Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

DEFF Research Database (Denmark)

Jamal-Hanjani, Mariam; Hackshaw, Alan; Ngai, Yenting

2014-01-01

. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic...... analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve...

Molecular evolution of colorectal cancer: from multistep carcinogenesis to the big bang.

Science.gov (United States)

Amaro, Adriana; Chiara, Silvana; Pfeffer, Ulrich

2016-03-01

Colorectal cancer is characterized by exquisite genomic instability either in the form of microsatellite instability or chromosomal instability. Microsatellite instability is the result of mutation of mismatch repair genes or their silencing through promoter methylation as a consequence of the CpG island methylator phenotype. The molecular causes of chromosomal instability are less well characterized. Genomic instability and field cancerization lead to a high degree of intratumoral heterogeneity and determine the formation of cancer stem cells and epithelial-mesenchymal transition mediated by the TGF-β and APC pathways. Recent analyses using integrated genomics reveal different phases of colorectal cancer evolution. An initial phase of genomic instability that yields many clones with different mutations (big bang) is followed by an important, previously not detected phase of cancer evolution that consists in the stabilization of several clones and a relatively flat outgrowth. The big bang model can best explain the coexistence of several stable clones and is compatible with the fact that the analysis of the bulk of the primary tumor yields prognostic information.

Analyzing the evolution of young people's brain cancer mortality in Spanish provinces.

Science.gov (United States)

Ugarte, M D; Adin, A; Goicoa, T; López-Abente, G

2015-06-01

To analyze the spatio-temporal evolution of brain cancer relative mortality risks in young population (under 20 years of age) in Spanish provinces during the period 1986-2010. A new and flexible conditional autoregressive spatio-temporal model with two levels of spatial aggregation was used. Brain cancer relative mortality risks in young population in Spanish provinces decreased during the last years, although a clear increase was observed during the 1990s. The global geographical pattern emphasized a high relative mortality risk in Navarre and a low relative mortality risk in Madrid. Although there is a specific Autonomous Region-time interaction effect on the relative mortality risks this effect is weak in the final estimates when compared to the global spatial and temporal effects. Differences in mortality between regions and over time may be caused by the increase in survival rates, the differences in treatment or the availability of diagnostic tools. The increase in relative risks observed in the 1990s was probably due to improved diagnostics with computerized axial tomography and magnetic resonance imaging techniques. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phenotypic heterogeneity in modeling cancer evolution.

Directory of Open Access Journals (Sweden)

Ali Mahdipour-Shirayeh

Full Text Available The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous population of stem cells (SCs and their associated progenitors. The fate of a malignant mutation is determined not only by overall stem cell and non-stem cell growth rates but also differentiation and dedifferentiation rates. We investigate the effect of such a complex population structure on the evolution of malignant mutations. We derive exactly calculated results for the fixation probability of a mutant arising in each of the subpopulations. The exactly calculated results are in almost perfect agreement with the numerical simulations. Moreover, a condition for evolutionary advantage of a mutant cell versus the wild type population is given in the present study. We also show that microenvironment-induced plasticity in invading mutants leads to more aggressive mutants with higher fixation probability. Our model predicts that decreasing polarity between stem and non-stem cells' turnover would raise the survivability of non-plastic mutants; while it would suppress the development of malignancy for plastic mutants. The derived results are novel and general with potential applications in nature; we discuss our model in the context of colorectal/intestinal cancer (at the epithelium. However, the model clearly needs to be validated through appropriate experimental data. This novel mathematical framework can be applied more generally to a variety of problems concerning selection in heterogeneous populations, in other contexts such as population genetics, and ecology.

Increased pancreatic cancer risk following radiotherapy for testicular cancer.

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Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S; Stovall, Marilyn; van Leeuwen, Flora E; Rajaraman, Preetha; Smith, Susan A; Weathers, Rita E; Aleman, Berthe M P; Andersson, Michael; Curtis, Rochelle E; Dores, Graça M; Fraumeni, Joseph F; Hall, Per; Holowaty, Eric J; Joensuu, Heikki; Kaijser, Magnus; Kleinerman, Ruth A; Langmark, Frøydis; Lynch, Charles F; Pukkala, Eero; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Morton, Lindsay M; Fossa, Sophie D; Travis, Lois B

2016-09-27

Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear. Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs). Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trendcancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.

Conditional Selection of Genomic Alterations Dictates Cancer Evolution and Oncogenic Dependencies.

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Mina, Marco; Raynaud, Franck; Tavernari, Daniele; Battistello, Elena; Sungalee, Stephanie; Saghafinia, Sadegh; Laessle, Titouan; Sanchez-Vega, Francisco; Schultz, Nikolaus; Oricchio, Elisa; Ciriello, Giovanni

2017-08-14

Cancer evolves through the emergence and selection of molecular alterations. Cancer genome profiling has revealed that specific events are more or less likely to be co-selected, suggesting that the selection of one event depends on the others. However, the nature of these evolutionary dependencies and their impact remain unclear. Here, we designed SELECT, an algorithmic approach to systematically identify evolutionary dependencies from alteration patterns. By analyzing 6,456 genomes from multiple tumor types, we constructed a map of oncogenic dependencies associated with cellular pathways, transcriptional readouts, and therapeutic response. Finally, modeling of cancer evolution shows that alteration dependencies emerge only under conditional selection. These results provide a framework for the design of strategies to predict cancer progression and therapeutic response. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome increase as a clock for the origin and evolution of life

Directory of Open Access Journals (Sweden)

Sharov Alexei A

2006-06-01

Full Text Available Abstract Background The size of non-redundant functional genome can be an indicator of biological complexity of living organisms. Several positive feedback mechanisms including gene cooperation and duplication with subsequent specialization may result in the exponential growth of biological complexity in macro-evolution. Results I propose a hypothesis that biological complexity increased exponentially during evolution. Regression of the logarithm of functional non-redundant genome size versus time of origin in major groups of organisms showed a 7.8-fold increase per 1 billion years, and hence the increase of complexity can be viewed as a clock of macro-evolution. A strong version of the exponential hypothesis is that the rate of complexity increase in early (pre-prokaryotic evolution of life was at most the same (or even slower than observed in the evolution of prokaryotes and eukaryotes. Conclusion The increase of functional non-redundant genome size in macro-evolution was consistent with the exponential hypothesis. If the strong exponential hypothesis is true, then the origin of life should be dated 10 billion years ago. Thus, the possibility of panspermia as a source of life on earth should be discussed on equal basis with alternative hypotheses of de-novo life origin. Panspermia may be proven if bacteria similar to terrestrial ones are found on other planets or satellites in the solar system. Reviewers This article was reviewed by Eugene V. Koonin, Chris Adami and Arcady Mushegian.

Increased cancer risk in patients with periodontitis.

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Dizdar, Omer; Hayran, Mutlu; Guven, Deniz Can; Yılmaz, Tolga Birtan; Taheri, Sahand; Akman, Abdullah C; Bilgin, Emre; Hüseyin, Beril; Berker, Ezel

2017-12-01

Previous studies have noted a possible association between periodontal diseases and the risk of various cancers. We assessed cancer risk in a cohort of patients with moderate to severe periodontitis. Patients diagnosed with moderate to severe periodontitis by a periodontist between 2001 and 2010 were identified from the hospital registry. Patients younger than 35 years of age or with a prior cancer diagnosis were excluded. The age- and gender-standardized incidence rates (SIR) were calculated by dividing the number of observed cases by the number of expected cases from Turkish National Cancer Registry 2013 data. A total of 280 patients were included (median age 49.6, 54% female). Median follow-up was 12 years. Twenty-five new cancer cases were observed. Patients with periodontitis had 77% increased risk of cancer (SIR 1.77, 95% CI 1.17-2.58, p = .004). Women with periodontitis had significantly higher risk of breast cancer (SIR 2.40, 95% CI 0.88-5.33) and men with periodontitis had significantly higher risk of prostate cancer (SIR 3.75, 95% CI 0.95-10.21) and hematological cancers (SIR 6.97, 95% CI 1.77-18.98). Although showing a causal association necessitates further investigation, our results support the idea that periodontitis might be associated with increased cancer risk, particularly with hematological, breast and prostate cancers.

Increased colon cancer risk after severe Salmonella infection.

Directory of Open Access Journals (Sweden)

Lapo Mughini-Gras

Full Text Available Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans.We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999-2015 for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264 were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1-2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA and Statistics Netherlands (CBS allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD, and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09-2.10 among patients with Salmonella infection diagnosed <60 years of age. Such increased risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38-3.09 after S. Enteritidis infection (SIR 2.97; 95%CI 1.73-4.76. Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade

Increasing incidence of thyroid cancer in the Commonwealth of Pennsylvania.

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Bann, Darrin V; Goyal, Neerav; Camacho, Fabian; Goldenberg, David

2014-12-01

The incidence of thyroid cancer in the United States has increased rapidly and Pennsylvania is the state with the highest rate of thyroid cancer in the country, although the factors driving this increase are unknown. Moreover, it remains unclear whether the increase in thyroid cancer represents a true increase in disease or is the result of overdiagnosis. To compare the increase in thyroid cancer incidence and tumor characteristics in Pennsylvania with the rest of the United States and gain insight into the factors influencing the increased incidence of thyroid cancer. In a population-based study, data on thyroid cancer from the Surveillance Epidemiology and End Results 9 (SEER-9) registry and the Pennsylvania Cancer Registry (PCR) from 1985 through 2009 were collected and reviewed for information regarding sex, race, histologic type of thyroid cancer, staging, and tumor size at diagnosis. International Classification of Diseases for Oncology, Third Edition code C739 (thyroid carcinoma) was used to identify 110,615 records in the SEER-9 registry and 29,030 records in the PCR. Average annual percent change (AAPC) in thyroid cancer incidence across various demographic groups in Pennsylvania. The AAPC for thyroid cancer in Pennsylvania was 7.1% per year (95% CI, 6.3%-7.9%) vs 4.2% (95% CI, 3.7%-4.7%) per year in the remainder of the United States, and trends in incidence were significantly different (P Pennsylvania than in the rest of the nation, as is the rate of tumors that are larger and higher stage at diagnosis. These findings suggest that rising disease burden has contributed to the increased incidence of thyroid cancer. Etiologic factors promoting the rise in thyroid cancer in Pennsylvania must be investigated and may provide insight into the drivers of the national increase in thyroid cancer.

Worldwide trends show oropharyngeal cancer rates increasing

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NCI scientists report that the incidence of oropharyngeal cancer significantly increased during the period 1983-2002 among people in countries that are economically developed. Oropharyngeal cancer occurs primarily in the middle part of the throat behind t

Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

DEFF Research Database (Denmark)

Dewhurst, Sally M.; McGranahan, Nicholas; Burrell, Rebecca A.

2014-01-01

The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells...

Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution

Science.gov (United States)

Niida, Atsushi; Shimamura, Teppei; Hirata, Hidenari; Sugimachi, Keishi; Sawada, Genta; Iwaya, Takeshi; Kurashige, Junji; Shinden, Yoshiaki; Iguchi, Tomohiro; Eguchi, Hidetoshi; Chiba, Kenichi; Shiraishi, Yuichi; Nagae, Genta; Yoshida, Kenichi; Nagata, Yasunobu; Haeno, Hiroshi; Yamamoto, Hirofumi; Ishii, Hideshi; Doki, Yuichiro; Iinuma, Hisae; Sasaki, Shin; Nagayama, Satoshi; Yamada, Kazutaka; Yachida, Shinichi; Kato, Mamoru; Shibata, Tatsuhiro; Oki, Eiji; Saeki, Hiroshi; Shirabe, Ken; Oda, Yoshinao; Maehara, Yoshihiko; Komune, Shizuo; Mori, Masaki; Suzuki, Yutaka; Yamamoto, Ken; Aburatani, Hiroyuki; Ogawa, Seishi; Miyano, Satoru; Mimori, Koshi

2016-01-01

Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients’ ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease. PMID:26890883

Evolution in breast cancer suspicion and extent of surgery at a radio-oncology center

International Nuclear Information System (INIS)

Lopez L, Veronica; Carvajal C, Claudia; Gallardo M, Manuel; Russo N, Moies

2014-01-01

Introduction: Breast cancer diagnosis and treatment ad evolved over the past quarter century. From self-examination to mammography as main suspicion tool and from radical to conservative surgery plus radiotherapy as prefered treatment. The aim of this review was to assess the evolution of presentation and local management of breast cancer at a Chilean radio-oncology center. Materials and Methods: We analyzed 1.204 breast cancer patients who received postoperative irradiation on two four-years periods.The first period included 223 patients and coincides with the introduction of mammography and conservative surgery. The second included 981 patients managed according to current guidelines. The variables analyzed were type of clinical suspicion, time between clinical suspicion and diagnosis confirmation, type of surgery, histology and tumor size. Data were obtained from medical records and analyzed using STATA 2. Results: In the second period mammographic suspicion reached 39.88%. Time between clinical suspicion and histological diagnosis was reduced to 50%, the proportion of tumors larger than 2 cm was reduced from 61 to 45%, the proportion of DCIS was tripled from 6 to 18%, use of conservative surgery as an absolute increase of 28%. All of these differences were statistically significant (p < 0.01). Conclusion: The introduction of mammography and conservative management allowed early diagnosis of breast cancer in the analyzed population

Increased colon cancer risk after severe Salmonella infection

Science.gov (United States)

Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

2018-01-01

Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999–2015) for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1–2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite) among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD), and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09–2.10) among patients with Salmonella infection diagnosed transverse colon (SIR 2.12; 95%CI 1.38–3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73–4.76). Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade. Conclusions Patients diagnosed with severe

Increasing incidence of testicular cancer--birth cohort effects.

Science.gov (United States)

Ekbom, A; Akre, O

1998-01-01

The incidence of testicular cancer is rising in most Western populations. A collaborative study between nine population-based cancer registries in countries around the Baltic Sea was utilized in order to analyze in detail geographic variations and temporal trends in the occurrence of testicular cancer. There were 34,309 cases registered up until 1989 starting in Denmark in 1942 and most recently in Latvia in 1977. From the descriptive epidemiology it was obvious that there was a substantial variation in the age-standardized incidence amounting to about a 10-fold difference between the different countries ranging from 0.8 per 100,000 person-years in Lithuania to 7.6 per 100,000 person-years in Denmark. Previous studies have indicated that this increase is due to birth cohort effects. A more detailed analysis was therefore performed in those six countries with a sufficiently long period of cancer registration; Poland, former East Germany, Norway, Finland, Denmark and Sweden. This analysis showed that birth cohort is a more important determinant of testicular cancer risk than year of diagnosis. In Poland, former East Germany and Finland, there was an increasing risk for all birth cohorts. Among men born in Denmark, Norway or Sweden between 1930 and 1945, this increasing trend in risk was interrupted in these birth cohorts but followed thereafter by an uninterrupted increase by birth cohort. In conclusion, life time exposure to environmental factors which are associated with the incidence of testicular cancer appear to be more related to birth cohort than to year of diagnosis. Because testicular cancer typically occurs at an early age, major etiological factors therefore need to operate early in life, perhaps even in utero.

The bowel cancer awareness campaign 'Be Clear on Cancer': sustained increased pressure on resources and over-accessed by higher social grades with no increase in cancer detected.

Science.gov (United States)

Hall, S J; Peacock, J D H; Cochrane, L A; Peacock, O; Tierney, G M; Tou, S I H; Lund, J N

2016-02-01

To evaluate the impact of the national 'Be Clear on Cancer' bowel cancer reminder campaign on service and diagnosis at a single UK institution. Secondly, to evaluate the socio-economic background of patients referred before and after the reminder campaign compared with the regional demographic. Suspected cancer 2-week wait patients in the 3 months precampaign, postcampaign and after the reminder campaign were included. Demographics, investigations and diagnosis were recorded. The postcode was used to allocate a National Readership Survey social grade. Three hundred and eighty-three referrals were received in the 3 months precampaign, 550 postcampaign and 470 postreminder campaign. There were significant increases in the monthly referral rates following the campaign (P social grades AB and C1C2 than expected from regional demographics were referred precampaign and after the reminder campaign (P < 0.001 in each case). There were no significant differences between the proportions of patients diagnosed with colorectal cancer in the three study periods (P = 0.710). The 'Be Clear on Cancer' bowel cancer campaign has had a significant sustained impact on resources. It has failed to increase referrals among lower socio-economic grades, leading to an increase in 'worried well' referrals and no change in numbers, or the stage, of colorectal cancers diagnosed. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Male Breast Cancer as a Second Primary Cancer: Increased Risk Following Lymphoma.

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Farr, Deborah E; Thomas, Alexandra; Khan, Seema Ahsan; Schroeder, Mary C

2017-08-01

Male breast cancer (MBC) as a second primary cancer (SPC) has a known association with prior MBC. However, its association with non-breast index malignancies, relative to population risk, has not been previously reported. Using Surveillance, Epidemiology, and End Results program (9 catchment area) data, we identified MBCs diagnosed from 1973-2012 as their SPC. Information regarding the index malignancy was also obtained. Standardized incidence ratios (SIR) of MBC as SPC were estimated, along with incidence rates and trends. Kaplan-Meier curves were used to estimate survival. Over a 38-year period, 464 MBCs were identified as SPC. The most common index malignancies were breast (SIR 30.86, 95% confidence interval [CI] 21.50-42.92, p  Male breast cancer as a SPC has increased markedly over 4 decades. Men with a history of lymphoma may experience higher-than-expected rates of breast SPC. These observations warrant further research, and suggest possible etiologic connections with disease biology, prior therapy, or genetics. This study reports that men are presenting more frequently to the clinic with breast cancer, both as an initial cancer and as a second cancer following an earlier malignancy. We also report the novel observation that men who survive lymphoma are at increased risk of developing a subsequent breast cancer. Further work is needed to better understand possible treatment or biologic causes of this association. More immediately, these findings suggest the need for heightened vigilance for male breast cancer overall and, in particular, for male lymphoma survivors. © AlphaMed Press 2017.

Increased colon cancer risk after severe Salmonella infection

OpenAIRE

Mughini-Gras, Lapo; Schaapveld, Michael; Kramers, Jolanda; Mooij, Sofie; Neefjes-Borst, E. Andra; van Pelt, Wilfrid; Neefjes, Jacques

2018-01-01

Background Colon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans. Methods and findings We performed a nationwide registry-b...

The importance of histopathological and clinical variables in predicting the evolution of colon cancer.

Science.gov (United States)

Diculescu, Mircea; Iacob, Răzvan; Iacob, Speranţa; Croitoru, Adina; Becheanu, Gabriel; Popeneciu, Valentin

2002-09-01

It has been a consensus that prognostic factors should always be taken into account before planning treatment in colorectal cancer. A 5 year prospective study was conducted, in order to assess the importance of several histopathological and clinical prognostic variables in the prediction of evolution in colon cancer. Some of the factors included in the analysis are still subject to dispute by different authors. 46 of 53 screened patients qualified to enter the study and underwent a potentially curative resection of the tumor, followed, when necessary, by adjuvant chemotherapy. Univariate and multivariate analyses were carried out in order to identify independent prognostic indicators. The endpoint of the study was considered the recurrence of the tumor or the detection of metastases. 65.2% of the patients had a good evolution during the follow up period. Multivariate survival analysis performed by Cox proportional hazard model identified 3 independent prognostic factors: Dukes stage (p = 0.00002), the grade of differentiation (p = 0.0009) and the weight loss index, representing the weight loss of the patient divided by the number of months when it was actually lost (p = 0.02). Age under 40 years, sex, microscopic aspect of the tumor, tumor location, anemia degree were not identified by our analysis as having prognostic importance. Histopathological factors continue to be the most valuable source of information regarding the possible evolution of patients with colorectal cancer. Individual clinical symptoms or biological parameters such as erytrocyte sedimentation rate or hemoglobin level are of little or no prognostic value. More research is required relating to the impact of a performance status index (which could include also weight loss index) as another reliable prognostic variable.

Ozone depletion, related UVB changes and increased skin cancer incidence

Science.gov (United States)

Kane, R. P.

1998-03-01

Stratospheric ozone at middle latitudes shows a seasonal variation of about +/-20%, a quasi-biennial oscillation of 1-10% range and a long-term variation in which the level was almost steady up to about 1979 and declined thereafter to the present day by about 10%. These variations are expected to be reflected in solar UVB observed at the ground, but in an opposite direction. Thus UVB should have had a long-term increase of about 10-20%, which should cause an increase in skin cancer incidence of about 20-40%. Skin cancer incidence has increased all over the world, e.g. about 90% in USA during 1974-1990. It is popularly believed that this increase in skin cancer incidence is related to the recent ozone depletion. This seems to be incorrect, for two reasons. Firstly, the observed skin cancer increase is too large (90%) compared with the expected value (40%) from ozone depletion. Secondly, cancer does not develop immediately after exposure to solar UVB. The sunburns may occur within hours; but cancer development and detection may take years, even decades. Hence the observed skin cancer increase since 1974 (no data available for earlier periods) must have occurred due to exposure to solar UVB in the 1950s and 1960s, when there was no ozone depletion. Thus, the skin cancer increase must be attributed to harmful solar UVB levels existing even in the 1960s, accentuated later not by ozone depletion (which started only much later, by 1979) but by other causes, such as a longer human life span, better screening, increasing tendencies of sunbathing at beaches, etc., in affluent societies. On the other hand, the recent ozone depletion and the associated UVB increases will certainly take their toll; only that the effects will not be noticed now but years or decades from now. The concern for the future expressed in the Montreal Protocol for reducing ozone depletion by controlling CFC production is certainly justified, especially because increased UVB is harmful to animal and

Endoscopic stenting in bile duct cancer increases liver volume.

Science.gov (United States)

Lee, Chang Hun; Kim, Seong Hun; Kim, In Hee; Kim, Sang Wook; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul; Cho, Baik Hwan; Lee, Seung Ok

2014-09-01

Objective evaluation tools for assessing the effectiveness of stenting in palliative treatment of malignant biliary obstruction are not satisfactory. Effects of biliary stenting on liver volume change have never been studied. We aimed to use volumetry to analyze liver volume changes after endoscopic stenting in bile duct cancer according to the location and number of stents. Retrospective review. University hospital. Patients with a diagnosis of hilar or distal bile duct cancer and who underwent biliary metal stenting. ERCP with self-expandable metal stent placement. Liver volume change after biliary stenting and its comparison according to the location (hilar vs distal common bile duct) and number (hilar bilateral vs hilar unilateral). There were 60 patients; 31 were treated for hilar bile duct cancer (13 for bilateral stent and 18 for unilateral stent) and 29 for distal bile duct cancer. Overall mean follow-up duration was 11.7 ± 4.9 weeks. Liver volume increased 17.4 ± 24.1%. The rate of liver growth was rapid during the early period from 4 to 8 weeks. Stenting in hilar bile duct cancer tended to increase liver volume more than distal biliary stents (22.5% vs 11.9%, P = .091). In hilar bile duct cancer, unilateral and bilateral stents showed similar liver volume increases (20.1% and 25.8%, respectively; P = .512). Single center, retrospective. Biliary stenting markedly increased liver volume in both hilar and distal bile duct cancer. Our data suggest that liver volume assessment could be a useful tool for evaluating stent efficacy. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Increased formate overflow is a hallmark of oxidative cancer.

Science.gov (United States)

Meiser, Johannes; Schuster, Anne; Pietzke, Matthias; Vande Voorde, Johan; Athineos, Dimitris; Oizel, Kristell; Burgos-Barragan, Guillermo; Wit, Niek; Dhayade, Sandeep; Morton, Jennifer P; Dornier, Emmanuel; Sumpton, David; Mackay, Gillian M; Blyth, Karen; Patel, Ketan J; Niclou, Simone P; Vazquez, Alexei

2018-04-10

Formate overflow coupled to mitochondrial oxidative metabolism\\ has been observed in cancer cell lines, but whether that takes place in the tumor microenvironment is not known. Here we report the observation of serine catabolism to formate in normal murine tissues, with a relative rate correlating with serine levels and the tissue oxidative state. Yet, serine catabolism to formate is increased in the transformed tissue of in vivo models of intestinal adenomas and mammary carcinomas. The increased serine catabolism to formate is associated with increased serum formate levels. Finally, we show that inhibition of formate production by genetic interference reduces cancer cell invasion and this phenotype can be rescued by exogenous formate. We conclude that increased formate overflow is a hallmark of oxidative cancers and that high formate levels promote invasion via a yet unknown mechanism.

Increased tolerance towards serine obtained by adaptive laboratory evolution

DEFF Research Database (Denmark)

Mundhada, Hemanshu; Seoane, Jose Miguel; Koza, Anna

2014-01-01

The amino acid serine has previously been identified as one of the top 30 candidates of value added chemicals, making the production of serine from glucose attractive. Production of serine have previously been attempted in E. coli and C. glutamicum, however, titers sufficient for commercial...... by glyA), the conversion of serine to pyruvate (encoded by sdaA, sdaB and tdcG) was also deleted. As expected, the resulting strain turned out to be susceptible to even low concentrations of serine in the media. In order to improve the tolerance of the strain towards serine, adaptive laboratory evolution....... During the evolution experiment, the serine tolerance was increased substantially. Genome re-sequencing was subsequently used to analyze the genotype of a number of selected strains. These results reveal insights towards the adaptation process as well as the mechanism of serine tolerance....

Assessment of the Evolution of Cancer Treatment Therapies

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Arruebo, Manuel [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Vilaboa, Nuria [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, Madrid 28046 (Spain); Sáez-Gutierrez, Berta; Lambea, Julio; Tres, Alejandro [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); Servicio de Oncología Médica, Hospital Clínico Universitario Lozano Blesa, Avda. San Juan Bosco 50009, Zaragoza (Spain); Instituto Aragonés de Ciencias de la Salud (I-CS), Avda. Gómez Laguna, 25, Zaragoza 50009 (Spain); Valladares, Mónica [Lonza Biologics Porriño, A relva s/n, Porriño (Pontevedra) 36410 (Spain); González-Fernández, África, E-mail: africa@uvigo.es [Immunology Department, Biomedical Research Center (CINBIO), University of Vigo, Campus Lagoas Marcosende, Vigo (Pontevedra) 36310 (Spain)

2011-08-12

Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

Assessment of the Evolution of Cancer Treatment Therapies

Science.gov (United States)

Arruebo, Manuel; Vilaboa, Nuria; Sáez-Gutierrez, Berta; Lambea, Julio; Tres, Alejandro; Valladares, Mónica; González-Fernández, África

2011-01-01

Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present. PMID:24212956

Assessment of the Evolution of Cancer Treatment Therapies

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Mónica Valladares

2011-08-01

Full Text Available Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.. In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine. We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

Assessment of the Evolution of Cancer Treatment Therapies

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Arruebo, Manuel; Vilaboa, Nuria; Sáez-Gutierrez, Berta; Lambea, Julio; Tres, Alejandro; Valladares, Mónica; González-Fernández, África

2011-01-01

Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present

Low dose diagnostic radiation does not increase cancer risk in cancer prone mice

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Boreham, D., E-mail: dboreham@nosm.ca [Northern Ontario School of Medicine, ON (Canada); Phan, N., E-mail: nghiphan13@yahoo.com [Univ. of Ottawa, Ottawa, ON (Canada); Lemon, J., E-mail: lemonja@mcmaster.ca [McMaster Univ., Hamilton, ON (Canada)

2014-07-01

The increased exposure of patients to low dose diagnostic ionizing radiation has created concern that these procedures will result in greater risk of carcinogenesis. However, there is substantial evidence that shows in many cases that low dose exposure has the opposite effect. We have investigated whether CT scans can modify mechanisms associated with carcinogenesis in cancer-prone mice. Cancer was induced in Trp53+/- mice with an acute high dose whole-body 4 Gy γ-radiation exposure. Four weeks following the cancer-inducing dose, weekly whole-body CT scans (10 mGy/scan, 75 kVp X-rays) were given for ten consecutive weeks adding an additional radiation burden of 0.1 Gy. Short-term biological responses and subsequent lifetime cancer risk were investigated. Five days following the last CT scan, there were no detectable differences in the spontaneous levels of DNA damage in blood cells (reticulocytes). In fact, CT scanned mice had significantly lower constitutive levels of oxidative DNA damage and cell death (apoptosis), compared to non-CT scanned mice. This shows that multiple low dose radiation exposures modified the radio response and indicates protective processes were induced in mice. In mice treated with the multiple CT scans following the high cancer-inducing 4 Gy dose, tumour latency was increased, significantly prolonging lifespan. We conclude that repeated CT scans can reduce the cancer risk of a prior high-dose radiation exposure, and delay the progression of specific types of radiation-induced cancers in Trp53+/-mice. This research shows for the first time that low dose exposure long after cancer initiation events alter risk and reduce cancer morbidity. Cancer induction following low doses does not follow a linear non-threshold model of risk and this model should not be used to extrapolate risk to humans following low dose exposure to ionizing radiation. (author)

Nutrition deficiency increases the risk of stomach cancer mortality

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Da Li Qing

2012-07-01

Full Text Available Abstract Background The purpose of the study is to determine whether exposure to malnutrition during early life is associated with increased risk of stomach cancer in later life. Methods The design protocol included analyzing the trend of gastric cancer mortality and nutrition and evaluating the association between nutrient deficiency in early life and the risk of gastric cancer by hierarchical age–period–birth cohort (APC analysis using general log-linear Poisson models and to compare the difference between birth cohorts who were exposed to the 1959–1961 Chinese famine and those who were not exposed to the famine. Data on stomach cancer mortality from 1970 to 2009 and the dietary patterns from 1955 to 1985 which included the 1959–1961 Chinese famine period in the Zhaoyuan County population were obtained. The nutrition information was collected 15 years prior to the mortality data as based on the latest reference of disease incubation. Results APC analysis revealed that severe nutrition deficiency during early life may increase the risk of stomach cancer. Compared with the 1960–1964 birth cohort, the risk for stomach cancer in all birth cohorts from 1900 to 1959 significantly increased; compared with the 1970–1974 cohort, the risk for stomach cancer in the 1975–1979 cohort significantly increased, whereas the others had a steadily decreased risk; compared with 85–89 age group in the 2005–2009 death survey, the ORs decreased with younger age and reached significant levels for the 50–54 age group after adjusting the confounding factors. The 1930 to 1964 group (exposed to famine had a higher mortality rate than the 1965 to 1999 group (not exposed to famine. For males, the relative risk (RR was 2.39 and the 95% confidence interval (CI was 1.51 to 3.77. For females, RR was 1.64 and 95% CI was 1.02 to 2.62. Conclusion The results of the present study suggested that prolonged malnutrition during early life may increase the risk of

Increased hydrostatic pressure enhances motility of lung cancer cells.

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Kao, Yu-Chiu; Lee, Chau-Hwang; Kuo, Po-Ling

2014-01-01

Interstitial fluid pressures within most solid tumors are significantly higher than that in the surrounding normal tissues. Therefore, cancer cells must proliferate and migrate under the influence of elevated hydrostatic pressure while a tumor grows. In this study, we developed a pressurized cell culture device and investigated the influence of hydrostatic pressure on the migration speeds of lung cancer cells (CL1-5 and A549). The migration speeds of lung cancer cells were increased by 50-60% under a 20 mmHg hydrostatic pressure. We also observed that the expressions of aquaporin in CL1-5 and A549 cells were increased under the hydrostatic pressure. Our preliminary results indicate that increased hydrostatic pressure plays an important role in tumor metastasis.

Subfertility increases risk of testicular cancer: evidence from population-based semen samples.

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Hanson, Heidi A; Anderson, Ross E; Aston, Kenneth I; Carrell, Douglas T; Smith, Ken R; Hotaling, James M

2016-02-01

To further understand the association between semen quality and cancer risk by means of well defined semen parameters. Retrospective cohort study. Not applicable. A total of 20,433 men who underwent semen analysis (SA) and a sample of 20,433 fertile control subjects matched by age and birth year. None. Risk of all cancers as well as site-specific results for prostate cancer, testicular cancer, and melanoma. Compared with fertile men, men with SA had an increased risk of testicular cancer (hazard rate [HR] 3.3). When the characterization of infertility was refined using individual semen parameters, we found that oligozoospermic men had an increased risk of cancer compared with fertile control subjects. This association was particularly strong for testicular cancer, with increased risk in men with oligozoospermia based on concentration (HR 11.9) and on sperm count (HR 10.3). Men in the in the lowest quartile of motility (HR 4.1), viability (HR 6.6), morphology (HR 4.2), or total motile count (HR 6.9) had higher risk of testicular cancer compared with fertile men. Men with sperm concentration and count in the 90th percentiles of the distribution (≥178 and ≥579 × 10(6)/mL, respectively), as well as total motile count, had an increased risk of melanoma (HRs 2.1, 2.7, and 2.0, respectively). We found no differences in cancer risk between azoospermic and fertile men. Men with SA had an increased risk of testicular cancer which varied by semen quality. Unlike earlier work, we did not find an association between azoospermia and increased cancer risk. Published by Elsevier Inc.

Increased mean lung density: Another independent predictor of lung cancer?

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Sverzellati, Nicola, E-mail: nicola.sverzellati@unipr.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Randi, Giorgia, E-mail: giorgia.randi@marionegri.it [Department of Epidemiology, Mario Negri Institute, Via La Masa 19, 20156 Milan (Italy); Spagnolo, Paolo, E-mail: paolo.spagnolo@unimore.it [Respiratory Disease Unit, Center for Rare Lung Disease, Department of Oncology, Hematology and Respiratory Disease, University of Modena and Reggio Emilia, Via del Pozzo 71, 44124 Modena (Italy); Marchianò, Alfonso, E-mail: alfonso.marchiano@istitutotumori.mi.it [Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy); Silva, Mario, E-mail: mac.mario@hotmail.it [Department of Department of Surgical Sciences, Section of Diagnostic Imaging, University of Parma, Padiglione Barbieri, University Hospital of Parma, V. Gramsci 14, 43100 Parma (Italy); Kuhnigk, Jan-Martin, E-mail: Jan-Martin.Kuhnigk@mevis.fraunhofer.de [Fraunhofer MEVIS, Universitaetsallee 29, 28359 Bremen (Germany); La Vecchia, Carlo, E-mail: carlo.lavecchia@marionegri.it [Department of Occupational Health, University of Milan, Via Venezian 1, 20133 Milan (Italy); Zompatori, Maurizio, E-mail: maurizio.zompatori@unibo.it [Department of Radiology, Cardio-Thoracic Section, S. Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna (Italy); Pastorino, Ugo, E-mail: ugo.pastorino@istitutotumori.mi.it [Department of Surgery, Section of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan (Italy)

2013-08-15

Objectives: To investigate the relationship between emphysema phenotype, mean lung density (MLD), lung function and lung cancer by using an automated multiple feature analysis tool on thin-section computed tomography (CT) data. Methods: Both emphysema phenotype and MLD evaluated by automated quantitative CT analysis were compared between outpatients and screening participants with lung cancer (n = 119) and controls (n = 989). Emphysema phenotype was defined by assessing features such as extent, distribution on core/peel of the lung and hole size. Adjusted multiple logistic regression models were used to evaluate independent associations of CT densitometric measurements and pulmonary function test (PFT) with lung cancer risk. Results: No emphysema feature was associated with lung cancer. Lung cancer risk increased with decreasing values of forced expiratory volume in 1 s (FEV{sub 1}) independently of MLD (OR 5.37, 95% CI: 2.63–10.97 for FEV{sub 1} < 60% vs. FEV{sub 1} ≥ 90%), and with increasing MLD independently of FEV{sub 1} (OR 3.00, 95% CI: 1.60–5.63 for MLD > −823 vs. MLD < −857 Hounsfield units). Conclusion: Emphysema per se was not associated with lung cancer whereas decreased FEV{sub 1} was confirmed as being a strong and independent risk factor. The cross-sectional association between increased MLD and lung cancer requires future validations.

Increased entropy of signal transduction in the cancer metastasis phenotype

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Teschendorff Andrew E

2010-07-01

Full Text Available Abstract Background The statistical study of biological networks has led to important novel biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Results Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis and provide examples of de-novo discoveries of gene modules with known roles in apoptosis, immune-mediated tumour suppression, cell-cycle and tumour invasion. Importantly, we also identify a novel gene module within the insulin growth factor signalling pathway, alteration of which may

Increasing awareness of gynaecological cancer symptoms: a GP perspective.

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Evans, Ruth E C; Morris, Melanie; Sekhon, Mandeep; Buszewicz, Marta; Walter, Fiona M; Waller, Jo; Simon, Alice E

2014-06-01

In the UK there has been an effort, through the National Awareness and Early Diagnosis Initiative (NAEDI), to increase early stage diagnoses and ultimately cancer survival. Encouraging early symptom presentation through awareness-raising activities in primary care is one method to achieve this goal. Understanding GPs' views about this type of activity, however, is crucial prior to implementation. To describe GPs' attitudes to raising public awareness of gynaecological cancers, and their views about the potential impact on primary care services. An online survey with a convenience sample recruited from 1860 UK general practices. An invitation was emailed to GPs via practice managers and included a weblink to a draft education leaflet and an online survey about the impact of sending a leaflet giving information about symptoms associated with gynaecological cancers to all women on GPs' lists. Participants could offer additional free text comments which were coded using content analysis. A total of 621 GPs participated. Most (77%, 477) felt that raising awareness of cancers was important. Only half (50%, 308), however, indicated that they would distribute such a leaflet from their practice. Barriers to implementation included concerns about financial costs; emotional impact on patients; increased demand for appointments and diagnostic services, such as ultrasound. GPs were generally positive about an intervention to improve patients' awareness of gynaecological cancers, but had concerns about increasing rates of presentation. There is a need for research quantifying the benefits of earlier diagnosis against resource costs such as increased consultations, investigations, and referrals. © British Journal of General Practice 2014.

Incidence of Cancers of the Lower Stomach Increasing among Younger Americans

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... News & Events Cancer Currents Blog Cancer Currents Blog Incidence of Cancers of the Lower Stomach Increasing among ... younger individuals, she added. Risk Factors and Shifting Incidence Rates Two of the main causes of noncardia ...

Increased incidence of bowel cancer after non-surgical treatment of appendicitis.

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Enblad, Malin; Birgisson, Helgi; Ekbom, Anders; Sandin, Fredrik; Graf, Wilhelm

2017-11-01

There is an ongoing debate on the use of antibiotics instead of appendectomy for treating appendicitis but diagnostic difficulties and longstanding inflammation might lead to increased incidence of bowel cancer in these patients. The aim of this population-based study was to investigate the incidence of bowel cancer after non-surgical treatment of appendicitis. Patients diagnosed with appendicitis but lacking the surgical procedure code for appendix removal were retrieved from the Swedish National Inpatient Register 1987-2013. The cohort was matched with the Swedish Cancer Registry and the standardised incidence ratios (SIR) with 95% confidence interval (95% CI) for appendiceal, colorectal and small bowel cancers were calculated. Of 13 595 patients with non-surgical treatment of appendicitis, 352 (2.6%) were diagnosed with appendiceal, colorectal or small bowel cancer (SIR 4.1, 95% CI 3.7-4.6). The largest incidence increase was found for appendiceal (SIR 35, 95% CI 26-46) and right-sided colon cancer (SIR 7.5, 95% CI 6.6-8.6). SIR was still elevated when excluding patients with less than 12 months since appendicitis and the incidence of right-sided colon cancer was elevated five years after appendicitis (SIR 3.5, 95% CI 2.1-5.4). An increased incidence of bowel cancer was found after appendicitis with abscess (SIR 4.6, 95% CI 4.0-5.2), and without abscess (SIR 3.5, 95% CI 2.9-4.1). Patients with non-surgical treatment of appendicitis have an increased short and long-term incidence of bowel cancer. This should be considered in the discussion about optimal management of patients with appendicitis. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Predicting opportunities to increase utilization of laparoscopy for colon cancer.

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Keller, Deborah S; Parikh, Niraj; Senagore, Anthony J

2017-04-01

Despite proven safety and efficacy, rates of minimally invasive approaches for colon cancer remain low in the USA. Given the known benefits, investigating the root causes of underutilization and methods to increase laparoscopy is warranted. Our goal was to develop a predictive model of factors impacting use of laparoscopic surgery for colon cancer. The Premier Hospital Database was reviewed for elective colorectal resections for colon cancer (2009-2014). Patients were identified by ICD-9-CM diagnosis code and then stratified into open or laparoscopic approaches by ICD-9-CM procedure codes. An adjusted multivariate logistic regression model identified variables predictive of use of laparoscopy for colon cancer. A total of 24,245 patients were included-12,523 (52 %) laparoscopic and 11,722 (48 %) open. General surgeons performed the majority of all procedures (77.99 % open, 71.60 % laparoscopic). Overall use of laparoscopy increased from 48.94 to 52.03 % over the study period (p colon cancer laparoscopically. Colorectal surgeons were 32 % more likely to approach a case laparoscopically than general surgeons (OR 1.315, 95 % CI [1.222, 1.415], p characteristics that can be identified preoperatively to predict who will undergo surgery for colon cancer using laparoscopy. However, additional patients may be eligible for laparoscopy based on patient-level characteristics. These results have implications for regionalization and increasing teaching of MIS. Recognizing and addressing these variables with training and recruiting could increase use of minimally invasive approaches, with the associated clinical and financial benefits.

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

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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  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.

Breast cancer in Mongolia: an increasingly important health policy issue

Directory of Open Access Journals (Sweden)

Demchig D

2017-01-01

Full Text Available Delgermaa Demchig, Claudia Mello-Thoms, Patrick C Brennan Medical Image Optimization and Perception Group (MIOPeG, Faculty of Health Science, The University of Sydney, Sydney, NSW, Australia Abstract: Breast cancer is a leading cause of cancer-related death for women in both developed and developing countries. The incidence and mortality of breast cancer in Mongolia, while low compared with other counties, has been increasing on an annual basis. In addition, in Mongolia, approximately 90% of the patients are diagnosed at a late stage, resulting in high mortality, with the majority of individuals diagnosed with breast cancer dying within 5 years of diagnosis. Breast cancer screening plays an important role in reducing mortality in Western countries and has been adopted by a number of Asian countries; however, no such approach exists in Mongolia. In a country of limited resources, implementation of expensive health strategies such as screening requires effective allocations of resources and the identification of the most effective imaging methods. This requirement relies on recent accurate data; however, at this time, there is a paucity of information around breast cancer in Mongolia. Until data around features of the disease are available, effective strategies to diagnose breast cancer that recognize the economic climate in Mongolia cannot be implemented and the impact of breast cancer is likely to increase. Keywords: incidence, mortality, breast screening, Mongolia

Cancer susceptibility and reproductive trade-offs: a model of the evolution of cancer defences.

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Boddy, Amy M; Kokko, Hanna; Breden, Felix; Wilkinson, Gerald S; Aktipis, C Athena

2015-07-19

The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer defence. We build a model that contrasts the probabilistic onset of cancer with other, extrinsic causes of mortality and use it to predict that intense reproductive competition will lower cancer defences and increase cancer incidence. We explore the trade-off between cancer defences and intraspecific competition across different extrinsic mortality conditions and different levels of trade-off intensity, and find the largest effect of competition on cancer in species where low extrinsic mortality combines with strong trade-offs. In such species, selection to delay cancer and selection to outcompete conspecifics are both strong, and the latter conflicts with the former. We discuss evidence for the assumed trade-off between reproductive competitiveness and cancer susceptibility. Sexually selected traits such as ornaments or large body size require high levels of cell proliferation and appear to be associated with greater cancer susceptibility. Similar associations exist for female traits such as continuous egg-laying in domestic hens and earlier reproductive maturity. Trade-offs between reproduction and cancer defences may be instantiated by a variety of mechanisms, including higher levels of growth factors and hormones, less efficient cell-cycle control and less DNA repair, or simply a larger number of cell divisions (relevant when reproductive success requires large body size or rapid reproductive cycles). These mechanisms can affect intra- and interspecific variation in cancer susceptibility arising from rapid cell proliferation during reproductive maturation, intrasexual competition and reproduction. © 2015 The Author

Is there an increased risk of cancer among spouses of patients with an HPV-related cancer: A systematic review.

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Mirghani, Haitham; Sturgis, Erich M; Aupérin, Anne; Monsonego, Joseph; Blanchard, Pierre

2017-04-01

High-risk human papillomaviruses (HR-HPV) are the cause of most ano-genital cancers and a fast growing subset of oropharyngeal cancer. As these malignancies occur as a result of an HPV- infection transmitted through intimate contact, many patients with HPV- induced cancer and their partners are concerned about HPV-transmission and the potential partners' cancer risk. Few studies have addressed this issue and whether the HPV-related cancer risk of partners of patients with HPV-related cancers is comparable to or greater than that of the general population. We performed a systematic review of the published literature addressing this issue. Out of 1055 references screened, 53 articles were found eligible for inclusion. Regarding the issue of coincidence of HPV-induced oropharyngeal and/or anogenital cancers in couples, 13 case-reports or case-series were reported and 9 larger studies based on population-registries. Four of these registry studies showed an increased risk of cervical cancer in the partner while four did not. Among the four positive studies, odds ratios for the development of HPV-related cancer among spouses were between 2.6 and 6.7. One study showed an increased risk of tongue or tonsil cancer among husbands of women with cervical dysplasia or cancer. Overall the absolute risk increase in all these studies was small, on the order of 1-3%, although potentially underestimated. Indeed, all these studies have assessed partner's cancer risk at only one anatomical site whereas HPV- related malignancies can affect different locations. This systematic review suggests a small trend of increase risk in HPV-associated cancers among spouses of patients with HPV-related cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Viral Evolution Core | FNLCR Staging

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Brandon F. Keele, Ph.D. PI/Senior Principal Investigator, Retroviral Evolution Section Head, Viral Evolution Core Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick, MD 21702-1201 Tel: 301-846-173

Cancer cells recovering from damage exhibit mitochondrial restructuring and increased aerobic glycolysis

Energy Technology Data Exchange (ETDEWEB)

Akakura, Shin; Ostrakhovitch, Elena; Sanokawa-Akakura, Reiko [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Tabibzadeh, Siamak, E-mail: fbs@bioscience.org [Frontiers in Bioscience Research Institute in Aging and Cancer, University of California, Irvine, CA (United States); Dept of Oncologic Radiology, University of California, Irvine, CA (United States)

2014-06-13

Highlights: • Some cancer cells recover from severe damage that causes cell death in majority of cells. • Damage-Recovered (DR) cancer cells show reduced mitochondria, mDNA and mitochondrial enzymes. • DR cells show increased aerobic glycolysis, ATP, cell proliferation, and resistance to damage. • DR cells recovered from in vivo damage also show increased glycolysis and proliferation rate. - Abstract: Instead of relying on mitochondrial oxidative phosphorylation, most cancer cells rely heavily on aerobic glycolysis, a phenomenon termed as “the Warburg effect”. We considered that this effect is a direct consequence of damage which persists in cancer cells that recover from damage. To this end, we studied glycolysis and rate of cell proliferation in cancer cells that recovered from severe damage. We show that in vitro Damage-Recovered (DR) cells exhibit mitochondrial structural remodeling, display Warburg effect, and show increased in vitro and in vivo proliferation and tolerance to damage. To test whether cancer cells derived from tumor microenvironment can show similar properties, we isolated Damage-Recovered (T{sup DR}) cells from tumors. We demonstrate that T{sup DR} cells also show increased aerobic glycolysis and a high proliferation rate. These findings show that Warburg effect and its consequences are induced in cancer cells that survive severe damage.

Increasingly strong reduction in breast cancer mortality due to screening

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van Schoor, G; Moss, S M; Otten, J D M; Donders, R; Paap, E; den Heeten, G J; Holland, R; Broeders, M J M; Verbeek, A L M

2011-01-01

Background: Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast cancer screening from 1975 to 2008. Methods: In Nijmegen, the Netherlands, 55 529 women received an invitation for screening between 1975 and 2008. We designed a case–referent study to evaluate the impact of mammographic screening on breast cancer mortality over time from 1975 to 2008. A total number of 282 breast cancer deaths were identified, and 1410 referents aged 50–69 were sampled from the population invited for screening. We estimated the effectiveness by calculating the odds ratio (OR) indicating the breast cancer death rate for screened vs unscreened women. Results: The breast cancer death rate in the screened group over the complete period was 35% lower than in the unscreened group (OR=0.65; 95% CI=0.49–0.87). Analysis by calendar year showed an increasing effectiveness from a 28% reduction in breast cancer mortality in the period 1975–1991 (OR=0.72; 95% CI=0.47–1.09) to 65% in the period 1992–2008 (OR=0.35; 95% CI=0.19–0.64). Conclusion: Our results show an increasingly strong reduction in breast cancer mortality over time because of mammographic screening. PMID:21343930

Increasing Age and Treatment Modality Are Predictors for Subsequent Diagnosis of Bladder Cancer Following Prostate Cancer Diagnosis

International Nuclear Information System (INIS)

Singh, Anurag K.; Mashtare, Terry L.; McCloskey, Susan A.; Seixas-Mikelus, Stefanie A.; Kim, Hyung L.; May, Kilian Salerno

2010-01-01

Purpose: To determine the effect of prostate cancer therapy (surgery or external beam irradiation, or both or none) on the actuarial incidence of subsequent bladder cancer. Methods and Materials: The Surveillance, Epidemiology, and End Results registry from 1973 to 2005 was analyzed. Treatment was stratified as radiotherapy, surgery, both surgery and adjuvant radiation, and neither modality. Brachytherapy was excluded. Results: In all, 555,337 prostate carcinoma patients were identified; 124,141 patients were irradiated; 235,341 patients were treated surgically; 32,744 patients had both surgery and radiation; and 163,111 patients received neither modality. Bladder cancers were diagnosed in: 1,836 (1.48%) men who were irradiated (mean age, 69.4 years), 2,753 (1.09%) men who were treated surgically (mean age, 66.9 years); 683 (2.09%) men who received both modalities (mean age, 67.4 years), and 1,603 (0.98%) men who were treated with neither modality (mean age, 71.8 years). In each treatment cohort, Kaplan-Meier analyses showed that increasing age (by decade) was a significant predictor of developing bladder cancer (p < 0.0001). Incidence of bladder cancer was significantly different for either radiation or surgery alone versus no treatment, radiation versus surgery alone, and both surgery and radiation versus either modality alone (p < 0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer. Conclusions: Following prostate cancer, increasing age and irradiation were highly significant predictors of being diagnosed with bladder cancer. While use of radiation increased the risk of bladder cancer compared to surgery alone or no treatment, the overall incidence of subsequent bladder cancer remained low. Routine bladder cancer surveillance is not warranted.

Second cancers after conservative surgery and radiation for stages I-II breast cancer: identifying a subset of women at increased risk

International Nuclear Information System (INIS)

Fowble, Barbara; Hanlon, Alexandra; Freedman, Gary; Nicolaou, Nicos; Anderson, Penny

2001-01-01

Purpose: To assess the risk and patterns of second malignancy in a group of women treated with conservative surgery and radiation in a relatively contemporary manner for early-stage invasive breast cancer, and to identify a subgroup of these women at increased risk for a second cancer. Methods and Materials: From 1978 to 1994, 1,253 women with unilateral Stage I-II breast cancer underwent wide excision, axillary dissection, and radiation. The median follow-up was 8.9 years, with 446 patients followed for ≥10 years. The median age was 55 years. Sixty-eight percent had T1 tumors and 74% were axillary-node negative. Radiation was directed to the breast only in 78%. Adjuvant therapy consisted of chemotherapy in 19%, tamoxifen in 19%, and both in 8%. Factors analyzed for their association with the cumulative incidence of all second malignancies, contralateral breast cancer, and non-breast cancer malignancy were: age, menopausal status, race, family history, obesity, smoking, tumor size, location, histology, pathologic nodal status, region(s) treated with radiation, and the use and type of adjuvant therapy. Results: One hundred seventy-six women developed a second malignancy (87 contralateral breast cancers at a median interval of 5.8 years, and 98 non-breast cancer malignancies at a median interval of 7.2 years). Nine women had both a contralateral breast cancer and non-breast cancer second malignancy. The 5- and 10-year cumulative incidences of a second malignancy were 5% and 16% for all cancers, 3% and 7% for contralateral breast cancer, 3% and 8%, for all second non-breast cancer malignancies, and 1% and 5%, respectively, for second non-breast cancer malignancies, excluding skin cancers. Patient age was a significant factor for contralateral breast cancer and non-breast cancer second malignancy. Young age was associated with an increased risk of contralateral breast cancer, while older age was associated with an increased the risk of a second non-breast cancer

Exercise Decreases and Smoking Increases Bladder Cancer Mortality.

Science.gov (United States)

Liss, Michael A; White, Martha; Natarajan, Loki; Parsons, J Kellogg

2017-06-01

The aim of this study was to investigate modifiable lifestyle factors of smoking, exercise, and obesity with bladder cancer mortality. We used mortality-linked data from the National Health Information Survey from 1998 through 2006. The primary outcome was bladder cancer-specific mortality. The primary exposures were self-reported smoking status (never- vs. former vs. current smoker), self-reported exercise (dichotomized as "did no exercise" vs. "light, moderate, or vigorous exercise in ≥ 10-minute bouts"), and body mass index. We utilized multivariable adjusted Cox proportional hazards regression models, with delayed entry to account for age at survey interview. Complete data were available on 222,163 participants, of whom 96,715 (44%) were men and 146,014 (66%) were non-Hispanic whites, and among whom we identified 83 bladder cancer-specific deaths. In multivariate analyses, individuals who reported any exercise were 47% less likely (adjusted hazard ratio [HR adj ], 0.53; 95% confidence interval [CI], 0.29-0.96; P = .038) to die of bladder cancer than "no exercise". Compared with never-smokers, current (HR adj , 4.24; 95% CI, 1.89-9.65; P = .001) and former (HR adj , 2.95; 95% CI, 1.50-5.79; P = .002) smokers were 4 and 3 times more likely, respectively, to die of bladder cancer. There were no significant associations of body mass index with bladder cancer mortality. Exercise decreases and current smoking increases the risk of bladder cancer-specific mortality. These data suggest that exercise and smoking cessation interventions may reduce bladder cancer death. Published by Elsevier Inc.

MTH1 deficiency selectively increases non-cytotoxic oxidative DNA damage in lung cancer cells: more bad news than good?

Science.gov (United States)

Abbas, Hussein H K; Alhamoudi, Kheloud M H; Evans, Mark D; Jones, George D D; Foster, Steven S

2018-04-16

Targeted therapies are based on exploiting cancer-cell-specific genetic features or phenotypic traits to selectively kill cancer cells while leaving normal cells unaffected. Oxidative stress is a cancer hallmark phenotype. Given that free nucleotide pools are particularly vulnerable to oxidation, the nucleotide pool sanitising enzyme, MTH1, is potentially conditionally essential in cancer cells. However, findings from previous MTH1 studies have been contradictory, meaning the relevance of MTH1 in cancer is still to be determined. Here we ascertained the role of MTH1 specifically in lung cancer cell maintenance, and the potential of MTH1 inhibition as a targeted therapy strategy to improve lung cancer treatments. Using siRNA-mediated knockdown or small-molecule inhibition, we tested the genotoxic and cytotoxic effects of MTH1 deficiency on H23 (p53-mutated), H522 (p53-mutated) and A549 (wildtype p53) non-small cell lung cancer cell lines relative to normal MRC-5 lung fibroblasts. We also assessed if MTH1 inhibition augments current therapies. MTH1 knockdown increased levels of oxidatively damaged DNA and DNA damage signaling alterations in all lung cancer cell lines but not normal fibroblasts, despite no detectable differences in reactive oxygen species levels between any cell lines. Furthermore, MTH1 knockdown reduced H23 cell proliferation. However, unexpectedly, it did not induce apoptosis in any cell line or enhance the effects of gemcitabine, cisplatin or radiation in combination treatments. Contrastingly, TH287 and TH588 MTH1 inhibitors induced apoptosis in H23 and H522 cells, but only increased oxidative DNA damage levels in H23, indicating that they kill cells independently of DNA oxidation and seemingly via MTH1-distinct mechanisms. MTH1 has a NSCLC-specific p53-independent role for suppressing DNA oxidation and genomic instability, though surprisingly the basis of this may not be reactive-oxygen-species-associated oxidative stress. Despite this, overall

Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks.

Science.gov (United States)

Fortunato, Angelo; Boddy, Amy; Mallo, Diego; Aktipis, Athena; Maley, Carlo C; Pepper, John W

2017-02-01

Evolution by natural selection is the conceptual foundation for nearly every branch of biology and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection and adaptation or by other evolutionary processes such as founder effects and drift. In cancer biology, as in organismal evolutionary biology, there is controversy about this question and also about the use of adaptation through natural selection as a guiding framework for research. In this review, we discuss the differences and similarities between evolution among somatic cells versus evolution among organisms. We review what is known about the parameters and rate of evolution in neoplasms, as well as evidence for adaptation. We conclude that adaptation is a useful framework that accurately explains the defining characteristics of cancer. Further, convergent evolution through natural selection provides the only satisfying explanation both for how a group of diverse pathologies have enough in common to usefully share the descriptive label of "cancer" and for why this convergent condition becomes life-threatening. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Cancer and environment - collective expertise

International Nuclear Information System (INIS)

Baldi, Isabelle; Bard, Denis; Barouki, Robert; Benhamou, Simone; Benichou, Jacques; Bernier, Marie-Odile; Bouchot, Olivier; Carayon, Pierre; Ceraline, Jocelyn; Charafe-Jauffret, Emmanuelle; Clavel, Jacqueline; Clavel-Chapelon, Francoise; De Vathaire, Florent; Gerber, Mariette; Gilg Soit Ilg, Anabelle; Guenel, Pascal; Guillouzo, Andre; Hainaut, Pierre; Jaurand, Marie-Claude; Jougla, Eric; Launoy, Guy; Laurier, Dominique; Levi, Yves; Maynadie, Marc; Momas, Isabelle; Pairon, Jean-Claude; Paris, Christophe; Parmentier, Claude; Sanson, Marc; Savouret, Jean-Francois; Stuecker, Isabelle; Thonneau, Patrick; Walschaerts, Marie; Billon-Galland, Marie-Annick; Coignard, Florence; Grosclaude, Pascale; Guignon, Nicole; Hours, Martine; Molinie, Florence; Sandret, Nicolas; Multigner, Luc; Sasco, Annie; Bonnin, Fabienne; Chenu, Catherine; Etiemble, Jeanne; Gomis, Cecile; Labro, Marie-Therese; Pellier, Anne-Laure; Rondet-Grellier, Chantal

2008-01-01

This document reports the work of two groups of experts on the impact of the environment on some cancers the incidence of which has increased during the past twenty years. After a first part discussing the general mechanisms of toxicity, the report discusses various aspects (notably classification, incidence and evolution, mortality, known and debated risk factors) for different cancer types: lung cancer, mesothelioma, malignant hemopathies, brain tumours, breast cancer, ovarian cancer, testicular cancer, prostate cancer, thyroid cancer. It also discusses knowledge on the exposure to chemical and physical agents (assessment modalities and exposure data in general environment and in professional environment, exposure to ionizing radiation, to electromagnetic fields and to endocrine disrupters)

Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact

Science.gov (United States)

Taylor, Jared F.; Khattab, Omar S.; Chen, Yu-Han; Chen, Yumay; Jacobsen, Steven E.; Wang, Ping H.

2015-01-01

Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp) and end (115 bp) of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer. PMID:26308346

Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact.

Directory of Open Access Journals (Sweden)

Puya G Yazdi

Full Text Available Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp and end (115 bp of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer.

Increased plasma soluble uPAR level is a risk marker of respiratory cancer in initially cancer-free individuals

DEFF Research Database (Denmark)

Langkilde, Anne A; Hansen, Tine Willum; Ladelund, Steen

2011-01-01

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a stable plasma biomarker associated with inflammation and disease. This study tested the association between suPAR levels and incident respiratory, gastrointestinal or other types of cancer in initially cancer-free individuals...... with respiratory, gastrointestinal and other cancer types, respectively.CONCLUSIONS: Elevated suPAR levels were associated with increased risk of incident respiratory cancer and other types of cancer, but not gastrointestinal cancers, independently of established risk factors, CRP and leukocyte numbers. Impact.......RESULTS: suPAR levels ranged from 0.6-22 ng/ml, and median suPAR level was 4.01 ng/ml. 1 ng/ml increase in baseline suPAR was associated with adjusted hazard ratios (HR) of 1.61 (95% CI: 1.23-2.11, P

Psycho Educational Group Intervention for Women at Increased Risk for Breast Cancer

National Research Council Canada - National Science Library

Kash, Kathryn

1998-01-01

... in women at increased risk for breast cancer; (2) examine the impact of a psychoeducational intervention on the endpoint variables of quality of life and adherence to screening in women at increased risk for breast cancer; and (3...

Rapid evolution of cancer/testis genes on the X chromosome

Directory of Open Access Journals (Sweden)

Simpson Andrew J

2007-05-01

Full Text Available Abstract Background Cancer/testis (CT genes are normally expressed only in germ cells, but can be activated in the cancer state. This unusual property, together with the finding that many CT proteins elicit an antigenic response in cancer patients, has established a role for this class of genes as targets in immunotherapy regimes. Many families of CT genes have been identified in the human genome, but their biological function for the most part remains unclear. While it has been shown that some CT genes are under diversifying selection, this question has not been addressed before for the class as a whole. Results To shed more light on this interesting group of genes, we exploited the generation of a draft chimpanzee (Pan troglodytes genomic sequence to examine CT genes in an organism that is closely related to human, and generated a high-quality, manually curated set of human:chimpanzee CT gene alignments. We find that the chimpanzee genome contains homologues to most of the human CT families, and that the genes are located on the same chromosome and at a similar copy number to those in human. Comparison of putative human:chimpanzee orthologues indicates that CT genes located on chromosome X are diverging faster and are undergoing stronger diversifying selection than those on the autosomes or than a set of control genes on either chromosome X or autosomes. Conclusion Given their high level of diversifying selection, we suggest that CT genes are primarily responsible for the observed rapid evolution of protein-coding genes on the X chromosome.

HIV infection is associated with an increased risk for lung cancer, independent of smoking.

Science.gov (United States)

Kirk, Gregory D; Merlo, Christian; O' Driscoll, Peter; Mehta, Shruti H; Galai, Noya; Vlahov, David; Samet, Jonathan; Engels, Eric A

2007-07-01

Human immunodeficiency virus (HIV)-infected persons have an elevated risk for lung cancer, but whether the increase reflects solely their heavy tobacco use remains an open question. The Acquired Immunodeficiency Syndrome (AIDS) Link to the Intravenous Experience Study has prospectively observed a cohort of injection drug users in Baltimore, Maryland, since 1988, using biannual collection of clinical, laboratory, and behavioral data. Lung cancer deaths were identified through linkage with the National Death Index. Cox proportional hazards regression was used to examine the effect of HIV infection on lung cancer risk, controlling for smoking status, drug use, and clinical variables. Among 2086 AIDS Link to the Intravenous Experience Study participants observed for 19,835 person-years, 27 lung cancer deaths were identified; 14 of the deaths were among HIV-infected persons. All but 1 (96%) of the patients with lung cancer were smokers, smoking a mean of 1.2 packs per day. Lung cancer mortality increased during the highly active antiretroviral therapy era, compared with the pre-highly active antiretroviral therapy period (mortality rate ratio, 4.7; 95% confidence interval, 1.7-16). After adjusting for age, sex, smoking status, and calendar period, HIV infection was associated with increased lung cancer risk (hazard ratio, 3.6; 95% confidence interval, 1.6-7.9). Preexisting lung disease, particularly noninfectious diseases and asthma, displayed trends for increased lung cancer risk. Illicit drug use was not associated with increased lung cancer risk. Among HIV-infected persons, smoking remained the major risk factor; CD4 cell count and HIV load were not strongly associated with increased lung cancer risk, and trends for increased risk with use of highly active antiretroviral therapy were not significant. HIV infection is associated with significantly increased risk for developing lung cancer, independent of smoking status.

Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.

Science.gov (United States)

Haricharan, Svasti; Dong, Jie; Hein, Sarah; Reddy, Jay P; Du, Zhijun; Toneff, Michael; Holloway, Kimberly; Hilsenbeck, Susan G; Huang, Shixia; Atkinson, Rachel; Woodward, Wendy; Jindal, Sonali; Borges, Virginia F; Gutierrez, Carolina; Zhang, Hong; Schedin, Pepper J; Osborne, C Kent; Tweardy, David J; Li, Yi

2013-12-31

While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy. DOI: http://dx.doi.org/10.7554/eLife.00996.001.

Domesticating Cancer: An Evolutionary Strategy in the War on Cancer

Directory of Open Access Journals (Sweden)

Gustav van Niekerk

2017-12-01

Full Text Available Since cancer shares the same molecular machinery as the host, most therapeutic interventions that aim to target cancer would inadvertently also adversely affect the host. In addition, cancer continuously evolves, streamlining its host-derived genome for a new single-celled existence. In particular, short-term clinical success observed with most antineoplastic therapies directly relate to the fact that cancer is constantly evolving. However, the clonal evolution of cancer occasionally also render cancer cells uniquely susceptible to therapeutic interventions, as is exemplified by the clinical relevance of synthetic lethality. Synthetic lethality describes a situation where the simultaneous loss of function in two genes results in lethality, but where a loss of function in either single gene is tolerated. This observation suggests that the evolution of cancer, usually seen as a major clinical challenge, may also afford a key opportunity in lowering on-target toxicities accosted with chemotherapy. As an example, by subjecting cancer to specific selection regimes, cancer can in effect be placed on evolutionary trajectories leading to the development of “targetable” phenotypes such as synthetic lethal interactions. However, such a selection regime would have to overcome a range of obstacles such as on-target toxicity and the selection of an evolvable trait. Since the majority of cancer evolution manifests as a loss of function, we suggest that the induction of auxotrophic phenotypes (i.e., where an organism lose the ability to synthesize specific organic compounds required for growth and thus become dependent on it from dietary sources may represent an attractive therapeutic option. As an example, animals can obtain vitamin C either by de novo synthesis or from their diet. However, since the maintenance of synthetic pathways is costly, such pathways are often lost if no longer necessary, resulting in the organism being auxotrophic toward the

Psycho Educational Group Intervention for Women at Increased Risk for Breast Cancer

National Research Council Canada - National Science Library

Kash, Kathryn

1997-01-01

... skills in women at increased risk for breast cancer; (2) to examine the impact of a psychoeducational intervention on the endpoint variables of quality of life and adherence to screening in women at increased risk for breast cancer; and (3...

Evolution of breast cancer management in Ireland: a decade of change

Directory of Open Access Journals (Sweden)

Malone C

2009-09-01

Full Text Available Abstract Background Over the last decade there has been a paradigm shift in the management of breast cancer, subsequent to revised surgical oncology guidelines and consensus statements which were derived in light of landmark breast cancer clinical trials conducted throughout the latter part of the 20th century. However the sheer impact of this paradigm shift upon all modalities of treatment, and the current trends in management of the disease, are largely unknown. We aimed to assess the changing practices of breast cancer management over the last decade within a specialist tertiary referral Breast Cancer Centre. Methods Comparative analysis of all aspects of the management of breast cancer patients, who presented to a tertiary referral Breast Cancer Centre in 1995/1996 and 2005/2006, was undertaken and measured against The European Society for Surgical Oncology guidelines for the surgical management of mammographically detected lesions [1998]. Results 613 patients' case profiles were analysed. Over the last decade we observed a dramatic increase in incidence of breast cancer [>100%], a move to less invasive diagnostic and surgical therapeutic techniques, as well as increased use of adjuvant therapies. We also witnessed the introduction of immediate breast reconstruction as part of routine practice Conclusion We demonstrate that radical changes have occurred in the management of breast cancer in the last decade, in keeping with international guidelines. It remains incumbent upon us to continue to adapt our practice patterns in light of emerging knowledge and best evidence.

Evolution of breast cancer management in Ireland: a decade of change.

LENUS (Irish Health Repository)

Heneghan, Helen M

2009-01-01

BACKGROUND: Over the last decade there has been a paradigm shift in the management of breast cancer, subsequent to revised surgical oncology guidelines and consensus statements which were derived in light of landmark breast cancer clinical trials conducted throughout the latter part of the 20th century. However the sheer impact of this paradigm shift upon all modalities of treatment, and the current trends in management of the disease, are largely unknown. We aimed to assess the changing practices of breast cancer management over the last decade within a specialist tertiary referral Breast Cancer Centre. METHODS: Comparative analysis of all aspects of the management of breast cancer patients, who presented to a tertiary referral Breast Cancer Centre in 1995\\/1996 and 2005\\/2006, was undertaken and measured against The European Society for Surgical Oncology guidelines for the surgical management of mammographically detected lesions [1998]. RESULTS: 613 patients\\' case profiles were analysed. Over the last decade we observed a dramatic increase in incidence of breast cancer [>100%], a move to less invasive diagnostic and surgical therapeutic techniques, as well as increased use of adjuvant therapies. We also witnessed the introduction of immediate breast reconstruction as part of routine practice CONCLUSION: We demonstrate that radical changes have occurred in the management of breast cancer in the last decade, in keeping with international guidelines. It remains incumbent upon us to continue to adapt our practice patterns in light of emerging knowledge and best evidence.

Evolution of emphysema in relation to smoking

International Nuclear Information System (INIS)

Bellomi, Massimo; Rampinelli, Cristiano; Veronesi, Giulia; Harari, Sergio; Lanfranchi, Federica; Raimondi, Sara; Maisonneuve, Patrick

2010-01-01

We have little knowledge about the evolution of emphysema, and relatively little is understood about its evolution in relation to smoking habits. This study aims to assess the evolution of emphysema in asymptomatic current and former smokers over 2 years and to investigate the association with subjects' characteristics. The study was approved by our Ethics Committee and all participants provided written informed consent. We measured emphysema by automatic low-dose computed tomography densitometry in 254 current and 282 former smokers enrolled in a lung-cancer screening. The measures were repeated after 2 years. The association between subjects' characteristics, smoking habits and emphysema were assessed by chi-squared and Wilcoxon tests. Univariate and multivariate odds ratios (OR) with 95% confidence intervals (CI) were calculated for the risk of emphysema worsening according to subjects' characteristics. We assessed the trend of increasing risk of emphysema progression by smoking habits using the Mantel-Haenszel chi-squared test. The median percentage increase in emphysema over a 2-year period was significantly higher in current than in former smokers (OR 1.8; 95% CI 1.3-2.6; p < 0.0001). The risk of worsening emphysema (by 30% in 2 years) in current smokers increased with smoking duration (p for trend <0.02). As emphysema is a known risk factor for lung cancer, its evaluation could be used as a potential factor for identification of a high-risk population. The evaluation of emphysema progression can be added to low-dose CT screening programmes to inform and incite participants to stop smoking. (orig.)

Evolution of emphysema in relation to smoking

Energy Technology Data Exchange (ETDEWEB)

Bellomi, Massimo [European Institute of Oncology, Department of Radiology, Milan (Italy); University of Milan - IT, School of Medicine, Milan (Italy); Rampinelli, Cristiano [European Institute of Oncology, Department of Radiology, Milan (Italy); Veronesi, Giulia [European Institute of Oncology, Department of Thoracic Surgery, Milan (Italy); Harari, Sergio [Fatebenefratelli-Milanocuore, Pneumology Operative Unit, San Giuseppe Hospital, Milan (Italy); Lanfranchi, Federica [University of Milan - IT, School of Medicine, Milan (Italy); Raimondi, Sara; Maisonneuve, Patrick [European Institute of Oncology, Department of Epidemiology and Biostatistics, Milan (Italy)

2010-02-15

We have little knowledge about the evolution of emphysema, and relatively little is understood about its evolution in relation to smoking habits. This study aims to assess the evolution of emphysema in asymptomatic current and former smokers over 2 years and to investigate the association with subjects' characteristics. The study was approved by our Ethics Committee and all participants provided written informed consent. We measured emphysema by automatic low-dose computed tomography densitometry in 254 current and 282 former smokers enrolled in a lung-cancer screening. The measures were repeated after 2 years. The association between subjects' characteristics, smoking habits and emphysema were assessed by chi-squared and Wilcoxon tests. Univariate and multivariate odds ratios (OR) with 95% confidence intervals (CI) were calculated for the risk of emphysema worsening according to subjects' characteristics. We assessed the trend of increasing risk of emphysema progression by smoking habits using the Mantel-Haenszel chi-squared test. The median percentage increase in emphysema over a 2-year period was significantly higher in current than in former smokers (OR 1.8; 95% CI 1.3-2.6; p < 0.0001). The risk of worsening emphysema (by 30% in 2 years) in current smokers increased with smoking duration (p for trend <0.02). As emphysema is a known risk factor for lung cancer, its evaluation could be used as a potential factor for identification of a high-risk population. The evaluation of emphysema progression can be added to low-dose CT screening programmes to inform and incite participants to stop smoking. (orig.)

Breast cancer patients with dense breasts do not have increased death risk

Science.gov (United States)

High mammographic breast density, which is a marker of increased risk of developing breast cancer, does not seem to increase the risk of death among breast cancer patients, according to a study led by Gretchen L. Gierach, Ph.D., NCI. Image shows physician

Evolution in students' understanding of thermal physics with increasing complexity

Science.gov (United States)

Langbeheim, Elon; Safran, Samuel A.; Livne, Shelly; Yerushalmi, Edit

2013-12-01

We analyze the development in students’ understanding of fundamental principles in the context of learning a current interdisciplinary research topic—soft matter—that was adapted to the level of high school students. The topic was introduced in a program for interested 11th grade high school students majoring in chemistry and/or physics, in an off-school setting. Soft matter was presented in a gradual increase in the degree of complexity of the phenomena as well as in the level of the quantitative analysis. We describe the evolution in students’ use of fundamental thermodynamics principles to reason about phase separation—a phenomenon that is ubiquitous in soft matter. In particular, we examine the impact of the use of free energy analysis, a common approach in soft matter, on the understanding of the fundamental principles of thermodynamics. The study used diagnostic questions and classroom observations to gauge the student’s learning. In order to gain insight on the aspects that shape the understanding of the basic principles, we focus on the responses and explanations of two case-study students who represent two trends of evolution in conceptual understanding in the group. We analyze changes in the two case studies’ management of conceptual resources used in their analysis of phase separation, and suggest how their prior knowledge and epistemological framing (a combination of their personal tendencies and their prior exposure to different learning styles) affect their conceptual evolution. Finally, we propose strategies to improve the instruction of these concepts.

Radiotherapy did not increase thyroid cancer risk among women with breast cancer: A nationwide population-based cohort study.

Science.gov (United States)

Sun, Li-Min; Lin, Cheng-Li; Liang, Ji-An; Huang, Wen-Sheng; Kao, Chia-Hung

2015-12-15

The aim of this study was to evaluate whether an increased risk of thyroid cancer exists among women with breast cancer in Taiwan, particularly among those receiving RT. We used data from the National Health Insurance system of Taiwan for the investigation. The breast cancer cohort contained 55,318 women (including 28,187 who received RT and 27,131 who received no RT), each of whom was randomly frequency matched according to age and index year with three women without breast cancer from the general population. Cox's proportion hazards regression analysis was conducted to estimate the effects of breast cancer with or without RT treatment on subsequent thyroid cancer risk. We found that women with breast cancer exhibited a significantly higher risk of subsequent thyroid cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.60-2.44). The two groups (with or without RT) in the breast cancer cohort exhibited significantly increased risks. However, in the breast cancer cohort, the risk of thyroid cancer among women who received RT was not significantly higher than that of women who received no RT (aHR = 1.28, 95% CI = 0.90-1.83). Stratified analysis according to age revealed that only younger women with breast cancer (20-54 y) had a significantly higher risk of developing thyroid cancer. This study determined that Taiwanese women with breast cancer had a higher risk of developing thyroid cancer; however, RT seems to not play a crucial role in this possible relationship. © 2015 UICC.

Increased Prevalence of Chronic Lymphocytic Thyroiditis in Korean Patients with Papillary Thyroid Cancer

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Oh, Chang-Mo; Park, Sohee; Lee, Joo Young; Won, Young-Joo; Shin, Aesun; Kong, Hyun-Joo; Choi, Kui-Sun; Lee, You Jin; Chung, Ki- Wook; Jung, Kyu-Won

2014-01-01

Background In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. Materials and Methods We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20–79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year. Results The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender. Conclusions Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change. PMID:24927027

Increased risk of antidepressant use in childhood cancer survivors

DEFF Research Database (Denmark)

Lund, Lasse Wegener; Winther, J.F.; Cederkvist, L

2015-01-01

to the National Prescription Drug Database, which worldwide is the oldest nationwide registry of prescription medication. Hazard ratios (HRs) for antidepressant use were estimated in a Cox proportional hazards model stratified on sex, with population comparisons as referents. RESULTS: Overall, childhood cancer......AIM: Childhood cancer survivors are at risk of both somatic and mental late effects, but large population-based studies of depression are lacking. METHODS: Risk of antidepressant use was evaluated in a population-based cohort of 5452 Danish children treated for cancer in 1975-2009 by linkage....... Increased HRs of 30-50% were seen for survivors of cancers of all main groups (haematological malignancies, central nervous system (CNS) and solid tumors); the highest risk was among children treated with haematopoietic stem cell transplantation (HR, 1.9; 95% CI, 1.2-3.1). Our data suggested that the risk...

Serum levels of polyamine synthesis enzymes increase in diabetic patients with breast cancer

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V Kenan Çelik

2017-09-01

Full Text Available In this study, it was aimed to investigate the relationship between diabetes and breast cancer and the detection of enzymes and ornithine levels in polyamine synthesis pathway in diabetes, breast cancer and diabetic breast cancer patients. Methods: Ornithine, arginine decarboxylase, ornithine decarboxylase and agmatinase levels have been measured in serum of all groups. Ornithine levels were measured spectrophotometrically. Arginine decarboxylase, ornithine decarboxylase and agmatinase levels were determined by ELISA kits. Results: Except for the diabetic group, the levels of enzymes in the polyamine synthesis pathway were increased in all and statistically significant (P < 0.05. The increase in the levels of agmatinase was very important among the enzymes (P < 0.001. Conclusions: Decreased levels of polyamine synthase enzymes in diabetes mellitus were found to be increased patients with breast cancer. Whether and how diabetes-based breast cancer development relates to increase activity of enzymes responsible for polyamine synthesis requires further mechanistic and prospective monitoring studies in larger patient cohorts.

Life after cancer: how does public stigma increase psychological distress of childhood cancer survivors?

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Kim, Min Ah; Yi, Jaehee

2014-12-01

Public stigma is a major source of stress for cancer survivors. However, factors that buffer or exacerbate the negative effects of public stigma on psychological distress have not been elucidated. This study examined how perceived public stigma affects psychological distress as mediated by cancer disclosure, internalized reactions to stigma, and social support availability. Cross-sectional study. The study was conducted in South Korea. The study sample was 223 adolescent and young adult survivors of childhood cancer diagnosed before the age of 19 and currently between 15 and 39 years old. Psychological distress was assessed using the Brief Symptom Inventory-18. Structural equation modeling was used with 1000 bootstrap samples. The goodness of model fit was acceptable. Public stigma perceived by cancer survivors influenced psychological distress via cancer disclosure, internalized shame, and social support availability. Higher levels of perceived public stigma predicted higher levels of internalized shame and self-blame and lower levels of social support availability, which subsequently increased psychological distress. Higher levels of perceived public stigma predicted lower levels of disclosure about cancer history and experiences. Cancer disclosure indirectly ameliorated psychological distress by reducing internalized shame. This study offers evidence that cognitive and social factors play important roles in mediating the effects of perceived public stigma on psychological distress in Korean cancer survivors. A greater understanding of factors that influence psychological distress may help psychosocial oncology service providers to identify childhood cancer survivors in need of psychosocial services and provide them with appropriate resources and interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Increased standardized incidence ratio of breast cancer in female electronics workers

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Lin Yi-Ping

2007-06-01

Full Text Available Abstract Background In 1994, a hazardous waste site, polluted by the dumping of solvents from a former electronics factory, was discovered in Taoyuan, Taiwan. This subsequently emerged as a serious case of contamination through chlorinated hydrocarbons with suspected occupational cancer. The objective of this study was to determine if there was any increased risk of breast cancer among female workers in a 23-year follow-up period. Methods A total of 63,982 female workers were retrospectively recruited from the database of the Bureau of Labor Insurance (BLI covering the period 1973–1997; the data were then linked with data, up to 2001, from the National Cancer Registry at the Taiwanese Department of Health, from which standardized incidence ratios (SIRs for different types of cancer were calculated as compared to the general population. Results There were a total of 286 cases of breast cancer, and after adjustment for calendar year and age, the SIR was close to 1. When stratified by the year 1974 (the year in which the regulations on solvent use were promulgated, the SIR of the cohort of workers who were first employed prior to 1974 increased to 1.38 (95% confidence interval, 1.11–1.70. No such trend was discernible for workers employed after 1974. When 10 years of employment was considered, there was a further increase in the SIR for breast cancer, to 1.62. Those workers with breast cancer who were first employed prior to 1974 were employed at a younger age and for a longer period. Previous qualitative studies of interviews with the workers, corroborated by inspection records, showed a short-term high exposure to chlorinated alkanes and alkenes, particularly trichloroethylene before 1974. There were no similar findings on other types of cancer. Conclusion Female workers with exposure to trichloroethylene and/or mixture of solvents, first employed prior to 1974, may have an excess risk of breast cancer.

Evolution of radiotherapy at MOH

International Nuclear Information System (INIS)

Passi, Kamalesh

2016-01-01

Mohan Dai Oswal Cancer Institute was started by Oswals, a philanthropist family of industrialists, in the memory of their mother Smt Mohan Dai Oswal, who died of cancer. This was the first of its kind charitable institute in the private sector in north providing comprehensive cancer care under one roof. The large number of patients that the hospital attracted in the very first year revealed the huge lacuna in cancer care that had been existent in the region. Since then this hospital has been catering to all of Punjab, Himachal, J and K and a large area of Haryana. It has built a reputation for high-tech, yet cost-effective, care. There are multiple dimensions to the evolution of Radiotherapy at MDOH- build-up of technical hardware, growth of skilled personnel, laying down and development of protocols and processes and the evolution of a unique work culture

Meta-analysis reveals evolution in invasive plant species but little support for Evolution of Increased Competitive Ability (EICA).

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Felker-Quinn, Emmi; Schweitzer, Jennifer A; Bailey, Joseph K

2013-03-01

Ecological explanations for the success and persistence of invasive species vastly outnumber evolutionary hypotheses, yet evolution is a fundamental process in the success of any species. The Evolution of Increased Competitive Ability (EICA) hypothesis (Blossey and Nötzold 1995) proposes that evolutionary change in response to release from coevolved herbivores is responsible for the success of many invasive plant species. Studies that evaluate this hypothesis have used different approaches to test whether invasive populations allocate fewer resources to defense and more to growth and competitive ability than do source populations, with mixed results. We conducted a meta-analysis of experimental tests of evolutionary change in the context of EICA. In contrast to previous reviews, there was no support across invasive species for EICA's predictions regarding defense or competitive ability, although invasive populations were more productive than conspecific native populations under noncompetitive conditions. We found broad support for genetically based changes in defense and competitive plant traits after introduction into new ranges, but not in the manner suggested by EICA. This review suggests that evolution occurs as a result of plant introduction and population expansion in invasive plant species, and may contribute to the invasiveness and persistence of some introduced species.

Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis.

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Fox, Amy C; Robertson, Charles M; Belt, Brian; Clark, Andrew T; Chang, Katherine C; Leathersich, Ann M; Dominguez, Jessica A; Perrone, Erin E; Dunne, W Michael; Hotchkiss, Richard S; Buchman, Timothy G; Linehan, David C; Coopersmith, Craig M

2010-03-01

Whereas most septic patients have an underlying comorbidity, most animal models of sepsis use mice that were healthy before the onset of infection. Malignancy is the most common comorbidity associated with sepsis. The purpose of this study was to determine whether mice with cancer have a different response to sepsis than healthy animals. Prospective, randomized controlled study. Animal laboratory in a university medical center. C57Bl/6 mice. Animals received a subcutaneous injection of either 250,000 cells of the transplantable pancreatic adenocarcinoma cell line Pan02 (cancer) or phosphate-buffered saline (healthy). Three weeks later, mice given Pan02 cells had reproducible, nonmetastatic tumors. Both groups of mice then underwent intratracheal injection of either Pseudomonas aeruginosa (septic) or 0.9% NaCl (sham). Animals were killed 24 hrs postoperatively or followed-up 7 days for survival. Mice with cancer and healthy mice appeared similar when subjected to sham operation, although cancer animals had lower levels of T- and B-lymphocyte apoptosis. Septic mice with cancer had increased mortality compared to previously healthy septic mice subjected to the identical injury (52% vs. 28%; p = .04). This was associated with increased bacteremia but no difference in local pulmonary infection. Septic mice with cancer also had increased intestinal epithelial apoptosis. Although sepsis induced an increase in T- and B-lymphocyte apoptosis in all animals, septic mice with cancer had decreased T- and B-lymphocyte apoptosis compared to previously healthy septic mice. Serum and pulmonary cytokines, lung histology, complete blood counts, and intestinal proliferation were similar between septic mice with cancer and previously healthy septic mice. When subjected to the same septic insult, mice with cancer have increased mortality compared to previously healthy animals. Decreased systemic bacterial clearance and alterations in intestinal epithelial and lymphocyte apoptosis may

Evolution in students’ understanding of thermal physics with increasing complexity

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Elon Langbeheim

2013-11-01

Full Text Available We analyze the development in students’ understanding of fundamental principles in the context of learning a current interdisciplinary research topic—soft matter—that was adapted to the level of high school students. The topic was introduced in a program for interested 11th grade high school students majoring in chemistry and/or physics, in an off-school setting. Soft matter was presented in a gradual increase in the degree of complexity of the phenomena as well as in the level of the quantitative analysis. We describe the evolution in students’ use of fundamental thermodynamics principles to reason about phase separation—a phenomenon that is ubiquitous in soft matter. In particular, we examine the impact of the use of free energy analysis, a common approach in soft matter, on the understanding of the fundamental principles of thermodynamics. The study used diagnostic questions and classroom observations to gauge the student’s learning. In order to gain insight on the aspects that shape the understanding of the basic principles, we focus on the responses and explanations of two case-study students who represent two trends of evolution in conceptual understanding in the group. We analyze changes in the two case studies’ management of conceptual resources used in their analysis of phase separation, and suggest how their prior knowledge and epistemological framing (a combination of their personal tendencies and their prior exposure to different learning styles affect their conceptual evolution. Finally, we propose strategies to improve the instruction of these concepts.

Chernobyl-Related Cancer and Precancerous Lesions: Incidence Increase vs. Late Diagnostics

Science.gov (United States)

Jargin, Sergei V.

2014-01-01

The reported incidence of thyroid cancer in children and adolescents in Soviet Union before the Chernobyl accident was lower than in other developed countries. This is not clearly recognizable from the literature because comparisons of the high incidence figures 4 years after the accident and later have been made with those from the first years after the accident, when the registered incidence had already started to increase. Considering the low pre-accident registered incidence, there was an accumulated pool of undiagnosed thyroid tumors before the accident. The percentage of more advanced cancers, larger in size and less differentiated, was higher after the accident, when the pool of neglected cancers was diagnosed due to the screening and improved diagnostics. Some of these advanced tumors found by screening were interpreted as aggressive radiogenic cancers. The same tendency might be true also for other cancers, e.g. renal cell carcinoma. Furthermore, the screening-effect, false-positivity and registration of non-exposed patients as Chernobyl victims has obviously contributed to the registered incidence increase of malignancy. PMID:25249833

Evolution of increased phenotypic diversity enhances population performance by reducing sexual harassment in damselflies.

Science.gov (United States)

Takahashi, Yuma; Kagawa, Kotaro; Svensson, Erik I; Kawata, Masakado

2014-07-18

The effect of evolutionary changes in traits and phenotypic/genetic diversity on ecological dynamics has received much theoretical attention; however, the mechanisms and ecological consequences are usually unknown. Female-limited colour polymorphism in damselflies is a counter-adaptation to male mating harassment, and thus, is expected to alter population dynamics through relaxing sexual conflict. Here we show the side effect of the evolution of female morph diversity on population performance (for example, population productivity and sustainability) in damselflies. Our theoretical model incorporating key features of the sexual interaction predicts that the evolution of increased phenotypic diversity will reduce overall fitness costs to females from sexual conflict, which in turn will increase productivity, density and stability of a population. Field data and mesocosm experiments support these model predictions. Our study suggests that increased phenotypic diversity can enhance population performance that can potentially reduce extinction rates and thereby influence macroevolutionary processes.

Colorectal cancer surveillance in Hodgkin lymphoma survivors at increased risk of therapy-related colorectal cancer : study design

NARCIS (Netherlands)

Rigter, Lisanne S; Spaander, Manon C W; Moons, Leon M; Bisseling, Tanya M; Aleman, Berthe M P; de Boer, Jan Paul; Lugtenburg, Pieternella J; Janus, Cecile P M; Petersen, Eefke J; Roesink, Judith M; Raemaekers, John M M; van der Maazen, Richard W M; Cats, Annemieke; Bleiker, Eveline M A; Snaebjornsson, Petur; Carvalho, Beatriz; Lansdorp-Vogelaar, Iris; Jóźwiak, Katarzyna; Te Riele, Hein; Meijer, Gerrit A; van Leeuwen, Flora E; van Leerdam, Monique E

2017-01-01

BACKGROUND: Second primary malignancies are a major cause of excess morbidity and mortality in cancer survivors. Hodgkin lymphoma survivors who were treated with infradiaphragmatic radiotherapy and/or high-dose procarbazine have an increased risk to develop colorectal cancer. Colonoscopy

Evolution of the TOR Pathway.

NARCIS (Netherlands)

Dam, T.J.P. van; Zwartkruis, F.J.; Bos, J.L.; Snel, B.

2011-01-01

The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and

Inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer

Institute of Scientific and Technical Information of China (English)

Zhao Li; Ma Yongjie; Gu Feng; Fu Li

2014-01-01

Background Paclitaxel (PAC) is the first-line chemotherapy drug for most breast cancer patients,but clinical studies showed that some breast cancer patients were insensitive to PAC,which led to chemotherapy failure.It was reported that Notch1 signaling participated in drug resistance of breast cancer.Here,we show whether Notch1 expression is related to PAC sensitivity of breast cancer.Methods We employed Notch1 siRNA and Notch1 inhibitor,N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester (DAPT),to down regulate Notch1 expression in human breast cancer cells MDA-MB-231,and detected the inhibition effect by Western blotting and reverse trans cription-polymerase chain reaction,respectively.After 24 hours exposure to different concentration of PAC (0,1,5,10,15,20,and 25 μg/ml),the viability of the control group and experimental group cells was tested by MTT.We also examined the expression of Notch1 in PAC sensitive and nonsensitive breast cancer patients,respectively by immunohistochemistry (IHC).The PAC sensitivity of breast cancer patients were identified by collagen gel droplet embedded culture-drug sensitivity test (CD-DST).Results Down regulation of Notch1 expression by Notch1siRNA interference or Notch1 inhibitor increased the PAC sensitivity in MDA-MB-231 cells (P ＜0.05).Also,the expression of Notch1 in PAC sensitive patients was much lower than that of PAC non-sensitive patients (P ＜0.01).Conclusion Notch1 expression has an effect on PAC sensitivity in breast cancer patients,and the inhibition of Notch1 increases paclitaxel sensitivity to human breast cancer.

Increase in intracellular PGE2 induces apoptosis in Bax-expressing colon cancer cell

International Nuclear Information System (INIS)

Lalier, Lisenn; Pedelaborde, François; Braud, Christophe; Menanteau, Jean; M Vallette, François; Olivier, Christophe

2011-01-01

NSAIDs exhibit protective properties towards some cancers, especially colon cancer. Yet, it is not clear how they play their protective role. PGE 2 is generally shown as the only target of the NSAIDs anticancerous activity. However, PGE 2 known targets become more and more manifold, considering both the molecular pathways involved and the target cells in the tumour. The role of PGE 2 in tumour progression thus appears complex and multipurpose. To gain understanding into the role of PGE 2 in colon cancer, we focused on the activity of PGE 2 in apoptosis in colon cancer cell lines. We observed that an increase in intracellular PGE 2 induced an apoptotic cell death, which was dependent on the expression of the proapoptotic protein Bax. This increase was induced by increasing PGE 2 intracellular concentration, either by PGE 2 microinjection or by the pharmacological inhibition of PGE 2 exportation and enzymatic degradation. We present here a new sight onto PGE 2 in colon cancer cells opening the way to a new prospective therapeutic strategy in cancer, alternative to NSAIDs

Views of Low-Income Women of Color at Increased Risk for Breast Cancer.

Science.gov (United States)

E Anderson, Emily; Tejada, Silvia; B Warnecke, Richard; Hoskins, Kent

2018-01-01

Individual risk assessment (IRA) for breast cancer may increase adherence to risk-appropriate screening and prevention measures. However, knowledge gaps exist regarding how best to communicate IRA results and support women at increased risk in future health care decisions, in part because patients conceptualize and make meaning of risk differently from the medical community. Better understanding the views of low-income women of color identified as being at increased risk for breast cancer can inform efforts to conduct IRA in an ethical and respectful manner. We conducted in-depth interviews with 13 low-income African American and Latina women who receive care at a federally qualified health center (FQHC) and had recently learned of their increased risk for breast cancer. These interviews explored their experience of the IRA process, their interpretation of what being at increased risk means, and their reactions to provider recommendations. Eight key themes were identified. We conclude with recommendations for the implementation of IRA for breast cancer in underserved primary care settings.

Radiosensitivity is increased by knockdown of FTS in uterine cervical cancer cells

Energy Technology Data Exchange (ETDEWEB)

Park, Wo Yoon; Anandharaj, Arunkumar; Cinghu, Senthikumar; Kim, Won Dong [Dept. of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju (Korea, Republic of); Yu, Jae Ran [Dept. of Environmental and Tropical Medicine, Konkuk University College of Medicine, Seoul (Korea, Republic of)

2012-04-15

Uterine cervical cancer is still the second largest cancer in women worldwide, despite of effective screening methods. Radiotherapy is used to treat all the stages of cervical cancer and more than 60% of cervical cancer patients receive radiotherapy. New therapeutic targets or approaches are needed to further increase the results of radiotherapy. In the present study, we demonstrated the radiation induced overexpression and nuclear export of FTS in cervical cancer cells. Furthermore, we showed that silencing of FTS expression with FTS shRNA enhanced radiosensitivity of cervical cancer cells, induced cell cycle arrest and apoptosis FTS is involved in radioresistance of cervical cancer. Targeted inhibition of FTS can shutdown the key elemental characteristics of cervical cancer and could lead to an effective therapeutic strategy.

Radiosensitivity is increased by knockdown of FTS in uterine cervical cancer cells

International Nuclear Information System (INIS)

Park, Wo Yoon; Anandharaj, Arunkumar; Cinghu, Senthikumar; Kim, Won Dong; Yu, Jae Ran

2012-01-01

Uterine cervical cancer is still the second largest cancer in women worldwide, despite of effective screening methods. Radiotherapy is used to treat all the stages of cervical cancer and more than 60% of cervical cancer patients receive radiotherapy. New therapeutic targets or approaches are needed to further increase the results of radiotherapy. In the present study, we demonstrated the radiation induced overexpression and nuclear export of FTS in cervical cancer cells. Furthermore, we showed that silencing of FTS expression with FTS shRNA enhanced radiosensitivity of cervical cancer cells, induced cell cycle arrest and apoptosis FTS is involved in radioresistance of cervical cancer. Targeted inhibition of FTS can shutdown the key elemental characteristics of cervical cancer and could lead to an effective therapeutic strategy

Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein.

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Aditi Gupta

2016-03-01

Full Text Available Epistatic interactions between residues determine a protein's adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It has been shown that strong selection increases epistatic interactions as well as the ruggedness of the fitness landscape, but little is known about how the epistatic interactions change under selection in the long-term evolution of a protein. Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1 using protease sequences collected for almost a decade from both treated and untreated patients, to understand how epistasis changes and how those changes impact the long-term evolvability of a protein. We use an information-theoretic proxy for epistasis that quantifies the co-variation between sites, and show that positive information is a necessary (but not sufficient condition that detects epistasis in most cases. We analyze the "fossils" of the evolutionary trajectories of the protein contained in the sequence data, and show that epistasis continues to enrich under strong selection, but not for proteins whose environment is unchanged. The increase in epistasis compensates for the information loss due to sequence variability brought about by treatment, and facilitates adaptation in the increasingly rugged fitness landscape of treatment. While epistasis is thought to enhance evolvability via valley-crossing early-on in adaptation, it can hinder adaptation later when the landscape has turned rugged. However, we find no evidence that the HIV-1 protease has reached its potential for evolution after 9 years of adapting to a drug environment that itself is constantly changing. We suggest that the mechanism of encoding new information into pairwise interactions is central to protein evolution not just in HIV-1 protease, but for any protein adapting to a changing

Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients.

Science.gov (United States)

Logozzi, Mariantonia; Angelini, Daniela F; Iessi, Elisabetta; Mizzoni, Davide; Di Raimo, Rossella; Federici, Cristina; Lugini, Luana; Borsellino, Giovanna; Gentilucci, Alessandro; Pierella, Federico; Marzio, Vittorio; Sciarra, Alessandro; Battistini, Luca; Fais, Stefano

2017-09-10

Prostate specific antigen (PSA) test is the most common, clinically validated test for the diagnosis of prostate cancer (PCa). While neoplastic lesions of the prostate may cause aberrant levels of PSA in the blood, the quantitation of free or complexed PSA poorly discriminates cancer patients from those developing benign lesions, often leading to invasive and unnecessary surgical procedures. Microenvironmental acidity increases exosome release by cancer cells. In this study we evaluated whether acidity, a critical phenotype of malignancy, could influence exosome release and increase the PSA expression in nanovesicles released by PCa cells. To this aim, we exploited Nanoparticle Tracking Analysis (NTA), an immunocapture-based ELISA, and nanoscale flow-cytometry. The results show that microenvironmental acidity induces an increased release of nanovesicles expressing both PSA and the exosome marker CD81. In order to verify whether the changes induced by the local selective pressure of extracellular acidity may correspond to a clinical pathway we used the same approach to evaluate the levels of PSA-expressing exosomes in the plasma of PCa patients and controls, including subjects with benign prostatic hypertrophy (BPH). The results show that only PCa patients have high levels of nanovesicles expressing both CD81 and PSA. This study shows that tumor acidity exerts a selective pressure leading to the release of extracellular vesicles that express both PSA and exosome markers. A comparable scenario was shown in the plasma of prostate cancer patients as compared to both BPH and healthy controls. These results suggest that microenvironmental acidity may represent a key factor which determines qualitatively and quantitatively the release of extracellular vesicles by malignant tumors, including prostate cancer. This condition leads to the spill-over of nanovesicles into the peripheral blood of prostate cancer patients, where the levels of tumor biomarkers expressed by

Natural Selection in Cancer Biology: From Molecular Snowflakes to Trait Hallmarks

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Fortunato, Angelo; Boddy, Amy; Mallo, Diego; Aktipis, Athena; Maley, Carlo C.; Pepper, John W.

2017-01-01

Evolution by natural selection is the conceptual foundation for nearly every branch of biology and increasingly also for biomedicine and medical research. In cancer biology, evolution explains how populations of cells in tumors change over time. It is a fundamental question whether this evolutionary process is driven primarily by natural selection and adaptation or by other evolutionary processes such as founder effects and drift. In cancer biology, as in organismal evolutionary biology, there is controversy about this question and also about the use of adaptation through natural selection as a guiding framework for research. In this review, we discuss the differences and similarities between evolution among somatic cells versus evolution among organisms. We review what is known about the parameters and rate of evolution in neoplasms, as well as evidence for adaptation. We conclude that adaptation is a useful framework that accurately explains the defining characteristics of cancer. Further, convergent evolution through natural selection provides the only satisfying explanation both for how a group of diverse pathologies have enough in common to usefully share the descriptive label of “cancer” and for why this convergent condition becomes life-threatening. PMID:28148564

Increased signaling entropy in cancer requires the scale-free property of protein interaction networks

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Teschendorff, Andrew E.; Banerji, Christopher R. S.; Severini, Simone; Kuehn, Reimer; Sollich, Peter

2015-01-01

One of the key characteristics of cancer cells is an increased phenotypic plasticity, driven by underlying genetic and epigenetic perturbations. However, at a systems-level it is unclear how these perturbations give rise to the observed increased plasticity. Elucidating such systems-level principles is key for an improved understanding of cancer. Recently, it has been shown that signaling entropy, an overall measure of signaling pathway promiscuity, and computable from integrating a sample's gene expression profile with a protein interaction network, correlates with phenotypic plasticity and is increased in cancer compared to normal tissue. Here we develop a computational framework for studying the effects of network perturbations on signaling entropy. We demonstrate that the increased signaling entropy of cancer is driven by two factors: (i) the scale-free (or near scale-free) topology of the interaction network, and (ii) a subtle positive correlation between differential gene expression and node connectivity. Indeed, we show that if protein interaction networks were random graphs, described by Poisson degree distributions, that cancer would generally not exhibit an increased signaling entropy. In summary, this work exposes a deep connection between cancer, signaling entropy and interaction network topology. PMID:25919796

Increase in Complexity and Information through Molecular Evolution

Directory of Open Access Journals (Sweden)

Peter Schuster

2016-11-01

Full Text Available Biological evolution progresses by essentially three different mechanisms: (I optimization of properties through natural selection in a population of competitors; (II development of new capabilities through cooperation of competitors caused by catalyzed reproduction; and (III variation of genetic information through mutation or recombination. Simplified evolutionary processes combine two out of the three mechanisms: Darwinian evolution combines competition (I and variation (III and is represented by the quasispecies model, major transitions involve cooperation (II of competitors (I, and the third combination, cooperation (II and variation (III provides new insights in the role of mutations in evolution. A minimal kinetic model based on simple molecular mechanisms for reproduction, catalyzed reproduction and mutation is introduced, cast into ordinary differential equations (ODEs, and analyzed mathematically in form of its implementation in a flow reactor. Stochastic aspects are investigated through computer simulation of trajectories of the corresponding chemical master equations. The competition-cooperation model, mechanisms (I and (II, gives rise to selection at low levels of resources and leads to symbiontic cooperation in case the material required is abundant. Accordingly, it provides a kind of minimal system that can undergo a (major transition. Stochastic effects leading to extinction of the population through self-enhancing oscillations destabilize symbioses of four or more partners. Mutations (III are not only the basis of change in phenotypic properties but can also prevent extinction provided the mutation rates are sufficiently large. Threshold phenomena are observed for all three combinations: The quasispecies model leads to an error threshold, the competition-cooperation model allows for an identification of a resource-triggered bifurcation with the transition, and for the cooperation-mutation model a kind of stochastic threshold for

BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

International Nuclear Information System (INIS)

Oommen, Deepu; Yiannakis, Dennis; Jha, Awadhesh N.

2016-01-01

Highlights: • BRCA1 deficient cancer cells exhibit increased DNA damage upon auranofin treatment. • Auranofin induces apoptosis in BRCA1 deficient cancer cells despite the activation of Nrf2. • Antioxidant protects BRCA1 deficient cancer cells from auranofin. - Abstract: Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2—related factor 2 (Nrf2) via direct protein–protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.

BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

Energy Technology Data Exchange (ETDEWEB)

Oommen, Deepu [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom); Yiannakis, Dennis [Plymouth Oncology Centre, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth PL6 8DH (United Kingdom); Jha, Awadhesh N., E-mail: a.jha@plymouth.ac.uk [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom)

2016-02-15

Highlights: • BRCA1 deficient cancer cells exhibit increased DNA damage upon auranofin treatment. • Auranofin induces apoptosis in BRCA1 deficient cancer cells despite the activation of Nrf2. • Antioxidant protects BRCA1 deficient cancer cells from auranofin. - Abstract: Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2—related factor 2 (Nrf2) via direct protein–protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.

Increasing physical activity and exercise in lung cancer: reviewing safety, benefits, and application.

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Bade, Brett C; Thomas, D David; Scott, JoAnn B; Silvestri, Gerard A

2015-06-01

Lung cancer continues to be a difficult disease frequently diagnosed in late stages with a high mortality and symptom burden. In part because of frequent lung comorbidity, even lung cancer survivors often remain symptomatic and functionally limited. Though targeted therapy continues to increase treatment options for advanced-stage disease, symptom burden remains high with few therapeutic options. In the last several decades, exercise and physical activity have arisen as therapeutic options for obstructive lung disease and lung cancer. To date, exercise has been shown to reduce symptoms, increase exercise tolerance, improve quality of life, and potentially reduce length of stay and postoperative complications. Multiple small trials have been performed in perioperative non-small-cell lung cancer patients, although fewer studies are available for patients with advanced-stage disease. Despite the increased interest in this subject over the last few years, a validated exercise regimen has not been established for perioperative or advanced-stage disease. Clinicians underutilize exercise and pulmonary rehabilitation as a therapy, in part because of the lack of evidence-based consensus as to how and when to implement increasing physical activity. This review summarizes the existing evidence on exercise in lung cancer patients.

Does the Risk of Metabolic Syndrome Increase in Thyroid Cancer Survivors?

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Kim, Min-Hee; Huh, Jin-Young; Lim, Dong-Jun; Kang, Moo-Il

2017-07-01

The steep rise in thyroid cancer observed in recent decades has caused an increase in the population of long-term thyroid cancer survivors. Other than recurrences of cancer, the long-term health consequences of surviving thyroid cancer, particularly metabolic syndrome, have not yet been determined. The aim of this study was to estimate the risk of metabolic syndrome in thyroid cancer survivors. Population-based data from the Korean National Health and Nutrition Examination Survey (KNHANES) were used for the analysis. The data of KNHANES IV-VI from 2007-2014 were obtained. After excluding subjects who were under 19 years old, whose fasting interval was less than 8 hours, and whose data for predefined variables including metabolic syndrome components were incomplete, 34,347 subjects were analyzed. The incidence of metabolic syndrome and its components were evaluated in three groups: subjects with no history of thyroid cancer, subjects diagnosed with thyroid cancer within 3 years of the survey date, and subjects diagnosed more than 3 years before the survey date. Thyroid cancer diagnoses were made within 3 years of the survey date for 95 subjects (group 1, short-term survivors) and more than 3 years earlier than the survey date for 60 subjects (group 2, long-term survivors). Metabolic syndrome was frequently observed with clinical significance (odds ratio [OR] 1.986 [95% confidence interval [CI] 1.0-3.70], p = 0.030) in short-term survivors compared with subjects with no thyroid cancer history. Risks for having high blood pressure and high fasting glucose were estimated to be higher in the short-term survivor group (OR 2.115 [CI 1.23-3.64], p = 0.006 and OR 1.792 [CI 1.03-3.11], p = 0.038, respectively). No significant associations were noticed in the long-term survivor group when compared with the group with no thyroid cancer history. Risks for metabolic syndrome, especially high blood pressure and high fasting glucose, were increased in short

Evolution of multicellularity coincided with increased diversification of cyanobacteria and the Great Oxidation Event

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Schirrmeister, Bettina E.; de Vos, Jurriaan M.; Antonelli, Alexandre; Bagheri, Homayoun C.

2013-01-01

Cyanobacteria are among the most diverse prokaryotic phyla, with morphotypes ranging from unicellular to multicellular filamentous forms, including those able to terminally (i.e., irreversibly) differentiate in form and function. It has been suggested that cyanobacteria raised oxygen levels in the atmosphere around 2.45–2.32 billion y ago during the Great Oxidation Event (GOE), hence dramatically changing life on the planet. However, little is known about the temporal evolution of cyanobacterial lineages, and possible interplay between the origin of multicellularity, diversification of cyanobacteria, and the rise of atmospheric oxygen. We estimated divergence times of extant cyanobacterial lineages under Bayesian relaxed clocks for a dataset of 16S rRNA sequences representing the entire known diversity of this phylum. We tested whether the evolution of multicellularity overlaps with the GOE, and whether multicellularity is associated with significant shifts in diversification rates in cyanobacteria. Our results indicate an origin of cyanobacteria before the rise of atmospheric oxygen. The evolution of multicellular forms coincides with the onset of the GOE and an increase in diversification rates. These results suggest that multicellularity could have played a key role in triggering cyanobacterial evolution around the GOE. PMID:23319632

Adolescent Cancer Education (ACE) to increase adolescent and parent cancer awareness and communication: study protocol for a cluster randomised controlled trial.

Science.gov (United States)

Kyle, Richard G; Macmillan, Iona; Rauchhaus, Petra; O'Carroll, Ronan; Neal, Richard D; Forbat, Liz; Haw, Sally; Hubbard, Gill

2013-09-08

Raising cancer awareness among adolescents has potential to increase their knowledge and confidence in identifying cancer symptoms and seeking timely medical help in adolescence and adulthood. Detecting cancer at an early stage is important because it reduces the risk of dying of some cancers and thereby contributes to improved cancer survival. Adolescents may also play an important role in increasing cancer communication within families. However, there are no randomised controlled trials (RCT) of the effectiveness of school-based educational interventions to increase adolescents' cancer awareness, and little is known about the role of adolescents in the upward diffusion of cancer knowledge to parents/carers. The aim of this study is to determine the effectiveness of a school-based educational intervention to raise adolescent and parent cancer awareness and adolescent-parent cancer communication. The Adolescent Cancer Education (ACE) study is a school-based, cluster RCT. Twenty secondary schools in the area covered by Glasgow City Council will be recruited. Special schools for adolescents whose additional needs cannot be met in mainstream education are excluded. Schools are randomised to receive a presentation delivered by a Teenage Cancer Trust educator in Autumn 2013 (intervention group) or Spring 2014 following completion of six-month follow-up measures (control group). Participants will be students recruited at the end of their first year of secondary education (S1) (age 12 to 13 years) and one parent/carer for each student, of the student's choice. The primary outcome is recognition of cancer symptoms two weeks post-intervention. Secondary outcomes are parents' cancer awareness and adolescent-parent cancer communication. Outcomes will be assessed at baseline (when adolescents are in the final term of S1), two-week, and six-month follow-up (when adolescents are in S2, age 13 to 14 years). Differences in outcomes between trial arms will be tested using

Incidence of pancreatic cancer in Denmark

DEFF Research Database (Denmark)

Weble, Tanja Cruusberg; Bjerregaard, Jon Kroll; Kissmeyer, Peter

2017-01-01

BACKGROUND: The aim of this study was to monitor the evolution of the incidence of pancreatic cancer in Denmark over 70 years. We also compared registrations of pancreatic cancer in a nationwide population-based database, the Danish Cancer Registry, and a clinical database, the Danish Pancreatic...... Cancer Database, in 2012-2013. MATERIAL AND METHODS: Registrations of pancreatic cancer from the Danish Cancer Registry over 1943-2012 were used to calculate age-specific incidence rates per 100 000 person years by sex and age in 5-year period, weighted by the Segi World Standard Population for age...... standardization. We used absolute numbers from the Cancer Registry and the Pancreatic Cancer Database, including distribution of topography of cancers registered in 2012-2013, to compare registration in the two data sources. RESULTS: The incidence rates of pancreatic cancer among Danish men increased until 1968...

Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

DEFF Research Database (Denmark)

Leeming, Diana J; Byrjalsen, Inger; Qvist, Per

2008-01-01

BACKGROUND: Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in ...... experiments revealed that osteoclasts released CTXI fragments but not CTXII from bone specimens. The same was observed for cathepsin K. CONCLUSION: Data suggest that an uncoupling between bone resorption and cartilage degradation occurs in breast and lung cancer patient....

Increasing Cervical Cancer Awareness and Screening in Jamaica: Effectiveness of a Theory-Based Educational Intervention

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Evelyn Coronado Interis

2015-12-01

Full Text Available Despite declines in cervical cancer mortality in developed countries, cervical cancer incidence and mortality rates remain high in Jamaica due to low levels of screening. Effective interventions are needed to decrease barriers to preventive behaviors and increase adoption of behaviors and services to improve prospects of survival. We enrolled 225 women attending health facilities in an intervention consisting of a pre-test, educational presentation and post-test. The questionnaires assessed attitudes, knowledge, risk factors, and symptoms of cervical cancer among women. Changes in knowledge and intention to screen were assessed using paired t-tests and tests for correlated proportions. Participants were followed approximately six months post-intervention to determine cervical cancer screening rates. We found statistically significant increases from pre-test to post-test in the percentage of questions correctly answered and in participants’ intention to screen for cervical cancer. The greatest improvements were observed in responses to questions on knowledge, symptoms and prevention, with some items increasing up to 62% from pre-test to post-test. Of the 123 women reached for follow-up, 50 (40.7% screened for cervical cancer. This theory-based education intervention significantly increased knowledge of and intention to screen for cervical cancer, and may be replicated in similar settings to promote awareness and increase screening rates.

Increased risk of breast cancer in splenectomized patients undergoing radiation therapy for Hodgkin's disease

International Nuclear Information System (INIS)

Chung, Chung T.; Bogart, Jeffrey A.; Adams, James F.; Sagerman, Robert H.; Numann, Patricia J.; Tassiopoulos, Apostolos; Duggan, David B.

1997-01-01

Purpose: Second malignancies have been reported among patients who were treated by radiation therapy or chemotherapy alone or in combination. Studies have implied an increased risk of breast cancer in women who received radiotherapy as part of their treatment for Hodgkin's disease. This review was performed to determine if there is an association between splenectomy and subsequent breast cancer. Methods and Materials: One hundred and thirty-six female patients with histologically proven Hodgkin's disease were seen in the Division of Radiation Oncology between 1962 and 1985. All patients received mantle or mediastinal irradiation as part of their therapy. The risk of breast cancer was assessed and multiple linear regression analysis was performed on the following variables: patient age, stage, dose and extent of radiation field, time after completing radiation therapy, splenectomy, and chemotheraphy. Results: Breast cancer was observed in 11 of 74 splenectomized patients and in none of 62 patients not splenectomized. The mean follow-up was 13 years in splenectomized patients and 16 years, 7 months in nonsplenectomized patients. Nine patients developed invasive breast cancer and two developed ductal carcinoma in situ. Splenectomy was the only variable independently associated with an increased risk of breast cancer (p < 0.005) in multiple linear regression analysis; age, latency, and splenectomy considered together were also associated with an increased risk of breast cancer (p < 0.01). Conclusion: Our data show an increased risk of breast cancer in splenectomized patients who had treatment for Hodgkin's disease. A multiinstitutional survey may better define the influence of splenectomy relative to developing breast cancer in patients treated for Hodgkin's disease. The risk of breast cancer should be considered when recommending staging laparotomy, and we recommend close follow-up examination including routine mammograms for female patients successfully treated for

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

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

2018-04-06

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

Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer

International Nuclear Information System (INIS)

Meyer-Siegler, Katherine L; Iczkowski, Kenneth A; Vera, Pedro L

2005-01-01

Macrophage migration inhibitory factor (MIF) is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum) levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate. MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis. Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 ± 3.91 ng/ml; ± interquartile range; n = 115) compared with patients with no documented diagnosis of prostate cancer (2.19 ± 2.65 ng/ml; n = 158). ELISA diluent reagents that included bovine serum albumin (BSA) significantly reduced MIF serum detection (p < 0.01). MIF mRNA was localized to prostatic epithelium in all samples, but cancer showed statistically greater MIF expression. MIF and its receptor (CD74) were localized to prostatic epithelium. Increased secreted MIF was detected in culture medium from prostate cancer cell lines (LNCaP and PC-3). Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot) found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic

Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis.

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Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

2009-01-01

Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute

Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

Science.gov (United States)

Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

2009-01-01

Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer

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SHAN, YAN-SHEN; HSU, HUI-PING; LAI, MING-DERG; YEN, MENG-CHI; LUO, YI-PEY; CHEN, YI-LING

2015-01-01

Aberrant expression of argininosuccinate synthetase (ASS1, also known as ASS) has been found in cancer cells and is involved in the carcinogenesis of gastric cancer. The aim of the present study was to investigate the level of ASS expression in human gastric cancer and to determine the possible correlations between ASS expression and clinicopathological findings. Immunohistochemistry was performed on paraffin-embedded tissues to determine whether ASS was expressed in 11 of 11 specimens from patients with gastric cancer. The protein was localized primarily to the cytoplasm of cancer cells and normal epithelium. In the Oncomine cancer microarray database, expression of the ASS gene was significantly increased in gastric cancer tissues. To investigate the clinicopathological and prognostic roles of ASS expression, we performed western blot analysis of 35 matched specimens of gastric adenocarcinomas and normal tissue obtained from patients treated at the National Cheng Kung University Hospital. The ratio of relative ASS expression (expressed as the ASS/β-actin ratio) in tumor tissues to that in normal tissues was correlated with large tumor size (P=0.007) and with the tumor, node, metastasis (TNM) stage of the American Joint Committee on Cancer staging system (P=0.031). Patients whose cancer had increased the relative expression of ASS were positive for perineural invasion and had poor recurrence-free survival. In summary, ASS expression in gastric cancer was associated with a poor prognosis. Further study of mechanisms to silence the ASS gene or decrease the enzymatic activity of ASS protein has the potential to provide new treatments for patients with gastric cancer. PMID:25333458

Increased Expression and Aberrant Localization of Mucin 13 in Metastatic Colon Cancer

Science.gov (United States)

Gupta, Brij K.; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Koch, Michael D.; Lynch, Douglas W.; Bohlmeyer, Teresa; Watanabe, Akira; Aburatani, Hiroyuki; Puumala, Susan E.; Jaggi, Meena

2012-01-01

MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (pcolon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (pcolon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer. PMID:22914648

Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells

DEFF Research Database (Denmark)

Dahl, Malin; Bouchelouche, Pierre; Kramer-Marek, Gabriela

2011-01-01

Increasing evidence suggests that Human epidermal growth factor receptor 2 (HER2/neu) is involved in progression of prostate cancer. Recently, sarcosine was reported to be highly increased during prostate cancer progression, and exogenous sarcosine induces an invasive phenotype in benign prostate...... epithelial cells. The aim of this work was to investigate the effect of sarcosine on HER2/neu expression in prostate cancer cell lines LNCaP (androgen dependent), PC-3 and DU145 (both androgen independent). Relative amounts of HER2/neu and androgen receptor (AR) transcripts were determined using RT...... that sarcosine is involved in the regulation of the oncoprotein HER2/neu. Thus, sarcosine may induce prostate cancer progression by increased HER2/neu expression. However, detailed information on cellular mechanisms remains to be elucidated....

High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma.

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Firdaus S Dhabhar

Full Text Available In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED, 3 times/week, 10-weeks. The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome, and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th, cytolytic (CTL, and regulatory (Treg T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden, increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression, lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity, and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis. These results suggest that the deleterious effects of high trait anxiety

Tumor progression: chance and necessity in Darwinian and Lamarckian somatic (mutationless) evolution.

Science.gov (United States)

Huang, Sui

2012-09-01

Current investigation of cancer progression towards increasing malignancy focuses on the molecular pathways that produce the various cancerous traits of cells. Their acquisition is explained by the somatic mutation theory: tumor progression is the result of a neo-Darwinian evolution in the tissue. Herein cells are the units of selection. Random genetic mutations permanently affecting these pathways create malignant cell phenotypes that are selected for in the disturbed tissue. However, could it be that the capacity of the genome and its gene regulatory network to generate the vast diversity of cell types during development, i.e., to produce inheritable phenotypic changes without mutations, is harnessed by tumorigenesis to propel a directional change towards malignancy? Here we take an encompassing perspective, transcending the orthodoxy of molecular carcinogenesis and review mechanisms of somatic evolution beyond the Neo-Darwinian scheme. We discuss the central concept of "cancer attractors" - the hidden stable states of gene regulatory networks normally not occupied by cells. Noise-induced transitions into such attractors provide a source for randomness (chance) and regulatory constraints (necessity) in the acquisition of novel expression profiles that can be inherited across cell divisions, and hence, can be selected for. But attractors can also be reached in response to environmental signals - thus offering the possibility for inheriting acquired traits that can also be selected for. Therefore, we face the possibility of non-genetic (mutation-independent) equivalents to both Darwinian and Lamarckian evolution which may jointly explain the arrow of change pointing toward increasing malignancy. Copyright © 2012 Elsevier Ltd. All rights reserved.

CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

DEFF Research Database (Denmark)

Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul

2012-01-01

PURPOSE We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS From 22 studies participating in the Breast Cancer Assoc...

Are cancer survivors at an increased risk for divorce? A Danish cohort study

DEFF Research Database (Denmark)

Carlsen, Kathrine; Dalton, Susanne Oksbjerg; Frederiksen, Kirsten

2007-01-01

for survivors of cervix cancer, who had an increased risk for divorce, we found that cancer survivors were not at greater risk for divorce than the general population (rate ratios (RR), 1.06; 95% confidence interval (CI), 1.0;1.1 and RR, 0.98; 95% CI, 0.9;1.0 for women and men, respectively). This finding shows......The purpose of this study was to determine the risk for divorce among cancer survivors. We conducted a nationwide, population-based study of 46,303 persons aged 30-60 years in whom selected cancers were diagnosed in 1981-2000 and 221,028 randomly sampled, cancer-free controls. Information...... that cancer survivors need not have unnecessary fears for their marriage....

The influence of UV radiation on protistan evolution

Science.gov (United States)

Rothschild, L. J.

1999-01-01

Ultraviolet radiation has provided an evolutionary challenge to life on Earth. Recent increases in surficial ultraviolet B fluxes have focused attention on the role of UV radiation in protistan ecology, cancer, and DNA damage. Exploiting this new wealth of data, I examine the possibility that ultraviolet radiation may have played a significant role in the evolution of the first eukaryotes, that is, protists. Protists probably arose well before the formation of a significant ozone shield, and thus were probably subjected to substantial ultraviolet A, ultraviolet B, and ultraviolet C fluxes early in their evolution. Evolution consists of the generation of heritable variations and the subsequent selection of these variants. Ultraviolet radiation has played a role both as a mutagen and as a selective agent. In its role as a mutagen, it may have been crucial in the origin of sex and as a driver of molecular evolution. As a selective agent, its influence has been broad. Discussed in this paper are the influence of ultraviolet radiation on biogeography, photosynthesis, and desiccation resistance.

Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4

LENUS (Irish Health Repository)

Cronin, Patricia A

2010-05-21

Abstract Background Chemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α. Methods Three breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability. Results CXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-α in vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness. Conclusions CXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.

The increasing incidence of anal cancer: can it be explained by trends in risk groups?

NARCIS (Netherlands)

van der Zee, R. P.; Richel, O.; de Vries, H. J. C.; Prins, J. M.

2013-01-01

Anal cancer incidence is gradually increasing. The cause of this increase is not exactly known. This systematic literature review aimed to investigate the trend in time of anal cancer incidence and to find an explanation for the supposed increase. The TRIP database and PubMed were searched for

The Increasing Incidence of Thyroid Cancer: The Influence of Access to Care

Science.gov (United States)

Sikora, Andrew G.; Tosteson, Tor D.

2013-01-01

Background The rapidly rising incidence of papillary thyroid cancer may be due to overdiagnosis of a reservoir of subclinical disease. To conclude that overdiagnosis is occurring, evidence for an association between access to health care and the incidence of cancer is necessary. Methods We used Surveillance, Epidemiology, and End Results (SEER) data to examine U.S. papillary thyroid cancer incidence trends in Medicare-age and non–Medicare-age cohorts over three decades. We performed an ecologic analysis across 497 U.S. counties, examining the association of nine county-level socioeconomic markers of health care access and the incidence of papillary thyroid cancer. Results Papillary thyroid cancer incidence is rising most rapidly in Americans over age 65 years (annual percentage change, 8.8%), who have broad health insurance coverage through Medicare. Among those under 65, in whom health insurance coverage is not universal, the rate of increase has been slower (annual percentage change, 6.4%). Over three decades, the mortality rate from thyroid cancer has not changed. Across U.S. counties, incidence ranged widely, from 0 to 29.7 per 100,000. County papillary thyroid cancer incidence was significantly correlated with all nine sociodemographic markers of health care access: it was positively correlated with rates of college education, white-collar employment, and family income; and negatively correlated with the percentage of residents who were uninsured, in poverty, unemployed, of nonwhite ethnicity, non-English speaking, and lacking high school education. Conclusion Markers for higher levels of health care access, both sociodemographic and age-based, are associated with higher papillary thyroid cancer incidence rates. More papillary thyroid cancers are diagnosed among populations with wider access to healthcare. Despite the threefold increase in incidence over three decades, the mortality rate remains unchanged. Together with the large subclinical reservoir of

Colorectal Cancer Screening: An Educational Intervention for Nurse Practitioners to Increase Screening Awareness and Participation
.

Science.gov (United States)

Slyne, Tai C; Gautam, Ramraj; King, Valerie

2017-10-01

Colorectal cancer screening aims to detect colorectal cancer at an early stage, when treatment is more likely to be curative. Lack of participation in such screening is a major issue in primary care practices, where nurse practitioners (NPs) often provide care. This study aimed to determine whether an educational intervention for NPs would increase their awareness of, and increase patients' participation in, colorectal cancer screening. 
.

Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma

Science.gov (United States)

Chen, Tiantian; Cheng, Hongwei; Chen, Xingdong; Yuan, Ziyu; Yang, Xiaorong; Zhuang, Maoqiang; Lu, Ming; Jin, Li; Ye, Weimin

2015-01-01

A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire, and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42–2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74–36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54–2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk. PMID:26526791

Contribution of increased mutagenesis to the evolution of pollutants-degrading indigenous bacteria

Science.gov (United States)

Ilmjärv, Tanel; Naanuri, Eve; Kivisaar, Maia

2017-01-01

Bacteria can rapidly evolve mechanisms allowing them to use toxic environmental pollutants as a carbon source. In the current study we examined whether the survival and evolution of indigenous bacteria with the capacity to degrade organic pollutants could be connected with increased mutation frequency. The presence of constitutive and transient mutators was monitored among 53 pollutants-degrading indigenous bacterial strains. Only two strains expressed a moderate mutator phenotype and six were hypomutators, which implies that constitutively increased mutability has not been prevalent in the evolution of pollutants degrading bacteria. At the same time, a large proportion of the studied indigenous strains exhibited UV-irradiation-induced mutagenesis, indicating that these strains possess error-prone DNA polymerases which could elevate mutation frequency transiently under the conditions of DNA damage. A closer inspection of two Pseudomonas fluorescens strains PC20 and PC24 revealed that they harbour genes for ImuC (DnaE2) and more than one copy of genes for Pol V. Our results also revealed that availability of other nutrients in addition to aromatic pollutants in the growth environment of bacteria affects mutagenic effects of aromatic compounds. These results also implied that mutagenicity might be affected by a factor of how long bacteria have evolved to use a particular pollutant as a carbon source. PMID:28777807

Evolution of the Sauropterygian Labyrinth with Increasingly Pelagic Lifestyles.

Science.gov (United States)

Neenan, James M; Reich, Tobias; Evers, Serjoscha W; Druckenmiller, Patrick S; Voeten, Dennis F A E; Choiniere, Jonah N; Barrett, Paul M; Pierce, Stephanie E; Benson, Roger B J

2017-12-18

Sauropterygia, a successful clade of marine reptiles abundant in aquatic ecosystems of the Mesozoic, inhabited nearshore to pelagic habitats over >180 million years of evolutionary history [1]. Aquatic vertebrates experience strong buoyancy forces that allow movement in a three-dimensional environment, resulting in structural convergences such as flippers and fish-like bauplans [2, 3], as well as convergences in the sensory systems. We used computed tomographic scans of 19 sauropterygian species to determine how the transition to pelagic lifestyles influenced the evolution of the endosseous labyrinth, which houses the vestibular sensory organ of balance and orientation [4]. Semicircular canal geometries underwent distinct changes during the transition from nearshore Triassic sauropterygians to the later, pelagic plesiosaurs. Triassic sauropterygians have dorsoventrally compact, anteroposteriorly elongate labyrinths, resembling those of crocodylians. In contrast, plesiosaurs have compact, bulbous labyrinths, sharing some features with those of sea turtles. Differences in relative labyrinth size among sauropterygians correspond to locomotory differences: bottom-walking [5, 6] placodonts have proportionally larger labyrinths than actively swimming taxa (i.e., all other sauropterygians). Furthermore, independent evolutionary origins of short-necked, large-headed "pliosauromorph" body proportions among plesiosaurs coincide with reductions of labyrinth size, paralleling the evolutionary history of cetaceans [7]. Sauropterygian labyrinth evolution is therefore correlated closely with both locomotory style and body proportions, and these changes are consistent with isolated observations made previously in other marine tetrapods. Our study presents the first virtual reconstructions of plesiosaur endosseous labyrinths and the first large-scale, quantitative study detailing the effects of increasingly aquatic lifestyles on labyrinth morphology among marine reptiles. Copyright

Redes En Acción. Increasing Hispanic participation in cancer research, training, and awareness.

Science.gov (United States)

Ramirez, Amelie G; Talavera, Gregory A; Marti, Jose; Penedo, Frank J; Medrano, Martha A; Giachello, Aida L; Pérez-Stable, Eliseo J

2006-10-15

Hispanics are affected by many health care disparities. The National Cancer Institute (NCI), through its Special Populations Branch, is supporting networking and capacity-building activities designed to increase Hispanic participation and leadership in cancer research. Redes En Acción established a national network of cancer research centers, community-based organizations, and federal partners to facilitate opportunities for junior Hispanic scientists to participate in training and research projects on cancer control. Since 2000, Redes En Acción has established a network of more than 1800 Hispanic leaders involved in cancer research and education. The project has sustained 131 training positions and submitted 29 pilot projects to NCI for review, with 16 awards for a total of $800,000, plus an additional $8.8 million in competing grant funding based on pilot study results to date. Independent research has leveraged an additional $32 million in non-Redes funding, and together the national and regional network sites have participated in more than 1400 community and professional awareness events. In addition, the program conducted extensive national survey research that provided the basis for the Redes En Acción Latino Cancer Report, a national agenda on Hispanic cancer issues. Redes En Acción has increased participation in cancer control research, training, and awareness among Hispanic scientists and within Hispanic communities. Cancer 2006. (c) 2006 American Cancer Society.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

Energy Technology Data Exchange (ETDEWEB)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Mok, Tony S.K. [Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Warner, Timothy D. [The William Harvey Research Institute, Queen Mary University of London, London (United Kingdom); Underwood, Malcolm J. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Chen, George G., E-mail: gchen@cuhk.edu.hk [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong)

2009-10-15

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB{sub 2}) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB{sub 2} but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

International Nuclear Information System (INIS)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S.; Mok, Tony S.K.; Warner, Timothy D.; Underwood, Malcolm J.; Chen, George G.

2009-01-01

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB 2 ) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB 2 but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Integrative exercise and lifestyle intervention increases leisure-time activity in breast cancer patients

DEFF Research Database (Denmark)

Casla, Soraya; Hojman, Pernille; Cubedo, Ricardo

2014-01-01

BACKGROUND: Physical activity has been demonstrated to increase survival in breast cancer patients, but few breast cancer patients meet the general recommendations for physical activity. The aim of this pilot study was to investigate if a supervised integrated counseling and group-based exercise...... program could increase leisure-time activity in women with breast cancer. METHODS: This pilot project, designed as a single-arm study with pre-post testing, consisted of 24 classes of combined aerobic and strength exercise training as well as classes on dietary and health behavior. A total of 48 women...... with breast cancer who were undergoing or had recently completed anticancer treatment completed the study. Leisure-time physical activity, grip strength, functional capacity, quality of life (QoL), and depression were assessed at baseline, after intervention, and at the 12-week follow-up after intervention...

Increasing Breast Cancer Surveillance among African American Breast Cancer Survivors

National Research Council Canada - National Science Library

Thompson, Hayley

2005-01-01

...; they also are at considerable risk for breast cancer recurrence. According to the American Society of Clinical Oncology, survivors should undergo careful breast cancer surveillance, including annual mammography and breast self-exam...

Increased risk of colorectal cancer in type 2 diabetes is independent of diet quality.

Directory of Open Access Journals (Sweden)

Soghra Jarvandi

Full Text Available Poor diet increases the risk of both colorectal cancer and type 2 diabetes. We investigated the role of diet in the association between diabetes and colorectal cancer.We analyzed data from 484,020 individuals, aged 50-71 years who participated in the prospective National Institutes of Health-AARP Diet and Health Study and were cancer free at baseline (1995-1996. History of diabetes was self-reported. Diet quality was measured with the Healthy Eating Index-2005 (HEI-2005, using a self-administered food-frequency questionnaire. Cox regression models were constructed to estimate the hazard ratios (HR and 95% confidence intervals (CI of first primary incident colorectal cancer, overall and by anatomical location.During an average follow-up of 9.2 years, we identified 7,598 new cases of colorectal cancer. After controlling for non-dietary confounders, diabetes was associated with increased risk of colorectal cancer (HR 1.27, 95% CI: 1.18, 1.36. Further adjustment for diet quality did not attenuate this association. Diabetes was associated with a HR of 1.23 (95% CI: 1.07, 1.40 in individuals with good diet (quartile 4 of HEI-2005 and 1.58 (95% CI: 1.34, 1.86 in those with poor diet (quartile 1 of HEI-2005, compared to those with no diabetes and good diet. Moreover, diabetes was associated with a stronger risk of proximal than distal colon cancer (HR: 1.33 vs. HR: 1.20, while poor diet was associated with a weaker risk of proximal colon cancer (HR: 1.18 vs. HR: 1.46.Diabetes and poor diet, independently and additively are associated with the increased risk of colorectal cancer.

Brain cancer mortality rates increase with Toxoplasma gondii seroprevalence in France

Science.gov (United States)

Vittecoq, Marion; Elguero, Eric; Lafferty, Kevin D.; Roche, Benjamin; Brodeur, Jacques; Gauthier-Clerc, Michel; Missé, Dorothée; Thomas, Frédéric

2012-01-01

The incidence of adult brain cancer was previously shown to be higher in countries where the parasite Toxoplasma gondii is common, suggesting that this brain protozoan could potentially increase the risk of tumor formation. Using countries as replicates has, however, several potential confounding factors, particularly because detection rates vary with country wealth. Using an independent dataset entirely within France, we further establish the significance of the association between T. gondii and brain cancer and find additional demographic resolution. In adult age classes 55 years and older, regional mortality rates due to brain cancer correlated positively with the local seroprevalence of T. gondii. This effect was particularly strong for men. While this novel evidence of a significant statistical association between T. gondii infection and brain cancer does not demonstrate causation, these results suggest that investigations at the scale of the individual are merited.

Increased frequency of single base substitutions in a population of transcripts expressed in cancer cells

Directory of Open Access Journals (Sweden)

Bianchetti Laurent

2012-11-01

Full Text Available Abstract Background Single Base Substitutions (SBS that alter transcripts expressed in cancer originate from somatic mutations. However, recent studies report SBS in transcripts that are not supported by the genomic DNA of tumor cells. Methods We used sequence based whole genome expression profiling, namely Long-SAGE (L-SAGE and Tag-seq (a combination of L-SAGE and deep sequencing, and computational methods to identify transcripts with greater SBS frequencies in cancer. Millions of tags produced by 40 healthy and 47 cancer L-SAGE experiments were compared to 1,959 Reference Tags (RT, i.e. tags matching the human genome exactly once. Similarly, tens of millions of tags produced by 7 healthy and 8 cancer Tag-seq experiments were compared to 8,572 RT. For each transcript, SBS frequencies in healthy and cancer cells were statistically tested for equality. Results In the L-SAGE and Tag-seq experiments, 372 and 4,289 transcripts respectively, showed greater SBS frequencies in cancer. Increased SBS frequencies could not be attributed to known Single Nucleotide Polymorphisms (SNP, catalogued somatic mutations or RNA-editing enzymes. Hypothesizing that Single Tags (ST, i.e. tags sequenced only once, were indicators of SBS, we observed that ST proportions were heterogeneously distributed across Embryonic Stem Cells (ESC, healthy differentiated and cancer cells. ESC had the lowest ST proportions, whereas cancer cells had the greatest. Finally, in a series of experiments carried out on a single patient at 1 healthy and 3 consecutive tumor stages, we could show that SBS frequencies increased during cancer progression. Conclusion If the mechanisms generating the base substitutions could be known, increased SBS frequency in transcripts would be a new useful biomarker of cancer. With the reduction of sequencing cost, sequence based whole genome expression profiling could be used to characterize increased SBS frequency in patient’s tumor and aid diagnostic.

Increased frequency of single base substitutions in a population of transcripts expressed in cancer cells

International Nuclear Information System (INIS)

Bianchetti, Laurent; Kieffer, David; Féderkeil, Rémi; Poch, Olivier

2012-01-01

Single Base Substitutions (SBS) that alter transcripts expressed in cancer originate from somatic mutations. However, recent studies report SBS in transcripts that are not supported by the genomic DNA of tumor cells. We used sequence based whole genome expression profiling, namely Long-SAGE (L-SAGE) and Tag-seq (a combination of L-SAGE and deep sequencing), and computational methods to identify transcripts with greater SBS frequencies in cancer. Millions of tags produced by 40 healthy and 47 cancer L-SAGE experiments were compared to 1,959 Reference Tags (RT), i.e. tags matching the human genome exactly once. Similarly, tens of millions of tags produced by 7 healthy and 8 cancer Tag-seq experiments were compared to 8,572 RT. For each transcript, SBS frequencies in healthy and cancer cells were statistically tested for equality. In the L-SAGE and Tag-seq experiments, 372 and 4,289 transcripts respectively, showed greater SBS frequencies in cancer. Increased SBS frequencies could not be attributed to known Single Nucleotide Polymorphisms (SNP), catalogued somatic mutations or RNA-editing enzymes. Hypothesizing that Single Tags (ST), i.e. tags sequenced only once, were indicators of SBS, we observed that ST proportions were heterogeneously distributed across Embryonic Stem Cells (ESC), healthy differentiated and cancer cells. ESC had the lowest ST proportions, whereas cancer cells had the greatest. Finally, in a series of experiments carried out on a single patient at 1 healthy and 3 consecutive tumor stages, we could show that SBS frequencies increased during cancer progression. If the mechanisms generating the base substitutions could be known, increased SBS frequency in transcripts would be a new useful biomarker of cancer. With the reduction of sequencing cost, sequence based whole genome expression profiling could be used to characterize increased SBS frequency in patient’s tumor and aid diagnostic

Benign Thyroid Conditions Associated with Increased Risk of Thyroid Cancer Later in Life

Science.gov (United States)

In a new study from the National Cancer Institute and Aarhus University Hospital in Denmark, researchers report an association between diagnosis of hyperthyroidism and thyroiditis (inflammation of the thyroid gland), two benign thyroid conditions, and increased risk of differentiated thyroid cancer.

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

Science.gov (United States)

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.

Cancer and Evolution

International Nuclear Information System (INIS)

Guevara Pardo, Gonzalo

2001-01-01

First it was the luminous idea of the natural selection, proposed by Alfred Russell Wallace and Talk Darwin, the one that allowed understanding the way as the living organisms are evolve. Then they were the brilliant Francis Crick and James Watson who discovered the curvilinear molecule of deoxyribonucleic acid (DNA) and then it was the great explosion of the molecular biology. The cancer, illness that wakes up our deepest fears, is analyzed in this article from an evolutionary conception that could give us a road but appropriate to understand it and maybe to guide us toward better therapeutic options

INCREASE INCOME AND MORTALITY OF COLORRECTAL CANCER IN BRAZIL, 2001-2009

Directory of Open Access Journals (Sweden)

Raphael Mendonca GUIMARAES

2013-03-01

Full Text Available Context Several international studies have observed a correlation between the improvement of socio-demographic indicators and rates of incidence and mortality from cancer of the colon and rectum. Objective The objective of this study is to estimate the correlation between average per capita income and the rate of colorectal cancer mortality in Brazil between 2001 and 2009. Methods We obtained data on income inequality (Gini index, population with low incomes (½ infer the minimum wage/month, average family income, per capita ICP and mortality from colon cancer and straight between 2001-2009 by DATASUS. A trend analysis was performed using linear regression, and correlation between variables by Pearson's correlation coefficient. Results There was a declining trend in poverty and income inequality, and growth in ICP per capita and median family income and standardized mortality rate for colorectal cancer in Brazil. There was also strong positive correlation between mortality from this site of cancer and inequality (men r = -0.30, P = 0.06, women r = -0.33, P = 0.05 income low income (men r = -0.80, P<0.001, women r = -0.76, P<0.001, median family income (men r = 0.79, P = 0.06, women r = 0.76, P<0.001 and ICP per capita (men r = 0.73, P<0.001, women r = 0.68, P<0.001 throughout the study period. Conclusion The increase of income and reducing inequality may partially explain the increased occurrence of colorectal cancer and this is possibly due to differential access to food recognized as a risk factor, such as red meat and high in fat. It is important therefore to assess the priority of public health programs addressing nutrition in countries of intermediate economy, as is the case of Brazil.

A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

Science.gov (United States)

Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

2017-04-01

Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of 25 nm and vertical distance of 1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.

Chemotherapy increases caspase-cleaved cytokeratin 18 in the serum of breast cancer patients

International Nuclear Information System (INIS)

Ulukaya, Engin; Karaagac, Esra; Ari, Ferda; Oral, Arzu Y.; Adim, Saduman B.; Tokullugil, Asuman H.; Evrensel, Türkkan

2011-01-01

Apoptosis is thought to be induced by chemotherapy in cancer patients. Therefore, the measurement of its amplitude may be a useful tool to predict the effectiveness of cancer treatment sooner than conventional methods do. In the study presented, apoptosis was assessed with an ELISA-based assay in which caspase-cleaved cytokeratin 18 (M30-antigen), a novel specific biomarker of apoptosis, is measured. Thirty seven patients with malignant (nonmetastatic and metastatic) breast cancer, 35 patients with benign breast disease, and 34 healthy subjects were studied. Cancer patients received neoadjuvant chemotherapy consisting of either fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin plus docetaxel (ED). Apoptosis was detected before chemotherapy, 24 and 48 h after chemotherapy in the malignant group. It was found that the baseline apoptosis level in either malignant but nonmetastatic group or benign group was not statistically different from that in the control group (p>0.05). However, it was statistically significantly higher in the metastatic group than that in the control group (p<0.05). Following the drug application, M30-antigen levels significantly increased at 24 h (p<0.05). The baseline M30-antigen levels increased about 3-times in patients showing tumor regression. M30-antigen level is increased after chemotherapy and its measurement may help clinicians to predict the effectiveness of chemotherapy sooner in breast cancer cases although confirmative larger trials are needed

Incidence, management, and course of cancer in patients with inflammatory bowel disease.

Science.gov (United States)

Algaba, Alicia; Guerra, Iván; Marín-Jiménez, Ignacio; Quintanilla, Elvira; López-Serrano, Pilar; García-Sánchez, María Concepción; Casis, Begoña; Taxonera, Carlos; Moral, Ignacio; Chaparro, María; Martín-Rodríguez, Daniel; Martín-Arranz, María Dolores; Manceñido, Noemí; Menchén, Luis; López-Sanromán, Antonio; Castaño, Ángel; Bermejo, Fernando

2015-04-01

Patients with inflammatory bowel disease [IBD] are at increased risk for developing some types of neoplasia. Our aims were to determin the risk for cancer in patients with IBD and to describe the relationship with immunosuppressive therapies and clinical management after tumor diagnosis. Retrospective, multicenter, observational, 5-year follow-up, cohort study. Relative risk [RR] of cancer in the IBD cohort and the background population, therapeutic strategies, and cancer evolution were analyzed. A total of 145 cancers were diagnosed in 133 of 9100 patients with IBD (global cumulative incidence 1.6% vs 2.4% in local population; RR = 0.67; 95% confidence interval [CI]: 0.57-0.78). Patients with IBD had a significantly increased RR of non-melanoma skin cancer [RR = 3.85; 2.53-5.80] and small bowel cancer [RR = 3.70; 1.23-11.13]. After cancer diagnosis, IBD treatment was maintained in 13 of 27 [48.1%] patients on thiopurines, in 2 of 3 on methotrexate [66.6%], none on anti-TNF-α monotherapy [n = 6] and 4 of 12 [33.3%] patients on combined therapy. Rate of death and cancer remission during follow-up did not differ [p > 0.05] between patients who maintained the treatment compared with patients who withdrew [5% vs 8% and 95% vs 74%, respectively]. An association between thiopurines [p = 0.20] or anti-TNF-α drugs [p = 0.77] and cancer was not found. Patients with IBD have an increased risk for non-melanoma skin cancer and small bowel cancer. Immunosuppresive therapy is not related to a higher overall risk for cancer or worse tumor evolution in patients who maintain these drugs after cancer diagnosis. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Does fertility treatment increase the risk of uterine cancer? A meta-analysis.

Science.gov (United States)

Saso, Srdjan; Louis, Louay S; Doctor, Farah; Hamed, Ali Hassan; Chatterjee, Jayanta; Yazbek, Joseph; Bora, Shabana; Abdalla, Hossam; Ghaem-Maghami, Sadaf; Thum, Meen-Yau

2015-12-01

An ongoing debate over the last two decades has focused on whether fertility treatment in women may lead to an increased risk of developing uterine cancer over a period of time. Uterine cancer (including mainly endometrial carcinoma and the less common uterine sarcoma) is the commonest reproductive tract cancer and the fourth commonest cancer in women in the UK. Our objective was to assess the association between fertility drugs used in the treatment of female infertility (both as an independent therapy and during in vitro fertilization cycles) and the development of uterine cancer. A literature search was performed using Medline, Embase, Cochrane Library and Google Scholar databases for comparative studies until December 2014 to investigate a clinical significance of fertility treatment on the incidence of developing uterine cancer. General and MESH search headings, as well as the 'related articles' function were applied. All comparative studies of 'fertility treatment' versus 'non-fertility treatment' reporting the incidence of uterine cancer as an outcome were included. Uterine cancer incorporated the following terms: uterine cancer, uterine body tumours, uterine sarcomas and endometrial cancers. The primary outcome of interest was the uterine cancer incidence in all 'fertility treatment' versus 'non-fertility treatment' patient groups. Secondary outcomes of interest were: (a) uterine cancer incidence in 'IVF' versus 'non-IVF' patient groups; and (b) uterine cancer incidence according to type of fertility drug used. Odds ratio was the summary statistic. Random-effects modelling, graphical exploration and sensitivity analysis were used to evaluate the consistency of the calculated treatment effect. We included six studies in our final analysis, which comprised 776,224 patients in total. Of these, 103,758 had undergone fertility treatment and 672,466 had not. There was 100% agreement between the two reviewers regarding the data extraction. All the studies

Cancer prehabilitation: an opportunity to decrease treatment-related morbidity, increase cancer treatment options, and improve physical and psychological health outcomes.

Science.gov (United States)

Silver, Julie K; Baima, Jennifer

2013-08-01

Cancer prehabilitation, a process on the continuum of care that occurs between the time of cancer diagnosis and the beginning of acute treatment, includes physical and psychological assessments that establish a baseline functional level, identifies impairments, and provides targeted interventions that improve a patient's health to reduce the incidence and the severity of current and future impairments. There is a growing body of scientific evidence that supports preparing newly diagnosed cancer patients for and optimizing their health before starting acute treatments. This is the first review of cancer prehabilitation, and the purpose was to describe early studies in the noncancer population and then the historical focus in cancer patients on aerobic conditioning and building strength and stamina through an appropriate exercise regimen. More recent research shows that opportunities exist to use other unimodal or multimodal prehabilitation interventions to decrease morbidity, improve physical and psychological health outcomes, increase the number of potential treatment options, decrease hospital readmissions, and reduce both direct and indirect healthcare costs attributed to cancer. Future research may demonstrate increased compliance with acute cancer treatment protocols and, therefore, improved survival outcomes. New studies suggest that a multimodal approach that incorporates both physical and psychological prehabilitation interventions may be more effective than a unimodal approach that addresses just one or the other. In an impairment-driven cancer rehabilitation model, identifying current and anticipating future impairments are the critical first steps in improving healthcare outcomes and decreasing costs. More research is urgently needed to evaluate the most effective prehabilitation interventions, and combinations thereof, for survivors of all types of cancer.

The evolution of the epidemiological landscape of head and neck cancer in Italy: Is there evidence for an increase in the incidence of potentially HPV-related carcinomas?

Directory of Open Access Journals (Sweden)

Paolo Boscolo-Rizzo

Full Text Available The current study aimed to investigate the incidence and survival patterns of HNSCCs arising from different anatomic sites, potentially related (the oropharynx or unrelated (the oral cavity, the larynx/hypopharynx to HPV, to provide clues on possible growing impact of HPV in the epidemiology of HNSCC in Italy. Epidemiological data were retrieved from ten long-term Cancer Registries covering a population of 7.8 million inhabitants. Trends were described by means of the estimated annual percent change (APC stratified by age and gender, and compared between HPV-related and HPV-unrelated anatomical sites. The data regarding 28,295 HNSCCs diagnosed in Italy between 1988 and 2012 were analyzed. In males, the incidence rate (IR of cancers arising from sites unrelated to HPV infection significantly decreased in all age groups (APC:-3.31 for larynx/hypopharynx; APC:-1.77 for oral cavity, whereas stable IR were observed for cancers arising from sites related to HPV infection. In females, IR for cancers from HPV-related sites increased significantly over the observed period; the largest increment was noted in those over 60 (APC:2.92% who also showed a significantly lower number of HNSCCs from the larynx/hypopharynx (APC:- 0.84 and a significantly higher number of oral cavity tumors (APC = 2.15. The five-year relative survival remained largely unchanged in the patients with laryngeal/hypopharyngeal SCC and, conversely, significantly improved in the patients with SCC at HPV-related sites. The trends observed suggest a potential increasing impact of HPV infection on the epidemiology of HNSCC in Italy, but to a lesser extent and with a different pattern from that observed in other Western countries.

Prostatic irradiation is not associated with any measurable increase in the risk of subsequent rectal cancer

International Nuclear Information System (INIS)

Kendal, Wayne S.; Eapen, Libni; MacRae, Robert; Malone, Shawn; Nicholas, Garth

2006-01-01

Purpose: To investigate a putative increased risk of rectal cancer subsequent to prostatic radiotherapy. Methods and Materials: In an analysis of the Surveillance, Epidemiology, and End Results registry, we compared men who had radiotherapy for prostatic carcinoma with those treated surgically and those treated with neither modality. Kaplan-Meier analyses for the time to failure from rectal cancer were performed between age-matched subgroups of the three cohorts. Cox proportional hazards analyses were performed to ascertain what influences might affect the incidence of subsequent rectal cancer. Results: In all, 33,831 men were irradiated, 167,607 were treated surgically, and 36,335 received neither modality. Rectal cancers developed in 243 (0.7%) of those irradiated (mean age, 70.7 years), 578 (0.3%) of those treated surgically (68.7 years), and 227 (0.8%) of those treated with neither modality (74.2 years). When age effects and the differences between the surgical and untreated cohorts were controlled for, we were unable to demonstrate any significant increased incidence of rectal cancer in men irradiated for prostatic cancer. Conclusions: An increased frequency of rectal cancer after prostatic irradiation, apparent on crude analysis, could be attributed to age confounding and other unmeasured confounders associated with prostate cancer treatment and rectal cancer risk

Increased fracture rate in women with breast cancer: a review of the hidden risk

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Body Jean-Jacques

2011-08-01

Full Text Available Abstract Background Women with breast cancer, particularly individuals diagnosed at a relatively early age, have an increased incidence of fractures. Fractures can have serious clinical consequences including the need for major surgery, increased morbidity and mortality, increased cost of disease management, and reduced quality of life for patients. The primary cause of the increased fracture risk appears to be an accelerated decrease in bone mineral density (BMD resulting from the loss of estrogenic signaling that occurs with most treatments for breast cancer, including aromatase inhibitors. However, factors other than BMD levels alone may influence treatment decisions to reduce fracture risk in this setting. Our purpose is to review current evidence for BMD loss and fracture risk during treatment for breast cancer and discuss pharmacologic means to reduce this risk. Results Fracture risk during treatment for breast cancer may be influenced by the rate of BMD loss and the consequent rapid alterations in bone microarchitecture, in addition to the established fracture risk factors in postmenopausal osteoporosis. The rapid decrease in BMD during adjuvant chemoendocrine therapy for breast cancer may necessitate more aggressive pharmacotherapy than is indicated for healthy postmenopausal women who develop osteoporosis. Over the last few years, clinical trials have established the effectiveness of bisphosphonates and other antiresorptive agents to preserve BMD during adjuvant therapy for early breast cancer. In addition, some bisphosphonates (eg, zoledronic acid may also delay disease recurrence in women with hormone-responsive tumors, thereby providing an adjuvant benefit in addition to preserving BMD and potentially preventing fractures. Conclusions It is likely that a combined fracture risk assessment (eg, as in the WHO FRAX algorithm will more accurately identify both women with postmenopausal osteoporosis and women with breast cancer who require

Increasing incidence of thyroid cancer in the Nordic countries with main focus on Swedish data.

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Carlberg, Michael; Hedendahl, Lena; Ahonen, Mikko; Koppel, Tarmo; Hardell, Lennart

2016-07-07

Radiofrequency radiation in the frequency range 30 kHz-300 GHz was evaluated to be Group 2B, i.e. 'possibly' carcinogenic to humans, by the International Agency for Research on Cancer (IARC) at WHO in May 2011. Among the evaluated devices were mobile and cordless phones, since they emit radiofrequency electromagnetic fields (RF-EMF). In addition to the brain, another organ, the thyroid gland, also receives high exposure. The incidence of thyroid cancer is increasing in many countries, especially the papillary type that is the most radiosensitive type. We used the Swedish Cancer Register to study the incidence of thyroid cancer during 1970-2013 using joinpoint regression analysis. In women, the incidence increased statistically significantly during the whole study period; average annual percentage change (AAPC) +1.19 % (95 % confidence interval (CI) +0.56, +1.83 %). Two joinpoints were detected, 1979 and 2001, with a high increase of the incidence during the last period 2001-2013 with an annual percentage change (APC) of +5.34 % (95 % CI +3.93, +6.77 %). AAPC for all men during 1970-2013 was +0.77 % (95 % CI -0.03, +1.58 %). One joinpoint was detected in 2005 with a statistically significant increase in incidence during 2005-2013; APC +7.56 % (95 % CI +3.34, +11.96 %). Based on NORDCAN data, there was a statistically significant increase in the incidence of thyroid cancer in the Nordic countries during the same time period. In both women and men a joinpoint was detected in 2006. The incidence increased during 2006-2013 in women; APC +6.16 % (95 % CI +3.94, +8.42 %) and in men; APC +6.84 % (95 % CI +3.69, +10.08 %), thus showing similar results as the Swedish Cancer Register. Analyses based on data from the Cancer Register showed that the increasing trend in Sweden was mainly caused by thyroid cancer of the papillary type. We postulate that the whole increase cannot be attributed to better diagnostic procedures. Increasing exposure to ionizing

Prevention of lymphocyte apoptosis in septic mice with cancer increases mortality.

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Fox, Amy C; Breed, Elise R; Liang, Zhe; Clark, Andrew T; Zee-Cheng, Brendan R; Chang, Katherine C; Dominguez, Jessica A; Jung, Enjae; Dunne, W Michael; Burd, Eileen M; Farris, Alton B; Linehan, David C; Coopersmith, Craig M

2011-08-15

Lymphocyte apoptosis is thought to have a major role in the pathophysiology of sepsis. However, there is a disconnect between animal models of sepsis and patients with the disease, because the former use subjects that were healthy prior to the onset of infection while most patients have underlying comorbidities. The purpose of this study was to determine whether lymphocyte apoptosis prevention is effective in preventing mortality in septic mice with preexisting cancer. Mice with lymphocyte Bcl-2 overexpression (Bcl-2-Ig) and wild type (WT) mice were injected with a transplantable pancreatic adenocarcinoma cell line. Three weeks later, after development of palpable tumors, all animals received an intratracheal injection of Pseudomonas aeruginosa. Despite having decreased sepsis-induced T and B lymphocyte apoptosis, Bcl-2-Ig mice had markedly increased mortality compared with WT mice following P. aeruginosa pneumonia (85 versus 44% 7-d mortality; p = 0.004). The worsened survival in Bcl-2-Ig mice was associated with increases in Th1 cytokines TNF-α and IFN-γ in bronchoalveolar lavage fluid and decreased production of the Th2 cytokine IL-10 in stimulated splenocytes. There were no differences in tumor size or pulmonary pathology between Bcl-2-Ig and WT mice. To verify that the mortality difference was not specific to Bcl-2 overexpression, similar experiments were performed in Bim(-/-) mice. Septic Bim(-/-) mice with cancer also had increased mortality compared with septic WT mice with cancer. These data demonstrate that, despite overwhelming evidence that prevention of lymphocyte apoptosis is beneficial in septic hosts without comorbidities, the same strategy worsens survival in mice with cancer that are given pneumonia.

AUTOMATED ANALYSIS OF CELL DENSITY IN BREAST CANCER AS AN ADDITIONAL METHOD OF INCREASING OBJECTIVITY AND ACCURACY OF BREAST CANCER PROGNOSIS

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R. M. Paltuev

2017-01-01

Full Text Available Introduction. In the last ten years, it became obvious that on the molecular level breast cancer is a group of heterogenous tumors. The current objective of routine clinical practice of treatment prescription includes accurate disease prognosis for every individual patient and conviction that the risk of breast cancer recurrence after adjuvant hormone therapy without adjuvant chemotherapy doesn’t increase.The study objective is to evaluate how clinical use of risk associated with cell density can in practice improve prognosis of recurrence risk in patients with breast cancer after standard clinical and pathomorphological examinations.Materials and methods. The article analyzes therapy results using data from the cumulative cancer registry of breast cancer diagnosis and treatment of the N.N. Petrov National Medical Research Oncology Center in 2000–2009. The database includes information on diagnosis, treatment, and survival of 5106 patients with breast cancer. Archived material (from 2000 to 2009 from paraffin blocks of the “targeted group” for methods of molecular and genetic profiling was poured into recipient blocks, stained with corresponding antibodies such as widely used ER, PR, HER2/neu, Ki-67 markers as well as poorly studied markers: cell density, р53, CK5/6, CK14, CD4/CD8, p63, EGFR, FOXP3, AR, FOX1.Results. The study of 1118 patients with stage T1–2N0M0 breast cancer has shown that analysis of risk associated with cell density allows to predict disease outcome. Correlation between the marker and the grade of histological malignancy is more rare than for Ki-67 determined in this patient group. As a result, determination of cell density is an additional method to increase objectivity and accuracy of breast cancer prognosis.Conclusions. Automated cell density analysis for breast cancer is almost fully operator-independent which increases accuracy and objectivity of the results. Cell density in breast cancer lower than 3000

Increasing Cervical Cancer Screening in Underserved Populations.

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Dorsainvil, Merlyn A

The incidence of cervical cancer has declined dramatically due to Papanicolaou smear testing. However, some minority populations continue to suffer with high incidences and/or death rates of cervical cancer, due to lack of screening. This article updates on cervical cancer screening and prevention and discusses cultural impacts on screening. Knowledge deficits disproportionately affect ethnic minority groups and contribute to cancer incidence, whereas lack of healthcare coverage and low socioeconomic status contribute to screening disparities. Although minority women have cultural beliefs and practices that influence screening, recommendation and/or education from a provider often lead to screening.

Increased risk for depression after breast cancer

DEFF Research Database (Denmark)

Suppli, Nis P; Johansen, Christoffer; Christensen, Jane

2014-01-01

PURPOSE: To investigate the risk for first depression, assessed as incident hospital contacts for depression and incident use of antidepressants, among women with breast cancer. PATIENTS AND METHODS: Danish national registries were used to identify 1,997,669 women with no diagnosis of cancer...... or a major psychiatric disorder. This cohort was followed from 1998 to 2011 for a diagnosis of breast cancer and for the two outcomes, hospital contact for depression and redeemed prescriptions for antidepressants. Rate ratios for incident hospital contacts for depression and incident use of antidepressants...... were estimated with Poisson regression models. Multivariable Cox regression was used to evaluate factors associated with the two outcomes among patients with breast cancer. RESULTS: We identified 44,494 women with breast cancer. In the first year after diagnosis, the rate ratio for a hospital contact...

Evolution of the Raman spectra from single-, few-, and many-layer graphene with increasing disorder

International Nuclear Information System (INIS)

Martins Ferreira, E. H.; Stavale, F.; Moutinho, Marcus V. O.; Lucchese, M. M.; Capaz, Rodrigo B.; Achete, C. A.; Jorio, A.

2010-01-01

We report on the micro-Raman spectroscopy of monolayer, bilayer, trilayer, and many layers of graphene (graphite) bombarded by low-energy argon ions with different doses. The evolution of peak frequencies, intensities, linewidths, and areas of the main Raman bands of graphene is analyzed as function of the distance between defects and number of layers. We describe the disorder-induced frequency shifts and the increase in the linewidth of the Raman bands by means of a spatial-correlation model. Also, the evolution of the relative areas A D /A G , A D ' /A G , and A G ' /A G is described by a phenomenological model. The present results can be used to fully characterize disorder in graphene systems.

Evolution of acoustically vaporized microdroplets in gas embolotherapy

KAUST Repository

Qamar, Adnan; Wong, ZhengZheng; Fowlkes, Brian Brian; Bull, Joseph L.

2012-01-01

Acoustic vaporization dynamics of a superheated dodecafluoropentane (DDFP) microdroplet inside a microtube and the resulting bubble evolution is investigated in the present work. This work is motivated by a developmental gas embolotherapy technique that is intended to treat cancers by infarcting tumors using gas bubbles. A combined theoretical and computational approach is utilized and compared with the experiments to understand the evolution process and to estimate the resulting stress distribution associated with vaporization event. The transient bubble growth is first studied by ultra-high speed imaging and then theoretical and computational modeling is used to predict the entire bubble evolution process. The evolution process consists of three regimes: an initial linear rapid spherical growth followed by a linear compressed oval shaped growth and finally a slow asymptotic nonlinear spherical bubble growth. Although the droplets are small compared to the tube diameter, the bubble evolution is influenced by the tube wall. The final bubble radius is found to scale linearly with the initial droplet radius and is approximately five times the initial droplet radius. A short pressure pulse with amplitude almost twice as that of ambient conditions is observed. The width of this pressure pulse increases with increasing droplet size whereas the amplitude is weakly dependent. Although the rise in shear stress along the tube wall is found to be under peak physiological limits, the shear stress amplitude is found to be more prominently influenced by the initial droplet size. The role of viscous dissipation along the tube wall and ambient bulk fluid pressure is found to be significant in bubble evolution dynamics. © 2012 American Society of Mechanical Engineers.

Free Base Lysine Increases Survival and Reduces Metastasis in Prostate Cancer Model.

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Ibrahim-Hashim, Arig; Wojtkowiak, Jonathan W; de Lourdes Coelho Ribeiro, Maria; Estrella, Veronica; Bailey, Kate M; Cornnell, Heather H; Gatenby, Robert A; Gillies, Robert J

2011-11-19

Malignant tumor cells typically metabolize glucose anaerobically to lactic acid even under normal oxygen tension, a phenomenon called aerobic glycolysis or the Warburg effect. This results in increased acid production and the acidification of the extracellular microenvironment in solid tumors. H + ions tend to flow along concentration gradients into peritumoral normal tissue causing extracellular matrix degradation and increased tumor cell motility thus promoting invasion and metastasis. We have shown that reducing this acidity with sodium bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in prostate cancer and other cancer models. Mathematical models of the tumor-host dynamics predicted that buffers with a pka around 7 will be more effective in reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6. Here we test this prediction the efficacy of free base lysine; a non-bicarbonate/non-volatile buffer with a higher pKa (~10), on prostate tumor metastases model. Oxygen consumption and acid production rate of PC3M prostate cancer cells and normal prostate cells were determined using the Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine started four days prior to inoculation on inhibition of metastasis was examined in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by bioluminescence imaging. PC3M prostate cancer cells are highly acidic in comparison to a normal prostate cell line indicating that reduction of intra- and perit-tumoral acidosis should inhibit metastases formation. In vivo administration of 200 mM free base lysine increased survival and reduced metastasis. PC3M prostate cancer cells are highly glycolytic and produce large amounts of acid when compared to normal prostate cells. Administration of non-volatile buffer decreased growth of metastases and improved survival

Mitochondria and the evolutionary roots of cancer

International Nuclear Information System (INIS)

Davila, Alfonso F; Zamorano, Pedro

2013-01-01

Cancer disease is inherent to, and widespread among, metazoans. Yet, some of the hallmarks of cancer such as uncontrolled cell proliferation, lack of apoptosis, hypoxia, fermentative metabolism and free cell motility (metastasis) are akin to a prokaryotic lifestyle, suggesting a link between cancer disease and evolution. In this hypothesis paper, we propose that cancer cells represent a phenotypic reversion to the earliest stage of eukaryotic evolution. This reversion is triggered by the dysregulation of the mitochondria due to cumulative oxidative damage to mitochondrial and nuclear DNA. As a result, the phenotype of normal, differentiated cells gradually reverts to the phenotype of a facultative anaerobic, heterotrophic cell optimized for survival and proliferation in hypoxic environments. This phenotype matches the phenotype of the last eukaryotic common ancestor (LECA) that resulted from the endosymbiosis between an α-proteobacteria (which later became the mitochondria) and an archaebacteria. As such, the evolution of cancer within one individual can be viewed as a recapitulation of the evolution of the eukaryotic cell from fully differentiated cells to LECA. This evolutionary model of cancer is compatible with the current understanding of the disease, and explains the evolutionary basis for most of the hallmarks of cancer, as well as the link between the disease and aging. It could also open new avenues for treatment directed at reestablishing the synergy between the mitochondria and the cancerous cell. (paper)

Breast cancer risk is increased in the years following false-positive breast cancer screening.

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Goossens, Mathijs C; De Brabander, Isabel; De Greve, Jacques; Vaes, Evelien; Van Ongeval, Chantal; Van Herck, Koen; Kellen, Eliane

2017-09-01

A small number of studies have investigated breast cancer (BC) risk among women with a history of false-positive recall (FPR) in BC screening, but none of them has used time-to-event analysis while at the same time quantifying the effect of false-negative diagnostic assessment (FNDA). FNDA occurs when screening detects BC, but this BC is missed on diagnostic assessment (DA). As a result of FNDA, screenings that detected cancer are incorrectly classified as FPR. Our study linked data recorded in the Flemish BC screening program (women aged 50-69 years) to data from the national cancer registry. We used Cox proportional hazards models on a retrospective cohort of 298 738 women to assess the association between FPR and subsequent BC, while adjusting for potential confounders. The mean follow-up was 6.9 years. Compared with women without recall, women with a history of FPR were at an increased risk of developing BC [hazard ratio=2.10 (95% confidence interval: 1.92-2.31)]. However, 22% of BC after FPR was due to FNDA. The hazard ratio dropped to 1.69 (95% confidence interval: 1.52-1.87) when FNDA was excluded. Women with FPR have a subsequently increased BC risk compared with women without recall. The risk is higher for women who have a FPR BI-RADS 4 or 5 compared with FPR BI-RADS 3. There is room for improvement of diagnostic assessment: 41% of the excess risk is explained by FNDA after baseline screening.

Increase in breast cancer incidence among older women in Mumbai: 30-year trends and predictions to 2025.

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Dikshit, Rajesh P; Yeole, B B; Nagrani, Rajini; Dhillon, P; Badwe, R; Bray, Freddie

2012-08-01

Increasing trends in the incidence of breast cancer have been observed in India, including Mumbai. These have likely stemmed from an increasing adoption of lifestyle factors more akin to those commonly observed in westernized countries. Analyses of breast cancer trends and corresponding estimation of the future burden are necessary to better plan rationale cancer control programmes within the country. We used data from the population-based Mumbai Cancer Registry to study time trends in breast cancer incidence rates 1976-2005 and stratified them according to younger (25-49) and older age group (50-74). Age-period-cohort models were fitted and the net drift used as a measure of the estimated annual percentage change (EAPC). Age-period-cohort models and population projections were used to predict the age-adjusted rates and number of breast cancer cases circa 2025. Breast cancer incidence increased significantly among older women over three decades (EAPC = 1.6%; 95% CI 1.1-2.0), while lesser but significant 1% increase in incidence among younger women was observed (EAPC = 1.0; 95% CI 0.2-1.8). Non-linear period and cohort effects were observed; a trends-based model predicted a close-to-doubling of incident cases by 2025 from 1300 mean cases per annum in 2001-2005 to over 2500 cases in 2021-2025. The incidence of breast cancer has increased in Mumbai during last two to three decades, with increases greater among older women. The number of breast cancer cases is predicted to double to over 2500 cases, the vast majority affecting older women. Copyright © 2012 Elsevier Ltd. All rights reserved.

Increased DHT levels in androgenic alopecia have been selected for to protect men from prostate cancer.

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Bhargava, Shiva

2014-04-01

Androgenic alopecia, a condition characterized by increased levels of DHT could have been selected for due to the benefits that prostaglandin D2 (PGD(2)) has on the prostate. A DHT metabolite can increase the transcription of prostaglandin D2 synthase through estrogen receptor beta. The increase of PGD(2) can decrease the risk of prostate cancer and proliferation of prostate cancer cells. Therefore, the mechanisms behind male pattern baldness may also curtail the advancement of prostate cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Increased expression of protease-activated receptor 4 and Trefoil factor 2 in human colorectal cancer.

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Guoyu Yu

Full Text Available Protease-activated receptor 4 (PAR4, a member of G-protein coupled receptors family, was recently reported to exhibit decreased expression in gastric cancer and esophageal squamous cancer, yet increased expression during the progression of prostate cancer. Trefoil factor 2 (TFF2, a small peptide constitutively expressed in the gastric mucosa, plays a protective role in restitution of gastric mucosa. Altered TFF2 expression was also related to the development of gastrointestinal cancer. TFF2 has been verified to promote cell migration via PAR4, but the roles of PAR4 and TFF2 in the progress of colorectal cancer are still unknown. In this study, the expression level of PAR4 and TFF2 in colorectal cancer tissues was measured using real-time PCR (n = 38, western blotting (n=38 and tissue microarrays (n = 66. The mRNA and protein expression levels of PAR4 and TFF2 were remarkably increased in colorectal cancer compared with matched noncancerous tissues, especially in positive lymph node and poorly differentiated cancers. The colorectal carcinoma cell LoVo showed an increased response to TFF2 as assessed by cell invasion upon PAR4 expression. However, after intervention of PAR4 expression, PAR4 positive colorectal carcinoma cell HT-29 was less responsive to TFF2 in cell invasion. Genomic bisulfite sequencing showed the hypomethylation of PAR4 promoter in colorectal cancer tissues and the hypermethylation in the normal mucosa that suggested the low methylation of promoter was correlated to the increased PAR4 expression. Taken together, the results demonstrated that the up-regulated expression of PAR4 and TFF2 frequently occurs in colorectal cancer tissues, and that overexpression of PAR4 may be resulted from promoter hypomethylation. While TFF2 promotes invasion activity of LoVo cells overexpressing PAR4, and this effect was significantly decreased when PAR4 was knockdowned in HT-29 cells. Our findings will be helpful in further investigations into the

Two developmentally temporal quantitative trait loci underlie convergent evolution of increased branchial bone length in sticklebacks

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Erickson, Priscilla A.; Glazer, Andrew M.; Cleves, Phillip A.; Smith, Alyson S.; Miller, Craig T.

2014-01-01

In convergent evolution, similar phenotypes evolve repeatedly in independent populations, often reflecting adaptation to similar environments. Understanding whether convergent evolution proceeds via similar or different genetic and developmental mechanisms offers insight towards the repeatability and predictability of evolution. Oceanic populations of threespine stickleback fish, Gasterosteus aculeatus, have repeatedly colonized countless freshwater lakes and streams, where new diets lead to morphological adaptations related to feeding. Here, we show that heritable increases in branchial bone length have convergently evolved in two independently derived freshwater stickleback populations. In both populations, an increased bone growth rate in juveniles underlies the convergent adult phenotype, and one population also has a longer cartilage template. Using F2 crosses from these two freshwater populations, we show that two quantitative trait loci (QTL) control branchial bone length at distinct points in development. In both populations, a QTL on chromosome 21 controls bone length throughout juvenile development, and a QTL on chromosome 4 controls bone length only in adults. In addition to these similar developmental profiles, these QTL show similar chromosomal locations in both populations. Our results suggest that sticklebacks have convergently evolved longer branchial bones using similar genetic and developmental programmes in two independently derived populations. PMID:24966315

The impact of increasing dose on overall survival in prostate cancer

International Nuclear Information System (INIS)

Hall, Matthew D.; Schultheiss, Timothy E.; Smith, David D.; Tseng, Bertrand P.; Wong, Jeffrey Y. C.

2015-01-01

To assess the impact of increasing dose on overall survival (OS) for prostate cancer patients. Treatment data were obtained on more than 20,000 patients in the National Oncology Data Alliance®, a proprietary database of merged tumor registries, who were treated for prostate cancer with definitive radiotherapy between 1995 and 2006. Eligible patients had complete data on total dose, T stage, use and timing of androgen deprivation therapy (ADT), and treatment start date (n = 20,028). Patients with prior malignancies were excluded. On multivariate analysis, dose, T stage, grade, marital status, age, and neoadjuvant ADT were significant predictors of OS. Hazard ratios for OS declined monotonically with increasing dose, reaching 0.63 (95 % Confidence Interval 0.53–0.76) at ≥80 Gy. On subset analysis, neoadjuvant ADT significantly improved OS in high risk patients but was not significant in lower risk patients. The dose response was maintained across all risk groups. Medical comorbidities were balanced across all dose strata and sensitivity analysis demonstrated that other prognostic factors were unlikely to explain the observed dose response. This study suggests that increasing dose significantly improves OS in prostate cancer patients treated with radiotherapy. The online version of this article (doi:10.1186/s13014-015-0419-3) contains supplementary material, which is available to authorized users

Reduced fatalism and increased prevention behavior after two high-profile lung cancer events.

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Portnoy, David B; Leach, Corinne R; Kaufman, Annette R; Moser, Richard P; Alfano, Catherine M

2014-01-01

The positive impact of media coverage of high-profile cancer events on cancer prevention behaviors is well-established. However, less work has focused on potential adverse psychological reactions to such events, such as fatalism. Conducting 3 studies, the authors explored how the lung cancer death of Peter Jennings and diagnosis of Dana Reeve in 2005 related to fatalism. Analysis of a national media sample in Study 1 found that media coverage of these events often focused on reiterating the typical profile of those diagnosed with lung cancer; 38% of the media mentioned at least 1 known risk factor for lung cancer, most often smoking. Data from a nationally representative survey in Study 2 found that respondents reported lower lung cancer fatalism, after, compared with before, the events (OR = 0.16, 95% CI [0.03, 0.93]). A sustained increase in call volume to the national tobacco Quitline after these events was found in Study 3. These results suggest that there is a temporal association between high-profile cancer events, the subsequent media coverage, psychological outcomes, and cancer prevention behaviors. These results suggest that high-profile cancer events could be leveraged as an opportunity for large-scale public heath communication campaigns through the dissemination of cancer prevention messages and services.

Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations.

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Smerhovsky, Z; Landa, K; Rössner, P; Brabec, M; Zudova, Z; Hola, N; Pokorna, Z; Mareckova, J; Hurychova, D

2001-01-01

We used cytogenetic analysis to carry out a cohort study in which the major objective was to test the association between frequency of chromosomal aberrations and subsequent risk of cancer. In spite of the extensive use of the cytogenetic analysis of human peripheral blood lymphocytes in biomonitoring of exposure to various mutagens and carcinogens on an ecologic level, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 8,962 cytogenetic tests and 3,973 subjects. We found a significant and strong association between the frequency of chromosomal aberrations and cancer incidence in a group of miners exposed to radon, where a 1% increase in frequency of chromosomal aberrations was followed by a 64% increase in risk of cancer (p < 0.000). In contrast, the collected data are inadequate for a critical evaluation of the association with exposure to other chemicals. PMID:11171523

Epidermal growth factor increases LRF/Pokemon expression in human prostate cancer cells.

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Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K

2011-10-01

Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer

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Iczkowski Kenneth A

2005-07-01

Full Text Available Abstract Background Macrophage migration inhibitory factor (MIF is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate. Methods MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis. Results Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 ± 3.91 ng/ml; ± interquartile range; n = 115 compared with patients with no documented diagnosis of prostate cancer (2.19 ± 2.65 ng/ml; n = 158. ELISA diluent reagents that included bovine serum albumin (BSA significantly reduced MIF serum detection (p Conclusion Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic adenocarcinoma compared to benign tissue from matched samples, supporting our earlier finding of increased MIF gene expression in prostate cancer.

Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10.

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J Mark Elwood

Full Text Available New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000-05 and 2006-10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia.

Evolution of the excess absolute risk (EAR) in the Valencian breast cancer screening programme

International Nuclear Information System (INIS)

Ferrer, S.; Ramos, M.; Villaescusa, J. I.; Verdu, G.; Salas, M. D.; Cuevas, M. D.

2004-01-01

Breast cancer is one of the most frequent diseases in women, with a high incidence rate. The best fight against the breast cancer is the early detection by menas of mammograms in a screening programme. The Valencian Breast Cancer Screening Programme (VBCSP) started at 1992, and it is composed of twenty-two mammography units. The programme is targeted towards asympotomatic women dfrom 45 to 69 years old, but this screening has a negative influence in the studied woman, whatever the diagnosis was. By means of MCNP-4c2 Monte Carlo code, some conversion factors from air kerma air kerma to glandular dose have been developed. Different breast woamn models, according to the Valencian brest anathomy (taking into account the relation breast radius / breast compression thickness obtained from real samples, have been simulated in order to obtain the glandular breast dose values. Quality control parameters as ESAK values were also employed for developing the methods. The conversion factors give a simple and fast wasy to obtain the mean glandular dose from mammography exposition parameters. The glandular dose has been also calculated following the European Protocol on Dosimetry in order to compare the results of the new methodology. Four sample populations of 100 omen from each uunit of the VBCSP have been taken innnn order to estimate the mean glandular dose and the associated excess absolute risk (EAR). Once the doses for each woman from the samples are obtained and according to the age of them, the EAR value for each sample has been determinated following the UNSCEAR 2000 projection risk model, which takes into account the characteristics of the Valencian population and gives the EAR for radio-induced breast cancer. The results have been calculated and compared by means of the ASQRAD software, but with an older risk projection model, the UNSCEAR 1994. Once the four sample average EAR have been calculated, the evolution of the induced risk in the Valencian Breast Cancer

Adaptive evolution of mitochondrial energy metabolism genes associated with increased energy demand in flying insects.

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Yang, Yunxia; Xu, Shixia; Xu, Junxiao; Guo, Yan; Yang, Guang

2014-01-01

Insects are unique among invertebrates for their ability to fly, which raises intriguing questions about how energy metabolism in insects evolved and changed along with flight. Although physiological studies indicated that energy consumption differs between flying and non-flying insects, the evolution of molecular energy metabolism mechanisms in insects remains largely unexplored. Considering that about 95% of adenosine triphosphate (ATP) is supplied by mitochondria via oxidative phosphorylation, we examined 13 mitochondrial protein-encoding genes to test whether adaptive evolution of energy metabolism-related genes occurred in insects. The analyses demonstrated that mitochondrial DNA protein-encoding genes are subject to positive selection from the last common ancestor of Pterygota, which evolved primitive flight ability. Positive selection was also found in insects with flight ability, whereas no significant sign of selection was found in flightless insects where the wings had degenerated. In addition, significant positive selection was also identified in the last common ancestor of Neoptera, which changed its flight mode from direct to indirect. Interestingly, detection of more positively selected genes in indirect flight rather than direct flight insects suggested a stronger selective pressure in insects having higher energy consumption. In conclusion, mitochondrial protein-encoding genes involved in energy metabolism were targets of adaptive evolution in response to increased energy demands that arose during the evolution of flight ability in insects.

Increased risk of intestinal cancer in Crohn's disease: A meta-analysis of population-based cohort studies

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Jess, Tine; Gamborg, Michael; Matzen, Peter

2005-01-01

the inclusion criteria and reported SIRs of colorectal cancer (CRC) in CD varying from 0.9 to 2.2. The pooled SIR for CRC was significantly increased (SIR, 1.9; 95% CI 1.4-2.5), as was the risk for colon cancer separately (SIR, 2.5; 95% CI 1.7-3.5). Regarding small bowel cancer, five studies reported SIRs...... ranging from 3.4 to 66.7, and the overall pooled estimate was 27.1 (95% CI 14.9-49.2). CONCLUSIONS: The present meta-analysis of intestinal cancer risk in CD, based on population-based studies only, revealed an overall increased risk of both CRC and small bowel cancer among patients with CD. However, some...

Chemoresistance of CD133(+) colon cancer may be related with increased survivin expression.

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Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah; Cho, Mee-Yon

2015-07-31

CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133(+) colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133(-) cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133(+) and siRNA-induced CD133(-) cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133(+) cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133(+) cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133(+) cells at 96 h after siRNA transfection. From this study, we conclude that CD133(+) cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133(+) colon cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Increasing colon cancer testing in rural Colorado: evaluation of the exposure to a community-based awareness campaign

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Norman Ned

2009-08-01

Full Text Available Abstract Background Despite effective prevention and early detection screening methods, colorectal cancer is the second leading cause of cancer death in the United States. Colorectal cancer screening community-based interventions are rare, and the literature lacks information about community-based intervention processes. Using participatory research methods, the High Plains Research Network developed a community-based awareness and educational intervention to increase colorectal cancer screening rates in rural northeastern Colorado. This study describes the program components and implementation and explores whether the target population was exposed to the intervention, the reach of the individual intervention components, and the effect on screening intentions. Methods A random digit dial survey was conducted of residents age 40 and older in the first 3 communities to receive the intervention to estimate exposure to the intervention and its effect on colorectal cancer screening intentions. Results Exposure to at least intervention component was reported by 68% of respondents (n = 460. As the level of exposure increased, intentions to talk to a doctor about colorectal cancer screening increased significantly more in respondents who had not been tested in the past 5 years than those who had (p = .025. Intentions to get tested increased significantly in both groups at the same rate as level of exposure increased (p Conclusion Using local community members led to the successful implementation of the intervention. Program materials and messages reached a high percentage of the target population and increased colorectal cancer screening intentions.

Erlotinib augmentation with dapsone for rash mitigation and increased anti-cancer effectiveness.

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Kast, R E

2015-01-01

The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib has failed in many ways to be as potent in the anti-cancer role as pre-clinical studies would have suggested. This paper traces some aspects of this failure to a compensatory erlotinib-mediated increase in interleukin-8. Many other-but not all- cancer chemotherapeutic cytotoxic drugs also provoke a compensatory increase in a malignant clone's interleukin-8 synthesis. Untreated glioblastoma and other cancer cells themselves natively synthesize interleukin-8. Interleukin-8 has tumor growth promoting, mobility and metastasis formation enhancing, effects as well as pro-angiogenesis effects. The old sulfone antibiotic dapsone- one of the very first antibiotics in clinical use- has demonstrated several interleukin-8 system inhibiting actions. Review of these indicates dapsone has potential to augment erlotinib effectiveness. Erlotinib typically gives a rash that has recently been proven to come about via an erlotinib triggered up-regulated keratinocyte interleukin-8 synthesis. The erlotinib rash shares histological features reminiscent of typical neutrophilic dermatoses. Dapsone has an established therapeutic role in current treatment of other neutrophilic dermatoses. Thus, dapsone has potential to both improve the quality of life in erlotinib treated patients by amelioration of rash as well as to short-circuit a growth-enhancing aspect of erlotinib when used in the anti-cancer role.

Elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis in the general population

DEFF Research Database (Denmark)

Johansen, J.S.; Bojesen, S.E.; Mylin, A.K.

2009-01-01

,899 subjects (20 to 95 years) from the Danish general population, the Copenhagen City Heart Study, observed for 11 years for cancer incidence and 14 years for death: 1,432 participants had a first incident cancer, 968 of these died. Hazard ratios (HRs) for cancer events and death after events according...... to plasma YKL-40 in sex and 10 years age percentile categories: 0% to 33%, 34% to 66%, 67% to 90%, 91% to 95%, and 96% to 100%. RESULTS: The cumulative incidence of gastrointestinal cancer increased with increasing YKL-40 (trend P ....0 (95% CI, 0.7 to 1.5) for YKL-40 in category 34% to 66%, 1.5 for 67% to 90% (95% CI, 1.0 to 2.3), 2.4 for 91% to 95%, (95% CI, 1.3 to 4.6), and 3.4 for 96% to 100% (95% CI, 1.9 to 6.1) versus YKL-40 category 0% to 33% (P any cancer event and YKL-40 category 91% to 100% had...

Chemoresistance of CD133{sup +} colon cancer may be related with increased survivin expression

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Lee, Mi-Ra; Ji, Sun-Young; Mia-Jan, Khalilullah [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Cho, Mee-Yon, E-mail: meeyon@yonsei.ac.kr [Department of Pathology, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of); Institute of Genomic Cohort, Yonsei University, Wonju College of Medicine, Wonju (Korea, Republic of)

2015-07-31

CD133, putative cancer stem cell marker, deemed to aid chemoresistance. However, this claim has been challenged recently and we previously reported that patients with CD133{sup +} colon cancer have benefit from 5-fluorouracil (5-FU) chemotherapy incontrast to no benefit in patients with CD133{sup −} cancer. To elucidate the role of CD133 expression in chemoresistance, we silenced the CD133 expression in a colon cancer cell line and determined its effect on the biological characteristics downstream. We comparatively analyzed the sequential changes of MDR1, ABCG2, AKT1 and survivin expression and the result of proliferation assay (WST-1 assay) with 5-FU treatment in CD133{sup +} and siRNA-induced CD133{sup −} cells, derived from Caco-2 colon cancer cell line. 5-FU treatment induced significantly increase of the mRNA expression of MDR1, ABCG2 and AKT1genes, but not protein level. CD133 had little to no effect on the mRNA and protein expression of these genes. However, survivin expression at mRNA and protein level were significantly increased in CD133{sup +} cells compared with siRNA-induced CD133-cells and Mock (not sorted CD133{sup +} cells) at 96 h after siRNA transfection. The cytotoxicity assay demonstrated notable increase of chemoresistance to 5-FU treatment (10 μM) in CD133{sup +} cells at 96 h after siRNA transfection. From this study, we conclude that CD133{sup +} cells may have chemoresistance to 5-FU through the mechanism which is related with survivin expression, instead of MDR1, ABCG2 and AKT1 expression. Therefore a survivin inhibitor can be a new target for effective treatment of CD133{sup +} colon cancer. - Highlights: • We evaluate the role of CD133 in chemoresistance of colon cancer. • We compared the chemoresistance of CD133{sup +} cells and siRNA-induced CD133{sup −} cells. • CD133 had little to no effect on MDR1, ABCG2 and AKT1 expression. • Survivin expression and chemoresistance were increased in CD133{sup +} colon cancer cells.

On the Use of Local Search in the Evolution of Neural Networks for the Diagnosis of Breast Cancer

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Agam Gupta

2015-07-01

Full Text Available With the advancement in the field of Artificial Intelligence, there have been considerable efforts to develop technologies for pattern recognition related to medical diagnosis. Artificial Neural Networks (ANNs, a significant piece of Artificial Intelligence forms the base for most of the marvels in the former field. However, ANNs face the problem of premature convergence at a local minimum and inability to set hyper-parameters (like the number of neurons, learning rate, etc. while using Back Propagation Algorithm (BPA. In this paper, we have used the Genetic Algorithm (GA for the evolution of the ANN, which overcomes the limitations of the BPA. Since GA alone cannot fit for a high-dimensional, complex and multi-modal optimization landscape of the ANN, BPA is used as a local search algorithm to aid the evolution. The contributions of GA and BPA in the resultant approach are adjudged to determine the magnitude of local search necessary for optimization, striking a clear balance between exploration and exploitation in the evolution. The algorithm was applied to deal with the problem of Breast Cancer diagnosis. Results showed that under optimal settings, hybrid algorithm performs better than BPA or GA alone.

Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.

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Chen, Hui-Chi; Schiffman, Mark; Lin, Ching-Yu; Pan, Mei-Hung; You, San-Lin; Chuang, Li-Chung; Hsieh, Chang-Yao; Liaw, Kai-Li; Hsing, Ann W; Chen, Chien-Jen

2011-09-21

Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma. At the baseline examination in 1991-1992, 11,923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method. Of 10,123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age. HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.

Radiotherapy for breast cancer is not associated with increased risk of cied implantation

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Johansen, J. B.; Rehammar, J. C.; Jorgensen, O. D.

2015-01-01

Introduction: Radiotherapy is an important treatment in early stage breast cancer but it is claimed that radiotherapy causes damage to the cardiac conduction system and increases the risk implantation of CIED (pacemaker or ICD). However, this paradigm is based on smaller series of case reports. Due...... to the anatomy, radiotherapy will potential mainly affect the conduction system in left sided breast cancer. The aim of this study was to evaluate risk of implantation of a CIED subsequent to radiotherapy for breast cancer by comparing left- versus right sided radiotherapy in a nationwide cohort. Methods: From...... the database of the Danish Breast Cancer Collaborative Group, we identified women treated with radiotherapy for early-stage breast cancer in Denmark from 1982 to 2005. By record linkage to the Danish Pacemaker and ICD Registry information was retrieved on CIED implants subsequent to radiotherapy. The rate...

Nanotechnology in cancer treatment

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Mironidou-Tzouveleki, Maria; Imprialos, Konstantinos; Kintsakis, Athanasios

2011-10-01

The purpose of this paper is to analyze the current evolutions on nanotechnology and its applications on cancer theragnostics.Rapid advances and emerging technologies in nanotechnology are having a profound impact on cancer treatment. Applications of nanotechnology, which include liposomes, nanoparticles, polymeric micelles, dendrimers, nanocantilever, carbon nanotubes and quantum dots have significantly revolutionized cancer theragnostics. From a pharmaceutical viewpoint, it is critical that the biodistribution of active agents has to be controlled as much as possible. This aspect is vital in order to assure the proper efficiency and safety of the anticancer agents. These biocompatible nanocomposites provide specific biochemical interactions with receptors expressed on the surface of cancer cells. With passive or active targeting strategies, an increased intracellular concentration of drugs can be achieved in cancer cells , while normal cells are being protected from the drug simultaneously. Thus, nanotechnology restricts the extent of the adverse effects of the anticancer therapy. Treatment for metastatic breast cancer, sarcoma in AIDS patients, ovarian and lung cancer is already on market or under final phases of many clinical trials, showing remarkable results. As nanotechnology is perfected, side effects due to normal cell damage will decrease, leading to better results and lengthening patient's survival.

Mathematical methods for cancer evolution

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Suzuki, Takashi

2017-01-01

The purpose of this monograph is to describe recent developments in mathematical modeling and mathematical analysis of certain problems arising from cell biology. Cancer cells and their growth via several stages are of particular interest. To describe these events, multi-scale models are applied, involving continuously distributed environment variables and several components related to particles. Hybrid simulations are also carried out, using discretization of environment variables and the Monte Carlo method for the principal particle variables. Rigorous mathematical foundations are the bases of these tools. The monograph is composed of four chapters. The first three chapters are concerned with modeling, while the last one is devoted to mathematical analysis. The first chapter deals with molecular dynamics occurring at the early stage of cancer invasion. A pathway network model based on a biological scenario is constructed, and then its mathematical structures are determined. In the second chapter mathematica...

Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

DEFF Research Database (Denmark)

Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan

2010-01-01

,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region......According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C...

The evolution of bladder cancer genomics: What have we learned and how can we use it?

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Audenet, François; Attalla, Kyrollis; Sfakianos, John P

2018-03-21

With advancements in molecular biology techniques, great progress has been made in the understanding of urothelial carcinoma pathogenesis. To examine the historic description of molecular alterations in bladder cancer and their evolution towards our current comprehension of the biology of the disease. Historically, a two-pathway model was described from histological and cytogenetic studies: low-grade papillary non-muscle invasive bladder cancers (NMIBC) were described to arise from epithelial hyperplasia with loss of chromosome 9 as an early event, whereas muscle-invasive bladder cancers (MIBC) were considered to develop from dysplasia, associated with genetic instability. Although there could be connections between the 2 pathways, NMIBC and MIBC were largely believed to develop secondary to different molecular alterations. Next-generation sequencing has allowed important insights into cancer biology and a better understanding of the pathways involved in bladder cancer pathogenesis and heterogeneity. Urothelial carcinoma has been found to have a high frequency of somatic mutations compared to other solid tumors, including several mutations in multiple signaling pathways, such as cell cycle regulators (TP53, RB1), RTK/RAS/RAF pathway, PI3K/AKT/mTOR pathway and TERT gene promoter. Epigenetic changes and mutations in chromatin remodeling genes are especially frequent in bladder cancer. Mutations in FGFR3 and KDM6A are more common in NMIBC than in MIBC, whereas mutations in TP53 and KMT2D are more common in MIBC, suggesting the previously hypothesized 2 different pathways, with a subset of tumors progressing from NMIBC to MIBC. Using comprehensive RNA expression profiling studies, at least 5 subtypes of bladder cancer have been identified, the most fundamental division being Basal/Squamous-like and Luminal. These subtypes have different prognoses, natural histories and responses to systemic treatments: Luminal subtypes are enriched with papillary histology and have a

Thyroid cancer risk is not increased in diabetic patients.

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Chin-Hsiao Tseng

-inflammatory drugs might be associated with a significantly lower risk. CONCLUSIONS: There is a lack of an overall association between diabetes and thyroid cancer, but patients with diabetes duration <5 years have a significantly lower risk. Sulfonylurea may increase the risk of thyroid cancer.

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

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van Eggermond, Anna M; Schaapveld, Michael; Janus, Cécile Pm

2017-01-01

incidence ratios (SIR) was 2.4-fold increased (95% confidence interval (95%CI) 1.8-3.2), leading to 5.7 excess cases per 10 000 patient-years. Risk was still increased 30 years after HL treatment (SIR: 2.8; 95%CI: 1.6-4.6). The highest (SIR: 6.5, 95%CI: 3.3-11.3) was seen for transverse colon cancer (15......BACKGROUND: Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. METHODS...... a hazard ratio of 6.8 (95%CI: 3.0-15.6) compared with patients receiving neither treatment, which is significantly higher than an additive joint effect (Padditivity=0.004). CONCLUSIONS: Colorectal cancer surveillance should be considered for HL survivors who received Infradiaphragmatic radiotherapy...

A mechanically-induced colon cancer cell population shows increased metastatic potential

KAUST Repository

Tang, Xin; Kuhlenschmidt, Theresa B; Li, Qian; Ali, Shahjahan; Lezmi, Stephane; Chen, Hong; Pires-Alves, Melissa; Laegreid, William W; Saif, Taher A; Kuhlenschmidt, Mark S

2014-01-01

Background: Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition.Methods: Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher's exact test.Results: Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells.Conclusions: Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular

A mechanically-induced colon cancer cell population shows increased metastatic potential

KAUST Repository

Tang, Xin

2014-05-29

Background: Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition.Methods: Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher\\'s exact test.Results: Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells.Conclusions: Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular

Investigation of the possible increased incidence of cancer in West Cumbria

International Nuclear Information System (INIS)

Rubery, E.D.

1985-01-01

The report of the Black Advisory Group on an investigation of the possible increased incidence of cancer in West Cumbria is briefly considered. The Advisory Group was unable to reach definite conclusions as to whether there is a link between discharges of radioactive material from BNFL Sellafield and the incidence of cancer due to uncertainties in the available epidemiological data and the radiation dose estimate data. The implementation of ten recommendations of the Black Advisory Group are briefly described covering epidemiological, radiation protection and organisational matters in an effort to clarify the situation and to enhance public safety. (U.K.)

Increased oxidative stress mediates the antitumor effect of PARP inhibition in ovarian cancer

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Dong Hou

2018-07-01

Full Text Available PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells. Inhibition or depletion of PARP leads to not only an increase in DNA damage, but also an elevation in the levels of reactive oxygen species (ROS. Importantly, antioxidant N-acetylcysteine (NAC significantly attenuated the induction of DNA damage and the perturbation of proliferation by PARP inhibition or depletion. We further showed that NADPH oxidases 1 and 4 were significantly upregulated by PARP inhibition and were partially responsible for the induction of oxidative stress. Depletion of NOX1 and NOX4 partially rescued the growth inhibition of PARP1-deficient tumor xenografts. Our findings suggest that in addition to compromising the repair of DNA damage, PARP inhibition or depletion may exert extra antitumor effect by elevating oxidative stress in ovarian cancer cells. Keywords: PARP1, Oxidative stress, NADPH oxidases, Ovarian cancer

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

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Hao Jiqing

2009-03-01

Full Text Available Abstract Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.

Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

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Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

2009-01-01

Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

Increasing trends in kidney cancer over the last 2 decades in Saudi Arabia.

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Alkhateeb, Sultan S; Alkhateeb, Jawaher M; Alrashidi, Eman A

2015-06-01

To examine the trends of kidney cancer over the last 2 decades in a subset of a Saudi Arabian population.   We conducted a retrospective study in a tertiary care center including all adult patients with primary kidney cancer who presented and were managed between 1990 and 2010. The time period was split into 4 quartiles, and variables tested and compared using chi-square, T-test, and Kaplan-Meier curves for survival.   The total was 215 patients with a mean age of 57.8 years. There was an increase in the number of kidney cancer cases over the last 2 decades. There was no significant difference in the mode of presentation or stage distribution between quartiles. A significant change was observed in the management towards minimally invasive and nephron-sparing surgeries (p less than 0.001). There was no change in recurrence-free and disease-specific survival over the last 20 years.   There have been an increasing number of kidney cancer patients over the last 2 decades with no observed migration towards more incidental and low stage tumors as compared with developed countries.

Combination of aging and dimethylhydrazine treatment causes an increase in cancer-stem cell population of rat colonic crypts.

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Levi, Edi; Misra, Sandhya; Du, Jianhua; Patel, Bhaumik B; Majumdar, Adhip P N

2009-07-31

Aging is associated with increased incidence of colon cancers. It is also becoming evident that cancer stem cells (CSC) play a vital role in the pathogenesis and prognosis of colon cancer. Recently, we reported the presence of colon cancer stem-like cells in macroscopically normal mucosa in patients with adenomatous polyps and that they increase with aging, suggesting that aging may predispose the colon to carcinogenesis. In the current study we have examined the combined effects of aging and carcinogen exposure on the status of colon CSCs in an experimental model. We used young (4-6 months) and aged (22-24 months) rats and exposed them to the carcinogen, dimethylhydroxide (DMH). We investigated the expression of colon cancer stem cell markers, CD44, CD166, EpCam, and ALDH1 as well as EGFR expression in normal colonic crypt epithelium following carcinogen treatment. Our results demonstrate that aging per se or carcinogen treatment alone causes an increase in the number of colon cancer stems cells, as evidenced by increased immunoreactive-CSC-markers positive cells in the colonic mucosa. In aged rats, carcinogen exposure results in a more pronounced increase in colon cancer stem cells. Our study shows that in aging colon the effects of carcinogens are more pronounced, and an increase in colon CSCs is one of the earliest changes preceding tumor development. Moreover, the current investigation of the use of a panel of immunohistochemical markers of colon CSC can potentially serve as a prognostic marker during screening for colon cancer.

Diabetes but not insulin increases the risk of lung cancer: a Taiwanese population-based study.

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Chin-Hsiao Tseng

Full Text Available BACKGROUND: The trend of lung cancer incidence in Taiwan is unknown, and the association between type 2 diabetes/insulin use and lung cancer is rarely studied. METHODS: The trends of lung cancer incidence in 1979-2007 in the Taiwanese general population were calculated. A random sample of 1,000,000 subjects covered by the National Health Insurance in 2005 was recruited. A total of 494,002 men and 502,948 women and without lung cancer were followed for the annual cumulative incidence of lung cancer in 2005, with calculation of the risk ratios between diabetic and non-diabetic subjects. Logistic regression estimated the adjusted odds ratios for risk factors. RESULTS: The trends increased significantly in both sexes (P<0.0001. The sex-specific annual cumulative incidence increased with age in either the diabetic or non-diabetic subjects, but the risk ratios attenuated with age. In logistic regressions, diabetes was associated with a significantly higher risk, with odds ratios (95% confidence interval for diabetes duration <1, 1-3, 3-5 and ≥5 years versus non-diabetes of 2.189 (1.498-3.200, 1.420 (1.014-1.988, 1.545 (1.132-2.109, and 1.329 (1.063-1.660, respectively. Such an association was not related to a higher detection with chest X-ray examination. Insulin use and medications including oral anti-diabetic drugs, statin, fibrate, and anti-hypertensive agents were not significantly associated with lung cancer. Age, male sex, and chronic obstructive pulmonary disease were positively; but dyslipidemia, stroke and higher socioeconomic status were negatively associated with lung cancer. CONCLUSIONS: Diabetes is significantly associated with a higher risk of lung cancer, but insulin use does not increase the risk.

Neutral evolution of drug resistant colorectal cancer cell populations is independent of their KRAS status.

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Krastan B Blagoev

Full Text Available Emergence of tumor resistance to an anti-cancer therapy directed against a putative target raises several questions including: (1 do mutations in the target/pathway confer resistance? (2 Are these mutations pre-existing? (3 What is the relative fitness of cells with/without the mutation? We addressed these questions in patients with metastatic colorectal cancer (mCRC. We conducted an exhaustive review of published data to establish a median doubling time for CRCs and stained a cohort of CRCs to document mitotic indices. We analyzed published data and our own data to calculate rates of growth (g and regression (d, decay of tumors in patients with CRC correlating these results with the detection of circulating MT-KRAS DNA. Additionally we estimated mathematically the caloric burden of such tumors using data on mitotic and apoptotic indices. We conclude outgrowth of cells harboring intrinsic or acquired MT-KRAS cannot explain resistance to anti-EGFR (epidermal growth factor receptor antibodies. Rates of tumor growth with panitumumab are unaffected by presence/absence of MT-KRAS. While MT-KRAS cells may be resistant to anti-EGFR antibodies, WT-KRAS cells also rapidly bypass this blockade suggesting inherent resistance mechanisms are responsible and a neutral evolution model is most appropriate. Using the above clinical data on tumor doubling times and mitotic and apoptotic indices we estimated the caloric intake required to support tumor growth and suggest it may explain in part cancer-associated cachexia.

Epidemiologic Evidence That Excess Body Weight Increases Risk of Cervical Cancer by Decreased Detection of Precancer.

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Clarke, Megan A; Fetterman, Barbara; Cheung, Li C; Wentzensen, Nicolas; Gage, Julia C; Katki, Hormuzd A; Befano, Brian; Demarco, Maria; Schussler, John; Kinney, Walter K; Raine-Bennett, Tina R; Lorey, Thomas S; Poitras, Nancy E; Castle, Philip E; Schiffman, Mark

2018-04-20

Purpose Obesity has been inconsistently linked to increased cervical cancer incidence and mortality; however, the effect of obesity on cervical screening has not been explored. We investigated the hypothesis that increased body mass might decrease detection of cervical precancer and increase risk of cervical cancer even in women undergoing state-of-the-art screening. Methods We conducted a retrospective cohort study of 944,227 women age 30 to 64 years who underwent cytology and human papillomavirus DNA testing (ie, cotesting) at Kaiser Permanente Northern California (January 2003 to December 2015). Body mass index was categorized as normal/underweight (< 25 kg/m 2 ), overweight (25 to < 30 kg/m 2 ), or obese (≥ 30 kg/m 2 ). We estimated 5-year cumulative risks of cervical precancer and cancer by category of body mass index using logistic Weibull survival models. Results We observed lower risk of cervical precancer (n = 4,489) and higher risk of cervical cancer (n = 490) with increasing body mass index. Specifically, obese women had the lowest 5-year risk of precancer (0.51%; 95% CI, 0.48% to 0.54% v 0.73%; 95% CI, 0.70% to 0.76% in normal/underweight women; P trend < .001). In contrast, obese women had the highest 5-year risk of cancer (0.083%; 95% CI, 0.072% to 0.096% v 0.056%; 95% CI, 0.048% to 0.066% in normal/underweight women; P trend < .001). Results were consistent in subgroups defined by age (30 to 49 v 50 to 64 years), human papillomavirus status (positive v negative), and histologic subtype (glandular v squamous). Approximately 20% of cervical cancers could be attributed to overweight or obesity in the women in our study who underwent routine cervical screening. Conclusion In this large, screened population, overweight and obese women had an increased risk of cervical cancer, likely because of underdiagnosis of cervical precancer. Improvements in equipment and/or technique to assure adequate sampling and visualization of women with elevated body mass

Enzalutamide inhibits proliferation of gemcitabine-resistant bladder cancer cells with increased androgen receptor expression.

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Kameyama, Koji; Horie, Kengo; Mizutani, Kosuke; Kato, Taku; Fujita, Yasunori; Kawakami, Kyojiro; Kojima, Toshio; Miyazaki, Tatsuhiko; Deguchi, Takashi; Ito, Masafumi

2017-01-01

Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling. Microarray analysis revealed upregulation of AR expression in T24GR cells compared with T24 cells. AR mRNA and protein expression was confirmed to be increased in T24GR cells, respectively, by quantitative RT-PCR and western blot analysis, which was associated with more potent AR transcriptional activity as measured by luciferase reporter assay. The copy number of AR gene in T24GR cells determined by PCR was twice as many as that of T24 cells. AR silencing by siRNA transfection resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Lastly, enzalutamide also inhibited cell proliferation of HTB5 bladder cancer cells that express AR and possess intrinsic resistance to gemcitabine. Our results suggest that enzalutamide may have the potential to treat patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.

Using genetics to explore whether the cholesterol-lowering drug ezetimibe may cause an increased risk of cancer

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Kobberø Lauridsen, Bo; Stender, Stefan; Frikke-Schmidt, Ruth

2017-01-01

Background: Results from randomized controlled trials (RCTs) have raised concern that the cholesterol-lowering drug ezetimibe might increase the risk of cancer. We tested the hypothesis that genetic variation in NPC1L1, mimicking treatment with ezetimibe, was associated with an increased risk...... of cancer. Methods: We included 67 257 individuals from the general population. Of these, 8333 developed cancer and 2057 died of cancer from 1968 to 2011. To mimic the effect of ezetimibe, we calculated weighted allele scores based on the low-density lipoprotein (LDL) cholesterol-lowering(= NPC1L1......-inhibitory) effect of each variant. We tested the associations of the NPC1L1 allele scores with LDL cholesterol and with risk of any cancer, death from any cancer and 27 site-specific cancers. As a positive control, we tested the association of the NPC1L1 allele scores with risk of ischaemic vascular disease...

Cancer Stem-Like Cells Enriched in Panc-1 Spheres Possess Increased Migration Ability and Resistance to Gemcitabine

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Yin, Tao; Wei, Hongji; Gou, Shanmiao; Shi, Pengfei; Yang, Zhiyong; Zhao, Gang; Wang, Chunyou

2011-01-01

Pancreatic cancer is one of the most lethal malignancies with poor prognosis. Previously, we found that a subpopulation of cancer stem cells (CSCs) in the Panc-1 pancreatic cancer cell line could propagate to form spheres. Here we characterized the malignant phenotypes of the pancreatic cancer stem CD44+/CD24+ cells, which were enriched under sphere forming conditions as analyzed by flow cytometry. These cells demonstrated increased resistance to gemcitabine and increased migration ability. Moreover, these cells exhibited epithelial to mesenchymal transition characterized by a decreased level of the epithelial marker E-cadherin and an increased level of the mesenchymal marker vimentin. Notably, abnormal expression of Bmi-1, ABCG2, Cyclin D1 and p16 were found in Panc-1 CSCs. Our results suggest that targeted inhibition of CSCs represents a novel therapeutic approach to overcome chemoresistance and metastasis of pancreatic cancer. PMID:21673909

[Feature extraction for breast cancer data based on geometric algebra theory and feature selection using differential evolution].

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Li, Jing; Hong, Wenxue

2014-12-01

The feature extraction and feature selection are the important issues in pattern recognition. Based on the geometric algebra representation of vector, a new feature extraction method using blade coefficient of geometric algebra was proposed in this study. At the same time, an improved differential evolution (DE) feature selection method was proposed to solve the elevated high dimension issue. The simple linear discriminant analysis was used as the classifier. The result of the 10-fold cross-validation (10 CV) classification of public breast cancer biomedical dataset was more than 96% and proved superior to that of the original features and traditional feature extraction method.

Evidence of increased chromosomal abnormalities in French Polynesian thyroid cancer patients

International Nuclear Information System (INIS)

Violot, D.; M'kacher, R.; Dossou, J.; Adjadj, E.; Vathaire, F. de; Parmentier, C.

2005-01-01

The aim of this study was to evaluate the frequency of chromosomal abnormalities in thyroid cancer patients before and after radioactive iodine administration in order to assess cytogenetic particularity in Polynesian thyroid cancer patients. Chromosomal abnormalities were studied in 30 Polynesian patients with differentiated thyroid cancer, prior to and 4 days after 131 I administration. Unstable chromosomal abnormalities were counted in peripheral blood lymphocytes using a conventional cytogenetic method. Peripheral blood was irradiated in vitro at different doses (0.5, 1 and 2 Gy) in order to establish the dose-response of the lymphocytes. Control groups were composed of 50 European thyroid cancer patients before and after first administration of 131 I, and of ten European healthy donors. In addition, in vitro irradiation assays were performed at different doses (0.5, 1 and 2 Gy). The relative risk of spontaneous dicentrics before any radiation treatment was 2.9 (95% CI 1.7-5.1) times higher among Polynesian thyroid patients than among European thyroid cancer patients. After in vitro irradiation, the rise in frequency of dicentrics was similar in the Polynesian thyroid cancer group and the European thyroid patients and healthy donors. Four days after administration of 3.7 GBq 131 I, the relative risk for a dicentric per cell was 1.3 (95% CI 1.0-1.5) times higher in Polynesian than in European patients. This can be explained by higher 131 I retention in Polynesian compared with European patients. The results obtained revealed an increased frequency of cytogenetic abnormalities in Polynesian thyroid cancer patients compared with European control patients. These preliminary findings are compatible with possible previous environmental aggression and therefore imply a need for further investigations on larger series including, in particular, French Polynesian healthy donors. In addition to French Polynesians, Maori and Hawaiian control groups could be useful. (orig.)

New Strategies Using Antibody Combinations to Increase Cancer Treatment Effectiveness

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Isabel Corraliza-Gorjón

2017-12-01

Full Text Available Antibodies have proven their high value in antitumor therapy over the last two decades. They are currently being used as the first-choice to treat some of the most frequent metastatic cancers, like HER2+ breast cancers or colorectal cancers, currently treated with trastuzumab (Herceptin and bevacizumab (Avastin, respectively. The impressive therapeutic success of antibodies inhibiting immune checkpoints has extended the use of therapeutic antibodies to previously unanticipated tumor types. These anti-immune checkpoint antibodies allowed the cure of patients devoid of other therapeutic options, through the recovery of the patient’s own immune response against the tumor. In this review, we describe how the antibody-based therapies will evolve, including the use of antibodies in combinations, their main characteristics, advantages, and how they could contribute to significantly increase the chances of success in cancer therapy. Indeed, novel combinations will consist of mixtures of antibodies against either different epitopes of the same molecule or different targets on the same tumor cell; bispecific or multispecific antibodies able of simultaneously binding tumor cells, immune cells or extracellular molecules; immunomodulatory antibodies; antibody-based molecules, including fusion proteins between a ligand or a receptor domain and the IgG Fab or Fc fragments; autologous or heterologous cells; and different formats of vaccines. Through complementary mechanisms of action, these combinations could contribute to elude the current limitations of a single antibody which recognizes only one particular epitope. These combinations may allow the simultaneous attack of the cancer cells by using the help of the own immune cells and exerting wider therapeutic effects, based on a more specific, fast, and robust response, trying to mimic the action of the immune system.

Biological research in the evolution of cancer surgery: a personal perspective.

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Fisher, Bernard

2008-12-15

During the 19th, and for most of the 20th century, malignant tumors were removed by mutilating radical anatomic dissection. Advances such as anesthesia, asepsis, and blood transfusion made possible increasingly more radical operations. There was no scientific rationale for the operations being performed. Surgery in the 20th century was dominated by the principles of William S. Halsted, who contended that the bloodstream was of little significance as a route of tumor cell dissemination; a tumor was autonomous of its host; and cancer was a local-regional disease that spread in an orderly fashion based on mechanical considerations. Halsted believed that both the extent and nuances of an operation influenced patient outcome and that inadequate surgical skill was responsible for the failure to cure. A new surgical era arose in 1957, when cancer surgery began to be influenced by laboratory and clinical research, with results contrary to Halstedian principles. A new hypothesis resulted in a scientific basis for cancer surgery. Clinical trials supported the thesis that operable cancer is a systemic disease and that variations in local-regional therapy are unlikely to substantially affect survival. Complex host-tumor relationships were shown to affect every aspect of cancer and, contrary to Halsted's thesis, the bloodstream is of considerable importance in tumor dissemination. Clinical trials also have shown that less radical surgery is justified. Studies have shown that improved survival can be achieved with systemic therapy after surgery. Such therapy can reduce both the incidence of distant disease and the tumor recurrence at the tumor site after minimal surgery. The use of systemic therapy in patients who have no identifiable metastatic disease is a drastic departure from previous strategies. New technological innovations resulting from engineering research have improved the quality of life of patients by eliminating the need for some surgical procedures. Because cancer

Update on Sporadic Colorectal Cancer Genetics.

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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.

Bidi smokers at increased risk of oral cancer.

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Warnakulasuriya, Saman

2005-01-01

Source articles were searched for using Medline, the Cochrane Library and within the references lists of identified articles. Articles were selected that included data enabling construction of 2 x 2 tables to estimate odds ratios (OR) and 95% confidence intervals (CI). For each study, two-way contingency tables were constructed, based on exposure frequency distributions, for cases and controls. Unadjusted OR and 95% CI were recalculated based on the reported data using standard procedures. Separate contingency tables were made for bidi smoking, cigarette smoking and both types of smoking if the data were available in the same article. The overall OR combined across all studies, and its 95% CI, was calculated using a random-effects model for bidi and cigarette smoking. Tests for publication bias and heterogeneity were conducted. Confounding factors, for example, betel quid chewing or alcohol use, were not included in the meta-regression model. An increased risk of oral cancer was found for bidi smokers compared with people who had never smoked (OR, 3.1; 95% CI, 2.0-5.0) whereas no significant pattern of risk was found for cigarette smokers (OR, 1.1; 95% CI, 0.7-1.8). There was substantial heterogeneity in the pooled OR estimate. The results clearly indicate that bidi smokers are at increased risk of oral cancer. It is important that this information be incorporated into smoking prevention and cessation efforts, particularly in the urban poor and rural mass in south Asian countries where bidi smoking is widespread.

Acceptance and adherence to chemoprevention among women at increased risk of breast cancer.

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Roetzheim, Richard G; Lee, Ji-Hyun; Fulp, William; Matos Gomez, Elizabeth; Clayton, Elissa; Tollin, Sharon; Khakpour, Nazanin; Laronga, Christine; Lee, Marie Catherine; Kiluk, John V

2015-02-01

Chemoprevention is an option for women who are at increased risk of breast cancer (five year risk ≥1.7%). It is uncertain, however, how often women accept and complete five years of therapy and whether clinical or demographic factors predict completion. Medical records were abstracted for 219 women whose five year risk of breast cancer was ≥1.7% and who were offered chemoprevention while attending a high risk breast clinic at the Moffitt Cancer Center. We examined the likelihood of accepting chemoprevention and completing five years of therapy, and potential clinical and demographic predictors of these outcomes, using multivariable logistic regression and survival analysis models. There were 118/219 women (54.4%) who accepted a recommendation for chemoprevention and began therapy. The likelihood of accepting chemoprevention was associated with lifetime breast cancer risk and was higher for women with specific high risk conditions (lobular carcinoma in situ and atypical ductal hyperplasia). Women with osteoporosis and those that consumed alcohol were also more likely to accept medication. There were 58/118 (49.2%) women who stopped medication at least temporarily after starting therapy. Based on survival curves, an estimated 60% of women who begin chemoprevention will complete five years of therapy. A substantial percentage of women at increased risk of breast cancer will decline chemoprevention and among those that accept therapy, approximately 40% will not be able to complete five years of therapy because of side effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

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Chun, Sung Kook [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Chung, Sooyoung [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Hee-Dae [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Lee, Ju Hyung [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Jang, Jaebong [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Kim, Jeongah; Kim, Doyeon [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Son, Gi Hoon [Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Oh, Young J. [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Suh, Young-Ger [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Lee, Cheol Soon [Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of); and others

2015-11-13

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

International Nuclear Information System (INIS)

Chun, Sung Kook; Chung, Sooyoung; Kim, Hee-Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young-Ger; Lee, Cheol Soon

2015-01-01

Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

An acute exercise session increases self-efficacy in sedentary endometrial cancer survivors and controls.

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Hughes, Daniel; Baum, George; Jovanovic, Jennifer; Carmack, Cindy; Greisinger, Anthony; Basen-Engquist, Karen

2010-11-01

Self-efficacy can be affected by mastery experiences and somatic sensations. A novel exercise experience and associated sensations may impact self-efficacy and subsequent behaviors. We investigated the effect of a single exercise session on self-efficacy for sedentary endometrial cancer survivors compared with sedentary women of a similar age, but with no cancer history. Twenty survivors and 19 controls completed an exercise session performed as a submaximal cycle ergometry test. Sensations and efficacy were measured before and after exercise. Repeated measures analysis of variance (ANOVA) was performed. Regression models were used to determine predictors of self-efficacy and subsequent exercise. Self-efficacy increased for both survivors and controls, but survivors had a higher rate of increase, and the change predicted subsequent exercise. The association between exercise-related somatic sensations and self-efficacy differed between the 2 groups. A novel exercise experience had a larger effect on self-efficacy and subsequent exercise activity for endometrial cancer survivors than controls. Somatic sensations experienced during exercise may differ for survivors, which may be related to the experience of having cancer. Understanding factors affecting confidence in novel exercise experiences for populations with specific cancer histories is of the utmost importance in the adoption of exercise behaviors.

Increased androgenic sensitivity in the hind limb muscular system marks the evolution of a derived gestural display.

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Mangiamele, Lisa A; Fuxjager, Matthew J; Schuppe, Eric R; Taylor, Rebecca S; Hödl, Walter; Preininger, Doris

2016-05-17

Physical gestures are prominent features of many species' multimodal displays, yet how evolution incorporates body and leg movements into animal signaling repertoires is unclear. Androgenic hormones modulate the production of reproductive signals and sexual motor skills in many vertebrates; therefore, one possibility is that selection for physical signals drives the evolution of androgenic sensitivity in select neuromotor pathways. We examined this issue in the Bornean rock frog (Staurois parvus, family: Ranidae). Males court females and compete with rivals by performing both vocalizations and hind limb gestural signals, called "foot flags." Foot flagging is a derived display that emerged in the ranids after vocal signaling. Here, we show that administration of testosterone (T) increases foot flagging behavior under seminatural conditions. Moreover, using quantitative PCR, we also find that adult male S. parvus maintain a unique androgenic phenotype, in which androgen receptor (AR) in the hind limb musculature is expressed at levels ∼10× greater than in two other anuran species, which do not produce foot flags (Rana pipiens and Xenopus laevis). Finally, because males of all three of these species solicit mates with calls, we accordingly detect no differences in AR expression in the vocal apparatus (larynx) among taxa. The results show that foot flagging is an androgen-dependent gestural signal, and its emergence is associated with increased androgenic sensitivity within the hind limb musculature. Selection for this novel gestural signal may therefore drive the evolution of increased AR expression in key muscles that control signal production to support adaptive motor performance.

The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

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Mierke, Claudia Tanja

2013-01-01

The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3high or αvβ3low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3high cells showed a threefold increased cell invasion compared to αvβ3low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3high cells but not in αvβ3low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3high cells, whereas the invasiveness of β3 specific knock

The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

International Nuclear Information System (INIS)

Mierke, Claudia Tanja

2013-01-01

The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3 high or αvβ3 low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3 high cells showed a threefold increased cell invasion compared to αvβ3 low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3 high cells but not in αvβ3 low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3 low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3 high cells, whereas the invasiveness of β3 specific knock

Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

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Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung; Ro, Jungsil; Yoon, Sungpil

2012-01-01

Highlights: ► Sal sensitizes antimitotic drugs-treated cancer cells. ► Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. ► Sal also sensitizes them by increasing DNA damage and reducing p21 level. ► A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitotic drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.

Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

Energy Technology Data Exchange (ETDEWEB)

Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung; Ro, Jungsil [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of); Yoon, Sungpil, E-mail: yoons@ncc.re.kr [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of)

2012-02-03

Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitotic drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.

Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis.

Science.gov (United States)

Lyons, John D; Mittal, Rohit; Fay, Katherine T; Chen, Ching-Wen; Liang, Zhe; Margoles, Lindsay M; Burd, Eileen M; Farris, Alton B; Ford, Mandy L; Coopersmith, Craig M

2016-01-01

Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered. C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival. Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003). Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury. Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on the models used.

Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis.

Directory of Open Access Journals (Sweden)

John D Lyons

Full Text Available Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered.C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival.Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003. Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury.Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on

Bridging the Gap: Racial concordance as a strategy to increase African American participation in breast cancer research.

Science.gov (United States)

Frierson, Georita M; Pinto, Bernardine M; Denman, Deanna C; Leon, Pierre A; Jaffe, Alex D

2017-11-01

Lack of African American females in breast cancer research has been receiving substantial attention. This study seeks to identify research perceptions and motivating factors needed to increase racial/ethnic minority participation in breast cancer research. A total of 57 African American women (Σ = 47.8 years), from Rhode Island and Texas, completed a questionnaire and focus group. While many participants were not breast cancer survivors, they reported knowledge of their racial group's risk for breast cancer. One major finding that could be seen as both a facilitator and barrier is racial concordance between participant and researcher. Cultural sensitivity and trust building is recommended to increase minority participation.

Evolution of increased competitiveness in cows trades off with reduced milk yield, fertility and more masculine morphology.

Science.gov (United States)

Sartori, Cristina; Mazza, Serena; Guzzo, Nadia; Mantovani, Roberto

2015-08-01

In some species females compete for food, foraging territories, mating, and nesting sites. Competing females can exhibit morphological, physiological, and behavioral adaptations typical of males, which are commonly considered as secondary sexual traits. Competition and the development of traits increasing competitiveness require much energy and may exert adverse effects on fecundity and survival. From an evolutionary perspective, positive selection for increased competitiveness would then result in evolution of reduced values for traits related to fitness such as fecundity and survival. There is recent evidence for such evolutionary trade-offs involving male competition, but no study has considered competing females so far. Using data from competitions for dominance in cows (Bos taurus), we found negative genetic correlations between traits providing success in competition, that is, fighting ability and fitness traits related to milk production and with fertility (the inverse of parity-conception interval). Fighting ability also showed low but positive genetic correlations with "masculine" morphological traits, and negative correlations with "feminine" traits. A genetic change in traits over time has occurred due to selection on competitiveness, corresponding to an evolutionary process of "masculinization" counteracting the official selection for milk yield. Similar evolutionary trade-off between success in competition and fitness components may be present in various species experiencing female competition. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Has Human Evolution Stopped?

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Alan R. Templeton

2010-07-01

Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

The proportion of cancer-related entries in PubMed has increased considerably; is cancer truly "The Emperor of All Maladies"?

Science.gov (United States)

Reyes-Aldasoro, Constantino Carlos

2017-01-01

In this work, the public database of biomedical literature PubMed was mined using queries with combinations of keywords and year restrictions. It was found that the proportion of Cancer-related entries per year in PubMed has risen from around 6% in 1950 to more than 16% in 2016. This increase is not shared by other conditions such as AIDS, Malaria, Tuberculosis, Diabetes, Cardiovascular, Stroke and Infection some of which have, on the contrary, decreased as a proportion of the total entries per year. Organ-related queries were performed to analyse the variation of some specific cancers. A series of queries related to incidence, funding, and relationship with DNA, Computing and Mathematics, were performed to test correlation between the keywords, with the hope of elucidating the cause behind the rise of Cancer in PubMed. Interestingly, the proportion of Cancer-related entries that contain "DNA", "Computational" or "Mathematical" have increased, which suggests that the impact of these scientific advances on Cancer has been stronger than in other conditions. It is important to highlight that the results obtained with the data mining approach here presented are limited to the presence or absence of the keywords on a single, yet extensive, database. Therefore, results should be observed with caution. All the data used for this work is publicly available through PubMed and the UK's Office for National Statistics. All queries and figures were generated with the software platform Matlab and the files are available as supplementary material.

MAPK inhibitors, particularly the JNK inhibitor, increase cell death effects in H2O2-treated lung cancer cells via increased superoxide anion and glutathione depletion.

Science.gov (United States)

Park, Woo Hyun

2018-02-01

Reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), induce apoptosis in cancer cells by regulating mitogen-activated protein kinase (MAPK) signaling pathways. The present study investigated the effects of MAPK inhibitors on cell growth and death as well as changes in ROS and glutathione (GSH) levels in H2O2-treated Calu-6 and A549 lung cancer cells. H2O2 inhibited growth and induced death of Calu-6 and A549 lung cancer cells. All MAPK inhibitors appeared to enhance growth inhibition in H2O2-treated Calu-6 and A549 lung cancer cells and increased the percentage of Annexin V-FITC-positive cells in these cancer cells. Among the MAPK inhibitors, a JNK inhibitor significantly augmented the loss of mitochondrial membrane potential (MMP; ΔΨm) in H2O2-treated Calu-6 and A549 lung cancer cells. Intracellular ROS levels were significantly increased in the H2O2-treated cells at 1 and 24 h. Only the JNK inhibitor increased ROS levels in the H2O2-treated cells at 1 h and all MAPK inhibitors raised superoxide anion levels in these cells at 24 h. In addition, H2O2 induced GSH depletion in Calu-6 and A549 cells and the JNK inhibitor significantly enhanced GSH depletion in H2O2‑treated cells. Each of the MAPK inhibitors altered ROS and GSH levels differently in the Calu-6 and A549 control cells. In conclusion, H2O2 induced growth inhibition and death in lung cancer cells through oxidative stress and depletion of GSH. The enhanced effect of MAPK inhibitors, especially the JNK inhibitor, on cell death in H2O2-treated lung cancer cells was correlated with increased O2•- levels and GSH depletion.

Anastomotic Leak Increases Distant Recurrence and Long-Term Mortality After Curative Resection for Colonic Cancer

DEFF Research Database (Denmark)

Krarup, Peter-Martin; Nordholm-Carstensen, Andreas; Jorgensen, Lars N

2014-01-01

OBJECTIVE: To investigate the impact of anastomotic leak (AL) on disease recurrence and long-term mortality in patients alive 120 days after curative resection for colonic cancer. BACKGROUND: There is no solid data as to whether AL after colonic cancer surgery increases the risk of disease...

Facilitators and Challenges in Psychosocial Adaptation to Being at Increased Familial Risk of Breast Cancer.

Science.gov (United States)

Heiniger, Louise; Price, Melanie A; Charles, Margaret; Butow, Phyllis N

2015-12-01

Little is known about the process of psychosocial adaptation to familial risk in tested and untested individuals at increased familial risk of cancer. This paper presents findings from a qualitative study of 36 women participating in the Kathleen Cuningham Consortium for Research into Familial Breast cancer (kConFab) Psychosocial study. Facilitators and challenges in psychosocial adaptation were identified through semi-structured interviews. The women, who were either tested (carriers or non-carriers of breast cancer susceptibility mutations) or untested (ineligible for testing or eligible but delayed or declined testing), described personal, support network and healthcare characteristics that impacted on the adaptation process. Challenges in one domain could be overcome by facilitators in other domains and key differences relating to whether women had undergone testing, or not, were identified. Tested and untested women with an increased familial risk of breast cancer may benefit from support tailored to their mutation testing status in order to enhance adaptation.

RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

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Thomas eKolodecik

2014-01-01

Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

Molecular Concordance Between Primary Breast Cancer and Matched Metastases

DEFF Research Database (Denmark)

Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads

2016-01-01

Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both....... The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors......, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight...

Teaching genetics prior to teaching evolution improves evolution understanding but not acceptance

Science.gov (United States)

Mead, Rebecca; Hejmadi, Momna

2017-01-01

What is the best way to teach evolution? As microevolution may be configured as a branch of genetics, it being a short conceptual leap from understanding the concepts of mutation and alleles (i.e., genetics) to allele frequency change (i.e., evolution), we hypothesised that learning genetics prior to evolution might improve student understanding of evolution. In the UK, genetics and evolution are typically taught to 14- to 16-y-old secondary school students as separate topics with few links, in no particular order and sometimes with a large time span between. Here, then, we report the results of a large trial into teaching order of evolution and genetics. We modified extant questionnaires to ascertain students’ understanding of evolution and genetics along with acceptance of evolution. Students were assessed prior to teaching, immediately post teaching and again after several months. Teachers were not instructed what to teach, just to teach in a given order. Regardless of order, teaching increased understanding and acceptance, with robust signs of longer-term retention. Importantly, teaching genetics before teaching evolution has a significant (p Teaching genetics first additionally had positive effects on genetics understanding, by increasing knowledge. These results suggest a simple, minimally disruptive, zero-cost intervention to improve evolution understanding: teach genetics first. This same alteration does not, however, result in a significantly increased acceptance of evolution, which reflects a weak correlation between knowledge and acceptance of evolution. Qualitative focus group data highlights the role of authority figures in determination of acceptance. PMID:28542179

Teaching genetics prior to teaching evolution improves evolution understanding but not acceptance.

Science.gov (United States)

Mead, Rebecca; Hejmadi, Momna; Hurst, Laurence D

2017-05-01

What is the best way to teach evolution? As microevolution may be configured as a branch of genetics, it being a short conceptual leap from understanding the concepts of mutation and alleles (i.e., genetics) to allele frequency change (i.e., evolution), we hypothesised that learning genetics prior to evolution might improve student understanding of evolution. In the UK, genetics and evolution are typically taught to 14- to 16-y-old secondary school students as separate topics with few links, in no particular order and sometimes with a large time span between. Here, then, we report the results of a large trial into teaching order of evolution and genetics. We modified extant questionnaires to ascertain students' understanding of evolution and genetics along with acceptance of evolution. Students were assessed prior to teaching, immediately post teaching and again after several months. Teachers were not instructed what to teach, just to teach in a given order. Regardless of order, teaching increased understanding and acceptance, with robust signs of longer-term retention. Importantly, teaching genetics before teaching evolution has a significant (p genetics was taught first. Teaching genetics first additionally had positive effects on genetics understanding, by increasing knowledge. These results suggest a simple, minimally disruptive, zero-cost intervention to improve evolution understanding: teach genetics first. This same alteration does not, however, result in a significantly increased acceptance of evolution, which reflects a weak correlation between knowledge and acceptance of evolution. Qualitative focus group data highlights the role of authority figures in determination of acceptance.

Toward the identification of communities with increased tobacco-associated cancer burden: Application of spatial modeling techniques

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Noella A Dietz

2011-01-01

Full Text Available Introduction: Smoking-attributable risks for lung, esophageal, and head and neck (H/N cancers range from 54% to 90%. Identifying areas with higher than average cancer risk and smoking rates, then targeting those areas for intervention, is one approach to more rapidly lower the overall tobacco disease burden in a given state. Our research team used spatial modeling techniques to identify areas in Florida with higher than expected tobacco-associated cancer incidence clusters. Materials and Methods: Geocoded tobacco-associated incident cancer data from 1998 to 2002 from the Florida Cancer Data System were used. Tobacco-associated cancers included lung, esophageal, and H/N cancers. SaTScan was used to identify geographic areas that had statistically significant (P<0.10 excess age-adjusted rates of tobacco-associated cancers. The Poisson-based spatial scan statistic was used. Phi correlation coefficients were computed to examine associations among block groups with/without overlapping cancer clusters. The logistic regression was used to assess associations between county-level smoking prevalence rates and being diagnosed within versus outside a cancer cluster. Community-level smoking rates were obtained from the 2002 Florida Behavioral Risk Factor Surveillance System (BRFSS. Analyses were repeated using 2007 BRFSS to examine the consistency of associations. Results: Lung cancer clusters were geographically larger for both squamous cell and adenocarcinoma cases in Florida from 1998 to 2002, than esophageal or H/N clusters. There were very few squamous cell and adenocarcinoma esophageal cancer clusters. H/N cancer mapping showed some squamous cell and a very small amount of adenocarcinoma cancer clusters. Phi correlations were generally weak to moderate in strength. The odds of having an invasive lung cancer cluster increased by 12% per increase in the county-level smoking rate. Results were inconsistent for esophageal and H/N cancers, with some

Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

OpenAIRE

Muranen, Taru A.; Mavaddat, Nasim; Khan, Sofia; Fagerholm, Rainer; Pelttari, Liisa; Lee, Andrew; Aittom?ki, Kristiina; Blomqvist, Carl; Easton, Douglas F.; Nevanlinna, Heli

2016-01-01

The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breas...

Betulinic acid selectively increases protein degradation and enhances prostate cancer-specific apoptosis: possible role for inhibition of deubiquitinase activity.

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Teresita Reiner

Full Text Available Inhibition of the ubiquitin-proteasome system (UPS of protein degradation is a valid anti-cancer strategy and has led to the approval of bortezomib for the treatment of multiple myeloma. However, the alternative approach of enhancing the degradation of oncoproteins that are frequently overexpressed in cancers is less developed. Betulinic acid (BA is a plant-derived small molecule that can increase apoptosis specifically in cancer but not in normal cells, making it an attractive anti-cancer agent. Our results in prostate cancer suggested that BA inhibited multiple deubiquitinases (DUBs, which resulted in the accumulation of poly-ubiquitinated proteins, decreased levels of oncoproteins, and increased apoptotic cell death. In normal fibroblasts, however, BA did not inhibit DUB activity nor increased total poly-ubiquitinated proteins, which was associated with a lack of effect on cell death. In the TRAMP transgenic mouse model of prostate cancer, treatment with BA (10 mg/kg inhibited primary tumors, increased apoptosis, decreased angiogenesis and proliferation, and lowered androgen receptor and cyclin D1 protein. BA treatment also inhibited DUB activity and increased ubiquitinated proteins in TRAMP prostate cancer but had no effect on apoptosis or ubiquitination in normal mouse tissues. Overall, our data suggests that BA-mediated inhibition of DUBs and induction of apoptotic cell death specifically in prostate cancer but not in normal cells and tissues may provide an effective non-toxic and clinically selective agent for chemotherapy.

Home care to Older adult with cancer

International Nuclear Information System (INIS)

Villagra, J; Castro, C; Meneses, S.

2004-01-01

Objective: Home care of the elderly with cancer. After the development of a program of oncology home care and over a period of five years, we believe that the evaluation allows us to have our proposal and challenges in the continuity of the program. This evidence is based in our old advanced Uruguayan population, and consequently increase this cancer population, we should define which pointed toward our objective, in order to get the best quality life. After one year with a project based on general rules, the evidence threw an evaluation, that we should review the model of care with which we were working. We continue to Auto-care model Dorothea Orem. The main objective became q uality of life : Take care as the primary Older Adult; Specific care their cancer to become symptomatic secondary complications to the evolution of tumor biology; Secondary prevention of cause therapeutic effect; Family integration, without changing the pace of life that the elderly had before being with cancer. Nursing challenge: Maintain autonomy achieved in these 5 years. Deepen the social equilibrium that we are committed daily between patient and family.Do not miss the professionalism achieved today.Proposal for nursing: Consider a wide field of nursing and for this achievement is need knowledge of 2nd level of community work, knowledge Clinical knowledge in Oncology Nursing, autonomy in decision making. For older adults with cancer: No out of its middle. Maintain priority habits and customs. Do not let it lose their self-esteem with their own values. Caution changes must take care to better manage the evolution of their illness. Conclusion: Oncology nursing is a specialty. Without this formation will be ever more away the development of these programs in our environment, or fall in applying for only economic convenience, losing professionalism. Our population is increasing

Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis

NARCIS (Netherlands)

Buis, C. C. M.; van Leeuwen, F. E.; Mooij, T. M.; Burger, C. W.; Lambalk, Cornelis B.; Kortman, Marian; Laven, Joop S. E.; Jansen, Cees A. M.; Helmerhorst, Frans M.; Cohlen, Ben J.; Willemsen, Wim N. P.; Smeenk, Jesper M. J.; Simons, Arnold H. M.; van der Veen, Fulco; Evers, Johannes L. H.; van Dop, Peter A.; Macklon, Nicholas S.

2013-01-01

Is ovarian or extra-ovarian endometriosis associated with an increased risk of ovarian cancer and borderline ovarian tumours (BOT)? We found a 3- to 8-fold increased risk of ovarian tumours associated with endometriosis: the magnitude of the risk increase depended on the definition of endometriosis.

THE EFFECTIVENESS OF MIXED JUICE MUNG BEAN AND GUAVA FOR INCREASING HEMOGLOBIN LEVEL IN CANCER PATIENT WITH CHEMOTHERAPY

Directory of Open Access Journals (Sweden)

Nurul Huda

2016-09-01

Full Text Available Cancer is a chronic disease with high morbidity and mortality rate in a year. One of therapy in curing cancer is chemotherapy. But unfortunately chemotherapy has some negative effects such as decreasing the level of hemoglobin (Hb. Mung bean that contain a lot of iron and Guava which is rich of vitamin C for iron absorption are useful in cancer patient with chemotherapy. Therefore, a mixture of both is believed in increasing hemoglobin level significantly. The purpose of this study was to determine the effectiveness of mixed juice mung bean and guava for increasing hemoglobin level in experiment and control group of cancer patient with chemotherapy.This research used Quasi Experiment design with pretest-posttest design control group approach. The total number of respondent was 30 chosen by purposive sampling method. Results of this study showed hemoglobin level in experiment group 14.07 and 10.42 in control group with p value (0,000 < α (0,05. It can be concluded that a mixture juice mung beans and guava effective for increasing hemoglobin level in cancer patient with chemotherapy. This research suggests that this mixture can be an option for nursing intervention in increasing hemoglobin level for cancer patient after receiving chemotherapy.

The intelligent clinical laboratory as a tool to increase cancer care management productivity.

Science.gov (United States)

Mohammadzadeh, Niloofar; Safdari, Reza

2014-01-01

Studies of the causes of cancer, early detection, prevention or treatment need accurate, comprehensive, and timely cancer data. The clinical laboratory provides important cancer information needed for physicians which influence clinical decisions regarding treatment, diagnosis and patient monitoring. Poor communication between health care providers and clinical laboratory personnel can lead to medical errors and wrong decisions in providing cancer care. Because of the key impact of laboratory information on cancer diagnosis and treatment the quality of the tests, lab reports, and appropriate lab management are very important. A laboratory information management system (LIMS) can have an important role in diagnosis, fast and effective access to cancer data, decrease redundancy and costs, and facilitate the integration and collection of data from different types of instruments and systems. In spite of significant advantages LIMS is limited by factors such as problems in adaption to new instruments that may change existing work processes. Applications of intelligent software simultaneously with existing information systems, in addition to remove these restrictions, have important benefits including adding additional non-laboratory-generated information to the reports, facilitating decision making, and improving quality and productivity of cancer care services. Laboratory systems must have flexibility to change and have the capability to develop and benefit from intelligent devices. Intelligent laboratory information management systems need to benefit from informatics tools and latest technologies like open sources. The aim of this commentary is to survey application, opportunities and necessity of intelligent clinical laboratory as a tool to increase cancer care management productivity.

Intrathoracic anastomotic leakage after gastroesophageal cancer resection is associated with increased risk of recurrence

DEFF Research Database (Denmark)

Kofoed, Steen C; Calatayud, Dan; Jensen, Lone S

2015-01-01

OBJECTIVE: Intrathoracic anastomotic leakage after intended curative resection for cancer in the esophagus or gastroesophageal junction has a negative impact on long-term survival. The aim of this study was to investigate whether an anastomotic leakage was associated with an increased recurrence......]: 1.17-2.29, P = .004) and all-cause mortality (HR = 1.57; 95% CI: 1.23-2.05, P cancer resection....

Laparoscopic vs. open approach for colorectal cancer: evolution over time of minimal invasive surgery.

Science.gov (United States)

Biondi, Antonio; Grosso, Giuseppe; Mistretta, Antonio; Marventano, Stefano; Toscano, Chiara; Drago, Filippo; Gangi, Santi; Basile, Francesco

2013-01-01

In the late '80s the successes of the laparoscopic surgery for gallbladder disease laid the foundations on the modern use of this surgical technique in a variety of diseases. In the last 20 years, laparoscopic colorectal surgery had become a popular treatment option for colorectal cancer patients. Many studies emphasized on the benefits stating the significant advantages of the laparoscopic approach compared with the open surgery of reduced blood loss, early return of intestinal motility, lower overall morbidity, and shorter duration of hospital stay, leading to a general agreement on laparoscopic surgery as an alternative to conventional open surgery for colon cancer. The reduced hospital stay may also decrease the cost of the laparoscopic surgery for colorectal cancer, despite th higher operative spending compared with open surgery. The average reduction in total direct costs is difficult to define due to the increasing cost over time, making challenging the comparisons between studies conducted during a time range of more than 10 years. However, despite the theoretical advantages of laparoscopic surgery, it is still not considered the standard treatment for colorectal cancer patients due to technical limitations or the characteristics of the patients that may affect short and long term outcomes. The laparoscopic approach to colectomy is slowly gaining acceptance for the management of colorectal pathology. Laparoscopic surgery for colon cancer demonstrates better short-term outcome, oncologic safety, and equivalent long-term outcome of open surgery. For rectal cancer, laparoscopic technique can be more complex depending on the tumor location. The advantages of minimally invasive surgery may translate better care quality for oncological patients and lead to increased cost saving through the introduction of active enhanced recovery programs which are likely cost-effective from the perspective of the hospital health-care providers.

Weak circadian rhythm increases neutropenia risk among breast cancer patients undergoing adjuvant chemotherapy.

Science.gov (United States)

Li, Wentao; Kwok, Carol Chi-Hei; Chan, Dominic Chun-Wan; Wang, Feng; Tse, Lap Ah

2018-04-01

Severe neutropenia is a common dose-limiting side effect of adjuvant breast cancer chemotherapy. We aimed to test the hypothesis that weak circadian rhythm is associated with an increased risk of neutropenia using a cohort study. We consecutively recruited 193 breast cancer patients who received adjuvant chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; doxorubicin and cyclophosphamide; docetaxel and cyclophosphamide). Participants wore a wrist actigraph continuously for 168 h at the beginning of chemotherapy. Values of percent rhythm and double amplitude below medians represented weak circadian rhythm. Mesor measured the mean activity level and acrophase symboled the peak time of the rhythm. We used Cox proportional hazard regression model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of grade 4 neutropenia and febrile neutropenia in relation to actigraphy-derived parameters. Low levels of percent rhythm (HR:2.59, 95% CI 1.50-4.72), double amplitude (HR:2.70, 95% CI 1.51-4.85), and mesor (HR: 2.48, 95% CI 1.44-4.29) were positively associated with the risk of grade 4 neutropenia during chemotherapy. Low levels of percent rhythm (HR: 2.41, 95% CI 1.02-5.69) and double amplitude (HR:2.49, 95% CI 1.05-5.90) were also associated with increased risks of febrile neutropenia. The HRs for acrophase were not statistically significant. This study provides the first epidemiological evidence that increased risks of grade 4 neutropenia and febrile neutropenia are associated with weak circadian rhythm among adjuvant breast cancer patients. The results suggest that circadian rhythm might be one potential target for the prevention of chemotherapy-induced neutropenia among cancer patients.

Implicating the H63D polymorphism in the HFE gene in increased incidence of solid cancers: a meta-analysis.

Science.gov (United States)

Shen, L L; Gu, D Y; Zhao, T T; Tang, C J; Xu, Y; Chen, J F

2015-10-29

A number of previous studies have demonstrated that the HFE H63D polymorphism is associated with increased risk of incidence multiple types of cancer, including colorectal cancer, breast cancer, liver cancer, pancreatic cancer, and gynecological malignant tumors. However, the clinical outcomes were inconsistent. Therefore, this meta-analysis was conducted to summarize the effect of the H63D variant on the incidence of solid tumor. PubMed and EMBASE databases were searched for articles associating the HFE H63D polymorphism with cancer risk. The relationships were evaluated by calculating the pooled odds ratios (ORs) with 95% confidence intervals (CIs). A total of 28 studies, including 7728 cancer cases and 11,895 controls, were identified. Statistically significant associations were identified between the HFE H63D polymorphism and solid cancer risk (CG vs CC, OR = 1.14, 95%CI = 1.07-1.23, P HFE H63D polymorphism may play a critical role in the increased aggressiveness of hepatocellular carcinoma and pancreatic cancer.

Strategies to Increase Cancer Detection: Review of True-Positive and False-Negative Results at Digital Breast Tomosynthesis Screening

Science.gov (United States)

Weinstein, Susan P.; McDonald, Elizabeth S.; Conant, Emily F.

2016-01-01

Digital breast tomosynthesis (DBT) represents a valuable addition to breast cancer screening by decreasing recall rates while increasing cancer detection rates. The increased accuracy achieved with DBT is due to the quasi–three-dimensional format of the reconstructed images and the ability to “scroll through” breast tissue in the reconstructed images, thereby reducing the effect of tissue superimposition found with conventional planar digital mammography. The margins of both benign and malignant lesions are more conspicuous at DBT, which allows improved lesion characterization, increased reader confidence, and improved screening outcomes. However, even with the improvements in accuracy achieved with DBT, there remain differences in breast cancer conspicuity by mammographic view. Early data suggest that breast cancers may be more conspicuous on craniocaudal (CC) views than on mediolateral oblique (MLO) views. While some very laterally located breast cancers may be visualized on only the MLO view, the increased conspicuity of cancers on the CC view compared with the MLO view suggests that DBT screening should be performed with two-view imaging. Even with the improved conspicuity of lesions at DBT, there may still be false-negative studies. Subtle lesions seen on only one view may be discounted, and dense and/or complex tissue patterns may make some cancers occult or extremely difficult to detect. Therefore, radiologists should be cognizant of both perceptual and cognitive errors to avoid potential pitfalls in lesion detection and characterization. ©RSNA, 2016 Online supplemental material is available for this article. PMID:27715711

Increased risk of severe depression in male partners of women with breast cancer

DEFF Research Database (Denmark)

Nakaya, Naoki; Saito-Nakaya, Kumi; Bidstrup, Pernille Envold

2010-01-01

BACKGROUND:: A few small studies published to date have suggested that major psychosocial problems develop in the partners of cancer patients; however, to the authors' knowledge, no studies to date have addressed their risk for severe depression. In a retrospective cohort study, the risk for hosp......BACKGROUND:: A few small studies published to date have suggested that major psychosocial problems develop in the partners of cancer patients; however, to the authors' knowledge, no studies to date have addressed their risk for severe depression. In a retrospective cohort study, the risk...... for hospitalization with an affective disorder of the male partners of women with breast cancer was investigated, using unbiased, nationwide, population-based information. METHODS:: Followed were 1,162,596 men born between 1925 and 1973 who were aged ≥30 years at study entry, resided in Denmark between 1994 and 2006......-related indicators obtained from national administrative and disease registers. RESULTS:: During the 13 years of follow-up, breast cancer was diagnosed in the partners of 20,538 men. On multivariable analysis, men whose partner was diagnosed with breast cancer were found to be at an increased risk of being...

The Evolution of Gero-Oncology Nursing.

Science.gov (United States)

Bond, Stewart M; Bryant, Ashley Leak; Puts, Martine

2016-02-01

This article summarizes the evolution of gero-oncology nursing and highlights key educational initiatives, clinical practice issues, and research areas to enhance care of older adults with cancer. Peer-reviewed literature, position statements, clinical practice guidelines, Web-based materials, and professional organizations' resources. Globally, the older adult cancer population is rapidly growing. The care of older adults with cancer requires an understanding of their diverse needs and the intersection of cancer and aging. Despite efforts to enhance competence in gero-oncology and to develop a body of evidence, nurses and health care systems remain under-prepared to provide high-quality care for older adults with cancer. Nurses must take a leadership role in integrating gerontological principles into oncology settings. Working closely with interdisciplinary team members, nurses should utilize available resources and continue to build evidence through gero-oncology nursing research. Copyright © 2016 Elsevier Inc. All rights reserved.

The Evolution of Gero-Oncology Nursing

Science.gov (United States)

Bond, Stewart M.; Bryant, Ashley Leak; Puts, Martine

2016-01-01

Objectives This article summarizes the evolution of gero-oncology nursing and highlights key educational initiatives, clinical practice issues, and research areas to enhance care of older adults with cancer. Data Sources Peer-reviewed literature, position statements, clinical practice guidelines, web-based materials, and professional organizations’ resources. Conclusion Globally, the older adult cancer population is rapidly growing. The care of older adults with cancer requires an understanding of their diverse needs and the intersection of cancer and aging. Despite efforts to enhance competence in gerooncology and to develop a body of evidence, nurses and healthcare systems remain under-prepared to provide high quality care for older adults with cancer. Implications for Nursing Practice Nurses need to take a leadership role in integrating gerontological principles into oncology settings. Working closely with interdisciplinary team members, nurses should utilize available resources and continue to build evidence through gero-oncology nursing research. PMID:26830263

Self-Sampling for Human Papillomavirus Testing among Non-Attenders Increases Attendance to the Norwegian Cervical Cancer Screening Programme

DEFF Research Database (Denmark)

Enerly, Espen; Bonde, Jesper; Schee, Kristina

2016-01-01

Increasing attendance to screening offers the best potential for improving the effectiveness of well-established cervical cancer screening programs. Self-sampling at home for human papillomavirus (HPV) testing as an alternative to a clinical sampling can be a useful policy to increase attendance....... To determine whether self-sampling improves screening attendance for women who do not regularly attend the Norwegian Cervical Cancer Screening Programme (NCCSP), 800 women aged 25-69 years in the Oslo area who were due to receive a 2nd reminder to attend regular screening were randomly selected and invited...... alternative for increasing cervical cancer screening coverage in Norway....

A randomized, controlled trial to increase discussion of breast cancer in primary care.

Science.gov (United States)

Kaplan, Celia P; Livaudais-Toman, Jennifer; Tice, Jeffrey A; Kerlikowske, Karla; Gregorich, Steven E; Pérez-Stable, Eliseo J; Pasick, Rena J; Chen, Alice; Quinn, Jessica; Karliner, Leah S

2014-07-01

Assessment and discussion of individual risk for breast cancer within the primary care setting are crucial to discussion of risk reduction and timely referral. We conducted a randomized controlled trial of a multiethnic, multilingual sample of women ages 40 to 74 years from two primary care practices (one academic, one safety net) to test a breast cancer risk assessment and education intervention. Patients were randomly assigned to control or intervention group. All patients completed a baseline telephone survey and risk assessment (via telephone for controls, via tablet computer in clinic waiting room before visit for intervention). Intervention (BreastCARE) patients and their physicians received an individualized risk report to discuss during the visit. One-week follow-up telephone surveys with all patients assessed patient-physician discussion of family cancer history, personal breast cancer risk, high-risk clinics, and genetic counseling/testing. A total of 655 control and 580 intervention women completed the risk assessment and follow-up interview; 25% were high-risk by family history, Gail, or Breast Cancer Surveillance Consortium risk models. BreastCARE increased discussions of family cancer history [OR, 1.54; 95% confidence interval (CI), 1.25-1.91], personal breast cancer risk (OR, 4.15; 95% CI, 3.02-5.70), high-risk clinics (OR, 3.84; 95% CI, 2.13-6.95), and genetic counseling/testing (OR, 2.22; 95% CI, 1.34-3.68). Among high-risk women, all intervention effects were stronger. An intervention combining an easy-to-use, quick risk assessment tool with patient-centered risk reports at the point of care can successfully promote discussion of breast cancer risk reduction between patients and primary care physicians, particularly for high-risk women. Next steps include scaling and dissemination of BreastCARE with integration into electronic medical record systems. ©2014 American Association for Cancer Research.

Loss of P53 Function in Colon Cancer Cells Results in Increased Phosphocholine and Total Choline

Directory of Open Access Journals (Sweden)

Noriko Mori

2004-10-01

Full Text Available Mutations in the p53 gene are the most frequently observed genetic lesions in human cancers. Human cancers that contain a p53 mutation are more aggressive, more apt to metastasize, and more often fatal. p53 controls numerous downstream targets that can influence various outcomes such as apoptosis, growth arrest, and DNA repair. Based on previous observations using 1H magnetic resonance spectroscopy (MRS, we have identified choline phospholipid metabolite intensities typical of increased malignancy. Here we have used 1H MRS to characterize the choline phospholipid metabolite levels of p53+/+ and p53−/– cells, and demonstrated that loss of p53 function results in increased phosphocholine and total choline. These data suggest that the increased malignancy of cancer cells resulting from loss of p53 may be mediated, in part, through the choline phospholipid pathway.

8q24 rs6983267G variant is associated with increased thyroid cancer risk

Science.gov (United States)

Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Echeverry, Guadalupe Polanco; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carvajal Carmona, Luis G.

2015-01-01

The G allele of the rs6983267 single nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in thyroid cancer susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3,067 cases and 8,575 controls. We detected significant associations between rs6983267G and thyroid cancer in the British Isles (Odds Ratio, OR= 1.19, 95% confidence interval, CI: 1.11–1.27, P= 4.03 × 10−7), Japan (OR= 1.20, 95% CI: 1.03–1.41, P= 0.022) and a borderline significant association of similar effect direction and size in Colombia (OR= 1.19, 95% CI: 0.99–1.44, P= 0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5,484 cases and 12,594 controls, confirmed the association between rs6983267G and thyroid cancer (P= 1.23 × 10−7, OR= 1.13, 95% CI: 1.07–1.18). Our results therefore support the notion that rs6983267G is a bona fide thyroid cancer risk variant that increases the risk of disease by ~13%. PMID:26290501

Post-inhaled corticosteroid pulmonary tuberculosis and pneumonia increases lung cancer in patients with COPD.

Science.gov (United States)

Wu, Ming-Fang; Jian, Zhi-Hong; Huang, Jing-Yang; Jan, Cheng-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Liaw, Yung-Po

2016-10-10

Inhaled corticosteroids (ICS) have been associated with decreased lung cancer risk. However, they have been associated with pulmonary infections (tuberculosis [TB] and pneumonia) in patients with chronic obstructive pulmonary disease (COPD). TB and pneumonia have increased lung cancer risk. The association between post-ICS pulmonary infections and lung cancer remains unclear. We conducted a retrospective cohort study from 2003 to 2010 using the Taiwan National Health Insurance Research Database. Among the 1,089,955 patients with COPD, we identified 8813 new users of ICS prescribed for a period of 3 months or more and 35,252 non-ICS users who were randomly matched for sex, age and date of ICS use from 2003 to 2005. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of pulmonary infections in patients with/without ICS use. The HRs for lung cancer in ICS users with sequential lung infections were as follows; 2.42 (95 % confidence interval [CI], 1.28-4.58) for individuals with TB, 2.37 (95 % CI, 1.01-5.54) for TB and pneumonia, and 1.17(95 % CI, 0.69-1.98) for those with pneumonia. For non-ICS users with pulmonary infections, the HRs were 1.68 (95 % CI, 0.78-3.65) for individual with TB and pneumonia, 1.42 (95 % CI, 0.89-2.26) for TB, and 0.95 (95 % CI, 0.62-1.46) for individuals with pneumonia. COPD patients with TB /or pneumonia who used ICS had increased risk of lung cancer. Because the overall prognosis of lung cancer remains poor, screening tests are recommended for patients with these conditions.

Increased risk of ischemic stroke in cervical cancer patients: a nationwide population-based study

International Nuclear Information System (INIS)

Tsai, Shiang-Jiun; Su, Yu-Chieh; Hung, Shih-Kai; Huang, Yung-Sung; Tung, Chien-Hsueh; Lee, Ching-Chih; Lee, Moon-Sing; Chiou, Wen-Yen; Lin, Hon-Yi; Hsu, Feng-Chun; Tsai, Chih-Hsin

2013-01-01

Increased risk of ischemic stroke has been validated for several cancers, but limited study evaluated this risk in cervical cancer patients. Our study aimed to evaluate the risk of ischemic stroke in cervical cancer patients. The study analyzed data from the 2003 to 2008 National Health Insurance Research Database (NHIRD) provided by the National Health Research Institutes in Taiwan. Totally, 893 cervical cancer patients after radiotherapy and 1786 appendectomy patients were eligible. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the risk of ischemic stroke. The 5-year cumulative risk of ischemic stroke was significantly higher for the cervical cancer group than for the control group (7.8% vs 5.1%; p <0.005). The risk of stroke was higher in younger (age <51 years) than in older (age ≥51 years) cervical cancer patients (HR = 2.73, p = 0.04; HR = 1.37, p = 0.07) and in patients with more than two comorbid risk factors (5 years cumulative stroke rate of two comorbidities: 15% compared to no comorbidities: 4%). These study demonstrated cervical cancer patients had a higher risk of ischemic stroke than the general population, especially in younger patients. Strategies to reduce this risk should be assessed

Evolution of motion uncertainty in rectal cancer: implications for adaptive radiotherapy

Science.gov (United States)

Kleijnen, Jean-Paul J. E.; van Asselen, Bram; Burbach, Johannes P. M.; Intven, Martijn; Philippens, Marielle E. P.; Reerink, Onne; Lagendijk, Jan J. W.; Raaymakers, Bas W.

2016-01-01

Reduction of motion uncertainty by applying adaptive radiotherapy strategies depends largely on the temporal behavior of this motion. To fully optimize adaptive strategies, insight into target motion is needed. The purpose of this study was to analyze stability and evolution in time of motion uncertainty of both the gross tumor volume (GTV) and clinical target volume (CTV) for patients with rectal cancer. We scanned 16 patients daily during one week, on a 1.5 T MRI scanner in treatment position, prior to each radiotherapy fraction. Single slice sagittal cine MRIs were made at the beginning, middle, and end of each scan session, for one minute at 2 Hz temporal resolution. GTV and CTV motion were determined by registering a delineated reference frame to time-points later in time. The 95th percentile of observed motion (dist95%) was taken as a measure of motion. The stability of motion in time was evaluated within each cine-MRI separately. The evolution of motion was investigated between the reference frame and the cine-MRIs of a single scan session and between the reference frame and the cine-MRIs of several days later in the course of treatment. This observed motion was then converted into a PTV-margin estimate. Within a one minute cine-MRI scan, motion was found to be stable and small. Independent of the time-point within the scan session, the average dist95% remains below 3.6 mm and 2.3 mm for CTV and GTV, respectively 90% of the time. We found similar motion over time intervals from 18 min to 4 days. When reducing the time interval from 18 min to 1 min, a large reduction in motion uncertainty is observed. A reduction in motion uncertainty, and thus the PTV-margin estimate, of 71% and 75% for CTV and tumor was observed, respectively. Time intervals of 15 and 30 s yield no further reduction in motion uncertainty compared to a 1 min time interval.

Increased COX-2 expression in patients with ovarian cancer

African Journals Online (AJOL)

ajl yemi

2011-10-26

Oct 26, 2011 ... 10%) subtypes (Kristensen et al., 2003; Green et al.,. 1999). The disease ... history of ovarian and/or breast cancer, and nulliparity, whereas the oral ... and molecular mechanisms of ovarian cancer remain unclear. It is most ..... chemotherapy on the prognosis in advanced epithelial ovarian cancer. N. Engl.

Dynamics of Tumor Heterogeneity Derived from Clonal Karyotypic Evolution

Directory of Open Access Journals (Sweden)

Ashley M. Laughney

2015-08-01

Full Text Available Numerical chromosomal instability is a ubiquitous feature of human neoplasms. Due to experimental limitations, fundamental characteristics of karyotypic changes in cancer are poorly understood. Using an experimentally inspired stochastic model, based on the potency and chromosomal distribution of oncogenes and tumor suppressor genes, we show that cancer cells have evolved to exist within a narrow range of chromosome missegregation rates that optimizes phenotypic heterogeneity and clonal survival. Departure from this range reduces clonal fitness and limits subclonal diversity. Mapping of the aneuploid fitness landscape reveals a highly favorable, commonly observed, near-triploid state onto which evolving diploid- and tetraploid-derived populations spontaneously converge, albeit at a much lower fitness cost for the latter. Finally, by analyzing 1,368 chromosomal translocation events in five human cancers, we find that karyotypic evolution also shapes chromosomal translocation patterns by selecting for more oncogenic derivative chromosomes. Thus, chromosomal instability can generate the heterogeneity required for Darwinian tumor evolution.

Increased risk of breast cancer development after diagnosis of salivary gland tumour

NARCIS (Netherlands)

In der Maur, Caroline D.; Klokman, Willem J.; van Leeuwen, Floor E.; Tan, I. Bing; Rutgers, Emiel J. Th; Balm, Alfons J. M.

2005-01-01

The aim of this study was to evaluate whether patients with salivary gland tumours are at increased risk of developing breast cancer. A retrospective cohort study was performed. Female patients (n = 439) with a salivary gland tumour (major and minor) were included. The diagnosis was confirmed

Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin-6 dependent.

Science.gov (United States)

Reddel, C J; Allen, J D; Ehteda, A; Taylor, R; Chen, V M Y; Curnow, J L; Kritharides, L; Robertson, G

2017-03-01

Essentials Cancer cachexia and cancer-associated thrombosis have not previously been mechanistically linked. We assessed thrombin generation and coagulation parameters in cachectic C26 tumor-bearing mice. C26 mice are hypercoagulable, partially corrected by blocking tumor derived interleukin-6. Coagulability and anti-inflammatory interventions may be clinically important in cancer cachexia. Background Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer, which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. Objectives To assess if cancer cachexia altered the coagulation state and if this was attributable to tumor IL-6 production. Methods In male BALB/c*DBA2 (F1 hybrid) mice with a C26 tumor we used modified calibrated automated thrombogram and fibrin generation (based on overall hemostatic potential) assays to assess the functional coagulation state, and also examined fibrinogen, erythrocyte sedimentation rate (ESR), platelet count, tissue factor pathway inhibitor (TFPI) and hepatic expression of coagulation factors by microarray. C26 mice were compared with non-cachectic NC26, pair-fed and sham control mice. IL-6 expression in C26 cells was knocked down by lentiviral shRNA constructs. Results C26 mice with significant weight loss and highly elevated IL-6 had elevated thrombin generation, fibrinogen, ESR, platelets and TFPI compared with all control groups. Fibrin generation was elevated compared with pair-fed and sham controls but not compared with NC26 tumor mice. Hepatic expression of coagulation factors and fibrinolytic inhibitors was increased. Silencing IL-6 in the tumor significantly, but incompletely, attenuated the increased thrombin generation, fibrinogen and TFPI. Conclusions Cachectic C26 tumor-bearing mice are in a

Infiltrating T Cells Promote Bladder Cancer Progression via Increasing IL1→Androgen Receptor→HIF1α→VEGFa Signals.

Science.gov (United States)

Tao, Le; Qiu, Jianxin; Jiang, Ming; Song, Wenbin; Yeh, Shuyuan; Yu, Hong; Zang, Lijuan; Xia, Shujie; Chang, Chawnshang

2016-08-01

The tumor microenvironment impacts tumor progression and individual cells, including CD4(+) T cells, which have been detected in bladder cancer tissues. The detailed mechanism of how these T cells were recruited to the bladder cancer tumor and their impact on bladder cancer progression, however, remains unclear. Using a human clinical bladder cancer sample survey and in vitro coculture system, we found that bladder cancer has a greater capacity to recruit T cells than surrounding normal bladder tissues. The consequences of higher levels of recruited T cells in bladder cancer included increased bladder cancer metastasis. Mechanism dissection revealed that infiltrating T cells might function through secreting the cytokine IL1, which increases the recruitment of T cells to bladder cancer and enhances the bladder cancer androgen receptor (AR) signaling that results in increased bladder cancer cell invasion via upregulation of hypoxia-inducible factor-1α (HIF1α)/VEGFa expression. Interruption of the IL1→AR→HIF1α→VEGFa signals with inhibitors of HIF1α or VEGFa partially reversed the enhanced bladder cancer cell invasion. Finally, in vivo mouse models of xenografted bladder cancer T24 cells with CD4(+) T cells confirmed in vitro coculture studies and concluded that infiltrating CD4(+) T cells can promote bladder cancer metastasis via modulation of the IL1→AR→HIF1α→VEGFa signaling. Future clinical trials using small molecules to target this newly identified signaling pathway may facilitate the development of new therapeutic approaches to better suppress bladder cancer metastasis. Mol Cancer Ther; 15(8); 1943-51. ©2016 AACR. ©2016 American Association for Cancer Research.

Zebrafish as a model to assess cancer heterogeneity, progression and relapse

Science.gov (United States)

Blackburn, Jessica S.; Langenau, David M.

2014-01-01

Clonal evolution is the process by which genetic and epigenetic diversity is created within malignant tumor cells. This process culminates in a heterogeneous tumor, consisting of multiple subpopulations of cancer cells that often do not contain the same underlying mutations. Continuous selective pressure permits outgrowth of clones that harbor lesions that are capable of enhancing disease progression, including those that contribute to therapy resistance, metastasis and relapse. Clonal evolution and the resulting intratumoral heterogeneity pose a substantial challenge to biomarker identification, personalized cancer therapies and the discovery of underlying driver mutations in cancer. The purpose of this Review is to highlight the unique strengths of zebrafish cancer models in assessing the roles that intratumoral heterogeneity and clonal evolution play in cancer, including transgenesis, imaging technologies, high-throughput cell transplantation approaches and in vivo single-cell functional assays. PMID:24973745

Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma.

Science.gov (United States)

Jian, Zhi-Hong; Huang, Jing-Yang; Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

2016-01-01

To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22-5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73-2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84-6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57-2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63-1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05-2.32; p = 0.261) for pneumonia+ TB, respectively. Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB.

Increased pancreatic cancer risk following radiotherapy for testicular cancer

DEFF Research Database (Denmark)

Hauptmann, Michael; Børge Johannesen, Tom; Gilbert, Ethel S

2016-01-01

with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum. CONCLUSIONS: A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small...

Bevacizumab increases the incidence of cardiovascular events in patients with metastatic breast or colorectal cancer

Directory of Open Access Journals (Sweden)

Ioannis Kapelakis

2017-05-01

Conclusions: The addition of bevacizumab to conventional chemotherapy for metastatic breast or colorectal cancer increases the incidence of cardiovascular events, which is mainly due to the increased prevalence of myocardial infarction and thromboembolic events.

[Possible cause of the increased incidence of lung cancer in 1987 in the 10th District of Budapest (1975-1989)].

Science.gov (United States)

Abrahám, E; Karácsonyi, L; Dinya, E

1990-12-30

In 1975 in one of the major industrial districts of Budapest some longitudinal epidemiological examinations were carried out with the aim of, among others, determination of connection between environmental injuries and lung cancer incidence in connection with determination of lung cancer risk groups. Between 1975-1989 out of the environmental injuries the most important was the radioactive contamination observed due to the atomic power station catastrophe in Chernobil (1986). In 1987 the incidence of lung cancer increased. The increase was significant among the 50-69-year-old women, and expressly among the heavy smokers. In 1987, especially among women, but also in both sexes, the ratio among the major cell types of lung cancer shifted towards micro-cellular ones. In 1988 and 1989 lung cancer incidence has decreased. In view of the above a hypothesis was raised: patients who have previously suffered immunobiological hurt, could not prevent the increased radioactive burden and got ill with lung cancer earlier, than it should have been happened without this increased burden. For clarification this question further examinations are considered to be necessary.

Evolution of breast cancer screening in the Medicare population: clinical and economic implications.

Science.gov (United States)

Killelea, Brigid K; Long, Jessica B; Chagpar, Anees B; Ma, Xiaomei; Wang, Rong; Ross, Joseph S; Gross, Cary P

2014-08-01

Newer approaches to mammography, including digital image acquisition and computer-aided detection (CAD), and adjunct imaging (e.g., magnetic resonance imaging [MRI]) have diffused into clinical practice. The impact of these technologies on screening-related cost and outcomes remains undefined, particularly among older women. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we constructed two cohorts of women without a history of breast cancer and followed each cohort for 2 years. We compared the use and cost of screening mammography including digital mammography and CAD, adjunct procedures including breast ultrasound, MRI, and biopsy between the period of 2001 and 2002 and the period of 2008 and 2009 using χ(2) and t test. We also assessed the change in breast cancer stage and incidence rates using χ(2) and Poisson regression. All statistical tests were two-sided. There were 137150 women (mean age = 76.0 years) in the early cohort (2001-2002) and 133097 women (mean age = 77.3 years) in the later cohort (2008-2009). The use of digital image acquisition for screening mammography increased from 2.0% in 2001 and 2002 to 29.8% in 2008 and 2009 (P screening-related cost per capita increased from $76 to $112 (P breast cancer screening-related costs increased substantially from 2001 through 2009 among Medicare beneficiaries, a clinically significant change in stage at diagnosis was not observed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Glucocorticoid receptor beta increases migration of human bladder cancer cells.

Science.gov (United States)

McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

2016-05-10

Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion

Directory of Open Access Journals (Sweden)

Michalski Christoph W

2007-12-01

Full Text Available Abstract Background Bone gamma-carboxyglutamate protein (BGLAP; osteocalcin is a small, highly conserved molecule first identified in the mineralized matrix of bone. It has been implicated in the pathophysiology of various malignancies. In this study, we analyzed the expression and role of BGLAP in the normal human pancreas, chronic pancreatitis (CP, and pancreatic ductal adenocarcinoma (PDAC using quantitative RT-PCR, immunohistochemistry, immunocytochemistry and enzyme immunoassays, as well as cell proliferation and invasion assays. Gene silencing was carried out using specific siRNA molecules. Results Compared to the normal pancreas, BGLAP mRNA and protein levels were not significantly different in CP and PDAC tissues. BGLAP was faintly present in the cytoplasm of normal acinar cells but was strongly expressed in the cytoplasm and nuclei of tubular complexes and PanIN lesions of CP and PDAC tissues. Furthermore, BGLAP expression was found in the cancer cells in PDAC tissues as well as in 4 cultured pancreatic cancer cell lines. TNFalpha reduced BGLAP mRNA and protein expression levels in pancreatic cancer cell lines. In addition, BGLAP silencing led to reduction of both cell growth and invasion in those cells. Conclusion BGLAP is expressed in pancreatic cancer cells, where it potentially increases pancreatic cancer cell growth and invasion through autocrine and/or paracrine mechanisms.

Suberoylanilide hydroxamic acid increases anti-cancer effect of tumor necrosis factor-α through up-regulation of TNF receptor 1 in lung cancer cells.

Science.gov (United States)

You, Bo Ra; Han, Bo Ram; Park, Woo Hyun

2017-03-14

Suberoylanilide hydroxamic acid (SAHA) as a histone deacetylase (HDAC) inhibitor has anti-cancer effect. Here, we evaluated the effect of SAHA on HDAC activity and cell growth in many normal lung and cancer cells. We observed that the HDAC activities of lung cancer cells were higher than that of normal lung cells. SAHA inhibited the growth of lung cancer cells regardless of the inhibitory effect on HDAC. This agent induced a G2/M phase arrest and apoptosis, which was accompanied by mitochondrial membrane potential (MMP: ΔΨm) loss in lung cancer cells. However, SAHA did not induce cell death in normal lung cells. All tested caspase inhibitors prevented apoptotic cell death in SAHA-treated A549 and Calu-6 lung cancer cells. Treatment with tumor necrosis factor-alpha (TNF-α) enhanced apoptosis in SAHA-treated lung cancer cells through caspase-8 and caspase-9 activations. Especially, SAHA increased the expression level of TNF-α receptor 1 (TNFR1), especially acetylation of the region of TNFR1 promoter -223/-29 in lung cancer cells. The down-regulation of TNFR1 suppressed apoptosis in TNF-α and SAHA-treated lung cancer cells. In conclusion, SAHA inhibited the growth of lung cancer cells via a G2/M phase arrest and caspase-dependent apoptosis. SAHA also enhanced apoptotic effect of TNF-α in human lung cancer cells through up-regulation of TNFR1. TNF-α may be a key to improve anti-cancer effect of HDAC inhibitors.

Urinary Tract Cancer in Lynch Syndrome; Increased Risk in Carriers of MSH2 Mutations

DEFF Research Database (Denmark)

Joost, Patrick; Therkildsen, Christina; Dominguez-Valentin, Mev

2015-01-01

and microsatellite instability in 23% of the tumors. Mutations in MSH2 were overrepresented (73%), and MSH2 mutation carriers were at a significantly increased risk of developing urinary tract cancer compared with individuals with mutations in MLH1 or MSH6. CONCLUSION: Cancers of the upper urinary tract...

The proportion of cancer-related entries in PubMed has increased considerably; is cancer truly “The Emperor of All Maladies”?

Science.gov (United States)

2017-01-01

In this work, the public database of biomedical literature PubMed was mined using queries with combinations of keywords and year restrictions. It was found that the proportion of Cancer-related entries per year in PubMed has risen from around 6% in 1950 to more than 16% in 2016. This increase is not shared by other conditions such as AIDS, Malaria, Tuberculosis, Diabetes, Cardiovascular, Stroke and Infection some of which have, on the contrary, decreased as a proportion of the total entries per year. Organ-related queries were performed to analyse the variation of some specific cancers. A series of queries related to incidence, funding, and relationship with DNA, Computing and Mathematics, were performed to test correlation between the keywords, with the hope of elucidating the cause behind the rise of Cancer in PubMed. Interestingly, the proportion of Cancer-related entries that contain “DNA”, “Computational” or “Mathematical” have increased, which suggests that the impact of these scientific advances on Cancer has been stronger than in other conditions. It is important to highlight that the results obtained with the data mining approach here presented are limited to the presence or absence of the keywords on a single, yet extensive, database. Therefore, results should be observed with caution. All the data used for this work is publicly available through PubMed and the UK’s Office for National Statistics. All queries and figures were generated with the software platform Matlab and the files are available as supplementary material. PMID:28282418

The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression.

Science.gov (United States)

Brown, Joel S; Cunningham, Jessica J; Gatenby, Robert A

2015-07-19

Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed--a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler-Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the 'cost' (decreased fecundity) of suppression verses the 'cost' of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

[Utility of Multiple Increased Lung Cancer Tumor Markers in Treatment of Patients with Advanced Lung Adenocarcinoma].

Science.gov (United States)

Peng, Yan; Wang, Yan; Hao, Xuezhi; Li, Junling; Liu, Yutao; Wang, Hongyu

2017-10-20

Among frequently-used tumor markers in lung cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), cytokeratin 19 (CYFRA21-1) and squamous carcinoma antigen (SCC), neuron specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP) are respectively expressed highly in lung adenocarcinoma, lung squamous carcinoma and small cell lung cancer. By comparing patients with multiple increased tumor markers (group A) and patients with increase of CEA and/or CA125 (group B), this study aims to investigate the utility of multiple increased tumor markers in therapeutic evaluation and prediction of disease relapsing in patients with advanced lung adenocarcinoma. Patients with stage IV lung adenocarcinoma who receiving the first line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic, serum tumor markers before chemotherapy, efficacy evaluation, progression-free survival (PFS) were analyzed. Except CEA and CA125, the highest ratio of increased tumor markersin group A was CYFRA21-1 (93%), then was NSE (36%), SCC (13%) and ProGRP (12%). Patients with multiple increased tumor markers tend to have more distant metastasis (Ptumor markers have high risk of relapse, and maintenance therapy can reduce relapse risk.

Cancer is an adaptation that selects in animals against energy dissipation.

Science.gov (United States)

Muller, Anthonie W J

2017-07-01

As cancer usually follows reproduction, it is generally assumed that cancer does not select. Graham has however argued that juvenile cancer, which precedes reproduction, could during evolution have implemented a "cancer selection" that resulted in novel traits that suppress this juvenile cancer; an example is protection against UV sunlight-induced cancer, required for the emergence of terrestrial animals from the sea. We modify the cancer selection mechanism to the posited "cancer adaptation" mechanism, in which juvenile mortality is enhanced through the diminished care received by juveniles from their (grand) parents when these suffer from cancer in old age. Moreover, it is posited that the cancer adaptation selects against germline "dissipative genes", genes that result in enhanced free energy dissipation. Cancer's progression is interpreted as a cascade at increasing scale of repeated amplification of energy dissipation, a cascade involving heat shock, the Warburg effect, the cytokine IL-6, tumours, and hypermetabolism. Disturbance of any physiological process must enhance energy dissipation if the animal remains functioning normally, what explains multicausality, why "everything gives you cancer". The hypothesis thus comprises two newly invoked partial processes-diminished (grand) parental care and dissipation amplification-and results in a "selection against enhanced energy dissipation" which gives during evolution the benefit of energy conservation. Due to this benefit, cancer would essentially be an adaptation, and not a genetic disease, as assumed in the "somatic mutation theory". Cancer by somatic mutations is only a side process. The cancer adaptation hypothesis is substantiated by (1) cancer's extancy, (2) the failure of the somatic mutation theory, (3) cancer's initiation by a high temperature, (4) the interpretation of cancer's progression as a thermal process, and (5) the interpretation of tumours as organs that implement thermogenesis. The hypothesis

The Role of Oral Contraceptive Pills on Increased Risk of Breast Cancer in Iranian Populations: A Meta-analysis.

Science.gov (United States)

Soroush, Ali; Farshchian, Negin; Komasi, Saeid; Izadi, Neda; Amirifard, Nasrin; Shahmohammadi, Afshar

2016-12-01

Cancer is one of the main public health issues in the world. Breast cancer is one of the most common types of cancer among women. It is also the second cause of mortality in women. The association between the use of oral contraceptive pills and breast cancer is controversial and a main issue in public health. Some findings have shown that taking these pills does not have a significant effect in increasing the risk of breast cancer, while others have confirmed the carcinogenic effect of these products. These contradictory findings necessitated this meta-analysis, through of all correlated studies in Iran. All published studies were considered from June 2000 until June 2015, using reliable Latin databases like PubMed, Google Scholar, Google search, Scopus, and Science Direct, and Persian database like SID, Irandoc, IranMedex, and Magiran. Finally, 26 papers were selected: 24 studies were case control while two were population based studies. A total of 26 papers with 46,260 participants were assessed since 2001. Overall estimate of OR for the effect of oral contraceptive pills on breast cancer is 1.521 (CI = 1.25-1.85), which shows that the intervention group had more chance (52%) compared to the control group ( P = 0.001). Using these pills increased the risk of breast cancer up to 1.52 times. Because of directly increasing levels of estrogen and the role of estrogen in gaining weight indirectly, oral contraceptive pills can stimulate the occurrence of breast cancer. More studies should be conducted for controlling the period of pill use.

Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis.

Science.gov (United States)

Chu, Xin-Yi; Jiang, Ling-Han; Zhou, Xiong-Hui; Cui, Ze-Jia; Zhang, Hong-Yu

2017-07-14

The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukaryota could control the unlimited proliferation of cancer cells, and the subnetwork originating from eumetazoa could recapitulate the other hallmarks of cancer. In addition, investigations based on multiple datasets revealed that cancer driver genes were enriched in genes originating from eukaryota, opisthokonta, and eumetazoa. These results have important implications for enhancing the robustness of cancer prognosis models through selecting the gene signatures by the gene age information.

miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor

International Nuclear Information System (INIS)

Park, Jong-Kook; Henry, Jon C.; Jiang, Jinmai; Esau, Christine; Gusev, Yuriy; Lerner, Megan R.; Postier, Russell G.; Brackett, Daniel J.; Schmittgen, Thomas D.

2011-01-01

Research highlights: → The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. → miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. → miR-132 and miR-212 expression is increased by a β2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- Abstract: Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G 2 /M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the β2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The β2 adrenergic pathway may play an important role in this novel mechanism.

Law 16.097 Prevention program of uterine cervix cancer in Uruguay: Uterine cervix cancer

International Nuclear Information System (INIS)

2004-01-01

Every year in Uruguay, is diagnosed around 600 new cases of cancer of uterine cervix. Next important information was related on this cancer and the evolution that will have the carrying of this illness, it was informed about the prevention, symptoms, I diagnose and treatment of the same one

antiEGFR conjugated gold nanoparticles for increasing radiosensitivity in lung cancer cells

International Nuclear Information System (INIS)

Pujari, Geetanjali; Sarma, Asitikantha; Avasthi, Devesh K.

2014-01-01

One of the set back that lies in lung cancer treatment is the over expression of Epidermal Growth Factor Receptor (EGFR). EGFR is a transmembrane receptor that is highly expressed in lung cancer that leads to cell survival, proliferation and spread of the disease. Over the years, EGFR inhibitors, monoclonal antibodies, are being used in combination with radiotherapy in lung cancer patients so as to achieve better results. In the recent time, application of Au nanoparticles (AuNPs) in diagnosis and treatment of cancer has been extensively used in biomedical research. Among various applications, there is considerable use of AuNPs seen on the dose enhancement effect (radiosensitization) in radiation therapy of cancer. The conjugation of AuNP with monoclonal antibody antiEGFR (antiEGFR-AuNP) may provide excellent agent to sensitize the cells to heavy ion radiation. We synthesized AuNPs by citrate reduction method. Most of AuNPs were in the size range of 6-8 nm as studies by Transmission Electron Microscope (TEM). These AuNPs were found to be non toxic in A549 cells and thus biocompatible. Further, we conjugated AuNPs with antiEGFR (antiEGFR-AuNP). The conjugation was confirmed by UV-Vis spectroscopy. A549 cells were treated with antiEGFR-AuNP. TEM was carried out of ultrathin cross sections of antiEGFR-AuNP treated A549 cells to check the attachment internalization of AuNPs. We observed that the AuNPs are attached on the cell membrane as well as internalized in cytoplasm. Upon exposure of antiEGFR-AuNP treated cells to heavy ion 12 C beam, showed increase in radiosensitization as studied by survival assay and MTT assay. We will also explain the EGFR expression and cell cycle proliferation in A549 cells upon heavy ion beam irradiation of these. The study aims to overcome the current limitations of cancer-targeted therapies and improve the treatment modality of lung cancer. (author)

Childhood height increases the risk of prostate cancer mortality

DEFF Research Database (Denmark)

Aarestrup, J; Gamborg, M; Cook, M B

2015-01-01

cancers. Cox proportional hazards regressions were performed. RESULTS: 630 men had prostate cancer recorded as the underlying cause of death. Childhood height at age 13years was positively associated with prostate cancer-specific mortality (hazard ratio [HR]per z-score=1.2, 95% confidence interval [CI]: 1.1-1.3......). Associations were significant at all other childhood ages. Growth analyses showed that height at age 13years had a stronger association with prostate cancer-specific mortality than height at age 7, suggesting the association at age 7 is largely mediated through later childhood height. The tallest boys at age...... 13years had a significantly worse survival, but only when restricted to a diagnosis at years of age (HRz-score of 1=1.7, 95% CI: 1.3-2.4). These associations were significant at all other childhood ages. Childhood BMI was not associated with prostate cancer mortality or survival. CONCLUSION...

Increased activity of the mannan-binding lectin complement activation pathway in patients with colorectal cancer

DEFF Research Database (Denmark)

Ytting, H; Jensenius, Jens Christian; Christensen, I J

2004-01-01

BACKGROUND: Postoperative bacterial infectious complications are frequent in patients with colorectal cancer (CRC), with subsequent increased recurrence rates and poor prognosis. Deficiency of the mannan-binding lectin (MBL) complement activation pathway may cause increased risk of infection......: Serum MBL concentrations and MBL/MASP activity were determined using immunofluorometric assays. The levels are presented as the median, inter-quartile range and range. RESULTS: Serum MBL levels were significantly (P cancer (1384 (400-2188) ng/mL) (median...... in the colon or rectum, and disease stages according to Dukes' classification. No statistical difference (P=0.20) in frequency of MBL deficiency was found between the patients (20%) and the donors (27%). CONCLUSIONS: Overall, the MBL complement activation pathway is significantly increased in patients...

Fast and scalable inference of multi-sample cancer lineages.

KAUST Repository

Popic, Victoria; Salari, Raheleh; Hajirasouliha, Iman; Kashef-Haghighi, Dorna; West, Robert B; Batzoglou, Serafim

2015-01-01

Somatic variants can be used as lineage markers for the phylogenetic reconstruction of cancer evolution. Since somatic phylogenetics is complicated by sample heterogeneity, novel specialized tree-building methods are required for cancer phylogeny reconstruction. We present LICHeE (Lineage Inference for Cancer Heterogeneity and Evolution), a novel method that automates the phylogenetic inference of cancer progression from multiple somatic samples. LICHeE uses variant allele frequencies of somatic single nucleotide variants obtained by deep sequencing to reconstruct multi-sample cell lineage trees and infer the subclonal composition of the samples. LICHeE is open source and available at http://viq854.github.io/lichee .

Fast and scalable inference of multi-sample cancer lineages.

KAUST Repository

Popic, Victoria

2015-05-06

Somatic variants can be used as lineage markers for the phylogenetic reconstruction of cancer evolution. Since somatic phylogenetics is complicated by sample heterogeneity, novel specialized tree-building methods are required for cancer phylogeny reconstruction. We present LICHeE (Lineage Inference for Cancer Heterogeneity and Evolution), a novel method that automates the phylogenetic inference of cancer progression from multiple somatic samples. LICHeE uses variant allele frequencies of somatic single nucleotide variants obtained by deep sequencing to reconstruct multi-sample cell lineage trees and infer the subclonal composition of the samples. LICHeE is open source and available at http://viq854.github.io/lichee .

Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma

Science.gov (United States)

Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

2016-01-01

Purpose To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. Methods The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. Results A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22–5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73–2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84–6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57–2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63–1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05–2.32; p = 0.261) for pneumonia+ TB, respectively. Conclusions Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB. PMID:27448321

Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

Directory of Open Access Journals (Sweden)

Ina Bähr

2017-01-01

Full Text Available Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity.

What implementation interventions increase cancer screening rates? a systematic review

Directory of Open Access Journals (Sweden)

Lent Barbara

2011-09-01

Full Text Available Abstract Background Appropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. However, effective implementation strategies are warranted if the full benefits of screening are to be realized. As part of a larger agenda to create an implementation guideline, we conducted a systematic review to evaluate interventions designed to increase the rate of breast, cervical, and colorectal cancer (CRC screening. The interventions considered were: client reminders, client incentives, mass media, small media, group education, one-on-one education, reduction in structural barriers, reduction in out-of-pocket costs, provider assessment and feedback interventions, and provider incentives. Our primary outcome, screening completion, was calculated as the overall median post-intervention absolute percentage point (PP change in completed screening tests. Methods Our first step was to conduct an iterative scoping review in the research area. This yielded three relevant high-quality systematic reviews. Serving as our evidentiary foundation, we conducted a formal update. Randomized controlled trials and cluster randomized controlled trials, published between 2004 and 2010, were searched in MEDLINE, EMBASE and PSYCHinfo. Results The update yielded 66 studies new eligible studies with 74 comparisons. The new studies ranged considerably in quality. Client reminders, small media, and provider audit and feedback appear to be effective interventions to increase the uptake of screening for three cancers. One-on-one education and reduction of structural barriers also appears effective, but their roles with CRC and cervical screening, respectively, are less established. More study is required to assess client incentives, mass media, group education, reduction of out-of-pocket costs, and provider incentive interventions. Conclusion The new evidence generally aligns with the evidence and conclusions from the original systematic

MiR-146a rs2910164 polymorphism increases the risk of digestive system cancer: A meta-analysis.

Science.gov (United States)

Xie, Wen Qun; Wang, Xiao Fan

2017-02-01

There is merging evidence suggesting that the miR-146a polymorphism might be associated with susceptibility to digestive system cancer. However, previous published studies have failed to achieve a definitive conclusion. To address this issue, an updated meta-analysis was performed. A comprehensive electronic search was conducted using the following source to identify the eligible studies: PubMed, Embase, China BioMedicine, the Cochrane Library, and Google Scholar. Odds ratios and its corresponding 95% confidence interval (CI) was used in the quantitative synthesis. The database search identified 1344 eligible studies, of which 32 (comprising 12,541 cases and 15,925 controls) were included. The results indicate that the miR-146a rs2910164 polymorphism was significantly associated with increased risk of digestive system cancer in heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02-1.30, P=0.02), and recessive model (GG vs. GC+CC: OR=1.11, 95% CI: 1.04-1.17, P=0.006). Subgroup analysis by cancer site revealed increased risk in gastric cancer above heterozygote comparison (GG vs. GC: OR=1.13, 95% CI: 1.02-1.25, P=0.02), and recessive model (GG vs. GC+CC: OR=1.15, 95% CI: 1.04-1.26, P=0.006). Similarly, increased cancer risk was observed in hepatocellular carcinoma when compared with homozygote comparison (GG vs. CC: OR=1.21, 95% CI: 1.04-1.42, P=0.02), heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02-1.29, P=0.02), and dominant model (GG+GC vs. CC: OR=1.16, 95% CI: 1.04-1.29, P=0.009). When stratified by ethnicity and quality score, increased cancer risks were also observed among Asians, Caucasians and high quality studies subgroup. The current study revealed that miR-146a G/C genetic polymorphism was more likely to be associated with digestive system cancer risk. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Basal stamcellebiologi og cancer

DEFF Research Database (Denmark)

Porse, Bo T; Petersen, Ole W; Helin, Kristian

2010-01-01

The finding that tumours, like normal tissues, are endowed with varying degrees of cellular heterogeneity has far-reaching consequences for our understanding of cancer. The cancer stem cell and clonal evolution models have both been proposed to explain tumour-associated cellular heterogeneity. Here......, we briefly review these two non-exclusive models with special emphasis on how they aid our understanding of cancer and their implications for therapeutic strategies. Finally, we discuss the close association between basic stem cell biology and cancer, focusing on the role of self-renewal....

Basal stamcellebiologi og cancer

DEFF Research Database (Denmark)

Porse, Bo T; Petersen, Ole W; Helin, Kristian

2010-01-01

, we briefly review these two non-exclusive models with special emphasis on how they aid our understanding of cancer and their implications for therapeutic strategies. Finally, we discuss the close association between basic stem cell biology and cancer, focusing on the role of self-renewal.......The finding that tumours, like normal tissues, are endowed with varying degrees of cellular heterogeneity has far-reaching consequences for our understanding of cancer. The cancer stem cell and clonal evolution models have both been proposed to explain tumour-associated cellular heterogeneity. Here...

The stepwise evolution of the exome during acquisition of docetaxel resistance in breast cancer cells

DEFF Research Database (Denmark)

Hansen, Stine Ninel; Ehlers, Natasja Spring; Zhu, Shida

2016-01-01

Background: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic...... alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. Results: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing...... resistance relevant genomic variation appeared to arise midway towards fully resistant cells corresponding to passage 31 (5 nM docetaxel) for MDA-MB-231 and passage 16 (1.2 nM docetaxel) for MCF-7, and where the cells also exhibited a period of reduced growth rate or arrest, respectively. MCF-7 cell acquired...

The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence.

NARCIS (Netherlands)

Mekel-Bobrov, N.; Posthuma, D.; Gilbert, S.L.; Lind, P.; Gosso, M.F.; Luciano, M.; Harris, S.E.; Bates, T.C.; Polderman, T.J.C.; Whalley, L.J.; Fox, H.; Starr, J.M.; Evans, P.D.; Montgomery, GW; Fernandes, C.; Heutink, P.; Martin, N.G.; Boomsma, D.I.; Deary, I.J.; Wright, M.J.; de Geus, E.J.C.; Lahn, B.T.

2007-01-01

Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary

Effects of Cognitive-Behavioral Group Therapy on Increased Life Expectancy of Male Patients with Gastric Cancer

Directory of Open Access Journals (Sweden)

E Mohammadian akerdi

2016-06-01

Full Text Available BACKGROUND AND OBJECTIVE: Cancers are a broad group of diseases, each having their own etiology, treatment, and prognosis. The majority of cancer patients experience a period of mental stress during their disease. Given the effective role of life expectancy in dealing with chronic diseases, such as stomach cancer, this study aimed to evaluate the effects of cognitive-behavioral group therapy on increased life expectancy of male patients with gastric cancer. METHODS: This quasi-experiment was conducted on 92 male patients with gastric cancer referring to Tuba Medical Center, Sari, Iran in 2014. Patients were randomly divided into two groups of test (n=46 and control (n=46. The two groups completed the Adult Hope Scale (AHS by Snyder in pretest stage. At the next stage, samples of the test group were exposed to 10 sessions of cognitive-behavioral group therapy (each session: 90 min, while the control group did not receive any special treatment. Both study groups completed the questionnaire again at the posttest stage, followed by the comparison of results. FINDINGS: In terms of life expectancy, mean scores of the test and control groups at the pretest stage were 37.21±4.7 and 36.26±4.73, respectively. Meanwhile, mean scores of the mentioned groups at the posttest stage were 40.02±3.87 and 36.23±4.8, respectively. A significant increase was observed in the mean scores of test and control groups at the posttest stage compared to before the intervention. Moreover, a significant difference was found between the study groups regarding life expectancy and its components (p<0.01. CONCLUSION: According to the results, cognitive-behavioral group therapy could increase life expectancy in patients with gastric cancer.

Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

International Nuclear Information System (INIS)

Roy, Lopamudra Das; Ghosh, Sriparna; Pathangey, Latha B; Tinder, Teresa L; Gruber, Helen E; Mukherjee, Pinku

2011-01-01

Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in

Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer.

Science.gov (United States)

Roy, Lopamudra Das; Ghosh, Sriparna; Pathangey, Latha B; Tinder, Teresa L; Gruber, Helen E; Mukherjee, Pinku

2011-08-22

Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in

Increased T-helper 17 cell differentiation mediated by exosome-mediated microRNA-451 redistribution in gastric cancer infiltrated T cells.

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Liu, Feng; Bu, Zhouyan; Zhao, Feng; Xiao, Daping

2018-01-01

MicroRNA (miR)-451 is a cell metabolism-related miRNA that can mediate cell energy-consuming models by several targets. As miR-451 can promote mechanistic target of rapamycin (mTOR) activity, and increased mTOR activity is related to increased differentiation of T-helper 17 (Th17) cells, we sought to investigate whether miR-451 can redistribute from cancer cells to infiltrated T cells and enhance the distribution of Th17 cells through mTOR. Real-time PCR was used for detecting expression of miR-451 in gastric cancer, tumor infiltrated T cells and exosomes, and distribution of Th17 was evaluated by both flow cytometry and immunohistochemistry (IHC). Immunofluorescence staining was used in monitoring the exosome-enveloped miR-451 from cancer cells to T cells with different treatments, and signaling pathway change was analyzed by western blot. miR-451 decreased significantly in gastric cancer (GC) tissues but increased in infiltrated T cells and exosomes; tumor miR-451 was negatively related to infiltrated T cells and exosome miR-451. Exosome miR-451 can not only serve as an indicator for poor prognosis of post-operation GC patients but is also related to increased Th17 distribution in gastric cancer. miR-451 can redistribute from cancer cells to T cells with low glucose treatment. Decreased 5' AMP-activated protein kinase (AMPK) and increased mTOR activity was investigated in miR-451 redistributed T cells and the Th17 polarized differentiation of these T cells were also increased. Exosome miR-451 derived from tumor tissues can serve as an indicator for poor prognosis and redistribution of miR-451 from cancer cells to infiltrated T cells in low glucose treatment can enhance Th17 differentiation by enhancing mTOR activity. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

A short-term increase in cancer risk associated with daytime napping is likely to reflect pre-clinical disease: prospective cohort study.

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Cairns, B J; Travis, R C; Wang, X-S; Reeves, G K; Green, J; Beral, V

2012-07-24

Sleep disturbance, a correlate of which is daytime napping, has been hypothesised to be associated with risk of breast and other cancers. We estimated relative risks (RR) of breast and other invasive cancers by the reported frequency of daytime napping in a large prospective cohort of middle-aged women in the UK. During an average of 7.4 years of follow-up, 20 058 breast cancers and 31 856 other cancers were diagnosed. Over the first 4 years of follow-up, daytime napping (sometimes/usually vs rarely/never) was associated with slightly increased risks of breast cancer (RR=1.10, 95% CI 1.06-1.15) and of other cancers (RR=1.12, 1.08-1.15), but the RRs decreased significantly with increasing follow-up time (P=0.001 and P=0.01, respectively, for trend). Four or more years after baseline, there was no elevated risk of breast cancer (RR=1.00, 0.96-1.05), and only marginally greater risk of other cancers (RR=1.04, 1.01-1.07). The effect of pre-clinical disease is a likely explanation for the short-term increased risk of breast and other cancers associated with daytime napping. © 2012 Cancer Research UK

A Decade of Never-smokers Among Lung Cancer Patients-Increasing Trend and Improved Survival.

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Toh, Chee-Keong; Ong, Whee-Sze; Lim, Wan-Teck; Tan, Daniel Shao-Weng; Ng, Quan-Sing; Kanesvaran, Ravindran; Seow, Wei-Jie; Ang, Mei-Kim; Tan, Eng-Huat

2018-03-17

It is not known whether clinicopathologic characteristics, treatment, and survival of never-smokers among lung cancer incident cases have changed over time. We assessed the trend and overall survival (OS) of these patients within our institution during a 10-year period. We reviewed 2 cohorts of non-small-cell lung cancer patients with a diagnosis from 1999 to 2002 and from 2008 to 2011. The patient characteristics and OS were compared by smoking status within each cohort and between the 2 cohorts over time. Of the 992 patients in the 1999-2002 cohort and the 1318 patients in the 2008-2011 cohort, 902 and 1272 had a known smoking status, respectively. The proportion of never-smokers increased from 31% in 1999-2002 to 48% in 2008-2011 (P never-, former-, and current-smokers have remained largely constant over time. A greater proportion of never-smokers had Eastern Cooperative Oncology Group performance status 0 to 1 and adenocarcinoma. The median OS increased from 15.5 months in 1999-2002 to 24.9 months in 2008-2011 (P = .001) for never-smokers, 12.3 to 15.9 months (P = .150) for former-smokers, and 10.5 to 13.9 months (P = .011) for current-smokers. The larger survival improvement among never-smokers was likely accounted for by the larger increase in never-smokers who were treated with tyrosine kinase inhibitors and pemetrexed over time. We found an increasing trend of never-smokers among incident lung cancer cases and improved survival for these patients during a 10-year period. The documentation of smoking status in any national cancer registry is vital to estimate the true incidence of lung cancer among never-smokers over time. Copyright © 2018 Elsevier Inc. All rights reserved.

Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

International Nuclear Information System (INIS)

Swisher-McClure, Samuel; Mitra, Nandita; Woo, Kaitlin; Smaldone, Marc; Uzzo, Robert; Bekelman, Justin E.

2014-01-01

Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment

The evolution of the sentinel node procedure in the treatment of breast cancer.

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Tvedskov, Tove Filtenborg

2017-10-01

This thesis is based on 10 original articles, of which 3 were previously included in the PhD thesis "Staging of women with breast cancer after introduction of sentinel node guided axillary dissection". In the PhD thesis is was shown that the introduction of sentinel lymph node dissection (SLND) in the treatment of breast cancer in Denmark has resulted in an increased identification of patients with micrometastases or isolated tumor cells (ITC) in the lymph nodes. Not all these small metastases are likely to disseminate to non-sentinel nodes. This thesis provides evidence that a previous surgical excision of a breast tumor is likely to lead to iatrogenic displacement of tumor cells resulting in a nearly four-fold increased risk of ITC in the sentinel node. These tumor cells are not associated with non-sentinel node metastases. Especially ITC, but also micrometastases and some macrometastases, are not identified on perioperative frozen sections, but found postoperatively at the conventional histopathological examination. These patients are offered an axillary lymph node dissection (ALND) as a second procedure. It has been suggested that this two-stage procedure reduces the number of lymph nodes removed, because of fibroses from previous surgery. In this thesis it was shown that a two-stage procedure does not result in a clinically relevant impairment of the number of lymph nodes removed by ALND. Based on patient, tumor, and sentinel node characteristics from the Danish Breast Cancer Group database, two predictive models for non-sentinel node metastases, when only micrometastases or ITC are found in the sentinel node, were developed, as a part of the PhD thesis. These two models have now been internally validated, and a cross-validation in a Finnish patient material has been performed in cooperation with researchers from Helsinki. The model for patients with micrometastases proved to be robust under internal as well as external validation and could be used to identify

Anti-Cancer Potential of Homemade Fresh Garlic Extract Is Related to Increased Endoplasmic Reticulum Stress

Directory of Open Access Journals (Sweden)

Voin Petrovic

2018-04-01

Full Text Available The use of garlic and garlic-based extracts has been linked to decreased incidence of cancer in epidemiological studies. Here we examine the molecular and cellular activities of a simple homemade ethanol-based garlic extract (GE. We show that GE inhibits growth of several different cancer cells in vitro, as well as cancer growth in vivo in a syngeneic orthotopic breast cancer model. Multiple myeloma cells were found to be especially sensitive to GE. The GE was fractionated using solid-phase extractions, and we identified allicin in one GE fraction; however, growth inhibitory activities were found in several additional fractions. These activities were lost during freeze or vacuum drying, suggesting that the main anti-cancer compounds in GE are volatile. The anti-cancer activity was stable for more than six months in −20 °C. We found that GE enhanced the activities of chemotherapeutics, as well as MAPK and PI3K inhibitors. Furthermore, GE affected hundreds of proteins involved in cellular signalling, including changes in vital cell signalling cascades regulating proliferation, apoptosis, and the cellular redox balance. Our data indicate that the reduced proliferation of the cancer cells treated by GE is at least partly mediated by increased endoplasmic reticulum (ER stress.

Potential spillover educational effects of cancer-related direct-to-consumer advertising on cancer patients' increased information seeking behaviors: results from a cohort study.

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Tan, Andy S L

2014-06-01

Spillover effects of exposure to direct-to-consumer advertising (DTCA) of cancer treatments on patients' general inquiry about their treatments and managing their illness are not well understood. This study examines the effects of cancer patients' exposure to cancer-related DTCA on subsequent health information seeking behaviors from clinician and non-clinician sources (lay media and interpersonal contacts). Using a longitudinal survey design over 3 years, data was collected from cancer survivors diagnosed with colorectal, breast, or prostate cancer who were randomly sampled from the Pennsylvania Cancer Registry. Study outcome measures include patients' information engagement with their clinicians and information seeking from non-medical sources about cancer treatment and quality of life issues, measured in the second survey. The predictor variable is the frequency of exposure to cancer-related DTCA since diagnosis, measured at the round 1 survey. The analyses utilized lagged-weighted multivariate regressions and adjusted for round 1 levels of patient-clinician engagement, information seeking from nonmedical sources, and confounders. Exposure to cancer-related DTCA is associated with increased levels of subsequent patient-clinician information engagement (B = .023, 95% CI = .005-.040, p = .012), controlling for confounders. In comparison, exposure to DTCA is marginally significant in predicting health information seeking from non-clinician sources (B = .009, 95% CI = -.001-.018, p = .067). Cancer-related DTCA has potentially beneficial spillover effects on health information seeking behaviors among cancer patients. Exposure to DTCA predicts (a little) more patient engagement with their physicians.

Potential Spillover Educational Effects Of Cancer-Related Direct-To-Consumer Advertising On Cancer Patients’ Increased Information Seeking Behaviors: Results From A Cohort Study

Science.gov (United States)

Tan, Andy SL

2014-01-01

Spillover effects of exposure to direct-to-consumer advertising (DTCA) of cancer treatments on patients’ general inquiry about their treatments and managing their illness are not well understood. This study examines the effects of cancer patients’ exposure to cancer-related DTCA on subsequent health information seeking behaviors from clinician and non-clinician sources (lay media and interpersonal contacts). Using a longitudinal survey design over three years, data was collected from cancer survivors diagnosed with colorectal, breast, or prostate cancer who were randomly sampled from the Pennsylvania Cancer Registry. Study outcome measures include patients’ information engagement with their clinicians and information seeking from non-medical sources about cancer treatment and quality of life issues, measured in the second survey. The predictor variable is the frequency of exposure to cancer-related DTCA since diagnosis, measured at the round 1 survey. The analyses utilized lagged weighted multivariate regressions and adjusted for round 1 levels of patient-clinician engagement, information seeking from non-medical sources, and confounders. Exposure to cancer-related DTCA is associated with increased levels of subsequent patient-clinician information engagement (B=.023, 95%CI=.005 to .040, p=.012), controlling for confounders. In comparison, exposure to DTCA is marginally significant in predicting health information seeking from non-clinician sources (B=.009, 95%CI=−.001 to .018, p=.067). Cancer-related DTCA has potentially beneficial spillover effects on health information seeking behaviors among cancer patients. Exposure to DTCA predicts (a little) more patient engagement with their physicians. PMID:24254248

Simulating the evolution of the human family: cooperative breeding increases in harsh environments.

Science.gov (United States)

Smaldino, Paul E; Newson, Lesley; Schank, Jeffrey C; Richerson, Peter J

2013-01-01

Verbal and mathematical models that consider the costs and benefits of behavioral strategies have been useful in explaining animal behavior and are often used as the basis of evolutionary explanations of human behavior. In most cases, however, these models do not account for the effects that group structure and cultural traditions within a human population have on the costs and benefits of its members' decisions. Nor do they consider the likelihood that cultural as well as genetic traits will be subject to natural selection. In this paper, we present an agent-based model that incorporates some key aspects of human social structure and life history. We investigate the evolution of a population under conditions of different environmental harshness and in which selection can occur at the level of the group as well as the level of the individual. We focus on the evolution of a socially learned characteristic related to individuals' willingness to contribute to raising the offspring of others within their family group. We find that environmental harshness increases the frequency of individuals who make such contributions. However, under the conditions we stipulate, we also find that environmental variability can allow groups to survive with lower frequencies of helpers. The model presented here is inevitably a simplified representation of a human population, but it provides a basis for future modeling work toward evolutionary explanations of human behavior that consider the influence of both genetic and cultural transmission of behavior.

Simulating the evolution of the human family: cooperative breeding increases in harsh environments.

Directory of Open Access Journals (Sweden)

Paul E Smaldino

Full Text Available Verbal and mathematical models that consider the costs and benefits of behavioral strategies have been useful in explaining animal behavior and are often used as the basis of evolutionary explanations of human behavior. In most cases, however, these models do not account for the effects that group structure and cultural traditions within a human population have on the costs and benefits of its members' decisions. Nor do they consider the likelihood that cultural as well as genetic traits will be subject to natural selection. In this paper, we present an agent-based model that incorporates some key aspects of human social structure and life history. We investigate the evolution of a population under conditions of different environmental harshness and in which selection can occur at the level of the group as well as the level of the individual. We focus on the evolution of a socially learned characteristic related to individuals' willingness to contribute to raising the offspring of others within their family group. We find that environmental harshness increases the frequency of individuals who make such contributions. However, under the conditions we stipulate, we also find that environmental variability can allow groups to survive with lower frequencies of helpers. The model presented here is inevitably a simplified representation of a human population, but it provides a basis for future modeling work toward evolutionary explanations of human behavior that consider the influence of both genetic and cultural transmission of behavior.

Night-shift work increases morbidity of breast cancer and all-cause mortality: a meta-analysis of 16 prospective cohort studies.

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Lin, Xiaoti; Chen, Weiyu; Wei, Fengqin; Ying, Mingang; Wei, Weidong; Xie, Xiaoming

2015-11-01

Night-shift work (NSW) has previously been related to incidents of breast cancer and all-cause mortality, but many published studies have reported inconclusive results. The aim of the present study was to quantify a potential dose-effect relationship between NSW and morbidity of breast cancer, and to evaluate the association between NSW and risk of all-cause mortality. The outcomes included NSW, morbidity of breast cancer, cardiovascular mortality, cancer-related mortality, and all-cause mortality. Sixteen investigations were included, involving 2,020,641 participants, 10,004 incident breast cancer cases, 7185 cancer-related deaths, 4820 cardiovascular end points, and 2480 all-cause mortalities. The summary risk ratio (RR) of incident breast cancer for an increase of NSW was 1.057 [95% confidence interval (CI) 1.014-1.102; test for heterogeneity p = 0.358, I(2) = 9.2%]. The combined RR (95% CI) of breast cancer risk for NSW vs daytime work was: 1.029 (0.969-1.093) in the 20-year exposure lengths. The overall RR was 1.089 (95% CI 1.016-1.166) in a fixed-effects model (test for heterogeneity p = 0.838, I(2) = 0%) comparing rotating NSW and day work. Night-shift work was associated with an increased risk of cardiovascular death (RR 1.027, 95% CI 1.001-1.053), and all-cause death 1.253 (95% CI 0.786-1.997). In summary, NSW increased the risk of breast cancer morbidity by: 1.9% for 5 years, 2.5% for 5-10 years, 7.4% for 10-20 years, and 8.8% for >20-years of NSW. Additionally, rotating NSW enhanced the morbidity of breast cancer by 8.9%. Moreover, NSW was associated with a 2.7% increase in cardiovascular death. Copyright © 2015. Published by Elsevier B.V.

Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

DEFF Research Database (Denmark)

Stahlberg, Claudia; Pedersen, Anette Tønnes; Lynge, Elsebeth

2004-01-01

was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases......Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort...

Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease.

Science.gov (United States)

Borges, Álvaro H; Lundgren, Jens D; Ridolfo, Annalisa; Katlama, Christine; Antunes, Francisco; Grzeszczuk, Anna; Blaxhult, Anders; Mitsura, Viktar M; Doroana, Manuela; Battegay, Manuel; Gargalianos, Panagiotis; Mocroft, Amanda

2014-11-13

To assess the relationship between platelet counts and risk of AIDS and non-AIDS-defining events. Prospective cohort. EuroSIDA patients with at least one platelet count were followed from baseline (first platelet ≥ 1 January 2005) until last visit or death. Multivariate Poisson regression was used to assess the relationship between current platelet counts and the incidence of non-AIDS-defining (pancreatitis, end-stage liver/renal disease, cancer, cardiovascular disease) and AIDS-defining events. There were 62 898 person-years of follow-up (PYFU) among 12 279 patients, including 1168 non-AIDS-defining events [crude incidence 18.6/1000 PYFU, 95% confidence interval (CI) 17.5-19.6] and 735 AIDS-defining events (crude incidence 11.7/1000 PYFU, 95% CI 10.8-12.5). Patients with thrombocytopenia (platelet count ≤100 × 10/l) had a slightly increased incidence of AIDS-defining events [adjusted incidence rate ratio (aIRR) 1.42, 95% CI 1.07-1.86], when compared to those with platelet counts 101-200 × 10/l, whereas the incidence of non-AIDS-defining events was more than two-fold higher (aIRR 2.66, 95% CI 2.17-3.26). Among non-AIDS-defining events, the adjusted incidence of cancer (aIRR 2.20, 95% CI 1.61-3.01), but not cardiovascular disease (aIRR 0.66, 95% CI 0.32-1.34), was significantly higher in patients with thrombocytopenia. The association between thrombocytopenia and cancer remained unaltered in sensitivity analyses requiring repeated platelet counts to confirm thrombocytopenia and lagging platelets by 1 year prior to clinical events. Patients with thrombocytopenia had increased incidence of AIDS-defining and non-AIDS-defining events, but the association with the latter, in particular cancer, was stronger. Future studies should investigate whether the pathophysiological processes underlying thrombocytopenia are associated with the development of cancer during treated HIV disease.

Social isolation induces autophagy in the mouse mammary gland: link to increased mammary cancer risk.

Science.gov (United States)

Sumis, Allison; Cook, Katherine L; Andrade, Fabia O; Hu, Rong; Kidney, Emma; Zhang, Xiyuan; Kim, Dominic; Carney, Elissa; Nguyen, Nguyen; Yu, Wei; Bouker, Kerrie B; Cruz, Idalia; Clarke, Robert; Hilakivi-Clarke, Leena

2016-10-01

Social isolation is a strong predictor of early all-cause mortality and consistently increases breast cancer risk in both women and animal models. Because social isolation increases body weight, we compared its effects to those caused by a consumption of obesity-inducing diet (OID) in C57BL/6 mice. Social isolation and OID impaired insulin and glucose sensitivity. In socially isolated, OID-fed mice (I-OID), insulin resistance was linked to reduced Pparg expression and increased neuropeptide Y levels, but in group-housed OID fed mice (G-OID), it was linked to increased leptin and reduced adiponectin levels, indicating that the pathways leading to insulin resistance are different. Carcinogen-induced mammary tumorigenesis was significantly higher in I-OID mice than in the other groups, but cancer risk was also increased in socially isolated, control diet-fed mice (I-C) and G-OID mice compared with that in controls. Unfolded protein response (UPR) signaling (GRP78; IRE1) was upregulated in the mammary glands of OID-fed mice, but not in control diet-fed, socially isolated I-C mice. In contrast, expression of BECLIN1, ATG7 and LC3II were increased, and p62 was downregulated by social isolation, indicating increased autophagy. In the mammary glands of socially isolated mice, but not in G-OID mice, mRNA expressions of p53 and the p53-regulated autophagy inducer Dram1 were upregulated, and nuclear p53 staining was strong. Our findings further indicated that autophagy and tumorigenesis were not increased in Atg7(+/-) mice kept in social isolation and fed OID. Thus, social isolation may increase breast cancer risk by inducing autophagy, independent of changes in body weight. © 2016 Society for Endocrinology.

Increased Risk of Rare Cancer as DES Daughters Age

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... Attitudes, and Practices Related to Colorectal Cancer in Brazil 2015 2 of 3 People Are Living At ... Mammography Promotion Campaign African American Women and Mass Media Campaign Evaluation Cancer Survival: The Start of Global ...

Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium

DEFF Research Database (Denmark)

Barrow, Hannah; Guo, Xiuli; Wandall, Hans H

2011-01-01

Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells...... to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion....

Increased cancer risk in patients referred to hospital with suspected fibromyalgia

DEFF Research Database (Denmark)

Dreyer, Lene; Mellemkjaer, Lene; Kendall, Sally

2007-01-01

OBJECTIVE: To analyze whether fibromyalgia (FM) and FM-like symptoms are related to an increased incidence of cancer. METHODS: We identified 1361 patients referred on suspicion of FM in the period 1984-99 from hospital records. Following the American College of Rheumatology (ACR) criteria, patien...... for FM. These patients should be investigated if they develop any new or warning symptoms of malignancy, and treating physicians should be vigilant with screening procedures such as mammography....

miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor

Energy Technology Data Exchange (ETDEWEB)

Park, Jong-Kook [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Henry, Jon C. [Department of Surgery, Ohio State University, Columbus, OH 43210 (United States); Jiang, Jinmai [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Esau, Christine [Regulus Therapeutics, Carlsbad, CA (United States); Gusev, Yuriy [Lombardi Cancer Center, Georgetown University, Washington, DC (United States); Lerner, Megan R. [Veterans Affairs Medical Center, Oklahoma City, OK (United States); Postier, Russell G. [Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Brackett, Daniel J. [Veterans Affairs Medical Center, Oklahoma City, OK (United States); Schmittgen, Thomas D., E-mail: Schmittgen.2@osu.edu [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States)

2011-03-25

Research highlights: {yields} The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. {yields} miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. {yields} miR-132 and miR-212 expression is increased by a {beta}2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- Abstract: Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G{sub 2}/M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the {beta}2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The {beta}2 adrenergic pathway may play an important role in this novel mechanism.

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

OpenAIRE

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

2014-01-01

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

Increase in mammography detected breast cancer over time at a community based regional cancer center: a longitudinal cohort study 1990–2005

International Nuclear Information System (INIS)

Malmgren, Judith A; Atwood, Mary K; Kaplan, Henry G

2008-01-01

Coincident with the advent of mammography screening, breast carcinoma in situ has increased in the US population. We conducted a prospective cohort study of all women presenting with primary breast cancer, aged 21–94, and biopsy confirmed Stage 0-IV from 1990–2005 identified and tracked by our registry. Clinical presentation characteristics including age, race, TNM stage, family and pregnancy history, histologic type and method of detection by patient (PtD), physician (PhysD) or mammography (MgD) were chart abstracted at time of diagnosis. Cases with unknown or other method of detection (n = 84), or unusual cell types (n = 26) were removed (n = 6074). From 1990 to 1998 the percentage of PtD and MgD cases was roughly equivalent. In 1999 the percentage of MgD cases increased to 56% and PtD dropped to 37%, a significant 20% differential, constant to 2005 (Pearson chi square = 120.99, p < .001). Overall, percent TNM stage 0 (breast carcinoma in situ) cases increased after 1990, percent stage I and III cases declined, and stage II and IV cases remained constant (Pearson chi square = 218.36, p < .001). Increase in MgD over time differed by age group with an 8.5% increase among women age 40–49 and 12% increase among women age 50–95. Women age 21–39 rarely had MgD BC. In forward stepwise logistic regression modeling, significant predictors of MgD BC by order of entry were TNM stage, age at diagnosis, diagnosis year, and race (chi square = 1867.56, p < .001). In our cohort the relative proportion of mammography detected breast cancer increased over time with a higher increase among women age 50+ and an increase of breast carcinoma in situ exclusively among MgD cases. The increase among women currently targeted by mammography screening programs (age ≥ 50) combined with an increase of breast carcinoma in situ most often detected by mammography screening indicates a possible incidence shift to lower stage breast cancer as a result of mammographic detection

Concepts in causality: chemically induced human urinary bladder cancer

International Nuclear Information System (INIS)

Lower, G.M. Jr.

1982-01-01

A significant portion of the incidence of human urinary bladder cancer can be attributed to occupational and cultural (tobacco smoking) situations associated with exposures to various arylamines, many of which represent established human carcinogens. A brief historical overview of research in bladder cancer causality indicates that the identification of causal agents and causal mechanism has been approached and rests upon information gathered at the organismal (geographical/historical), cellular, and molecular levels of biologic organization. This viewpoint speaks of a natural evolution within the biomedical sciences; a natural evolution from descriptive approaches to mechanistic approaches; and a natural evolution from more or less independent discipline-oriented approaches to hierarchically organized multidisciplinary approaches. Available information relevant to bladder cancer causality can be readily integrated into general conceptual frameworks to yield a hierarchial view of the natural history of urinary bladder cancer, a view consistent with contemporary natural systems and information theory and perhaps relevant also to other chemically induced epithelial cancers. Such frameworks are useful in appreciating the spatial and temporal boundaries and interrelationships in causality and the conceptual interrelationships within the biomedical sciences. Recent approaches in molecular epidemiology and the assessment of relative individual susceptibility to bladder cancer indicate that such frameworks are useful in forming hypotheses

Seroma indicates increased risk of lymphedema following breast cancer treatment

DEFF Research Database (Denmark)

Toyserkani, Navid Mohamadpour; Jørgensen, Mads Gustaf; Haugaard, Karen

2017-01-01

in one of the largest retrospective cohort studies. Material and methods We included all patients with unilateral breast cancer treated in the period of 2008-2014. Data regarding treatment and breast cancer characteristics were retrieved from the national breast cancer registry. Data regarding lymphedema...

Parallel evolution under chemotherapy pressure in 29 breast cancer cell lines results in dissimilar mechanisms of resistance.

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Bálint Tegze

Full Text Available BACKGROUND: Developing chemotherapy resistant cell lines can help to identify markers of resistance. Instead of using a panel of highly heterogeneous cell lines, we assumed that truly robust and convergent pattern of resistance can be identified in multiple parallel engineered derivatives of only a few parental cell lines. METHODS: Parallel cell populations were initiated for two breast cancer cell lines (MDA-MB-231 and MCF-7 and these were treated independently for 18 months with doxorubicin or paclitaxel. IC50 values against 4 chemotherapy agents were determined to measure cross-resistance. Chromosomal instability and karyotypic changes were determined by cytogenetics. TaqMan RT-PCR measurements were performed for resistance-candidate genes. Pgp activity was measured by FACS. RESULTS: All together 16 doxorubicin- and 13 paclitaxel-treated cell lines were developed showing 2-46 fold and 3-28 fold increase in resistance, respectively. The RT-PCR and FACS analyses confirmed changes in tubulin isofom composition, TOP2A and MVP expression and activity of transport pumps (ABCB1, ABCG2. Cytogenetics showed less chromosomes but more structural aberrations in the resistant cells. CONCLUSION: We surpassed previous studies by parallel developing a massive number of cell lines to investigate chemoresistance. While the heterogeneity caused evolution of multiple resistant clones with different resistance characteristics, the activation of only a few mechanisms were sufficient in one cell line to achieve resistance.

Increased Chromosomal and Oxidative DNA Damage in Patients with Multinodular Goiter and Their Association with Cancer

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Hamiyet Donmez-Altuntas

2017-01-01

Full Text Available Thyroid nodules are a common clinical problem worldwide. Although thyroid cancer accounts for a small percentage of thyroid nodules, the majority are benign. 8-Hydroxy-2′-deoxyguanosine (8-OHdG levels are a marker of oxidative stress and play a key role in the initiation and development of a range of diseases and cancer types. This study evaluates cytokinesis-block micronucleus cytome (CBMN-cyt assay parameters and plasma 8-OHdG levels and their association with thyroid nodule size and thyroid hormones in patients with multinodular goiter. The study included 32 patients with multinodular goiter and 18 age- and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of patients with multinodular goiter and controls were evaluated, and plasma 8-OHdG levels were measured. The micronucleus (MN frequency (chromosomal DNA damage, apoptotic and necrotic cells (cytotoxicity, and plasma 8-OHdG levels (oxidative DNA damage were significantly higher among patients with multinodular goiter. Our study is the first report of increased chromosomal and oxidative DNA damage in patients with multinodular goiter, which may predict an increased risk of thyroid cancer in these patients. MN frequency and plasma 8-OHdG levels may be markers of the carcinogenic potential of multinodular goiters and could be used for early detection of different cancer types, including thyroid cancer.

Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

2009-06-18

Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also

Germline mutation in RNASEL predicts increased risk of head and neck, uterine cervix and breast cancer.

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Bo Eskerod Madsen

Full Text Available UNLABELLED: THE BACKGROUND: Ribonuclease L (RNASEL, encoding the 2'-5'-oligoadenylate (2-5A-dependent RNase L, is a key enzyme in the interferon induced antiviral and anti-proliferate pathway. Mutations in RNASEL segregate with the disease in prostate cancer families and specific genotypes are associated with an increased risk of prostate cancer. Infection by human papillomavirus (HPV is the major risk factor for uterine cervix cancer and for a subset of head and neck squamous cell carcinomas (HNSCC. HPV, Epstein Barr virus (EBV and sequences from mouse mammary tumor virus (MMTV have been detected in breast tumors, and the presence of integrated SV40 T/t antigen in breast carcinomas correlates with an aggressive phenotype and poor prognosis. A genetic predisposition could explain why some viral infections persist and induce cancer, while others disappear spontaneously. This points at RNASEL as a strong susceptibility gene. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the implication of an abnormal activity of RNase L in the onset and development of viral induced cancers, the study was initiated by searching for germline mutations in patients diagnosed with uterine cervix cancer. The rationale behind is that close to 100% of the cervix cancer patients have a persistent HPV infection, and if a defective RNase L were responsible for the lack of ability to clear the HPV infection, we would expect to find a wide spectrum of mutations in these patients, leading to a decreased RNase L activity. The HPV genotype was established in tumor DNA from 42 patients diagnosed with carcinoma of the uterine cervix and somatic tissue from these patients was analyzed for mutations by direct sequencing of all coding and regulatory regions of RNASEL. Fifteen mutations, including still uncharacterized, were identified. The genotype frequencies of selected single nucleotide polymorphisms (SNPs established in the cervix cancer patients were compared between 382 patients

Increased reactive oxygen species levels cause ER stress and cytotoxicity in andrographolide treated colon cancer cells.

Science.gov (United States)

Banerjee, Aditi; Banerjee, Vivekjyoti; Czinn, Steven; Blanchard, Thomas

2017-04-18

Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress (ER stress) leading to the unfolded protein response (UPR). The goal of the present study was to determine the mechanism by which andrographolide induces ER stress and to further evaluate its role in promoting cell death pathways. The T84 and COLO 205 cancer cell lines were used to demonstrate that andrographolide induces increased ROS levels, corresponding anti-oxidant response molecules, and reduced mitochondrial membrane potential. No increases in ROS levels were detected in control colon fibroblast cells. Andrographolide-induced cell death, UPR signaling, and CHOP, Bax, and caspase 3 apoptosis elements were all inhibited in the presence of the ROS scavenger NAC. Additionally, andrographolide-induced suppression of cyclins B1 and D1 were also reversed in the presence of NAC. Finally, Akt phosphorylation and phospho-mTOR levels that are normally suppressed by andrographolide were also expressed at normal levels in the absence of ROS. These data demonstrate that andrographolide induces ER stress leading to apoptosis through the induction of ROS and that elevated ROS also play an important role in down-regulating cell cycle progression and cell survival pathways as well.

Increased survival with enzalutamide in prostate cancer after chemotherapy

NARCIS (Netherlands)

H.I. Scher (Howard I.); K. Fizazi (Karim); F. Saad (Fred); M.-E. Taplin (Mary-Ellen); C.N. Sternberg (Cora); K. Miller (Kurt); R. de Wit (Ronald); P.F.A. Mulders (P. F A); K.N. Chi (Kim Nguyen); N.D. Shore (Neal); A.J. Armstrong (Andrew); T.W. Flaig (Thomas); A. Flechon (Aude); P. Mainwaring (Paul); M. Fleming; J.D. Hainsworth (John); M. Hirmand (Mohammad); B. Selby (Bryan); L. Seely (Lynn); J.S. de Bono (Johann)

2012-01-01

textabstractBACKGROUND: Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor-signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after

Increased survival with enzalutamide in prostate cancer after chemotherapy

NARCIS (Netherlands)

Scher, H.I.; Fizazi, K.; Saad, F.; Taplin, M.E.; Sternberg, C.N.; Miller, K.; de Wit, R.; Mulders, P.F.A.; Chi, K.N.; Shore, N.D.; Armstrong, A.J.; Flaig, T.W.; Flechon, A.; Mainwaring, P.; Fleming, M.; Hainsworth, J.D.; Hirmand, M.; Selby, B.; Seely, L.; Bono, J. De; Investigators, A.

2012-01-01

BACKGROUND: Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor-signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy. METHODS:

Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

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Gruber Helen E

2011-08-01

Full Text Available Abstract Background Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA. Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. Methods To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. Results A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17, interleukin-6 (IL-6, Pro- Matrix metallopeptidase 9 (Pro-MMP9, insulin like growth factor-II (GF-II and macrophage colony stimulating factor (M-CSF in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors

HFE H63D mutation frequency shows an increase in Turkish women with breast cancer

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Guler Emine

2006-02-01

Full Text Available Abstract Background The hereditary hemochromatosis gene HFE plays a pivotal role in iron homeostasis. The association between cancer and HFE hetero- or homozygosity has previously been shown including hepatocellular and nonhepatocellular malignancies. This study was performed to compare frequencies of HFE C282Y and H63D variants in Turkish women with breast cancer and healthy controls. Methods Archived DNA samples of Hacettepe University Oncology Institute were used in this study. The HFE gene was investigated by PCR-RFLP. Results All subjects studied were free from C282Y mutation. Thirty-nine patients had H63D mutation and were all heterozygous. H63D allele frequency was 22.2% (39/176 in the breast cancer patients, and 14% (28/200 in the healthy volunteers. Statistical analysis of cases with HFE H63D phenotype showed significant difference between breast cancer and healthy volunteers (P = 0.02. Conclusion Our results suggest that HFE H63D mutation frequencies were increased in the breast cancer patients in comparison to those in the general population. Also, odds ratios (odds ratio = 2.05 computed in this study suggest that H63D has a positive association with breast cancer.

International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer

NARCIS (Netherlands)

Canto, Marcia Irene; Harinck, Femme; Hruban, Ralph H.; Offerhaus, George Johan; Poley, Jan-Werner; Kamel, Ihab; Nio, Yung; Schulick, Richard S.; Bassi, Claudio; Kluijt, Irma; Levy, Michael J.; Chak, Amitabh; Fockens, Paul; Goggins, Michael; Bruno, Marco; Arcidiacono, Paolo Giorgio; Bartsch, Detlef; Biermann, Katharina; Brentnall, Terri; Dite, Petr; Donahue, Timothy; Early, Dayna; Farrell, James; Fernandez-del Castillo, Carlos; Frucht, Harold; Fukushima, Noriyoshi; Geurts, Jenny; Hamell, Pascal; Iglesias-Garcia, Julio; Klein, Alison; Kloeppel, Guenter; Lachter, Jesse; Langer, Peter; Lee, Jeffrey; Levy, Michael; Maguchi, Hiroyuki; Margolis, Daniel; Ohtsuka, Takao; Olson, Sara; Petersen, Gloria; Savides, Thomas; Syngal, Sapna; Tamm, Eric; Tanaka, Masao; Vasen, Hans; Wagner, Anja; Wang, Huamin; Williams, David; Yamao, Kenjii

2013-01-01

Screening individuals at increased risk for pancreatic cancer (PC) detects early, potentially curable, pancreatic neoplasia. To develop consortium statements on screening, surveillance and management of high-risk individuals with an inherited predisposition to PC. A 49-expert multidisciplinary

Evolution of thyroid cancer occurrence in metropolitan France. Assessment over 25 years

International Nuclear Information System (INIS)

Rogel, Agnes; Caserio-Schonemann, Celine; Cherie-Challine, Laurence; Rudant, Jeremie; Bloch, Juliette; Thuret, Anne; Colonna, Marc; Uhry, Zoe; Kudjawu, Yao; Danzon, Arlette; Lacour, Brigitte; Schvartz, Claire; Pascal, Laurence; Lasalle, Jean-Luc; Borson-Chazot, Francoise; Sassolas, Genevieve; Hafdi-Nejjari, Zakia; Boutron-Ruault, Marie-Christine; Guenel, Pascal; Vathaire, Florent de; Guillas, Gwenaelle; Mesrine, Sylvie; Clavel-Chapelon, Francoise; Clero, Enora; Adjadj, Elisabeth; Bedouche, Lallia; Belot, Aurelien; Fieffe, Sandrine; Dalac, Audrey; Goncalves, Katia; Kaplan, Martine; Pochart, Jean-Marie; Desenclos, Jean-Claude

2011-04-01

After a presentation of the epidemiological context of thyroid cancer in France, this report, based on cancer record data, analyzes the occurrence of thyroid cancers between 1982 and 2006. It discusses the contribution and limits of medical-administrative data for the epidemiological monitoring of thyroid cancer occurrence between 1997 and 2009. It proposes a descriptive analysis of thyroid cancers in two districts (Marne and Ardennes) between 1975 and 2008, and a descriptive analysis of thyroid cancer for children under 14 between 2000 and 2008. It proposes an estimation of thyroid cancer occurrence in Corsica between 1998 and 2006. It reports and discusses a pilot study performed in two regions (Ile de France and Nord Pas-de-Calais), based on a multi-source system of cancer monitoring (SMSC), and comments studies on risk factors for differentiated thyroid cancers in France

Setting the Threshold for Surgical Prevention in Women at Increased Risk of Ovarian Cancer.

Science.gov (United States)

Manchanda, Ranjit; Menon, Usha

2018-01-01

considered at younger than 45. In other moderate-risk gene mutation carriers and those with polygenic risk, RRSO needs be considered at 50. There is need for establishment/expansion of well-defined pathways to increase clinical access to RRSO. It is time to lower the risk threshold for RRSO to enable introduction of a targeted primary prevention approach, which could significantly impact the future burden of ovarian cancer.

Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

Science.gov (United States)

According to a January 28, 2011 article in the Journal of the National Cancer Institute, women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later.

Providing written information increases patient satisfaction: a web-based questionnaire survey of Japanese cancer survivors.

Science.gov (United States)

Sakai, Hitomi; Katsumata, Noriyuki; Takahashi, Miyako

2017-07-01

The Institute of Medicine (IOM) of the United States recommends that all cancer survivors be provided with a survivorship care plan (SCP), which includes a patient treatment summary and a follow-up care plan. However, SCPs have not been widely adopted in Japan. To provide basic data necessary for implementing SCPs in Japan, we aimed to investigate the forms of clinical and survivorship-related information that Japanese cancer survivors receive from their healthcare providers, and to examine whether written information increases their satisfaction. We performed a cross-sectional online survey of cancer survivors who underwent acute cancer treatment and had at least one follow-up with a physician in the past year. Cancer survivors provided the elements and forms (verbally and/or written) of information they received, as well as the degree of satisfaction with the information provided. Responses were obtained from 545 cancer survivors. Information elements such as surgical procedure (98.3%), surgical outcome (98.1%), and names of administered chemotherapy agents (97.8%) were commonly provided, whereas mental care resources and providers (29.7%), effects on marital relationship and sexual health (35.7%), and effects on fertility (43.4%) were less common. A large proportion of cancer survivors received verbal information only. For 18 of 20 elements, except for effects on fertility and duration of hormonal therapy, satisfaction was significantly higher when both forms of information were provided (P information can better meet the needs of Japanese cancer survivors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Increased Susceptibility to Apoptosis and Growth Arrest of Human Breast Cancer Cells Treated by a Snake Venom-Loaded Silica Nanoparticles

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Gamal Badr

2014-11-01

Full Text Available Background: The development of effective treatments against metastatic cancers, including breast cancer, is among the most important challenges in current experimental and clinical cancer research. We recently demonstrated that Walterinnesia aegyptia venom (WEV, either alone or in combination with silica nanoparticles (WEV+NP, resulted in the growth arrest and apoptosis of different cancer cell lines. Aims: In the present study, we evaluated the impact of WEV alone and WEV+NP on human breast cancer cells isolated from cancer biopsies. Methods: The potential effects of WEV alone and WEV+NP on the proliferation, induction of apoptosis and generation of free radicals in breast cancer cells isolated from 80 patients clinically diagnosed with breast cancer were evaluated by flow cytometry and ELISA. Results: WEV alone and WEV+NP inhibited the proliferation, altered the cell cycle and enhanced the induction of apoptosis of the breast cancer cells by increasing the activities of caspase-3, caspase-8 and caspase-9. In addition, the combination of WEV and NP robustly sensitized the breast cancer cells to growth arrest and apoptosis by increasing the generation of free radicals, including reactive oxygen species (ROS, hydroperoxide and nitric oxide. The combination of WEV with NP significantly enhanced the anti-tumor effect of WEV in breast cancer cells. Conclusion: Our data indicate the therapeutic potential of the nanoparticle-sustained delivery of snake venom for the treatment of breast cancer.

APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability.

Science.gov (United States)

Sansregret, Laurent; Patterson, James O; Dewhurst, Sally; López-García, Carlos; Koch, André; McGranahan, Nicholas; Chao, William Chong Hang; Barry, David J; Rowan, Andrew; Instrell, Rachael; Horswell, Stuart; Way, Michael; Howell, Michael; Singleton, Martin R; Medema, René H; Nurse, Paul; Petronczki, Mark; Swanton, Charles

2017-02-01

Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization. APC/C impairment caused adaptation to MPS1 inhibitors, revealing a likely resistance mechanism to therapies targeting the spindle assembly checkpoint. Finally, CRISPR-mediated introduction of cancer somatic mutations in the APC/C subunit cancer driver gene CDC27 reduces chromosome segregation errors, whereas reversal of an APC/C subunit nonsense mutation increases CIN. Subtle variations in mitotic duration, determined by APC/C activity, influence the extent of CIN, allowing cancer cells to dynamically optimize fitness during tumor evolution. We report a mechanism whereby cancers balance the evolutionary advantages associated with CIN against the fitness costs caused by excessive genome instability, providing insight into the consequence of CDC27 APC/C subunit driver mutations in cancer. Lengthening of mitosis through APC/C modulation may be a common mechanism of resistance to cancer therapeutics that increase chromosome segregation errors. Cancer Discov; 7(2); 218-33. ©2017 AACR.See related commentary by Burkard and Weaver, p. 134This article is highlighted in the In This Issue feature, p. 115. ©2017 American Association for Cancer Research.

The Genomic Evolution of Prostate Cancer

Science.gov (United States)

2017-06-01

the proposed project : 1. To continue to acquire a comprehensive understanding of prostate cancer genomics . 2. To develop an understanding of... Genetics I • ECEV 35901 Evolutionary Genomics • Fundamentals of Clinical Research • HGEN 47400 Introduction to Probability and Statistics for Geneticists...Marc Gillard,2 David M. Hatcher,5 Westin R. Tom,5 Walter M. Stadler2 and Kevin P. White1,2,3 1Institute for Genomics and Systems Biology , Departments of

Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome

NARCIS (Netherlands)

Boparai, K. S.; Reitsma, J. B.; Lemmens, V.; van Os, T. A. M.; Mathus-Vliegen, E. M. H.; Koornstra, J. J.; Nagengast, F. M.; van Hest, L. P.; Keller, J. J.; Dekker, E.

2010-01-01

Introduction Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome.

NARCIS (Netherlands)

Boparai, K.S.; Reitsma, J.B.; Lemmens, V.; Os, T.A. van; Mathus-Vliegen, E.M.H.; Koornstra, J.J.; Nagengast, F.M.; Hest, L.P. van; Keller, J.J.; Dekker, E. den

2010-01-01

INTRODUCTION: Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

Increased colorectal cancer risk in first-degree relatives of patients with hyperplastic polyposis syndrome

NARCIS (Netherlands)

Boparai, K. S.; Lemmens, V.; van Os, T. A. M.; Mathus-Vliegen, E. M. H.; Koornstra, J. J.; Nagengast, F. M.; van Hest, L. P.; Keller, J. J.; Dekker, E.; Reitsma, J.

Introduction Hyperplastic polyposis syndrome (HPS) is characterised by the presence of multiple colorectal hyperplastic polyps and is associated with an increased colorectal cancer (CRC) risk. For first-degree relatives of HPS patients (FDRs) this has not been adequately quantified. Reliable

Evolution of thyroid cancer occurrence in metropolitan France. Assessment over 25 years; evolution de l'incidence du cancer de la thyroide en France metropolitaine. Bilan sur 25 ans

Energy Technology Data Exchange (ETDEWEB)

Rogel, Agnes; Caserio-Schonemann, Celine; Cherie-Challine, Laurence; Rudant, Jeremie; Bloch, Juliette; Thuret, Anne [Unite cancer, Departement des maladies chroniques et traumatismes - DMCT, Institut de veille sanitaire - InVS (France); Colonna, Marc [Registre des cancers de l' Isere, Reseau francais des registres de cancer (Francim) (France); Uhry, Zoe; Kudjawu, Yao; Danzon, Arlette [Unite cancer, DMCT, InVS (France); Lacour, Brigitte [Registre national des tumeurs solides de l' enfant, Francim (France); Schvartz, Claire [Registre des cancers de la thyroide Marne-Ardennes, Francim (France); Pascal, Laurence; Lasalle, Jean-Luc [Cellule interregionale d' epidemiologie - Cire Sud (France); Borson-Chazot, Francoise; Sassolas, Genevieve; Hafdi-Nejjari, Zakia [Registre des cancers thyroidiens de la region Rhone-Alpes (France); Boutron-Ruault, Marie-Christine; Guenel, Pascal; Vathaire, Florent de; Guillas, Gwenaelle; Mesrine, Sylvie; Clavel-Chapelon, Francoise; Clero, Enora; Adjadj, Elisabeth; Bedouche, Lallia [Institut national de la sante et de la recherche medicale (Inserm) U1018 (France); Belot, Aurelien [Unite Cancer, DMCT, InVS (France); Hospices civils de Lyon - HCL (France); Fieffe, Sandrine; Dalac, Audrey; Goncalves, Katia; Kaplan, Martine; Pochart, Jean-Marie [Registre des cancers de la thyroide Marne-Ardennes, Francim, Centre de luttre contre le cancer de Reims (France); Desenclos, Jean-Claude [Direction scientifique, InVS (France)

2011-04-15

After a presentation of the epidemiological context of thyroid cancer in France, this report, based on cancer record data, analyzes the occurrence of thyroid cancers between 1982 and 2006. It discusses the contribution and limits of medical-administrative data for the epidemiological monitoring of thyroid cancer occurrence between 1997 and 2009. It proposes a descriptive analysis of thyroid cancers in two districts (Marne and Ardennes) between 1975 and 2008, and a descriptive analysis of thyroid cancer for children under 14 between 2000 and 2008. It proposes an estimation of thyroid cancer occurrence in Corsica between 1998 and 2006. It reports and discusses a pilot study performed in two regions (Ile de France and Nord Pas-de-Calais), based on a multi-source system of cancer monitoring (SMSC), and comments studies on risk factors for differentiated thyroid cancers in France

A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

Science.gov (United States)

Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

2016-04-01

Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

Hormonal Involvement in Breast Cancer Gene Amplification

Science.gov (United States)

2010-10-01

been shown to induce DN A amplification in yeast (Gopalakrishnan et al., 2001; Nguy en et al., 2001; Green et al., 2006) an d increased Cdt1 results in...re-replication in human cells (Dorn et al., 2008). The N- terminus of Cdt1 is important for re-replication, perhaps through interactions with PCNA...evolution of a cancer genome. Genome Res. (Epub. Dec. 3, 2008). Harris TD, Buzby PR, Babcock H, Beer E, Bowers J, Bras lavsky I, Causey M

Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

International Nuclear Information System (INIS)

Cai, Kun; Mulatz, Kirk; Ard, Ryan; Nguyen, Thanh; Gee, Stephen H

2014-01-01

Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

Evolution of movement rate increases the effectiveness of marine reserves for the conservation of pelagic fishes.

Science.gov (United States)

Mee, Jonathan A; Otto, Sarah P; Pauly, Daniel

2017-06-01

Current debates about the efficacy of no-take marine reserves (MR) in protecting large pelagic fish such as tuna and sharks have usually not considered the evolutionary dimension of this issue, which emerges because the propensity to swim away from a given place, like any other biological trait, will probably vary in a heritable fashion among individuals. Here, based on spatially explicit simulations, we investigated whether selection to remain in MRs to avoid higher fishing mortality can lead to the evolution of more philopatric fish. Our simulations, which covered a range of life histories among tuna species (skipjack tuna vs. Atlantic bluefin tuna) and shark species (great white sharks vs. spiny dogfish), suggested that MRs were most effective at maintaining viable population sizes when movement distances were lowest. Decreased movement rate evolved following the establishment of marine reserves, and this evolution occurred more rapidly with higher fishing pressure. Evolutionary reductions in movement rate led to increases in within-reserve population sizes over the course of the 50 years following MR establishment, although this varied among life histories, with skipjack responding fastest and great white sharks slowest. Our results suggest the evolution of decreased movement can augment the efficacy of marine reserves, especially for species, such as skipjack tuna, with relatively short generation times. Even when movement rates did not evolve substantially over 50 years (e.g., given long generation times or little heritable variation), marine reserves were an effective tool for the conservation of fish populations when mean movement rates were low or MRs were large.

Effectiveness of a theory-based intervention to increase colorectal cancer screening among Iranian health club members: a randomized trial.

Science.gov (United States)

Salimzadeh, Hamideh; Eftekhar, Hassan; Majdzadeh, Reza; Montazeri, Ali; Delavari, Alireza

2014-10-01

Colorectal cancer is the third most commonly diagnosed cancer and the fourth leading cause of death in the world. There are few published studies that have used theory-based interventions designed to increase colorectal cancer screening in community lay health organizations. The present study was guided by the theoretical concepts of the preventive health model. Twelve health clubs of a municipal district in Tehran were randomized to two study groups with equal ratio. The control group received usual services throughout the study while the intervention group also received a theory-based educational program on colorectal cancer screening plus a reminder call. Screening behavior, the main outcome, was assessed 4 months after randomization. A total of 360 members aged 50 and older from 12 health clubs completed a baseline survey. Participants in the intervention group reported increased knowledge of colorectal cancer and screening tests at 4 months follow-up (p's theory-based intervention significantly improved self-efficacy, perceived susceptibility, efficacy of screening, social support, and intention to be screened for colorectal cancer, from baseline to 4 months follow-up (p's theory-based intervention was found to have a significant effect on colorectal cancer screening use as measured by self-report. The findings could have implications for colorectal cancer screening program development and implementation in primary health care settings and through other community organizations.

Cholecystectomy can increase the risk of colorectal cancer: A meta-analysis of 10 cohort studies.

Directory of Open Access Journals (Sweden)

Yong Zhang

Full Text Available This study aimed to elucidate the effects of cholecystectomy on the risk of colorectal cancer (CRC by conducting a meta-analysis of 10 cohort studies.The eligible cohort studies were selected by searching the PubMed and EMBASE databases from their origination to June 30, 2016, as well as by consulting the reference lists of the selected articles. Two authors individually collected the data from the 10 papers. When the data showed marked heterogeneity, we used a random-effects model to estimate the overall pooled risk; otherwise, a fixed effects model was employed.The final analysis included ten cohort studies. According to the Newcastle-Ottawa Scale (NOS, nine papers were considered high quality. After the data of these 9 studies were combined, an increased risk of CRC was found among the individuals who had undergone cholecystectomy (risk ratio (RR 1.22; 95% confidence interval (CI 1.08-1.38. In addition, we also found a promising increased risk for colon cancer (CC (RR 1.30, 95% CI 1.07-1.58, but no relationship between cholecystectomy and rectum cancer (RC (RR 1.09; 95% CI 0.89-1.34 was observed. Additionally, in the sub-group analysis of the tumor location in the colon, a positive risk for ascending colon cancer (ACC was found (RR 1.18, 95% CI 1.11-1.26. After combining the ACC, transverse colon cancer (TCC, sigmoid colon cancer (SCC and descending colon cancer (DCC patients, we found a positive relationship with cholecystectomy (RR 1.18, 95% CI 1.11-1.26. Furthermore, after combining the ACC and DCC patients, we also found a positive relationship with cholecystectomy (RR 1.28; 95% CI 1.11-1.26 in the sub-group analysis. In an additional sub-group analysis of patients from Western countries, there was a positive relationship between cholecystectomy and the risk of CRC (RR 1.20; 95% CI 1.05-1.36. Furthermore, a positive relationship between female gender and CRC was also found (RR 1.17; 95% CI 1.03-1.34. However, there was no relationship

Paclitaxel-induced hypothermia and hypoperfusion increase breast cancer metastasis and angiogenesis in mice

Science.gov (United States)

Ami, Nozomi; Sato, Hideki; Hayakawa, Yoshihiro

2018-01-01

Housing temperature has been shown to influence thermoregulation and behavior of preclinical cancer models; and anti-cancer drugs typically reduce peripheral blood flow and body temperature. In the present study, the effects of paclitaxel (PTX)-induced reduction of body temperature and peripheral blood flow on metastatic 4T1 breast cancer was investigated in a mouse model and the modification of these effects by thermoneutral temperature was also assessed. A single dose of PTX decreased the body temperature and peripheral blood flow in mice housed at a standard temperature (23°C). Furthermore, although lung metastasis and angiogenesis of inoculated 4T1 cells increased in mice pretreated with PTX, mice housed at a thermoneutral temperature (30°C) could compensate their body temperature and peripheral blood flow compared with control mice, and also suppressed 4T1 angiogenesis and metastasis to lung. The present results imply that maintenance of body temperature or efficient energy supply for thermogenesis may prevent tumor relapse or metastasis after chemotherapy. PMID:29434941

Evolution of echocardiography in subclinical detection of cancer therapy-related cardiac dysfunction.

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Moudgil, Rohit; Hassan, Saamir; Palaskas, Nicolas; Lopez-Mattei, Juan; Banchs, Jose; Yusuf, Syed Wamique

2018-05-11

Cancer therapies have resulted in increased survivorship in oncological patients. However, the benefits have been marred by the development of premature cardiovascular disease. The current definition outlines measurement of ejection fraction as a mean to diagnose cancer therapeutic-related cardiac dysfunction (CTRCD); however, up to 58% of the patients do not regain their cardiac function after the CTRCD diagnosis, despite therapeutic interventions. Therefore, there has been a growing interest in the markers for early myocardial changes (ie, changes with normal left ventricular ejection fraction [LVEF]) that may predict the development of subsequent left ventricular ejection fraction reduction or progression to heart failure. This review will highlight the use of diastolic parameters, tissue Doppler imaging (TDI), and speckle tracking echocardiogram (STE) as emerging technologies which can potentially detect cardiac dysfunction thereby stratifying patients for cardioprotective therapies. The goal of this manuscript was to highlight the concepts and discuss the current controversies surrounding these echocardiographic imaging modalities. © 2018 Wiley Periodicals, Inc.

Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

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Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

2014-01-01

The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

Program spending to increase adherence: South African cervical cancer screening.

Directory of Open Access Journals (Sweden)

Jeremy D Goldhaber-Fiebert

2009-05-01

Full Text Available Adherence is crucial for public health program effectiveness, though the benefits of increasing adherence must ultimately be weighed against the associated costs. We sought to determine the relationship between investment in community health worker (CHW home visits and increased attendance at cervical cancer screening appointments in Cape Town, South Africa.We conducted an observational study of 5,258 CHW home visits made in 2003-4 as part of a community-based screening program. We estimated the functional relationship between spending on these visits and increased appointment attendance (adherence. Increased adherence was noted after each subsequent CHW visit. The costs of making the CHW visits was based on resource use including both personnel time and vehicle-related expenses valued in 2004 Rand. The CHW program cost R194,018, with 1,576 additional appointments attended. Adherence increased from 74% to 90%; 55% to 87%; 48% to 77%; and 56% to 80% for 6-, 12-, 24-, and 36-month appointments. Average per-woman costs increased by R14-R47. The majority of this increase occurred with the first 2 CHW visits (90%, 83%, 74%, and 77%; additional cost: R12-R26.We found that study data can be used for program planning, identifying spending levels that achieve adherence targets given budgetary constraints. The results, derived from a single disease program, are retrospective, and should be prospectively replicated.

Magnetic nanoparticles for cancer therapy

International Nuclear Information System (INIS)

Bakuzis, Andris F.

2014-01-01

Full text: Magnetic nanoparticles have been used in several biomedical applications, spanning from cell separation, early diagnosis of metastasis to even the treatment of cancer via magnetic hyperthermia (MH). This last technique consists in the increase of temperature of nanoparticles when their magnetic moments interact with a magnetic alternating field. This effect has been suggested as an innovative therapy to cancer treatment, due to the delivery of heat or therapeutic agents, such as drugs, genes, and others. In addition, several clinical studies has demonstrated synergetic effects between hyperthermia and radiotherapy [1]. This indicates a great therapeutic potential for this noninvasive and targeted technique. In this talk we will discuss results from the literature and from our own group in the treatment of cancer via magnetic hyperthermia. Several types of magnetic nanoparticles suggested for this application will be discussed, as well as the historical evolution of this procedure, which although suggested in the late 50' only recently was approved in Europe for treatment of humans with brain tumors. (author) [pt

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

NARCIS (Netherlands)

Eggermond, A.M. van; Schaapveld, M.; Janus, C.P.; Boer, J.P. de; Krol, A.D.; Zijlstra, J.M.; Maazen, R.W.M. van der; Kremer, L.C.; Leerdam, M.E. van; Louwman, M.W.; Visser, O; Bruin, M.L. De; Aleman, B.M.; Leeuwen, F.E. van

2017-01-01

BACKGROUND: Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. METHODS: In a

The KinFact intervention - a randomized controlled trial to increase family communication about cancer history.

Science.gov (United States)

Bodurtha, Joann N; McClish, Donna; Gyure, Maria; Corona, Rosalie; Krist, Alexander H; Rodríguez, Vivian M; Maibauer, Alisa M; Borzelleca, Joseph; Bowen, Deborah J; Quillin, John M

2014-10-01

Knowing family history is important for understanding cancer risk, yet communication within families is suboptimal. Providing strategies to enhance communication may be useful. Four hundred ninety women were recruited from urban, safety-net, hospital-based primary care women's health clinics. Participants were randomized to receive the KinFact intervention or the control handout on lowering risks for breast/colon cancer and screening recommendations. Cancer family history was reviewed with all participants. The 20-minute KinFact intervention, based in communication and behavior theory, included reviewing individualized breast/colon cancer risks and an interactive presentation about cancer and communication. Study outcomes included whether participants reported collecting family history, shared cancer risk information with relatives, and the frequency of communication with relatives. Data were collected at baseline, 1, 6, and 14 months. Overall, intervention participants were significantly more likely to gather family cancer information at follow-up (odds ratio [OR]: 2.73; 95% confidence interval [CI]: 2.01, 3.71) and to share familial cancer information with relatives (OR: 1.85; 95% CI: 1.37, 2.48). Communication frequency (1=not at all; 4=a lot) was significantly increased at follow-up (1.67 vs. 1.54). Differences were not modified by age, race, education, or family history. However, effects were modified by pregnancy status and genetic literacy. Intervention effects for information gathering and frequency were observed for nonpregnant women but not for pregnant women. Additionally, intervention effects were observed for information gathering in women with high genetic literacy, but not in women with low genetic literacy. The KinFact intervention successfully promoted family communication about cancer risk. Educating women to enhance their communication skills surrounding family history may allow them to partner more effectively with their families and ultimately

Low to moderate alcohol intake is not associated with increased mortality after breast cancer.

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Flatt, Shirley W; Thomson, Cynthia A; Gold, Ellen B; Natarajan, Loki; Rock, Cheryl L; Al-Delaimy, Wael K; Patterson, Ruth E; Saquib, Nazmus; Caan, Bette J; Pierce, John P

2010-03-01

Both alcohol consumption and obesity have been linked with breast cancer morbidity and mortality. An inverse association between alcohol intake and obesity suggests possible confounding between these variables (and perhaps other factors) with breast cancer outcomes. Alcohol intake (beer, wine, spirits, and total) was examined in 3,088 women previously diagnosed and treated for breast cancer within an intervention trial that targeted vegetables, fiber, and fat but not alcohol or weight loss. Factors associated with baseline alcohol intake were included in Cox proportional hazards models for recurrence and mortality. Alcohol intake was significantly associated with higher education and physical activity levels. Neither light alcohol intake nor obesity was significantly associated with breast cancer recurrence, but moderate alcohol intake >300 g/mo was protective against all-cause mortality (hazard ratio, 0.69; 95% confidence intervals, 0.49-0.97) in a proportional hazards model adjusted for obesity. Obese women were 61% more likely to be nondrinkers than drinkers, and 76% more likely to be light drinkers than moderate/heavy drinkers. In nonobese women, alcohol intake >10 g/mo was associated with lower risk of all-cause mortality (hazard ratio, 0.68; 95% confidence intervals, 0.51-0.91). Light alcohol intake, regardless of body weight, did not increase the risk of breast cancer recurrence or all-cause mortality in this cohort of middle-aged women previously diagnosed with breast cancer. Alcohol intake was associated with other favorable prognostic indicators, which may explain its apparent protective effect in nonobese women.

miR-146a C/G polymorphism increased the risk of head and neck cancer, but overall cancer risk: an analysis of 89 studies.

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Sun, Dezhong; Zhang, Xiaoyan; Zhang, Xiaolei

2018-02-28

Several studies have evaluated the association of miR-146a C/G with head and neck cancer (HNC) susceptibility, and overall cancer risk, but with inconclusive outcomes. To drive a more precise estimation, we carried out this meta-analysis. The literature was searched from MEDLINE (mainly PubMed), Embase, the Cochrane Library, and Google Scholar databases to identify eligible studies. A total of 89 studies were included. The results showed that miR-146a C/G was significantly associated with increased HNC risk in dominant model ( I 2 =15.6%, P heterogeneity =0.282, odds ratio (OR) =1.088, 95% confidence interval (CI) =1.002-1.182, P =0.044). However, no cancer risk was detected under all genetic models. By further stratified analysis, we found that rs4919510 mutation contributed to the risk of HNC amongst Asians under homozygote model ( I 2 =0, P heterogeneity =0.541, OR =1.189, 95% CI =1.025-1.378, P =0.022), and dominant model ( I 2 =0, P heterogeneity =0.959, OR =1.155, 95% CI =1.016-1.312, P =0.028). Simultaneously, in the stratified analysis by source of controls, a significantly increased cancer risk amongst population-based studies was found under homozygote model, dominant model, recessive model, and allele comparison model. However, no significant association was found in the stratified analysis by ethnicity and source of control. The results indicated that miR-146a C/G polymorphism may contribute to the increased HNC susceptibility and could be a promising target to forecast cancer risk for clinical practice. However, no significant association was found in subgroup analysis by ethnicity and source of control. To further confirm these results, well-designed large-scale case-control studies are needed in the future. © 2018 The Author(s).

Adaptive Evolution Coupled with Retrotransposon Exaptation Allowed for the Generation of a Human-Protein-Specific Coding Gene That Promotes Cancer Cell Proliferation and Metastasis in Both Haematological Malignancies and Solid Tumours: The Extraordinary Case of MYEOV Gene

Directory of Open Access Journals (Sweden)

Spyros I. Papamichos

2015-01-01

Full Text Available The incidence of cancer in human is high as compared to chimpanzee. However previous analysis has documented that numerous human cancer-related genes are highly conserved in chimpanzee. Till date whether human genome includes species-specific cancer-related genes that could potentially contribute to a higher cancer susceptibility remains obscure. This study focuses on MYEOV, an oncogene encoding for two protein isoforms, reported as causally involved in promoting cancer cell proliferation and metastasis in both haematological malignancies and solid tumours. First we document, via stringent in silico analysis, that MYEOV arose de novo in Catarrhini. We show that MYEOV short-isoform start codon was evolutionarily acquired after Catarrhini/Platyrrhini divergence. Throughout the course of Catarrhini evolution MYEOV acquired a gradually elongated translatable open reading frame (ORF, a gradually shortened translation-regulatory upstream ORF, and alternatively spliced mRNA variants. A point mutation introduced in human allowed for the acquisition of MYEOV long-isoform start codon. Second, we demonstrate the precious impact of exonized transposable elements on the creation of MYEOV gene structure. Third, we highlight that the initial part of MYEOV long-isoform coding DNA sequence was under positive selection pressure during Catarrhini evolution. MYEOV represents a Primate Orphan Gene that acquired, via ORF expansion, a human-protein-specific coding potential.

Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression

DEFF Research Database (Denmark)

Wang, Qian; Bailey, Charles G; Ng, Cynthia

2011-01-01

was sufficient to decrease cell growth and mTORC1 signaling in prostate cancer cells. These cells maintained levels of amino acid influx through androgen receptor-mediated regulation of LAT3 expression and ATF4 regulation of LAT1 expression after amino acid deprivation. These responses remained intact in primary......L-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential amino acids. Here, we report that prostate cancer cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 signaling and cell growth. Inhibiting LAT function...... prostate cancer, as indicated by high levels of LAT3 in primary disease, and by increased levels of LAT1 after hormone ablation and in metastatic lesions. Taken together, our results show how prostate cancer cells respond to demands for increased essential amino acids by coordinately activating amino acid...

Time evolution of scattering states and velocity increase due to nonlinear processes in the quantum hall regime

International Nuclear Information System (INIS)

Riess, J.; Duport, C.

1991-01-01

We report the first numerical results (with realistic parameter values) for the time evolution of a scattered Landau function in a model system. They give a striking illustration for the Hall velocity increase beyond the classical value of the conduction electrons in the quantum Hall regime. This phenomenon, which is crucial for the integer quantum Hall effect, is caused by a special kind of nonclassical particle dynamics induced by disorder and cannot be described by linear response theory

DUOX2 Expression Is Increased in Barrett Esophagus and Cancerous Tissues of Stomach and Colon

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Ran Qi

2016-01-01

Full Text Available Aim. To detect the expression of dual oxidase (DUOX 2 in Barrett esophagus, gastric cancer, and colorectal cancer (CRC. Materials and Methods. The endoscopic biopsies were collected from patients with Barrett esophagus, while the curative resection tissues were obtained from patients with gastric cancer, CRC, or hepatic carcinoma. The DUOX2 protein and mRNA levels were detected with immunohistochemistry (IHC and real-time quantitative PCR (qPCR. The correlation of DUOX2 expression with clinicopathological parameters of tumors was identified. Results. Low levels of DUOX2 mRNA were detected in Barrett esophagus and the adjacent normal tissues, and there was no difference between these two groups. DUOX2 protein was found in Barrett esophagus and undetectable in the normal epithelium. The DUOX2 mRNA and protein levels in the gastric cancer and CRC were increased compared to the adjacent nonmalignant tissues. The elevated DUOX2 in the gastric cancer was significantly associated with smoking history. In CRC tissues, the DUOX2 protein expression level in stages II–IV was significantly higher than that in stage I. In both hepatic carcinoma and the adjacent nonmalignant tissue, the DUOX2 was virtually undetectable. Conclusion. DUOX2 in Barrett esophagus, gastric cancer, and CRC may be involved in the tumorigenesis of these tissues.

Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

Science.gov (United States)

Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

2009-08-01

The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

Increasing Awareness of Gynecologic Cancer Risks and Symptoms among Asian, Native Hawaiian and Pacific Islander Women in the US-Associated Pacific Island Jurisdictions

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Novinson, Daniel; Puckett, Mary; Townsend, Julie; Reichhardt, Martina; Tareg, Aileen; Palemar, Jennifer; Wichilib, Ritchie; Stewart, Sherri L

2017-08-27

Background: Gynecologic cancers are common among Asian/Native Hawaiian/Pacific Islander (A/NH/PI) women. Prevention is important in United States associated Pacific Island jurisdictions (USAPIJ) because there are limited resources to treat cancer. The objective of this study was to educate A/NH/PI women and providers about evidence-based interventions to prevent and control gynecologic cancers in Yap, one of four major islands comprising the Federated States of Micronesia (FSM). This was done through a partnership between Inside Knowledge: Get The Facts About Gynecologic Cancer national campaign and the Yap comprehensive cancer control program, both funded by the Center for Disease Control and Prevention (CDC). Methods: Inside Knowledge educational materials were obtained from the CDC website and used in facilitated educational sessions. Sessions were planned according to leading health education theories, and were implemented and led by local Yap public health practitioners. Pre- and post-session surveys were used to assess changes in gynecologic cancer awareness, confidence and behavioral intentions related to prevention/early detection for gynecologic cancer. Results: Twenty-nine providers and 326 adult women participated in sessions. All participants demonstrated significant increases in knowledge across all measured domains post-session. Public knowledge that HPV causes cervical, vulvar and vaginal cancer increased from 4.9% pre-session to 51.4% post-session (pgynecologic cancer knowledge pre-session compared to 91.7% post-session. Conclusion: Targeted education about gynecologic cancer symptoms and risk factors can be effective at increasing awareness, behavioral intention, confidence and knowledge. These increases can lead to more widespread prevention of these five cancers. Creative Commons Attribution License

Prior history of non-melanoma skin cancer is associated with increased mortality in patients with chronic lymphocytic leukemia

Science.gov (United States)

Toro, Jorge R.; Blake, Patrick W.; Björkholm, Magnus; Kristinsson, Sigurdur Y.; Wang, Zhuoqiao; Landgren, Ola

2009-01-01

We investigated whether a previous diagnosis of non-melanoma skin cancer among chronic lymphocytic leukemia patients is a predictor of poor outcome. Using the Swedish Cancer Registry, we conducted a population-based study to evaluate the survival patterns among chronic lymphocytic leukemia patients with and without non-melanoma skin cancer. Cox proportional hazards regression models were used and Kaplan-Meier curves were constructed. Of a total of 12,041 chronic lymphocytic leukemia cases identified, 236 cases, including 111 squamous cell cancer, had a prior history of non-melanoma skin cancer. Chronic lymphocytic leukemia patients with a prior history of non-melanoma skin cancer had a 1.29-fold (95% CI 1.10–1.52; p=0.0024) increased risk of dying; and those with a history of squamous cell cancer had a further elevated 1.86-fold (95% CI 1.46–2.36; p<0.0001) risk of dying. Kaplan-Meier plots showed that patients with a history of non-melanoma skin cancer, particularly those with squamous cell cancer, had significantly poorer survival than chronic lymphocytic leukemia patients without non-melanoma skin cancer (p<0.0001; log-rank test). Non-melanoma skin cancer may be a novel clinical predictor of worse chronic lymphocytic leukemia outcome. PMID:19794092

Infradiaphragmatic irradiation and high procarbazine doses increase colorectal cancer risk in Hodgkin lymphoma survivors

NARCIS (Netherlands)

van Eggermond, Anna M.; Schaapveld, Michael; Janus, Cécile Pm; de Boer, Jan Paul; Krol, Augustinus Dg; Zijlstra, Josée M.; van der Maazen, Richard Wm; Kremer, Leontien C.; van Leerdam, Monique E.; Louwman, Marieke Wj; Visser, Otto; de Bruin, Marie L.; Aleman, Berthe Mp; van Leeuwen, Flora E.

2017-01-01

Hodgkin lymphoma (HL) survivors are at increased risk of second malignancies, but few studies have assessed colorectal cancer (CRC) risk after HL treatment. We assessed long-term, subsite-specific CRC risk associated with specific radiation fields and chemotherapy regimens. In a Dutch cohort of 3121

Standard psychological consultations and follow up for women at increased risk of hereditary breast cancer considering prophylactic mastectomy

NARCIS (Netherlands)

M.B.M. Tan; E.M.A. Bleiker (Eveline); M.B.E. Menke-Pluymers (Marian); A.R. van Gool (Arthur); S. van Dooren (Silvia); B.N. van Geel (Bert); M.M.A. Tilanus-Linthorst (Madeleine); C.C.M. Bartels (Carina); J.G.M. Klijn (Jan); C.T. Brekelmans (Cecile); C.M. Seynaeve (Caroline)

2009-01-01

textabstractBackground: Women at increased (genetic) risk of breast cancer have to weigh the personal pros and cons of prophylactic mastectomy (PM) as an option to reduce their cancer risk. So far, no routine referral to a psychologist has been investigated for women considering PM. Aim of this

Co-Care: A Registry for Individuals at Increased Risk for Colorectal Cancer.

Science.gov (United States)

Sperling, Dylan; Jandorf, Lina; Sriphanlop, Pathu; Martinez, Clarissa; Brown, Karen L; Soper, Emily R; Hiraki, Susan; Itzkowitz, Steven H

2017-01-01

INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of cancer death for both men and women in the United States. Several factors can increase one’s risk of CRC, including a personal or family history of CRC, a diagnosis or family history of a hereditary colon cancer syndrome, or a diagnosis of chronic inflammatory bowel disease. The purpose of this project was to create a colorectal cancer registry (Co-Care) for individuals with a personal or family history of CRC, and those with disorders of the colon or rectum that are associated with an increased risk for developing CRC. Methods: To be eligible for the registry, patients either had a personal or family history of CRC, a diagnosis or family history of Lynch syndrome, familial adenomatous polyposis, or a diagnosis of Crohn’s colitis or ulcerative colitis with dysplasia. Participants were recruited after seeing their gastroenterologist or genetic counselor, or after undergoing a full or partial colectomy at Mount Sinai Hospital in New York City. Eligible patients who agreed to participate were interviewed by a member of the research staff and asked a wide range of questions pertaining to CRC risk. RESULTS: A total of 224 patients were enrolled in the registry. Participants are mostly white, born in the United States, and married, with a bachelor’s or graduate degree, reporting an annual household income of $100,000 or more. The largest portion have a family history of CRC (27.2%), and almost half of participants are of Jewish descent (46.2%) and have undergone full or partial colectomy (48.2%). More than half of participants have neither received genetic counseling (54.5%) nor undergone genetic testing (59.7%). Only 3.6% report that they currently smoke cigarettes, and 41.1% consume alcohol at least once per week. Lastly, 18.3%, 10.3%, and 27.7% of participants report that they currently take aspirin, folic acid/folate pills or tablets, or calcium pills/tablets, respectively. CONCLUSIONS: This

Transcriptome sequencing in prostate cancer identifies inter-tumor heterogeneity

Directory of Open Access Journals (Sweden)

Janet Mendonca

2015-06-01

Full Text Available Given the dearth of gene mutations in prostate cancer, [1] ,[2] it is likely that genomic rearrangements play a significant role in the evolution of prostate cancer. However, in the search for recurrent genomic alterations, "private alterations" have received less attention. Such alterations may provide insights into the evolution, behavior, and clinical outcome of an individual tumor. In a recent report in "Genome Biology" Wyatt et al. [3] defines unique alterations in a cohort of high-risk prostate cancer patient with a lethal phenotype. Utilizing a transcriptome sequencing approach they observe high inter-tumor heterogeneity; however, the genes altered distill into three distinct cancer-relevant pathways. Their analysis reveals the presence of several non-ETS fusions, which may contribute to the phenotype of individual tumors, and have significance for disease progression.

Plant domestication slows pest evolution.

Science.gov (United States)

Turcotte, Martin M; Lochab, Amaneet K; Turley, Nash E; Johnson, Marc T J

2015-09-01

Agricultural practices such as breeding resistant varieties and pesticide use can cause rapid evolution of pest species, but it remains unknown how plant domestication itself impacts pest contemporary evolution. Using experimental evolution on a comparative phylogenetic scale, we compared the evolutionary dynamics of a globally important economic pest - the green peach aphid (Myzus persicae) - growing on 34 plant taxa, represented by 17 crop species and their wild relatives. Domestication slowed aphid evolution by 13.5%, maintained 10.4% greater aphid genotypic diversity and 5.6% higher genotypic richness. The direction of evolution (i.e. which genotypes increased in frequency) differed among independent domestication events but was correlated with specific plant traits. Individual-based simulation models suggested that domestication affects aphid evolution directly by reducing the strength of selection and indirectly by increasing aphid density and thus weakening genetic drift. Our results suggest that phenotypic changes during domestication can alter pest evolutionary dynamics. © 2015 John Wiley & Sons Ltd/CNRS.

Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing

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Yang, Haitao; Jaeger, MariaLynn; Walker, Averi; Wei, Daniel; Leiker, Katie; Weitao, Tao

2018-01-01

Breast cancer is the leading diagnosed cancer for women globally. Evolution of breast cancer in tumorigenesis, metastasis and treatment resistance appears to be driven by the aberrant gene expression and protein degradation encoded by the cancer genomes. The uncontrolled cancer growth relies on these cellular events, thus constituting the cancerous programs and rendering the addiction towards them. These programs are likely the potential anticancer biomarkers for Personalized Medicine of brea...

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

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Jaroslaw Suchanski

Full Text Available In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

Science.gov (United States)

Suchanski, Jaroslaw; Tejchman, Anna; Zacharski, Maciej; Piotrowska, Aleksandra; Grzegrzolka, Jedrzej; Chodaczek, Grzegorz; Nowinska, Katarzyna; Rys, Janusz; Dziegiel, Piotr; Kieda, Claudine; Ugorski, Maciej

2017-01-01

In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such

PDGF-AB rich-trombocyte lysate supplementation from breast cancer patients increased the proliferation of breast cancer stem cells

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Wiwi A. Kartolo

2018-05-01

Full Text Available Background: Thrombocytosis in breast cancer (BC patient was thought to play a role in the invasiveness of breast cancer stem cells (BCSCs. Modification of tumor microenvironment was proposed to increase the efficacy of anticancer therapy. This study was aimed to analyze the effect of platelet lysate (PL as well as its PDGF-AB content as a tumor microenvironment on (CD24-/CD44+ BCSC proliferation.Methods: This was an experimental study that treated culture of BCSCs with PL from breast cancer (BC patients or healthy donors. Venous blood from all subjects were subjected to prior hematology test and then processed to obtain platelet rich plasma  (PRP. Platelet counts in PRP were determined. PRP was processed to obtain PL. PDGF-AB contents in PL were measured. PL at concentrations of 0.01% (v/v was supplemented into DMEM-F12 medium and used for culturing BCSCs (CD24-/CD44+ cells. After 48 hours, total cell count, population doubling time (PDT, and cell viability were calculated and their correlation with platelet count and PDGF-AB levels were analyzed.Results: BC patients (n=5 had higher platelet counts and PDGF-AB levels in PL compared to healthy donors (n=15, (p=0.02. PL from BC patients could stimulate the proliferation of BCSCs higher than healthy donors (p<0.001 and showed lower PDT value (p=0.001. Cell proliferation and PDT showed strong correlation with PDGF-AB level. This observation suggests that PDGF-AB has a role on BCSCs proliferation. PL showed no effect on BCSCs viability.Conclusion: Breast cancer patient platelet lysate stimulated BCSC proliferation.

Thyroid autoantibodies and differentiated thyroid cancer: revue of 662 cases

International Nuclear Information System (INIS)

Izembart, M.; Dagousset, F.; Chevalier, A.; Hassid, V.; Leger, A.; Barritault, L.; Clerc, J.

1999-01-01

The incidence of thyroid autoantibodies is clearly increased in patients with differentiated thyroid cancer. The aim of this study was to re-evaluate frequency and evolution of anti-thyroglobulin and anti-microsomal (anti-peroxidase) autoantibodies in 662 patients with thyroid carcinoma treated with 131 radioiodine. Ours results obtained with 'classical' methods confirmed others earlier reports. When using more sensitive methods to detect thyroglobulin antibodies we obtained an increase in positive results and a more frequent association with anti-microsomal antibodies. Antibodies became undetectable with a variable period, ranging from a few months to 13 years in one case. If we suppose that the disappearance of antibodies is linked to the thyroid tissue disappearance, thyroid cancer follow up ought to include anti-thyroglobulin and anti-peroxidase antibodies, both directed against thyroid antigens. A decrease of both antibodies seems to indicate a favorable prognostic factor whereas an increase may suggest relapse. (author)

The evolution of urban sprawl: evidence of spatial heterogeneity and increasing land fragmentation.

Science.gov (United States)

Irwin, Elena G; Bockstael, Nancy E

2007-12-26

We investigate the dynamics and spatial distribution of land use fragmentation in a rapidly urbanizing region of the United States to test key propositions regarding the evolution of sprawl. Using selected pattern metrics and data from 1973 and 2000 for the state of Maryland, we find significant increases in developed and undeveloped land fragmentation but substantial spatial heterogeneity as well. Estimated fragmentation gradients that describe mean fragmentation as a function of distance from urban centers confirm the hypotheses that fragmentation rises and falls with distance and that the point of maximum fragmentation shifted outward over time. However, rather than outward increases in sprawl balanced by development infill, we find substantial and significant increases in mean fragmentation values along the entire urban-rural gradient. These findings are in contrast to the results of Burchfield et al. [Burchfield M, Overman HG, Puga D, Turner MA (2006) Q J Econ 121:587-633], who conclude that the extent of sprawl remained roughly unchanged in the Unites States between 1976 and 1992. As demonstrated here, both the data and pattern measure used in their study are systematically biased against recording low-density residential development, the very land use that we find is most strongly associated with fragmentation. Other results demonstrate the association between exurban growth and increasing fragmentation and the systematic variation of fragmentation with nonurban factors. In particular, proximity to the Chesapeake Bay is negatively associated with fragmentation, suggesting that an attraction effect associated with this natural amenity has concentrated development.

Night Shift Work Increases the Risks of Multiple Primary Cancers in Women: A Systematic Review and Meta-analysis of 61 Articles.

Science.gov (United States)

Yuan, Xia; Zhu, Chenjing; Wang, Manni; Mo, Fei; Du, Wei; Ma, Xuelei

2018-01-01

A growing number of studies have examined associations between night shift work and the risks of common cancers among women, with varying conclusions. We did a meta-analysis to identify whether long-term night shift work increased the risks of common cancers in women. We enrolled 61 articles involving 114,628 cases and 3,909,152 participants from Europe, North America, Asia, and Australia. Risk estimates were performed with a random-effect model or a fixed-effect model. Subgroup analyses and meta-regression analyses about breast cancer were conducted to explore possible sources of heterogeneity. In addition, we carried out a dose-response analysis to quantitatively estimate the accumulative effect of night shift work on the risk of breast cancer. A positive relationship was revealed between long-term night shift work and the risks of breast [OR = 1.316; 95% confidence interval (CI), 1.196-1.448], digestive system (OR = 1.177; 95% CI, 1.065-1.301), and skin cancer (OR = 1.408; 95% CI, 1.024-1.934). For every 5 years of night shift work, the risk of breast cancer in women was increased by 3.3% (OR = 1.033; 95% CI, 1.012-1.056). Concerning the group of nurses, long-term night shift work presented potential carcinogenic effect in breast cancer (OR = 1.577; 95% CI, 1.235-2.014), digestive system cancer (OR = 1.350; 95% CI, 1.030-1.770), and lung cancer (OR = 1.280; 95% CI, 1.070-1.531). This systematic review confirmed the positive association between night shift work and the risks of several common cancers in women. We identified that cancer risk of women increased with accumulating years of night shift work, which might help establish and implement effective measures to protect female night shifters. Cancer Epidemiol Biomarkers Prev; 27(1); 25-40. ©2018 AACR . ©2018 American Association for Cancer Research.