guidelines. Other proteins show changes in antigenicity in both directions. Future studies that extend the time range and normalize for heterogeneity will provide more comprehensive information on preanalytic variation due to cold ischemic time. PMID:23090068

Association of Torsion With Testicular Cancer: A Retrospective Study.

PubMed

Uguz, Sami; Yilmaz, Sercan; Guragac, Ali; Topuz, Bahadır; Aydur, Emin

2016-02-01

Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported with the association of torsion in surgical specimens, and the published data remain scant on the association of torsion with testicular tumors. By retrospective medical record review, we identified 32 patients who had been diagnosed with testicular torsion, 20 of whom had undergone orchiectomy. Of these 20 patients, 2 were diagnosed with a malignancy. Our study, the largest case series to date, has shown an association between testicular torsion and testicular cancer of 6.4%. Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported in association with torsion in surgical specimens. However, the published data remain scant on the association between torsion and the presence of testicular tumors. The present retrospective study explored the association between torsion and testicular cancer in patients with testicular torsion undergoing orchiectomy during scrotal exploration. A medical record review was performed of patients who had had a diagnosis of testicular torsion from January 2003 to February 2015. The clinicopathologic characteristics of the patients were recorded. A total of 32 patients were identified. Their mean age was 21.1 years (range, 7-39 years). All the patients had unilateral testicular torsion, which affected the left side in 17 and the right side in 15. Manual detorsion was successful in 6 patients, and 26 patients underwent emergency surgery with testicular detorsion (6 fixation surgery and 20 orchiectomy). The type of incision was scrotal in 6, inguinal in 10, and unspecified in 4. Pathologic examination of the orchiectomy specimens showed malignancy in 2 cases (seminoma and malign mixed germ cell tumor). To the best of our knowledge, the present single-center case series is the largest case series to date of testicular torsion and showed an association between testicular torsion and testicular cancer of 6.4%. However, further larger series of the association between testicular torsion and cancer are needed to explore the relationship between testicular torsion and testicular cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Demographic Trends in the Republic of Zaire. Caltech Population Program Occasional Papers, Series 1, Number 5.

ERIC Educational Resources Information Center

Boute, Joseph

This paper, one in a series of occasional publications, discusses population growth and trends in the African Republic of Zaire. The series is intended to increase understanding of the interrelationships between population growth and socioeconomic and cultural patterns throughout the world, and to communicate this understanding to scholars and…

Index to the Understanding the Atom Series.

ERIC Educational Resources Information Center

Atomic Energy Commission, Oak Ridge, TN. Div. of Technical Information.

This index was prepared for the set of 51 booklets in the "Understanding the Atom Series" published by the U. S. Atomic Energy Commission for high school students and their teachers. In addition to the index, a complete list of the series is provided in which the booklets are grouped into the categories of physics, chemistry, biology, nuclear…

"It's not Just Camp!": Understanding the Meaning of Children's Cancer Camps for Children and Families.

PubMed

Laing, Catherine M; Moules, Nancy J

2016-01-01

The purpose of this philosophical hermeneutic inquiry was to understand the meaning of children's cancer camps for the child with cancer and the family. Six childhood cancer families and 5 cancer camp counselors were interviewed, in order to bring understanding to this topic. Findings from this research revealed that camp means different things for different families, and that much is at play in the cancer camp experience: the healing and developmental power of play, finding acceptance and fit, grief as something to live with versus "get over," storytelling as a means of reshaping and understanding traumatic experiences, and the solidarity of the community as one that creates intense, healing bonds. Children's cancer camps, we conclude, should be considered a necessity, versus a luxury, and could even be thought of as a psychosocial intervention for some children and families. Barriers such as structure of funding and access to resources are present and likely due to the separateness of camps from hospital programs. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

[Metastasis of breast cancer in gastointestinal tract - report of a case and review of the literature].

PubMed

Němeček, D; Levý, M; Rosová, B; Sečkařová, D; Simša, J

2012-06-01

Metastatic breast cancer affecting the gastrointestinal tract except from the liver is very rare, however, some case reports can be found in literature, autopsy series and several retrospective studies focusing on this issue. In our surgery department we have also documented a case report of metastatic breast cancer manifesting as an obstructive tumor of small intestine.

Nano-scale processes behind ion-beam cancer therapy

NASA Astrophysics Data System (ADS)

Surdutovich, Eugene; Garcia, Gustavo; Mason, Nigel; Solov'yov, Andrey V.

2016-04-01

This topical issue collates a series of papers based on new data reported at the third Nano-IBCT Conference of the COST Action MP1002: Nanoscale Insights into Ion Beam Cancer Therapy, held in Boppard, Germany, from October 27th to October 31st, 2014. The Nano-IBCT COST Action was launched in December 2010 and brought together more than 300 experts from different disciplines (physics, chemistry, biology) with specialists in radiation damage of biological matter from hadron-therapy centres, and medical institutions. This meeting followed the first and the second conferences of the Action held in October 2011 in Caen, France and in May 2013 in Sopot, Poland respectively. This conference series provided a focus for the European research community and has highlighted the pioneering research into the fundamental processes underpinning ion beam cancer therapy. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey V. Solov'yov, Nigel Mason, Gustavo Garcia and Eugene Surdutovich.

The Development of the Milwaukee Consortium for Hmong Health: Capacity Building Through Direct Community Engagement.

PubMed

Sparks, Shannon M; Vang, Pang C

2015-01-01

Hmong women experience increased incidence and mortality rates for cervical cancer, yet their cancer risk is often masked by their inclusion within the comparatively low-risk Asian American and Pacific Islander (AAPI) category. Key to this disparity is late stage at diagnosis, a consequence of low rates of screening. This article describes the establishment and community engagement efforts of the Milwaukee Consortium for Hmong Health, established in 2008 to build capacity to investigate and address barriers to screening and cancer care. The Consortium facilitated a series of three community dialogues to explore with community members effective ways to overcome barriers to accessing screening and cancer care. The community dialogues produced a series of six recommendations for action, detailed herein, supported and prioritized by the community. We posit that the integral involvement of the Hmong community from the outset promoted buy-in of ensuing Consortium education and outreach efforts, and helped to ensure fit with community perspectives, needs, and priorities.

Homeostasis 5: nurses as external agents of control in breast cancer.

PubMed

Clancy, John; McVicar, Andrew

Breast cancer is caused by a homeostatic imbalance of cell division. Healthcare practitioners need to understand cellular activities to appreciate the physiological basis of health (homeostasis), the pathophysiological basis of illness and the physiological rationale of healthcare. Cells are the 'basic unit of life' (Clancy and McVicar, 2011a). This article describes normal cell division and the anatomy and physiology of the breast and, using a case study, will show how breast cancer is a homeostatic imbalance of cell division. There are analogies between the components of homeostasis and the components of the nursing (healthcare) process (Clancy and McVicar, 2011b) in the condition of breast cancer. After reading this article, nurses should be able to: understand that breast cancer is a cellular hence chemical imbalance that causes uncontrollable mitotic division of breast cells; understand how the cell cycle of cancer cells differs from that of normal cells; identify nature-nurture interactions involved in the aetiology of breast cancer; understand that when caring for people with breast cancer, health professionals including oncology nurses are acting as external agents of homeostatic control as the patient 'recovers' from breast cancer, and also to some extent when reducing signs and symptoms, hence quality of life, by providing palliative care.

The contribution of molecular genetics to the understanding and management of cancer: potential future applications and implications for nurses.

PubMed

Bradley, A N

1999-06-01

Cancer is an immense medical problem and as a cause of mortality it is second only to cardiovascular disease. Much of the current understanding of cancer is owed to epidemiologists who have discovered a number of causative factors implicated in its development. These causative factors can be divided into genetic, chemical, physical, viral, radiation, immune and hormonal factors. Further advances in understanding have been made over the past decade from contributions made by the field of molecular biology. From investigation and examination of the molecular processes involved in the development of cancer it is becoming increasingly clear that changes in the genetic material of the cell nuclei are the final common pathway to cancer, whatever the initial aetiology. This article will attempt to elucidate the contribution of molecular genetics to the understanding of the likely mechanisms of carcinogenesis, the management of cancer, potential future applications and directions and the implications for nurses arising from this relatively new and evolving field of knowledge.

Overview of epidemiologic studies of radiation and cancer risk based on medical series

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howe, G.R.

1997-03-01

Epidemiologic studies of individuals exposed to ionizing radiation for medical reasons have made important contributions to understanding of the relationship between such radiation and subsequent cancer risk. In this paper the strengths and limitations of medical studies are considered and their future potential usefulness is discussed. Studies may be broadly classified into two types, namely, those of individuals exposed for therapeutic purposes such as the study of ankylosing spondylytics and those of individuals exposed for diagnostic or examination purposes such as those of tuberculosis patients routinely examined by chest fluoroscopy. In general, studies of therapeutic exposures tend to involve highmore » doses of radiation given at high dose rates and in a relatively small number of fractions, whereas studies of diagnostic exposures tend to involve relatively low doses, low dose rates and many fractions. However, these generalizations are not always true: for example, in the fluoroscopy studies some patients received doses to organs such as breast and lung which were substantially higher than those experienced in the atomic bomb survivors study and in a study of Israeli children treated with radiation for tinea capitis the average thyroid dose was reported to be low, and only about 0.09 gray. These studies illustrate one of the most important advantages of medical series, namely the variety of such studies in terms of the characteristics of the radiation involved (linear energy transfer characteristics, dose range, dose rate, and fractionation), the organs exposed and hence potentially at risk, and the characteristics of those exposed to such radiation.« less

Surgical management of oligometastatic non-small cell lung cancer.

PubMed

Novoa, Nuria M; Varela, Gonzalo; Jiménez, Marcelo F

2016-11-01

The oligometastatic stage IV non-small cell lung cancer (NSCLC) offers a new surgical opportunity. New reported data is showing that surgery can offer a reasonable benefit, in terms of long-term survival, to some patients. The advantages of surgical treatment rely on a more adequate patient selection and a better understanding of the biology of these tumors. Currently, mediastinal involvement of the primary tumor can be identified as the most important prognostic variable after curative-intent of synchronous or metachronous metastasis. It seems clear that the routine use of combined FDG-PET and CT will help to detect the more favorable cohort of oligometastatic patients. As expected, pathological T staging of the primary tumor and the completeness of its resection are also crucial factors influencing final results. The real benefit of the local treatment over synchronous or metachronous metastasis is controversial with series showing better outcomes for metachronous lesions than for synchronous and others offering equal results. Also non conclusive results appear when analyzing different sites of metastasis. Retrospective series tend to show different outcomes depending on the affected organ while usually no differences are found in prospective ones. Most of the current evidence is based on retrospective studies on patients collected along extended periods of time. That represents a great limitation to the knowledge on this topic. Some prospective analyses have added some insight, but still the quality of the evidence is too low to allow drawing robust conclusions. As frequently concluded, prospective well designed investigation is requested to ascertain the value of surgery in this specific population of patients with extended NSCLC.

Cancer cachexia: understanding the molecular basis.

PubMed

Argilés, Josep M; Busquets, Sílvia; Stemmler, Britta; López-Soriano, Francisco J

2014-11-01

Cancer cachexia is a devastating, multifactorial and often irreversible syndrome that affects around 50-80% of cancer patients, depending on the tumour type, and that leads to substantial weight loss, primarily from loss of skeletal muscle and body fat. Since cachexia may account for up to 20% of cancer deaths, understanding the underlying molecular mechanisms is essential. The occurrence of cachexia in cancer patients is dependent on the patient response to tumour progression, including the activation of the inflammatory response and energetic inefficiency involving the mitochondria. Interestingly, crosstalk between different cell types ultimately seems to result in muscle wasting. Some of the recent progress in understanding the molecular mechanisms of cachexia may lead to new therapeutic approaches.

Genetically engineered mouse models for epithelial ovarian cancer: are we there yet?

PubMed

Howell, Viive M

2014-03-01

The development of preclinical spontaneous genetically engineered mouse models (GEMMs) requires an understanding of the genetic basis of the human disease. Such robust models have proven invaluable for increasing understanding of human malignancies as well as identifying new biomarkers and testing new therapies for these diseases. While GEMMs have been reported for ovarian cancer, the majority have proven disappointing overall in their recapitulation of paired genetic and histological features especially for serous ovarian epithelial cancer. This review describes GEMMs for ovarian cancer, in particular, high grade serous ovarian cancer and assesses these in light of recent changes in our understanding of the human malignancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

PBOV1 Is a Human De Novo Gene with Tumor-Specific Expression That Is Associated with a Positive Clinical Outcome of Cancer

PubMed Central

Samusik, Nikolay; Krukovskaya, Larisa; Meln, Irina; Shilov, Evgeny; Kozlov, Andrey P.

2013-01-01

PBOV1 is a known human protein-coding gene with an uncharacterized function. We have previously found that PBOV1 lacks orthologs in non-primate genomes and is expressed in a wide range of tumor types. Here we report that PBOV1 protein-coding sequence is human-specific and has originated de novo in the primate evolution through a series of frame-shift and stop codon mutations. We profiled PBOV1 expression in multiple cancer and normal tissue samples and found that it was expressed in 19 out of 34 tumors of various origins but completely lacked expression in any of the normal adult or fetal human tissues. We found that, unlike the cancer/testis antigens that are typically controlled by CpG island-containing promoters, PBOV1 was expressed from a GC-poor TATA-containing promoter which was not influenced by CpG demethylation and was inactive in testis. Our analysis of public microarray data suggests that PBOV1 activation in tumors could be dependent on the Hedgehog signaling pathway. Despite the recent de novo origin and the lack of identifiable functional signatures, a missense SNP in the PBOV1 coding sequence has been previously associated with an increased risk of breast cancer. Using publicly available microarray datasets, we found that high levels of PBOV1 expression in breast cancer and glioma samples were significantly associated with a positive outcome of the cancer disease. We also found that PBOV1 was highly expressed in primary but not in recurrent high-grade gliomas, suggesting the presence of a negative selection against PBOV1-expressing cancer cells. Our findings could contribute to the understanding of the mechanisms behind de novo gene origin and the possible role of tumors in this process. PMID:23418531

Understanding coping with cancer: how can qualitative research help?

PubMed

Chittem, Mahati

2014-01-01

Research in psycho-oncology investigates the psycho-social and emotional aspects of cancer and how this is related to health, well-being and overall patient care. Coping with cancer is a prime focus for researchers owing to its impact on patients' psychological processing and life in general. Research so far has focused mainly on quantitative study designs such as questionnaires to examine the coping strategies used by cancer patients. However, in order to gain a rich and deep understanding of the reasons, processes and types of strategies that patients use to deal with cancer, qualitative study designs are necessary. Few studies have used qualitative designs such as semi-structured interviews to explore coping with cancer. The current paper aims to review the suitability and benefits of using qualitative research designs to understand coping with cancer with the help of some key literature in psycho-oncology research.

Cancer Theory from Systems Biology Point of View

NASA Astrophysics Data System (ADS)

Wang, Gaowei; Tang, Ying; Yuan, Ruoshi; Ao, Ping

In our previous work, we have proposed a novel cancer theory, endogenous network theory, to understand mechanism underlying cancer genesis and development. Recently, we apply this theory to hepatocellular carcinoma (HCC). A core endogenous network of hepatocyte was established by integrating the current understanding of hepatocyte at molecular level. Quantitative description of the endogenous network consisted of a set of stochastic differential equations which could generate many local attractors with obvious or non-obvious biological functions. By comparing with clinical observation and experimental data, the results showed that two robust attractors from the model reproduced the main known features of normal hepatocyte and cancerous hepatocyte respectively at both modular and molecular level. In light of our theory, the genesis and progression of cancer is viewed as transition from normal attractor to HCC attractor. A set of new insights on understanding cancer genesis and progression, and on strategies for cancer prevention, cure, and care were provided.

Hybrid analysis for indicating patients with breast cancer using temperature time series.

PubMed

Silva, Lincoln F; Santos, Alair Augusto S M D; Bravo, Renato S; Silva, Aristófanes C; Muchaluat-Saade, Débora C; Conci, Aura

2016-07-01

Breast cancer is the most common cancer among women worldwide. Diagnosis and treatment in early stages increase cure chances. The temperature of cancerous tissue is generally higher than that of healthy surrounding tissues, making thermography an option to be considered in screening strategies of this cancer type. This paper proposes a hybrid methodology for analyzing dynamic infrared thermography in order to indicate patients with risk of breast cancer, using unsupervised and supervised machine learning techniques, which characterizes the methodology as hybrid. The dynamic infrared thermography monitors or quantitatively measures temperature changes on the examined surface, after a thermal stress. In the dynamic infrared thermography execution, a sequence of breast thermograms is generated. In the proposed methodology, this sequence is processed and analyzed by several techniques. First, the region of the breasts is segmented and the thermograms of the sequence are registered. Then, temperature time series are built and the k-means algorithm is applied on these series using various values of k. Clustering formed by k-means algorithm, for each k value, is evaluated using clustering validation indices, generating values treated as features in the classification model construction step. A data mining tool was used to solve the combined algorithm selection and hyperparameter optimization (CASH) problem in classification tasks. Besides the classification algorithm recommended by the data mining tool, classifiers based on Bayesian networks, neural networks, decision rules and decision tree were executed on the data set used for evaluation. Test results support that the proposed analysis methodology is able to indicate patients with breast cancer. Among 39 tested classification algorithms, K-Star and Bayes Net presented 100% classification accuracy. Furthermore, among the Bayes Net, multi-layer perceptron, decision table and random forest classification algorithms, an average accuracy of 95.38% was obtained. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inferring the 1985-2014 impact of mobile phone use on selected brain cancer subtypes using Bayesian structural time series and synthetic controls.

PubMed

de Vocht, Frank

2016-12-01

Mobile phone use has been increasing rapidly in the past decades and, in parallel, so has the annual incidence of certain types of brain cancers. However, it remains unclear whether this correlation is coincidental or whether use of mobile phones may cause the development, promotion or progression of specific cancers. The 1985-2014 incidence of selected brain cancer subtypes in England were analyzed and compared to counterfactual 'synthetic control' timeseries. Annual 1985-2014 incidence of malignant glioma, glioblastoma multiforme, and malignant neoplasms of the temporal and parietal lobes in England were modelled based on population-level covariates using Bayesian structural time series models assuming 5,10 and 15year minimal latency periods. Post-latency counterfactual 'synthetic England' timeseries were nowcast based on covariate trends. The impact of mobile phone use was inferred from differences between measured and modelled time series. There is no evidence of an increase in malignant glioma, glioblastoma multiforme, or malignant neoplasms of the parietal lobe not predicted in the 'synthetic England' time series. Malignant neoplasms of the temporal lobe however, have increased faster than expected. A latency period of 10years reflected the earliest latency period when this was measurable and related to mobile phone penetration rates, and indicated an additional increase of 35% (95% Credible Interval 9%:59%) during 2005-2014; corresponding to an additional 188 (95%CI 48-324) cases annually. A causal factor, of which mobile phone use (and possibly other wireless equipment) is in agreement with the hypothesized temporal association, is related to an increased risk of developing malignant neoplasms in the temporal lobe. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

Understanding stigma as a barrier to accessing cancer treatment in South Africa: implications for public health campaigns

PubMed Central

Blasco, Drew; He, Emily; Huang, Debbie; Schear, Rebekkah; McGoldrick, Devon; Link, Bruce; Yang, Lawrence Hsin

2018-01-01

Introduction Cancer contributes to significant illness burden in South Africa, with delayed diagnosis resulting from limited knowledge of cancer, lack of biomedical treatment and stigma. This study examines ways in which people are identified as having cancer through perspectives of traditional healing or the biomedical model. Additionally, we sought to understand the stigma associated with cancer, including stereotypes, anticipated discrimination and coping styles. Methods Livestrong Foundation conducted 11 semi-structured focus groups with key community stakeholders in three South African townships. Interviews examined the negative consequences of being labeled with a cancer diagnosis as well as causes of, possible prevention of and barriers and methods to improve access to cancer treatment. Analyses were completed using directed content analysis. Results Revealed three main labeling mechanisms: physical appearance of perceived signs/symptoms of cancer, diagnosis by a traditional healer, or a biomedical diagnosis by a Western physician. Being labeled led to anticipated discrimination in response to prevalent cancer stereotypes. This contributed to delayed treatment, use of traditional healers instead of biomedical treatment and secrecy of symptoms and/or diagnosis. Further, perceptions of cancer were commonly conflated with HIV/TB owing to prior educational campaigns. Conclusion Our study deepens the understanding of the cancer labeling process in South Africa and the resulting negative effects of stigma. Future anti-stigma interventions should partner with traditional healers due to their respected community status and consider how previous health interventions may significantly impact current understandings of illness. PMID:29875954

Nuclear autophagy: An evolutionarily conserved mechanism of nuclear degradation in the cytoplasm.

PubMed

Luo, Majing; Zhao, Xueya; Song, Ying; Cheng, Hanhua; Zhou, Rongjia

2016-11-01

Macroautophagy/autophagy is a catabolic process that is essential for cellular homeostasis. Studies on autophagic degradation of cytoplasmic components have generated interest in nuclear autophagy. Although its mechanisms and roles have remained elusive, tremendous progress has been made toward understanding nuclear autophagy. Nuclear autophagy is evolutionarily conserved in eukaryotes that may target various nuclear components through a series of processes, including nuclear sensing, nuclear export, autophagic substrate encapsulation and autophagic degradation in the cytoplasm. However, the molecular processes and regulatory mechanisms involved in nuclear autophagy remain largely unknown. Numerous studies have highlighted the importance of nuclear autophagy in physiological and pathological processes such as cancer. This review focuses on current advances in nuclear autophagy and provides a summary of its research history and landmark discoveries to offer new perspectives.

Discursive constructions of youth cancer: findings from creative methods research with healthy young people.

PubMed

Mooney-Somers, Julie; Lewis, Peter; Kerridge, Ian

2016-06-01

As part of work to understand the experiences of young people who had cancer, we were keen to examine the perspectives of peers who share their social worlds. Our study aimed to examine how cancer in young people, young people with cancer and young cancer survivors are represented through language, metaphor and performance. We generated data using creative activities and focus group discussions with three high school drama classes and used Foucauldian discourse analysis to identify the discursive constructions of youth cancer. Our analysis identified two prevailing discursive constructions: youth cancer as an inevitable decline towards death and as overwhelming personhood by reducing the young person with cancer to 'cancer victim'. If we are to understand life after cancer treatment and how to support young people who have been treated for cancer, we need a sophisticated understanding of the social contexts they return to. Discourses shape the way young people talk and think about youth cancer; cancer as an inevitable decline towards death and as overwhelming personhood is a key discursive construction that young people draw on when a friend discloses cancer. The way cancer is constructed shapes how friends react to and relate to a young person with cancer. These constructions are likely to shape challenging social dynamics, such as bullying, that many young cancer survivors experience. Awareness of these discursive constructions can better equip young cancer survivors, their family and health professionals negotiate life after cancer.

Prognostic Relevance of Urinary Bladder Cancer Susceptibility Loci

PubMed Central

Grotenhuis, Anne J.; Dudek, Aleksandra M.; Verhaegh, Gerald W.; Witjes, J. Alfred; Aben, Katja K.; van der Marel, Saskia L.; Vermeulen, Sita H.; Kiemeney, Lambertus A.

2014-01-01

In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive evaluation of the prognostic relevance of all confirmed UBC susceptibility loci. Detailed clinical data concerning diagnosis, stage, treatment, and disease course of a population-based series of 1,602 UBC patients were collected retrospectively based on a medical file survey. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed, and log-rank tests calculated, to evaluate the association between 12 confirmed UBC susceptibility variants and recurrence and progression in non-muscle invasive bladder cancer (NMIBC) patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients, association of these variants with overall survival was tested. Subgroup analyses by tumor aggressiveness and smoking status were performed in NMIBC patients. In the overall NMIBC group (n = 1,269), a statistically significant association between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR = 1.08 (95% CI: 0.76–1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23–2.66), P for trend = 2.6×10−3). In subgroup analyses, several other variants showed suggestive, though non-significant, prognostic relevance for recurrence and progression in NMIBC and survival in MIBC. This study provides suggestive evidence that genetic loci involved in UBC etiology may influence disease prognosis. Elucidation of the causal variant(s) could further our understanding of the mechanism of disease, could point to new therapeutic targets, and might aid in improvement of prognostic tools. PMID:24586564

Introduction to the Special Series.

ERIC Educational Resources Information Center

Peterson, Lizette

1986-01-01

Presents a special series of seven articles dealing with biopsychosocial oncology, the role of psychology in cancer treatment. Includes an introduction by Lizette Peterson and articles by Thomas Burish and Michael Carey, Susan Jay et al., Shelley Taylor et al., David Cella and Susan Tross, Gerald Koocher, and Leonard Derogatis. (KS)

Young people's beliefs about the risk of bowel cancer and its link with physical activity.

PubMed

Newby, Katie V; Cook, Chloe; Meisel, Susanne F; Webb, Thomas L; Fisher, Bernadette; Fisher, Abi

2017-09-01

The primary objective was to explore young people's risk appraisals of bowel cancer, including whether they had a coherent understanding of the protective effects of physical activity (PA). A secondary objective was to examine whether the illness risk representations (IRRs) framework could be used to understand beliefs underlying bowel cancer risk appraisals. Qualitative. Framework analysis of semi-structured interviews with 19 people aged 14-17 years. Participants judged their risk of getting bowel cancer as low. This was based on a lack of family history of cancer and their current lifestyle behaviours, which were viewed as having a protective effect, or because they planned on making change to their lifestyle in the future when disease risk became more relevant. Participants were not aware of, and struggled to understand, the link between PA and bowel cancer. They also lacked knowledge of the effects of, or treatments for, bowel cancer. Beliefs underlying judgements about the risk of bowel cancer fitted the IRR framework reasonably well. The present research suggests that interventions designed to increase PA with a view to reducing the risk of bowel cancer should aim to make the future risk of bowel cancer feel more tangible, help young people to understand the full range of consequences, explain how and why preventative behaviours such as PA are effective in reducing risk, and emphasize that the typical late presentation of symptoms, and therefore investigation by health care services, reduces treatability. Statement of contribution What is already known on this subject? Physical activity (PA) performed throughout the lifespan can have a protective effect on bowel cancer, but levels of PA are low among young people. Changing beliefs about the risk of getting bowel cancer may be a useful strategy in motivating PA. What does this study add? Increased understanding of how young people think about bowel cancer and the relationship between PA and cancer. Identification of strategies for increasing young adults' appraisals of the likelihood and severity of bowel cancer. Evidence to support the validity of illness risk representations framework. © 2017 The British Psychological Society.

"It's because it's cancer, not because you're a Traveller"-exploring lay understanding of cancer in English Romany Gypsy and Irish Traveller communities.

PubMed

Berlin, Jenni; Smith, David; Newton, Paul

2018-06-01

The lay understanding of cancer among English Romany Gypsies and Irish Travellers, has not been studied in depth before. Lay understandings of cancer, and illness in general, varies between different ethnic groups suggesting that procedures that work for one community may not work for another. Therefore, the measures that are in place in the UK to educate and treat people with cancer may not work for the - often hard to reach - Gypsy and Traveller communities. This study explores Gypsies and Travellers lay perceptions of cancer. In collaboration with community interviewers, 18 Gypsies and Travellers were recruited to take part in this study. Data comes from four semi-structured focus groups that were transcribed and thematically analysed using data-driven coding. A lack of trust of the wider society has contributed to some Gypsies and Travellers' health related practices as has the persistence of old customs that negatively influence their health. As a reticence towards seeking outside help often exists, information about cancer is sought from family members. When engaged with cancer services however, Gypsies and Travellers generally feel them to be non-discriminative. Health professionals need to develop a better understanding of Gypsy and Travellers' health beliefs and practices in order to successfully interact with them. Information about cancer has to be delivered in an understandable form and to places where it reaches these communities. Because of historical societal discrimination, including by some health services, engaging with Gypsies and Travellers may require considerably more time and effort. Copyright © 2018 Elsevier Ltd. All rights reserved.

Validation of a contemporary prostate cancer grading system using prostate cancer death as outcome.

PubMed

Berney, Daniel M; Beltran, Luis; Fisher, Gabrielle; North, Bernard V; Greenberg, David; Møller, Henrik; Soosay, Geraldine; Scardino, Peter; Cuzick, Jack

2016-05-10

Gleason scoring (GS) has major deficiencies and a novel system of five grade groups (GS⩽6; 3+4; 4+3; 8; ⩾9) has been recently agreed and included in the WHO 2016 classification. Although verified in radical prostatectomies using PSA relapse for outcome, it has not been validated using prostate cancer death as an outcome in biopsy series. There is debate whether an 'overall' or 'worst' GS in biopsies series should be used. Nine hundred and eighty-eight prostate cancer biopsy cases were identified between 1990 and 2003, and treated conservatively. Diagnosis and grade was assigned to each core as well as an overall grade. Follow-up for prostate cancer death was until 31 December 2012. A log-rank test assessed univariable differences between the five grade groups based on overall and worst grade seen, and using univariable and multivariable Cox proportional hazards. Regression was used to quantify differences in outcome. Using both 'worst' and 'overall' GS yielded highly significant results on univariate and multivariate analysis with overall GS slightly but insignificantly outperforming worst GS. There was a strong correlation with the five grade groups and prostate cancer death. This is the largest conservatively treated prostate cancer cohort with long-term follow-up and contemporary assessment of grade. It validates the formation of five grade groups and suggests that the 'worst' grade is a valid prognostic measure.

A Training Program in Breast Cancer Research Using NMR Techniques

DTIC Science & Technology

2002-07-01

Howard University Cancer Center. The trainees have continued to learn the theory and instrumentation of nuclear magnetic resonance imaging and spectroscopy. The trainees have rotated through the mammography service in the Department of Radiology in the hospital to learn the mammography procedures. Besides attending the weekly seminars in the Cancer Center, the trainees also have attended a special seminar series on the breast imaging sponsored by this grant and

Acromegaly is associated with increased cancer risk: a survey in Italy.

PubMed

Terzolo, Massimo; Reimondo, Giuseppe; Berchialla, Paola; Ferrante, Emanuele; Malchiodi, Elena; De Marinis, Laura; Pivonello, Rosario; Grottoli, Silvia; Losa, Marco; Cannavo, Salvatore; Ferone, Diego; Montini, Marcella; Bondanelli, Marta; De Menis, Ernesto; Martini, Chiara; Puxeddu, Efisio; Velardo, Antonino; Peri, Alessandro; Faustini-Fustini, Marco; Tita, Patrizia; Pigliaru, Francesca; Peraga, Giulia; Borretta, Giorgio; Scaroni, Carla; Bazzoni, Nicoletta; Bianchi, Antonio; Berton, Alessandro; Serban, Andreea Liliana; Baldelli, Roberto; Fatti, Letizia Maria; Colao, Annamaria; Arosio, Maura

2017-09-01

It is debated if acromegalic patients have an increased risk to develop malignancies. The aim of the present study was to assess the standardized incidence ratios (SIRs) of different types of cancer in acromegaly on a large series of acromegalic patients managed in the somatostatin analogs era. It was evaluated the incidence of cancer in an Italian nationwide multicenter cohort study of 1512 acromegalic patients, 624 men and 888 women, mean age at diagnosis 45 ± 13 years, followed up for a mean of 10 years (12573 person-years) in respect to the general Italian population. Cancer was diagnosed in 124 patients, 72 women and 52 men. The SIRs for all cancers was significantly increased compared to the general Italian population (expected: 88, SIR 1.41; 95% CI, 1.18-1.68, P  < 0.001). In the whole series, we found a significantly increased incidence of colorectal cancer (SIR 1.67; 95% CI, 1.07-2.58, P  = 0.022), kidney cancer (SIR 2.87; 95% CI, 1.55-5.34, P  < 0.001) and thyroid cancer (SIR 3.99; 95% CI, 2.32-6.87, P  < 0.001). The exclusion of 11 cancers occurring before diagnosis of acromegaly (all in women) did not change remarkably the study outcome. In multivariate analysis, the factors significantly associated with an increased risk of malignancy were age and family history of cancer, with a non-significant trend for the estimated duration of acromegaly before diagnosis. In conclusion, we found evidence that acromegaly in Italy is associated with a moderate increase in cancer risk. © 2017 Society for Endocrinology.

Colorectal cancer trends in Kerman province, the largest province in Iran, with forecasting until 2016.

PubMed

Roya, Nikbakht; Abbas, Bahrampour

2013-01-01

Colorectal cancer is one of the most common cancers. The aim of this study is determination its trends in Kerman province and individual cities separately until year 2016. This analytical and modeling study was based of cancer registry data of Kerman University of Medical Sciences, collected during 2001-2010. Among 20,351 cancer case, 792 were colorectal cancer cases in age group 18-93 years with a mean of 59.4 and standard deviation of 15.1. By applying time series and data trends, incidences were predicted until 2016 for the province and each city, with adjustment for population size. In colorectal cases, 413 (52%) were male, and 379 (48%) were female. The annual increasing rate in Kerman province overall was and can be expected to be 6%, and in the cities of the province Rafsanjan, Bardsir, Bam, Kerman, Baft, Sirjan, Jiroft, Kahnuj and Manujan had an increasing range from 5 to 14% by the year 2016. But in Ravar, Zarand and Shahrbabak reduction in rates of at least 2% could be predicted. The time series showed that the trend of colorectal cancer in female will increase 15% and in male 7% by year 2016. Given the trend of this cancer is increasing so that resources will be consumed in the treatment of the patients, efforts shoudlbe focused on prevention and early diagnosis of the disease. Screening could have an important role leading to improved survival.

Control of Disease Recurrence by Tumor-Infiltrating T Cells in Ovarian Cancer

DTIC Science & Technology

2010-03-01

effective for established tumors. alf a century later, a series of definitive experiments by Prehn and ain [3] showed that inoculation with tumor, but...Third Scientific Report on the Investigations of the Imperial Cancer Research Fund. London: Taylor and Fran- cis; 1908. [3] Prehn RT,Main JM

NCI International EBV-Gastric Cancer Consortium

Cancer.gov

A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

Discovery of tumor-specific irreversible inhibitors of stearoyl CoA desaturase | Office of Cancer Genomics

Cancer.gov

A hallmark of targeted cancer therapies is selective toxicity among cancer cell lines. We evaluated results from a viability screen of over 200,000 small molecules to identify two chemical series, oxalamides and benzothiazoles, that were selectively toxic at low nanomolar concentrations to the same 4 of 12 human lung cancer cell lines. Sensitive cell lines expressed cytochrome P450 (CYP) 4F11, which metabolized the compounds into irreversible inhibitors of stearoyl CoA desaturase (SCD). SCD is recognized as a promising biological target in cancer and metabolic disease.

Roles of stromal microenvironment in colon cancer progression.

PubMed

Taketo, Makoto Mark

2012-05-01

Although our understanding of epithelial cancer cells has advanced significantly, our understanding of the cancer microenvironment is still fragmentary. In contrast to our intuitive impression that our body always suppresses cancer growth, recent pieces of evidence show that cancer often exploits our body reactions to expand, invade local tissues and metastasize to distant organs. Accordingly, investigations of such body reactions in the tumour microenvironment should help us to design novel therapeutic strategies that can be combined with the traditional therapeutics targeted at the cancer cells themselves. In this article, I am going to review our recent efforts in search of novel therapeutic strategies against colon cancer using mouse models.

Observing Clonal Dynamics across Spatiotemporal Axes: A Prelude to Quantitative Fitness Models for Cancer.

PubMed

McPherson, Andrew W; Chan, Fong Chun; Shah, Sohrab P

2018-02-01

The ability to accurately model evolutionary dynamics in cancer would allow for prediction of progression and response to therapy. As a prelude to quantitative understanding of evolutionary dynamics, researchers must gather observations of in vivo tumor evolution. High-throughput genome sequencing now provides the means to profile the mutational content of evolving tumor clones from patient biopsies. Together with the development of models of tumor evolution, reconstructing evolutionary histories of individual tumors generates hypotheses about the dynamics of evolution that produced the observed clones. In this review, we provide a brief overview of the concepts involved in predicting evolutionary histories, and provide a workflow based on bulk and targeted-genome sequencing. We then describe the application of this workflow to time series data obtained for transformed and progressed follicular lymphomas (FL), and contrast the observed evolutionary dynamics between these two subtypes. We next describe results from a spatial sampling study of high-grade serous (HGS) ovarian cancer, propose mechanisms of disease spread based on the observed clonal mixtures, and provide examples of diversification through subclonal acquisition of driver mutations and convergent evolution. Finally, we state implications of the techniques discussed in this review as a necessary but insufficient step on the path to predictive modelling of disease dynamics. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

Co-Expression of Putative Cancer Stem Cell Markers CD44 and CD133 in Prostate Carcinomas.

PubMed

Kalantari, Elham; Asgari, Mojgan; Nikpanah, Seyedehmoozhan; Salarieh, Naghme; Asadi Lari, Mohammad Hossein; Madjd, Zahra

2017-10-01

Cancer stem cells (CSCs) are the main players of prostate tumorigenesis thus; characterization of CSCs can pave the way for understanding the early detection, drug resistance, metastasis and relapse. The current study was conducted to evaluate the expression level and clinical significance of the potential CSC markers CD44 and CD133 in a series of prostate tissues. One hundred and forty eight prostate tissues composed of prostate cancer (PCa), high-grade prostatic intraepithelial neoplasia (HGPIN), and benign prostate hyperplasia (BPH) were immunostained for the putative CSC markers CD44 and CD133. Subsequently, the correlation between the expression of these markers and the clinicopathological variables was examined. A higher level of CD44 expression was observed in 42% of PCa, 57% of HGPIN, and 42% BPH tissues. In the case of CD133 expression PCa, HGPIN, and BPH samples demonstrated high immunoreactivity in 46%, 43%, and 42% of cells, respectively. Statistical analysis showed an inverse significant correlation between CD44 expression with Gleason score of PCa (P = 0.02), while no significant correlation was observed between CD133 expression and clinicopathological parameters. A significant reciprocal correlation was observed between the expression of two putative CSC markers CD44 and CD133 in PCa specimens while not indicating clinical significance. Further clinical investigation is required to consider these markers as targets of new therapeutic strategies for PCa.

Biological Response of Cancer and Normal Cells on Irradiation from Electrons with Energies up to 200 keV.

NASA Astrophysics Data System (ADS)

Prilepskiy, Yuriy

2007-03-01

This paper presents continuation data of the series of experiments with the electron gun of the CEBAF machine at Jefferson Lab (Newport News, VA), which is capable of delivering electrons with energies up to 200 keV. This 1.5 GHz beam permits to generate cellular damage within minutes. We have performed irradiation of cancer and normal cells with different electron energies and currents to investigate cell biological responses. The biological response is measured through proteomics analysis before and after irradiation. The living cells are encased in special air containers allowing proper positioning in vacuum where the electrons are present. The containers receive the irradiation from the mono energetic electrons with energy up to 120 keV, resulting in an irradiation from both electrons and a small number of photons from the original beam passing through the thin container window. This window allows approximately half of the beam to come through. The study will permit to address the physical processes involved in the RBE and LET at a level that supersedes current data listed in the literature. We will discuss the experimental setup and the second stage of data collected with the new more developed system. This research is part of a global program to provide detailed information for the understanding of radiation based cancer treatments.

A cancer center's approach to engaging African American men about cancer: the men's fellowship breakfast, Southeastern Michigan, 2008-2014.

PubMed

Langford, Aisha T; Griffith, Derek M; Beasley, Derrick D; Braxton, Effat Id-Deen

2014-09-25

Despite disproportionate rates of cancer morbidity and mortality among African American men, few community-based efforts have been developed and sustained to educate African American men about cancer. The University of Michigan Comprehensive Cancer Center implemented a series of breakfasts to improve cancer awareness, screening, and education among African American men. This article describes the rationale for and history of the community intervention. The 21 breakfasts were held from 2008 through mid-2014 in Ypsilanti and Ann Arbor, Michigan. Ypsilanti ranks below Michigan and the nation on most socioeconomic indicators, although most residents are high school graduates (88% in Ypsilanti and 96.5% in Ann Arbor). African American men in Ypsilanti have higher death rates for diseases associated with poor diet and inadequate physical activity compared with Ypsilanti whites and general populations in Michigan and the nation. We conducted a multicomponent qualitative process evaluation including staff meetings, conversations with participants, and focus groups. We collected 425 post-event surveys to evaluate the breakfasts quantitatively. Participants were African American (85%), were aged 51 to 70 years (54%), had health insurance (89%), and had some college education (38%). Fifty-three percent of participants reported interest in the breakfast topics including nutrition; 46%, prostate cancer; 34%, colorectal cancer, and 32%, pain management; 62% reported willingness to participate in a clinical trial. African American men are interested in learning about health and are willing to attend a health-focused breakfast series. The Men's Fellowship Breakfast is a promising strategy for bringing men together to discuss cancer screening and risk reduction.

Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer

PubMed Central

Selinski, Silvia; Blaszkewicz, Meinolf; Ickstadt, Katja; Gerullis, Holger; Otto, Thomas; Roth, Emanuel; Volkert, Frank; Ovsiannikov, Daniel; Moormann, Oliver; Banfi, Gergely; Nyirady, Peter; Vermeulen, Sita H; Garcia-Closas, Montserrat; Figueroa, Jonine D; Johnson, Alison; Karagas, Margaret R; Kogevinas, Manolis; Malats, Nuria; Schwenn, Molly; Silverman, Debra T; Koutros, Stella; Rothman, Nathaniel; Kiemeney, Lambertus A; Hengstler, Jan G; Golka, Klaus

2017-01-01

Abstract Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case–control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case–control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93–3.47; P = 1.87 × 10−10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10–2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers. PMID:29028944

A pilot study on understanding the journey of advanced prostate cancer patients.

PubMed

Wagholikar, Amol; Fung, Maggie; Nelson, Colleen

2011-01-01

To understand the journey of advanced prostate cancer patients for supporting development of an innovative patient journey browser. Prostate cancer is one of the common cancers in Australia. Due to the chronic nature of the disease, it is important to have effective disease management strategy and care model. Multi-disciplinary care is a well-proven approach for chronic disease management. The Multi-disciplinary team (MDT) can function more effectively if all the required information is available for the clinical decision support. The development of innovative technology relies on an accurate understanding of the advanced prostate cancer patient's journey over a prolonged period. This need arises from the fact that advanced prostate cancer patients may follow various treatment paths and change their care providers. As a result of this, it is difficult to understand the actual sources of patient's clinical records and their treatment patterns. The aim of the research is to understand variable sources of clinical records, treatment patterns, alternative therapies, over the counter (OTC) medications of advanced prostate cancer patients. This study provides better and holistic understanding of advanced prostate cancer journey. The study was conducted through an on-line survey developed to seek and analyse the responses from the participants. The on-line questionnaire was carefully developed through consultations with the clinical researchers at the Australian Prostate Cancer Research Centre-Queensland, prostate cancer support group representatives and health informaticians at the Australian E-Health Research Centre. The non-identifying questionnaire was distributed to the patients through prostate cancer support groups in Queensland, Australia. The pilot study was carried out between August 2010 and December 2010. The research made important observations about the advanced prostate cancer journey. It showed that General Practitioner (GP) was the common source of patient's clinical records (41%) followed by Urologist (14%) and other clinicians (14%). The data analysis also showed that selenium was the common complementary supplement (55%) used by the patients and about 48% patients did not use any OTC drugs. The most common OTC used by the patients was Paracetamol (about 45%). The results have provided a foundation to the architecture of the proposed technology solution. The outcomes of this study are incorporated in design of the proposed patient journey browser system. A basic version of the system is currently being used at the advanced prostate cancer MDT meetings.

Quinazoline clubbed 1,3,5-triazine derivatives as VEGFR2 kinase inhibitors: design, synthesis, docking, in vitro cytotoxicity and in ovo antiangiogenic activity.

PubMed

Pathak, Prateek; Shukla, Parjanya Kumar; Kumar, Vikas; Kumar, Ankit; Verma, Amita

2018-04-16

A series of quinazoline clubbed 1,3,5-triazine derivatives (QCT) were synthesized and evaluated for their in vitro anticancer activity against HeLa (human cervical cancer), MCF-7 (human breast cancer cell), HL-60 (human promyelocytic leukemia cell), HepG2 (human Hepatocellular carcinoma cell), and one normal cell line HFF (human foreskin fibroblasts). In vitro assay result encouraged to further move towards in ovo anticancer evaluation using chick embryo. The series of QCT derivatives showed higher anticancer and antiangiogenic activity against HeLa and MCF-7 cell lines. In the series, synthetic molecule 8d, 8l, and 8m displayed significant activity. Further, these results substantiated by docking study on VGFR2. SAR study concluded that the potency of drugs depends on the nature of aliphatic substitution and the heterocyclic ring system.

Implementation and spread of interventions into the multilevel context of routine practice and policy: implications for the cancer care continuum.

PubMed

Yano, Elizabeth M; Green, Lawrence W; Glanz, Karen; Ayanian, John Z; Mittman, Brian S; Chollette, Veronica; Rubenstein, Lisa V

2012-05-01

The promise of widespread implementation of efficacious interventions across the cancer continuum into routine practice and policy has yet to be realized. Multilevel influences, such as communities and families surrounding patients or health-care policies and organizations surrounding provider teams, may determine whether effective interventions are successfully implemented. Greater recognition of the importance of these influences in advancing (or hindering) the impact of single-level interventions has motivated the design and testing of multilevel interventions designed to address them. However, implementing research evidence from single- or multilevel interventions into sustainable routine practice and policy presents substantive challenges. Furthermore, relatively few multilevel interventions have been conducted along the cancer care continuum, and fewer still have been implemented, disseminated, or sustained in practice. The purpose of this chapter is, therefore, to illustrate and examine the concepts underlying the implementation and spread of multilevel interventions into routine practice and policy. We accomplish this goal by using a series of cancer and noncancer examples that have been successfully implemented and, in some cases, spread widely. Key concepts across these examples include the importance of phased implementation, recognizing the need for pilot testing, explicit engagement of key stakeholders within and between each intervention level; visible and consistent leadership and organizational support, including financial and human resources; better understanding of the policy context, fiscal climate, and incentives underlying implementation; explication of handoffs from researchers to accountable individuals within and across levels; ample integration of multilevel theories guiding implementation and evaluation; and strategies for long-term monitoring and sustainability.

Implementation and Spread of Interventions Into the Multilevel Context of Routine Practice and Policy: Implications for the Cancer Care Continuum

PubMed Central

Green, Lawrence W.; Glanz, Karen; Ayanian, John Z.; Mittman, Brian S.; Chollette, Veronica; Rubenstein, Lisa V.

2012-01-01

The promise of widespread implementation of efficacious interventions across the cancer continuum into routine practice and policy has yet to be realized. Multilevel influences, such as communities and families surrounding patients or health-care policies and organizations surrounding provider teams, may determine whether effective interventions are successfully implemented. Greater recognition of the importance of these influences in advancing (or hindering) the impact of single-level interventions has motivated the design and testing of multilevel interventions designed to address them. However, implementing research evidence from single- or multilevel interventions into sustainable routine practice and policy presents substantive challenges. Furthermore, relatively few multilevel interventions have been conducted along the cancer care continuum, and fewer still have been implemented, disseminated, or sustained in practice. The purpose of this chapter is, therefore, to illustrate and examine the concepts underlying the implementation and spread of multilevel interventions into routine practice and policy. We accomplish this goal by using a series of cancer and noncancer examples that have been successfully implemented and, in some cases, spread widely. Key concepts across these examples include the importance of phased implementation, recognizing the need for pilot testing, explicit engagement of key stakeholders within and between each intervention level; visible and consistent leadership and organizational support, including financial and human resources; better understanding of the policy context, fiscal climate, and incentives underlying implementation; explication of handoffs from researchers to accountable individuals within and across levels; ample integration of multilevel theories guiding implementation and evaluation; and strategies for long-term monitoring and sustainability. PMID:22623601

Computational immune profiling in lung adenocarcinoma reveals reproducible prognostic associations with implications for immunotherapy

PubMed Central

Varn, Frederick S.; Tafe, Laura J.; Amos, Christopher I.; Cheng, Chao

2018-01-01

ABSTRACT Non-small cell lung cancer is one of the leading causes of cancer-related death in the world. Lung adenocarcinoma, the most common type of non-small cell lung cancer, has been well characterized as having a dense lymphocytic infiltrate, suggesting that the immune system plays an active role in shaping this cancer's growth and development. Despite these findings, our understanding of how this infiltrate affects patient prognosis and its association with lung adenocarcinoma-specific clinical factors remains limited. To address these questions, we inferred the infiltration level of six distinct immune cell types from a series of four lung adenocarcinoma gene expression datasets. We found that naive B cell, CD8+ T cell, and myeloid cell-derived expression signals of immune infiltration were significantly predictive of patient survival in multiple independent datasets, with B cell and CD8+ T cell infiltration associated with prolonged prognosis and myeloid cell infiltration associated with shorter survival. These associations remained significant even after accounting for additional clinical variables. Patients stratified by smoking status exhibited decreased CD8+ T cell infiltration and altered prognostic associations, suggesting potential immunosuppressive mechanisms in smokers. Survival analyses accounting for immune checkpoint gene expression and cellular immune infiltrate indicated checkpoint protein-specific modulatory effects on CD8+ T cell and B cell function that may be associated with patient sensitivity to immunotherapy. Together, these analyses identified reproducible associations that can be used to better characterize the role of immune infiltration in lung adenocarcinoma and demonstrate the utility in using computational approaches to systematically characterize tissue-specific tumor-immune interactions. PMID:29872556

Radio frequency radiation-related cancer: assessing causation in the occupational/military setting.

PubMed

Peleg, Michael; Nativ, Or; Richter, Elihu D

2018-05-01

We reexamine whether radio frequency radiation (RFR) in the occupational and military settings is a human carcinogen. We extended an analysis of an already-reported case series of patients with cancer previously exposed to whole-body prolonged RFR, mainly from communication equipment and radar. We focused on hematolymphatic (HL) cancers. We used analysis by percentage frequency (PF) of a cancer type, which is the proportion of a specific cancer type relative to the total number of cancer cases. We also examined and analyzed the published data on three other cohort studies from similar military settings from different countries. The PF of HL cancers in the case series was very high, at 40% with only 23% expected for the series age and gender profile, confidence interval CI95%: 26-56%, p<0.01, 19 out of 47 patients had HL cancers. We also found high PF for multiple primaries. As for the three other cohort studies: In the Polish military sector, the PF of HL cancers was 36% in the exposed population as compared to 12% in the unexposed population, p<0.001. In a small group of employees exposed to RFR in Israeli defense industry, the PF of HL cancers was 60% versus 17% expected for the group age and gender profile, p<0.05. In Belgian radar battalions the HL PF was 8.3% versus 1.4% in the control battalions as shown in a causes of deaths study and HL cancer mortality rate ratio was 7.2 and statistically significant. Similar findings were reported on radio amateurs and Korean war technicians. Elevated risk ratios were previously reported in most of the above studies. The consistent association of RFR and highly elevated HL cancer risk in the four groups spread over three countries, operating different RFR equipment types and analyzed by different research protocols, suggests a cause-effect relationship between RFR and HL cancers in military/occupational settings. While complete measurements of RFR exposures were not available and rough exposure assessments from patients interviews and from partial exposure data were used instead, we have demonstrated increased HL cancers in occupational groups with relatively high RFR exposures. Our findings, combined with other studies, indicate that exposures incurred in the military settings evaluated here significantly increased the risk of HL cancers. Accordingly, the RFR military exposures in these occupations should be substantially reduced and further efforts should be undertaken to monitor and measure those exposures and to follow cohorts exposed to RFR for cancers and other health effects. Overall, the epidemiological studies on excess risk for HL and other cancers together with brain tumors in cellphone users and experimental studies on RFR and carcinogenicity make a coherent case for a cause-effect relationship and classifying RFR exposure as a human carcinogen (IARC group 1). Copyright © 2018 Elsevier Inc. All rights reserved.

Colloquia | Cancer Prevention Fellowship Program

Cancer.gov

The Cancer Prevention and Control Colloquia Series features current research findings from guest researchers from a variety of research disciplines. Topics cover current challenges and methods used by investigators to address gaps, advance the field of cancer prevention and control, and promote the application of successful strategies. When Usually twice a month on Tuesday from 11:00 am - noon between September and June. Where NCI's Shady Grove Campus, 9609 Medical Center Drive, Rockville, MD (conference room locations vary).

Contribution of vascular endothelial growth factor to the Nottingham prognostic index in node-negative breast cancer

PubMed Central

Coradini, D; Boracchi, P; Daidone, M Grazia; Pellizzaro, C; Miodini, P; Ammatuna, M; Tomasic, G; Biganzoli, E

2001-01-01

The prognostic contribution of intratumour VEGF, the most important factor in tumour-induced angiogenesis, to NPI was evaluated by using flexible modelling in a series of 226 N-primary breast cancer patients in which steroid receptors and cell proliferation were also accounted for. VEGF provided an additional prognostic contribution to NPI mainly within ER-poor tumours. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11556826

University of Texas MD Anderson Cancer Center: Phenotypic Examination of PIK3CA Allelic Series using In Vitro/In Vivo Sensor Platforms | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at the University of Texas MD Anderson Cancer Center utilized an established and operational MCF10A normal breast epithelial cell model to assess the ability of candidate driver aberrations to promote cell grow in anchorage-independent conditions (soft agar assay) and proliferate in the absence of insulin and epidermal growth factor (EGF).

Classification of biosensor time series using dynamic time warping: applications in screening cancer cells with characteristic biomarkers.

PubMed

Rai, Shesh N; Trainor, Patrick J; Khosravi, Farhad; Kloecker, Goetz; Panchapakesan, Balaji

2016-01-01

The development of biosensors that produce time series data will facilitate improvements in biomedical diagnostics and in personalized medicine. The time series produced by these devices often contains characteristic features arising from biochemical interactions between the sample and the sensor. To use such characteristic features for determining sample class, similarity-based classifiers can be utilized. However, the construction of such classifiers is complicated by the variability in the time domains of such series that renders the traditional distance metrics such as Euclidean distance ineffective in distinguishing between biological variance and time domain variance. The dynamic time warping (DTW) algorithm is a sequence alignment algorithm that can be used to align two or more series to facilitate quantifying similarity. In this article, we evaluated the performance of DTW distance-based similarity classifiers for classifying time series that mimics electrical signals produced by nanotube biosensors. Simulation studies demonstrated the positive performance of such classifiers in discriminating between time series containing characteristic features that are obscured by noise in the intensity and time domains. We then applied a DTW distance-based k -nearest neighbors classifier to distinguish the presence/absence of mesenchymal biomarker in cancer cells in buffy coats in a blinded test. Using a train-test approach, we find that the classifier had high sensitivity (90.9%) and specificity (81.8%) in differentiating between EpCAM-positive MCF7 cells spiked in buffy coats and those in plain buffy coats.

Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer

PubMed Central

Lin, Nancy U.; Kidd, John; Allen, Brian A.; Singh, Nanda; Wenstrup, Richard J.; Hartman, Anne-Renee; Winer, Eric P.; Garber, Judy E.

2016-01-01

Purpose Testing for germline mutations in BRCA1/2 is standard for select patients with breast cancer to guide clinical management. Next-generation sequencing (NGS) allows testing for mutations in additional breast cancer predisposition genes. The frequency of germline mutations detected by using NGS has been reported in patients with breast cancer who were referred for BRCA1/2 testing or with triple-negative breast cancer. We assessed the frequency and predictors of mutations in 25 cancer predisposition genes, including BRCA1/2, in a sequential series of patients with breast cancer at an academic institution to examine the utility of genetic testing in this population. Methods Patients with stages I to III breast cancer who were seen at a single cancer center between 2010 and 2012, and who agreed to participate in research DNA banking, were included (N = 488). Personal and family cancer histories were collected and germline DNA was sequenced with NGS to identify mutations. Results Deleterious mutations were identified in 10.7% of women, including 6.1% in BRCA1/2 (5.1% in non-Ashkenazi Jewish patients) and 4.6% in other breast/ovarian cancer predisposition genes including CHEK2 (n = 10), ATM (n = 4), BRIP1 (n = 4), and one each in PALB2, PTEN, NBN, RAD51C, RAD51D, MSH6, and PMS2. Whereas young age (P < .01), Ashkenazi Jewish ancestry (P < .01), triple-negative breast cancer (P = .01), and family history of breast/ovarian cancer (P = .01) predicted for BRCA1/2 mutations, no factors predicted for mutations in other breast cancer predisposition genes. Conclusion Among sequential patients with breast cancer, 10.7% were found to have a germline mutation in a gene that predisposes women to breast or ovarian cancer, using a panel of 25 predisposition genes. Factors that predict for BRCA1/2 mutations do not predict for mutations in other breast/ovarian cancer susceptibility genes when these genes are analyzed as a single group. Additional cohorts will be helpful to define individuals at higher risk of carrying mutations in genes other than BRCA1/2. PMID:26976419

Oral cancer. The importance of early diagnosis and treatment.

PubMed

Sciubba, J J

2001-01-01

Oral cancer is an important health issue. The WHO predicts a continuing worldwide increase in the number of patients with oral cancer, extending this trend well into the next several decades. In the US the projected number of new cases of oral and oropharyngeal cancer will exceed 31,000 per year. Mortality due to cancers in this region exceeds the annual death rate is the US caused by either cutaneous melanoma or cervical cancer. Significant agents involved in the etiology of oral cancer in Western countries include sunlight exposure, smoking and alcohol consumption. Use of the areca or betel nut in many cultures is a major etiological factor outside of the USA. Other etiologic factors associated with oral squamous cell carcinoma, but far less significant statistically, include syphilis and sideropenic dysphagia. Recently, strong evidence for an etiological relationship between human papilloma virus and a subset of head and neck cancers has been noted. It is generally accepted that most sporadic tumors are the result of a multi-step process of accumulated genetic alterations. These alterations affect epithelial cell behavior by way of loss of chromosomal heterozygosity which in turn leads to a series of events progressing to the ultimate stage of invasive squamous cell carcinoma. The corresponding genetic alterations are reflected in clinical and microscopic pathology from hyperplasia through invasiveness. A wide range of mucosal alternations fall within the rubric of leukoplakia. Proliferative verrucous leukoplakia represents a relatively new type of leukoplakia that is separate from the more common or less innocuous form of this condition. Erythroplakia is particularly relevant considering its almost certain relationship with dysplasia or invasive carcinoma. Squamous cell carcinoma will develop from antecedent dysplastic oral mucosal lesions if an early diagnosis has not been made and treatment given. Early diagnosis within stages I and II correspond to a vastly improved 5-year survival rate when compared with more advanced stage III and IV lesions. Surgical management of this disease remains the mainstay of treatment. Other therapies include radiation and chemotherapy options that may be used adjunctively and palliatively. Following treatment, it is important to understand the significant risks of second primary cancers developing within the upper aerodigestive tract as a result of field cancerization. The most important message is that early detection of the asymptomatic early stage oral cancer translates in general terms to satisfactory clinical outcome and cure in most patients.

Cancer among farmers in central Italy.

PubMed

Forastiere, F; Quercia, A; Miceli, M; Settimi, L; Terenzoni, B; Rapiti, E; Faustini, A; Borgia, P; Cavariani, F; Perucci, C A

1993-12-01

This case-referent study evaluated cancer risks among farmers in central Italy. Cancer cases (N = 1674, 17 sites) were selected from all deceased men aged 35-80 years; a random sample of 480 decedents formed the reference series. Farmers had a decreased risk of lung and bladder cancer and melanoma and nonsignificant excess risks for stomach, rectal, kidney, and nonmelanoma skin cancer. Stomach and kidney cancer were significantly increased among the farmers with > 10 years' experience, and stomach, rectal, and pancreatic cancer were increased among licensed pesticide users with > 10 years' experience. Possible relationships emerged between specific crops and cancer: fruit and colon and bladder cancer, wheat and prostate cancer, olives and kidney cancer, and potato and kidney cancer. The results regarding stomach, pancreatic, lung, bladder, and prostate cancer and melanoma congrue with earlier results. The kidney cancer excess, the association of colon and bladder cancer with orchard farming, and the excess of rectal cancer among licensed farmers are new and unexpected findings.

The Pleiotropic Phenotype of Apc Mutations in the Mouse: Allele Specificity and Effects of the Genetic Background

PubMed Central

Halberg, Richard B.; Chen, Xiaodi; Amos-Landgraf, James M.; White, Alanna; Rasmussen, Kristin; Clipson, Linda; Pasch, Cheri; Sullivan, Ruth; Pitot, Henry C.; Dove, William F.

2008-01-01

Familial adenomatous polyposis (FAP) is a human cancer syndrome characterized by the development of hundreds to thousands of colonic polyps and extracolonic lesions including desmoid fibromas, osteomas, epidermoid cysts, and congenital hypertrophy of the pigmented retinal epithelium. Afflicted individuals are heterozygous for mutations in the APC gene. Detailed investigations of mice heterozygous for mutations in the ortholog Apc have shown that other genetic factors strongly influence the phenotype. Here we report qualitative and quantitative modifications of the phenotype of Apc mutants as a function of three genetic variables: Apc allele, p53 allele, and genetic background. We have found major differences between the Apc alleles Min and 1638N in multiplicity and regionality of intestinal tumors, as well as in incidence of extracolonic lesions. By contrast, Min mice homozygous for either of two different knockout alleles of p53 show similar phenotypic effects. These studies illustrate the classic principle that functional genetics is enriched by assessing penetrance and expressivity with allelic series. The mouse permits study of an allelic gene series on multiple genetic backgrounds, thereby leading to a better understanding of gene action in a range of biological processes. PMID:18723878

The pleiotropic phenotype of Apc mutations in the mouse: allele specificity and effects of the genetic background.

PubMed

Halberg, Richard B; Chen, Xiaodi; Amos-Landgraf, James M; White, Alanna; Rasmussen, Kristin; Clipson, Linda; Pasch, Cheri; Sullivan, Ruth; Pitot, Henry C; Dove, William F

2008-09-01

Familial adenomatous polyposis (FAP) is a human cancer syndrome characterized by the development of hundreds to thousands of colonic polyps and extracolonic lesions including desmoid fibromas, osteomas, epidermoid cysts, and congenital hypertrophy of the pigmented retinal epithelium. Afflicted individuals are heterozygous for mutations in the APC gene. Detailed investigations of mice heterozygous for mutations in the ortholog Apc have shown that other genetic factors strongly influence the phenotype. Here we report qualitative and quantitative modifications of the phenotype of Apc mutants as a function of three genetic variables: Apc allele, p53 allele, and genetic background. We have found major differences between the Apc alleles Min and 1638N in multiplicity and regionality of intestinal tumors, as well as in incidence of extracolonic lesions. By contrast, Min mice homozygous for either of two different knockout alleles of p53 show similar phenotypic effects. These studies illustrate the classic principle that functional genetics is enriched by assessing penetrance and expressivity with allelic series. The mouse permits study of an allelic gene series on multiple genetic backgrounds, thereby leading to a better understanding of gene action in a range of biological processes.

Understanding breast cancer - The long and winding road.

PubMed

Lukong, Kiven Erique

2017-06-01

Despite a remarkable increase in the depth of our understanding and management of breast cancer in the past 50 years, the disease is still a major public health problem worldwide and poses significant challenges. The palpability of breast tumors has facilitated diagnosis and documentation since ancient times. The earliest descriptions of breast cancer date back to around 3500 BCE. For centuries to follow, theories by Hippocrates (460 BCE) and Galen (200 CE), attributing the cause of breast cancer to an "excess of black bile" and treatment options including the use of opium and castor oil, prevailed. Surgical resection was introduced in the 18th century. The advent of modern medicine led to the development of novel treatment options that include hormonal, targeted and chemo-therapies. There are still several therapeutic challenges including the treatment of triple negative breast cancer (TNBC), and overcoming drug resistance. The increased incidence and awareness of breast cancer has led to significant changes in diagnosis and treatment in recent decades. But, mankind has come a long way. Herein, I have traced how our understanding of breast cancer has evolved from the early description of the disease around 460 BCE as "black bile-containing crab-like tumors" to the conventional as a heterogeneous disease with high degree of diversity between and within tumors, as well as among breast cancer patients. How is breast cancer treated today and how do risk factors, breast cancer subtype and drug resistance contribute to the therapeutic challenges at the turn of the 21st century? Breast cancer remains a serious public health issue worldwide. However, appreciable growth in our understanding of breast cancer in the past century has led to remarkable progress in the early detection, treatment and prevention of the disease. The clinical focus is shifting more towards tailored therapy as more targets are characterized and novel highly innovative approaches are developed. Tracing the history of breast cancer, highlights how increased awareness of the disease, and progress in research and development have enhance our understanding of the disease.

What Are Cancer Disparities?

Cancer.gov

This infographic shows the factors associated with cancer disparities, examples of how the cancer burden differs across certain population groups, and NCI actions to understand and reduce cancer disparities.

G Protein-Coupled Estrogen Receptor (GPER) Agonist Dual Binding Mode Analyses toward Understanding of its Activation Mechanism: A Comparative Homology Modeling Approach.

PubMed

Arnatt, Christopher K; Zhang, Yan

2013-07-01

G protein-coupled estrogen receptor (GPER) has been shown to be important in several disease states such as estrogen sensitive cancers. While several selective ligands have been identified for the receptor, little is known about how they interact with GPER and how their structures influence their activity. Specifically, within one series of ligands, whose structure varied only at one position, the replacement of a hydrogen atom with an acetyl group changed a potent antagonist into a potent agonist. In this study, two GPER homology models were constructed based on the x-ray crystal structures of both the active and inactive β 2 -adrenergic receptors (β 2 AR) in an effort to characterize the differences of binding modes between agonists and antagonists to the receptor, and to understand their activity in relation to their structures. The knowledge attained in this study is expected to provide valuable information on GPER ligands structure activity relationship to benefit future rational design of potent agonists and antagonists of the receptor for potential therapeutic applications.

G Protein-Coupled Estrogen Receptor (GPER) Agonist Dual Binding Mode Analyses toward Understanding of its Activation Mechanism: A Comparative Homology Modeling Approach

PubMed Central

Arnatt, Christopher K.; Zhang, Yan

2015-01-01

G protein-coupled estrogen receptor (GPER) has been shown to be important in several disease states such as estrogen sensitive cancers. While several selective ligands have been identified for the receptor, little is known about how they interact with GPER and how their structures influence their activity. Specifically, within one series of ligands, whose structure varied only at one position, the replacement of a hydrogen atom with an acetyl group changed a potent antagonist into a potent agonist. In this study, two GPER homology models were constructed based on the x-ray crystal structures of both the active and inactive β2-adrenergic receptors (β2AR) in an effort to characterize the differences of binding modes between agonists and antagonists to the receptor, and to understand their activity in relation to their structures. The knowledge attained in this study is expected to provide valuable information on GPER ligands structure activity relationship to benefit future rational design of potent agonists and antagonists of the receptor for potential therapeutic applications. PMID:26229572

The effect of novel rhenium compounds on lymphosarcoma, PC-3 prostate and myeloid leukemia cancer cell lines and an investigation on the DNA binding properties of one of these compounds through electronic spectroscopy

PubMed Central

Parson, Carl; Smith, Valerie; Krauss, Christopher; Banerjee, Hirendra N.; Reilly, Christopher; Krause, Jeanette A.; Wachira, James M.; Giri, Dipak; Winstead, Angela; Mandal, Santosh K.

2014-01-01

Despite the tremendous success of cisplatin and other platinum-based anticancer drugs, severe toxicity and resistance to tumors limit their applications. It is believed that the coordination (formation of covalent bond) of the metal (platinum) to the nitrogen bases of DNA cause the ruptures of the cancer as well as normal cells. A search for anticancer drugs with different modes of action resulted in the synthesis of variety of novel compounds. Many of them are in clinical trials now. Recently we synthesized a series of novel rhenium pentylcarbonato compounds (PC1–PC6). The rhenium atom in each compound is coordinated (bonded) to a planar polypyridyl aromatic ligand, thereby forcing each compound to intercalate between the DNA bases. We have investigated the DNA binding properties of one of the PC-series of compounds (PC6) using electronic spectroscopy. The UV absorption titration of PC6 with DNA shows hypochromic effect with concomitant bathochromic shift of the charge transfer band at 290 nm. These results suggest that the compound PC6 binds to DNA through intercalation. It is therefore likely that the other PC-series of compounds will behave in a similar manner. Thus it is expected that these compounds will exhibit negligible or no side effect. We have observed that the PC-series of compounds are strong cytotoxic agents against lymphosarcoma (average GI50 ≈ 2±2.6 µM), PC-3 prostate (average GI50 ≈ 3±2.8 µM) and myeloid leukemia (average GI50 ≈ 3±2.8 µM) cancer cell lines. The average GI50 values of the PC-series of compounds are 2–3 less than the corresponding GI50 values of cisplatin. Also each of the PC-series of compounds exhibits less toxicity than cisplatin in the glomerular mesangial cells. PMID:25221731

A New Series of Thalidomide Analogs That Have Potent Anti-Angiogenic Properties | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) have synthesized novel thalidomide derivatives that have therapeutic potential for a broad spectrum of cancer related diseases alone, or in combination with existing therapies. The compounds can also be useful for the treatment of autoimmune diseases.

Cancer Prevention Programs in the Workplace. WBGH Worksite Wellness Series.

ERIC Educational Resources Information Center

Eriksen, Michael P.

When employees develop cancer, businesses bear not only the direct medical costs of the disease, but also the indirect costs associated with lost work time, disability payments, loss of a trained employee, and retraining. Research has confirmed that aggressive prevention and screening programs can be, and indeed are, effective in limiting the…

'Walk with Us…' Student Peer-Mentoring in Interdisciplinary Cancer Education.

PubMed

Al-Maqrashi, Zainab; Al-Lawati, Yasser; Al-Sadi, Amira; Al-Wahaiby, Malak; Lakhtakia, Ritu

2017-02-27

'Walk with us…' reflects on a series of innovative educational journeys that have offered value addition in cancer education of health professions students. It provides an insight into interdisciplinary peer education through extra-curricular pathways. It taps on student creativity and inspirational techniques in health education that stimulate student-centered learning.

Multiple primary cancers of breast and cervix uteri: An epidemiological approach to analysis

PubMed Central

Prior, P.; Waterhouse, J. A. H.

1981-01-01

Index sites of breast and cervix uteri were selected from populationbased data held at the West Midlands and Birmingham Regional Cancer Registry, and the expected numbers of second primary cancers in cervix and breast were computed (sequence analyses). In the breast series (17,756 patients) a small deficit of cervical tumours was observed (O = 16, E = 2·119, O/E = 0·76, P > 0·05), while in the cervix series (4817 patients) a small excess of breast tumours was found (O = 29, E = 23·38, O/E = 1·24, P > 0·05) over a period of 15 years. A theoretical statement of the combined risk of the 2 tumours occurring in the same individual of a general population was developed and was compared with the practical approach of summing the sequence analyses (complementary analysis). Complementary analysis indicated that there was no excess of women with the 2 primary tumours (O = 45, E = 44·57, O/E = 1·01) and that cancers of the breast and cervix uteri are not aetiologically related. PMID:7248147

Radium-223 in the treatment of osteoblastic metastases: a critical clinical review.

PubMed

Humm, John L; Sartor, Oliver; Parker, Chris; Bruland, Oyvind S; Macklis, Roger

2015-04-01

The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development. Moreover, the most common isotope of Ra has an exceptionally long half-life (>1600 years for (226)Ra) that proved daunting when aiming for a systemic cancer therapy. Fortunately, other radium isotopes have more convenient half-lives while still producing cytotoxic α particles. Radium-223 dichloride has a half-life of 11.4 days, and this isotope was identified as an excellent candidate for radionuclide therapy of cancers metastatic to bone. The calcium-mimetic chemical properties of the radium allowed intravenous infusion with rapid uptake to sites of new bone formation. The highly efficient bone localization suggested a potential therapeutic role for osteoblastic bone metastases, and a series of phase 1, 2, and 3 clinical trials was undertaken to explore this possibility. This series of clinical explorations culminated in the ALSYMPCA trial, an international, placebo-controlled, phase 3 study that accrued 921 symptomatic men with bone-metastatic, castrate-resistant prostate cancer. Results of this trial demonstrated a prolongation of overall survival, and regulatory agencies around the world have now approved this product as a treatment for advanced prostate cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Radium-223 in the Treatment of Osteoblastic Metastases: A Critical Clinical Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Humm, John L.; Sartor, Oliver; Parker, Chris

2015-04-01

The element radium (Ra) was discovered by the Curies in 1898 and within a decade was in broad scientific testing for the management of several forms of cancer. The compound was known to give rise to a series of both high-energy particulate and penetrating γ-emissions. The latter found an important role in early 20th century brachytherapy applications, but the short-range α-particles seemed much less useful. Although highly cytotoxic when released within a few cell diameters of critical cell nuclei, the dense double-strand break damage was poorly repaired, and concerns regarding treatment-related toxicities and secondary malignancies halted clinical development. Moreover, themore » most common isotope of Ra has an exceptionally long half-life (>1600 years for {sup 226}Ra) that proved daunting when aiming for a systemic cancer therapy. Fortunately, other radium isotopes have more convenient half-lives while still producing cytotoxic α particles. Radium-223 dichloride has a half-life of 11.4 days, and this isotope was identified as an excellent candidate for radionuclide therapy of cancers metastatic to bone. The calcium-mimetic chemical properties of the radium allowed intravenous infusion with rapid uptake to sites of new bone formation. The highly efficient bone localization suggested a potential therapeutic role for osteoblastic bone metastases, and a series of phase 1, 2, and 3 clinical trials was undertaken to explore this possibility. This series of clinical explorations culminated in the ALSYMPCA trial, an international, placebo-controlled, phase 3 study that accrued 921 symptomatic men with bone-metastatic, castrate-resistant prostate cancer. Results of this trial demonstrated a prolongation of overall survival, and regulatory agencies around the world have now approved this product as a treatment for advanced prostate cancer.« less

Perceptions of HPV and cervical cancer among Haitian immigrant women: implications for vaccine acceptability.

PubMed

Kobetz, E; Menard, J; Hazan, G; Koru-Sengul, T; Joseph, T; Nissan, J; Barton, B; Blanco, J; Kornfeld, J

2011-12-01

Women in Haiti and throughout the Haitian Diaspora shoulder a disproportionate burden of cervical cancer morbidity and mortality. The widespread Human Papillomavirus (HPV) vaccination holds promise for helping to attenuate this disparity. However, previous research has not fully examined Haitian women's perceptions of, and barriers to, HPV vaccination, which is essential for informing future intervention. The current paper aims to fill this gap. As part of ongoing Community-Based Participatory Research (CBPR) efforts, we conducted a series of focus groups with Haitian immigrant women in Little Haiti, the predominantly Haitian neighborhood in Miami, Florida, U.S. Focus group questions assessed women's knowledge and beliefs about cervical cancer and HPV, their opinions of vaccines in general, their knowledge and perceptions of the HPV vaccine specifically and health communications preferences for cervical cancer prevention. Among the participants who had heard of HPV, many held misconceptions about virus transmission and did not understand the role of HPV in the development of cervical cancer. Virtually all participants expressed support for vaccines in general as beneficial for health. Some women had heard of the HPV vaccine, primarily as the result of a contemporary popular media campaign promoting the Gardasil® vaccine. Physician recommendation was commonly mentioned as a reason for vaccination, in addition to having more than one sex partner. Women felt the HPV vaccine was less appropriate for adolescent girls who are presumed as not sexually active. Women indicated a strong preference to obtain health information through trusted sources, such as Haitian physicians, Haitian Community Health Workers, and especially Kreyol-language audiovisual media. Study findings indicate a need for culturally and linguistically appropriate educational initiatives to promote awareness of HPV and its role in cervical cancer, the importance of vaccination against the virus, explicitly differentiating HPV from HIV and providing specific information about vaccine safety. In the U.S., there is a substantial lack of educational information available in Haitian about HPV and cervical cancer. This gap results in missed opportunities to promote disease prevention through vaccination and regular screening. Addressing such gaps is essential for achieving health equity among Haitian immigrant women and other, similarly underserved women, who are disproportionately burdened by cervical cancer.

Impact of marital status in patients undergoing radical cystectomy for bladder cancer.

PubMed

Pruthi, Raj S; Lentz, Aaron C; Sand, Matthew; Kouba, Erik; Wallen, Eric M

2009-08-01

Married (vs. unmarried) individuals have improved health status and longer life expectancies in a variety of benign and malignant disease states, including prostate, breast, head/neck, and lung cancers. We sought to evaluate a cohort of patients undergoing cystectomy for bladder cancer to evaluate the impact of marital status on demographic, peri-operative, and pathological outcomes in order to better understand the factors which may contribute to the survival differences observed. Two-hundred and two patients underwent radical cystectomy and urinary diversion for bladder cancer. Patients were categorized based on marital status as either married or unmarried (widowed, divorced, never married). Correlations were made to demographic factors (age, race, gender, BMI, tobacco use, alcohol use), perioperative factors (pre-op renal function (creatinine), hematocrit, EBL, hospital stay, choice of diversion), and pathological outcomes (organ-confined status, LN positivity). Of the 202 patients, 74% were married. Married individuals (vs. unmarried) were more often male (84 vs. 62%) and had a higher BMI (28.1 vs. 25.9). Married persons had a significantly lower pre-op creatinine (1.1 vs. 1.4) and higher hematocrit (39 vs. 34). Hospital stay was shorter in married patients by a mean of 1.6 days. Regarding operative pathology, married patients had a higher rate of organ-confined disease (59 vs. 47%) (P = 0.05, 0.08 on multivariate) and trended towards a lower rate of LN positivity (15 vs. 21%; P = 0.10, 0.12 multivariate). In patients undergoing cystectomy for bladder cancer, married individuals appear to have improved pre-operative laboratory variables, shorter hospitalization, and improved pathological outcomes versus unmarried patients in our case series. These findings may support the evidence (observed in other tumor types and other disease states) that married persons present earlier than unmarried individuals, and this may help explain the improved survival outcomes that have been observed in married patients with bladder cancer.

Risk assessment due to environmental exposures to fibrous particulates associated with taconite ore.

PubMed

Wilson, Richard; McConnell, Ernest E; Ross, M; Axten, Charles W; Nolan, Robert P

2008-10-01

In the early 1970s, it became a concern that exposure to the mineral fibers associated taconite ore processed in Silver Bay, Minnesota would cause asbestos-related disease including gastrointestinal cancer. At that time data gaps existed which have now been significantly reduced by further research. To further our understanding of the types of airborne fibers in Silver Bay we undertook a geological survey of their source the Peter Mitchell Pit, and found that there are no primary asbestos minerals at a detectable level. However we identified two non-asbestos types of fibrous minerals in very limited geological locales. Air sampling useful for risk assessment was done to determine the type, concentrations and size distribution of the population of airborne fibers around Silver Bay. Approximately 80% of the airborne fibers have elemental compositions consistent with cummingtonite-grunerite and the remaining 20% have elemental compositions in the tremolite-actinolite series. The mean airborne concentration of both fiber types is less than 0.00014 fibers per milliliter that is within the background level reported by the World Health Organization. We calculate the risk of asbestos-related mesothelioma and lung cancer using a variety of different pessimistic assumptions. (i) that all the non-asbestos fibers are as potent as asbestos fibers used in the EPA-IRIS listing for asbestos; with a calculated risk of asbestos-related cancer for environmental exposure at Silver Bay of 1 excess cancer in 28,500 lifetimes (or 35 excess cancers per 1,000,000 lifetimes) and secondly that taconite associated fibers are as potent as chrysotile the least potent form of asbestos. The calculated risk is less than 0.77 excess cancer case in 1,000,000 lifetimes. Finally, we briefly review the epidemiology studies of grunerite asbestos (amosite) focusing on the exposure conditions associated with increased risk of human mesothelioma.

The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy.

PubMed

Gopalakrishnan, Vancheswaran; Helmink, Beth A; Spencer, Christine N; Reuben, Alexandre; Wargo, Jennifer A

2018-04-09

The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses. Copyright © 2018 Elsevier Inc. All rights reserved.

Optimistic honesty: understanding surgeon and patient perspectives on hopeful communication in pancreatic cancer care.

PubMed

Blakely, Kim; Karanicolas, Paul J; Wright, Frances C; Gotlib Conn, Lesley

2017-07-01

Prognosis conversations between surgical oncologists and patients with pancreatic cancer are critically important and challenging. Surgeons and their patients often have discrepant understandings of prognosis despite extensive conversations. Little is known about how surgeons approach prognosis conversations with these patients; patients' experiences with these conversations are also not well understood. This qualitative study sought to better understand surgeon and patient perspectives on communication in pancreatic cancer care with a view toward improvement. Grounded theory methodology was used. Semi-structured interviews were conducted with surgical oncologists and patients who had undergone surgical resection with curative intent for periampullary cancer. Data were collected and analyzed inductively and iteratively to the point of theoretical saturation. 10 surgeons and 10 patients participated. Three inter-linking concepts were found to drive surgeon-patient conversations: understanding, trust and hope. Surgeons delicately and purposefully tailored information for patients, striving to deliver essential though honest, empathetic and hopeful messages. Patients desired simple, truthful explanations that demonstrated caring and fostered optimism. Surgeons and patients with pancreatic cancer value optimistic honesty in tailored prognosis conversations. Perceived discrepancies in surgeon-patient understanding must be contextualized within efforts to establish a sufficient understanding, high level of trust, and optimistic stance of hope. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Mutation-profile-based methods for understanding selection forces in cancer somatic mutations: a comparative analysis.

PubMed

Zhou, Zhan; Zou, Yangyun; Liu, Gangbiao; Zhou, Jingqi; Wu, Jingcheng; Zhao, Shimin; Su, Zhixi; Gu, Xun

2017-08-29

Human genes exhibit different effects on fitness in cancer and normal cells. Here, we present an evolutionary approach to measure the selection pressure on human genes, using the well-known ratio of the nonsynonymous to synonymous substitution rate in both cancer genomes ( C N / C S ) and normal populations ( p N / p S ). A new mutation-profile-based method that adopts sample-specific mutation rate profiles instead of conventional substitution models was developed. We found that cancer-specific selection pressure is quite different from the selection pressure at the species and population levels. Both the relaxation of purifying selection on passenger mutations and the positive selection of driver mutations may contribute to the increased C N / C S values of human genes in cancer genomes compared with the p N / p S values in human populations. The C N / C S values also contribute to the improved classification of cancer genes and a better understanding of the onco-functionalization of cancer genes during oncogenesis. The use of our computational pipeline to identify cancer-specific positively and negatively selected genes may provide useful information for understanding the evolution of cancers and identifying possible targets for therapeutic intervention.

Dual functions of silver nanoparticles in F9 teratocarcinoma stem cells, a suitable model for evaluating cytotoxicity- and differentiation-mediated cancer therapy

PubMed Central

Han, Jae Woong; Gurunathan, Sangiliyandi; Choi, Yun-Jung; Kim, Jin-Hoi

2017-01-01

Background Silver nanoparticles (AgNPs) exhibit strong antibacterial and anticancer activity owing to their large surface-to-volume ratios and crystallographic surface structure. Owing to their various applications, understanding the mechanisms of action, biological interactions, potential toxicity, and beneficial effects of AgNPs is important. Here, we investigated the toxicity and differentiation-inducing effects of AgNPs in teratocarcinoma stem cells. Materials and methods AgNPs were synthesized and characterized using various analytical techniques such as UV–visible spectroscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. The cellular responses of AgNPs were analyzed by a series of cellular and biochemical assays. Gene and protein expressions were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Results The AgNPs showed typical crystalline structures and spherical shapes (average size =20 nm). High concentration of AgNPs induced cytotoxicity in a dose-dependent manner by increasing lactate dehydrogenase leakage and reactive oxygen species. Furthermore, AgNPs caused mitochondrial dysfunction, DNA fragmentation, increased expression of apoptotic genes, and decreased expression of antiapoptotic genes. Lower concentrations of AgNPs induced neuronal differentiation by increasing the expression of differentiation markers and decreasing the expression of stem cell markers. Cisplatin reduced the viability of F9 cells that underwent AgNPs-induced differentiation. Conclusion The results showed that AgNPs caused differentially regulated cytotoxicity and induced neuronal differentiation of F9 cells in a concentration-dependent manner. Therefore, AgNPs can be used for differentiation therapy, along with chemotherapeutic agents, for improving cancer treatment by targeting specific chemotherapy-resistant cells within a tumor. Furthermore, understanding the molecular mechanisms of apoptosis and differentiation in stem cells could also help in developing new strategies for cancer stem cell (CSC) therapies. The findings of this study could significantly contribute to the nanomedicine because this study is the first of its kind, and our results will lead to new strategies for cancer and CSC therapies. PMID:29066898

Novel Stool-Based Protein Biomarkers for Improved Colorectal Cancer Screening: A Case-Control Study.

PubMed

Bosch, Linda J W; de Wit, Meike; Pham, Thang V; Coupé, Veerle M H; Hiemstra, Annemieke C; Piersma, Sander R; Oudgenoeg, Gideon; Scheffer, George L; Mongera, Sandra; Sive Droste, Jochim Terhaar; Oort, Frank A; van Turenhout, Sietze T; Larbi, Ilhame Ben; Louwagie, Joost; van Criekinge, Wim; van der Hulst, Rene W M; Mulder, Chris J J; Carvalho, Beatriz; Fijneman, Remond J A; Jimenez, Connie R; Meijer, Gerrit A

2017-12-19

The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement. To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas. Case-control study. Colonoscopy-controlled referral population from several centers. 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples). Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples. In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001). Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples. Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening. Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.

Health Literacy Approaches to Improving Communication between Dental Hygienists and Patients for HPV-Related Oral Cancer Prevention.

PubMed

Thompson, Erika L; Daley, Ellen M; Vamos, Cheryl A; Horowitz, Alice M; Catalanotto, Frank A; DeBate, Rita D; Merrell, Laura K; Griner, Stacey B; Vazquez-Otero, Coralia; Kline, Nolan S

2017-08-01

Purpose: Human Papillomavirus (HPV) has been identified as a causal agent for oropharyngeal cancers, suggesting a new role for dental hygienists in HPV-related cancer prevention strategies. Health literacy assessment is an approach that can be used to understand providers' informational assets and needs for educating and discussing HPV prevention with patients. This study aimed to understand dental hygienists' level of health literacy regarding HPV-related oropharyngeal cancers. Methods: Four focus group sessions with dental hygienists (n=48) were conducted at a national conference. The constant comparison method, with a priori codes for health literacy competencies (i.e., access/understand/appraise/apply), was utilized for this qualitative study. Results: Participants mentioned a variety of modes (e.g., magazines, journals) for accessing HPV-information; however, descriptions of understanding HPV and its relationship to oropharyngeal cancer varied. Participants considered patients' personal characteristics, the dental practice environment, and professional factors to appraise HPV-related information. Additionally, participants self-described themselves as being "prevention specialists." These factors influenced how dental hygienists applied primary and secondary prevention of HPV-related care issues with their patients (e.g., education and oral-cancer screenings). Conclusions: Dental hygienists recognized the importance of HPV and oropharyngeal cancer prevention efforts, including oral-cancer screenings and promotion of the HPV vaccine. The study findings identified opportunities for intervention focusing on primary prevention. Copyright © 2017 The American Dental Hygienists’ Association.

Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities

Cancer.gov

Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

Nutritional Science | Division of Cancer Prevention

Cancer.gov

This group promotes and supports studies establishing a comprehensive understanding of the precise role of diet and fo | Establishing a comprehensive understanding of diet and food components in cancer risk and tumor cell behavior.

CDC Vital Signs: Cervical Cancer is Preventable

MedlinePlus

... die of cervical cancer. Doctors, nurses, and health systems can: Help women understand what screening tests are ... Title X Family Planning Doctors, nurses, and health systems can Help women understand which screening tests are ...

Screening for breast cancer in a high-risk series

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodard, E.D.; Hempelmann, L.H.; Janus, J.

1982-01-01

A unique cohort of women at increased risk of breast cancer because of prior X-ray treatment of acute mastitis and their selected high-risk siblings were offered periodic breast cancer screening including physical examination of the breasts, mammography, and thermography. Twelve breast cancers were detected when fewer than four would have been expected based on age-specific breast cancer detection rates from the National Cancer institute/American Cancer Society Breast Cancer Demonstration Detection Projects. Mammograpy was positive in all cases but physical examination was positive in only three cases. Thermography was an unreliable indicator of disease. Given the concern over radiation-induced risk, usemore » of low-dose technique and of criteria for participation that select women at high risk of breast cancer will maximize the benefit/risk ratio for mammography screening.« less

Screening for breast cancer in a high-risk series

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodard, E.D.; Hempelmann, L.H.; Janus, J.

1982-01-01

A unique cohort of women at increased risk of breast cancer because of prior X-ray treatment of acute mastitis and their selected high-risk siblings were offered periodic breast cancer screening including physical examination of the breasts, mammography, and thermography. Twelve breast cancers were detected when fewer than four would have been expected based on age-specific breast cancer detection rates from the National Cancer Institute/American Cancer Society Breast Cancer Demonstration Detection Projects. Mammography was positive in all cases but physical examination was positive in only three cases. Thermography was an unreliable indicator of disease. Given the concern over radiation-induced risk, usemore » of low-dose technique and of criteria for participation that select women at high risk of breast cancer will maximize the benefit/risk ratio for mammography screening.« less

Quality of life and disease understanding: impact of attending a patient-centered cancer symposium.

PubMed

Padrnos, Leslie; Dueck, Amylou C; Scherber, Robyn; Glassley, Pamela; Stigge, Rachel; Northfelt, Donald; Mikhael, Joseph; Aguirre, Annette; Bennett, Robert M; Mesa, Ruben A

2015-06-01

To evaluate the impact of a patient-centered symposium as an educational intervention on a broad population of cancer patients. We developed a comprehensive patient symposium. Through voluntary questionnaires, we studied the impact of this cancer symposium on quality of life, cancer-specific knowledge, and symptom management among cancer patients. Symposium attendees were provided surveys prior to and 3 months following the educational intervention. Surveys included (1) EORTC-QLQ-C30; (2) disease understanding tool developed for this conference; (3) validated disease-specific questionnaires. Changes over time were assessed using McNemar's tests and paired t-tests for categorical and continuous variables, respectively. A total of 158 attendees completed the pre-convention survey. Most respondents reported at least "quite a bit" of understanding regarding treatment options, screening modalities, symptomatology, and cancer-related side effects. Attendees endorsed the least understanding of disease-related stress, risk factors, fatigue management, and legal issues related to disease/treatment. At 3 months, there was improvement in understanding (12 of 14 areas of self-reported knowledge especially regarding nutrition, and stress/fatigue management). However, no significant change was seen in QLQ-C30 functioning, fatigue, pain, or insomnia. A patient symposium, as an educational intervention improves a solid knowledge base amongst attendees regarding their disease, increases knowledge in symptom management, but may be insufficient to impact QoL as a single intervention. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Exploitation of necroptosis for treatment of caspase-compromised cancers.

PubMed

Cho, Young Sik; Park, Hey Li

2017-08-01

Programmed necrosis, or necroptosis, is a type of specialized cell death with necrotic characteristics, including the loss of membrane integrity and swollen organelles in dying cells. However, unlike simple necrosis, it may be induced as an alternative form of cell death when apoptosis is blocked and it is mediated in an orchestrated manner, similar to apoptosis, by a series of signaling molecules. Necroptosis-associated proteins and their specific small molecules have been extensively identified in order to illuminate the underlying mechanisms by which necroptosis is activated through a novel signaling pathway. However, the biological significance of necroptosis, which is known as a secondary route of apoptosis, remains under debate. Concurrent with these concerns, the clinical application of necroptosis has been cautiously proposed to treat necroptosis-associated diseases, and to overcome resistance to anticancer drugs. Accordingly, the present review will highlight the harnessing of necroptosis for anticancer therapy. To this end, the state-of-the art technique of necroptosis as a cancer therapy will be briefly described, and then its potential for clinical purposes will be delineated. For a further understanding of necroptosis, the present review begins with a basic introduction to necroptosis and its multifaceted physiological consequences.

Exploitation of necroptosis for treatment of caspase-compromised cancers

PubMed Central

Cho, Young Sik; Park, Hey Li

2017-01-01

Programmed necrosis, or necroptosis, is a type of specialized cell death with necrotic characteristics, including the loss of membrane integrity and swollen organelles in dying cells. However, unlike simple necrosis, it may be induced as an alternative form of cell death when apoptosis is blocked and it is mediated in an orchestrated manner, similar to apoptosis, by a series of signaling molecules. Necroptosis-associated proteins and their specific small molecules have been extensively identified in order to illuminate the underlying mechanisms by which necroptosis is activated through a novel signaling pathway. However, the biological significance of necroptosis, which is known as a secondary route of apoptosis, remains under debate. Concurrent with these concerns, the clinical application of necroptosis has been cautiously proposed to treat necroptosis-associated diseases, and to overcome resistance to anticancer drugs. Accordingly, the present review will highlight the harnessing of necroptosis for anticancer therapy. To this end, the state-of-the art technique of necroptosis as a cancer therapy will be briefly described, and then its potential for clinical purposes will be delineated. For a further understanding of necroptosis, the present review begins with a basic introduction to necroptosis and its multifaceted physiological consequences. PMID:28789335

Improving outcomes for people with progressive cancer: interrupted time series trial of a needs assessment intervention.

PubMed

Waller, Amy; Girgis, Afaf; Johnson, Claire; Lecathelinais, Christophe; Sibbritt, David; Forstner, Dion; Liauw, Winston; Currow, David C

2012-03-01

Improving the effectiveness of cancer care delivery has become a major focus of research. This study assessed the uptake and impact of the Palliative Care Needs Assessment Guidelines and Needs Assessment Tool: Progressive Disease--Cancer (NAT: PD-C) on the outcomes of people with advanced cancer. Given widely varying survival in people with advanced cancer, an interrupted time series design was used, with data on unmet needs, depression, anxiety, and quality of life collected from 195 patients using telephone interviews every two months, for up to 18 months. Patients completed at least two baseline interviews before health professionals were academically detailed in the use of the Palliative Care Needs Assessment Guidelines and NAT: PD-C. Health professionals completed the NAT: PD-C with patients approximately monthly for the remainder of the study. Changes in patients' outcomes were compared prior to and following the introduction of the NAT: PD-C using general estimating equations. Moderate to high needs across all domains were frequently seen in the preintervention phase. The use of the NAT: PD-C was associated with a significant reduction in health system and information and patient care and support needs. These resources have the potential as an efficient and acceptable strategy for supporting needs-based cancer care. Further work is required to determine their unique contribution to improvements in patient outcomes. Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Adenocarcinoma metastatic to the uterine cervix: a case series.

PubMed

Pérez-Montiel, Delia; Serrano-Olvera, Alberto; Salazar, Luz Calderón; Cetina-Pérez, Lucely; Candelaria, Myrna; Coronel, Jaime; Montalvo, Luis Alonso Herrera; de León, David Cantú

2012-03-01

The objectives of this report are, first, to describe the clinical behavior of cases of carcinoma metastatic to the uterine cervix treated at our institution in order to carry out a systematic review to establish the behavioral patterns of the most frequent metastases to the cervix and, second, to generate guidelines for their diagnosis and treatment. At the National Institute of Cancer of Mexico (INCan), we performed a review of the clinical files with a diagnosis of malignant neoplasm metastatic to the uterine cervix between 1990 and 2009. For a systematic review, we conducted a PubMed search between the years 1970 and 2009 of case reports and series of cases of patients with metastatic gastric, breast, ovarian and colorectal cancer. We analyzed each report individually and extracted the patients' clinical data from our cases and reports, including the primary tumor, cervical metastases and survival rates. There were 10 cases of tumors metastatic to the uterine cervix. Metastasis was documented in one-half of the patients during follow up, with two of these cases having the cervix as the only site. We included the following reports in the systematic review: 13 reports of gastric-associated cancer, 30 related to breast cancer, nine with ovarian-associated cancer and 10 related to colorectal cancer. Metastatic cervical activity is an infrequent event. The prognosis of survival is poor in the presence of gastric or ovarian cancer and cervical metastases. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

Validation of a contemporary prostate cancer grading system using prostate cancer death as outcome

PubMed Central

Berney, Daniel M; Beltran, Luis; Fisher, Gabrielle; North, Bernard V; Greenberg, David; Møller, Henrik; Soosay, Geraldine; Scardino, Peter; Cuzick, Jack

2016-01-01

Background: Gleason scoring (GS) has major deficiencies and a novel system of five grade groups (GS⩽6; 3+4; 4+3; 8; ⩾9) has been recently agreed and included in the WHO 2016 classification. Although verified in radical prostatectomies using PSA relapse for outcome, it has not been validated using prostate cancer death as an outcome in biopsy series. There is debate whether an ‘overall' or ‘worst' GS in biopsies series should be used. Methods: Nine hundred and eighty-eight prostate cancer biopsy cases were identified between 1990 and 2003, and treated conservatively. Diagnosis and grade was assigned to each core as well as an overall grade. Follow-up for prostate cancer death was until 31 December 2012. A log-rank test assessed univariable differences between the five grade groups based on overall and worst grade seen, and using univariable and multivariable Cox proportional hazards. Regression was used to quantify differences in outcome. Results: Using both ‘worst' and ‘overall' GS yielded highly significant results on univariate and multivariate analysis with overall GS slightly but insignificantly outperforming worst GS. There was a strong correlation with the five grade groups and prostate cancer death. Conclusions: This is the largest conservatively treated prostate cancer cohort with long-term follow-up and contemporary assessment of grade. It validates the formation of five grade groups and suggests that the ‘worst' grade is a valid prognostic measure. PMID:27100731

Unconventional therapies for cancer: 1. Essiac

PubMed Central

Kaegi, E

1998-01-01

Physicians and patients have been frustrated by the lack of reliable information on unconventional therapies. To help fill this gap in the area of breast cancer therapy, the Canadian Breast Cancer Research Initiative formed a task force to advise it on how best to promote research into unconventional therapies. As part of the work of the task force, a review of the available literature was carried out for each of the following products: Essiac, green tea, Iscador, hydrazine sulfate, vitamins A, C and E, and 714-X. The first article in this series on unconventional therapies for cancer describes the methodology used to obtain and evaluate the information and provides a summary of the findings on Essiac. Subsequent articles will cover the other products. For most of the products reviewed, there has been some indication of possible benefit but no definitive evidence. Innovative and collaborative research needed to meet the information needs of growing numbers of patients and their physicians is now being sponsored by the Canadian Breast Cancer Research Initiative. Open communication between patients and physicians is also necessary for the maintenance of an appropriate therapeutic partnership and for the identification and control of side effects. The Ontario Division of the Canadian Cancer Society, a partner in the Canadian Breast Cancer Research Initiative, supported the preparation of a patient-information piece on unconventional therapies to accompany the series. This item will assist patients who are considering such therapies and will promote open communication between patients and their physicians. PMID:9559016

Clinicopathologic and prognostic features of breast cancer in young women: a series from North of Morocco.

PubMed

Bakkach, Joaira; Mansouri, Mohamed; Derkaoui, Touria; Loudiyi, Ali; Fihri, Mohamed; Hassani, Samia; Barakat, Amina; Ghailani Nourouti, Naima; Bennani Mechita, Mohcine

2017-11-09

Literature data reported a higher frequency of breast cancer in young women (BCYW) in developing countries. BCYW is associated with delayed diagnosis, aggressive biology and poor prognosis. However, our knowledge of biological profile, treatment received and outcome of young patients is still limited in Morocco. We propose to analyze clinicopathologic, therapeutic and prognostic features of BCYW among a series of patients native and/or inhabitant of North of Morocco. We carried out a retro-prospective study of 331 infiltrating breast cancer cases registered between January 2010 and December 2015. Details of tumor pathology, treatment and outcome were collected. Disease-Free Survival (DFS) and Overall Survival (OS) were assessed by Kaplan-Meier analysis. A total of 82 patients were diagnosed with breast cancer at the age of 40 or younger (24.8%). Median age was 36 years. More than one quarter (26%) of patients had family history of breast or ovarian cancer. Advanced stages accounted for 34.2% of cases. Median tumor diameter was 2.8 cm. Intermediate and high-grade tumors represented 47.6% and 40.2%, respectively. Nodal involvement was present in 58.5% and lymphovascular invasion was found in 47.7% of the patients. About two thirds (66.2%) of tumors were hormone receptor positive, 29.2% over-expressed HER2 receptor and 23% were triple negative. Patients underwent breast conserving surgery in 38.2% of cases, 61.7% were offered adjuvant chemotherapy and 84.6% received hormone therapy. Five-year DFS and OS were respectively 88.9% and 75.6%. Locoregional recurrence occurred in 2.8% of cases and 8.3% of patients developed distant metastases. Our findings are in accordance with previous studies that have shown a higher frequency of breast cancer among Moroccan young women. In line with literature data, clinicopathologic profile seems to be aggressive and prognosis is pejorative in our series.

Is there a role for prophylactic colectomy in Lynch syndrome patients with inflammatory bowel disease?

PubMed

McNamara, Kate L; Aronson, Melyssa D; Cohen, Zane

2016-01-01

Lynch syndrome and chronic inflammatory bowel disease are two important risk factors for colorectal cancer. It is unclear whether Lynch syndrome patients with inflammatory bowel disease are at sufficiently increased risk for colorectal cancer to warrant prophylactic colectomy. This study aims to identify all cases of Lynch syndrome and concurrent inflammatory bowel disease in a large familial gastrointestinal cancer registry, define incidence of colorectal cancer, and characterize mismatch repair protein gene mutation status and inflammatory bowel disease-associated colorectal cancer risk factors. We retrospectively identified and collected clinical data for all cases with confirmed diagnoses of Lynch syndrome and inflammatory bowel disease in the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital in Toronto, Canada. Twelve cases of confirmed Lynch syndrome, and concurrent inflammatory bowel disease were identified. Four cases developed colorectal cancer. An additional five cases had colectomy; one was performed for severe colitis, and four were performed for low-grade dysplasia. None of these surgical specimens contained malignancy or high-grade dysplasia. The presentation of Lynch syndrome with inflammatory bowel disease is uncommon and not well described in the literature. This small but important series of twelve cases is the largest reported to date. In this series, patients with Lynch syndrome and concurrent inflammatory bowel disease do not appear to have sufficiently increased risk for colorectal cancer to recommend prophylactic surgery. Therefore, the decision to surgery should continue to be guided by surgical indications for each disease. Further evaluation of this important area will require multi-institutional input.

University of Texas MD Anderson Cancer Center (UT-MDACC): Phenotypic Examination of PIK3CA Allelic Series using In Vitro/In Vivo Sensor Platforms | Office of Cancer Genomics

Cancer.gov

The CTD2 Center at the University of Texas MD Anderson Cancer Center utilized an established and operational MCF10A normal breast epithelial cell model to assess the ability of candidate driver aberrations to promote cell grow in anchorage-independent conditions (soft agar assay) and proliferate in the absence of insulin and epidermal growth factor (EGF).

Opportunities During Early Life for Cancer Prevention: Highlights From a Series of Virtual Meetings With Experts

PubMed Central

Holman, Dawn M.; Buchanan, Natasha D.

2018-01-01

Compelling evidence suggests that early life exposures can affect lifetime cancer risk. In 2014, the Centers for Disease Control and Prevention’s (CDC’s) Cancer Prevention Across the Lifespan Workgroup hosted a series of virtual meetings with select experts to discuss the state of the evidence linking factors during the prenatal period and early childhood to subsequent risk of both pediatric and adult cancers. In this article, we present the results from a qualitative analysis of the meeting transcripts and summarize themes that emerged from our discussions with meeting participants. Themes included the state of the evidence linking early life factors to cancer risk, research gaps and challenges, the level of evidence needed to support taking public health action, and the challenges of communicating complex, and sometimes conflicting, scientific findings to the public. Opportunities for collaboration among public health agencies and other stakeholders were identified during these discussions. Potential next steps for the CDC and its partners included advancing and building upon epidemiology and surveillance work, developing and using evidence from multiple sources to inform decision-making, disseminating and communicating research findings in a clear and effective way, and expanding collaborations with grantees and other partners. As the science on early life factors and cancer risk continues to evolve, there are opportunities for collaboration to translate science into actionable public health practice. PMID:27940972

GPER-targeted, 99mTc-labeled, nonsteroidal ligands demonstrate selective tumor imaging and in vivo estrogen binding

PubMed Central

Nayak, Tapan K.; Ramesh, Chinnasamy; Hathaway, Helen J.; Norenberg, Jeffrey P.; Arterburn, Jeffrey B.; Prossnitz, Eric R.

2014-01-01

Our understanding of estrogen (E2) receptor biology has evolved in recent years with the discovery and characterization of a 7-transmembrane-spanning G protein-coupled estrogen receptor (GPER1/GPER/GPR30) and the development of GPER-selective functional chemical probes. GPER is highly expressed in certain breast, endometrial and ovarian cancers, establishing the importance of non-invasive methods to evaluate GPER expression in vivo. Herein, we developed 99mTc-labeled GPER ligands to demonstrate the in vivo status of GPER as an estrogen receptor and for GPER visualization in whole animals. A series of 99mTc(I)-labeled non-steroidal tetrahydro-3H-cyclopenta[c]quinolone derivatives was synthesized utilizing pyridin-2-yl hydrazine and picolylamine chelates. Radioligand receptor binding studies revealed binding affinities in the 10–30 nM range. Cell signaling assays previously demonstrated that derivatives retaining a ketone functionality displayed agonist properties whereas those lacking such a hydrogen bond acceptor were antagonists. In vivo biodistribution and imaging studies performed on mice bearing human endometrial and breast cancer cell xenografts yielded significant tumor uptake (0.4–1.1 %ID/g). Blocking studies revealed specific uptake in multiple organs (adrenals, uterus, mammary tissue) as well as tumor uptake with similar levels of competition by E2 and G-1, a GPER-selective agonist. In conclusion, we synthesized and evaluated a series of first generation 99mTc-labeled GPER-specific radioligands, demonstrating GPER as an estrogen-binding receptor for the first time in vivo using competitive binding principles, and establishing the utility of such ligands as tumor imaging agents. These results warrant further investigation into the role of GPER in estrogen-mediated carcinogenesis and as a target for diagnostic/therapeutic/ image-guided drug delivery. PMID:25030373

Cancer biology and genomics: translating discoveries, transforming pathology.

PubMed

Ladanyi, Marc; Hogendoorn, Pancras C W

2011-01-01

Advances in our understanding of cancer biology and discoveries emerging from cancer genomics are being translated into real clinical benefits for patients with cancer. The 2011 Journal of Pathology Annual Review Issue provides a snapshot of recent rapid progress on multiple fronts in the war on cancer or, more precisely, the wars on cancers. Indeed, perhaps the most notable recent shift is reflected by the sharp increase in understanding the biology of multiple specific cancers and using these new insights to inform rationally targeted therapies, with often striking successes. These recent developments, as reviewed in this issue, show how the long-term investments in basic cancer research are finally beginning to bear fruit. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Head and neck cancer: proteomic advances and biomarker achievements.

PubMed

Rezende, Taia Maria Berto; de Souza Freire, Mirna; Franco, Octávio Luiz

2010-11-01

Tumors of the head and neck comprise an important neoplasia group, the incidence of which is increasing in many parts of the world. Recent advances in diagnostic and therapeutic techniques for these lesions have yielded novel molecular targets, uncovered signal pathway dominance, and advanced early cancer detection. Proteomics is a powerful tool for investigating the distribution of proteins and small molecules within biological systems through the analysis of different types of samples. The proteomic profiles of different types of cancer have been studied, and this has provided remarkable advances in cancer understanding. This review covers recent advances for head and neck cancer; it encompasses the risk factors, pathogenesis, proteomic tools that can help in understanding cancer, and new proteomic findings in this type of cancer. Copyright © 2010 American Cancer Society.

Research information knowledge, perceived adequacy, and understanding in cancer clinical trial participants.

PubMed

Biedrzycki, Barbara A

2011-07-01

To describe the adequacy of research information among people with cancer at the time they accept or decline participation in a cancer clinical trial. Cross-sectional, descriptive. An urban, academic, National Cancer Institute-designated comprehensive cancer center. 197 patients with advanced gastrointestinal cancer. Mailed survey; self-reported data. Adequacy of research information (actual knowledge, perceived adequacy of information, and perceived understanding), cancer clinical trial participation, and satisfaction with the decision to participate. Most respondents (88%) perceived themselves as having adequate information to make an informed decision regarding cancer clinical trial participation. In addition, 35% demonstrated adequate knowledge of basic clinical research. Patients decide to accept or decline cancer clinical trials without having adequate knowledge. Nurses have an important role in educating patients regarding cancer clinical trials. The ideal teachable moment may not occur at the time of diagnosis; other less stressful opportunities may present when the patient is more receptive.

Targeted Delivery of Drugs to Brain Tumors (LBNL Summer Lecture Series)

ScienceCinema

Forte, Trudy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; Children’s Hospital Oakland Research Inst. (CHORI), Oakland, CA (United States)

2017-12-15

Summer Lecture Series 2007: Trudy Forte of Berkeley Lab's Life Sciences Division will discuss her work developing nano-sized low-density lipoprotein (LDL) particles that can be used as a safe and effective means of delivering anticancer drugs to brain tumors, particularly glioblastoma multiforme. This is the most common malignant brain tumor in adults and one of the deadliest forms of cancer. Her research team found that the synthetic LDL particles can target and kill such tumors cells in vitro. The nanoparticles are composed of a lipid core surrounded by a peptide. The peptide contains an amino acid sequence that recognizes the LDL receptor, and the lipid core has the ability to accumulate anti-cancer drugs.

The problem of `chronic mastitis' with epitheliosis

PubMed Central

Macgillivray, J. B.

1969-01-01

The incidence of breast cancer complicating chronic mastitis with epitheliosis has been reported to be as high as 45% and as low as 6%. At least part of this discrepancy appears to be due to difficulty in distinguishing between benign and malignant intraduct epithelial proliferation. A small series is presented here in which the incidence of invasive cancer after local excision of breast tissue showing chronic mastitis with epitheliosis was nil. It is concluded that it is necessary to follow up larger series of cases longer before it can be said that severe epitheliosis and borderline lesions should in all cases be treated by anything more radical than local excision. Images PMID:5814739

The Natural History and Treatment Outcomes of Perineural Spread of Malignancy within the Head and Neck.

PubMed

Warren, Timothy A; Nagle, Christina M; Bowman, James; Panizza, Benedict J

2016-04-01

Understanding the natural history of diseases enables the clinician to better diagnose and treat their patients. Perineural spread of head and neck cancers are poorly understood and often diagnosis is delayed resulting in poorer outcomes and more debilitating treatments. This article reviews a large personal series of head and neck malignancy presenting with perineural spread along almost exclusively the trigeminal and/or facial nerves. A detailed analysis of squamous cell carcinoma of cutaneous origin is presented including an analysis of likely primaries, which most often have occurred months to years prior. The importance of early detection is reinforced by the highly significant (p < 0.0001) differences in disease specific survival, which occur, depending on how far along a cranial nerve the disease has been allowed to spread.

The Natural History and Treatment Outcomes of Perineural Spread of Malignancy within the Head and Neck

PubMed Central

Warren, Timothy A.; Nagle, Christina M.; Bowman, James; Panizza, Benedict J.

2016-01-01

Understanding the natural history of diseases enables the clinician to better diagnose and treat their patients. Perineural spread of head and neck cancers are poorly understood and often diagnosis is delayed resulting in poorer outcomes and more debilitating treatments. This article reviews a large personal series of head and neck malignancy presenting with perineural spread along almost exclusively the trigeminal and/or facial nerves. A detailed analysis of squamous cell carcinoma of cutaneous origin is presented including an analysis of likely primaries, which most often have occurred months to years prior. The importance of early detection is reinforced by the highly significant (p < 0.0001) differences in disease specific survival, which occur, depending on how far along a cranial nerve the disease has been allowed to spread. PMID:27123386

Intraoperative laparoscopic complications for urological cancer procedures.

PubMed

Montes, Sergio Fernández-Pello; Rodríguez, Ivan Gonzalez; Ugarteburu, Rodrigo Gil; Villamil, Luis Rodríguez; Mendez, Begoña Diaz; Gil, Patricio Suarez; Madera, Javier Mosquera

2015-05-16

To structure the rate of intraoperative complications that requires an intraoperative or perioperative resolution. We perform a literature review of Medline database. The research was focused on intraoperative laparoscopic procedures inside the field of urological oncology. General rate of perioperative complications in laparoscopic urologic surgery is described to be around 12.4%. Most of the manuscripts published do not make differences between pure intraoperative, intraoperative with postoperative consequences and postoperative complications. We expose a narrative statement of complications, possible solutions and possible preventions for most frequent retroperitoneal and pelvic laparoscopic surgery. We expose the results with the following order: retroperitoneal laparoscopic surgery (radical nephrectomy, partial nephrectomy, nephroureterectomy and adrenalectomy) and pelvic laparoscopic surgery (radical prostatectomy and radical cystectomy). Intraoperative complications vary from different series. More scheduled reports should be done in order to better understand the real rates of complications.

Laboratory of Viral Diseases Guest Researcher Seminar Series | Center for Cancer Research

Cancer.gov

Laboratory of Viral Diseases Guest Researcher Seminar Series New Epigenetic Regulators of HIV Latency Speaker: Melanie Ott, M.D., Ph.D, Senior Investigator & Professor of Medicine Gladstone Institutes & University of California Building 33, Main Conference Room 1N09 Main NIH CAMPUS *BLDG 33 is a secure facility, please allow time to pass through security.

78 FR 2678 - Proposed Collection; Comment Request (60-Day FRN): The National Cancer Institute (NCI...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-14

... text message smoking cessation intervention designed for young adult smokers ages 18-29. The SmokefreeTXT program is a component of a larger series of eHealth/mHealth tobacco cessation intervention... using the bidirectional aspect of text- messaging service and a series of web-based surveys. All web...

A Cancer Center’s Approach to Engaging African American Men About Cancer: The Men’s Fellowship Breakfast, Southeastern Michigan, 2008–2014

PubMed Central

Griffith, Derek M.; Beasley, Derrick D.; Braxton, Effat Id-Deen

2014-01-01

Background Despite disproportionate rates of cancer morbidity and mortality among African American men, few community-based efforts have been developed and sustained to educate African American men about cancer. The University of Michigan Comprehensive Cancer Center implemented a series of breakfasts to improve cancer awareness, screening, and education among African American men. This article describes the rationale for and history of the community intervention. Community Context The 21 breakfasts were held from 2008 through mid-2014 in Ypsilanti and Ann Arbor, Michigan. Ypsilanti ranks below Michigan and the nation on most socioeconomic indicators, although most residents are high school graduates (88% in Ypsilanti and 96.5% in Ann Arbor). African American men in Ypsilanti have higher death rates for diseases associated with poor diet and inadequate physical activity compared with Ypsilanti whites and general populations in Michigan and the nation. Methods We conducted a multicomponent qualitative process evaluation including staff meetings, conversations with participants, and focus groups. We collected 425 post-event surveys to evaluate the breakfasts quantitatively. Outcomes Participants were African American (85%), were aged 51 to 70 years (54%), had health insurance (89%), and had some college education (38%). Fifty-three percent of participants reported interest in the breakfast topics including nutrition; 46%, prostate cancer; 34%, colorectal cancer, and 32%, pain management; 62% reported willingness to participate in a clinical trial. Interpretation African American men are interested in learning about health and are willing to attend a health-focused breakfast series. The Men’s Fellowship Breakfast is a promising strategy for bringing men together to discuss cancer screening and risk reduction. PMID:25254982

Using the Theory of Planned Behavior to Understand Cervical Cancer Screening among Latinas

ERIC Educational Resources Information Center

Roncancio, Angelica M.; Ward, Kristy K.; Sanchez, Ingrid A.; Cano, Miguel A.; Byrd, Theresa L.; Vernon, Sally W.; Fernandez-Esquer, Maria Eugenia; Fernandez, Maria E.

2015-01-01

To reduce the high incidence of cervical cancer among Latinas in the United States it is important to understand factors that predict screening behavior. The aim of this study was to test the utility of theory of planned behavior in predicting cervical cancer screening among a group of Latinas. A sample of Latinas (N = 614) completed a baseline…

Understanding the intersections between metabolism and cancer biology

PubMed Central

Heiden, Matthew G. Vander; DeBerardinis, Ralph J.

2017-01-01

Transformed cells adapt metabolism to support tumor initiation and progression. Specific metabolic activities can participate directly in the process of transformation or support the biological processes that enable tumor growth. Exploiting cancer metabolism for clinical benefit requires defining the pathways that are limiting for cancer progression and understanding the context specificity of metabolic preferences and liabilities in malignant cells. Progress towards answering these questions is providing new insight into cancer biology and can guide the more effective targeting of metabolism to help patients. PMID:28187287

Younger British men's understandings of prostate cancer: A qualitative study.

PubMed

Grogan, Sarah; Parlane, Victoria L; Buckley, Emily

2017-05-01

The purpose of this study was to explore young British men's understandings of prostate health and cancer of the prostate. A total of 16 White-British men between 31-50 years of age took part in interviews face-to-face or through computer-mediated communication. Thematic analysis broadly informed by grounded theory identified two key themes; 'limited knowledge about the prostate' and 'early detection & unpleasant procedures'. Accounts are discussed with reference to implications for improving men's understandings of prostate cancer, and likelihood of self-referral for prostate screening where necessary.

Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer; Report From the 2016 Coffey-Holden Prostate Cancer Academy Meeting.

PubMed

Miyahira, Andrea K; Roychowdhury, Sameek; Goswami, Sangeeta; Ippolito, Joseph E; Priceman, Saul J; Pritchard, Colin C; Sfanos, Karen S; Subudhi, Sumit K; Simons, Jonathan W; Pienta, Kenneth J; Soule, Howard R

2017-02-01

The 2016 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer," was held from June 23 to June 26, 2016, in Coronado, California. For the 4th year in a row, the Prostate Cancer Foundation (PCF) hosted the CHPCA Meeting, a think tank-structured scientific conference, which focuses on a specific topic of critical unmet need on the biology and treatment of advanced prostate cancer. The 2016 CHPCA Meeting was attended by 71 investigators from prostate cancer and other fields, who discussed the biology, study methodologies, treatment strategies, and critical unmet needs concerning metastatic prostate cancer, with the ultimate goal of advancing strategies to treat and eliminate this disease. The major topics of discussion included: the molecular landscape and molecular heterogeneity of metastatic prostate cancer, the role of the metastatic microenvironment, optimizing immunotherapy in metastatic prostate cancer, learning from exceptional responders and non-responders, targeting DNA repair deficiency in advanced prostate cancer, developing and applying novel biomarkers and imaging techniques, and potential roles for the microbiome in prostate cancer. This article reviews the topics presented and discussions held at the CHPCA Meeting, with a focus on the unknowns and next steps needed to advance our understanding of the biology and most effective treatment strategies for metastatic prostate cancer. Prostate 77:123-144, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Landscaping the epigenetic landscape of cancer.

PubMed

Aranda-Anzaldo, Armando; Dent, Myrna A R

2018-06-08

Waddington's epigenetic landscape was introduced in biology for understanding the complex process of metazoan development in an accessible fashion. The epigenetic landscape concept implies the coupling of cell differentiation and tissue/organ morphogenesis under a simple visual metaphor or analogy with significant heuristic value. Yet in recent times the epigenetic landscape has been reduced to an illustration device just for cell differentiation thus diminishing its explanatory power and heuristic value. On the other hand, the current mainstream in cancer research is concentrated on the search for proximate causes but not on achieving a deeper understanding of the phenomenon. Nevertheless an emerging alternative perspective that understands cancer as a problem related to tissue/organ morphology and structural organization is getting wider attention. Within such a perspective here we present and discuss a historically restored, non-reductionist, version of the epigenetic landscape that when applied to the problem of cancer improves our understanding of it as a common biological phenomenon resulting from the uncoupling of morphogenesis and cell differentiation as a consequence of the progressive erosion of the epigenetic landscape. The following discussion aims at finding a general framework, not dependent on proximate causes, for understanding the phenomenon of cancer and suggests new research strategies on this problem but away from the current emphasis on the putative genetic causes of cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

The role of evolutionary biology in research and control of liver flukes in Southeast Asia.

PubMed

Echaubard, Pierre; Sripa, Banchob; Mallory, Frank F; Wilcox, Bruce A

2016-09-01

Stimulated largely by the availability of new technology, biomedical research at the molecular-level and chemical-based control approaches arguably dominate the field of infectious diseases. Along with this, the proximate view of disease etiology predominates to the exclusion of the ultimate, evolutionary biology-based, causation perspective. Yet, historically and up to today, research in evolutionary biology has provided much of the foundation for understanding the mechanisms underlying disease transmission dynamics, virulence, and the design of effective integrated control strategies. Here we review the state of knowledge regarding the biology of Asian liver Fluke-host relationship, parasitology, phylodynamics, drug-based interventions and liver Fluke-related cancer etiology from an evolutionary biology perspective. We consider how evolutionary principles, mechanisms and research methods could help refine our understanding of clinical disease associated with infection by Liver Flukes as well as their transmission dynamics. We identify a series of questions for an evolutionary biology research agenda for the liver Fluke that should contribute to an increased understanding of liver Fluke-associated diseases. Finally, we describe an integrative evolutionary medicine approach to liver Fluke prevention and control highlighting the need to better contextualize interventions within a broader human health and sustainable development framework. Copyright © 2016 Elsevier B.V. All rights reserved.

The Role of Evolutionary Biology in Research and Control of Liver Flukes in Southeast Asia

PubMed Central

Echaubard, Pierre; Sripa, Banchob; Mallory, Frank F.; Wilcox, Bruce A.

2016-01-01

Stimulated largely by the availability of new technology, biomedical research at the molecular-level and chemical-based control approaches arguably dominate the field of infectious diseases. Along with this, the proximate view of disease etiology predominates to the exclusion of the ultimate, evolutionary biology-based, causation perspective. Yet, historically and up to today, research in evolutionary biology has provided much of the foundation for understanding the mechanisms underlying disease transmission dynamics, virulence, and the design of effective integrated control strategies. Here we review the state of knowledge regarding the biology of Asian liver Fluke-host relationship, parasitology, phylodynamics, drug-based interventions and liver Fluke-related cancer etiology from an evolutionary biology perspective. We consider how evolutionary principles, mechanisms and research methods could help refine our understanding of clinical disease associated with infection by Liver Flukes as well as their transmission dynamics. We identify a series of questions for an evolutionary biology research agenda for the liver Fluke that should contribute to an increased understanding of liver Fluke-associated diseases. Finally, we describe an integrative evolutionary medicine approach to liver Fluke prevention and control highlighting the need to better contextualize interventions within a broader human health and sustainable development framework. PMID:27197053

Assessing needs and assets for building a regional network infrastructure to reduce cancer related health disparities.

PubMed

Wells, Kristen J; Lima, Diana S; Meade, Cathy D; Muñoz-Antonia, Teresita; Scarinci, Isabel; McGuire, Allison; Gwede, Clement K; Pledger, W Jack; Partridge, Edward; Lipscomb, Joseph; Matthews, Roland; Matta, Jaime; Flores, Idhaliz; Weiner, Roy; Turner, Timothy; Miele, Lucio; Wiese, Thomas E; Fouad, Mona; Moreno, Carlos S; Lacey, Michelle; Christie, Debra W; Price-Haywood, Eboni G; Quinn, Gwendolyn P; Coppola, Domenico; Sodeke, Stephen O; Green, B Lee; Lichtveld, Maureen Y

2014-06-01

Significant cancer health disparities exist in the United States and Puerto Rico. While numerous initiatives have been implemented to reduce cancer disparities, regional coordination of these efforts between institutions is often limited. To address cancer health disparities nation-wide, a series of regional transdisciplinary networks through the Geographic Management Program (GMaP) and the Minority Biospecimen/Biobanking Geographic Management Program (BMaP) were established in six regions across the country. This paper describes the development of the Region 3 GMaP/BMaP network composed of over 100 investigators from nine institutions in five Southeastern states and Puerto Rico to develop a state-of-the-art network for cancer health disparities research and training. We describe a series of partnership activities that led to the formation of the infrastructure for this network, recount the participatory processes utilized to develop and implement a needs and assets assessment and implementation plan, and describe our approach to data collection. Completion, by all nine institutions, of the needs and assets assessment resulted in several beneficial outcomes for Region 3 GMaP/BMaP. This network entails ongoing commitment from the institutions and institutional leaders, continuous participatory and engagement activities, and effective coordination and communication centered on team science goals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detection of skeletal muscle metastases on initial staging of lung cancer: a retrospective case series.

PubMed

Bocchino, Marialuisa; Valente, Tullio; Somma, Francesco; de Rosa, Ilaria; Bifulco, Marco; Rea, Gaetano

2014-03-01

Estimation of skeletal muscle metastases (SMMs) at the time of diagnosis and/or initial staging of lung cancer. Retrospective evaluation of clinical charts and imaging data suggestive of SMMs of patients with histology-proved lung cancer over a 5-year period. SMMs were identified in 46 out of 1,754 patients. Single and multiple (62.9% of cases) SMMs were detected by total body multi-detector computed tomography (MDCT). They were associated with poorly differentiated (43%) and advanced adenocarcinomas (52%) without clinically relevant symptoms and/or signs. Psoas and buttock muscles were most frequently involved (33.3%). MDCT findings consisted of well-defined homogeneously hyperdense oval masses (31%), lesions with ring-like enhancement and central hypoattenuation (68%), or large abscess-like necrotic lesions (24%). Sonography revealed well-defined hypoechoic masses (41.6%), ill-defined hypoechoic lesions (33.3%), or anechoic areas with a necrotic centre (25%). Positron emission tomography revealed that all SMMs were metabolically active. SMMs are uncommon but not negligible in lung cancer, with an estimated prevalence of 2.62% in our series. Although histology remains the recommended method, use of high-performance imaging techniques and increased clinical suspicion may improve their early detection. Efforts addressing their effect on the natural history of lung cancer are needed.

Expression of neurotensin and NT1 receptor in human breast cancer: a potential role in tumor progression.

PubMed

Souazé, Frédérique; Dupouy, Sandra; Viardot-Foucault, Véronique; Bruyneel, Erik; Attoub, Samir; Gespach, Christian; Gompel, Anne; Forgez, Patricia

2006-06-15

Emerging evidence supports neurotensin as a trophic and antiapoptotic factor, mediating its control via the high-affinity neurotensin receptor (NT1 receptor) in several human solid tumors. In a series of 51 patients with invasive ductal breast cancers, 34% of all tumors were positive for neurotensin and 91% positive for NT1 receptor. We found a coexpression of neurotensin and NT1 receptor in a large proportion (30%) of ductal breast tumors, suggesting a contribution of the neurotensinergic signaling cascade within breast cancer progression. Functionally expressed NT1 receptor, in the highly malignant MDA-MB-231 human breast cancer cell line, coordinated a series of transforming functions, including cellular migration, invasion, induction of the matrix metalloproteinase (MMP)-9 transcripts, and MMP-9 gelatinase activity. Disruption of NT1 receptor signaling by silencing RNA or use of a specific NT1 receptor antagonist, SR48692, caused the reversion of these transforming functions and tumor growth of MDA-MB-231 cells xenografted in nude mice. Our findings support the contribution of neurotensin in human breast cancer progression and point out the utility to develop therapeutic molecules targeting neurotensin or NT1 receptor signaling cascade. These strategies would increase the range of therapeutic approaches and be beneficial for specific patients.

Assessing Needs and Assets for Building a Regional Network Infrastructure to Reduce Cancer Related Health Disparities

PubMed Central

Wells, Kristen J.; Lima, Diana S.; Meade, Cathy D.; Muñoz-Antonia, Teresita; Scarinci, Isabel; McGuire, Allison; Gwede, Clement K.; Pledger, W. Jack; Partridge, Edward; Lipscomb, Joseph; Matthews, Roland; Matta, Jaime; Flores, Idhaliz; Weiner, Roy; Turner, Timothy; Miele, Lucio; Wiese, Thomas E.; Fouad, Mona; Moreno, Carlos S.; Lacey, Michelle; Christie, Debra W.; Price-Haywood, Eboni G.; Quinn, Gwendolyn P.; Coppola, Domenico; Sodeke, Stephen O.; Green, B. Lee; Lichtveld, Maureen Y.

2015-01-01

Significant cancer health disparities exist in the United States and Puerto Rico. While numerous initiatives have been implemented to reduce cancer disparities, regional coordination of these efforts between institutions is often limited. To address cancer health disparities nationwide, a series of regional transdisciplinary networks through the Geographic Management Program (GMaP) and the Minority Biospecimen/Biobanking Geographic Management Program (BMaP) were established in six regions across the country. This paper describes the development of the Region 3 GMaP/BMaP network composed of over 100 investigators from nine institutions in five Southeastern states and Puerto Rico to develop a state-of-the-art network for cancer health disparities research and training. We describe a series of partnership activities that led to the formation of the infrastructure for this network, recount the participatory processes utilized to develop and implement a needs and assets assessment and implementation plan, and describe our approach to data collection. Completion, by all nine institutions, of the needs and assets assessment resulted in several beneficial outcomes for Region 3 GMaP/BMaP. This network entails ongoing commitment from the institutions and institutional leaders, continuous participatory and engagement activities, and effective coordination and communication centered on team science goals. PMID:24486917

Understanding the stereospecific interactions of 3-deoxyphosphatidylinositol derivatives with the PTEN phosphatase domain

PubMed Central

Wang, Qin; Wei, Yang; Mottamal, Madhusoodanan; Roberts, Mary F.; Krilov, Goran

2011-01-01

PTEN is an important control element of PI3K/AKT signaling involved in controlling the processes of embryonic development, cell migration and apoptosis. While its dysfunction is implicated in a large fraction of cancers, PTEN activity in the same pathway may also contribute to metabolic syndromes such as diabetes. In those cases, selective inhibitors of PTEN may be useful. A new class of chiral PTEN inhibitors based on the 3-deoxy-phosphatidylinositol derivatives was recently identified [Wang et al. (2008) J. Am. Chem. Soc. 130, 7746]. However, lack of detailed understanding of protein-ligand interactions has hampered efforts to develop effective agonists or antagonists of PTEN. Here, we use computational modeling to characterize the interactions of the diverse 3-deoxyphosphatidylinositol inhibitors with the PTEN protein. We show that, while each of the compounds binds with the inositol headgroup inserting into the proposed active site of the PTEN phosphatase domain, hydrogen bonding restrictions lead to distinct binding geometries for ligand pairs of opposite chirality. We furthermore demonstrate that the binding modes differ primarily in the orientation of acyl tails of the ligands and that the activity of the compounds is primarily controlled by the effectiveness of tail-protein contacts. These findings are confirmed by binding affinity calculations which are in good agreement with experiment. Finally, we show that while more potent D-series ligands bind in a manner similar to that of the native substrate, an alternate hydrophobic pocket suitable for binding the opposite chirality L-series inhibitors exists, offering the possibility of designing highly selective PTEN- targeting compounds. PMID:20538496

Induction of Colon Cancer in Mice with 1,2-Dimethylhydrazine.

PubMed

Gurley, Kay E; Moser, Russell D; Kemp, Christopher J

2015-09-01

In this protocol, colon cancer is induced in mice through a series of injections with 1,2-dimethylhydrazine. Mice will develop primarily colon tumors starting at about 3 mo after the first injection. Tumors in the lung, uterus, and small intestine may also be seen, as well as lymphomas. © 2015 Cold Spring Harbor Laboratory Press.

Identity reconstruction among older cancer survivors: Age and meaning in the context of a life-altering illness.

PubMed

Hannum, Susan M; Clegg Smith, Katherine; Coa, Kisha; Klassen, Ann C

2016-01-01

This article evaluates how older cancer patients describe cancer survivorship and incorporate the cancer experience into long-term evaluations of health. From a series of 53 qualitative interviews with adults with histories of breast and prostate cancers and non-Hodgkin's lymphoma, we analyzed age-related discussions among those 65 and older (n = 21). Emergent themes revealed the: (1) historical conceptualization of cancer, (2) changed perspective following diagnosis, (3) cancer in the context of a long biography, (4) cancer in the context of the aging body and decline, and (5) meaning of time remaining and quality of life. One important suggestion from our work, relevant to all clinicians regardless of specialty or role, is to incorporate goals for the future into individualized survivor care plans for older survivors.

Understanding Lymphatic Drainage Pathways of the Ovaries to Predict Sites for Sentinel Nodes in Ovarian Cancer

PubMed Central

Kleppe, Marjolein; Kraima, Anne C.; Kruitwagen, Roy F.P.M.; Van Gorp, Toon; Smit, Noeska N.; van Munsteren, Jacoba C.; DeRuiter, Marco C.

2015-01-01

Objective In ovarian cancer, detection of sentinel nodes is an upcoming procedure. Perioperative determination of the patient’s sentinel node(s) might prevent a radical lymphadenectomy and associated morbidity. It is essential to understand the lymphatic drainage pathways of the ovaries, which are surprisingly up till now poorly investigated, to predict the anatomical regions where sentinel nodes can be found. We aimed to describe the lymphatic drainage pathways of the human ovaries including their compartmental fascia borders. Methods A series of 3 human female fetuses and tissues samples from 1 human cadaveric specimen were studied. Immunohistochemical analysis was performed on paraffin-embedded transverse sections (8 or 10 μm) using antibodies against Lyve-1, S100, and α-smooth muscle actin to identify the lymphatic endothelium, Schwann, and smooth muscle cells, respectively. Three-dimensional reconstructions were created. Results Two major and 1 minor lymphatic drainage pathways from the ovaries were detected. One pathway drained via the proper ligament of the ovaries (ovarian ligament) toward the lymph nodes in the obturator fossa and the internal iliac artery. Another pathway drained the ovaries via the suspensory ligament (infundibulopelvic ligament) toward the para-aortic and paracaval lymph nodes. A third minor pathway drained the ovaries via the round ligament to the inguinal lymph nodes. Lymph vessels draining the fallopian tube all followed the lymphatic drainage pathways of the ovaries. Conclusions The lymphatic drainage pathways of the ovaries invariably run via the suspensory ligament (infundibulopelvic ligament) and the proper ligament of the ovaries (ovarian ligament), as well as through the round ligament of the uterus. Because ovarian cancer might spread lymphogenously via these routes, the sentinel node can be detected in the para-aortic and paracaval regions, obturator fossa and surrounding internal iliac arteries, and inguinal regions. These findings support the strategy of injecting tracers in both ovarian ligaments to identify sentinel nodes. PMID:26397066

Understanding participation by African Americans in cancer genetics research.

PubMed

McDonald, Jasmine A; Barg, Frances K; Weathers, Benita; Guerra, Carmen E; Troxel, Andrea B; Domchek, Susan; Bowen, Deborah; Shea, Judy A; Halbert, Chanita Hughes

2012-01-01

Understanding genetic factors that contribute to racial differences in cancer outcomes may reduce racial disparities in cancer morbidity and mortality. Achieving this goal will be limited by low rates of African American participation in cancer genetics research. We conducted a qualitative study with African American adults (n = 91) to understand attitudes about participating in cancer genetics research and to identify factors that are considered when making a decision about participating in this type of research. Participants would consider the potential benefits to themselves, family members, and their community when making a decision to participate in cancer genetics research. However, concerns about exploitation, distrust of researchers, and investigators' motives were also important to participation decisions. Individuals would also consider who has access to their personal information and what would happen to these data. Side effects, logistical issues, and the potential to gain knowledge about health issues were also described as important factors in decision making. African Americans may consider a number of ethical, legal, and social issues when making a decision to participate in cancer genetics research. These issues should be addressed as part of recruitment efforts.

The Carolina Center of Cancer Nanotechnology Excellence: Past Accomplishments and Future Perspectives

PubMed Central

JULIANO, R.L.; SUNNARBORG, S.; DESIMONE, J.; HAROON, Z.

2013-01-01

SUMMARY The Carolina Center of Cancer Nanotechnology Excellence (C-CCNE) is funded by the National Cancer Institute and is based at the University of North Carolina. The C-CCNE features interactions among physical and biological scientists in a series of projects and cores that work together to quickly harness innovations in nanotechnology for the early diagnosis and treatment of cancer. Two key focus areas of the C-CCNE are, first the selective delivery of drugs and imaging agents utilizing advanced nanoparticle technology, and second novel approaches to imaging and radiotherapy utilizing carbon nanotube based X-ray sources. PMID:21182415

Is Reliance on Mitochondrial Respiration a “Chink in the Armor” of Therapy-Resistant Cancer?

PubMed Central

Wolf, Dieter A.

2016-01-01

Summary A series of recent reports has suggested PGC1α-driven upregulation of mitochondrial oxidative phosphorylation as a selective vulnerability of drug-resistant cancers. Accordingly, chemical inhibitors of respiration led to selective eradication of such cancer cells due to their preferential sensitivity to mitochondrial production of reactive oxygen species. These novel insights create a timely opportunity for a biomarker guided application of already existing and newly emerging mitochondrial inhibitors in recurrent drug resistant cancer, including lymphomas, melanomas, and other malignant diseases marked by increased mitochondrial respiration. PMID:25490445

Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease.

PubMed

Press, M F; Pike, M C; Chazin, V R; Hung, G; Udove, J A; Markowicz, M; Danyluk, J; Godolphin, W; Sliwkowski, M; Akita, R

1993-10-15

The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced recurrent disease (relapsed cases) 105 were matched with 105 women with no recurrence (disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Peto's paradox and the promise of comparative oncology

PubMed Central

Nunney, Leonard; Maley, Carlo C.; Breen, Matthew; Hochberg, Michael E.; Schiffman, Joshua D.

2015-01-01

The past several decades have seen a paradigm shift with the integration of evolutionary thinking into studying cancer. The evolutionary lens is most commonly employed in understanding cancer emergence, tumour growth and metastasis, but there is an increasing realization that cancer defences both between tissues within the individual and between species have been influenced by natural selection. This special issue focuses on discoveries of these deeper evolutionary phenomena in the emerging area of ‘comparative oncology’. Comparing cancer dynamics in different tissues or species can lead to insights into how biology and ecology have led to differences in carcinogenesis, and the diversity, incidence and lethality of cancers. In this introduction to the special issue, we review the history of the field and outline how the contributions use empirical, comparative and theoretical approaches to address the processes and patterns associated with ‘Peto's paradox’, the lack of a statistical relationship of cancer incidence with body size and longevity. This burgeoning area of research can help us understand that cancer is not only a disease but is also a driving force in biological systems and species life histories. Comparative oncology will be key to understanding globally important health issues, including cancer epidemiology, prevention and improved therapies. PMID:26056361

Barriers to overcome for effective cancer control in Africa.

PubMed

Harford, Joe B

2015-08-01

Cancer control in Africa is complicated due to large differences in cancer incidence between countries caused by differences in exposure to known risk factors. For example, substantial differences are seen when selected cancers in north Africa are compared with those in sub-Saharan Africa. In the future, population growth and demographic shifts are likely to have profound effects on the prevalence of cancer across the continent. Likewise, many factors outside of health care such as language differences, conflict, and poverty can affect cancer control efforts. Although cooperation in cancer control efforts is desirable, differences in cultural and geopolitical factors that characterise African countries and their populations, together with the sheer size of the continent, present unique challenges to effective cancer control. This Series paper discusses factors related to the size, diversity, and conditions within Africa that present barriers to optimal collaboration in cancer control efforts across the continent. Copyright © 2015 Elsevier Ltd. All rights reserved.

The 150 most important questions in cancer research and clinical oncology series: Questions 25-30 : Edited by Chinese Journal of Cancer.

PubMed

2017-05-04

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 6 more questions are presented as followed. Question 25: Does imprinting of immune responses to infections early in life predict future risk of childhood and adult cancers? Question 26: How to induce homogeneous tumor antigen expression in a heterogeneous tumor mass to enhance the efficacy of cancer immunotherapy? Question 27: Could we enhance the therapeutic effects of immunotherapy by targeting multiple tumor antigens simultaneously or sequentially? Question 28: Can immuno-targeting to cytokines halt cancer metastasis? Question 29: How can we dynamically and less-invasively monitor the activity of CD8 + T killer cells at tumor sites and draining lymph nodes? Question 30: How can the immune system destroy the niches for cancer initiation?

P-MartCancer-Interactive Online Software to Enable Analysis of Shotgun Cancer Proteomic Datasets.

PubMed

Webb-Robertson, Bobbie-Jo M; Bramer, Lisa M; Jensen, Jeffrey L; Kobold, Markus A; Stratton, Kelly G; White, Amanda M; Rodland, Karin D

2017-11-01

P-MartCancer is an interactive web-based software environment that enables statistical analyses of peptide or protein data, quantitated from mass spectrometry-based global proteomics experiments, without requiring in-depth knowledge of statistical programming. P-MartCancer offers a series of statistical modules associated with quality assessment, peptide and protein statistics, protein quantification, and exploratory data analyses driven by the user via customized workflows and interactive visualization. Currently, P-MartCancer offers access and the capability to analyze multiple cancer proteomic datasets generated through the Clinical Proteomics Tumor Analysis Consortium at the peptide, gene, and protein levels. P-MartCancer is deployed as a web service (https://pmart.labworks.org/cptac.html), alternatively available via Docker Hub (https://hub.docker.com/r/pnnl/pmart-web/). Cancer Res; 77(21); e47-50. ©2017 AACR . ©2017 American Association for Cancer Research.

Pathobiology and Chemoprevention of Bladder Cancer

PubMed Central

Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

2011-01-01

Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

Children's cancer camps: a sense of community, a sense of family.

PubMed

Laing, Catherine M; Moules, Nancy J

2014-05-01

Childhood cancer is a family affair, and each year in Canada, approximately 1,400 children and adolescents under the age of 20 are diagnosed with cancer. Innumerable challenges accompany this diagnosis, and in recognition of the stress of childhood cancer, children's cancer camps arose in the 1970s to help children and their families escape the rigidity and severity of cancer treatment. Very little is known about these cancer camps, and to that end, a philosophical hermeneutic study was conducted to understand the meaning of children's cancer camps for the child with cancer and the family. Six families were interviewed to bring understanding to this topic. While the research included findings related to the concept of play, fit and acceptance, storytelling, and grief, this paper will detail the finding related to the solidarity of the community--the "camp family"--as one that creates intense, healing bonds.

Helping cancer patients to quit smoking by understanding their risk perception, behavior, and attitudes related to smoking.

PubMed

Li, William H C; Chan, Sophia S C; Lam, T H

2014-08-01

Evidence shows that smoking is a major cause of cancer, and cancer patients who continue smoking are at greater risk for all causes of mortality, cancer recurrence, and second primary cancers. Nevertheless, many cancer patients still smoke and are not willing to quit. This study aimed at understanding the needs and concerns of current and ex-smoking cancer patients, including their risk perceptions, and the behavior and attitudes related to smoking. A qualitative research was conducted in an oncology outpatient clinic. A one-to-one semi-structured interview was conducted with current Chinese smokers and ex-smokers after they had been diagnosed with cancer. Data saturation was achieved after interviewing a total of 20 current smokers and 20 ex-smokers. A total of 241 patients who were smokers prior to their diagnosis of cancer were identified. Of 241 patients, 208 (86.31%) quitted and 33 (13.69%) continued smoking after receiving a cancer diagnosis. In general, patients who refused to quit smoking subsequent to a cancer diagnosis thought that the perceived barriers to quitting outweighed the perceived benefits of quitting. In contrast, most cancer patients who quit after their cancer diagnoses thought that the perceived benefits of quitting greatly outweighed the perceived barriers to quitting. It is vital that healthcare professionals should help cancer patients to quit smoking. Understanding how current smokers and ex-smokers perceive the risks of smoking, and their behavior, attitudes, and experiences related to smoking is an essential prerequisite for the design of an effective smoking cessation intervention. Copyright © 2014 John Wiley & Sons, Ltd.

Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer.

PubMed

Shukla, Hem D

2017-10-25

During the past century, our understanding of cancer diagnosis and treatment has been based on a monogenic approach, and as a consequence our knowledge of the clinical genetic underpinnings of cancer is incomplete. Since the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A number of novel and promising cancer targets have emerged from the genome project for diagnostics, therapeutics, and prognostic markers, which are being used to monitor response to cancer treatment. The heterogeneous nature of cancer has hindered progress in understanding the underlying mechanisms that lead to abnormal cellular growth. Since, the start of The Cancer Genome Atlas (TCGA), and the International Genome consortium projects, there has been tremendous progress in genome sequencing and immense numbers of cancer genomes have been completed, and this approach has transformed our understanding of the diagnosis and treatment of different types of cancers. By employing Genomics and proteomics technologies, an immense amount of genomic data is being generated on clinical tumors, which has transformed the cancer landscape and has the potential to transform cancer diagnosis and prognosis. A complete molecular view of the cancer landscape is necessary for understanding the underlying mechanisms of cancer initiation to improve diagnosis and prognosis, which ultimately will lead to personalized treatment. Interestingly, cancer proteome analysis has also allowed us to identify biomarkers to monitor drug and radiation resistance in patients undergoing cancer treatment. Further, TCGA-funded studies have allowed for the genomic and transcriptomic characterization of targeted cancers, this analysis aiding the development of targeted therapies for highly lethal malignancy. High-throughput technologies, such as complete proteome, epigenome, protein-protein interaction, and pharmacogenomics data, are indispensable to glean into the cancer genome and proteome and these approaches have generated multidimensional universal studies of genes and proteins (OMICS) data which has the potential to facilitate precision medicine. However, due to slow progress in computational technologies, the translation of big omics data into their clinical aspects have been slow. In this review, attempts have been made to describe the role of high-throughput genomic and proteomic technologies in identifying a panel of biomarkers which could be used for the early diagnosis and prognosis of cancer.

Recent advances in the biology and treatment of brain metastases of non-small cell lung cancer: summary of a multidisciplinary roundtable discussion

PubMed Central

Preusser, Matthias; Winkler, Frank; Valiente, Manuel; Manegold, Christian; Moyal, Elizabeth; Widhalm, Georg; Tonn, Jörg-Christian; Zielinski, Christoph

2018-01-01

This article is the result of a round table discussion held at the European Lung Cancer Conference (ELCC) in Geneva in May 2017. Its purpose is to explore and discuss the advances in the knowledge about the biology and treatment of brain metastases originating from non-small cell lung cancer. The authors propose a series of recommendations for research and treatment within the discussed context. PMID:29387475

Characterizing Mechanisms of Resistance to Androgen Deprivation in Prostate Cancer

DTIC Science & Technology

2015-11-01

of my training in cancer biology has included the attendance of regular seminars and conferences. Indeed, each Tuesday I have attended the meeting of...the Cancer Program of the Broad Institute, and on Tuesday afternoon the institute-wide series of Seminars in Oncology at DFCI, where invited speakers...24(6): p. 719-36. 23. Morris , T.A., R.J. DeLorenzo, and R.M. Tombes, CaMK-II inhibition reduces cyclin D1 levels and enhances the association of

Remedial Investigation Report Area of Contamination (AOC) 43J. Volume 1 of 2

DTIC Science & Technology

1996-02-01

produced risks within the USEPA range (1x1W05 and 3x10’, respectively). If the modified cancer slope factor (CSF) for arsenic was used to estimate excess...lifetime cancer risks for both source area and downgradient groundwater quality, then the cancer risks associated with exposure to both average and...very poorly drained; nearly level, organic; occurs in depressions and on flat areas of uplands and glacial outwash plains. Windsor Series. Deep

Standard Specimen Reference Set: Lung — EDRN Public Portal

Cancer.gov

The NCI/EDRN/SPORE Lung Cancer Biomarkers Group (LCBG) began its activities back in November 2004 and developed clear objectives and strategies on how to begin validating a series of candidate biomarkers for the early detection of lung cancer. The initial goal of the LCBG is to develop the requisite sample resources to validate serum/plasma biomarkers for the early diagnosis of lung cancer. Researchers may use these resources and process for continued biomarker refinement but this is not the primary activity of the LCBG.

Gender differences in the evolution of illness understanding among patients with advanced cancer

PubMed Central

Fletcher, Kalen; Prigerson, Holly G.; Paulk, Elizabeth; Temel, Jennifer; Finlay, Esme; Marr, Lisa; McCorkle, Ruth; Rivera, Lorna; Munoz, Francisco; Maciejewski, Paul K.

2014-01-01

Background Patient understanding of advanced metastatic disease is central to decisions about care near death. Prior studies have focused on gender differences in communication style rather than on illness understanding. Objectives To evaluate gender differences in terminal illness acknowledgement (TIA), understanding that the disease is incurable and the advanced stage of the disease. To evaluate gender differences in patients’ reports of discussions of life expectancy with oncology providers and its effect on differences in illness understanding. Methods Coping with Cancer 2 patients (N = 68) were interviewed before and after a visit with their oncology providers to discuss scan results. Results At the prescan interview, there were no statistically significant gender differences in patient measures of illness understanding. At the postscan interview, women were more likely than men to recognize that their illness was incurable (Adjusted Odds Ratio, [AOR] = 5.29; P = .038), know that their cancer was at an advanced stage (AOR = 6.38; P = .013), and report having had discussions of life expectancy with their oncologist (AOR = 4.77; P = .021). Controlling discussions of life expectancy, women were more likely than men to report that their cancer was at an advanced stage (AOR = 9.53; P = .050). Controlling for gender, discussions of life expectancy were associated with higher rates of TIA (AOR = 4.65; P = .036) and higher rates of understanding that the cancer was incurable (AOR = 4.09; P = .085). Conclusions Due largely to gender differences in communication, women over time have a better understanding of their illness than men. More frequent discussions of life expectancy should enhance illness understanding and reduce gender differences. PMID:24400392

The Elusive Neutrino, Understanding the Atom Series.

ERIC Educational Resources Information Center

Bernstein, Jeremy

This booklet is one of the booklets in the "Understanding the Atom Series" published by the U. S. Atomic Energy Commission for high school science teachers and their students. The discovery of the neutrino and the research involving this important elementary particle of matter is discussed. The introductory section reviews topics basic…

Spectroscopy, Understanding the Atom Series.

ERIC Educational Resources Information Center

Hellman, Hal

This booklet is one of the "Understanding the Atom" Series. The science of spectroscopy is presented by a number of topics dealing with (1) the uses of spectroscopy, (2) its origin and background, (3) the basic optical systems of spectroscopes, spectrometers, and spectrophotometers, (4) the characteristics of wave motion, (5) the…

Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer.

PubMed

Tamura, Koji; Yu, Jun; Hata, Tatsuo; Suenaga, Masaya; Shindo, Koji; Abe, Toshiya; MacGregor-Das, Anne; Borges, Michael; Wolfgang, Christopher L; Weiss, Matthew J; He, Jin; Canto, Marcia Irene; Petersen, Gloria M; Gallinger, Steven; Syngal, Sapna; Brand, Randall E; Rustgi, Anil; Olson, Sara H; Stoffel, Elena; Cote, Michele L; Zogopoulos, George; Potash, James B; Goes, Fernando S; McCombie, Richard W; Zandi, Peter P; Pirooznia, Mehdi; Kramer, Melissa; Parla, Jennifer; Eshleman, James R; Roberts, Nicholas J; Hruban, Ralph H; Klein, Alison Patricia; Goggins, Michael

2018-05-01

To evaluate whether germline variants in genes encoding pancreatic secretory enzymes contribute to pancreatic cancer susceptibility, we sequenced the coding regions of CPB1 and other genes encoding pancreatic secretory enzymes and known pancreatitis susceptibility genes ( PRSS1 , CPA1 , CTRC , and SPINK1 ) in a hospital series of pancreatic cancer cases and controls. Variants in CPB1 , CPA1 (encoding carboxypeptidase B1 and A1), and CTRC were evaluated in a second set of cases with familial pancreatic cancer and controls. More deleterious CPB1 variants, defined as having impaired protein secretion and induction of endoplasmic reticulum (ER) stress in transfected HEK 293T cells, were found in the hospital series of pancreatic cancer cases (5/986, 0.5%) than in controls (0/1,045, P = 0.027). Among familial pancreatic cancer cases, ER stress-inducing CPB1 variants were found in 4 of 593 (0.67%) vs. 0 of 967 additional controls ( P = 0.020), with a combined prevalence in pancreatic cancer cases of 9/1,579 vs. 0/2,012 controls ( P < 0.01). More ER stress-inducing CPA1 variants were also found in the combined set of hospital and familial cases with pancreatic cancer than in controls [7/1,546 vs. 1/2,012; P = 0.025; odds ratio, 9.36 (95% CI, 1.15-76.02)]. Overall, 16 (1%) of 1,579 pancreatic cancer cases had an ER stress-inducing CPA1 or CPB1 variant, compared with 1 of 2,068 controls ( P < 0.00001). No other candidate genes had statistically significant differences in variant prevalence between cases and controls. Our study indicates ER stress-inducing variants in CPB1 and CPA1 are associated with pancreatic cancer susceptibility and implicate ER stress in pancreatic acinar cells in pancreatic cancer development.

Home - The Cancer Genome Atlas - Cancer Genome - TCGA

Cancer.gov

The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

Personality and psychological distress among older adult, long-term cancer survivors.

PubMed

Deimling, Gary T; Albitz, Casey; Monnin, Kara; Renzhofer Pappada, Holly T; Nalepa, Elizabeth; Boehm, Melinda Laroco; Mitchell, Claire

2017-01-01

This research examines a model of how personality (Five-Factor Model) is related to adjustment to cancer in later life in terms of the presence of continuing cancer-related worry and depression among older adult, long-term cancer survivors. Data from an NCI-funded study with 275 older adult (age 60+), long-term (5+ years) survivors of breast, prostate, and colorectal cancer were examined. Regression analyses identified neuroticism as the strongest predictor of cancer-related worry along with continuing cancer-related symptoms. For depression, three personality dimensions (neuroticism, conscientiousness, and agreeableness) were significant predictors. Findings suggest the importance of considering the central role that survivors' personality characteristics play in understanding cancer-related worries and depression. Understanding these dispositional characteristics is key for social workers and health-care practitioners in counseling survivors experiencing these common mental health effects.

“It’s Not JUST Skin Cancer”: Understanding Their Cancer Experience From Melanoma Survivor Narratives Shared Online

PubMed Central

Banerjee, Smita C.; D’Agostino, Thomas A.; Gordon, Mallorie L.; Hay, Jennifer L.

2016-01-01

Cancer survivors narrate their experiences in unique ways, articulating different aspects of the cancer journey. The purpose of this study was to analyze the content of cancer narratives that melanoma survivors share online in order to present the ways that survivors narrate their cancer experience, to identify survivors’ motivations for sharing, and to better understand the ways in which survivors are impacted by and cope with the diagnosis and treatment of cancer. The sample consisted of 95 unique melanoma survivor narratives, accessed from the Melanoma Research Foundation in November 2015, that were inductively and deductively coded for key themes and subthemes. Emergent themes described different aspects of the melanoma experience during prediagnosis (identification of selfphenotype, searching for causes, suspicious findings, delay in diagnosis), diagnosis (communication of diagnosis, emotional responses), transition from diagnosis to beginning treatment (second opinion), treatment (positive reframing of attitude, proactive cancer management, side effects), and posttreatment phases (social support, vigilance behaviors posttreatment). Two themes that cut across all phases of the cancer journey included recognizing and dealing with uncertainty and survivors’ motive for sharing narrative. These findings have implications for understanding how melanoma survivors may benefit personally from sharing their cancer experience online and for the potential for survivor narratives to motivate behavior change and facilitate coping among readers. PMID:27982699

How children with cancer communicate and think about symptoms.

PubMed

Vatne, Torun M; Slaugther, Laura; Ruland, Cornelia M

2010-01-01

For clinicians to effectively help children with their illness and symptoms, it is important to communicate with them in a language they can understand. This study investigates how well children with cancer and healthy children understood 44 symptom terms; their thoughts about these symptoms in terms of causes, consequences, and cures; and what other terms the children use to express these symptoms. It also explores if there are differences in understanding and thoughts about symptoms between children who have the experience of cancer and those who do not. In all, 6 children with cancer and 8 healthy children participated in semistructured interviews. Children demonstrated a good understanding of symptom terms, yet were not always able to explain the symptoms. They had a rich vocabulary to talk about symptoms but did not use childish terms. Children with cancer had a more varied vocabulary for symptoms, but they did not use more medical terms. This study contributes to knowledge about children's understanding of symptoms that can be helpful to clinicians when communicating with children about their illness.

The Immunologic Revolution: Photoimmunology

PubMed Central

Ullrich, Stephen E.; Byrne, Scott N.

2011-01-01

UV radiation targets the skin and is a primary cause of skin cancer (both melanoma and non-melanoma skin cancer). Exposure to UV also suppresses the immune response, and UV-induced immune suppression is a major risk factor for skin cancer induction. The efforts of Dermatologists and Cancer Biologists to understand how UV exposure suppresses the immune response and contributes to skin cancer induction led to the development of the sub-discipline we call photoimmunology. Advances in photoimmunology have generally paralleled advances in immunology. However, there are a number of examples where investigations into the mechanisms underlying UV-induced immune suppression reshaped our understanding of basic immunological concepts. Unconventional immune regulatory roles for Langerhans cells, mast cells, and NKT cells as well as the immune suppressive function of lipid mediators of inflammation and alarmins, are just some examples of how advances in immunodermatology have altered our understanding of basic immunology. In this anniversary issue celebrating 75 years of Cutaneous Science, we will provide examples of how concepts that grew out of efforts by Immunologists and Dermatologists to understand immune regulation by UV radiation impacted on immunology in general. PMID:22170491

Beliefs about weight and breast cancer: an interview study with high risk women following a 12 month weight loss intervention.

PubMed

Wright, Claire E; Harvie, Michelle; Howell, Anthony; Evans, D Gareth; Hulbert-Williams, Nick; Donnelly, Louise S

2015-01-01

Breast cancer is the most common cancer in the UK. Lifestyle factors including excess weight contribute to risk of developing the disease. Whilst the exact links between weight and breast cancer are still emerging, it is imperative to explore how women understand these links and if these beliefs impact on successful behaviour change. Overweight/obese premenopausal women (aged 35-45) with a family history of breast cancer (lifetime risk 17-40%) were invited to a semi-structured interview following their participation in a 12 month weight loss intervention aimed at reducing their risk of breast cancer. Interviews were carried out with 9 women who successfully achieved ≥5% weight loss and 11 who were unsuccessful. Data were transcribed verbatim and analysed using thematic analysis. Three themes were developed from the analysis. The first theme how women construct and understand links between weight and breast cancer risk is composed of two subthemes, the construction of weight and breast cancer risk and making sense of weight and breast cancer risk. This theme explores women's understanding of what contributes to breast cancer risk and whether they believe that weight loss could reduce their breast cancer risk. The second theme motivation and adherence to weight loss interventions explains that breast cancer risk can be a motivating factor for adherence to a weight loss intervention. The final theme, acceptance of personal responsibility for health is composed of two subthemes responsibility for one's own health and responsibility for family health through making sensible lifestyle choices. Beliefs about weight and breast cancer risk were informed by social networks, media reports and personal experiences of significant others diagnosed with breast cancer. Our study has highlighted common doubts, anxieties and questions and the importance of providing a credible rationale for weight control and weight loss which addresses individual concerns. Counselling and health education material should be tailored to facilitate understanding of both genetic and modifiable risk factors and should do more help individuals to visualise the weight and breast cancer link.

Providing clinicians and patients with actual prognosis: cancer in the context of competing causes of death.

PubMed

Howlader, Nadia; Mariotto, Angela B; Woloshin, Steven; Schwartz, Lisa M

2014-11-01

To isolate progress against cancer from changes in competing causes of death, population cancer registries have traditionally reported cancer prognosis (net measures). But clinicians and cancer patients generally want to understand actual prognosis (crude measures): the chance of surviving, dying from the specific cancer and from competing causes of death in a given time period. To compare cancer and actual prognosis in the United States for four leading cancers-lung, breast, prostate, and colon-by age, comorbidity, and cancer stage and to provide templates to help patients, clinicians, and researchers understand actual prognosis. Using population-based registry data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated cancer prognosis (relative survival) and actual prognosis (five-year overall survival and the "crude" probability of dying from cancer and competing causes) for three important prognostic determinants (age, comorbidity [Charlson-score from 2012 SEER-Medicare linkage dataset] and cancer stage at diagnosis). For younger, healthier, and earlier stage cancer patients, cancer and actual prognosis estimates were quite similar. For older and sicker patients, these prognosis estimates differed substantially. For example, the five-year overall survival for an 85-year-old patient with colorectal cancer is 54% (cancer prognosis) versus 22% (actual prognosis)-the difference reflecting the patient's substantial chance of dying from competing causes. The corresponding five-year chances of dying from the patient's cancer are 46% versus 37%. Although age and comorbidity lowered actual prognosis, stage at diagnosis was the most powerful factor: The five-year chance of colon cancer death was 10% for localized stage and 83% for distant stage. Both cancer and actual prognosis measures are important. Cancer registries should routinely report both cancer and actual prognosis to help clinicians and researchers understand the difference between these measures and what question they can and cannot answer. We encourage them to use formats like the ones presented in this paper to communicate them clearly. Published by Oxford University Press 2014.

Immunotherapy of Cancer in 2012

PubMed Central

Kirkwood, John M.; Butterfield, Lisa H.; Tarhini, Ahmad A.; Zarour, Hassane; Kalinski, Pawel; Ferrone, Soldano

2012-01-01

The immunotherapy of cancer has made significant strides in the past few years due to improved understanding of the underlying principles of tumor biology and immunology. These principles have been critical in the development of immunotherapy in the laboratory and in the implementation of immunotherapy in the clinic. This improved understanding of immunotherapy, enhanced by increased insights into the mechanism of tumor immune response and its evasion by tumors, now permits manipulation of this interaction and elucidates the therapeutic role of immunity in cancer. Also important, this improved understanding of immunotherapy and the mechanisms underlying immunity in cancer has fueled an expanding array of new therapeutic agents for a variety of cancers. Pegylated interferon-α2b as an adjuvant therapy and ipilimumab as therapy for advanced disease, both of which were approved by the United States Food and Drug Administration for melanoma in March 2011, are 2 prime examples of how an increased understanding of the principles of tumor biology and immunology have been translated successfully from the laboratory to the clinical setting. Principles that guide the development and application of immunotherapy include antibodies, cytokines, vaccines, and cellular therapies. The identification and further elucidation of the role of immunotherapy in different tumor types, and the development of strategies for combining immunotherapy with cytotoxic and molecularly targeted agents for future multimodal therapy for cancer will enable even greater progress and ultimately lead to improved outcomes for patients receiving cancer immunotherapy. PMID:22576456

Non-malignant causes of hypercalcemia in cancer patients: a frequent and neglected occurrence.

PubMed

Soyfoo, M S; Brenner, K; Paesmans, M; Body, J J

2013-05-01

Hypercalcemia is a frequent finding in cancer patients and can be observed in any type of cancer. The physician in charge of cancer patients often ignores non-malignant causes of hypercalcemia. Our objective was to review the causes of hypercalcemia in a large series of cancer patients. We have retrospectively studied in a Cancer Centre all consecutive hypercalcemic (Ca> 10.5 mg/dl) patients over an 8-year period. Of 699 evaluated patients, 642 were analyzed after exclusion of patients whose hypercalcemia resolved after rehydration or who had a normal Ca level after correction for protein concentrations. Clinical information was gathered on the type of cancer, its histology, whether the disease was active or in complete remission, and on the presence of bone metastases. Biochemical data included serum Ca, P(i), proteins in all patients, PTH in most patients, and PTHrP, 25OH-Vitamin D, 1,25(OH)(2)-Vitamin D, TSH, and T4 in selected cases. By order of decreasing frequency, the main causes of hypercalcemia were cancer (69.0 %), primary hyperparathyroidism (24.6 %), hyperthyroidism (2.2 %), milk alkali syndrome (0.9 %), and sarcoidosis (0.45 %). In cancer-related causes, bone metastases accounted for 53.0 % of the cases, humoral hypercalcemia of malignancy (HHM) for 35.3 % while there were 11.7 % of cases apparently due to both HHM and bone metastases. Hypercalcemia was not due to cancer in 97 % (84/87) of the patients who were in complete remission. Even in patients with active neoplastic disease, the number of patients whose hypercalcemia was not due to cancer remained clinically relevant (115/555 = 20.5 %). In the 158 patients with primary hyperparathyroidism, 92 patients were in complete remission and 66 patients had active neoplastic disease. In this large series of hypercalcemia in cancer patients, the cause was not due to cancer in almost one third of the cases. Most patients considered to be in complete remission had hypercalcemia due to a benign condition. In that perspective, serum PTH determination is essential in the approach of hypercalcemic cancer patients since primary hyperparathyroidism is by far the first non-malignant cause of hypercalcemia.

Antitumor evaluation and 3D-QSAR studies of a new series of the spiropyrroloquinoline isoindolinone/aza-isoindolinone derivatives by comparative molecular field analysis (CoMFA).

PubMed

Sadeghzadeh, Masoud; Salahinejad, Maryam; Zarezadeh, Nahid; Ghandi, Mehdi; Baghery, Maryam Keshavarz

2017-11-01

In current study, antitumor activity of two series of the newly synthesized spiropyrroloquinoline isoindolinone and spiropyrroloquinoline aza-isoindolinone scaffolds was evaluated against three human breast normal and cancer cell lines (MCF-10A, MCF-7 and SK-BR-3) and compared with cytotoxicity values of doxorubicin and colchicine as the standard drugs. It was found that several compounds were endowed with cytotoxicity in the low micromolar range. Among these two series, compounds 6i, 6j, 6k and 7l, 7m, 7n, 7o containing 3-ethyl-1H-indole moiety were found to be highly effective against both cancer cell lines ranging from [Formula: see text] to [Formula: see text] in comparison with the corresponding analogs. Compared with human cancer cells, the most potent compounds did not show high cytotoxicity against human breast normal MCF-10A cells. Generally, most of the evaluated compounds 6a-l and 7a-o series showed more antitumor activity against SK-BR-3 than MCF-7 cells. Moreover, comparative molecular field analysis (CoMFA) as a popular tools of three-dimensional quantitative structure-activity relationship (3D-QSAR) studies was carried out on 27 spiropyrroloquinolineisoindolinone and spiropyrroloquinolineaza-isoindolinone derivatives with antitumor activity against on SK-BR-3 cells. The obtained CoMFA models showed statistically excellent performance, which also possessed good predictive ability for an external test set. The results confirm the important effect of molecular steric and electrostatic interactions of these compounds on in vitro cytotoxicity against SK-BR-3.

Cholesterol and Prostate Cancer

PubMed Central

Pelton, Kristine; Freeman, Michael R.; Solomon, Keith R.

2012-01-01

Summary Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations. PMID:22824430

Single center experience with third-generation cryosurgery for management of organ-confined prostate cancer: critical evaluation of short-term outcomes, complications, and patient quality of life.

PubMed

Hubosky, Scott G; Fabrizio, Michael D; Schellhammer, Paul F; Barone, Bethany B; Tepera, Christopher M; Given, Robert W

2007-12-01

Technical refinements such as improved ultrasonographic localization and the routine use of urethral warmers and small-gauge needle delivery systems have renewed interest in cryosurgical treatment as a minimally invasive option for selected patients with localized prostate cancer. Only three reports of quality of life (QoL) in prostate cryoablation exist, and none report on patients treated with third-generation cryoablative technology. We critically examine our initial series of consecutive patients at a single institution undergoing primary third-generation cryosurgical treatment of localized prostate cancer with respect to treatment outcome, morbidity profile, and QoL parameters. To our knowledge, this is the first QoL report on third-generation cryoablation of the prostate. We retrospectively review the records of 89 consecutive patients with median followup of 11 months (1-32) who have undergone third-generation cryosurgical ablation of the prostate as primary treatment for localized prostate cancer with intention to cure. Patients were risk stratified according to preprocedural parameters of prostate-specific antigen (PSA), clinical stage, and Gleason score. PSA trends were recorded and treatment effectiveness was observed using different definitions of biochemical failure. Charts were reviewed for postprocedure complications. Quality of life was measured prospectively using the University of California, Los Angeles, Prostate Cancer Index as well as American Urological Association symptom scores. We compare a percent of baseline score (%BS) for various domains between our series of patients treated with primary cryoablation with a series of patients undergoing brachytherapy for localized prostate cancer. Treatment success was defined by achievement of a PSA nadir of < or =0.1 ng/mL and by biochemical disease-free survival (BDFS) assessed with both a PSA threshold of < or =0.4 ng/dL over time and the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of three consecutive rises in PSA. According to risk stratification, 86%, 81.5%, and 78% of low-, intermediate-, and high-risk patients, respectively, achieved a PSA nadir of < or =0.1 ng/mL. Overall, at 12 months follow-up, 94% of patients achieved BDFS using ASTRO criteria while 70% achieved BDFS using a PSA threshold of < or =0.4 ng/mL. With risk stratification, 74%, 70%, and 60% of low-, intermediate-, and high-risk patients, respectively, achieved BDFS defined by PSA threshold of < or =0.4 ng/mL. Complications were rare. The response rate for Health Related Quality of Life (HRQoL) questionnaires was 71% for cryoablation patients and 51% for brachytherapy patients. At 12 months follow-up, patients undergoing cryoablation on average achieved urinary and bowel domain scores comparable to baseline, but sexual domains remained well below baseline. When compared with a brachytherapy series with better baseline sexual function (P = 0.04) and urinary function (P = 0.03), cryotherapy patients experienced more negative impact on sexual function steadily for up to 12 months (P = 0.02). Urinary function was similar between the groups until 18 months, at which time cryoablation patients fared better (P = 0.01); this was sustained up to 24 months (P = 0.04). Treatment success with cryosurgery varies with definition; however, our results are comparable to other series with regard to short-term cancer control. Complication rates in this series of third-generation cryosurgical patients are low. QoL characteristics of third-generation cryoablation are similar to those described in second-generation cryoablation series. Compared with brachytherapy, cryotherapy results in less irritative and obstructive voiding symptoms in the early post-treatment period and may improve urinary function up to 24 months after treatment. In a small group of older patients with baseline erectile dysfunction undergoing cryoablation, sexual function returns to 20% of its baseline value with up to 12 months follow-up.

The UF family of hybrid phantoms of the developing human fetus for computational radiation dosimetry

NASA Astrophysics Data System (ADS)

Maynard, Matthew R.; Geyer, John W.; Aris, John P.; Shifrin, Roger Y.; Bolch, Wesley

2011-08-01

Historically, the development of computational phantoms for radiation dosimetry has primarily been directed at capturing and representing adult and pediatric anatomy, with less emphasis devoted to models of the human fetus. As concern grows over possible radiation-induced cancers from medical and non-medical exposures of the pregnant female, the need to better quantify fetal radiation doses, particularly at the organ-level, also increases. Studies such as the European Union's SOLO (Epidemiological Studies of Exposed Southern Urals Populations) hope to improve our understanding of cancer risks following chronic in utero radiation exposure. For projects such as SOLO, currently available fetal anatomic models do not provide sufficient anatomical detail for organ-level dose assessment. To address this need, two fetal hybrid computational phantoms were constructed using high-quality magnetic resonance imaging and computed tomography image sets obtained for two well-preserved fetal specimens aged 11.5 and 21 weeks post-conception. Individual soft tissue organs, bone sites and outer body contours were segmented from these images using 3D-DOCTOR™ and then imported to the 3D modeling software package Rhinoceros™ for further modeling and conversion of soft tissue organs, certain bone sites and outer body contours to deformable non-uniform rational B-spline surfaces. The two specimen-specific phantoms, along with a modified version of the 38 week UF hybrid newborn phantom, comprised a set of base phantoms from which a series of hybrid computational phantoms was derived for fetal ages 8, 10, 15, 20, 25, 30, 35 and 38 weeks post-conception. The methodology used to construct the series of phantoms accounted for the following age-dependent parameters: (1) variations in skeletal size and proportion, (2) bone-dependent variations in relative levels of bone growth, (3) variations in individual organ masses and total fetal masses and (4) statistical percentile variations in skeletal size, individual organ masses and total fetal masses. The resulting series of fetal hybrid computational phantoms is applicable to organ-level and bone-level internal and external radiation dosimetry for human fetuses of various ages and weight percentiles

Improving the Instruction of Infinite Series

ERIC Educational Resources Information Center

Lindaman, Brian; Gay, A. Susan

2012-01-01

Calculus instructors struggle to teach infinite series, and students have difficulty understanding series and related concepts. Four instructional strategies, prominently used during the calculus reform movement, were implemented during a 3-week unit on infinite series in one class of second-semester calculus students. A description of each…

Synthesis and in vitro antiproliferative activity of 2-methyl-3-(2-piperazin-1-yl-ethyl)-pyrido[1,2-a]pyrimidin-4-one derivatives against human cancer cell lines.

PubMed

Mallesha, Lingappa; Mohana, Kikkeri N; Veeresh, Bantal; Alvala, Ravi; Mallika, Alvala

2012-01-01

A series of new 2-methyl-3-(2-piperazin-1-yl-ethyl)-pyrido[1,2-a]pyrimidin-4-one derivatives 6a-j were synthesized by a nucleophilic substitution reaction of 2-methyl-3-(2-piperazin-1-ylethyl)-pyrido[1,2-a]pyrimidin-4-one with various sulfonyl chlorides. The compounds were characterized by different spectral studies. All the compounds were evaluated for their antiproliferative effect using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method against four human cancer cell lines (K562, Colo-205, MDA-MB 231, IMR-32) for the time period of 24 h. Among the series, compounds 6d, 6e and 6i showed good activity on all cell lines except K562, whereas the other compounds in the series exhibited moderate activity. Compound 6d could be a potential anticancer agent and therefore deserves further research.

The molecular understanding of cancer: from the unspeakable illness to a curable disease.

PubMed

Pierotti, Marco A

2017-01-01

The beginning of our understanding of the molecular basis of cancer and the discovery in the 1980s of cancer associated genes, oncogenes, and tumour suppressor genes has led to cancer becoming a treatable condition rather than an unspeakable disease. In 1971, the then USA President, Richard Nixon, declared 'war against cancer' with a far too optimistic perspective of winning in just a few years. This tactic failed because our knowledge of the disease was still very limited and even its origin-viral or due to exposure to external agents-was still highly debated. A better understanding of the cause(s) of the origin of cancer led to its definition as a genetic disease at the somatic level and heralded a new era for molecular diagnosis and the development of more mechanistic evidence-based, targeted cancer therapies. However, the initial positive results were soon overshadowed by a major limitation of targeted agents, namely resistance mechanisms, which still represent an obstacle for the full eradication of the disease. More recently, effective therapeutic approaches have been developed in the field of 'immunotherapy'. The combination of novel therapies will hopefully result in effective cancer growth control and make the disease 'chronic'. The launch of the 'Moonshot Cancer Program' by President Barack Obama aims to significantly reduce cancer deaths in the next decade-let us see.

Should I Get Screened for Prostate Cancer?

MedlinePlus

... about being screened for prostate cancer with a prostate specific antigen (PSA) test. Before making a decision, men should ... Task Force Prostate Cancer Screening Final Recommendation Understanding Prostate Changes: A Health ... Cancer Institute) What Is Screening? ...

Understanding your colon cancer risk

MedlinePlus

Colon cancer - prevention; Colon cancer - screening ... We do not know what causes colon cancer, but we do know some of the things that may increase the risk of getting it, such as: Age. Your risk increases after ...

Providing Clinicians and Patients With Actual Prognosis: Cancer in the Context of Competing Causes of Death

PubMed Central

Mariotto, Angela B.; Woloshin, Steven; Schwartz, Lisa M.

2014-01-01

Background To isolate progress against cancer from changes in competing causes of death, population cancer registries have traditionally reported cancer prognosis (net measures). But clinicians and cancer patients generally want to understand actual prognosis (crude measures): the chance of surviving, dying from the specific cancer and from competing causes of death in a given time period. Objective To compare cancer and actual prognosis in the United States for four leading cancers—lung, breast, prostate, and colon—by age, comorbidity, and cancer stage and to provide templates to help patients, clinicians, and researchers understand actual prognosis. Method Using population-based registry data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated cancer prognosis (relative survival) and actual prognosis (five-year overall survival and the “crude” probability of dying from cancer and competing causes) for three important prognostic determinants (age, comorbidity [Charlson-score from 2012 SEER-Medicare linkage dataset] and cancer stage at diagnosis). Result For younger, healthier, and earlier stage cancer patients, cancer and actual prognosis estimates were quite similar. For older and sicker patients, these prognosis estimates differed substantially. For example, the five-year overall survival for an 85-year-old patient with colorectal cancer is 54% (cancer prognosis) versus 22% (actual prognosis)—the difference reflecting the patient’s substantial chance of dying from competing causes. The corresponding five-year chances of dying from the patient’s cancer are 46% versus 37%. Although age and comorbidity lowered actual prognosis, stage at diagnosis was the most powerful factor: The five-year chance of colon cancer death was 10% for localized stage and 83% for distant stage. Conclusion Both cancer and actual prognosis measures are important. Cancer registries should routinely report both cancer and actual prognosis to help clinicians and researchers understand the difference between these measures and what question they can and cannot answer. We encourage them to use formats like the ones presented in this paper to communicate them clearly. PMID:25417239

KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control

PubMed Central

Le Calvez-Kelm, Florence; Foll, Matthieu; Wozniak, Magdalena B.; Delhomme, Tiffany M.; Durand, Geoffroy; Chopard, Priscilia; Pertesi, Maroulio; Fabianova, Eleonora; Adamcakova, Zora; Holcatova, Ivana; Foretova, Lenka; Janout, Vladimir; Vallee, Maxime P.; Rinaldi, Sabina; Brennan, Paul; McKay, James D.; Byrnes, Graham B.; Scelo, Ghislaine

2016-01-01

The utility of KRAS mutations in plasma circulating cell-free DNA (cfDNA) samples as non-invasive biomarkers for the detection of pancreatic cancer has never been evaluated in a large case-control series. We applied a KRAS amplicon-based deep sequencing strategy combined with analytical pipeline specifically designed for the detection of low-abundance mutations to screen plasma samples of 437 pancreatic cancer cases, 141 chronic pancreatitis subjects, and 394 healthy controls. We detected mutations in 21.1% (N=92) of cases, of whom 82 (89.1%) carried at least one mutation at hotspot codons 12, 13 or 61, with mutant allelic fractions from 0.08% to 79%. Advanced stages were associated with an increased proportion of detection, with KRAS cfDNA mutations detected in 10.3%, 17,5% and 33.3% of cases with local, regional and systemic stages, respectively. We also detected KRAS cfDNA mutations in 3.7% (N=14) of healthy controls and in 4.3% (N=6) of subjects with chronic pancreatitis, but at significantly lower allelic fractions than in cases. Combining cfDNA KRAS mutations and CA19-9 plasma levels on a limited set of case-control samples did not improve the overall performance of the biomarkers as compared to CA19-9 alone. Whether the limited sensitivity and specificity observed in our series of KRAS mutations in plasma cfDNA as biomarkers for pancreatic cancer detection are attributable to methodological limitations or to the biology of cfDNA should be further assessed in large case-control series. PMID:27705932

Discovery of a new series of imidazo[1,2-a]pyridine compounds as selective c-Met inhibitors.

PubMed

Liu, Tong-Chao; Peng, Xia; Ma, Yu-Chi; Ji, Yin-Chun; Chen, Dan-Qi; Zheng, Ming-Yue; Zhao, Dong-Mei; Cheng, Mao-Sheng; Geng, Mei-Yu; Shen, Jing-Kang; Ai, Jing; Xiong, Bing

2016-05-01

Aberrant c-Met activation plays a critical role in cancer formation, progression and dissemination, as well as in development of resistance to anticancer drugs. Therefore, c-Met has emerged as an attractive target for cancer therapy. The aim of this study was to develop new c-Met inhibitors and elaborate the structure-activity relationships of identified inhibitors. Based on the predicted binding modes of Compounds 5 and 14 in docking studies, a new series of c-Met inhibitor-harboring 3-((1H-pyrrolo[3,2-c]pyridin-1-yl)sulfonyl)imidazo[1,2-a]pyridine scaffolds was discovered. Potent inhibitors were identified through extensive optimizations combined with enzymatic and cellular assays. A promising compound was further investigated in regard to its selectivity, its effects on c-Met signaling, cell proliferation and cell scattering in vitro. The most potent Compound 31 inhibited c-Met kinase activity with an IC50 value of 12.8 nmol/L, which was >78-fold higher than those of a panel of 16 different tyrosine kinases. Compound 31 (8, 40, 200 nmol/L) dose-dependently inhibited the phosphorylation of c-Met and its key downstream Akt and ERK signaling cascades in c-Met aberrant human EBC-1 cancer cells. In 12 human cancer cell lines harboring different background levels of c-Met expression/activation, Compound 31 potently inhibited c-Met-driven cell proliferation. Furthermore, Compound 31 dose-dependently impaired c-Met-mediated cell scattering of MDCK cells. This series of c-Met inhibitors is a promising lead for development of novel anticancer drugs.

Dendritic cells for active anti-cancer immunotherapy: targeting activation pathways through genetic modification.

PubMed

Breckpot, Karine; Escors, David

2009-12-01

Tumour immunotherapy has become a treatment modality for cancer, harnessing the immune system to recognize and eradicate tumour cells specifically. It is based on the expression of tumour associated antigens (TAA) by the tumour cells and aims at the induction of TAA-specific effector T cell responses, whilst overruling various mechanisms that can hamper the anti-tumour immune response, e.g. regulatory T cells (Treg). (Re-) activation of effector T cells requires the completion of a carefully orchestrated series of specific steps. Particularly important is the provision of TAA presentation and strong stimulatory signals, delivered by co-stimulatory surface molecules and cytokines. These can only be delivered by professional antigen-presenting cells, in particular dendritic cells (DC). Therefore, DC need to be loaded with TAA and appropriately activated. It is not surprising that an extensive part of DC research has focused on the delivery of both TAA and activation signals to DC, developing a one step approach to obtain potent stimulatory DC. The simultaneous delivery of TAA and activation signals is therefore the topic of this review, emphasizing the role of DC in mediating T cell activation and how we can manipulate DC for the pill-pose of enhancing tumour immunotherapy. As we gain a better understanding of the molecular and cellular mechanisms that mediate induction of TAA-specific T cells, rational approaches for the activation of T cell responses can be developed for the treatment of cancer.

Autoimmune Neurology of the Central Nervous System.

PubMed

Tobin, W Oliver; Pittock, Sean J

2017-06-01

This article reviews the rapidly evolving spectrum of autoimmune neurologic disorders with a focus on those that involve the central nervous system, providing an understanding of how to approach the diagnostic workup of patients presenting with central nervous system symptoms or signs that could be immune mediated, either paraneoplastic or idiopathic, to guide therapeutic decision making. The past decade has seen a dramatic increase in the discovery of novel neural antibodies and their targets. Many commercial laboratories can now test for these antibodies, which serve as diagnostic markers of diverse neurologic disorders that occur on an autoimmune basis. Some are highly specific for certain cancer types, and the neural antibody profiles may help direct the physician's cancer search. The diagnosis of an autoimmune neurologic disorder is aided by the detection of an objective neurologic deficit (usually subacute in onset with a fluctuating course), the presence of a neural autoantibody, and improvement in the neurologic status after a course of immunotherapy. Neural autoantibodies should raise concern for a paraneoplastic etiology and may inform a targeted oncologic evaluation (eg, N-methyl-D-aspartate [NMDA] receptor antibodies are associated with teratoma, antineuronal nuclear antibody type 1 [ANNA-1, or anti-Hu] are associated with small cell lung cancer). MRI, EEG, functional imaging, videotaped evaluations, and neuropsychological evaluations provide objective evidence of neurologic dysfunction by which the success of immunotherapy may be measured. Most treatment information emanates from retrospective case series and expert opinion. Nonetheless, early intervention may allow reversal of deficits in many patients and prevention of future disability.

A mixed methods assessment of coping with pediatric cancer

PubMed Central

Alderfer, Melissa A.; Deatrick, Janet A.; Marsac, Meghan L.

2014-01-01

The purpose of this study was to describe child coping and parent coping assistance with cancer-related stressors during treatment. Fifteen children (aged 6-12) with cancer and their parents (N = 17) completed semi-structured interviews and self-report measures to assess coping and coping assistance. Results suggest families utilized a broad array of approach and avoidance strategies to manage cancer and its treatment. Quantitative and qualitative assessments provided complementary and unique contributions to understanding coping among children with cancer and their parents. Using a mixed methods approach to assess coping provides a richer understanding of families’ experiences, which can better inform clinical practice. PMID:24428250

Preventable Exposures Associated With Human Cancers

PubMed Central

Baan, Robert; Straif, Kurt; Grosse, Yann; Lauby-Secretan, Béatrice; El Ghissassi, Fatiha; Bouvard, Véronique; Benbrahim-Tallaa, Lamia; Guha, Neela; Freeman, Crystal; Galichet, Laurent; Wild, Christopher P.

2011-01-01

Information on the causes of cancer at specific sites is important to cancer control planners, cancer researchers, cancer patients, and the general public. The International Agency for Research on Cancer (IARC) Monograph series, which has classified human carcinogens for more than 40 years, recently completed a review to provide up-to-date information on the cancer sites associated with more than 100 carcinogenic agents. Based on IARC’s review, we listed the cancer sites associated with each agent and then rearranged this information to list the known and suspected causes of cancer at each site. We also summarized the rationale for classifications that were based on mechanistic data. This information, based on the forthcoming IARC Monographs Volume 100, offers insights into the current state-of-the-science of carcinogen identification. Use of mechanistic data to identify carcinogens is increasing, and epidemiological research is identifying additional carcinogens and cancer sites or confirming carcinogenic potential under conditions of lower exposure. Nevertheless, some common human cancers still have few (or no) identified causal agents. PMID:22158127

Understandability of Patient Information Booklets for Patients with Cancer.

PubMed

Keinki, Christian; Zowalla, Richard; Wiesner, Martin; Koester, Marie Jolin; Huebner, Jutta

2018-06-01

The improvement of health literacy in general and the information of individual patient is a major concern of the German national cancer plan and similar initiatives in other western countries. The aim of our study was to assess the readability and understandability of information booklets for cancer patients available at German Web sites. A support vector machine (SVM) was used to discriminate between laymen- and expert-centric patient information booklets about nine most common tumor types. All booklets had to be available for free at the Internet. A total of 52 different patient booklets were downloaded and assessed. Overall, the assessment of all booklets showed that an understandability level L of 4.6 and therefore increased medical background knowledge is required to understand a random text selected from the sample. The assessed information booklets on cancer show very limited suitability for laymen. We were able to demonstrate that a medical background is necessary to understand the examined booklets. The current study highlights the need to create information material adjusted to the needs of laymen. Assessing understandability before publication, especially for laymen with low health literacy, could ensure the suitability and thus quality of the information material.

Cancer Imaging Phenomics Software Suite: Application to Brain and Breast Cancer | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

The transition of oncologic imaging from its “industrial era” to it is “information era” demands analytical methods that 1) extract information from this data that is clinically and biologically relevant; 2) integrate imaging, clinical, and genomic data via rigorous statistical and computational methodologies in order to derive models valuable for understanding cancer mechanisms, diagnosis, prognostic assessment, response evaluation, and personalized treatment management; 3) are available to the biomedical community for easy use and application, with the aim of understanding, diagnosing, an

In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival.

PubMed

Ladoire, Sylvain; Mignot, Grégoire; Dabakuyo, Sandrine; Arnould, Laurent; Apetoh, Lionel; Rébé, Cedric; Coudert, Bruno; Martin, Francois; Bizollon, Marie Hélène; Vanoli, André; Coutant, Charles; Fumoleau, Pierre; Bonnetain, Franck; Ghiringhelli, François

2011-07-01

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. However, the predictive value of tumour-infiltrating lymphocytes after neoadjuvant chemotherapy for breast cancer remains unknown. We hypothesized that the nature of the immune infiltrate following neoadjuvant chemotherapy would predict patient survival. In a series of 111 consecutive HER2- and a series of 51 non-HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy, we studied by immunohistochemistry tumour infiltration by FOXP3 and CD8 T lymphocytes before and after chemotherapy. Kaplan-Meier analysis and Cox modelling were used to assess relapse-free survival (RFS) and overall survival (OS). A predictive scoring system using American Joint Committee on Cancer (AJCC) pathological staging and immunological markers was created. Association of high CD8 and low FOXP3 cell infiltrates after chemotherapy was significantly associated with improved RFS (p = 0.02) and OS (p = 0.002), and outperformed classical predictive factors in multivariate analysis. A combined score associating CD8/FOXP3 ratio and pathological AJCC staging isolated a subgroup of patients with a long-term overall survival of 100%. Importantly, this score also identified patients with a favourable prognosis in an independent cohort of HER2-negative breast cancer patients. These results suggest that immunological CD8 and FOXP3 cell infiltrate after treatment is an independent predictive factor of survival in breast cancer patients treated with neoadjuvant chemotherapy and provides new insights into the role of the immune milieu and cancer. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

HORIZONS: Understanding the Impact of Cancer Diagnosis and Treatment on Everyday Life

ClinicalTrials.gov

2018-04-09

Breast Cancer Female; Breast Neoplasm; Non-Hodgkin's B-cell Lymphoma; Non-Hodgkin's Lymphoma, Adult High Grade; NonHodgkin Lymphoma; Diffuse Large B Cell Lymphoma; Diffuse Large Cell Lymphoma, Adult; Ovarian Cancer; Ovarian Neoplasm; Endometrial Cancer; Endometrial Neoplasms; Cervical Cancer; Cervical Neoplasm; Primary Peritoneal Carcinoma; Fallopian Tube Cancer; Fallopian Tube Neoplasms; Vulvar Cancer; Vulvar Neoplasms

Elaeodendron orientale as a source of cytotoxic cardenolides.

PubMed

Osorio, Alex A; López, Manuel R; Jiménez, Ignacio A; Moujir, Laila M; Rodríguez, Matías L; Bazzocchi, Isabel L

2014-09-01

In the present study, we report six cardiac glycosides (1-6) along with four known ones (7-10) isolated from the leaves and fruits of Elaeodendron orientale. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR, and the absolute configuration of 1 was determined by X-ray diffraction analysis. The compounds were evaluated for growth inhibitory activity against a panel of human cancer cell lines, HeLa, A-549, MCF-7 and HL-60, and normal Vero cells. Four compounds from this series (5 and 7-9, IC50 values ranging from 0.01 to 0.07μM) exhibited cytotoxicity against three of the cancer cell lines assayed that was similar to or higher than the well-known therapies digoxin and digitoxigenin. Taking into account the narrow safety range of cardiac glycosides used in clinic, this series shows a selectivity index higher than 3 for three of the cancer cell lines assayed, increasing their interest for further study. Copyright © 2014 Elsevier Ltd. All rights reserved.

Male unemployment and cause-specific mortality in postwar Scotland.

PubMed

Forbes, J F; McGregor, A

1987-01-01

This article reports a time-series analysis of male unemployment and mortality in postwar Scotland. The results provide little evidence to support the hypothesis that unemployment exerts a significant and consistent positive impact on mortality from all causes, lung cancer, ischemic heart disease, and cerebrovascular disease. Although significant positive associations between unemployment and mortality from lung cancer and ischemic heart disease were detected for older males in the short term, the long-term association between unemployment and mortality tends to be negative. Further progress on establishing possible causal relationships between unemployment and health requires both the collaboration of medical and social scientists and a well designed prospective study that avoids many of the problems associated with time-series and cross-sectional analyses.

Synthesis, characterization, and anticancer activity of a series of ketone-N(4)-substituted thiosemicarbazones and their ruthenium(II) arene complexes.

PubMed

Su, Wei; Qian, Quanquan; Li, Peiyuan; Lei, Xiaolin; Xiao, Qi; Huang, Shan; Huang, Chusheng; Cui, Jianguo

2013-11-04

A series of ketone-N(4)-substituted thiosemicarbazone (TSC) compounds (L1-L9) and their corresponding [(η(6)-p-cymene)Ru(II)(TSC)Cl](+/0) complexes (1-9) were synthesized and characterized by NMR, IR, elemental analysis, and HR-ESI-mass spectrometry. The molecular structures of L4, L9, 1-6, and 9 were determined by single-crystal X-ray diffraction analysis. The compounds were further evaluated for their in vitro antiproliferative activities against the SGC-7901 human gastric cancer, BEL-7404 human liver cancer, and HEK-293T noncancerous cell lines. Furthermore, the interactions of the compounds with DNA were followed by electrophoretic mobility spectrometry studies.

Design and optimization of a series of 1-sulfonylpyrazolo[4,3-b]pyridines as selective c-Met inhibitors.

PubMed

Ma, Yuchi; Sun, Guangqiang; Chen, Danqi; Peng, Xia; Chen, Yue-Lei; Su, Yi; Ji, Yinchun; Liang, Jin; Wang, Xin; Chen, Lin; Ding, Jian; Xiong, Bing; Ai, Jing; Geng, Meiyu; Shen, Jingkang

2015-03-12

c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonylpyrazolo[4,3-b]pyridine 9 with improved DMPK properties was discovered. Further elaboration of π-π stacking interactions and solvent accessible polar moieties led to a series of highly potent and selective type I c-Met inhibitors. On the basis of in vitro and in vivo pharmacological and pharmacokinetics studies, compound 46 was selected as a preclinical candidate for further anticancer drug development.

[Prospectic evaluation of the Italian Workers' Compensation Authority in a large case series of Occupational sino-nasal cancers].

PubMed

Casà, M; Bonzini, M; Parassoni, D; Tavecchio, D; Facchinetti, N; Castelnuovo, P; Ferrario, M M

2012-01-01

Sino-nasal cancer (SNC) are rare tumours with an elevated occupational etiological fraction, due both to well-established risk factors (wood and leather) and to more rare carcinogens. We evaluated the assessment for workers' compensation performed by the Italian Authority (INAL) in a case-series of occupational SNC (N = 45). We observed an elevated proportion of cases that were recognised as occupational, overall (36 on 39) and for any histotype. INAIL tended to recognize as professional not only patients with exposure to wood and leather but also cases with a documented exposure to formaldehyde, metal, polycyclic hydrocarbons. Significant differences across Italian macro-regions appeared, when the amount of worker compensation was investigated.

Foundation laid for understanding essentials of cell division | Center for Cancer Research

Cancer.gov

NCI Center for Cancer Research (CCR) scientists reported new molecular insights into understanding a critical aspect of cell division through a cross-disciplinary effort that combines cryo-electron microscopy (cryo-EM), biochemical and cell biological approaches. Errors in segregation of chromosomes during mitosis can lead to an aberrant number of chromosomes, a condition known as aneuploidy, which can lead to cancer and birth defects. Read more…

Integrated Cancer Research in Five Thematic Areas of Interest

DTIC Science & Technology

2007-07-01

understand cancer genetics. CDMRP funding also enabled many young investigators to initiate new research projects to better advance the body of understanding...vital to this year of CDMRP funding are summarized below. Over the life -span of the award, CDMRP funding focused in cancer research infrastructure which...Instrumentation- Continued support of an ISO 7 clean room for the Digital Transmission Electron Microscope *. 7) Instrumentation- On going suport and

Synthesis, antiproliferative and antibacterial activity of new amides of salinomycin.

PubMed

Antoszczak, Michał; Maj, Ewa; Stefańska, Joanna; Wietrzyk, Joanna; Janczak, Jan; Brzezinski, Bogumil; Huczyński, Adam

2014-04-01

A series of 11 novel amides of salinomycin were synthesized for the first time. All the obtained compounds were found to show potent antiproliferative activity against human cancer cell lines including the drug-resistant cancer cells. Four new salinomycin derivatives revealed good antibacterial activity against clinical isolates of methicillin-resistant Staphylococcus epidermidis (MRSE). Copyright © 2014 Elsevier Ltd. All rights reserved.

Characterization of BRCA2 Mutation in a Series of Functional Assays

DTIC Science & Technology

2005-05-01

9 Appendices .................................................................................... 10 Abstract Mutations in the BRCA2 gene account for...approximately 20% of all hereditary breast cancer. Many individuals undergo expensive clinical testing for mutations in the BRCA2 gene in order to...BRCA2 breast and ovarian cancer predisposition gene was identified in 1995. Mutations in the gene account for approximately 20% of all hereditary breast

Function of ZFAND3 in the DNA Damage Response

DTIC Science & Technology

2012-06-01

Training My training in molecular cancer biology has continued in the past year. Primary training activities include attendance at the following seminar...series: Vanderbilt-Ingram Cancer Center, bi- monthly seminars, Center in Molecular Toxicology weekly seminars, Department of Biochemistry weekly... thesis committee. I presented both written and oral progress reports at these meetings and received feedback on research directions. Reportable

Hyperspectral imaging of skin and lung cancers

NASA Astrophysics Data System (ADS)

Zherdeva, Larisa A.; Bratchenko, Ivan A.; Alonova, Marina V.; Myakinin, Oleg O.; Artemyev, Dmitry N.; Moryatov, Alexander A.; Kozlov, Sergey V.; Zakharov, Valery P.

2016-04-01

The problem of cancer control requires design of new approaches for instrumental diagnostics, as the accuracy of cancer detection on the first step of diagnostics in clinics is slightly more than 50%. In this study, we present a method of visualization and diagnostics of skin and lung tumours based on registration and processing of tissues hyperspectral images. In a series of experiments registration of hyperspectral images of skin and lung tissue samples is carried out. Melanoma, basal cell carcinoma, nevi and benign tumours are studied in skin ex vivo and in vivo experiments; adenocarcinomas and squamous cell carcinomas are studied in ex vivo lung experiments. In a series of experiments the typical features of diffuse reflection spectra for pathological and normal tissues were found. Changes in tissues morphology during the tumour growth lead to the changes of blood and pigments concentration, such as melanin in skin. That is why tumours and normal tissues maybe differentiated with information about spectral response in 500-600 nm and 600 - 670 nm areas. Thus, hyperspectral imaging in the visible region may be a useful tool for cancer detection as it helps to estimate spectral properties of tissues and determine malignant regions for precise resection of tumours.

Discovery and Pharmacokinetic and Pharmacological Properties of the Potent and Selective MET Kinase Inhibitor 1-{6-[6-(4-Fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-ylsulfanyl]benzothiazol-2-yl}-3-(2-morpholin-4-ylethyl)urea (SAR125844).

PubMed

Ugolini, Antonio; Kenigsberg, Mireille; Rak, Alexey; Vallée, Francois; Houtmann, Jacques; Lowinski, Maryse; Capdevila, Cécile; Khider, Jean; Albert, Eva; Martinet, Nathalie; Nemecek, Conception; Grapinet, Sandrine; Bacqué, Eric; Roesner, Manfred; Delaisi, Christine; Calvet, Loreley; Bonche, Fabrice; Semiond, Dorothée; Egile, Coumaran; Goulaouic, Hélène; Schio, Laurent

2016-08-11

The HGF/MET pathway is frequently activated in a variety of cancer types. Several selective small molecule inhibitors of the MET kinase are currently in clinical evaluation, in particular for NSCLC, liver, and gastric cancer patients. We report herein the discovery of a series of triazolopyridazines that are selective inhibitors of wild-type (WT) MET kinase and several clinically relevant mutants. We provide insight into their mode of binding and report unprecedented crystal structures of the Y1230H variant. A multiparametric chemical optimization approach allowed the identification of compound 12 (SAR125844) as a development candidate. In this chemical series, absence of CYP3A4 inhibition was obtained at the expense of satisfactory oral absorption. Compound 12, a promising parenteral agent for the treatment of MET-dependent cancers, promoted sustained target engagement at tolerated doses in a human xenograft tumor model. Preclinical pharmacokinetics conducted in several species were predictive for the observed pharmacokinetic behavior of 12 in cancer patients.

Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

PubMed

Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

2014-01-10

The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

The emerging role of skeletal muscle oxidative metabolism as a biological target and cellular regulator of cancer-induced muscle wasting.

PubMed

Carson, James A; Hardee, Justin P; VanderVeen, Brandon N

2016-06-01

While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle's metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Emerging Role of Skeletal Muscle Metabolism as a Biological Target and Cellular Regulator of Cancer-Induced Muscle Wasting

PubMed Central

Carson, James A.; Hardee, Justin P.; VanderVeen, Brandon N.

2015-01-01

While skeletal muscle mass is an established primary outcome related to understanding cancer cachexia mechanisms, considerable gaps exist in our understanding of muscle biochemical and functional properties that have recognized roles in systemic health. Skeletal muscle quality is a classification beyond mass, and is aligned with muscle’s metabolic capacity and substrate utilization flexibility. This supplies an additional role for the mitochondria in cancer-induced muscle wasting. While the historical assessment of mitochondria content and function during cancer-induced muscle loss was closely aligned with energy flux and wasting susceptibility, this understanding has expanded to link mitochondria dysfunction to cellular processes regulating myofiber wasting. The primary objective of this article is to highlight muscle mitochondria and oxidative metabolism as a biological target of cancer cachexia and also as a cellular regulator of cancer-induced muscle wasting. Initially, we examine the role of muscle metabolic phenotype and mitochondria content in cancer-induced wasting susceptibility. We then assess the evidence for cancer-induced regulation of skeletal muscle mitochondrial biogenesis, dynamics, mitophagy, and oxidative stress. In addition, we discuss environments associated with cancer cachexia that can impact the regulation of skeletal muscle oxidative metabolism. The article also examines the role of cytokine-mediated regulation of mitochondria function regulation, followed by the potential role of cancer-induced hypogonadism. Lastly, a role for decreased muscle use in cancer-induced mitochondrial dysfunction is reviewed. PMID:26593326

Proceedings of the 3rd Annual Albert Institute for Bladder Cancer Research Symposium.

PubMed

Flaig, Thomas W; Kamat, Ashish M; Hansel, Donna; Ingersoll, Molly A; Barton Grossman, H; Mendelsohn, Cathy; DeGraff, David; Liao, Joseph C; Taylor, John A

2017-07-27

The Third Annual Albert Institute Bladder Symposium was held on September 8-10th, 2016, in Denver Colorado. Participants discussed several critical topics in the field of bladder cancer: 1) Best practices for tissue analysis and use to optimize correlative studies, 2) Modeling bladder cancer to facilitate understanding and innovation, 3) Targeted therapies for bladder cancer, 4) Tumor phylogeny in bladder cancer, 5) New Innovations in bladder cancer diagnostics. Our understanding of and approach to treating urothelial carcinoma is undergoing rapid advancement. Preclinical models of bladder cancer have been leveraged to increase our basic and mechanistic understanding of the disease. With the approval of immune checkpoint inhibitors for the treatment of advanced urothelial carcinoma, the treatment approach for these patients has quickly changed. In this light, molecularly-defined subtypes of bladder cancer and appropriate pre-clinical models are now essential to the further advancement and appropriate application of these therapeutic improvements. The optimal collection and processing of clinical urothelial carcinoma tissues samples will also be critical in the development of predictive biomarkers for therapeutic selection. Technological advances in other areas including optimal imaging technologies and micro/nanotechnologies are being applied to bladder cancer, especially in the localized setting, and hold the potential for translational impact in the treatment of bladder cancer patients. Taken together, advances in several basic science and clinical areas are now converging in bladder cancer. These developments hold the promise of shaping and improving the clinical care of those with the disease.

Patient preference: a comparison of electronic patient-completed questionnaires with paper among cancer patients.

PubMed

Martin, P; Brown, M C; Espin-Garcia, O; Cuffe, S; Pringle, D; Mahler, M; Villeneuve, J; Niu, C; Charow, R; Lam, C; Shani, R M; Hon, H; Otsuka, M; Xu, W; Alibhai, S; Jenkinson, J; Liu, G

2016-03-01

In this study, we compared cancer patients preference for computerised (tablet/web-based) surveys versus paper. We also assessed whether the understanding of a cancer-related topic, pharmacogenomics is affected by the survey format, and examined differences in demographic and medical characteristics which may affect patient preference and understanding. Three hundred and four cancer patients completed a tablet-administered survey and another 153 patients completed a paper-based survey. Patients who participated in the tablet survey were questioned regarding their preference for survey format administration (paper, tablet and web-based). Understanding was assessed with a 'direct' method, by asking patients to assess their understanding of genetic testing, and with a 'composite' score. Patients preferred administration with tablet (71%) compared with web-based (12%) and paper (17%). Patients <65 years old, non-Caucasians and white-collar professionals significantly preferred the computerised format following multivariate analysis. There was no significant difference in understanding between the paper and tablet survey with direct questioning or composite score. Age (<65 years) and white-collar professionals were associated with increased understanding (both P = 0.03). There was no significant difference in understanding between the tablet and print survey in a multivariate analysis. Patients overwhelmingly preferred computerised surveys and understanding of pharmacogenomics was not affected by survey format. © 2015 John Wiley & Sons Ltd.

Utilization of hospital services for cancer care in Mexico.

PubMed

Hernández-Ávila, Juan Eugenio; Palacio-Mejía, Lina Sofía; González-González, Leonel; Morales-Carmona, Evangelina; Espín-Arellano, Lucino Iván; Fernández-Niño, Julián Alfredo; Mohar-Betancourt, Alejandro; Hernández-Ávila, Mauricio

2016-04-01

To analyze the utilization of hospital services for cancer care by location, sex, age group and care institution in Mexico from 2004-2013. Time series study from 2004-2013, based on administrative records of hospital discharges for cancer in the health sector, including the private sector. The utilization rate increased significantly from 290 to 360 per 100 000 inhabitants. A total of 62% of hospital discharges related to malignant tumors were concentrated in eight types of cancer. Leukemia, breast and colorectal cancers almost doubled in the period. While lung cancer showed a decline among men, it increased among women. A total of 63.1% of cancer patients were women, and 81% of cases occurred in the public sector. From 2011, the Ministry of Health was the main provider of hospital services for cancer care. Increases in utilization were mainly found in the Ministry of Health, quite possibly as a result of the implementation of universal insurance.

Evolutionary foundations for cancer biology.

PubMed

Aktipis, C Athena; Nesse, Randolph M

2013-01-01

New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles-cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations-provide a foundation for understanding, preventing, and treating cancer.

Evolutionary foundations for cancer biology

PubMed Central

Aktipis, C Athena; Nesse, Randolph M

2013-01-01

New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles—cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations—provide a foundation for understanding, preventing, and treating cancer. PMID:23396885

Atomic Particle Detection, Understanding the Atom Series.

ERIC Educational Resources Information Center

Hellman, Hal

This booklet is one of the booklets in the "Understanding the Atom Series" published by the U. S. Atomic Energy Commission for high school science teachers and their students. The instruments used to detect both particles and electromagnetic radiation that emerge from the nucleus are described. The counters reviewed include ionization chambers,…

Key Understandings in School Mathematics: 1

ERIC Educational Resources Information Center

Watson, Anne

2010-01-01

This article is the first in a series which draws on findings from Nunes, Watson and Bryant (2009): "Key understandings in school mathematics: a report to the Nuffield Foundation." The Nuffield report is soundly based on research about how children learn some of the concepts involved in mathematics. In this series of articles the author takes key…

Nuclear Power and the Environment, Understanding the Atom Series.

ERIC Educational Resources Information Center

Atomic Energy Commission, Oak Ridge, TN. Div. of Technical Information.

This booklet is one of the booklets in the "Understanding the Atom Series" published by the U. S. Atomic Energy Commission for high school science teachers and their students. Discussion concentrates on the radiological and thermal aspects of the environmental effects of nuclear power plants; on the procedures followed by the Atomic Energy…

From hazard identification to weighing the benefits and drawbacks of prevention

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vainio, Harri; Weiderpass, Elisabete

2005-09-01

In this commentary, we briefly summarize and give examples of evaluations done by the International Agency for Research on Cancer, WHO (IARC-WHO, Lyon, France) about the identification of carcinogenic substances or agents and the evaluation of the efficacy and effectiveness of cancer preventive substances, agents or strategies. In the 1970's the IARC initiated a series of Monographs on the Evaluation of Carcinogenic Risks to Humans for the purposes of primary prevention. During the last 35 years of the IARC Monographs, many agents that are important to the public health perspective have been evaluated. The agent or exposure is described andmore » classified according to the wording of one of the following groups: group 1, carcinogenic to humans; group 2A, probably carcinogenic to humans; group 2B, possibly carcinogenic to humans; group 3, not classifiable as to its carcinogenicity to humans; group 4, probably not carcinogenic to humans. In 1997, the IARC started a new series of handbooks, the IARC Handbooks of Cancer Prevention, which aimed for the evaluation of efficacy and effectiveness of cancer preventive agents and strategies. The process of evaluation is quite similar to the IARC Monographs. In total, 10 Handbooks were published in topics such as mammography screening, cervical cancer screening, consumption of fruits and vegetables, cruciferous vegetables, and weight control and physical activity. We discuss in general terms ways of preventing cancer and of evaluating preventive strategies, giving as example mammography screening.« less

Advances in Molecular Pathology and Treatment of Periampullary Cancers.

PubMed

Chandrasegaram, Manju D; Chen, John W; Price, Timothy J; Zalcberg, John; Sjoquist, Katrin; Merrett, Neil D

2016-01-01

Periampullary cancers (PACs) include the following 4 traditional anatomic subtypes: pancreatic, ampullary, biliary, or duodenal cancers. This review was performed to highlight recent advances in the genomic and molecular understanding of each PAC subtype and the advances in chemotherapeutic and molecular trials in these cancer subtypes. Recent advances have highlighted differences in the genomic and molecular features within each PAC subtype. Ampullary cancers can now be further defined accurately into their intestinal and pancreatobiliary subtypes using histomolecular profiling. K-ras mutation, which occurs in most pancreatic cancers, is found to occur less frequently in ampullary (42%-52%), biliary (22%-23%), and duodenal cancers (32%-35%), suggesting crucial differences in targetable mutations in these cancer subtypes.Ampullary cancers of intestinal subtype and duodenal cancers seem to share similarities with colorectal cancer, given that they respond to similar chemotherapeutic regimens. This has potential implications for clinical trials and treatment selection, where PACs are often considered together. Future trials should be designed in view of our increased understanding of the different anatomic and histomolecularly profiled subtypes of PAC cancers, which respects their individual molecular characteristics, phenotype, and response to treatment.

Investigation of prostate cancer cells using NADH and Tryptophan as biomarker: multiphoton FLIM-FRET microscopy

NASA Astrophysics Data System (ADS)

Rehman, Shagufta; O'Melia, Meghan J.; Wallrabe, Horst; Svindrych, Zdenek; Chandra, Dhyan; Periasamy, Ammasi

2016-03-01

Fluorescence Lifetime Imaging (FLIM) can be used to understand the metabolic activity in cancer. Prostate cancer is one of the leading cancers in men in the USA. This research focuses on FLIM measurements of NAD(P)H and Tryptophan, used as biomarkers to understand the metabolic activity in prostate cancer cells. Two prostate cancers and one normal cell line were used for live-cell FLIM measurements on Zeiss780 2P confocal microscope with SPCM FLIM board. Glucose uptake and glycolysis proceeds about ten times faster in cancer than in non-cancerous tissues. Therefore, we assessed the glycolytic activity in the prostate cancer in comparison to the normal cells upon glucose stimulation by analyzing the NAD(P)H and Trp lifetime distribution and efficiency of energy transfer (E%). Furthermore, we treated the prostate cancer cells with 1μM Doxorubicin, a commonly used anti-cancer chemotherapeutic. Increase in NADH a2%, an indicator of increased glycolysis and increased E% between Trp and NAD(P)H were seen upon glucose stimulation for 30min. The magnitude of shift to the right for NAD(P)H a2% and E% distribution was higher in prostate cancer versus the normal cells. Upon treatment with Doxorubicin decrease in cellular metabolism was seen at 15 and 30 minutes. The histogram for NAD(P)H a2% post-treatment for prostate cancer cells showed a left shift compared to the untreated control suggesting decrease in glycolysis and metabolic activity opposite to what was observed after glucose stimulation. Hence, NAD(P)H and Trp lifetimes can be used biomarkers to understand metabolic activity in prostate cancer and upon chemotherapeutic interventions.

Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy.

PubMed

Zhang, Jin; Wang, Guan; Zhou, Yuxin; Chen, Yi; Ouyang, Liang; Liu, Bo

2018-05-01

Autophagy is an evolutionarily conserved, multi-step lysosomal degradation process for the clearance of damaged or superfluous proteins and organelles. Accumulating studies have recently revealed that autophagy is closely related to a variety of types of cancer; however, elucidation of its Janus role of either tumor-suppressive or tumor-promoting still remains to be discovered. In this review, we focus on summarizing the context-dependent role of autophagy and its complicated molecular mechanisms in different types of cancer. Moreover, we discuss a series of small-molecule compounds targeting autophagy-related proteins or the autophagic process for potential cancer therapy. Taken together, these findings would shed new light on exploiting the intricate mechanisms of autophagy and relevant small-molecule compounds as potential anti-cancer drugs to improve targeted cancer therapy.

Cancer through black eyes - The views of UK based black men towards cancer: A constructivist grounded theory study.

PubMed

Mulugeta, Betselot; Williamson, Susan; Monks, Rob; Hack, Thomas; Beaver, Kinta

2017-08-01

Little is known about black African (BA) and black African-Caribbean (BAC) men's views towards cancer; yet culture and acculturation can contribute to the way in which people understand, explain and develop their attitudes towards cancer. Hence, cancer prevention and early detection strategies may not be sensitive to United Kingdom (UK)-based black men's views, affecting their awareness of risk factors and early detection services. This study explored the views of UK-based BA and BAC men towards cancer. In collaboration with black community organisations based in four major cities in the UK, 25 participants were recruited using convenience and theoretical sampling methods. Data were collected using 33 semi-structured interviews, and analysed using grounded theory analytic procedures. One core category (cancer through black eyes) and seven sub-categories emerged; 'cultural views', 'religious beliefs', 'avoiding Babylon', 'alienation', 'suspicious mind', 'advertisements and information influence very little', and 'gap in service provision (bridging the gap)'. Participants' views towards cancer were linked to socially constructed perspectives, linked with cultural and religious beliefs, and shaped by what being a black male means in society. Risk factors such as smoking and obesity had different meanings and symbolisation through black eyes. There were macro- and micro-level similarities and differences between BA and BAC men. Cancer services and related public-health campaigns aimed at black men need to understand cancer through black eyes. Public health campaigns based solely on the clinical meaning of cancer are incongruent with black men's understandings of cancer, and therefore ineffective at reducing health inequality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Complexity in cancer stem cells and tumor evolution: Toward precision medicine.

PubMed

La Porta, Caterina A M; Zapperi, Stefano

2017-06-01

In this review, we discuss recent advances on the plasticity of cancer stem cells and highlight their relevance to understand the metastatic process and to guide therapeutic interventions. Recent results suggest that the strict hierarchical structure of cancer cell populations advocated by the cancer stem cell model must be reconsidered since the depletion of cancer stem cells leads the other tumor cells to switch back into the cancer stem cell phenotype. This plasticity has important implications for metastasis since migrating cells do not need to be cancer stem cells in order to seed a metastasis. We also discuss the important role of the immune system and the microenvironment in modulating phenotypic switching and suggest possible avenues to exploit our understanding of this process to develop an effective strategy for precision medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Epigenetics: origins and implications for cancer epidemiology.

PubMed

Nise, Melissa S; Falaturi, Puran; Erren, Thomas C

2010-02-01

This paper provides information on the evolution of the 'epigenetics' concept since Aristotle and draws attention to the importance of epigenetic implications for cancer epidemiology in the years to come. Clearly, to understand origins of the concept of epigenetics, it is worthwhile to consider historical arguments associated with evolution. Equally clearly, in the last half of the 20th century, great advances in the understanding of epigenetics and, more specifically, great advances in the understanding of epigenetics in cancer have been made. However, reaping the full benefits of epigenetics lies beyond the predominant experimental studies of today. In general, epigenetics opens many doors in the field of cancer, but it also adds another level of complex, inter-related, and multi-dimensional information to research, and to its interpretation. Overall, future cancer studies should consider, or at least be sensitive to, epigenetic effects and mechanisms. Moving the focus beyond 'pristine' inheritance via DNA alone, cancer epidemiology investigating epigenetic exposures such as environmental factors (exposure to heavy metals, air pollution, arsenic and other toxins), dietary patterns (starvation, famine, contamination), and lifestyle habits (smoking, level of physical activity, and BMI) in populations has the prospect to significantly benefit future cancer prevention and treatment schemes.

Relationships between perceived diagnostic disclosure, patient characteristics, psychological distress and illness perceptions in Indian cancer patients.

PubMed

Chittem, Mahati; Norman, Paul; Harris, Peter R

2013-06-01

Non-disclosure of a cancer diagnosis is a common practice in many Asian cultures where family-based medical decision making is the norm. The present study sought to compare Indian cancer patients who were aware versus unaware of their cancer diagnosis on a range of patient characteristics, levels of psychological distress and illness perceptions. A sample of 329 Indian cancer patients were interviewed about their understanding of their illness (to assess awareness of a cancer diagnosis) and administered the following measures: the modified Rotterdam Symptom Checklist, the Hospital Anxiety and Depression Scale, and the Brief Illness Perceptions Questionnaire. Demographic and medical details were also obtained. Over half of the sample (54.1%) was unaware of their cancer diagnosis. A logistic regression analysis predicting perceived diagnostic disclosure indicated that awareness of a cancer diagnosis was associated with being involved in medical decisions, receiving multiple treatments, longer treatment durations, greater perceived understanding of one's illness (illness coherence) and citing a cause for one's illness. The results highlight the importance of the context in which decisions about the patient's illness are made (e.g. by whom) as well as illness perceptions relating to patients' understanding of their illness. Copyright © 2012 John Wiley & Sons, Ltd.

Current understanding of mdig/MINA in human cancers

PubMed Central

Thakur, Chitra; Chen, Fei

2015-01-01

Mineral dust-induced gene, mdig has recently been identified and is known to be overexpressed in a majority of human cancers and holds predictive power in the poor prognosis of the disease. Mdig is an environmentally expressed gene that is involved in cell proliferation, neoplastic transformation and immune regulation. With the advancement in deciphering the prognostic role of mdig in human cancers, our understanding on how mdig renders a normal cell to undergo malignant transformation is still very limited. This article reviews the current knowledge of the mdig gene in context to human neoplasias and its relation to the clinico-pathologic factors predicting the outcome of the disease in patients. It also emphasizes on the promising role of mdig that can serve as a potential candidate for biomarker discovery and as a therapeutic target in inflammation and cancers. Considering the recent advances in understanding the underlying mechanisms of tumor formation, more preclinical and clinical research is required to validate the potential of using mdig as a novel biological target of therapeutic and diagnostic value. Summary Expression level of mdig influences the prognosis of several human cancers especially cancers of the breast and lung. Evaluation of mdig in cancers can offer novel biomarker with potential therapeutic interventions for the early assessment of cancer development in patients. PMID:26413213

Current understanding of mdig/MINA in human cancers.

PubMed

Thakur, Chitra; Chen, Fei

2015-07-01

Mineral dust-induced gene, mdig has recently been identified and is known to be overexpressed in a majority of human cancers and holds predictive power in the poor prognosis of the disease. Mdig is an environmentally expressed gene that is involved in cell proliferation, neoplastic transformation and immune regulation. With the advancement in deciphering the prognostic role of mdig in human cancers, our understanding on how mdig renders a normal cell to undergo malignant transformation is still very limited. This article reviews the current knowledge of the mdig gene in context to human neoplasias and its relation to the clinico-pathologic factors predicting the outcome of the disease in patients. It also emphasizes on the promising role of mdig that can serve as a potential candidate for biomarker discovery and as a therapeutic target in inflammation and cancers. Considering the recent advances in understanding the underlying mechanisms of tumor formation, more preclinical and clinical research is required to validate the potential of using mdig as a novel biological target of therapeutic and diagnostic value. Expression level of mdig influences the prognosis of several human cancers especially cancers of the breast and lung. Evaluation of mdig in cancers can offer novel biomarker with potential therapeutic interventions for the early assessment of cancer development in patients.

A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer.

PubMed

Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min

2012-12-01

According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research.

Cultural perceptions in cancer care among African-American and Caucasian patients.

PubMed Central

Matsuyama, Robin K.; Grange, Christina; Lyckholm, Laurie J.; Utsey, Shawn O.; Smith, Thomas J.

2007-01-01

PURPOSE: This exploratory study examined perceptions and beliefs of African Americans and Caucasians related to cancer care. Understanding belief systems and cultures optimizes cancer treatment and care delivery to ethnic minority individuals. PATIENTS AND METHODS: Focus groups were conducted with 39 African-American and Caucasian cancer patients. Data analysis included whole group analysis with a team of five researchers. RESULTS: Regardless of ethnicity, cancer patients share many of the same emotions and experiences, and want complete information and quality care. Differences were also apparent. African-American participants were more likely to report increased religious behaviors, believe that healthcare providers demonstrate care with simple actions and provision of practical assistance, and use church and community information sources. Caucasian participants were more likely to report spiritual but not overtly religious changes, and depend on healthcare providers for information. CONCLUSION: Understanding how culture colors perceptions, communication and information requirements is critical to providing effective care to ethnically diverse cancer patients. Findings have implications for professionals understanding ways patients seek information, the role of spirituality and religion in care, and ways healthcare providers demonstrate care. PMID:17987914

Cell- and Tissue-based Proteome Profiling and Bioimaging with the Probes Derived from a Potent AXL Kinase Inhibitor.

PubMed

Li, Zhengqiu; Zheng, Binbin; Guo, Haijun; Xu, Jiaqian; Ma, Nan; Ni, Yun; Li, Lin; Hao, Piliang; Ding, Ke

2018-06-25

AXL has been defined as a novel target for cancer therapeutics. However, only a few potent and selective inhibitors targeting AXL are available to date. Our group has developed a lead compound, 9im, capable of excellent inhibition against AXL. With the aim of understanding its cellular and tissue mechanism of actions and direct subsequent structure optimization, a study on competitive affinity-based proteome profiling and bioimaging was carried out. A series of unknown cellular and tissue targets, including RYK, PCK, ATP1A3, EIF4A, Ptprn and Cox5b were discovered. In addition, trans-cyclooctene (TCO) and acedan-containing probes were developed to image the binding between 9im and its target proteins inside live cells and tumor tissues. These probes would be useful tools in the detection of expression and activity of AXL. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Compassion fatigue and burnout: prevalence among oncology nurses.

PubMed

Potter, Patricia; Deshields, Teresa; Divanbeigi, Joyce; Berger, Julie; Cipriano, Doreen; Norris, Lori; Olsen, Sarah

2010-10-01

This descriptive, cross-sectional survey was conducted in inpatient nursing units and outpatient clinics in a cancer center in the midwestern United States. The sample of 153 healthcare providers included RNs, medical assistants, and radiology technicians. The fourth revision of the 30-item Professional Quality of Life (ProQOL R-IV) scale was used for measuring compassion fatigue, compassion satisfaction, and burnout. A series of cross tab analyses examined the relationship between participant demographics and three ProQOL R-IV subscales. The study sample scored similarly on compassion satisfaction and burnout when compared with participants who used the ProQOL R-IV in previous studies. Value exists in analyzing the prevalence of burnout and compassion fatigue among oncology healthcare providers. Understanding the needs of distinct demographic groups offers valuable direction for intervention program development. Applying internal evidence in the design of a relevant stress-reduction program will better equip healthcare providers to recognize and manage compassion fatigue and burnout.

Intraoperative laparoscopic complications for urological cancer procedures

PubMed Central

Montes, Sergio Fernández-Pello; Rodríguez, Ivan Gonzalez; Ugarteburu, Rodrigo Gil; Villamil, Luis Rodríguez; Mendez, Begoña Diaz; Gil, Patricio Suarez; Madera, Javier Mosquera

2015-01-01

AIM: To structure the rate of intraoperative complications that requires an intraoperative or perioperative resolution. METHODS: We perform a literature review of Medline database. The research was focused on intraoperative laparoscopic procedures inside the field of urological oncology. General rate of perioperative complications in laparoscopic urologic surgery is described to be around 12.4%. Most of the manuscripts published do not make differences between pure intraoperative, intraoperative with postoperative consequences and postoperative complications. RESULTS: We expose a narrative statement of complications, possible solutions and possible preventions for most frequent retroperitoneal and pelvic laparoscopic surgery. We expose the results with the following order: retroperitoneal laparoscopic surgery (radical nephrectomy, partial nephrectomy, nephroureterectomy and adrenalectomy) and pelvic laparoscopic surgery (radical prostatectomy and radical cystectomy). CONCLUSION: Intraoperative complications vary from different series. More scheduled reports should be done in order to better understand the real rates of complications. PMID:25984519

Rectal cancer surgery: a brief history.

PubMed

Galler, Avi S; Petrelli, Nicholas J; Shakamuri, Shanthi P

2011-12-01

In the last 250 years, the treatment of rectal cancer has changed dramatically. Once considered an incurable disease, combined modality therapy has improved mortality from 100% to less than 4% for locally advanced rectal cancer. This dramatic reduction paralleled surgical techniques based on a growing understanding of anatomy and disease pathology. In order to understand modern treatment, it is necessary to recognize the achievements of preceding surgeons. Copyright © 2010 Elsevier Ltd. All rights reserved.

Is modern external beam radiotherapy with androgen deprivation therapy still a viable alternative for prostate cancer in an era of robotic surgery and brachytherapy: a comparison of Australian series.

PubMed

Wilcox, Shea William; Aherne, Noel J; McLachlan, Craig Steven; McKay, Michael J; Last, Andrew J; Shakespeare, Thomas P

2015-02-01

We compare the results of modern external-beam radiotherapy (EBRT), using combined androgen deprivation and dose-escalated intensity-modulated radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers (DE-IG-IMRT), with recently published Australian series of brachytherapy and surgery. Five-year actuarial biochemical disease-free survival (bDFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A search was conducted identifying Australian reports from 2005 onwards of IR and HR patients treated with surgery or brachytherapy, reporting actuarial outcomes at 3 years or later. With a median follow-up of 59 months, our 5-year bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9% overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR). Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was 1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3 gastrointestinal toxicity. Eight reports of brachytherapy and surgery were identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0% and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR patients. One LDR series reported 5-year bDFS of 85% for IR patients. Modern EBRT is at least as effective as modern Australian surgical and brachytherapy techniques. All patients considering treatment for localised prostate cancer should be referred to a radiation oncologist to discuss EBRT as an equivalent option. © 2015 The Royal Australian and New Zealand College of Radiologists.

Modeling Signaling Networks to Advance New Cancer Therapies.

PubMed

Saez-Rodriguez, Julio; MacNamara, Aidan; Cook, Simon

2015-01-01

Cell signaling pathways control cells' responses to their environment through an intricate network of proteins and small molecules partitioned by intracellular structures, such as the cytoskeleton and nucleus. Our understanding of these pathways has been revised recently with the advent of more advanced experimental techniques; no longer are signaling pathways viewed as linear cascades of information flowing from membrane-bound receptors to the nucleus. Instead, such pathways must be understood in the context of networks, and studying such networks requires an integration of computational and experimental approaches. This understanding is becoming more important in designing novel therapies for diseases such as cancer. Using the MAPK (mitogen-activated protein kinase) and PI3K (class I phosphoinositide-3' kinase) pathways as case studies of cellular signaling, we give an overview of these pathways and their functions. We then describe, using a number of case studies, how computational modeling has aided in understanding these pathways' deregulation in cancer, and how such understanding can be used to optimally tailor current therapies or help design new therapies against cancer.

Oral Cancer in African Americans: Addressing Health Disparities

ERIC Educational Resources Information Center

Dodd, Virginia J.; Watson, Jennifer M.; Choi, Youjin; Tomar, Scott L.; Logan, Henrietta L.

2008-01-01

Objectives: To explore factors underlying African Americans' perceptions of oral cancer and the oral cancer exam. Study findings were used to guide development of oral cancer messages designed to increase oral cancer exams among African Americans. Methods: Focus groups were conducted to understand African Americans' attitudes and expectations…

Exploring stigma as a barrier to cancer service engagement with breast cancer survivors in Kampala, Uganda.

PubMed

Meacham, Elizabeth; Orem, Jackson; Nakigudde, Gertrude; Zujewski, Jo Anne; Rao, Deepa

2016-10-01

To understand the role of stigma in the delay of cancer service engagement by women with breast cancer in Kampala, Uganda. Women in Sub-Saharan African countries are twice as likely to die from cancer as women in high-income countries, which is largely attributable to late diagnosis. While breast cancer-related stigma has been identified in Sub-Saharan Africa, limited research focuses on how stigma impacts the behavior of breast cancer patients in Uganda. This qualitative study used a grounded theory approach to examine illness narratives from 20 breast cancer survivors in Uganda, gathered through semistructured interviews. Thematic analysis showed that perceived and internalized stigma associated with breast cancer influenced care engagement throughout illness, delaying engagement and inhibiting treatment completion. Women identified key factors for overcoming stigma including acceptance of diagnosis, social support, and understanding of breast cancer. The growing burden of mortality associated with breast cancer in Uganda can be mitigated by improving early detection and treatment engagement through interventions which account for key psychosocial barriers such as stigma. Copyright © 2016 John Wiley & Sons, Ltd.

Histogram analysis of apparent diffusion coefficient for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

PubMed

Meng, Jie; Zhu, Lijing; Zhu, Li; Ge, Yun; He, Jian; Zhou, Zhengyang; Yang, Xiaofeng

2017-11-01

Background Apparent diffusion coefficient (ADC) histogram analysis has been widely used in determining tumor prognosis. Purpose To investigate the dynamic changes of ADC histogram parameters during concurrent chemo-radiotherapy (CCRT) in patients with advanced cervical cancers. Material and Methods This prospective study enrolled 32 patients with advanced cervical cancers undergoing CCRT who received diffusion-weighted (DW) magnetic resonance imaging (MRI) before CCRT, at the end of the second and fourth week during CCRT and one month after CCRT completion. The ADC histogram for the entire tumor volume was generated, and a series of histogram parameters was obtained. Dynamic changes of those parameters in cervical cancers were investigated as early biomarkers for treatment response. Results All histogram parameters except AUC low showed significant changes during CCRT (all P < 0.05). There were three variable trends involving different parameters. The mode, 5th, 10th, and 25th percentiles showed similar early increase rates (33.33%, 33.99%, 34.12%, and 30.49%, respectively) at the end of the second week of CCRT. The pre-CCRT 5th and 25th percentiles of the complete response (CR) group were significantly lower than those of the partial response (PR) group. Conclusion A series of ADC histogram parameters of cervical cancers changed significantly at the early stage of CCRT, indicating their potential in monitoring early tumor response to therapy.

Cryotherapy for primary treatment of prostate cancer: intermediate term results of a prospective study from a single institution.

PubMed

Rodríguez, S Alvarez; Arias Fúnez, F; Bueno Bravo, C; Rodríguez-Patrón Rodríguez, R; Sanz Mayayo, E; Palacios, V Hevia; Burgos Revilla, F J

2014-01-01

Purpose. Published data about cryotherapy for prostate cancer (PC) treatment are based on case series with a lack of clinical trials and the inexistence of a validated definition of biochemical failure. A prospective study with standardized followup protocol was conducted in our institution. Material and Methods. Prospective study of a series of cases including 108 patients diagnosed with localized PC at clinical stage T1c-T2c treated by primary cryoablation and median followup of 61 months. Criteria of biochemical recurrence were unified according to the American Society for Therapeutic Radiology and Oncology (ASTRO). End points were biochemical progression-free survival (BPFS), cancer-specific survival, and overall survival. Rate of complications was reported. Results. The BPFS for low-, medium-, and high-risk patients was 96.4%, 91.2%, and 62.2%, respectively. Cancer-specific survival was 98.1%. Overall survival reached 94.4%. Complications included incontinence in 5.6%, urinary tract obstruction in 1.9%, urethral sloughing in 5.6%, haematuria in 1.9%, perineal pain in 11.1%, and prostatorectal fistula in 0.9%. Erectile disfunction was found in 98.1%. Conclusions. Cryotherapy is an effective and minimally invasive treatment for primary PC in well-selected cases, with low surgical risk and good results in terms of BPFS, cancer-specific survival, and overall survival.

Cryotherapy for Primary Treatment of Prostate Cancer: Intermediate Term Results of a Prospective Study from a Single Institution

PubMed Central

Rodríguez, S. Alvarez; Arias Fúnez, F.; Bueno Bravo, C.; Rodríguez-Patrón Rodríguez, R.; Sanz Mayayo, E.; Palacios, V. Hevia; Burgos Revilla, F. J.

2014-01-01

Purpose. Published data about cryotherapy for prostate cancer (PC) treatment are based on case series with a lack of clinical trials and the inexistence of a validated definition of biochemical failure. A prospective study with standardized followup protocol was conducted in our institution. Material and Methods. Prospective study of a series of cases including 108 patients diagnosed with localized PC at clinical stage T1c-T2c treated by primary cryoablation and median followup of 61 months. Criteria of biochemical recurrence were unified according to the American Society for Therapeutic Radiology and Oncology (ASTRO). End points were biochemical progression-free survival (BPFS), cancer-specific survival, and overall survival. Rate of complications was reported. Results. The BPFS for low-, medium-, and high-risk patients was 96.4%, 91.2%, and 62.2%, respectively. Cancer-specific survival was 98.1%. Overall survival reached 94.4%. Complications included incontinence in 5.6%, urinary tract obstruction in 1.9%, urethral sloughing in 5.6%, haematuria in 1.9%, perineal pain in 11.1%, and prostatorectal fistula in 0.9%. Erectile disfunction was found in 98.1%. Conclusions. Cryotherapy is an effective and minimally invasive treatment for primary PC in well-selected cases, with low surgical risk and good results in terms of BPFS, cancer-specific survival, and overall survival. PMID:24693437

The rise of genomic profiling in ovarian cancer

PubMed Central

Previs, Rebecca A.; Sood, Anil K.; Mills, Gordon B.; Westin, Shannon N.

2017-01-01

Introduction Next-generation sequencing and advances in ‘omics technology have rapidly increased our understanding of the molecular landscape of epithelial ovarian cancers. Areas covered Once characterized only by histologic appearance and clinical behavior, we now understand many of the molecular phenotypes that underlie the different ovarian cancer subtypes. While the current approach to treatment involves standard cytotoxic therapies after cytoreductive surgery for all ovarian cancers regardless of histologic or molecular characteristics, focus has shifted beyond a ‘one size fits all’ approach to ovarian cancer. Expert commentary Genomic profiling offers potentially ‘actionable’ opportunities for development of targeted therapies and a more individualized approach to treatment with concomitant improved outcomes and decreased toxicity. PMID:27828713

KRAS Mouse Models

PubMed Central

O’Hagan, Rónán C.; Heyer, Joerg

2011-01-01

KRAS is a potent oncogene and is mutated in about 30% of all human cancers. However, the biological context of KRAS-dependent oncogenesis is poorly understood. Genetically engineered mouse models of cancer provide invaluable tools to study the oncogenic process, and insights from KRAS-driven models have significantly increased our understanding of the genetic, cellular, and tissue contexts in which KRAS is competent for oncogenesis. Moreover, variation among tumors arising in mouse models can provide insight into the mechanisms underlying response or resistance to therapy in KRAS-dependent cancers. Hence, it is essential that models of KRAS-driven cancers accurately reflect the genetics of human tumors and recapitulate the complex tumor-stromal intercommunication that is manifest in human cancers. Here, we highlight the progress made in modeling KRAS-dependent cancers and the impact that these models have had on our understanding of cancer biology. In particular, the development of models that recapitulate the complex biology of human cancers enables translational insights into mechanisms of therapeutic intervention in KRAS-dependent cancers. PMID:21779503

Communicating and understanding the purpose of pediatric phase I cancer trials.

PubMed

Cousino, Melissa K; Zyzanski, Stephen J; Yamokoski, Amy D; Hazen, Rebecca A; Baker, Justin N; Noll, Robert B; Rheingold, Susan R; Geyer, J Russell; Alexander, Stewart C; Drotar, Dennis; Kodish, Eric D

2012-12-10

Quality informed consent should provide a clear understanding of the purpose of the research. Given the ethical challenges of pediatric phase I cancer trials, it is important to investigate physician-parent communication during informed consent conferences (ICCs) and parental understanding of the purpose of these studies. In the multisite Informed Consent in Pediatric Phase I Cancer Trials study, 85 ICCs for phase I research between June 2008 and May 2011 were directly observed, and 60 parents were subsequently interviewed. The scientific purpose was defined as composite understanding of drug safety, dose finding, and dose escalation. We determined the frequency with which physicians explained these and other phase I-related concepts during the ICC. Parent interviews were analyzed to determine understanding. The child was present at 83 of 85 ICCs. Only 32% of parents demonstrated substantial understanding of the scientific purpose of phase I cancer trials; 35% demonstrated little or no understanding. Parents of higher socioeconomic status and racial majority status were more likely to understand the scientific purpose. Factors associated with understanding included physician explanation of the goal of the applicable phase I protocol offered (explained in 85% of ICCs) and explanation of the dose cohorts (explained in 43% of ICCs). Physicians explained drug safety in 23% of ICCs, dose finding in 52% of ICCs, and dose escalation in 53% of ICCs. Many parents of children participating in phase I trials do not understand the purpose of these trials. Physician-parent communication about the purpose of phase I research is lacking during ICCs.

Emerging science and therapies in non-small-cell lung cancer: targeting the MET pathway.

PubMed

Kris, Mark G; Arenberg, Douglas A; Herbst, Roy S; Riely, Gregory J

2014-11-01

During this enduring, learner-driven, interactive CME webseries, lung cancer specialists will address the science and targeted therapies for the MET pathway in non-small cell lung cancer. Over the past decade, research has evolved in the science of identifying targeted biological changes in DNA and individual cancer cells. Along with the advanced understanding of lung cancer mutations, has come the development of specific targeted therapies that improve patient outcomes. The first step in treating a patient with lung cancer is proper diagnosis and staging, applying to the principles of personalize medicine. Our current understanding of lung cancer is that of a collection of diseases individualized through specific mutations. This CME activity reviews the role of the pulmonologist and pathologist in proper tissue acquisition and analysis. This new era of personalized medicine and clinical research advances has changed the way clinicians evaluate and treat patients with lung cancer. The data on lung cancer cell mutations and newer targeted therapies have improved the progression free survival and quality of life of lung cancer patients. This CME activity is designed to present a practical overview of recent evidenced based data of MET targeted therapies for patients with lung cancer. As research continues to evolve, we continue to advance our understanding in the science of lung cancers involving the MET pathway. Evidenced based data supporting newer targeted therapeutics provides insight on applying treatment for optimal outcomes. This CME activity will focus on the individualized treatment strategies using practical decision making for patients with MET expression. This activity has been designed to meet the educational needs of medical oncologists, pathologists, radiation oncologists, surgeons, pulmonologists, internists, and other healthcare clinicians responsible for the care of patients with lung cancer. Online access:http://www.elseviercme.com/516/.

Surgical Management of Lung Cancer Involving the Chest Wall.

PubMed

Lanuti, Michael

2017-05-01

The prevalence of chest wall invasion by non-small cell lung cancer is < 10% in published surgical series. The role of radiation or chemotherapy around the complete resection of lung cancer invading the chest wall, excluding the superior sulcus of the chest, is poorly defined. Survival of patients with lung cancer invading the chest wall is dependent on lymph node involvement and completeness of en-bloc resection. In some patients harboring T3N0 disease, 5-year survival in excess of 50% can be achieved. Offering en-bloc resection of lung cancer invading chest wall to patients with T3N1 or T3N2 disease is controversial. Copyright © 2017 Elsevier Inc. All rights reserved.

Understanding Statistics - Cancer Statistics

Cancer.gov

Annual reports of U.S. cancer statistics including new cases, deaths, trends, survival, prevalence, lifetime risk, and progress toward Healthy People targets, plus statistical summaries for a number of common cancer types.

Epidemiology & Genomics Research Program

Cancer.gov

The Epidemiology and Genomics Research Program, in the National Cancer Institute's Division of Cancer Control and Population Sciences, funds research in human populations to understand the determinants of cancer occurrence and outcomes.

Understanding and Effectively Addressing Breast Cancer in African American Women: Unpacking the Social Context

PubMed Central

Williams, David R.; Mohammed, Selina A.; Shields, Alexandra E.

2017-01-01

Black women have higher incidence of breast cancer before the age of 40, more severe disease at all ages, and elevated mortality risk compared to white women. There is limited understanding of the contribution of social factors to these patterns. Elucidating the role of the social determinants of health in breast cancer disparities requires greater attention to how risk factors for breast cancer unfold over the lifecourse, and the complex ways that socioeconomic status and racism shape exposure to psychosocial, physical, chemical and other individual and community-level assaults that increase the risk of breast cancer. Research that takes seriously the social context in which Black women live is also needed to maximize the opportunities to prevent breast cancer among this underserved group. PMID:26930024

Cancer stem cells of the digestive system.

PubMed

Colvin, Hugh S; Nishida, Naohiro; Koseki, Jun; Konno, Masamitsu; Kawamoto, Koichi; Tsunekuni, Kenta; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

2014-12-01

Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sarcoma-The standard-bearer in cancer discovery.

PubMed

Potter, Jared W; Jones, Kevin B; Barrott, Jared J

2018-06-01

Sarcoma is a rare tumor type that occurs most frequently in connective tissue. Despite its uncommon occurrence, sarcoma research has provided the means for groundbreaking research that has advanced our understanding of general cancer mechanisms. It is through sarcoma research that the pioneering efforts of cancer immunotherapy were explored, that we understand the inherent genetic nature of cancer mutations, and that we appreciate the subclassification of general cancer types to make more accurate prognoses. This review explores the brief history of sarcoma research and what sarcomas can still teach us about the future of cancer research, especially in regard to novel immunotherapy targets, the role of epigenetics in disease progression and chemoresistance, and the benefits of more focused clinical trials. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Books on Atomic Energy for Adults and Children, Understanding the Atom Series.

ERIC Educational Resources Information Center

Atomic Energy Commission, Oak Ridge, TN. Div. of Technical Information.

This booklet in the "Understanding the Atom" series includes annotated bibliographies for children (grade level indicated) and adults. Over 100 basic books on atomic energy and closely related subjects are alphabetized by title and an author index. A list of publisher addresses are included. A brief introduction to library usage is given. The…

Atomic Energy Basics, Understanding the Atom Series.

ERIC Educational Resources Information Center

Atomic Energy Commission, Oak Ridge, TN. Div. of Technical Information.

This booklet is part of the "Understanding the Atom Series," though it is a later edition and not included in the original set of 51 booklets. A basic survey of the principles of nuclear energy and most important applications are provided. These major topics are examined: matter has molecules and atoms, the atom has electrons, the nucleus,…

The First Reactor, Understanding the Atom Series.

ERIC Educational Resources Information Center

Allardice, Corbin; And Others

This booklet is one of the "Understanding the Atom" Series. Consisting of three sections, it is an account of the development of the first nuclear reactor by a team of scientists led by Enrico Farmi. The first section briefly reviews the early work on nuclear fission and neutron emission, the impact of Einstein's letter to President Roosevelt, the…

Understanding the Role of Muscle and Body Composition in Studies of Cancer Risk and Prognosis in Cancer Survivors

Cancer.gov

The purpose of this conference is to bring together a community of researchers across the cancer control continuum using geospatial tools, models and approaches to address cancer prevention and control.

Knowledge-guided fuzzy logic modeling to infer cellular signaling networks from proteomic data

PubMed Central

Liu, Hui; Zhang, Fan; Mishra, Shital Kumar; Zhou, Shuigeng; Zheng, Jie

2016-01-01

Modeling of signaling pathways is crucial for understanding and predicting cellular responses to drug treatments. However, canonical signaling pathways curated from literature are seldom context-specific and thus can hardly predict cell type-specific response to external perturbations; purely data-driven methods also have drawbacks such as limited biological interpretability. Therefore, hybrid methods that can integrate prior knowledge and real data for network inference are highly desirable. In this paper, we propose a knowledge-guided fuzzy logic network model to infer signaling pathways by exploiting both prior knowledge and time-series data. In particular, the dynamic time warping algorithm is employed to measure the goodness of fit between experimental and predicted data, so that our method can model temporally-ordered experimental observations. We evaluated the proposed method on a synthetic dataset and two real phosphoproteomic datasets. The experimental results demonstrate that our model can uncover drug-induced alterations in signaling pathways in cancer cells. Compared with existing hybrid models, our method can model feedback loops so that the dynamical mechanisms of signaling networks can be uncovered from time-series data. By calibrating generic models of signaling pathways against real data, our method supports precise predictions of context-specific anticancer drug effects, which is an important step towards precision medicine. PMID:27774993

Lnc2Cancer: a manually curated database of experimentally supported lncRNAs associated with various human cancers

PubMed Central

Ning, Shangwei; Zhang, Jizhou; Wang, Peng; Zhi, Hui; Wang, Jianjian; Liu, Yue; Gao, Yue; Guo, Maoni; Yue, Ming; Wang, Lihua; Li, Xia

2016-01-01

Lnc2Cancer (http://www.bio-bigdata.net/lnc2cancer) is a manually curated database of cancer-associated long non-coding RNAs (lncRNAs) with experimental support that aims to provide a high-quality and integrated resource for exploring lncRNA deregulation in various human cancers. LncRNAs represent a large category of functional RNA molecules that play a significant role in human cancers. A curated collection and summary of deregulated lncRNAs in cancer is essential to thoroughly understand the mechanisms and functions of lncRNAs. Here, we developed the Lnc2Cancer database, which contains 1057 manually curated associations between 531 lncRNAs and 86 human cancers. Each association includes lncRNA and cancer name, the lncRNA expression pattern, experimental techniques, a brief functional description, the original reference and additional annotation information. Lnc2Cancer provides a user-friendly interface to conveniently browse, retrieve and download data. Lnc2Cancer also offers a submission page for researchers to submit newly validated lncRNA-cancer associations. With the rapidly increasing interest in lncRNAs, Lnc2Cancer will significantly improve our understanding of lncRNA deregulation in cancer and has the potential to be a timely and valuable resource. PMID:26481356

Insurance company denial of payment and enforced changes in the type and dose of opioid analgesics for patients with cancer pain.

PubMed

Tanco, Kimberson; Bruera, Sofia E; Bruera, Eduardo

2014-12-01

Opioids are the mainstay of treatment for moderate to severe cancer pain. The variations in average monthly cost can make it difficult for most patients to procure them without adequate insurance coverage. There are increasing numbers of denials of payment and statements made by insurance agents and other sources regarding inappropriate opioid use, resulting in severe pain and emotional distress for cancer patients and their families. This case series describes five events where the insurer was a major barrier to opioid access.

From the Bench to the Clinic Part 1: Martin McIntosh, Ph.D., Introduces His Lab's Immunotherapy Research | Office of Cancer Genomics

Cancer.gov

The field of immunotherapy is rapidly advancing and genomics techniques are being incorporated to add a “precision” approach. OCG spoke with two CTD2 investigators from the Fred Hutchinson Cancer Research Center (FHCRC) about new advances in immunotherapy. For the first article of this two-part series, we interviewed Martin McIntosh, Ph.D., member of the Fred Hutchinson Translational Research program and previously Program Head in Computational Biology at FHCRC/University of Washington Comprehensive Cancer Center.

Something Old, Something New, Something Borrowed, Something Fused: Novel EGFR Rearrangements in Lung Adenocarcinomas.

PubMed

Paik, Paul K

2016-06-01

Mutations in EGFR stand as the archetype for somatic alterations that lead to oncogene addiction and that predict for response to targeted therapies. In this issue of Cancer Discovery, Konduri and colleagues report on a pair of novel oncogenic and actionable EGFR fusion events in a series of patients with lung adenocarcinomas, casting new light on this model gene. Cancer Discov; 6(6); 574-5. ©2016 AACRSee related article by Konduri et al., p. 601. ©2016 American Association for Cancer Research.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bilbao, Cristina, E-mail: cbilbao@dbbf.ulpgc.e; Department of Radiation Oncology, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Canary Islands; Lara, Pedro Carlos

Purpose: To elucidate whether microsatellite instability (MSI) predicts clinical outcome in radiation-treated endometrioid endometrial cancer (EEC). Methods and Materials: A consecutive series of 93 patients with EEC treated with extrafascial hysterectomy and postoperative radiotherapy was studied. The median clinical follow-up of patients was 138 months, with a maximum of 232 months. Five quasimonomorphic mononucleotide markers (BAT-25, BAT-26, NR21, NR24, and NR27) were used for MSI classification. Results: Twenty-five patients (22%) were classified as MSI. Both in the whole series and in early stages (I and II), univariate analysis showed a significant association between MSI and poorer 10-year local disease-free survival,more » disease-free survival, and cancer-specific survival. In multivariate analysis, MSI was excluded from the final regression model in the whole series, but in early stages MSI provided additional significant predictive information independent of traditional prognostic and predictive factors (age, stage, grade, and vascular invasion) for disease-free survival (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.01-10.49; p = 0.048) and cancer-specific survival (HR 4.20, 95% CI 1.23-14.35; p = 0.022) and was marginally significant for local disease-free survival (HR 3.54, 95% CI 0.93-13.46; p = 0.064). Conclusions: These results suggest that MSI may predict radiotherapy response in early-stage EEC.« less

Genetic tumor profiling and genetically targeted cancer therapy.

PubMed

Goetsch, Cathleen M

2011-02-01

To discuss how understanding and manipulation of tumor genetics information and technology shapes cancer care today and what changes might be expected in the near future. Published articles, web resources, clinical practice. Advances in our understanding of genes and their regulation provide a promise of more personalized cancer care, allowing selection of the most safe and effective therapy in an individual situation. Rapid progress in the technology of tumor profiling and targeted cancer therapies challenges nurses to keep up-to-date to provide quality patient education and care. Copyright © 2011 Elsevier Inc. All rights reserved.

What a Shock: No Apoptosis without Heat Shock Protein 90α | Center for Cancer Research

Cancer.gov

Apoptosis, also known as programmed cell death, consists of a series of reactions designed to systematically chop up a cell and its contents. The process is used to eliminate specific cells during development or to remove old or damaged cells without harming any surrounding cells. Since cancer cells can develop mechanisms to avoid apoptosis, researchers may be able to identify

Ten Years' Experience with an E-Learning Lecture Series on Cancer Biology and Pharmacology

ERIC Educational Resources Information Center

Efferth, Thomas

2013-01-01

In life sciences, the internet is an indispensable medium for research, but has not yet realized its full potential for teaching. The concept of e-learning has been developed over the past decades for undergraduate, graduate and postgraduate programs. We set up an e-learning lecture on cancer biology and pharmacology that was first offered in 2003…

Dual Roles of RNF2 in Melanoma Progression | Office of Cancer Genomics

Cancer.gov

Epigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic.

Cancer surveillance in northern Africa, and central and western Asia: challenges and strategies in support of developing cancer registries.

PubMed

Znaor, Ariana; Eser, Sultan; Anton-Culver, Hoda; Fadhil, Ibtihal; Ryzhov, Anton; Silverman, Barbara G; Bendahou, Karima; Demetriou, Anna; Nimri, Omar; Yakut, Cankut; Bray, Freddie

2018-02-01

The Global Initiative for Cancer Registry Development partnership, led by the International Agency for Research on Cancer (IARC), was established in response to an overwhelming need for high-quality cancer incidence data from low-income and middle-income countries. The IARC Regional Hub for cancer registration in North Africa, Central and West Asia was founded in 2013 to support capacity building for cancer registration in each of the countries in this region. In this Series paper, we advocate the necessity for tailored approaches to cancer registration given the rapidly changing cancer landscape for this region, and the challenges faced at a national level in developing data systems to help support this process given present disparities in resources and health infrastructure. In addition, we provide an overview of the status of cancer surveillance and activities country-by-country, documenting tailored approaches that are informing local cancer-control policy, and potentially curbing the growing cancer burden across the region. Copyright © 2018 Elsevier Ltd. All rights reserved.

Understanding cancer staging

MedlinePlus

... detailed information about the cancer stage. TNM Staging System The most common system for staging cancer in ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

Communicating Evidence-Based Information on Cancer Prevention to State-Level Policy Makers

PubMed Central

Dodson, Elizabeth A.; Stamatakis, Katherine A.; Casey, Christopher M.; Elliott, Michael B.; Luke, Douglas A.; Wintrode, Christopher G.; Kreuter, Matthew W.

2011-01-01

Background Opportunities exist to disseminate evidence-based cancer control strategies to state-level policy makers in both the legislative and executive branches. We explored factors that influence the likelihood that state-level policy makers will find a policy brief understandable, credible, and useful. Methods A systematic approach was used to develop four types of policy briefs on the topic of mammography screening to reduce breast cancer mortality: data-focused brief with state-level data, data-focused brief with local-level data, story-focused brief with state-level data, and story-focused brief with local-level data. Participants were recruited from three groups of state-level policy makers—legislative staff, legislators, and executive branch administrators— in six states that were randomly chosen after stratifying all 50 states by population size and dominant political party in state legislature. Participants from each of the three policy groups were randomly assigned to receive one of the four types of policy briefs and completed a questionnaire that included a series of Likert scale items. Primary outcomes—whether the brief was understandable, credible, likely to be used, and likely to be shared—were measured by a 5-point Likert scale according to the degree of agreement (1 = strongly disagree, 5 = strongly agree). Data were analyzed with analysis of variance and with classification trees. All statistical tests were two-sided. Results Data on response to the policy briefs (n = 291) were collected from February through December 2009 (overall response rate = 35%). All three policy groups found the briefs to be understandable and credible, with mean ratings that ranged from 4.3 to 4.5. The likelihood of using the brief (the dependent variable) differed statistically significantly by study condition for staffers (P = .041) and for legislators (P = .018). Staffers found the story-focused brief containing state-level data most useful, whereas legislators found the data-focused brief containing state-level data most useful. Exploratory classification trees showed distinctive patterns for brief usefulness across the three policy groups. Conclusion Our results suggest that taking a “one-size-fits-all” approach when delivering information to policy makers may be less effective than communicating information based on the type of policy maker. PMID:21212381

The role of Human Papilloma Virus (HPV) vaccination in the prevention of anal cancer in individuals with Human Immunodeficiency Virus-1 (HIV-1) infection

PubMed Central

2013-01-01

The incidence of anal cancer is increasing in the general population and especially in high-risk groups. A total of 90% of anal cancers are caused by human papilloma virus (HPV) infection of the anal canal. Similar to cervical cancer, anal cancer progresses through a predictable series of premalignant stages before resulting in invasive cancer; this process begins with persistent HPV infection. The HPV vaccine represents a promising strategy to combat the increasing incidence of anal cancer. Human Immunodeficiency Virus (HIV) predisposes people to persistent HPV infection, dysplasia, and subsequent anal cancer. Patients infected with HIV should be targeted for vaccination against HPV. There are difficulties in targeting this population, the most notable being that the optimal age for vaccination is prior to identification with any high-risk groups. Universal vaccination against HPV represents the best strategy to achieve maximum protection against anal cancer in high-risk groups. PMID:24757517

Emerging clinical importance of the cancer biomarkers kallikrein-related peptidases (KLK) in female and male reproductive organ malignancies

PubMed Central

Schmitt, Manfred; Magdolen, Viktor; Yang, Feng; Kiechle, Marion; Bayani, Jane; Yousef, George M.; Scorilas, Andreas; Diamandis, Eleftherios P.; Dorn, Julia

2013-01-01

Background Tumor tissue-associated KLKs (kallikrein-related peptidases) are clinically important biomarkers that may allow prognosis of the cancer disease and/or prediction of response/failure of cancer patients to cancer-directed drugs. Regarding the female/male reproductive tract, remarkably, all of the fifteen KLKs are expressed in the normal prostate, breast, cervix uteri, and the testis, whereas the uterus/endometrium and the ovary are expressing a limited number of KLKs only. Conclusions Most of the information regarding elevated expression of KLKs in tumor-affected organs is available for ovarian cancer; depicting them as valuable biomarkers in the cancerous phenotype. In contrast, for breast cancer, a series of KLKs was found to be downregulated. However, in breast cancer, KLK4 is elevated which is also true for ovarian and prostate cancer. In such cases, selective synthetic KLK inhibitors that aim at blocking the proteolytic activities of certain KLKs may serve as future candidate therapeutic drugs to interfere with tumor progression and metastasis. PMID:24294176

Cluster analysis of dynamic contrast enhanced MRI reveals tumor subregions related to locoregional relapse for cervical cancer patients.

PubMed

Torheim, Turid; Groendahl, Aurora R; Andersen, Erlend K F; Lyng, Heidi; Malinen, Eirik; Kvaal, Knut; Futsaether, Cecilia M

2016-11-01

Solid tumors are known to be spatially heterogeneous. Detection of treatment-resistant tumor regions can improve clinical outcome, by enabling implementation of strategies targeting such regions. In this study, K-means clustering was used to group voxels in dynamic contrast enhanced magnetic resonance images (DCE-MRI) of cervical cancers. The aim was to identify clusters reflecting treatment resistance that could be used for targeted radiotherapy with a dose-painting approach. Eighty-one patients with locally advanced cervical cancer underwent DCE-MRI prior to chemoradiotherapy. The resulting image time series were fitted to two pharmacokinetic models, the Tofts model (yielding parameters K trans and ν e ) and the Brix model (A Brix , k ep and k el ). K-means clustering was used to group similar voxels based on either the pharmacokinetic parameter maps or the relative signal increase (RSI) time series. The associations between voxel clusters and treatment outcome (measured as locoregional control) were evaluated using the volume fraction or the spatial distribution of each cluster. One voxel cluster based on the RSI time series was significantly related to locoregional control (adjusted p-value 0.048). This cluster consisted of low-enhancing voxels. We found that tumors with poor prognosis had this RSI-based cluster gathered into few patches, making this cluster a potential candidate for targeted radiotherapy. None of the voxels clusters based on Tofts or Brix parameter maps were significantly related to treatment outcome. We identified one group of tumor voxels significantly associated with locoregional relapse that could potentially be used for dose painting. This tumor voxel cluster was identified using the raw MRI time series rather than the pharmacokinetic maps.

Identifying New Candidate Genes and Chemicals Related to Prostate Cancer Using a Hybrid Network and Shortest Path Approach

PubMed Central

Wang, Meng; Wu, Kai; Lu, Changhong; Kong, Xiangyin

2015-01-01

Prostate cancer is a type of cancer that occurs in the male prostate, a gland in the male reproductive system. Because prostate cancer cells may spread to other parts of the body and can influence human reproduction, understanding the mechanisms underlying this disease is critical for designing effective treatments. The identification of as many genes and chemicals related to prostate cancer as possible will enhance our understanding of this disease. In this study, we proposed a computational method to identify new candidate genes and chemicals based on currently known genes and chemicals related to prostate cancer by applying a shortest path approach in a hybrid network. The hybrid network was constructed according to information concerning chemical-chemical interactions, chemical-protein interactions, and protein-protein interactions. Many of the obtained genes and chemicals are associated with prostate cancer. PMID:26504486

Macrophages and cellular immunity in Drosophila melanogaster.

PubMed

Gold, Katrina S; Brückner, Katja

2015-12-01

The invertebrate Drosophila melanogaster has been a powerful model for understanding blood cell development and immunity. Drosophila is a holometabolous insect, which transitions through a series of life stages from embryo, larva and pupa to adulthood. In spite of this, remarkable parallels exist between Drosophila and vertebrate macrophages, both in terms of development and function. More than 90% of Drosophila blood cells (hemocytes) are macrophages (plasmatocytes), making this highly tractable genetic system attractive for studying a variety of questions in macrophage biology. In vertebrates, recent findings revealed that macrophages have two independent origins: self-renewing macrophages, which reside and proliferate in local microenvironments in a variety of tissues, and macrophages of the monocyte lineage, which derive from hematopoietic stem or progenitor cells. Like vertebrates, Drosophila possesses two macrophage lineages with a conserved dual ontogeny. These parallels allow us to take advantage of the Drosophila model when investigating macrophage lineage specification, maintenance and amplification, and the induction of macrophages and their progenitors by local microenvironments and systemic cues. Beyond macrophage development, Drosophila further serves as a paradigm for understanding the mechanisms underlying macrophage function and cellular immunity in infection, tissue homeostasis and cancer, throughout development and adult life. Copyright © 2016. Published by Elsevier Ltd.

Macrophages and cellular immunity in Drosophila melanogaster

PubMed Central

Gold, Katrina S.; Brückner, Katja

2016-01-01

The invertebrate Drosophila melanogaster has been a powerful model for understanding blood cell development and immunity. Drosophila is a holometabolous insect, which transitions through a series of life stages from embryo, larva and pupa to adulthood. In spite of this, remarkable parallels exist between Drosophila and vertebrate macrophages, both in terms of development and function. More than 90% of Drosophila blood cells (hemocytes) are macrophages (plasmatocytes), making this highly tractable genetic system attractive for studying a variety of questions in macrophage biology. In vertebrates, recent findings revealed that macrophages have two independent origins: self-renewing macrophages, which reside and proliferate in local microenvironments in a variety of tissues, and macrophages of the monocyte lineage, which derive from hematopoietic stem or progenitor cells. Like vertebrates, Drosophila possesses two macrophage lineages with a conserved dual ontogeny. These parallels allow us to take advantage of the Drosophila model when investigating macrophage lineage specification, maintenance and amplification, and the induction of macrophages and their progenitors by local microenvironments and systemic cues. Beyond macrophage development, Drosophila further serves as a paradigm for understanding the mechanisms underlying macrophage function and cellular immunity in infection, tissue homeostasis and cancer, throughout development and adult life. PMID:27117654

Epigenetics and Colorectal Cancer

PubMed Central

Lao, Victoria Valinluck; Grady, William M.

2012-01-01

Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203

Office of Cancer Genomics |

Cancer.gov

The mission of the NCI’s Office of Cancer Genomics (OCG) is to enhance the understanding of the molecular mechanisms of cancer, advance and accelerate genomics science and technology development, and efficiently translate the genomics data to improve cancer research, prevention, early detection, diagnosis and treatment.

CCR Magazines | Center for Cancer Research

Cancer.gov

The Center for Cancer Research (CCR) has two magazines, MILESTONES and LANDMARKS, that highlight our annual advances and top contributions to the understanding, detection, treatment and prevention of cancer over the years.

Trends in the survival of patients diagnosed with cancer in the Nordic countries 1964-2003 followed up to the end of 2006. Material and methods.

PubMed

Engholm, Gerda; Gislum, Mette; Bray, Freddie; Hakulinen, Timo

2010-06-01

Comparable data on cancer incidence and mortality in Denmark, Finland, Iceland, Norway, and Sweden are available for analysis through a collaboration of the national Cancer Registries via the NORDCAN website (http://ancr.nu). In the continued spirit of Nordic collaborative research, a number of studies examining trends in cancer survival are published in this journal. The data were divided into eight 5-year periods by sex in five Nordic countries. Age-standardised 5-year relative survival ratios and excess mortality rates in the short-term (first month and 1-3 months following diagnosis), and the long-term (2-5 years after diagnosis) were calculated, as were age-specific 5-year relative survival using cohort-survival methods. A hybrid method combining the cohort and period methods was used for the period 1999-2003 as not all patients were followed for five years. Age-standardisation used the International Cancer Survival Standard, and calculation of expected deaths used country-specific population mortality rates. The data series constitutes 3 360 397 tumours among 3 160 802 patients followed up for death through 2006 for 39 different cancer sites diagnosed in the years 1964-2003. The paper describes the data, exclusions and imputations, design and analysis, age structure and standardisation procedures, follow-up, and case-mix adjustment methods. The strengths of this study include the overall comparability and quality of the data, the national coverage, and the length of the time series. Collecting and analysing data from the five Nordic countries for 39 different cancer sites over 40 years in a systematised and comparable way is a major undertaking. A thorough description of the analyses, definitions and exclusions in the survival study, supplemented with corresponding information on cancer incidence and mortality is needed for appropriate interpretation and comparison between countries, and between and within cancer sites. This information must be made available to provide appropriate interpretation of the site-specific results.

Free radical derivatives formed from cyclooxygenase-catalyzed dihomo-γ-linolenic acid peroxidation can attenuate colon cancer cell growth and enhance 5-fluorouracil's cytotoxicity.

PubMed

Xu, Yi; Qi, Jin; Yang, Xiaoyu; Wu, Erxi; Qian, Steven Y

2014-01-01

Dihomo-γ-linolenic acid (DGLA) and its downstream fatty acid arachidonic acid (AA) are both nutritionally important ω-6 polyunsaturated fatty acids (ω-6s). Evidence shows that, via COX-mediated peroxidation, DGLA and its metabolites (1-series prostaglandins) are associated with anti-tumor activity, while AA and its metabolites (2-series prostaglandins) could be tightly implicated in various cancer diseases. However, it still remains a mystery why DGLA and AA possess contrasting bioactivities. Our previous studies showed that DGLA could go through an exclusive C-8 oxygenation pathway during COX-catalyzed lipid peroxidation in addition to a C-15 oxygenation pathway shared by both DGLA and AA, and that the exclusive C-8 oxygenation could lead to the production of distinct DGLA׳s free radical derivatives that may be correlated with DGLA׳s anti-proliferation activity. In the present work, we further investigate the anti-cancer effect of DGLA׳s free radical derivatives and their associated molecular mechanisms. Our study shows that the exclusive DGLA׳s free radical derivatives from C-8 oxygenation lead to cell growth inhibition, cell cycle arrest and apoptosis in the human colon cancer cell line HCA-7 colony 29, probably by up-regulating the cancer suppressor p53 and the cell cycle inhibitor p27. In addition, these exclusive radical derivatives were also able to enhance the efficacy of 5-Fluorouracil (5-FU), a widely used chemo-drug for colon cancer. For the first time, we show how DGLA׳s radical pathway and metabolites are associated with DGLA׳s anti-cancer activities and able to sensitize colon cancer cells to chemo-drugs such as 5-FU. Our findings could be used to guide future development of a combined chemotherapy and dietary care strategy for colon cancer treatment.

Oncogene activation and tumor suppressor gene inactivation find their sites of expression in the changes in time and space of the age-adjusted cancer incidence rate.

PubMed

Kodama, M; Kodama, T; Murakami, M

2000-01-01

The purpose of the present investigation is to elucidate the relation between the distribution pattern of the age-adjusted incidence rate (AAIR) changes in time and space of 15 tumors of bothe sexes and the locations of centers of centripetal-(oncogene type) and centrifugal-(tumoe suppressor gene type) forces. The fitness of the observed log AAIR data sets to the oncogene type- and the tumor suppressor gene type-equilibrium models and the locations of 2 force centers were calculated by applying the least square method of Gauss to log AAIR pair data series with and without topological data manipulations, which are so designed as to let log AAIR pair data series fit to 2 variant (x, y) frameworks, the Rect-coordinates and the Para-coordinates. The 2 variant (x, y) coordinates are defined each as an (x, y) framework with its X axis crossed at a right angle to the regression line of the original log AAIR data (the Rect-coordinates) and as another framework with its X axis run in parallel with the regression line of the original log AAIR pair data series (the Para-coordinates). The fitness test of log AAIR data series to either the oncogene activation type equilibrium model (r = -1.000) or the tumor suppressor gene inactivation type (r = 1.000) was conducted for each of the male-female type pair data and the female-male type data, for each of log AAIR changes in space and log AAIR changes in time, and for each of the 3 (x, y) frameworks in a given neoplasia of both sexes. The results obtained are given as follows: 1) The positivity rates of the fitness test to the oncogene type equilibrium model and the tumor suppressor gene type model were each 63.3% and 56.7% with the log AAIR changes in space, and 73.3% and 73.3% with log AAIR changes in time, as tested in 15 human neoplasias of both sexes. 2) Evidence was presented to indicate that the clearance of oncogene activation and tumor suppressor gene inactivation is the sine qua non premise of carciniogenesis. 3) The r profile in which the correlation coefficient r, a measure of fitness to the 2 equilibrium models, is converted to either +(r > 0) or -(0 > r) for each of the original-, the Rect-, and the Para-coordinates was found to be informative in identifying a group of tumors with sex discrimination of cancer risk (log AAIR changes in space) or another group of environmental hormone-linked tumors (log AAIR changes in time and space)--a finding to indicate that the r-profile of a given tumor, when compared with other neoplasias, may provide a clue to investigating the biological behavior of the tumor. 4) The recent risk increase of skin cancer of both sexes, being classified as an example of environmental hormone-linked neoplasias, was found to commit its ascension of cancer risk along the direction of the centrifugal forces of the time- and space-linked tumor suppressor gene inactivation plotted in the 2-dimension diagram. In conclusion, the centripetal force of oncogene activation and centrifugal force of tumor suppressor gene inactivation found their sites of expression in the distribution pattern of a cancer risk parameter, log AAIR, of a given neoplasias of both sexes on the 2-dimension diagram. The application of the least square method of Gauss to the log AAIR changes in time and space, and also with and without topological modulations of the original sets, when presented in terms of the r-profile, was found to be informative in understanding behavioral characteristics of human neoplaisias.

Discovery of a new series of imidazo[1,2-a]pyridine compounds as selective c-Met inhibitors

PubMed Central

Liu, Tong-chao; Peng, Xia; Ma, Yu-chi; Ji, Yin-chun; Chen, Dan-qi; Zheng, Ming-yue; Zhao, Dong-mei; Cheng, Mao-sheng; Geng, Mei-yu; Shen, Jing-kang; Ai, Jing; Xiong, Bing

2016-01-01

Aim: Aberrant c-Met activation plays a critical role in cancer formation, progression and dissemination, as well as in development of resistance to anticancer drugs. Therefore, c-Met has emerged as an attractive target for cancer therapy. The aim of this study was to develop new c-Met inhibitors and elaborate the structure-activity relationships of identified inhibitors. Methods: Based on the predicted binding modes of Compounds 5 and 14 in docking studies, a new series of c-Met inhibitor-harboring 3-((1H-pyrrolo[3,2-c]pyridin-1-yl)sulfonyl)imidazo[1,2-a]pyridine scaffolds was discovered. Potent inhibitors were identified through extensive optimizations combined with enzymatic and cellular assays. A promising compound was further investigated in regard to its selectivity, its effects on c-Met signaling, cell proliferation and cell scattering in vitro. Results: The most potent Compound 31 inhibited c-Met kinase activity with an IC50 value of 12.8 nmol/L, which was >78-fold higher than those of a panel of 16 different tyrosine kinases. Compound 31 (8, 40, 200 nmol/L) dose-dependently inhibited the phosphorylation of c-Met and its key downstream Akt and ERK signaling cascades in c-Met aberrant human EBC-1 cancer cells. In 12 human cancer cell lines harboring different background levels of c-Met expression/activation, Compound 31 potently inhibited c-Met-driven cell proliferation. Furthermore, Compound 31 dose-dependently impaired c-Met-mediated cell scattering of MDCK cells. Conclusion: This series of c-Met inhibitors is a promising lead for development of novel anticancer drugs. PMID:27041462

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients.

PubMed

de Jong, Monique C; Ten Hoeve, Jelle J; Grénman, Reidar; Wessels, Lodewyk F; Kerkhoven, Ron; Te Riele, Hein; van den Brekel, Michiel W M; Verheij, Marcel; Begg, Adrian C

2015-12-15

Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells, and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biologic processes that could be targeted to overcome intrinsic resistance. We analyzed both microRNA and mRNA expression in a large panel of head and neck squamous cell carcinoma (HNSCC) cell lines. Expression was measured on both irradiated and unirradiated samples. Results were validated using modified cell lines and a series of patients with laryngeal cancer. miRs, mRNAs, and gene sets that correlated with resistance could be identified from expression data of unirradiated cells. The presence of epithelial-to-mesenchymal transition (EMT) and low expression of miRs involved in the inhibition of EMT were important radioresistance determinants. This finding was validated in two independent cell line pairs, in which the induction of EMT reduced radiosensitivity. Moreover, low expression of the most important miR (miR-203) was shown to correlate with local disease recurrence after radiotherapy in a series of patients with laryngeal cancer. These findings indicate that EMT and low expression of EMT-inhibiting miRs, especially miR-203, measured in pretreatment material, causes intrinsic radioresistance of HNSCC, which could enable identification and treatment modification of radioresistant tumors. Clin Cancer Res; 21(24); 5630-8. ©2015 AACR. ©2015 American Association for Cancer Research.

High frequency of genes' promoter methylation, but lack of BRAF V600E mutation among Iranian colorectal cancer patients.

PubMed

Naghibalhossaini, Fakhraddin; Hosseini, Hamideh Mahmoodzadeh; Mokarram, Pooneh; Zamani, Mozhdeh

2011-12-01

Gene silencing due to DNA hypermethylation is a major mechanism for loss of tumor suppressor genes function in colorectal cancer. Activating V600E mutation in BRAF gene has been linked with widespread methylation of CpG islands in sporadic colorectal cancers. The aim of the present study was to evaluate the methylation status of three cancer-related genes, APC2, p14ARF, and ECAD in colorectal carcinogenesis and their association with the mutational status of BRAF and KRAS among Iranian colorectal cancer patients. DNA from 110 unselected series of sporadic colorectal cancer patients was examined for BRAF V600E mutation by PCR-RFLP. Promoter methylation of genes in tumors was determined by methylation specific PCR. The frequency of APC2, E-CAD, and p14 methylation was 92.6%, 40.4% and 16.7%, respectively. But, no V600E mutation was identified in the BRAF gene in any sample. No association was found in cases showing epigenetic APC, ECAD, and p14 abnormality with the clinicopathological parameters under study. The association between KRAS mutations and the so called methylator phenotype was previously reported. Therefore, we also analyzed the association between the hot spot KRAS gene mutations in codons of 12 and 13 with genes' promoter hypermethylation in a subset of this group of patients. Out of 86 tumors, KRAS was mutated in 24 (28%) of tumors, the majority occurring in codon 12. KRAS mutations were not associated with genes' methylation in this tumor series. These findings suggest a distinct molecular pathway for methylation of APC2, p14, and ECAD genes from those previously described for colorectal cancers with BRAF or KRAS mutations.

Spectrum of mismatch repair gene mutations and clinical presentation of Hispanic individuals with Lynch syndrome.

PubMed

Sunga, Annette Y; Ricker, Charité; Espenschied, Carin R; Castillo, Danielle; Melas, Marilena; Herzog, Josef; Bannon, Sarah; Cruz-Correa, Marcia; Lynch, Patrick; Solomon, Ilana; Gruber, Stephen B; Weitzel, Jeffrey N

2017-04-01

Lynch syndrome (LS), the most common hereditary colorectal cancer syndrome, is caused by mismatch repair (MMR) gene mutations. However, data about MMR mutations in Hispanics are limited. This study aims to describe the spectrum of MMR mutations in Hispanics with LS and explore ancestral origins. This case series involved an IRB-approved retrospective chart review of self-identified Hispanic patients (n = 397) seen for genetic cancer risk assessment at four collaborating academic institutions in California, Texas, and Puerto Rico who were evaluated by MMR genotyping and/or tumor analysis. A literature review was conducted for all mutations identified. Of those who underwent clinical genetic testing (n = 176), 71 had MMR gene mutations. Nine mutations were observed more than once. One third (3/9) of recurrent mutations and two additional mutations (seen only once) were previously reported in Spain, confirming the influence of Spanish ancestry on MMR mutations in Hispanic populations. The recurrent mutations identified (n = 9) included both previously reported mutations as well as unique mutations not in the literature. This is the largest report of Hispanic MMR mutations in North America; however, a larger sample and haplotype analyses are needed to better understand recurrent MMR mutations in Hispanic populations. Copyright © 2017. Published by Elsevier Inc.

Tanning and Teens: Is Indoor Exposure the Tip of the Iceberg?

PubMed

Hay, Jennifer L; Riley, Kristen E; Geller, Alan C

2017-08-01

Because of recent state regulations and the reduced availability of free-standing tanning salons, indoor tanning (IT) prevalence is beginning to decline. This may lead to unintended consequences, such as increases in outdoor intentional tanning. We advance a series of research directions to track and intervene to address all forms of intentional tanning. First, we advocate for enforcement of IT regulation and encourage collection of data on tanning salon compliance and alternative IT strategies. Second, we suggest questions about outdoor and IT should be included in national surveys. Third, we need to understand the potentially complex patterns of indoor and outdoor tanning that may exist among those who tan. Fourth, research examining changing motivations for intentional tanning is needed. Finally, IT intervention studies should include outdoor tanning as an outcome to examine the effect of interventions on these related risk behaviors. These advances will ensure the development of novel interventions to address intentional tanning through multiple routes, and to avoid any unintended negative consequence of IT regulation. The promising downward direction of IT use in the United States should now lead the public health field to sharpen its focus on outdoor tanning. Cancer Epidemiol Biomarkers Prev; 26(8); 1170-4. ©2017 AACR . ©2017 American Association for Cancer Research.

Valency and density matter: Deciphering impacts of immunogen structures on immune responses against a tumor associated carbohydrate antigen using synthetic glycopolymers.

PubMed

Qin, Qian; Yin, Zhaojun; Wu, Xuanjun; Haas, Karen M; Huang, Xuefei

2016-09-01

For successful carbohydrate based anti-cancer vaccines, it is critical that B cells are activated to secret antibodies targeting the tumor associated carbohydrate antigens (TACAs). Despite the availability of many TACA based constructs, systematic understanding of the effects of structural features on anti-glycan antibody responses is lacking. In this study, a series of defined synthetic glyco-polymers bearing a representative TACA, i.e., the Thomsen-nouveau (Tn) antigen, have been prepared to probe the induction of early B cell activation and antibody production via a T cell independent mechanism. Valency and density of the antigen in the polymers turned out to be critical. An average of greater than 6 Tn per chain was needed to induce antibody production. Glycopolymers with 40 antigens per chain and backbone molecular weight of 450 kDa gave the strongest stimulation to B cells in vitro, which correlated well with its in vivo activity. Deviations from the desired valency and density led to decreased antibody production or even antigen specific B cell non-responsiveness. These findings provide important insights on how to modulate anti-TACA immune responses facilitating the development of TACA based anti-cancer vaccines using glycopolymers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hsp90 can Accommodate the Simultaneous Binding of the FKBP52 and HOP Proteins

PubMed Central

Hildenbrand, Zacariah L.; Molugu, Sudheer K.; Herrera, Nadia; Ramirez, Citlally; Xiao, Chuan; Bernal, Ricardo A.

2011-01-01

The regulation of steroidogenic hormone receptor-mediated activity plays an important role in the development of hormone-dependent cancers. For example, during prostate carcinogenesis, the regulatory function played by the androgen receptor is often converted from a growth suppressor to an oncogene thus promoting prostate cancer cell survival and eventual metastasis. Within the cytoplasm, steroid hormone receptor activity is regulated by the Hsp90 chaperone in conjunction with a series of co-chaperone proteins. Collectively, Hsp90 and its binding associates form a large heteromeric complex that scaffold the fully mature receptor for binding with the respective hormone. To date our understanding of the interactions between Hsp90 with the various TPR domain-containing co-chaperone proteins is limited due to a lack of available structural information. Here we present the stable formation of Hsp902-FKBP521- HOP2 and Hsp902-FKBP521-p232-HOP2 complexes as detected by immunoprecipitation, time course dynamic light scattering and electron microscopy. The simultaneous binding of FKBP52 and HOP to the Hsp90 dimer provide direct evidence of a novel chaperone sub-complex that likely plays a transient role in the regulation of the fully mature steroid hormone receptor. PMID:21378414

Design and synthesis of imidazopyridine analogues as inhibitors of phosphoinositide 3-kinase signaling and angiogenesis.

PubMed

Kim, Okseon; Jeong, Yujeong; Lee, Hyunseung; Hong, Sun-Sun; Hong, Sungwoo

2011-04-14

Phosphatidylinositol 3-kinase α (PI3Kα) is an important regulator of intracellular signaling pathways, controlling remarkably diverse arrays of physiological processes. Because the PI3K pathway is frequently up-regulated in human cancers, the inhibition of PI3Kα can be a promising approach to cancer therapy. In this study, we have designed and synthesized a new series of imidazo[1,2-a]pyridine derivatives as PI3Kα inhibitors through the fragment-growing strategy. By varying groups at the 3- and 6-positions of imidazo[1,2-a]pyridines, we studied the structure-activity relationships (SAR) profiles and identified a series of potent PI3Kα inhibitors. Representative derivatives showed good activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.

Synthesis, characterisation, and in vitro anticancer activity of curcumin analogues bearing pyrazole/pyrimidine ring targeting EGFR tyrosine kinase.

PubMed

Ahsan, Mohamed Jawed; Khalilullah, Habibullah; Yasmin, Sabina; Jadav, Surender Singh; Govindasamy, Jeyabalan

2013-01-01

In search of potential therapeutics for cancer, we described herein the synthesis, characterization, and in vitro anticancer activity of a novel series of curcumin analogues. The anticancer effects were evaluated on a panel of 60 cell lines, according to the National Cancer Institute (NCI) screening protocol. There were 10 tested compounds among 14 synthesized compounds, which showed potent anticancer activity in both one-dose and 5-dose assays. The most active compound of the series was 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1-yl(phenyl)methanone which showed mean growth percent of -28.71 in one-dose assay and GI₅₀ values between 0.0079 and 1.86 µM in 5-dose assay.

A note from history: landmarks in history of cancer, part 1.

PubMed

Hajdu, Steven I

2011-03-01

Review of the earliest written descriptions and reports of cancer show that ancient physicians and surgeons made gradual progress in understanding cancer. It became clear to most of them that early detection and complete removal, before the cancer became ulcerated, afforded the best outcome. Copyright © 2010 American Cancer Society.

Mechanisms of Cancer Cell Dormancy--Another Hallmark of Cancer?

PubMed

Yeh, Albert C; Ramaswamy, Sridhar

2015-12-01

Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. ©2015 American Association for Cancer Research.

Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii.

PubMed

Lun, Zhao-Rong; Lai, De-Hua; Wen, Yan-Zi; Zheng, Ling-Ling; Shen, Ji-Long; Yang, Ting-Bo; Zhou, Wen-Liang; Qu, Liang-Hu; Hide, Geoff; Ayala, Francisco J

2015-07-21

Cancer is a general name for more than 100 malignant diseases. It is postulated that all cancers start from a single abnormal cell that grows out of control. Untreated cancers can cause serious consequences and deaths. Great progress has been made in cancer research that has significantly improved our knowledge and understanding of the nature and mechanisms of the disease, but the origins of cancer are far from being well understood due to the limitations of suitable model systems and to the complexities of the disease. In view of the fact that cancers are found in various species of vertebrates and other metazoa, here, we suggest that cancer also occurs in parasitic protozoans such as Trypanosoma brucei, a blood parasite, and Toxoplasma gondii, an obligate intracellular pathogen. Without treatment, these protozoan cancers may cause severe disease and death in mammals, including humans. The simpler genomes of these single-cell organisms, in combination with their complex life cycles and fascinating life cycle differentiation processes, may help us to better understand the origins of cancers and, in particular, leukemias.

Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii

PubMed Central

Lun, Zhao-Rong; Lai, De-Hua; Wen, Yan-Zi; Zheng, Ling-Ling; Shen, Ji-Long; Yang, Ting-Bo; Zhou, Wen-Liang; Qu, Liang-Hu; Hide, Geoff; Ayala, Francisco J.

2015-01-01

Cancer is a general name for more than 100 malignant diseases. It is postulated that all cancers start from a single abnormal cell that grows out of control. Untreated cancers can cause serious consequences and deaths. Great progress has been made in cancer research that has significantly improved our knowledge and understanding of the nature and mechanisms of the disease, but the origins of cancer are far from being well understood due to the limitations of suitable model systems and to the complexities of the disease. In view of the fact that cancers are found in various species of vertebrates and other metazoa, here, we suggest that cancer also occurs in parasitic protozoans such as Trypanosoma brucei, a blood parasite, and Toxoplasma gondii, an obligate intracellular pathogen. Without treatment, these protozoan cancers may cause severe disease and death in mammals, including humans. The simpler genomes of these single-cell organisms, in combination with their complex life cycles and fascinating life cycle differentiation processes, may help us to better understand the origins of cancers and, in particular, leukemias. PMID:26195778

Factors associated with late stage at diagnosis among Puerto Rico's government health plan colorectal cancer patients: a cross-sectional study.

PubMed

Ortiz-Ortiz, Karen J; Ríos-Motta, Ruth; Marín-Centeno, Heriberto; Cruz-Correa, Marcia; Ortiz, Ana Patricia

2016-08-03

Late stage at diagnosis of cancer is considered a key predictor factor for a lower survival rate. Knowing and understanding the barriers to an early diagnosis of colorectal cancer is critical in the fight to reduce the social and economic burden caused by cancer in Puerto Rico. This study evaluates factors associated to colorectal cancer stage at diagnosis among Puerto Rico's Government Health Plan (GHP) patients. We conducted a cross-sectional study based on a secondary data analysis using information from the Puerto Rico Central Cancer Registry (PRCCR) and the Puerto Rico Health Insurance Administration (PRHIA). Logistic regression models were used to estimate the unadjusted odds ratio (ORs) and adjusted odds ratio (AORs), and their 95 % confidence intervals (CIs). Colorectal cancer cases diagnosed between January 1, 2012 and December 31, 2012, among persons 50 to 64 years of age, participants of the GHP and with a cancer diagnosis reported to the PRCCR were included in the study. There were 68 (35.79 %) colorectal cancer patients diagnosed at early stage while 122 (64.21 %) where diagnosed at late stage. In the multivariate analysis having a diagnostic delay of more than 59 days (AOR 2.94, 95 % CI: 1.32 to 6.52) and having the first visit through the emergency room (AOR 3.48, 95 % CI: 1.60 to 7.60) were strong predictors of being diagnosed with colorectal cancer at a late stage. These results are relevant to understand the factors that influence the outcomes of colorectal cancer patients in the GHP. Therefore, it is important to continue developing studies to understand the Government Health Plan patient's pathways to a cancer diagnosis, in order to promote assertive decisions to improve patient outcomes.

Validating a mouse model of ovarian cancer for early detection through imaging | Division of Cancer Prevention

Cancer.gov

Despite advances in treatment strategies, ovarian cancer remains the deadliest gynecological malignancy and the 5th largest cancer killer in women. Located deep in the body, with few early symptoms and no effective screening technique, ovarian cancer has remained stubbornly difficult to understand, much less effectively combat. Ovarian cancer is almost always discovered at an

Interventions to improve patient understanding of cancer clinical trial participation: a systematic review.

PubMed

Kao, C Y; Aranda, S; Krishnasamy, M; Hamilton, B

2017-03-01

Patient misunderstanding of cancer clinical trial participation is identified as a critical issue and researchers have developed and tested a variety of interventions to improve patient understanding. This systematic review identified nine papers published between 2000 and 2013, to evaluate the effects of interventions to improve patient understanding of cancer clinical trial participation. Types of interventions included audio-visual information, revised written information and a communication training workshop. Interventions were conducted alone or in combination with other forms of information provision. The nine papers, all with methodological limitations, reported mixed effects on a small range of outcomes regarding improved patient understanding of cancer clinical trial participation. The methodological limitations included: (1) the intervention development process was poorly described; (2) only a small element of the communication process was addressed; (3) studies lacked evidence regarding what information is essential and critical to enable informed consent; (4) studies lacked reliable and valid outcome measures to show that patients are sufficiently informed to provide consent; and (5) the intervention development process lacked a theoretical framework. Future research needs to consider these factors when developing interventions to improve communication and patient understanding during the informed consent process. © 2016 John Wiley & Sons Ltd.

Computational Reconstruction of NFκB Pathway Interaction Mechanisms during Prostate Cancer

PubMed Central

Börnigen, Daniela; Tyekucheva, Svitlana; Wang, Xiaodong; Rider, Jennifer R.; Lee, Gwo-Shu; Mucci, Lorelei A.; Sweeney, Christopher; Huttenhower, Curtis

2016-01-01

Molecular research in cancer is one of the largest areas of bioinformatic investigation, but it remains a challenge to understand biomolecular mechanisms in cancer-related pathways from high-throughput genomic data. This includes the Nuclear-factor-kappa-B (NFκB) pathway, which is central to the inflammatory response and cell proliferation in prostate cancer development and progression. Despite close scrutiny and a deep understanding of many of its members’ biomolecular activities, the current list of pathway members and a systems-level understanding of their interactions remains incomplete. Here, we provide the first steps toward computational reconstruction of interaction mechanisms of the NFκB pathway in prostate cancer. We identified novel roles for ATF3, CXCL2, DUSP5, JUNB, NEDD9, SELE, TRIB1, and ZFP36 in this pathway, in addition to new mechanistic interactions between these genes and 10 known NFκB pathway members. A newly predicted interaction between NEDD9 and ZFP36 in particular was validated by co-immunoprecipitation, as was NEDD9's potential biological role in prostate cancer cell growth regulation. We combined 651 gene expression datasets with 1.4M gene product interactions to predict the inclusion of 40 additional genes in the pathway. Molecular mechanisms of interaction among pathway members were inferred using recent advances in Bayesian data integration to simultaneously provide information specific to biological contexts and individual biomolecular activities, resulting in a total of 112 interactions in the fully reconstructed NFκB pathway: 13 (11%) previously known, 29 (26%) supported by existing literature, and 70 (63%) novel. This method is generalizable to other tissue types, cancers, and organisms, and this new information about the NFκB pathway will allow us to further understand prostate cancer and to develop more effective prevention and treatment strategies. PMID:27078000

Understanding of prognosis among parents of children with cancer: parental optimism and the parent-physician interaction.

PubMed

Mack, Jennifer W; Cook, E Francis; Wolfe, Joanne; Grier, Holcombe E; Cleary, Paul D; Weeks, Jane C

2007-04-10

Patients often overestimate their chances of surviving cancer. Factors that contribute to accurate understanding of prognosis are not known. We assessed understanding of likelihood of cure and functional outcome among parents of children with cancer and sought to identify factors that place parents at risk for overly optimistic beliefs about prognosis. We conducted a cross-sectional survey of 194 parents of children with cancer (response rate, 70%) who were treated at the Dana-Farber Cancer Institute and Children's Hospital in Boston, MA, and the children's physicians. Parent and physician expectations for likelihood of cure and functional outcome were compared. In 152 accurate or optimistic parents, we determined factors associated with accurate understanding of likelihood of cure compared with optimism. The majority of parents (61%) were more optimistic than physicians about the likelihood of cure. Parents' beliefs about other outcomes of cancer treatment were similar (quality-of-life impairment, P = .70) or more pessimistic (physical impairment, P = .01; intellectual impairment, P = .01) than physicians' beliefs. Parents and physicians were more likely to agree about chances of cure when physicians had confidence in knowledge of prognosis (odds ratio [OR] = 2.55, P = .004) and allowed parents to take their preferred decision-making role (OR = 1.89, P = .019). Parents of children with cancer are overly optimistic about chances of cure but not about other outcomes of cancer therapy. Parents tend to be overly optimistic about cure when physicians have little confidence and when the decision-making process does not meet parents' preferences. These findings suggest that physicians are partly responsible for parents' unrealistic expectations about cure.

Understanding Prostate Changes

Cancer.gov

Prostate changes and symptoms that are not cancer. Learn about symptoms, risk factors, and treatment for prostatitis, enlarged prostate (BPH), prostate cancer. Talk with doctor about prostate cancer screening tests (DRE, PSA), biopsy, and Gleason score.

NCI Contact Center

Cancer.gov

The NCI Contact Center (formerly the Cancer Information Service) provides accurate, up-to-date, and reliable information on cancer that is easy to understand. Trained information specialists provide personalized responses to a range of cancer questions.

Summer Events at the Scientific Library | Poster

Cancer.gov

If it’s summer, then it’s time for Jeopardy and videos at the National Cancer Institute at Frederick! Traditionally, the Scientific Library has hosted a Science Jeopardy Tournament in July and offered a Summer Video Series in June, July, and August. This year will be no different, as the Scientific Library will host the 11th Annual Student Science Jeopardy Tournament and a six-week series of film screenings.

Is screening and surveillance for early detection of gastric cancer needed in Korean Americans?

PubMed Central

Kim, Gwang Ha; Bang, Sung Jo; Ende, Alexander R.; Hwang, Joo Ha

2015-01-01

The incidence rate of gastric cancer in Korean Americans is over five times higher than that in non-Hispanic whites, and is similar to the incidence of colorectal cancer in the overall United States population. In Korea, the National Cancer Screening Program recommends endoscopy or upper gastrointestinal series for people aged 40 years and older every 2 years. However, the benefit of gastric cancer screening in Korean Americans has not been evaluated. Based on epidemiologic studies, Korean Americans appear to have more similar gastric cancer risk factors to Koreans as opposed to Americans of European descent, though the risk of gastric cancer appears to decrease for subsequent generations. Therefore, in accordance with recent recommendations regarding screening for gastric cancer in Korea, endoscopic screening for gastric cancer in Korean Americans should be considered, especially in those with known atrophic gastritis/intestinal metaplasia or a family history of gastric cancer. In the future, additional studies will needed to assess whether a screening program for gastric cancer in Korean Americans will result in a survival benefit. PMID:26552450

Understanding Cancer Prevention, Detection, Treatment, Control

MedlinePlus

... on cancer research and treatment. August 5 of this year marks the 70th anniversary of the National Cancer ... the United States in 2003 than in 2002. This was the first decrease in cancer deaths since 1930, the year our country began compiling statistics on the disease's ...

The LOX Invasion: Stopping the Spread of Breast Cancer | Center for Cancer Research

Cancer.gov

Metastasis is the primary cause of death in breast cancer patients. In 10% of breast cancer diagnoses, the cancer has already spread to distant organs in the body. Although breast cancer has the potential to spread to almost any region of the body, the most common is the bone, followed by the lung and liver. Understanding the mechanisms for breast cancer invasion and

Targeting the tumour microenvironment in ovarian cancer.

PubMed

Hansen, Jean M; Coleman, Robert L; Sood, Anil K

2016-03-01

The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype. Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Photodynamic Cancer Therapy—Recent Advances

NASA Astrophysics Data System (ADS)

Abrahamse, Heidi

2011-09-01

The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when "photoradiation therapy" was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular localization of PS is of vital importance when cell death mechanism is identified. Programmed cell death (PCD) viz. apoptosis, necrosis and autophagy have all been identified as inducible cell death mechanisms during PDT. While apoptosis is probably the preferred cell death mechanism, understanding the molecular differences and identifying the cross-talk between these mechanisms are crucial to the development of new PSs aimed at improving the killing efficiency and overall effectiveness of PDT as a cancer treatment modality. This paper reviews the process of PDT cancer therapy, the available PSs, their effectiveness for different cancers as well as the cell death mechanisms identified during PDT of different cancers associated with specific PSs.

Photodynamic Cancer Therapy - Recent Advances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abrahamse, Heidi

The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first ormore » second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular localization of PS is of vital importance when cell death mechanism is identified. Programmed cell death (PCD) viz. apoptosis, necrosis and autophagy have all been identified as inducible cell death mechanisms during PDT. While apoptosis is probably the preferred cell death mechanism, understanding the molecular differences and identifying the cross-talk between these mechanisms are crucial to the development of new PSs aimed at improving the killing efficiency and overall effectiveness of PDT as a cancer treatment modality. This paper reviews the process of PDT cancer therapy, the available PSs, their effectiveness for different cancers as well as the cell death mechanisms identified during PDT of different cancers associated with specific PSs.« less

Environmental effects on molecular biomarkers expression in pancreatic and brain cancer

NASA Astrophysics Data System (ADS)

Mensah, Lawrence; Mallidi, Srivalleesha; Massodi, Iqbal; Anbil, Sriram; Mai, Zhiming; Hasan, Tayyaba

2013-03-01

A complete understanding of the biological mechanisms regulating devastating disease such as cancer remains elusive. Pancreatic and brain cancers are primary among the cancer types with poor prognosis. Molecular biomarkers have emerged as group of proteins that are preferentially overexpressed in cancers and with a key role in driving disease progression and resistance to chemotherapy. The epidermal growth factor receptor (EGFR), a cell proliferative biomarker is particularly highly expressed in most cancers including brain and pancreatic cancers. The ability of EGFR to sustain prolong cell proliferation is augmented by biomarkers such as Bax, Bcl-XL and Bcl-2, proteins regulating the apoptotic process. To better understand the role and effect of the microenvironment on these biomarkers in pancreatic cancer (PaCa); we analysed two pancreatic tumor lines (AsPc-1 and MiaPaCa-2) in 2D, 3D in-vitro cultures and in orthotopic tumors at different growth stages. We also investigated in patient derived glioblastoma (GBM) tumor cultures, the ability to utilize the EGFR expression to specifically deliver photosensitizer to the cells for photodynamic therapy. Overall, our results suggest that (1) microenvironment changes affect biomarker expression; thereby it is critical to understand these effects prior to designing combination therapies and (2) EGFR expression in tumor cells indeed could serve as a reliable and a robust biomarker that could be used to design targeted and image-guided photodynamic therapy.

Understanding cellular architecture in cancer cells

NASA Astrophysics Data System (ADS)

Bianco, Simone; Tang, Chao

2011-03-01

Understanding the development of cancer is an important goal for today's science. The morphology of cellular organelles, such as the nucleus, the nucleoli and the mitochondria, which is referred to as cellular architecture or cytoarchitecture, is an important indicator of the state of the cell. In particular, there are striking difference between the cellular architecture of a healthy cell versus a cancer cell. In this work we present a dynamical model for the evolution of organelles morphology in cancer cells. Using a dynamical systems approach, we describe the evolution of a cell on its way to cancer as a trajectory in a multidimensional morphology state. The results provided by this work may increase our insight on the mechanism of tumorigenesis and help build new therapeutic strategies.

Helping your child understand a cancer diagnosis

MedlinePlus

... or movie together, or buy your child some comic books. Visit with other children who have had ... guide for parents. www.cancer.gov/publications/patient-education/children-with-cancer.pdf . Updated September 2015. Accessed ...

Childhood Cancer Survivor Study: An Overview

Cancer.gov

Health problems that develop years later as a result of a cancer treatment are known as late effects. The Childhood Cancer Survivor Study (CCSS) was started in 1994 to better understand these late effects.

Cancer Research in the Media

Cancer.gov

Cancer Research in the Media (CRiM) is a two-day seminar designed for international journalists to increase their understanding of complex scientific findings, improving their ability to communicate accurate cancer-related information to the public.

Mechanisms of Cancer - Annual Plan

Cancer.gov

NCI works to understand the mechanisms of cancer cell growth, survival, and metastasis. Get more information on how NCI supports basic scientific research that will lead to new ways to prevent, detect, and treat cancer.

Mammographic density and breast cancer risk: current understanding and future prospects

PubMed Central

2011-01-01

Variations in percent mammographic density (PMD) reflect variations in the amounts of collagen and number of epithelial and non-epithelial cells in the breast. Extensive PMD is associated with a markedly increased risk of invasive breast cancer. The PMD phenotype is important in the context of breast cancer prevention because extensive PMD is common in the population, is strongly associated with risk of the disease, and, unlike most breast cancer risk factors, can be changed. Work now in progress makes it likely that measurement of PMD will be improved in the near future and that understanding of the genetics and biological basis of the association of PMD with breast cancer risk will also improve. Future prospects for the application of PMD include mammographic screening, risk prediction in individuals, breast cancer prevention research, and clinical decision making. PMID:22114898

A global view of regulatory networks in lung cancer: An approach to understand homogeneity and heterogeneity.

PubMed

Lu, Jiapei; Wang, William; Xu, Menglin; Li, Yuping; Chen, Chengshui; Wang, Xiangdong

2017-02-01

A number of new biotechnologies are used to identify potential biomarkers for the early detection of lung cancer, enabling a personalized therapy to be developed in response. The combinatorial cross-regulation of hundreds of biological function-specific transcription factors (TFs) is defined as the understanding of regulatory networks of molecules within the cell. Here we integrated global databases with 537 patients with lung adenocarcinoma (ADC), 140 with lung squamous carcinoma (SCC), 9 with lung large-cell carcinoma (LCC), 56 with small-cell lung cancer (SCLC), and 590 without cancer with the understanding of TF functions. The present review aims at the homogeneity or heterogeneity of gene expression profiles among subtypes of lung cancer. About 5, 136, 52, or 16 up-regulated or 19, 24, 122, or 97down-regulated type-special TF genes were identified in ADC, SCC, LCC or SCLC, respectively. DNA-binding and transcription regulator activity associated genes play a dominant role in the differentiation of subtypes in lung cancer. Subtype-specific TF gene regulatory networks with elements should be an alternative for diagnostic and therapeutic targets for early identification of lung cancer and can provide insightful clues to etiology and pathogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk-reducing mastectomy for the prevention of primary breast cancer.

PubMed

Carbine, Nora E; Lostumbo, Liz; Wallace, Judi; Ko, Henry

2018-04-05

Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased interest in RRM as a method of preventing breast cancer. This is an update of a Cochrane Review first published in 2004 and previously updated in 2006 and 2010. (i) To determine whether risk-reducing mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of risk-reducing mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes. For this Review update, we searched Cochrane Breast Cancer's Specialized Register, MEDLINE, Embase and the WHO International Clinical Trials Registry Platform (ICTRP) on 9 July 2016. We included studies in English. Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer. At least two review authors independently abstracted data from each report. We summarized data descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. We analyzed data separately for bilateral risk-reducing mastectomy (BRRM) and contralateral risk-reducing mastectomy (CRRM). Four review authors assessed the methodological quality to determine whether or not the methods used sufficiently minimized selection bias, performance bias, detection bias, and attrition bias. All 61 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer, who underwent RRM.Twenty-one BRRM studies looking at the incidence of breast cancer or disease-specific mortality, or both, reported reductions after BRRM, particularly for those women with BRCA1/2 mutations. Twenty-six CRRM studies consistently reported reductions in incidence of contralateral breast cancer but were inconsistent about improvements in disease-specific survival. Seven studies attempted to control for multiple differences between intervention groups and showed no overall survival advantage for CRRM. Another study showed significantly improved survival following CRRM, but after adjusting for bilateral risk-reducing salpingo-oophorectomy (BRRSO), the CRRM effect on all-cause mortality was no longer significant.Twenty studies assessed psychosocial measures; most reported high levels of satisfaction with the decision to have RRM but greater variation in satisfaction with cosmetic results. Worry over breast cancer was significantly reduced after BRRM when compared both to baseline worry levels and to the groups who opted for surveillance rather than BRRM, but there was diminished satisfaction with body image and sexual feelings.Seventeen case series reporting on adverse events from RRM with or without reconstruction reported rates of unanticipated reoperations from 4% in those without reconstruction to 64% in participants with reconstruction.In women who have had cancer in one breast, removing the other breast may reduce the incidence of cancer in that other breast, but there is insufficient evidence that this improves survival because of the continuing risk of recurrence or metastases from the original cancer. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention, when considering RRM. While published observational studies demonstrated that BRRM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies are suggested. BRRM should be considered only among those at high risk of disease, for example, BRCA1/2 carriers. CRRM was shown to reduce the incidence of contralateral breast cancer, but there is insufficient evidence that CRRM improves survival, and studies that control for multiple confounding variables are recommended. It is possible that selection bias in terms of healthier, younger women being recommended for or choosing CRRM produces better overall survival numbers for CRRM. Given the number of women who may be over-treated with BRRM/CRRM, it is critical that women and clinicians understand the true risk for each individual woman before considering surgery. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention when considering RRM.

Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies.

PubMed

Bianchi, Diana W; Chudova, Darya; Sehnert, Amy J; Bhatt, Sucheta; Murray, Kathryn; Prosen, Tracy L; Garber, Judy E; Wilkins-Haug, Louise; Vora, Neeta L; Warsof, Stephen; Goldberg, James; Ziainia, Tina; Halks-Miller, Meredith

2015-07-14

Understanding the relationship between aneuploidy detection on noninvasive prenatal testing (NIPT) and occult maternal malignancies may explain results that are discordant with the fetal karyotype and improve maternal clinical care. To evaluate massively parallel sequencing data for patterns of copy-number variations that might prospectively identify occult maternal malignancies. Case series identified from 125,426 samples submitted between February 15, 2012, and September 30, 2014, from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening. Analyses were conducted in a clinical laboratory that performs DNA sequencing. Among the clinical samples, abnormal results were detected in 3757 (3%); these were reported to the ordering physician with recommendations for further evaluation. NIPT for fetal aneuploidy screening (chromosomes 13, 18, 21, X, and Y). Detailed genome-wide bioinformatics analysis was performed on available sequencing data from 8 of 10 women with known cancers. Genome-wide copy-number changes in the original NIPT samples and in subsequent serial samples from individual patients when available are reported. Copy-number changes detected in NIPT sequencing data in the known cancer cases were compared with the types of aneuploidies detected in the overall cohort. From a cohort of 125,426 NIPT results, 3757 (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. From this set of 3757 samples, 10 cases of maternal cancer were identified. Detailed clinical and sequencing data were obtained in 8. Maternal cancers most frequently occurred with the rare NIPT finding of more than 1 aneuploidy detected (7 known cancers among 39 cases of multiple aneuploidies by NIPT, 18% [95% CI, 7.5%-33.5%]). All 8 cases that underwent further bioinformatics analysis showed unique patterns of nonspecific copy-number gains and losses across multiple chromosomes. In 1 case, blood was sampled after completion of treatment for colorectal cancer and the abnormal pattern was no longer evident. In this preliminary study, a small number of cases of occult malignancy were subsequently diagnosed among pregnant women whose noninvasive prenatal testing results showed discordance with the fetal karyotype. The clinical importance of these findings will require further research.

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

PubMed Central

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

Surface modification of esophageal stent materials by a polyethylenimine layer aiming at anti-cancer function.

PubMed

Zhang, Kun; Bai, Yuxin; Wang, Xiaofeng; Li, Qian; Guan, Fangxia; Li, Jingan

2017-08-01

Esophageal cancer is difficult to cure globally and possesses high mortality rate, and it is generally accepted that palliative care such as stent implantation is the main therapy method for esophageal cancer in later period. However, the restenosis caused by tumor cells and inflammatory cells seriously interferes the stent clinical application and limits its long-term services. To solve this problem, series of drug delivery stents were developed and proven rather effective in the early stage of implantation, but more serious restenosis occurred after the drug delivery was over, which endangered the patients' life. Therefore, endowing the esophageal stent continuous anti-cancer function become an ideal strategy for inhibiting the restenosis. In this contribution, the functional layer composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of molecular weights (MW, 1.8 × 10 3 , 1 × 10 4 , 2.5 × 10 4 and 7 × 10 4  Da) were fabricated onto the esophageal stent material 317L stainless steel (317L SS) surface. The surface characterization including amine quantitative, atomic force microscopy (AFM) and water contact angle measurement indicated successful preparation of the PDA/PEI layer. The Eca109 cells culture results proved that the PDA/PEI layers significantly improve Eca109 cells apoptosis and necrosis, suggesting excellent anti-cancer function. In addition, we also found that the anti-cancer function of the PDA/PEI layers was positively correlated to the immobilized PEIs' MW. All the results demonstrated the potential application of the PDA/PEI layers on the surface modification of esophageal stent for continuous anti-cancer function. It is generally accepted that the restenosis caused by tumor cells seriously interferes the esophageal stent clinical application. Thus, endowing the esophageal stent continuous anti-cancer function is the ideal strategy for inhibiting the restenosis. In this work, we fabricated functional layers composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of molecular weights (MW, 1.8 × 10 3 , 1 × 10 4 , 2.5 × 10 4 and 7 × 10 4  Da) onto the esophageal stent material 317L stainless steel (317L SS) surface to inhibit the tumor cells growth, and this function was related to the PEIs' molecular weights. The functional PDA/PEI layers were expected potentially applied for surface modification of esophageal stent materials.

Understanding Microbiome Effect on Immune Checkpoint Inhibition in Lung Cancer: Placing the Puzzle Pieces Together.

PubMed

Swami, Umang; Zakharia, Yousef; Zhang, Jun

2018-05-17

Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations.

Risk communication and decision-making in the prevention of invasive breast cancer.

PubMed

Partridge, Ann H

2017-08-01

Risk communication surrounding the prevention of invasive breast cancer entails not only understanding of the disease, risks and opportunities for intervention. But it also requires understanding and implementation of optimal strategies for communication with patients who are making these decisions. In this article, available evidence for the issues surrounding risk communication and decision making in the prevention of invasive breast cancer are reviewed and strategies for improvement are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cancer survivors' understanding of the cause and cure of their illness: Religious and secular appraisals.

PubMed

Carney, Lauren M; Park, Crystal L

2018-02-28

Little is known about survivors' understanding of the cause of their cancer and of their recovery, nor how these ways of understanding relate to their well-being. No study has examined both secular and religious appraisals of the same event. The current study aimed to examine both religious (God) and secular (self) appraisals of both the cause (attributions) and course/cure of cancer in relation to multiple aspects of adjustment. Data were obtained from a sample of cancer survivors at Time 1 (n = 250) and 1 year later (Time 2, n = 167). Cancer survivors endorsed higher appraisals relating to course/cure of their cancer than those relating to cause, and they endorsed both secular and religious appraisals. Appraisals of the cause and course/cure of cancer were differentially related to adjustment, such that self-attributions of cause and God-attributions of cause were related to negative aspects of adjustment (eg, negative affect and pessimism), while appraisals of self and God's control over the course/cure were related to positive aspects of adjustment (eg, perceived positive life and health changes since cancer). Religiosity did not moderate most of relationships between religious appraisals and adjustment outcomes. Secular and religious appraisals of cancer are not mutually exclusive, and religious appraisals are associated with adjustment regardless of survivors' religiosity. Appraisals relating to cause and course/cure have differential relationships with well-being. Addressing cancer survivors' appraisals-religious or nonreligious-in a therapeutic setting may be beneficial regardless of their reported religiosity. Copyright © 2018 John Wiley & Sons, Ltd.

Prevalence of MLH1 constitutional epimutations as a cause of Lynch syndrome in unselected versus selected consecutive series of patients with colorectal cancer.

PubMed

Castillejo, Adela; Hernández-Illán, Eva; Rodriguez-Soler, María; Pérez-Carbonell, Lucía; Egoavil, Cecilia; Barberá, Victor M; Castillejo, María-Isabel; Guarinos, Carla; Martínez-de-Dueñas, Eduardo; Juan, María-Jose; Sánchez-Heras, Ana-Beatriz; García-Casado, Zaida; Ruiz-Ponte, Clara; Brea-Fernández, Alejandro; Juárez, Miriam; Bujanda, Luis; Clofent, Juan; Llor, Xavier; Andreu, Montserrat; Castells, Antoni; Carracedo, Angel; Alenda, Cristina; Payá, Artemio; Jover, Rodrigo; Soto, José-Luis

2015-07-01

The prevalence of MLH1 constitutional epimutations in the general population is unknown. We sought to analyse the prevalence of MLH1 constitutional epimutations in unselected and selected series of patients with colorectal cancer (CRC). Patients with diagnoses of CRC (n=2123) were included in the unselected group. For comparison, a group of 847 selected patients with CRC who fulfilled the revised Bethesda guidelines (rBG) were also included. Somatic and constitutional MLH1 methylation was assayed via methylation-specific multiplex ligation-dependent probe amplification of cases lacking MLH1 expression. Germline alterations in mismatch-repair (MMR) genes were assessed via Sanger sequencing and methylation-specific multiplex ligation-dependent probe amplification. Loss of MLH1 expression occurred in 5.5% of the unselected series and 12.5% of the selected series (p<0.0001). No constitutional epimutations in MLH1 were detected in the unselected population (0/62); five cases from the selected series were positive for MLH1 epimutations (15.6%, 5/32; p=0.004). Our results suggest a negligible prevalence of MLH1 constitutional epimutations in unselected cases of CRC. Therefore, MLH1 constitutional epimutation analysis should be conducted only for patients who fulfil the rBG and who lack MLH1 expression with methylated MLH1. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design

PubMed Central

Kalusa, Andrew; Cano, Celine; Travers, Jon; Boxall, Kathy; Chow, Chiau Ling; Burns, Sam; Schmitt, Jessica; Pickard, Lisa; Barillari, Caterina; McAndrew, P. Craig; Clarke, Paul A.; Linardopoulos, Spiros; Griffin, Roger J.; Aherne, G. Wynne; Raynaud, Florence I.; Workman, Paul; Jones, Keith; van Montfort, Rob L.M.

2013-01-01

The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we describe the identification of three series of chemically distinct S6K1 inhibitors. In addition, we report a novel PKA-S6K1 chimeric protein with five mutations in or near its ATP-binding site, which was used to determine the binding mode of two of the three inhibitor series, and provided a robust system to aid the optimisation of the oxadiazole-substituted benzimidazole inhibitor series. We show that the resulting oxadiazole-substituted aza-benzimidazole is a potent and ligand efficient S6 kinase inhibitor, which blocks the phosphorylation of RPS6 at Ser235/236 in TSC negative HCV29 human bladder cancer cells by inhibiting S6 kinase activity and thus provides a useful tool compound to investigate the function of S6 kinases. PMID:24072592

Prostate Upgrading Team Project — EDRN Public Portal

Cancer.gov

Aim 1: We will develop a risk assessment tool using commonly-collected clinical information from a series of contemporary radical prostatectomies to predict the risk of prostate cancer upgrading to high grade cancer at radical prostatectomy. These data will be combined as a part of our Early Detection Research Network (EDRN) GU Working Group into a risk assessment tool; this tool will be named the EDRN Prostatectomy Upgrading Calculator or (EPUC).

A Novel Approach to Assay DNA Methylation in Prostate Cancer

DTIC Science & Technology

2017-12-01

concordant with repression or activation of those nearby genes.15 More recently, a series of chromosome conformation capture (3C)-based approaches ...AWARD NUMBER: W81XWH-13-1-0319 TITLE: A Novel Approach to Assay DNA Methylation in Prostate Cancer PRINCIPAL INVESTIGATOR: Jindan Yu...Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No

Synthesis and evaluation of 3-amino/guanidine substituted phenyl oxazoles as a novel class of LSD1 inhibitors with anti-proliferative properties.

PubMed

Dulla, Balakrishna; Kirla, Krishna Tulasi; Rathore, Vandana; Deora, Girdhar Singh; Kavela, Sridhar; Maddika, Subbareddy; Chatti, Kiranam; Reiser, Oliver; Iqbal, Javed; Pal, Manojit

2013-05-21

A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in vitro for their activities against LSD1 and for effects on viability of cervical and breast cancer cells, and in vivo for effects using zebrafish embryos. These compounds are likely to act via multiple epigenetic mechanisms specific to cancer cells including LSD1 inhibition.

Promoter-Based Theranostics for Prostate Cancer

DTIC Science & Technology

2015-10-01

PD/PI(s) or senior/key personnel since the last reporting period?  Marty Pomper Ended Title: PSMA -Based Cancer Imaging Agents Time Commitments...for PSMA . Aim #2: Synthetic optimization of the best compounds of Aim 1 en route to GMP and/or facilitated use. Aim #3: Synthesis and evaluation of a...series of homo- and heterodimeric imaging agents for PSMA . Title: BETR Therapy of Herpesvirus-associated Tumors Time Commitments

Lnc2Cancer: a manually curated database of experimentally supported lncRNAs associated with various human cancers.

PubMed

Ning, Shangwei; Zhang, Jizhou; Wang, Peng; Zhi, Hui; Wang, Jianjian; Liu, Yue; Gao, Yue; Guo, Maoni; Yue, Ming; Wang, Lihua; Li, Xia

2016-01-04

Lnc2Cancer (http://www.bio-bigdata.net/lnc2cancer) is a manually curated database of cancer-associated long non-coding RNAs (lncRNAs) with experimental support that aims to provide a high-quality and integrated resource for exploring lncRNA deregulation in various human cancers. LncRNAs represent a large category of functional RNA molecules that play a significant role in human cancers. A curated collection and summary of deregulated lncRNAs in cancer is essential to thoroughly understand the mechanisms and functions of lncRNAs. Here, we developed the Lnc2Cancer database, which contains 1057 manually curated associations between 531 lncRNAs and 86 human cancers. Each association includes lncRNA and cancer name, the lncRNA expression pattern, experimental techniques, a brief functional description, the original reference and additional annotation information. Lnc2Cancer provides a user-friendly interface to conveniently browse, retrieve and download data. Lnc2Cancer also offers a submission page for researchers to submit newly validated lncRNA-cancer associations. With the rapidly increasing interest in lncRNAs, Lnc2Cancer will significantly improve our understanding of lncRNA deregulation in cancer and has the potential to be a timely and valuable resource. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Complex Interplay between Chronic Inflammation, the Microbiome, and Cancer: Understanding Disease Progression and What We Can Do to Prevent It

PubMed Central

Bording-Jorgensen, Michael; Dijk, Stephanie

2018-01-01

Cancer is a multifaceted condition, in which a senescent cell begins dividing in an irregular manner due to various factors such as DNA damage, growth factors and inflammation. Inflammation is not typically discussed as carcinogenic; however, a significant percentage of cancers arise from chronic microbial infections and damage brought on by chronic inflammation. A hallmark cancer-inducing microbe is Helicobacter pylori and its causation of peptic ulcers and potentially gastric cancer. This review discusses the recent developments in understanding microbes in health and disease and their potential role in the progression of cancer. To date, microbes can be linked to almost every cancer, including colon, pancreatic, gastric, and even prostate. We discuss the known mechanisms by which these microbes can induce cancer growth and development and how inflammatory cells may contribute to cancer progression. We also discuss new treatments that target the chronic inflammatory conditions and their associated cancers, and the impact microbes have on treatment success. Finally, we examine common dietary misconceptions in relation to microbes and cancer and how to avoid getting caught up in the misinterpretation and over inflation of the results. PMID:29558443

Research Biopsies: An Integrative Review of the Experiences of Patients With Cancer.

PubMed

Abraham, Elizabeth; Post, Kathryn; Spring, Laura; Malvarosa, Giuliana; Tripp, Elizabeth; Peppercorn, Jeffrey M; Bardia, Aditya; Habin, Karleen

2018-06-01

Research biopsies (RBs) are essential to understanding tumor biology and mechanisms of resistance and to advancing precision medicine. However, RBs have associated risks and may not benefit the patient. The purpose of this integrative review is to summarize and synthesize the current literature on the experience, attitudes, and understanding of patients with cancer related to RBs. Articles from January 2010 to February 2017 were retrieved via a search of MEDLINE®. Articles included reported on the willingness, perceptions, understanding, attitudes, and/or experience of patients with cancer related to RBs. Nine of 216 identified studies were selected. Studies exploring patient willingness to undergo RBs (n = 6) identified RBs as a potential barrier to clinical trial participation. Studies exploring patient understanding and informed consent (n = 3) revealed variable patient knowledge of the risks and benefits of RBs.