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Sample records for cancer cells delays

  1. Carrageenan delays cell cycle progression in human cancer cells in vitro demonstrated by FUCCI imaging.

    Science.gov (United States)

    Prasedya, Eka Sunarwidhi; Miyake, Masao; Kobayashi, Daisuke; Hazama, Akihiro

    2016-08-04

    Carrageenan is a sulfated polysaccharide that exists in red seaweeds recently shown to have anticancer properties. Previous findings show various effects of carrageenan suppressing tumor cell growth. One of the hallmarks of cancer is uncontrolled proliferation, a consequence of loss of normal cell-cycle control, that underlies tumor growth. Recently there is an increasing interest in potential anticancer agents that affect cell cycle in cancer cells. Thus, in this study we investigated the effects of carrageenan on the tumor cell cycle. Using human cervical carcinoma cells (HeLa) cells as and human umbilical vein endothelial cells (HUVEC), the cytotoxic effects of kappa carrageenan (k-CO) and lambda carrageenan (λ-CO) at the concentrations of 250-2500 μg/mL were observed. Cell viability was determined using the MTT assay while cell death rates were determined using staining with calcein-AM/propidium iodide. Cell-cycle profile and progression were demonstrated with HeLa cells expressing FUCCI (fluorescence ubiquitination-based cell-cycle indicator) probes (HeLa-FUCCI). Carrageenan had no significant effect on HUVEC (normal cells). In contrast both forms of carrageenan were cytotoxic towards HeLa cells (cancer cells). Furthermore, according to cell-cycle analysis with FUCCI cells, the cell cycle of HeLa cells was delayed in specific phases due to different carrageenan treatments. Considering these results, it could be suggested that carrageenan affects the cell-cycle of HeLa cells not only by arresting the cell cycle in specific phases but also by delaying the time needed for the cell to progress through the cell cycle. Additionally, different types of carrageenans have different effects on cell cycle progression. This effect of carrageenan towards cancer cells could possibly be developed into a tumor cell-specific anticancer agent.

  2. Delayed luminescence to monitor programmed cell death induced by berberine on thyroid cancer cells

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    Scordino, Agata; Campisi, Agata; Grasso, Rosaria; Bonfanti, Roberta; Gulino, Marisa; Iauk, Liliana; Parenti, Rosalba; Musumeci, Francesco

    2014-11-01

    Correlation between apoptosis and UVA-induced ultraweak photon emission delayed luminescence (DL) from tumor thyroid cell lines was investigated. In particular, the effects of berberine, an alkaloid that has been reported to have anticancer activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell lines, as representative of follicular and anaplastic thyroid human cancer, respectively, were chosen. The results show that berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since berberine acts especially at the mitochondrial level. The decrease of DL blue component for both cell lines could be related to the decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a hallmark of induced apoptosis. In contrast, the response in the red spectral range is different for the two cell lines and may be ascribed to a different iron homeostasis.

  3. Systemic alkalinisation delays prostate cancer cell progression in TRAMP mice.

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    Astigiano, Simonetta; Puglisi, Andrea; Mastracci, Luca; Fais, Stefano; Barbieri, Ottavia

    2017-12-01

    The microenvironment of solid tumours is extremely acidic and this condition arises since the precancerous stage. This acidic milieu could therefore provide a useful target for both prophylactic and therapeutic approaches. In TRAMP transgenic mice, an in vivo model of prostate adenocarcinoma (AC), oral administration of alkaline water was devoid of unwanted side effects, and when started from an early age was as effective as NaHCO3 in significantly delaying tumour progression, while when started when prostate tumours were already present, a nonstatistically significant trend in the same direction was detected. These findings indicate that the use of alkalinizing drugs should be considered for chemoprevention and, in association with standard chemotherapy, for treatment of human prostate AC.

  4. CALCULUS FROM THE PAST: MULTIPLE DELAY SYSTEMS ARISING IN CANCER CELL MODELLING

    KAUST Repository

    WAKE, G. C.

    2013-01-01

    Nonlocal calculus is often overlooked in the mathematics curriculum. In this paper we present an interesting new class of nonlocal problems that arise from modelling the growth and division of cells, especially cancer cells, as they progress through the cell cycle. The cellular biomass is assumed to be unstructured in size or position, and its evolution governed by a time-dependent system of ordinary differential equations with multiple time delays. The system is linear and taken to be autonomous. As a result, it is possible to reduce its solution to that of a nonlinear matrix eigenvalue problem. This method is illustrated by considering case studies, including a model of the cell cycle developed recently by Simms, Bean and Koeber. The paper concludes by explaining how asymptotic expressions for the distribution of cells across the compartments can be determined and used to assess the impact of different chemotherapeutic agents. Copyright © 2013 Australian Mathematical Society.

  5. Amygdalin delays cell cycle progression and blocks growth of prostate cancer cells in vitro.

    Science.gov (United States)

    Makarević, Jasmina; Tsaur, Igor; Juengel, Eva; Borgmann, Hendrik; Nelson, Karen; Thomas, Christian; Bartsch, Georg; Haferkamp, Axel; Blaheta, Roman A

    2016-02-15

    Despite impressive survival benefits from new agents to treat metastasized prostate cancer (PCa), progressive drug resistance hinders long-term response and restricts the efficacy of subsequent therapy. Due to reported antitumor activity of amygdalin and growing popularity for complementary and alternative medicine the potential of this natural, widely used substance to exert antineoplastic effects on prostate cancer cells has been assessed. LNCaP (castration-sensitive), DU-145 and PC3 cells (castration-resistant) were exposed to different concentrations of amygdalin for 24h or 2weeks. Cell growth was measured by the MTT test, clonal formation by the clonogenic assay. Flow cytometry served to investigate apoptosis and cell cycle phases. Cell cycle regulating proteins and the mTOR-akt signaling axis were analyzed by western blotting. Amygdalin dose-dependently diminished tumor cell growth with maximum effects at 10mg/ml. Apoptosis of PC3 and LNCaP but not of DU-145 cells was reduced, whereas colony formation was suppressed in all cell lines. A decrease in the number of G2/M- and S-phase cells along with an elevated number of G0/G1-phase cells was recorded. The cell cycle proteins cdk 1, cdk 2 and cdk 4 as well as cyclin A, cyclin B and cyclin D3 were modulated by amygdalin after both 24h and 2weeks. Distinct effects on p19 and p27 expression and on Akt, Rictor and Raptor activation became evident only after 2weeks. Amygdalin exhibits significant antitumor activity in both castration-sensitive and castration-resistant PCa cell lines and merits further evaluation for therapeutic purposes. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Influence of distributed delays on the dynamics of a generalized immune system cancerous cells interactions model

    Science.gov (United States)

    Piotrowska, M. J.; Bodnar, M.

    2018-01-01

    We present a generalisation of the mathematical models describing the interactions between the immune system and tumour cells which takes into account distributed time delays. For the analytical study we do not assume any particular form of the stimulus function describing the immune system reaction to presence of tumour cells but we only postulate its general properties. We analyse basic mathematical properties of the considered model such as existence and uniqueness of the solutions. Next, we discuss the existence of the stationary solutions and analytically investigate their stability depending on the forms of considered probability densities that is: Erlang, triangular and uniform probability densities separated or not from zero. Particular instability results are obtained for a general type of probability densities. Our results are compared with those for the model with discrete delays know from the literature. In addition, for each considered type of probability density, the model is fitted to the experimental data for the mice B-cell lymphoma showing mean square errors at the same comparable level. For estimated sets of parameters we discuss possibility of stabilisation of the tumour dormant steady state. Instability of this steady state results in uncontrolled tumour growth. In order to perform numerical simulation, following the idea of linear chain trick, we derive numerical procedures that allow us to solve systems with considered probability densities using standard algorithm for ordinary differential equations or differential equations with discrete delays.

  7. DNA damage enhanced by the attenuation of SLD5 delays cell cycle restoration in normal cells but not in cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Yuan Gong

    Full Text Available SLD5 is a member of the GINS complex composed of PSF1, PSF2, PSF3 and SLD5, playing a critical role in the formation of the DNA replication fork with CDC45 in yeast. Previously, we had isolated a PSF1 orthologue from a murine hematopoietic stem cell DNA library and were then able to identify orthologues of all the other GINS members by the yeast two hybrid approach using PSF1 as the bait. These GINS orthologues may also function in DNA replication in mammalian cells because they form tetrameric complexes as observed in yeast, and gene deletion mutants of both PSF1 and SLD5 result in a lack of epiblast proliferation and early embryonic lethality. However, we found that PSF1 is also involved in chromosomal segregation in M phase, consistent with recent suggestions that homologues of genes associated with DNA replication in lower organisms also regulate cellular events other than DNA replication in mammalian cells. Here we analyzed the function of SLD5 other than DNA replication and found that it is active in DNA damage and repair. Attenuation of SLD5 expression results in marked DNA damage in both normal cells and cancer cells, suggesting that it protects against DNA damage. Attenuation of SLD5 delays the DNA repair response and cell cycle restoration in normal cells but not in cancer cells. These findings suggest that SLD5 might represent a therapeutic target molecule acting at the level of tumor stromal cells rather than the cancerous cells themselves, because development of the tumor microenvironment could be delayed or disrupted by the suppression of its expression in the normal cell types within the tumor.

  8. Transfer between hospitals as a predictor of delay in diagnosis and treatment of patients with Non-Small Cell Lung Cancer

    DEFF Research Database (Denmark)

    Iachina, Maria; Jakobsen, Erik; Fallesen, Anne Kudsk

    2017-01-01

    as a potential cause of the poor prognosis and as consequence, fast track cancer care pathways were implemented describing maximum acceptable time thresholds from referral to treatment. In Denmark, patients with lung cancer are often transferred between hospitals with diagnostic facilities to hospitals...... and accelerate the diagnosis and treatment of cancer. We found that the transfer between hospitals during the care pathway might cause delay from diagnosis to treatment as well as in the total time from referral to treatment in patients with Non Small-Cell Lung Cancer. The difference between no......BACKGROUND: Lung cancer is the second most frequent cancer diagnosis in Denmark. Although improved during the last decade, the prognosis of lung cancer is still poor with an overall 5-year survival rate of approximately 12%. Delay in diagnosis and treatment of lung cancer has been suggested...

  9. Expression of (NES-hTERT in cancer cells delays cell cycle progression and increases sensitivity to genotoxic stress.

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    Olga A Kovalenko

    Full Text Available Telomerase is a reverse transcriptase associated with cellular immortality through telomere maintenance. This enzyme is activated in 90% of human cancers, and inhibitors of telomerase are currently in clinical trials to counteract tumor growth. Many aspects of telomerase biology have been investigated for therapy, particularly inhibition of the enzyme, but little was done regarding its subcellular shuttling. We have recently shown that mutations in the nuclear export signal of hTERT, the catalytic component of telomerase, led to a mutant ((NES-hTERT that failed to immortalize cells despite nuclear localization and catalytic activity. Expression of (NES-hTERT in primary fibroblast resulted in telomere-based premature senescence and mitochondrial dysfunction. Here we show that expression of (NES-hTERT in LNCaP, SQ20B and HeLa cells rapidly and significantly decreases their proliferation rate and ability to form colonies in soft agar while not interfering with endogenous telomerase activity. The cancer cells showed increased DNA damage at telomeric and extra-telomeric sites, and became sensitive to ionizing radiation and hydrogen peroxide exposures. Our data show that expression of (NES-hTERT efficiently counteracts cancer cell growth in vitro in at least two different ways, and suggest manipulation with the NES of hTERT or its subcellular shuttling as a new strategy for cancer treatment.

  10. p53 dependent apoptosis and cell cycle delay induced by heteroleptic complexes in human cervical cancer cells.

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    Sharma, Gunjan; Rana, Nishant Kumar; Singh, Priya; Dubey, Pradeep; Pandey, Daya Shankar; Koch, Biplob

    2017-04-01

    We previously reported synthesis of novel arene ruthenium (Ru) complexes and evaluated their antitumor activity in murine lymphoma (DL) cells. In this present study we further investigated the mechanism of action of two ruthenium complexes [complex 1 (η6-arene)RuCl(2-pcdpm)] and complex 2 (η6-arene)RuCl(4-mtdpm)] in cervical cancer cell line (HeLa). Our studies demonstrate that anticancer property of these two complexes was due to induction of apoptosis through p53 mediated pathway as well as arrest of cells in G2/M phase of cell cycle. It is worth to note that the complexes did not cause any substantial cytotoxic effect on normal cells. Further in comprehensive studies, apoptosis inducing property of both complexes were established in accordance with array of morphological changes ranging from membrane blebbing to formation of apoptotic bodies and followed by DNA fragmentation assay. Furthermore, Flow cytometry by Annexin V/PI staining delineate that complex 1 and 2 have strident impact to induce apoptosis in HeLa cells. The complex 1 and 2 treated cells show increased level of intracellular ROS generation which was preceded by p53 activation. Apoptosis induced by 1 and 2 was preceded by mitochondrial aggregations which were monitored by mitotracker. In addition flow cytometry analysis showed that both complexes also effectively arrest cells at G2/M phase of cell cycle. Western blot, RT-PCR as well as Real Time analysis were used to further confirm that the complexes induced apoptosis in p53 dependent pathway. Thus, our promising results can contribute to the rational design of novel potential anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. HAMLET treatment delays bladder cancer development.

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    Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

    2010-04-01

    HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  12. Transfer between hospitals as a predictor of delay in diagnosis and treatment of patients with Non-Small Cell Lung Cancer - a register based cohort-study.

    Science.gov (United States)

    Iachina, Maria; Jakobsen, Erik; Fallesen, Anne Kudsk; Green, Anders

    2017-04-12

    Lung cancer is the second most frequent cancer diagnosis in Denmark. Although improved during the last decade, the prognosis of lung cancer is still poor with an overall 5-year survival rate of approximately 12%. Delay in diagnosis and treatment of lung cancer has been suggested as a potential cause of the poor prognosis and as consequence, fast track cancer care pathways were implemented describing maximum acceptable time thresholds from referral to treatment. In Denmark, patients with lung cancer are often transferred between hospitals with diagnostic facilities to hospitals with treatment facilities during the care pathway. We wanted to investigate whether this organizational set-up influenced the time that patients wait for the diagnosis and treatment. Therefore, the objective of this study was to uncover the impact of transfer between hospitals on the delay in the diagnosis and treatment of Non-Small Cell Lung Cancer (NSCLC). We performed a historical prospective cohort study using data from the Danish Lung Cancer Registry (DLCR). All patients diagnosed with primary NSCLC from January 1st 2008 to December 31st 2012 were included. Patients with unresolved pathology and incomplete data on the dates of referral, diagnosis and treatment were excluded. A total of 11 273 patients were included for further analyses. Transfer patients waited longer for treatment after the diagnosis, (Hazard ratio (HR) 0.81 (0.68-0.96)) and in total time from referral to treatment (HR 0.84 (0.77-0.92)), than no-transfer patients. Transfer patients had lower odds of being diagnosed (Odds Ratio (OR) 0.82 (0.74-0.94) and treated (OR 0.66 (0.61-0.72) within the acceptable time thresholds described in the care pathway. Fast track cancer care pathways were implemented to unify and accelerate the diagnosis and treatment of cancer. We found that the transfer between hospitals during the care pathway might cause delay from diagnosis to treatment as well as in the total time from referral to

  13. HDAC8 Inhibition Blocks SMC3 Deacetylation and Delays Cell Cycle Progression without Affecting Cohesin-dependent Transcription in MCF7 Cancer Cells.

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    Dasgupta, Tanushree; Antony, Jisha; Braithwaite, Antony W; Horsfield, Julia A

    2016-06-10

    Cohesin, a multi-subunit protein complex involved in chromosome organization, is frequently mutated or aberrantly expressed in cancer. Multiple functions of cohesin, including cell division and gene expression, highlight its potential as a novel therapeutic target. The SMC3 subunit of cohesin is acetylated (ac) during S phase to establish cohesion between replicated chromosomes. Following anaphase, ac-SMC3 is deacetylated by HDAC8. Reversal of SMC3 acetylation is imperative for recycling cohesin so that it can be reloaded in interphase for both non-mitotic and mitotic functions. We blocked deacetylation of ac-SMC3 using an HDAC8-specific inhibitor PCI-34051 in MCF7 breast cancer cells, and examined the effects on transcription of cohesin-dependent genes that respond to estrogen. HDAC8 inhibition led to accumulation of ac-SMC3 as expected, but surprisingly, had no influence on the transcription of estrogen-responsive genes that are altered by siRNA targeting of RAD21 or SMC3. Knockdown of RAD21 altered estrogen receptor α (ER) recruitment at SOX4 and IL20, and affected transcription of these genes, while HDAC8 inhibition did not. Rather, inhibition of HDAC8 delayed cell cycle progression, suppressed proliferation and induced apoptosis in a concentration-dependent manner. We conclude that HDAC8 inhibition does not change the estrogen-specific transcriptional role of cohesin in MCF7 cells, but instead, compromises cell cycle progression and cell survival. Our results argue that candidate inhibitors of cohesin function may differ in their effects depending on the cellular genotype and should be thoroughly tested for predicted effects on cohesin's mechanistic roles. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway.

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    Jing, Zhao; Sui, Xinbing; Yao, Junlin; Xie, Jiansheng; Jiang, Liming; Zhou, Yubin; Pan, Hongming; Han, Weidong

    2016-03-28

    Store-operated Ca(2+) entry (SOCE) inhibitors are emerging as an attractive new generation of anti-cancer drugs. Here, we report that SKF-96365, an SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells. In the meantime, SKF-96365 also induces cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 treatment inhibited the calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ)/AKT signaling cascade in vitro and in vivo. Overexpression of CaMKIIγ or AKT abolished the effects of SKF-96365 on cancer cells, suggesting a critical role of the CaMKIIγ/AKT signaling pathway in SFK-96365-induced biological effects. Moreover, Hydroxychloroquine (HCQ), an FDA-approved drug used to inhibit autophagy, could significantly augment the anti-cancer effect of SFK-96365 in a mouse xenograft model. To our best knowledge, this is the first report to demonstrate that calcium/CaMKIIγ/AKT signaling can regulate apoptosis and autophagy simultaneously in cancer cells, and the combination of the SOCE inhibitor SKF-96365 with autophagy inhibitors represents a promising strategy for treating patients with colorectal cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. M867, a novel selective inhibitor of caspase-3 enhances cell death and extends tumor growth delay in irradiated lung cancer models.

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    Kwang Woon Kim

    Full Text Available BACKGROUND: Lung cancer remains the leading cause of cancer death worldwide. Radioresistance of lung cancer cells results in unacceptable rate of loco-regional failure. Although radiation is known to induce apoptosis, our recent study showed that knockdown of pro-apoptotic proteins Bak and Bax resulted in an increase in autophagic cell death and lung cancer radiosensitivity in vitro. To further explore the potential of apoptosis inhibition as a way to sensitize lung cancer for therapy, we tested M867, a novel chemical and reversible caspase-3 inhibitor, in combination with ionizing radiation in vivo and in vitro. METHODS AND FINDINGS: M867 reduced clonogenic survival in H460 lung cancer cells (DER = 1.27, p = 0.007 compared to the vehicle-treated treated cells. We found that administration of M867 with ionizing radiation in an in vivo mouse hind limb lung cancer model was well tolerated, and produced a significant tumor growth delay compared to radiation alone. A dramatic decrease in tumor vasculature was observed with M867 and radiation using von Willebrand factor staining. In addition, Ki67 index showed >5-fold reduction of tumor proliferation in the combination therapy group, despite the reduced levels of apoptosis observed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Radiosensitizing effect of M867 through inhibiting caspases was validated using caspase-3/-7 double-knockout (DKO mouse embryonic fibroblasts (MEF cell model. Consistent with our previous study, autophagy contributed to the mechanism of increased cell death, following inhibition of apoptosis. In addition, matrigel assay showed a decrease in in vitro endothelial tubule formation during the M867/radiation combination treatment. CONCLUSIONS: M867 enhances the cytotoxic effects of radiation on lung cancer and its vasculature both in vitro and in vivo. M867 has the potential to prolong tumor growth delay by inhibiting tumor proliferation

  16. Diagnosis delay in Libyan female breast cancer

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    Ermiah Eramah

    2012-08-01

    Full Text Available Abstract Aims To study the diagnosis delay and its impact on stage of disease among women with breast cancer on Libya. Methods 200 women, aged 22 to 75 years with breast cancer diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. This period (diagnosis time was categorized into 3 periods: 6 months. If diagnosis time was longer than 3 months, the diagnosis was considered delayed (diagnosis delay. Consultation time was the time taken to visit the general practitioner after the first symptoms. Retrospective preclinical and clinical data were collected on a form (questionnaire during an interview with each patient and from medical records. Results The median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3–6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: Symptoms were not considered serious in 27% of patients. Alternative therapy (therapy not associated with cancer was applied in 13.0% of the patients. Fear and shame prevented the visit to the doctor in 10% and 4.5% of patients, respectively. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom(s that did not include a lump (p  Diagnosis delay was associated with bigger tumour size (p Conclusions Diagnosis delay is very serious problem in Libya. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer awareness and training of general practitioners to reduce breast cancer mortality by promoting early detection. The treatment guidelines should pay more attention to the early phases of breast cancer. Especially, guidelines for good practices in managing

  17. Alternating Treatment With Pazopanib and Everolimus vs Continuous Pazopanib to Delay Disease Progression in Patients With Metastatic Clear Cell Renal Cell Cancer: The ROPETAR Randomized Clinical Trial.

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    Cirkel, Geert A; Hamberg, Paul; Sleijfer, Stefan; Loosveld, Olaf J L; Dercksen, M Wouter; Los, Maartje; Polee, Marco B; van den Berkmortel, Franchette; Aarts, Maureen J; Beerepoot, Laurens V; Groenewegen, Gerard; Lolkema, Martijn P; Tascilar, Metin; Portielje, Johanna E A; Peters, Frank P J; Klümpen, Heinz-Josef; van der Noort, Vincent; Haanen, John B A G; Voest, Emile E

    2017-04-01

    To our knowledge, this is the first randomized clinical trial evaluating an alternating treatment regimen in an attempt to delay disease progression in clear cell renal cell carcinoma. To test our hypothesis that an 8-week rotating treatment schedule with pazopanib and everolimus delays disease progression, exhibits more favorable toxic effects, and improves quality of life when compared with continuous treatment with pazopanib. This was an open-label, randomized (1:1) study (ROPETAR trial). In total, 101 patients with treatment-naive progressive metastatic clear cell renal cell carcinoma were enrolled between September 2012 and April 2014 from 17 large peripheral or academic hospitals in The Netherlands and followed for at least one year. First-line treatment consisted of either an 8-week alternating treatment schedule of pazopanib 800 mg/d and everolimus 10 mg/d (rotating arm) or continuous pazopanib 800 mg/d (control arm) until progression. After progression, patients made a final rotation to either pazopanib or everolimus monotherapy (rotating arm) or initiated everolimus (control arm). The primary end point was survival until first progression or death. Secondary end points included time to second progression or death, toxic effects, and quality of life. A total of 52 patients were randomized to the rotating arm (median [range] age, 65 [44-87] years) and 49 patients to the control arm (median [range] age, 67 [38-82] years). Memorial Sloan Kettering Cancer Center risk category was favorable in 26% of patients, intermediate in 58%, and poor in 15%. Baseline characteristics and risk categories were well balanced between arms. One-year PFS1 for rotating treatment was 45% (95% CI, 33-60) and 32% (95% CI, 21-49) for pazopanib (control). Median time until first progression or death for rotating treatment was 7.4 months (95% CI, 5.6-18.4) and 9.4 months (95% CI, 6.6-11.9) for pazopanib (control) (P = .37). Mucositis, anorexia, and dizziness were more prevalent in

  18. System delays in breast cancer

    African Journals Online (AJOL)

    In South Africa (SA), breast cancer is the 4th most common cause of death from all malignancies.[1] In SA, we notice a discrepancy in incidence rates between various ethnic/race groups. African women have rates similar to those in other developing countries. Caucasian women have rates that are comparable with ...

  19. Growth of human colon cancer cells in nude mice is delayed by ketogenic diet with or without omega-3 fatty acids and medium-chain triglycerides.

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    Hao, Guang-Wei; Chen, Yu-Sheng; He, De-Ming; Wang, Hai-Yu; Wu, Guo-Hao; Zhang, Bo

    2015-01-01

    Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.

  20. Adjuvant treatment delay in breast cancer patients

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    Damila Cristina Trufelli

    2015-10-01

    Full Text Available Summary Background: to evaluate if time between surgery and the first adjuvant treatment (chemotherapy, radiotherapy or hormone therapy in patients with breast cancer is a risk factor for lower overall survival (OS. Method: data from a five-year retrospective cohort study of all women diagnosed with invasive breast cancer at an academic oncology service were collected and analyzed. Results: three hundred forty-eight consecutive women were included. Time between surgery and the first adjuvant treatment was a risk factor for shorter overall survival (HR=1.3, 95CI 1.06-1.71, p=0.015, along with negative estrogen receptor, the presence of lymphovascular invasion and greater tumor size. A delay longer than 4 months between surgery and the first adjuvant treatment was also associated with shorter overall survival (cumulative survival of 80.9% for delays ≤ 4 months vs. 72.6% for delays > 4 months; p=0.041, log rank test. Conclusion: each month of delay between surgery and the first adjuvant treatment in women with invasive breast cancer increases the risk of death in 1.3-fold, and this effect is independent of all other well-established risk factors. Based on these results, we recommend further public strategies to decrease this interval.

  1. Delay in the diagnosis of cancer

    DEFF Research Database (Denmark)

    Hansen, Rikke Pilegaard

    . Chaper 1 introduces the concept of delay in the diagnosis of cancer. The chapter aims to provide insight into the time interval from symptom to treatment and into the patient and GP characteristics that potentially influence this interval. In addition, the chapter gives a brief overview of cancer...... epidemiology in Denmark and into how cancer is diagnosed in Denmark. A symptom-oriented approach to the patient's help-seeking behaviour is introduced as patients and GPs are expected to react to symptoms of cancer rather than to a specific cancer diagnosis. The study was therefore designed and analyzed...... for a detailed description of the patients' diagnostic pathways, allowing the researchers to draw the time line from symptom onset to treatment start, and to describe the characteristics of the patients and the GPs. Existing scales were used whenever possible; otherwise, ad hoc questions were constructed...

  2. Delay estimation for CMOS functional cells

    DEFF Research Database (Denmark)

    Madsen, Jan

    1991-01-01

    Presents a new RC tree network model for delay estimation of CMOS functional cells. The model is able to reflect topological changes within a cell, which is of particular interest when doing performance driven layout synthesis. Further, a set of algorithms to perform worst case analysis on arbitr...... on arbitrary CMOS functional cells using the proposed delay model, is presented. Both model and algorithms have been implemented as a part of a cell compiler (CELLO) working in an experimental silicon compiler environment....

  3. Factors Associated with Delayed Cancer Diagnosis in Egyptian Children

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    E.R. Abdelkhalek

    2014-01-01

    Full Text Available Background Despite tremendous importance of early cancer diagnosis in children, few studies on this topic have been conducted in Egypt. Early stage diagnosis can have a positive effect on prognoses and the quality of life of children with cancer. We investigated delays in the diagnosis of childhood cancers in Egypt and determined the factors associated with these delays. Methods This retrospective study included 172 children with cancer from two pediatric oncology units. The interval between symptoms onset and final diagnosis for each child was estimated and examined by univariate and multivariate analyses to determine correlations with the child's sex, age at diagnosis, type and site of malignancy, family residence, socioeconomic status, and parental educational level. Findings The median total diagnosis delay period was 47 days caused by patients and/or parents (8 days and diagnosis (28 days. Statistically significant patient factors associated with delayed diagnosis were age (<5 years, lower parental education, and socioeconomic status. Sex residence and family size were not significant. Malignancy type and tumor site significantly affected the time for diagnosis. The lowest median value was associated with germ cell tumors (GCTs and leukemia, and the highest value was in children with brain tumor. Missed diagnoses were initially recorded in 39.5% of the patients and were associated with patient and tumor factors. Interpretation Delayed diagnosis of childhood cancer is related to age, family, socioeconomic status and parental education, and cancer type and site. Efforts should be made to promote awareness, develop effective steps to eliminate possible contributing factors, and determine the best intervention method.

  4. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay.

    Science.gov (United States)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas T; Cramer, Frederik; Roth, Jack A; Poulsen, Hans S

    2010-04-15

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1). Therapeutic effect was evaluated in vitro in SCLC cell lines and in vivo in SCLC xenografted nude mice using the nonviral nanoparticle DOTAP/cholesterol for transgene delivery. INSM1-YCD/5-FC and INSM1-YCD-YUPRT/5-FC therapy induced high cytotoxicity in a range of SCLC cell lines. The highest therapeutic effect was obtained from the YCD-YUPRT fusion gene strategy. No cytotoxicity was induced after treatment of cell lines of other origin than SCLC. In addition the INSM1-YCD-YUPRT/5-FC therapy was superior to an established suicide gene system consisting of the herpes simplex virus thymidine kinase (HSVTK) gene and the prodrug ganciclovir. The superior effect was in part due to massive bystander cytotoxicity of YCD-YUPRT-produced toxins. Finally, INSM1-YCD-YUPRT/5-FC therapy induced significant tumor growth delay in SCLC xenografts compared with control-treated xenografts. The current study is the first to test cytosine deaminase-based suicide gene therapy for SCLC and the first to show an antitumor effect from the delivery of suicide gene therapeutics for SCLC in vivo.

  5. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer specific cytotoxicity and tumor growth delay

    Science.gov (United States)

    Christensen, Camilla L.; Gjetting, Torben; Poulsen, Thomas T.; Cramer, Frederik; Roth, Jack A.; Poulsen, Hans S.

    2012-01-01

    Purpose Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment and novel therapies are therefore in high demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug Experimental design The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter Insulinoma-associated 1 (INSM1). Therapeutic effect was evaluated in vitro in SCLC cell lines and in vivo in SCLC xenografted nude mice using the non-viral nanoparticle, DOTAP:Cholesterol for transgene delivery. Results INSM1-YCD/5-FC and INSM1-YCD-YUPRT/5-FC therapy induced high cytotoxicity in a range of SCLC cell lines. The highest therapeutic effect was obtained from the YCD-YUPRT fusion gene strategy. No cytotoxicity was induced after treatment of cell lines of other origin than SCLC. In addition the INSM1-YCD-YUPRT/5-FC therapy was superior to an established suicide gene system consisting of the Herpes Simplex Virus Thymidine Kinase (HSVTK) gene and prodrug Ganciclovir (GCV). The superior effect was in part due to massive bystander cytotoxicity of YCD-YUPRT-produced toxins. Finally, INSM1-YCD-YUPRT/5-FC therapy induced significant tumor growth delay in SCLC xenografts compared to control treated xenografts. Conclusions The current study is the first to test cytosine deaminase-based suicide gene therapy for SCLC and the first to demonstrate an anti-tumor effect from the delivery of suicide gene therapeutics for SCLC in vivo. PMID:20371678

  6. Meiotic multivalent orientation and cell developmental delay.

    Science.gov (United States)

    Sybenga, J; Hsiao, C; de Vries, J M

    1989-01-01

    In the heterozygote for the combination of an interchange (662W;3R/6R) and a Robertsonian split (3R) of rye, one type of adjacent orientation leads to trisomy in the progeny. Pollen mother cells with adjacent orientation of the translocation quinquivalent or with a trivalent and a bivalent were delayed in their development and appeared at prometaphase and metaphase later than cells with alternate quinquivalents. Delay in cell development is ascribed to unfavorable (early) prophase positioning of chromosomes.

  7. Expression of metastasis suppressor BRMS1 in breast cancer cells results in a marked delay in cellular adhesion to matrix

    Science.gov (United States)

    Metastatic dissemination is a multi-step process that depends on cancer cells’ ability to respond to microenvironmental cues by adapting adhesion abilities and undergoing cytoskeletal rearrangement. Breast Cancer Metastasis Suppressor 1 (BRMS1) affects several steps of the metastatic cascade: it dec...

  8. Delays for diagnosis and treatment of lung cancers: a systematic review.

    Science.gov (United States)

    Vinas, Florent; Ben Hassen, Ikram; Jabot, Laurence; Monnet, Isabelle; Chouaid, Christos

    2016-05-01

    The impact of diagnosis and treatment delays for non-small cell lung cancer management is poorly understood, even if the literature on the subject is currently increasing in importance. We have few indicators that can serve as reference for quality assurance actions. The objective of this review was to review the literature on the subject. A literature search, using the words 'human lung cancer delay' and 'human lung cancer waiting time', was undertaken in Medline database. Several studies analyzed these delays mostly in a monocentric setting. There is an important variability in the definition of these delays, in the collection methods and in the results obtained. However, it seems distinctly clear that long delays are frequently observed in less symptomatic patients and, therefore, are accompanied by better prognosis. More standardized definitions and procedures to calculate time intervals between cancer diagnosis and treatment should be implemented to better understand the delays of lung cancer management. © 2014 John Wiley & Sons Ltd.

  9. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides.

    Science.gov (United States)

    Otto, Christoph; Kaemmerer, Ulrike; Illert, Bertram; Muehling, Bettina; Pfetzer, Nadja; Wittig, Rainer; Voelker, Hans Ullrich; Thiede, Arnulf; Coy, Johannes F

    2008-04-30

    Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 +/- 8.5 days versus only 23.3 +/- 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further

  10. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    Directory of Open Access Journals (Sweden)

    Voelker Hans

    2008-04-01

    Full Text Available Abstract Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT. Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12 or a standard diet (SD group; n = 12 ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume. Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT

  11. The association of treatment delay and prognosis in head and neck squamous cell carcinoma (HNSCC) patients in a Dutch comprehensive cancer center.

    Science.gov (United States)

    van Harten, Michel C; de Ridder, Mischa; Hamming-Vrieze, Olga; Smeele, Ludi E; Balm, Alfons J M; van den Brekel, Michiel W M

    2014-04-01

    The increasing volume of head and neck squamous cell carcinoma (HNSCC) patients can lead to longer intervals between histopathological diagnosis and primary treatment. This could cause psychological distress to the patient, but more importantly could possibly lead to tumor progression and decreased survival. Accordingly, this study investigates these relationships. The correlation of professional delay and clinical characteristics of 2493 patients, treated between 1990 and 2011 with oral, oropharyngeal, hypopharyngeal and laryngeal SCC, was investigated. Patients were divided in two groups based on treatment delay, defined as the interval between histopathological diagnosis and initial treatment. Univariate and multivariate proportional hazards models were used to assess disease specific survival (DSS) and disease free survival (DFS). Year of diagnosis, tumor site and therapy were significantly related to treatment delay. Tumor stage was not related to treatment delay. Multivariate regression models revealed that the group with a delay of more than 30 days had a better DSS (HR .838, CI .697-.922, p=.041) and DFS (HR .816, CI .702-.947), p=.007) than the group treated within 30 days. In our study, treatment delay up to 90 days is not related to impaired survival. This argument can be used extremely cautiously to comfort patients who have to wait several weeks for treatment. Although, possible tumor progression during treatment delay could have led to increased morbidity subsequent to more extensive treatment. Also, possible negative psychological impact of delay in treatment should not be underestimated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Delays in presentation and treatment of breast cancer in Enugu ...

    African Journals Online (AJOL)

    To assess the delays and define the causes of delay in presentation and treatment of breast cancer patients inEnugu,Nigeria. Across-sectional survey of breast cancer patients using a semi structured questionnaire. SurgicalOncology unit,University ofNigeriaTeachingHospitalEnugu, (UNTH-E),Nigeria. 164 consecutively ...

  13. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

    2010-01-01

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...

  14. PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53

    DEFF Research Database (Denmark)

    Zandi, Roza; Selivanova, Galina; Christensen, Camilla Laulund

    2011-01-01

    Small cell lung cancer (SCLC) is a highly malignant disease with poor prognosis, necessitating the need to develop new and efficient treatment modalities. PRIMA-1(Met) (p53-dependent reactivation of massive apoptosis), also known as APR-246, is a small molecule, which restores tumor suppressor fu...... function to mutant p53 and induces cancer cell death in various cancer types. Since p53 is mutated in more than 90% of SCLC, we investigated the ability of PRIMA-1(Met) to induce apoptosis and inhibit tumor growth in SCLC with different p53 mutations....

  15. A new method for analyzing diagnostic delay in gynecological cancer.

    Science.gov (United States)

    Vandborg, Mai Partridge; Edwards, Kasper; Kragstrup, Jakob; Vedsted, Peter; Hansen, Dorte Gilså; Mogensen, Ole

    2012-06-01

    The aim of this article is to present a new methodology to illustrate, understand, and measure delay in health care. The method is inspired by process mapping tools as analytical framework and demonstrates its usefulness for studying diagnostic delay in gynecological cancer. Six women with a diagnostic delay of 6 weeks or more before treatment of gynecological cancer at a specialized regional department (the Department of Gynecology and Obstetrics, Odense University Hospital, Denmark) were included in the study. Maps of existing processes were performed for each patient reflecting the patients' pathway through the course of the disease. We combined 2 process mapping tools, namely, value stream mapping and business process modeling notation. The first method identifies the flow in a process as timelines. The latter introduces a set of easily recognizable graphical elements. Detailed information concerning the cancer patients' pathway was obtained. The method visualized the complexities within the diagnostic pathway. The role of different participants (patient, general practitioner, and local hospitals) became clear by arranging activities according to responsibilities and was shown to recurrently influence and contribute to the delay in the diagnostic process. Some important contributors to diagnostic delay in gynecological cancer, such as lack of cancer suspicion, competing diseases, negative test results, inexpedient referral patterns, and referrals without cancer suspicion, were found. Our results point out process mapping tools as a potential analytical framework to illustrate, understand, and measure delay in health care. Furthermore, the method was able to identify important contributors to the diagnostic delay in gynecological cancer patients.

  16. Delayed cell cycle progression from SEPW1 depletion is p53- and p21-dependent in MCF-7 breast cancer cells

    Science.gov (United States)

    Selenium (Se) is an essential redox-active element with close connections to cancer. Most of Se’s biological functions have been attributed to the antioxidant properties of Se-containing proteins. The relative contribution of selenoproteins and small Se compounds in cancer protection is a matter of ...

  17. System delays in breast cancer | Dalwai | South African Journal of ...

    African Journals Online (AJOL)

    Background: Centralised multidisciplinary management of breast cancer occurs in KwaZulu-Natal, South Africa, and requires a diagnostic and staging pathway at the referring hospital. Delays in this pathway are unknown. This study, conducted at a referring hospital, R K Khan (RKK), quantifies and analyses these delays.

  18. A new method for analyzing diagnostic delay in gynecological cancer

    DEFF Research Database (Denmark)

    Vandborg, Mai Partridge; Edwards, Kasper; Kragtrup, Jakob

    2012-01-01

    OBJECTIVE: The aim of this article is to present a new methodology to illustrate, understand, and measure delay in health care. The method is inspired by process mapping tools as analytical framework and demonstrates its usefulness for studying diagnostic delay in gynecological cancer. MATERIALS...

  19. Biosynthesized Platinum Nanoparticles Inhibit the Proliferation of Human Lung-Cancer Cells in vitro and Delay the Growth of a Human Lung-Tumor Xenograft in vivo -In vitro and in vivo Anticancer Activity of bio-Pt NPs-

    Directory of Open Access Journals (Sweden)

    Bendale Yogesh

    2016-06-01

    Full Text Available Objectives: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. Methods: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached 70 ─ 75 mm3, the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human-lung-cancer xenografts growing in SCID mice. Results: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. Conclusion: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer.

  20. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

    2010-01-01

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...

  1. Delayed treatment of symptomatic breast cancer: The experience ...

    African Journals Online (AJOL)

    Background. A cross-sectional study carried out at a teaching hospital in Kaduna, Nigeria, to investigate the extent and reasons for the delay between onset of symptoms and admission for treatment of symptomatic breast cancer. Methods. The patients had histologically proven breast cancer and had been admitted for ...

  2. MAZ-binding G4-decoy with locked nucleic acid and twisted intercalating nucleic acid modifications suppresses KRAS in pancreatic cancer cells and delays tumor growth in mice

    DEFF Research Database (Denmark)

    Cogoi, Susanna; Zorzet, Sonia; Rapozzi, Valentina

    2013-01-01

    transcription. To knockdown oncogenic KRAS in pancreatic cancer cells, we designed oligonucleotides that mimic one of the G-quadruplexes formed by NHE (G4-decoys). To increase their nuclease resistance, two locked nucleic acid (LNA) modifications were introduced at the 3'-end, whereas to enhance the folding...... cell growth and colony formation by activating apoptosis. We finally injected 2998 and control oligonucleotides 5153, 5154 (2 nmol/mouse) intratumorally in SCID mice bearing a Panc-1 xenograft. After three treatments, 2998 reduced tumor xenograft growth by 64% compared with control and increased......KRAS mutations are primary genetic lesions leading to pancreatic cancer. The promoter of human KRAS contains a nuclease-hypersensitive element (NHE) that can fold in G4-DNA structures binding to nuclear proteins, including MAZ (myc-associated zinc-finger). Here, we report that MAZ activates KRAS...

  3. Controlling flow time delays in flexible manufacturing cells

    NARCIS (Netherlands)

    Slomp, J.; Caprihan, R.; Bokhorst, J. A. C.

    2009-01-01

    Flow time delays in Flexible Manufacturing Cells (FMCs) are caused by transport and clamping/reclamping activities. This paper shows how dynamic scheduling parameters may control the flow times of jobs and the available task windows for flow time delays.

  4. Diagnostic delay in oral squamous cell carcinoma: the role of cognitive and psychological variables.

    Science.gov (United States)

    Panzarella, Vera; Pizzo, Giuseppe; Calvino, Francesco; Compilato, Domenico; Colella, Giuseppe; Campisi, Giuseppina

    2014-03-01

    This retrospective study investigated, in two cohorts of subjects living in Southern Italy and awaiting treatment for oral squamous cell carcinoma (OSCC), the variables related to diagnostic delay ascribable to the patient, with particular reference to the cognitive and psychological ones. A total of 156 patients with OSCC (mean age: 62 years, M/F: 2.39∶1) were recruited at the Universities of Palermo and Naples. Risk factors related to patient delay included: sociodemographic, health-related, cognitive and psychological variables. The analysis was conducted by considering two different delay ranges: dichotomous (≤1 month vs. >1 month) and polytomous (3 months) delay. Data were investigated by univariate and multivariate analyses and a P value ≤0.05 was considered statistically significant. For both delay measurements, the most relevant variables were: 'Personal experience of cancer' (dichotomous delay: P=0.05, odds ratio (OR)=0.33, 95% confidence interval (CI)=0.11-0.99; polytomous delay: P=0.006, Chi-square=10.224) and 'Unawareness' (dichotomous delay: Pdichotomous and for polytomous categorization of delay, respectively. The findings of this study indicated that, in the investigated cohorts, the knowledge about cancer issues is strongly linked to the patient delay. Educational interventions on the Mediterranean population are necessary in order to increase the patient awareness and to emphasize his/her key role in early diagnosis of OSCC.

  5. A New Method for Analyzing Diagnostic Delay in Gynecological Cancer

    DEFF Research Database (Denmark)

    Vandborg, Mai Partridge; Edwards, Kasper; Kragstrup, Jakob

    2012-01-01

    patient reflecting the patients' pathway through the course of the disease. We combined 2 process mapping tools, namely, value stream mapping and business process modeling notation. The first method identifies the flow in a process as timelines. The latter introduces a set of easily recognizable graphical......OBJECTIVE: The aim of this article is to present a new methodology to illustrate, understand, and measure delay in health care. The method is inspired by process mapping tools as analytical framework and demonstrates its usefulness for studying diagnostic delay in gynecological cancer. MATERIALS...... AND METHODS: Six women with a diagnostic delay of 6 weeks or more before treatment of gynecological cancer at a specialized regional department (the Department of Gynecology and Obstetrics, Odense University Hospital, Denmark) were included in the study. Maps of existing processes were performed for each...

  6. Delayed presentation of breast cancer patients | Otieno | East ...

    African Journals Online (AJOL)

    Objective: To determine the extent and nature of delayed presentation of patients treated for breast cancer at Kenyatta National Hospital (KNH). Setting: Kenyatta National Hospital (KNH) which is a tertiary, teaching and referral hospital in Nairobi, Kenya. Results: A total of 166 patients were recruited into the study. The mean ...

  7. Hyperbaric oxygen therapy for delayed radiation injuries in gynecological cancers.

    Science.gov (United States)

    Fink, D; Chetty, N; Lehm, J P; Marsden, D E; Hacker, N F

    2006-01-01

    Delayed radiation-induced injuries are difficult to treat. The treatment of delayed radiation injuries with hyperbaric oxygen therapy (HBOT) is reported in small case series and case reports. This study reports the experience of a single institution with HBOT in delayed radiation injuries in patients with gynecological cancers. At least 20 sessions of 100% oxygen inhalation at 2.4 Atmospheric Absolutes (ATA) for 90 min in a hyperbaric chamber were carried out. Of the 14 patients included in the study, 10 patients have healed or showed improvement of more than 50%, resulting in a success rate of 71%. Mean follow-up was 31.6 months (range 6-70 months). The adverse events were acceptable. HBOT should be considered for patients with delayed radiation injuries, not responding to other treatments.

  8. Factors that influence treatment delay in patients with colorectal cancer

    Science.gov (United States)

    Zarcos-Pedrinaci, Irene; Fernández-López, Alberto; Téllez, Teresa; Rivas-Ruiz, Francisco; Rueda A, Antonio; Suarez-Varela, María Manuela Morales; Briones, Eduardo; Baré, Marisa; Escobar, Antonio; Sarasqueta, Cristina; de Larrea, Nerea Fernández; Aguirre, Urko; Quintana, José María; Redondo, Maximino

    2017-01-01

    A prospective study was performed of patients diagnosed with colorectal cancer (CRC), distinguishing between colonic and rectal location, to determine the factors that may provoke a delay in the first treatment (DFT) provided. 2749 patients diagnosed with CRC were studied. The study population was recruited between June 2010 and December 2012. DFT is defined as time elapsed between diagnosis and first treatment exceeding 30 days. Excessive treatment delay was recorded in 65.5% of the cases, and was more prevalent among rectal cancer patients. Independent predictor variables of DFT in colon cancer patients were a low level of education, small tumour, ex-smoker, asymptomatic at diagnosis and following the application of screening. Among rectal cancer patients, the corresponding factors were primary school education and being asymptomatic. We conclude that treatment delay in CRC patients is affected not only by clinicopathological factors, but also by sociocultural ones. Greater attention should be paid by the healthcare provider to social groups with less formal education, in order to optimise treatment attention. PMID:27888636

  9. Lung cancer - small cell

    Science.gov (United States)

    ... carcinoma Small cell carcinoma Squamous cell carcinoma Secondhand smoke and lung cancer Normal lungs and alveoli Respiratory system Smoking hazards Bronchoscope References Horn L, Eisenberg R, ...

  10. Cell phones and cancer

    Science.gov (United States)

    Cancer and cell phones; Do cell phones cause cancer? ... Several major studies show no link between cell phones and cancer at this time. However, since the information available is based on short-term studies, the impact of many years of exposure ...

  11. Delayed breast reconstruction with implants after invasive breast cancer does not impair prognosis

    DEFF Research Database (Denmark)

    Holmich, L.R.; During, M.; Henriksen, T.F.

    2008-01-01

    We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women......We investigated if delayed breast implant reconstruction after breast cancer impairs prognosis. Using data from the Danish Breast Cancer Cooperative Group register, we identified all women...

  12. Liver Cancer Stem Cells

    OpenAIRE

    Sameh Mikhail; Aiwu Ruth He

    2011-01-01

    Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor properties susceptible to neoplastic transformation. Identification of specific cell surface markers fo...

  13. Cancer stem cell metabolism

    National Research Council Canada - National Science Library

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Sotgia, Federica; Lisanti, Michael P

    2016-01-01

    .... Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes...

  14. Diagnostic delay, quality of life and patient satisfaction among women diagnosed with endometrial or ovarian cancer

    DEFF Research Database (Denmark)

    Robinson, Kirstine M; Christensen, Karl Bang; Ottesen, Bent

    2012-01-01

    This study investigates the association between diagnostic delay (total delay), quality of life (QoL) and patient satisfaction, and the associations between QoL and patient satisfaction scores and survival for women diagnosed with ovarian or endometrial cancer.......This study investigates the association between diagnostic delay (total delay), quality of life (QoL) and patient satisfaction, and the associations between QoL and patient satisfaction scores and survival for women diagnosed with ovarian or endometrial cancer....

  15. Reduced ultraviolet irradiation delays subsequent squamous cell carcinomas in hairless mice

    DEFF Research Database (Denmark)

    Togsverd-Bo, Katrine; Lerche, Catharina M; Poulsen, Thomas

    2009-01-01

    BACKGROUND: Ultraviolet (UV) radiation induces non-melanoma skin cancer (NMSC), and UV prophylaxis is essential to prevent skin cancer. It is unclear whether patients diagnosed with squamous cell carcinomas (SCC) may benefit from reduced UV exposures in terms of delaying the development of new...... tumors. The objective was to evaluate the significance of discontinued or reduced UV exposure for the development of subsequent skin tumors. METHODS: Seven groups of mice (n = 175) were irradiated with UV doses of 2 and 4 standard erythema doses (SED) that were continued, reduced or discontinued...... at the time of appearance of the first skin tumor. RESULTS: The development of new tumors was delayed, corresponding to the degree of reductions in UV dose in an inversely linear manner. Discontinuation of UV doses delayed the median times to the second tumor by 24 days (2 SED, P = 0.0549) and 33.5 days (4...

  16. Religiosity, spirituality, and cancer fatalism beliefs on delay in breast cancer diagnosis in African American women.

    Science.gov (United States)

    Gullatte, Mary Magee; Brawley, Otis; Kinney, Anita; Powe, Barbara; Mooney, Kathi

    2010-03-01

    African American women are more likely than any other racial or ethnic group to present with a later stage of breast cancer at initial diagnosis. Delay in breast cancer detection is a critical factor in diagnosis at a later stage. Available data indicate a delay of 3 months or more is a significant factor in breast cancer mortalty. Numerous factors have been reported as contributing to delay in time to seek medical care including religiosity, spirituality, and fatalistic beliefs. This study examined the influence of religiosity, spirituality, and cancer fatalism on delay in diagnosis and breast cancer stage in African American women with self-detected breast symptoms. A descriptive correlation, retrospective methodology using an open-ended questionnaire and three validated measurement scales were used: the Religious Problem Solving Scale (RPSS), the Religious Coping Activity Scale (RCAS) subscale measuring spiritually based coping, and the modified Powe Fatalism Inventory (mPFI). A convenience sample of 129 women ages between 30 and 84 years who self-reported detecting a breast symptom before diagnosis of breast cancer within the preceding 12 months were included in the study. Outcome variables were time to seek medical care and breast cancer stage. Other variables of interest included marital status, income, education, insurance status, and to whom the women spoke about their breast symptoms. Data were analyzed using descriptive statistics, logistic regression analysis, Pearson r correlations, Mann-Whitney U analysis, and Chi Square analysis. Participants were found to be highly religious and spiritual but not fatalistic. While most women delayed more than 3 months in seeking medical care, no associations were found between the three predictor variables and time to seek medical care. The median delay in time from self detection of a breast symptom to seeking medical care was 5.5 months. Women who were less educated, unmarried, and talked to God only about their

  17. Delayed haemolytic transfusion reactions in patients with sickle cell disease.

    OpenAIRE

    Cummins, D; Webb, G.; Shah, N; Davies, S C

    1991-01-01

    We describe two cases which illustrate the difficult diagnostic and therapeutic problems posed by delayed haemolytic transfusion reactions in patients with sickle-cell disease. The cases emphasize the need for meticulous phenotypic and serological assessment of sickle-cell patients prior to transfusion therapy.

  18. Basal cell cancer (image)

    Science.gov (United States)

    ... biopsy is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and location of the cancer. Early treatment by a dermatologist may result in a cure ... is required to watch for new sites of basal cell cancer.

  19. Prostate cancer stem cells.

    Science.gov (United States)

    Tu, Shi-Ming; Lin, Sue-Hwa

    2012-06-01

    Stem cells have long been implicated in prostate gland formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggest that these cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of prostate cancer indicate that it originates from stem cells. For example, the putative androgen receptor-negative (AR(-)) status of prostate stem cells renders them inherently insensitive to androgen blockade therapy. The androgen-regulated gene fusion TMPRSS2-ERG could be used to clarify both the cells of origin and the evolution of prostate cancer cells. In this review, we show that the hypothesis that distinct subtypes of cancer result from abnormalities within specific cell types-the stem cell theory of cancer-may instigate a major paradigm shift in cancer research and therapy. Ultimately, the stem cell theory of cancers will affect how we practice clinical oncology: our diagnosis, monitoring, and therapy of prostate and other cancers. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Diagnostic delay experienced among gynecological cancer patients: a nationwide survey in Denmark

    DEFF Research Database (Denmark)

    Robinson, Kirstine M; Ottesen, Bent; Christensen, Karl Bang

    2009-01-01

    OBJECTIVE: To examine diagnostic delay among gynecological cancer patients. DESIGN: Nationwide study. SETTING: The cohort comprised all women receiving their first treatment for cervical, endometrial, or ovarian cancer between 1 October 2006 and 1 December 2007 in four of the five centers...... for gynecological cancer surgery in Denmark. SAMPLE: Of the 911 women alive, 648 participated, resulting in a response rate of 71.1%; of these, 30.1% were diagnosed with cervical cancer, 31.0% with endometrial cancer, and 38.9% with ovarian cancer. METHODS: Questionnaire survey. MAIN OUTCOME MEASURES: Diagnostic...... experiencing very long delays. Ovarian cancer patients experienced significantly shorter delays compared with other gynecological cancer patients in all parts of the health care system. CONCLUSIONS: Delays occur in all parts of the diagnostic process, suggesting that a multifaceted approach should be adopted...

  1. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Thomas W Owens

    2013-08-01

    Full Text Available Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumours are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs. Understanding how CSCs form and how they contribute to the pathology of breast cancer will greatly aid the pursuit of novel therapies targeted at eliminating these cells. This review will summarise what is currently known about the origins of breast CSCs, their role in disease progression and ways in which they may be targeted therapeutically.

  2. Hurthle Cell Cancer

    Science.gov (United States)

    ... breath Hurthle cell cancer Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  3. Basal cell skin cancer

    Science.gov (United States)

    Basal cell skin cancer almost never spreads. If it is left untreated, it may spread into surrounding areas and nearby tissues and bone. In these cases, treatment can injure the appearance of the skin.

  4. Socioeconomic patient characteristics predict delay in cancer diagnosis: a Danish cohort study

    Directory of Open Access Journals (Sweden)

    Sokolowski Ineta

    2008-02-01

    Full Text Available Abstract Background Delay in cancer diagnosis may be important for cancer prognosis. Large individual variations in the duration of delay have been observed. This study examines whether patients' socioeconomic characteristics are predictors of long patient-, doctor- and system-related delay in cancer diagnosis. Methods Danish population-based cohort study. From September 2004 to September 2005, newly diagnosed cancer patients were enrolled from administrative registries. A total of 467 general practitioners in the County of Aarhus, Denmark, completed questionnaires on 2,212 cancer patients' diagnostic pathways. A total of 1,252 cancer patients filled in questionnaires on their socioeconomic characteristics (e.g. marital status, education, occupation, household income and fortune. Delay was categorised as short or long based on quartiles. Predictors of long delay were assessed in a logistic regression model using odds ratios (ORs as a proxy of relative risks. Results In regard to patient delay, retired female patients experienced shorter delays (OR 0.35, 95% confidence interval (95%CI 0.13 to 0.98 than employed female patients, while female smokers experienced longer delays (OR 2.42, 95%CI 1.21 to 4.85 than female non-smokers. In regard to doctor delay, female patients with a large household fortune experienced shorter delays (OR 0.07, 95%CI 0.01 to 0.45 than economically less privileged female patients. Well-educated men experienced shorter delays (OR 0.40, 95%CI 0.16 to 1.00 than men with short education. Male patients experienced longer doctor delays (OR 2.11, 95%CI 1.11 to 4.02 than women when gender-specific cancers were excluded. In regard to system delay, female patients with a large household fortune experienced shorter delays (OR 0.46, 95%CI 0.21 to 0.99 than economically less privileged women, while female patients with a high alcohol intake experienced longer delays (OR 2.82, 95%CI 1.18 to 6.72 than women with an average intake

  5. Factors affecting professional delay in diagnosis and treatment of oral cancer in Iran.

    Science.gov (United States)

    Esmaelbeigi, Farhad; Hadji, Maryam; Harirchi, Iraj; Omranipour, Ramesh; vand Rajabpour, Mojtaba; Zendehdel, Kazem

    2014-04-01

    Oral cancer is the most common malignant tumor among head and neck cancers. Delay in diagnosis affects the treatment and prognosis of oral cancer. We measured the professional delay in the diagnosis and its attributes in the Cancer Institute of Iran, the largest referral center for oral cancer patients in the country.  We interviewed oral cancer patients to measure the delay and used case-control approach to study association of various prognostic factors with professional delay and tumor stage. Out of 206 patients, 71.4% were diagnosed at the advanced stage. The median of the patient, professional and total delays were 45, 86 and 140 day, receptively. In the univariate model, prescription of medicines like analgesics (OR = 5.3, 95% CI 2.2-12.9) and history of dental procedure (OR=6.8, 95% CI 1.7-26.9) were associated with higher risk of delay compared to patient who were biopsied from the beginning. History of loose teeth increased risk of delay 4 times (OR = 4.0, 95% CI 1.6-9.8). Patients with primary education had 70% lower risk of delay compared to the illiterate patients (OR = 0.3, 95% CI 0.1-0.7) and the risk was lower among patients who had diploma (OR = 0.04, 95% CI 0-0.7) and college education (OR = 0.1, 95% CI 0-0.4). The delayed patients were diagnosed in more advanced stage compared to the patients without delay (OR = 2.1, 95% CI 1.0-4.4). Development of a national guideline for follow-up of oral lesions, training and awareness of health care professionals about oral cancer diagnosis may decrease the delay and improve the oral cancer outcome in Iran.

  6. Delayed menopause due to granulosa cell tumor of the ovary

    Directory of Open Access Journals (Sweden)

    Bhushan Murkey

    2011-01-01

    Full Text Available A 52-year-old patient presented with complaints of menorrhagia. Endometrial biopsy revealed simple hyperplasia of the endometrium. Total abdominal hysterectomy with bilateral oophorectomy was carried out. The ovaries looked grossly normal, but histopathology reported granulosa cell tumor of the right ovary. Granulosa cell tumors belong to the sexcord stromal category and account for approximately 2% of all ovarian tumors. We review the features and treatment of granulosa cell tumors and the importance of screening for ovarian tumors in a case of endometrial hyperplasia and delayed menopause.

  7. Fast track diagnosis as a means of reducing diagnostic delay in cancer

    DEFF Research Database (Denmark)

    Larsen, Mette Bach; Vedsted, Peter; Olesen, Frede

    Background: Denmark has the highest morbidity and mortality from cancer in Western Europe, and studies suggest that Danish cancer patients are diagnosed at a later stage than patients in the other Nordic countries. To address this issue a Danish hospital has introduced fast track diagnosis...... of cancer and expanded services to the general practitioners. Objective: To investigate the diagnostic delay of cancer, patient and provider satisfaction and health economic aspects in two Danish regions with special emphasis on the possible benefits of fast track diagnosis. Methods: The study...... in diagnostic delay will be described in uni- and multivariate analysis models based on three types of delay (patient, doctors and system delay) and stratified by diagnosis. The second part of the analysis will focus on the possible benefits from fast track diagnosis in terms of reduced diagnostic delay...

  8. Factors associated with delayed diagnosis of cervical cancer in Iran--a survey in Isfahan City.

    Science.gov (United States)

    Behnamfar, Fariba; Azadehrah, Mahboobeh

    2015-01-01

    In the absence of routine screening program for cervical cancer in Iran and high rate of diagnosed cancer in its advanced stage, recognition of sociodemographic factors related to delayed diagnosis of cancer in Iran could be helpful in reducing the burden of disease in our community. The aim of this study was to determine the stage of cervical cancer at diagnosis and factors related to delayed diagnosis of cervical cancer in Isfahan, Iran. In this cross sectional study women diagnosed with cervical cancer for the first time by histo-pathological examination were enrolled. According to the clinical and paraclinical findings and staging of the cancer, they were classified into early and delayed diagnosis of cervical cancer. Sociodemographic factors were compared in the two groups. In this study of 55 women mean age was 48.3±12.0. According to our classification 6/55 (10.9%) and 49/55 (89.1%) of them had early and delayed diagnosis of cervical cancer. Delayed diagnosis of the cancer was significantly higher in patients with lower degree of education, lower socioeconomic status, having smoker and addict husband and those who did not have a history of Pap smear test (pdiagnosis of cervical cancer. The affected women should be targeted for implementation of specialized educational programmes for improving knowledge and screening test.

  9. Delays and Refusal in Treatment for Breast Cancer Among Native American and Hispanic Women with Breast Cancer.

    Science.gov (United States)

    1998-08-01

    AD GRANT NUMBER DAMD17-96-1-6191 TITLE: Delays and Refusal in Treatment for Breast Cancer Among Native American and Hispanic Women with Breast Cancer...Jul 98) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Delays and Refusals in Treatment for Breast Cancer Among Native American and Hispanic Women with...of treatment modality and compliance with treatment . Compliance with treatment has been anecdotally cited among physicians in New Mexico as a

  10. Cancer stem cells revisited

    NARCIS (Netherlands)

    Batlle, Eduard; Clevers, Hans

    2017-01-01

    The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their

  11. Inflammation and cancer stem cells.

    Science.gov (United States)

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei

    2014-04-10

    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Patient Related Factors Associated with Delayed Reporting in Oral Cavity and Oropharyngeal Cancer

    Directory of Open Access Journals (Sweden)

    Mohammad Akram

    2014-01-01

    Conclusions: The results of this study provide guidance towards interventions to reduce patient delay. Interventions should target the rural, older age group and lower socioeconomic population for educating them and to change their psychosocial behavior for oral and oropharyngeal cancer.

  13. The effects of early versus delayed castration targeting androgen on prolonging survival in a mouse model of bladder cancer.

    Science.gov (United States)

    Zhang, Zaixian; Xu, Qingquan; Huang, Xiaobo; Yang, Jia; Xu, Yanhong; Zhang, Guixiang

    2015-01-01

    To compare the efficacy of early versus delayed surgical castration on prolonging survival and further to investigate the anticancer effect and potential value of targeting androgen in the therapeutic intervention of bladder cancer. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) was used to induce bladder cancer in male mice. Mice were randomly divided into three groups: the early castration group (on which castration was perform at 4 weeks after first time of BBN administration), the delayed castration group (on which castration was perform at 20 weeks after first time of BBN administration), and the sham-castrated group. Mice were monitored daily throughout their lifespan until cancer-related death or the progress of an obviously moribund appearance, at which time the mice were killed. Androgen receptor expression and cell proliferation and apoptosis analysis were also evaluated. The average lifespan in early castration, delayed castration and sham-castrated groups were 315.8 days, 300.1 days and 254.6 days, respectively. Early castration conferred a statistically significant survival advantage when compared with the sham-castrated group (P cancer mice. This finding may enhance the feasibility of androgen ablation treatment in patients with bladder cancer.

  14. Delays and Refusal in Treatment for Breast Cancer Among Native American and Hispanic Women with Breast Cancer

    National Research Council Canada - National Science Library

    Saavedra, Elba

    2000-01-01

    ..., attitudinal, spiritual and demographic variables associated with delays and refusals in breast cancer treatment The focus of the semi-structured interview is to encourage the women in story-telling...

  15. Squamous cell skin cancer

    Science.gov (United States)

    ... squamous cell cancer include: Having light-colored skin, blue or green eyes, or blond or red hair Long-term, daily sun exposure (such as in people who work outside) Many severe sunburns early in life Older age Having had many x-rays Chemical exposure A weakened immune system, especially in ...

  16. A Delayed Virus Infection Model with Cell-to-Cell Transmission and CTL Immune Response

    Science.gov (United States)

    Yang, Yu; Zhang, Tonghua; Xu, Yancong; Zhou, Jinling

    In this paper, a delayed virus infection model with cell-to-cell transmission and CTL immune response is investigated. In the model, time delay is incorporated into the CTL response. By constructing Lyapunov functionals, global dynamical properties of the two boundary equilibria are established. Our results show that time delay in the CTL response process may lead to sustained oscillation. To further investigate the nature of the oscillation, we apply the method of multiple time scales to calculate the normal form on the center manifold of the model. At the end of the paper, numerical simulations are carried out, which support our theoretical results.

  17. Socio-demographic factors, comorbidity and diagnostic delay among women diagnosed with cervical, endometrial or ovarian cancer

    DEFF Research Database (Denmark)

    Robinson, Kirstine Magtengaard; Christensen, K B; Ottesen, B

    2011-01-01

    patient delays were associated with diagnosis with a greater risk of experiencing long delays among women diagnosed with cervical and endometrial cancer as opposed to ovarian cancer. The risk of experiencing long GP referral delays was associated with residential area, with a greater risk of long delays...... diagnosed with cervical and endometrial cancer as opposed to ovarian cancer, and with working as opposed to being retired. In conclusion, this study found that socio-demographic factors and comorbidity play a role in the probability of experiencing long delays. If delays in diagnosis are to be reduced......This study investigates the association between socio-demographic factors, comorbidity and diagnostic delay among gynaecological cancer patients. A questionnaire was sent to 1052 women diagnosed with cervical, endometrial or ovarian cancer between October 2006 and December 2007 in Denmark. Long...

  18. Alcohol and Cancer Stem Cells

    OpenAIRE

    Mei Xu; Jia Luo

    2017-01-01

    Heavy alcohol consumption has been associated with increased risk of several cancers, including cancer of the colon, rectum, female breast, oral cavity, pharynx, larynx, liver, and esophagus. It appears that alcohol exposure not only promotes carcinogenesis but also enhances the progression and aggressiveness of existing cancers. The molecular mechanisms underlying alcohol tumor promotion, however, remain unclear. Cancer stem cells (CSC), a subpopulation of cancer cells with self-renewal and ...

  19. Delays in Referral of Oral Cancer Patients, A10 yr Retrospective ...

    African Journals Online (AJOL)

    The study attempts to find out who delays in the management of oral cancer patients viz: the General Medical Practitioner (GMP), the Consultants or on the other hand, the patients. All oral cancer patients referred to our Hospital between 1987 and 1996 were reviewed. The most important findings are that 68 patients were ...

  20. General practitioner characteristics and delay in cancer diagnosis. a population-based cohort study

    Directory of Open Access Journals (Sweden)

    Vedsted Peter

    2011-09-01

    Full Text Available Abstract Background Delay in cancer diagnosis may have serious prognostic consequences, and some patients experience delays lasting several months. However, we have no knowledge whether such delays are associated with general practitioner (GP characteristics. The aim of the present study was to analyse whether GP and practice characteristics are associated with the length of delay in cancer diagnosis. Methods The study was designed as a population-based cohort study. The setting was the County of Aarhus, Denmark (640,000 inhabitants. Participants include 334 GPs and their 1,525 consecutive, newly diagnosed cancer patients. During one year (September 2004 to August 2005, patients with incident cancer were enrolled from administrative registries. GPs completed questionnaires on the patients' diagnostic pathways and on GP and practice characteristics. Delay was categorised as patient-related (more than 60 days, doctor-related (more than 30 days and system-related (more than 90 days. The associations between delay and characteristics were assessed in a logistic regression model using odds ratios (ORs. Results No GP characteristics (seniority, practice organization, list size, participation in continuing medical education, job satisfaction and level of burnout were associated with doctor delay. Patients of female GPs more often had a short patient delay than patients of male GPs (OR 0.44, 95% confidence interval (95%CI 0.28 to 0.71. Patients whose GPs provided many services (OR 0.66, 95%CI 0.44 to 0.95 and patients attending GPs with little former knowledge of their patients (OR 0.68, 95%CI 0.47 to 0.99 more often experienced a short system delay than patients attending GPs with less activity and more knowledge of their patients. Patients listed with a female GP more often experienced a long system delay than patients of male GPs (OR 1.50, 95%CI 1.02 to 2.21. Finally, patients with low GP-reported compliance more often experienced a long system delay

  1. Breast cancer delay in Latinas: the role of cultural beliefs and acculturation.

    Science.gov (United States)

    Tejeda, Silvia; Gallardo, Rani I; Ferrans, Carol Estwing; Rauscher, Garth H

    2017-04-01

    Cultural beliefs about breast cancer may act as a barrier to Latina women seeking preventive services or timely follow-up for breast symptoms regardless of access. This study examines the association between factors and breast cancer cultural beliefs and the extent to which cultural beliefs are associated with delays in breast cancer care. Participants who were Latina, ages 30-79, and had been diagnosed with a primary breast cancer were examined (n = 181). Interviews included a 15-item cultural beliefs scale spanning beliefs inconsistent with motivation to seek timely healthcare. Self-reported date of symptom discovery, date of first medical presentation, and date of first treatment were used to construct measures of prolonged patient, clinical, and total delay. Logistic regression with model-based standardization was used to estimate crude and confounder-adjusted prevalence differences for prolonged delay by number of cultural beliefs held. Women held a mean score of three cultural beliefs. The belief most commonly held was, "Faith in God can protect you from breast cancer" (48 %). Holding three or more cultural beliefs was associated with lower acculturation, lower socioeconomic status and less access to care (p beliefs (p = 0.02). Cultural beliefs may predispose Latina women to prolong delays in seeking diagnosis and treatment for breast symptoms. Cultural beliefs represent a potential point of intervention to decrease delays among Latina breast cancer patients.

  2. Impact of social and clinical factors on diagnostic delay of breast cancer

    OpenAIRE

    Dianatinasab, Mostafa; Fararouei, Mohammad; Mohammadianpanah, Mohammad; Zare-Bandamiri, Mohammad

    2016-01-01

    Abstract One of the reasons for high mortality of breast cancer is long delay in seeking medical care. This study was designed to measure the association of a wide range of socio-demographic and clinical factors with the diagnostic delay in breast cancer among Iranian patients. This study was conducted on 505 newly diagnosed patients with breast cancer from southern part of Iran. Medical files of the patients who were admitted to the hospital from November 2013 to May 2015 were examined and c...

  3. Lack of association between diagnostic and therapeutic delay and stage of colorectal cancer.

    Science.gov (United States)

    Ramos, Maria; Esteva, Magdalena; Cabeza, Elena; Llobera, Joan; Ruiz, Amador

    2008-03-01

    A recent review suggests that there is no association between diagnostic and therapeutic delays and survival in colorectal cancer patients. However, the effect of tumour stage on the relationship between delay and survival in CRC should be clarified. We review here the evidence on the relationship between diagnostic and therapeutic delays and stage in colorectal cancer. We conducted a systematic review of Medline, Embase, Cancerlit and the Cochrane Database of Systematic Reviews to identify publications published between 1965 and 2006 dealing with delay, stage and colorectal cancer. A meta-analysis was performed based on the estimation of the odds ratios (OR) and on a random effects model. We identified 50 studies, representing 18,649 patients. Thirty studies were excluded due to excessively restricted samples (e.g. exclusion of patients with intestinal obstruction or who died 1-3 months after surgery) or because they studied only a portion of the delay. Of the 37 remaining studies, great variability was noted in connection with the type of classification used for disease stage and the type of measurement used for the delay. Meta-analysis was performed based on 17 studies that included 5209 patients. The combined OR was 0.98 (95% confidence interval (CI): 0.76-1.25), suggesting a lack of association between delay and disease stage. In four studies, cancers of the colon and rectum were dealt with separately, and a meta-analysis was performed using the data for colon cancer (1001 patients) and for rectal cancer (799 patients). In both cases, the combined ORs overlapped 1.0, and showed opposite associations when studied separately: 0.86 (95% CI: 0.63-1.19) for the colon (i.e. more delay is associated with the earlier stage at diagnosis) and 1.93 (95% CI: 0.89-4.219) for the rectum (i.e. less delay is associated with the earlier stage). When colorectal cancers are taken as a whole, there appears to be no association between diagnostic delay and disease stage when

  4. Relationship of diagnostic and therapeutic delay with survival in colorectal cancer: a review.

    Science.gov (United States)

    Ramos, Maria; Esteva, Magdalena; Cabeza, Elena; Campillo, Carlos; Llobera, Joan; Aguiló, Antonio

    2007-11-01

    Early diagnosis of colorectal cancer before the onset of symptoms improves survival. Once symptoms have occurred, however, the effect of delay on survival is unclear. We review here evidence on the relationship of diagnostic and therapeutic delay with survival in colorectal cancer. We conducted a systematic of Medline, Embase, Cancerlit and the Cochrane Database of Systematic Reviews to identify publications published between 1962 and 2006 dealing with delay, survival and colon cancer. A meta-analysis was performed based on the calculation of the relative risk (RR) and on a model of random effects. We identified 40 studies, representing 20,440 patients. Fourteen studies were excluded due to excessively restricted samples (e.g. exclusion of patients with intestinal obstruction, with tumours at stage C or D at the time of diagnosis, or who died 1-3 months after surgery); or because they studied only a portion of the delay. Of the 26 remaining studies, 20 showed no association between delay and survival. In contrast, four studies showed that delay was a factor contributing to better prognosis, and two showed that it contributed to poorer prognosis. There was no association between delay and survival when the colon and rectum were considered separately, when a multivariate analysis was performed, and when the effects of tumour stage and degree of differentiation were taken into account. To perform a meta-analysis, 18 additional studies were excluded, since the published articles did not specify the absolute numbers. In the remaining eight studies, the combined relative risk (RR) of delay was 0.92 (confidence interval (CI) 95%: 0.87-0.97). The results of the review suggest that there is no association between diagnostic and therapeutic delay and survival in colorectal cancer patients. Colon and rectum should be assessed separately, and it is necessary to adjust for other relevant variables such as tumour stage.

  5. Pregnancy-associated breast cancer in Taiwanese women: potential treatment delay and impact on survival.

    Science.gov (United States)

    Yang, Ya-Ling; Chan, K Arnold; Hsieh, Fon-Jou; Chang, Li-Yun; Wang, Ming-Yang

    2014-01-01

    This study investigated the clinicopathologic characteristics and survival of women diagnosed with pregnancy-associated breast cancer (PABC) in Taiwan. PABC is defined as breast cancer diagnosed during pregnancy or within 1 year after obstetric delivery. Our sample of PABC patients (N = 26) included all patients diagnosed at a major medical center in northern Taiwan from 1984 through 2009. Among these patients, 15 were diagnosed during pregnancy and 11 were diagnosed within 1 year after delivery. The comparison group included 104 patients within the same age range as the PABC patients and diagnosed with breast cancer not associated with pregnancy from 2004 through 2009 at the same hospital. Patients' initiating treatment delayed, 5-year and 10-year overall survival were delineated by stratified Kaplan-Meier estimates. Patients' characteristics were associated with initiating treatment delayed was evaluated with multivariate proportional hazards modeling. Antepartum PABC patients were younger and had longer time between diagnosis and treatment initiation than postpartum PABC patients. The predictor of treatment delayed was including birth parity, cancer stage, and pregnancy. The PABC group had larger tumors, more advanced cancer stage, and tumors with less progesterone receptor than the comparison group. The antepartum PABC patients had higher mortality than postpartum PABC and comparison groups within 5 years after diagnosis. Based on these results, we confirmed that pregnant women with breast cancer were more likely to delay treatment. Therefore, we recommend that breast cancer screening should be integrated into the prenatal and postnatal routine visits for early detection of the women's breast problems.

  6. Episodic, transient systemic acidosis delays evolution of the malignant phenotype: Possible mechanism for cancer prevention by increased physical activity

    Directory of Open Access Journals (Sweden)

    Maini Philip K

    2010-04-01

    Full Text Available Abstract Background The transition from premalignant to invasive tumour growth is a prolonged multistep process governed by phenotypic adaptation to changing microenvironmental selection pressures. Cancer prevention strategies are required to interrupt or delay somatic evolution of the malignant invasive phenotype. Empirical studies have consistently demonstrated that increased physical activity is highly effective in reducing the risk of breast cancer but the mechanism is unknown. Results Here we propose the hypothesis that exercise-induced transient systemic acidosis will alter the in situ tumour microenvironment and delay tumour adaptation to regional hypoxia and acidosis in the later stages of carcinogenesis. We test this hypothesis using a hybrid cellular automaton approach. This model has been previously applied to somatic evolution on epithelial surfaces and demonstrated three phases of somatic evolution, with cancer cells escaping in turn from the constraints of limited space, nutrient supply and waste removal. In this paper we extend the model to test our hypothesis that transient systemic acidosis is sufficient to arrest, or at least delay, transition from in situ to invasive cancer. Conclusions Model simulations demonstrate that repeated episodes of transient systemic acidosis will interrupt critical evolutionary steps in the later stages of carcinogenesis resulting in substantial delay in the evolution to the invasive phenotype. Our results suggest transient systemic acidosis may mediate the observed reduction in cancer risk associated with increased physical activity. Reviewers This article was reviewed by Natalia Komarova (nominated by Marek Kimmel, Heiko Enderling (nominated by Marek Kimmel, Mark Little (nominated by Marek Kimmel and Yang Kuang.

  7. Cancer Stem Cells and Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Sheetal Dyall

    2010-01-01

    Full Text Available The cancer stem cell hypothesis is becoming more widely accepted as a model for carcinogenesis. Tumours are heterogeneous both at the molecular and cellular level, containing a small population of cells that possess highly tumourigenic “stem-cell” properties. Cancer stem cells (CSCs, or tumour-initiating cells, have the ability to self-renew, generate xenografts reminiscent of the primary tumour that they were derived from, and are chemoresistant. The characterisation of the CSC population within a tumour that drives its growth could provide novel target therapeutics against these cells specifically, eradicating the cancer completely. There have been several reports describing the isolation of putative cancer stem cell populations in several cancers; however, no defined set of markers has been identified that conclusively characterises “stem-like” cancer cells. This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer.

  8. Delays in diagnosis of young females with symptomatic cervical cancer in England: an interview-based study.

    Science.gov (United States)

    Lim, Anita W; Ramirez, Amanda J; Hamilton, William; Sasieni, Peter; Patnick, Julietta; Forbes, Lindsay Jl

    2014-10-01

    Diagnosis may be delayed in young females with cervical cancer because of a failure to recognise symptoms. To examine the extent and determinants of delays in diagnosis of young females with symptomatic cervical cancer. A national descriptive study of time from symptoms to diagnosis of cervical cancer and risk factors for delay in diagnosis at all hospitals diagnosing cervical cancer in England. One-hundred and twenty-eight patients diagnosis of cervical cancer were interviewed. Patient delay was defined as ≥3 months from symptom onset to first presentation and provider delay as ≥ 3 months from first presentation to diagnosis. Forty (31%) patients had presented symptomatically: 11 (28%) delayed presentation. Patient delay was more common in patients cancer symptom. Provider delay was reported by 24/40 (60%); in some no report was found in primary care records of a visual inspection of the cervix and some did not re-attend after the first presentation for several months. Gynaecological symptoms were common (84%) among patients who presented via screening. Young females with cervical cancer frequently delay presentation, and not recognising symptoms as serious may increase the risk of delay. Delay in diagnosis after first presentation is also common. There is some evidence that UK guidelines for managing young females with abnormal bleeding are not being followed. © British Journal of General Practice 2014.

  9. Cancer treatments transform residual cancer cell phenotype

    Directory of Open Access Journals (Sweden)

    Harless William W

    2011-01-01

    Full Text Available Abstract Background Physiologic wound repair and tissue regeneration are associated with distinct cellular behaviors triggered by tissue damage. Normally quiescent stem cells proliferate to regenerate damaged tissue, while relatively immobile epithelial cells can transform into a motile, tissue invasive phenotype through a partial epithelial-mesenchymal transition. These distinct cellular behaviors may have particular relevance to how cancer cells can be predicted to behave after treatments damaging a tumor. Presentation of the hypothesis Surgery, chemotherapy, and radiation therapy trigger highly conserved wound healing pathways that: (1 facilitate the phenotypic transformation of surviving cancer cells into a highly mobile, metastatic phenotype through an EMT or epithelial-mesenchymal transition and (2 induce residual cancer stem cell proliferation. Testing the hypothesis Tissue damage caused by cancer treatments will trigger the release of distinct cytokines with established roles in physiologic wound healing, EMT induction, and stem cell activation. They will be released rapidly after treatment and detectable in the patient's blood. Careful histologic evaluation of cancerous tissue before and after treatment will reveal cellular changes suggestive of EMT induction (down regulation of cytokeratin expression and cancer stem cell enrichment (stem cell markers upregulated. Implications of the hypothesis Cancer cells surviving treatment will be more capable of metastasis and resistant to conventional therapies than the pre-treatment population of cancer cells. These changes will develop rapidly after treatment and, in distinct contrast to selection pressures fostering such changes, be triggered by highly conserved wound repair signals released after tissue damage. This pattern of tissue (tumor repair may be amenable to treatment intervention at the time it is upregulated.

  10. Stem cells and solid cancers.

    Science.gov (United States)

    McDonald, Stuart A C; Graham, Trevor A; Schier, Stefanie; Wright, Nicholas A; Alison, Malcolm R

    2009-07-01

    Recently, there have been significant advances in our knowledge of stem cells found in tissues that can develop solid tumours. In particular, novel stem cell markers have been identified for the first time identifying multipotential cells: a required characteristic of a stem cell. The scarcity of cancer stem cells has been questioned. Current dogma states that they are rare, but novel research has suggested that this may not be the case. Here, we review the latest literature on stem cells, particularly cancer stem cells within solid tumours. We discuss current thinking on how stem cells develop into cancer stem cells and how they protect themselves from doing so and do they express unique markers that can be used to detect stem cells. We attempt to put into perspective these latest advances in stem cell biology and their potential for cancer therapy.

  11. Cancer stem cells and personalized cancer nanomedicine.

    Science.gov (United States)

    Gener, Petra; Rafael, Diana Fernandes de Sousa; Fernández, Yolanda; Ortega, Joan Sayós; Arango, Diego; Abasolo, Ibane; Videira, Mafalda; Schwartz, Simo

    2016-02-01

    Despite the progress in cancer treatment over the past years advanced cancer is still an incurable disease. Special attention is pointed toward cancer stem cell (CSC)-targeted therapies, because this minor cell population is responsible for the treatment resistance, metastatic growth and tumor recurrence. The recently described CSC dynamic phenotype and interconversion model of cancer growth hamper even more the possible success of current cancer treatments in advanced cancer stages. Accordingly, CSCs can be generated through dedifferentiation processes from non-CSCs, in particular, when CSC populations are depleted after treatment. In this context, the use of targeted CSC nanomedicines should be considered as a promising tool to increase CSC sensitivity and efficacy of specific anti-CSC therapies.

  12. A retrospective analysis of delays in the diagnosis of lung cancer and associated costs

    Directory of Open Access Journals (Sweden)

    Gildea TR

    2017-05-01

    Full Text Available Thomas R Gildea,1 Stacey DaCosta Byfield,2 D Kyle Hogarth,3 David S Wilson,4 Curtis C Quinn5 1Department of Pulmonary, Allergy, and Critical Care Medicine and Transplant Center, Cleveland Clinic, Cleveland, OH, 2Health Economics and Outcomes Research, Optum, Eden Prairie, MN, 3Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago Medical Center, Chicago, IL, 4The Lung Institute, Columbus Regional Hospital, Columbus, IN, 5Cardiothoracic Surgery/Thoracic Surgery, Cardiothoracic Surgery of Charleston, Roper St. Francis Physician Partners Group, Charleston, SC, USA Purpose: Diagnosis of lung cancer at advanced stages can result in missed treatment opportunities, worse outcomes, and higher health care costs. This study evaluated the wait time to diagnose non-small-cell lung cancer (NSCLC and the cost of diagnosis and treatment based on the stage at diagnosis. Patients and methods: Adult patients diagnosed with NSCLC between January 2007 and September 2011 were identified from a proprietary oncology registry and linked to health insurance claims from a large US health insurance company. Continuous enrollment in the health plan was required for at least 12 months prediagnosis (baseline and at least 3 months postdiagnosis (follow-up. Use of diagnostic tests and time to diagnosis were examined. The rates of health care utilization and per-patient per-month (PPPM health care costs were calculated. Results: A total of 1,210 patients with NSCLC were included in the analysis. Most patients (93.6% had evidence of diagnostic tests beginning 5 to 6 months prior to diagnosis, and most were diagnosed at an advanced stage (23% Stage IIIb and 46% Stage IV. The PPPM total health care costs in USD pre- and postdiagnosis were $2,407±$3,364 (mean±standard deviation and $16,577±$33,550, respectively. PPPM total health care costs and utilization after lung cancer diagnosis were significantly higher among patients diagnosed at Stage

  13. Delayed Diagnosis: Giant Basal Cell Carcinoma of Scalp

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    Didem Didar Balcı,

    2008-07-01

    Full Text Available Although basal cell carcinoma (BCC is the most common form of skin cancer, the scalp lesions of BCC have been rarely reported. Giant BCC is defined as a tumor larger than 5 cm in diameter and only 0.5-1 % of all BCCs achieve this size. We report a case of giant BCC on the scalp that was treated with topical coticosteroids and antifungal shampoo for five years. BCC should be considered in the differential diagnosis in erythematous plaque type lesions resistant to therapy with long duration localized on the scalp.

  14. Telomerase Inhibition Effectively Targets Mouse and Human AML Stem Cells and Delays Relapse Following Chemotherapy

    Science.gov (United States)

    Bruedigam, Claudia; Bagger, Frederik O.; Heidel, Florian H.; Kuhn, Catherine Paine; Guignes, Solene; Song, Axia; Austin, Rebecca; Vu, Therese; Lee, Erwin; Riyat, Sarbjit; Moore, Andrew S.; Lock, Richard B.; Bullinger, Lars; Hill, Geoffrey R.; Armstrong, Scott A.; Williams, David A.; Lane, Steven W.

    2014-01-01

    SUMMARY Acute myeloid leukemia (AML) is an aggressive and lethal blood cancer maintained by rare populations of leukemia stem cells (LSCs). Selective targeting of LSCs is a promising approach for treating AML and preventing relapse following chemotherapy, and developing such therapeutic modalities is a key priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc−/− LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia progression, and delays relapse following chemotherapy. Together, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs. PMID:25479751

  15. Clinical presentation and causes of the delayed diagnosis of breast cancer in patients with pregnancy associated breast cancer

    Directory of Open Access Journals (Sweden)

    Ali M Al-Amri

    2015-01-01

    Full Text Available Objective: The objective was to assess the clinical presentation, delay of diagnosis, and the causes of delay in the diagnosis of patients with pregnancy-associated breast cancer (PABC and patients with non-PABC. Patients and Methods: This was a face-to-face interview with women who had histologically confirmed BC. All respondents were interviewed at our hospital. Results: We interviewed 56 patients, 36 with non-PABC and 20 with PABC. Of the 20 patients with PABC, BC was diagnosed in 12 (60% during pregnancy and 8 (40% during postpartum. 18 of the patients (90% with PABC presented mainly with a mass 3 (15% with pain and ulcer, 5 (25% with skin redness and thickening, 6 (30% with nipple retraction and 4 (20% with discharge 12 (60% patients with PABC had delayed diagnosis and 8 (40% of this delay was due to physicians′ reassurance, and 2 (10% because of fear of cancer. Similarly, 35 (97% patients with non-PABC presented with breast mass, 3 (8.3% with infrequent pain 4 (11.11% with inflammation 2 (5.55% with ulcer 2 (5.55% with nipple discharge and4 (11.11% with thickening of the skin compared with PABC patients. Only 4 (11.11% in non-PABC had delayed diagnosis, and for half of them the delay was due to the fear of cancer. Two patients with PABC and non-PABC were afraid of cancer 16.66% and 5.55%, respectively. However, 8 (60% of patients with PABC had delayed diagnosis compared to 0% of patients with non-PABC. Conclusion: In this study, the majority of patients with PABC or non-PABC presented with a breast lump. Other symptoms were more common in patients with PABC than in patients with non-PABC. An increased awareness of clinicians may help reduce delay in the diagnosis of patients with PABC.

  16. Efficacy and safety of denosumab versus zoledronic acid in delaying skeletal-related events in patients with gastrointestinal cancer, pancreas-biliary system cancer, and other rare cancers

    Directory of Open Access Journals (Sweden)

    Hiroo Imai

    2017-03-01

    Conclusion: From the perspective of the efficacy and safety of denosumab for delaying the time to SREs, denosumab should be used to prevent SREs in patients with bone metastases from gastrointestinal cancer, pancreas-biliary system cancer, and other rare cancers.

  17. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer

    Science.gov (United States)

    Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min

    2012-01-01

    According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research. PMID:22507219

  19. Is cancer a severe delayed hypersensitivity reaction and histamine a blueprint?

    Science.gov (United States)

    Khatami, Mahin

    2016-12-01

    Longevity and accumulation of multiple context-dependent signaling pathways of long-standing inflammation (antigen-load or oxidative stress) are the results of decreased/altered regulation of immunity and loss of control switch mechanisms that we defined as Yin and Yang of acute inflammation or immune surveillance. Chronic inflammation is initiated by immune disruptors-induced progressive changes in physiology and function of susceptible host tissues that lead to increased immune suppression and multistep disease processes including carcinogenesis. The interrelated multiple hypotheses that are presented for the first time in this article are extension of author's earlier series of 'accidental' discoveries on the role of inflammation in developmental stages of immune dysfunction toward tumorigenesis and angiogenesis. Detailed analyses of data on chronic diseases suggest that nearly all age-associated illnesses, generally categorized as 'mild' (e.g., increased allergies), 'moderate' (e.g., hypertension, colitis, gastritis, pancreatitis, emphysema) or 'severe' (e.g., accelerated neurodegenerative and autoimmune diseases or site-specific cancers and metastasis) are variations of hypersensitivity responses of tissues that are manifested as different diseases in immune-responsive or immune-privileged tissues. Continuous release/presence of low level histamine (subclinical) in circulation could contribute to sustained oxidative stress and induction of 'mild' or 'moderate' or 'severe' (immune tsunami) immune disorders in susceptible tissues. Site-specific cancers are proposed to be 'severe' (irreversible) forms of cumulative delayed hypersensitivity responses that would induce immunological chaos in favor of tissue growth in target tissues. Shared or special features of growth from fetus development into adulthood and aging processes and carcinogenesis are briefly compared with regard to energy requirements of highly complex function of Yin and Yang. Features of Yang

  20. Does Embarrassment Contribute to Delay in Seeking Medical Care for Breast Cancer? A Review

    Directory of Open Access Journals (Sweden)

    Mohamadreza Neishaboury

    2015-08-01

    Full Text Available Background: Embarrassment and shame of visiting a doctor for a breast disease are among psychosocial factors that potentially contribute to delay in seeking medical advice. The purpose of this study is to review the published literature to determine if embarrassment regarding breast examination, diagnosis and treatment is associated with patient delay.Methods: We searched PubMed with the following key terms: patient acceptance of health care (MeSH, breast neoplasms/psychology (MeSH, shame (MeSH, embarrassment, delayed diagnosis, to find relevant literature published before August 2015.Results: The studies that explicitly assessed the association between embarrassment and delay for seeking medical advice for breast cancer were very limited. Among these studies, only 2 were quantitative studies, 4 were based on qualitative research and 4 were reviews. Other studies assessed attitudes in population-based surveys or included patients (females and males suffering from different types of cancer.Conclusions: Women should be educated that diseases of the breast need to be cared for as health issues in other parts of the body. They should be informed that embarrassment in this regard is not related to grace and integrity but can be potentially life-threatening. Further research is necessary to quantify the association of embarrassment or shame with delay in seeking diagnosis and treatment of breast cancer. More research can elucidate the ways that the negative impact of shame/embarrassment can be minimized in different ethnic groups.

  1. Epigenetics in cancer stem cells.

    Science.gov (United States)

    Toh, Tan Boon; Lim, Jhin Jieh; Chow, Edward Kai-Hua

    2017-02-01

    Compelling evidence have demonstrated that bulk tumors can arise from a unique subset of cells commonly termed "cancer stem cells" that has been proposed to be a strong driving force of tumorigenesis and a key mechanism of therapeutic resistance. Recent advances in epigenomics have illuminated key mechanisms by which epigenetic regulation contribute to cancer progression. In this review, we present a discussion of how deregulation of various epigenetic pathways can contribute to cancer initiation and tumorigenesis, particularly with respect to maintenance and survival of cancer stem cells. This information, together with several promising clinical and preclinical trials of epigenetic modulating drugs, offer new possibilities for targeting cancer stem cells as well as improving cancer therapy overall.

  2. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Horn L, Eisenberg R, Gius D, et al. Cancer of the lung. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan ...

  3. Delayed diagnosis of coeliac disease increases cancer risk

    Directory of Open Access Journals (Sweden)

    Di Benedetto Rita

    2007-03-01

    Full Text Available Abstract Background The association between coeliac disease (CD and neoplasms has been long established, but few data are available about the risk factors. The aim of this paper is to estimate the risk of developing a neoplasm among non diagnosed coeliac patients and to evaluate if this risk correlates with the age of patients at diagnosis of coeliac disease. Methods The study population consists of patients (n = 1968 diagnosed with CD at 20 Italian gastroenterology referral Centers between 1st January 1982 and 31st March 2005. Results The SIR for all cancers resulted to be 1.3; 95% CI = 1.0–1.7 p Conclusion Coeliac patients have an increased risk of developing cancer in relation to the age of diagnosis of CD. This risk results higher for malignancies of the gastro-intestinal sites. An accurate screening for tumors should be performed in patients diagnosed with CD in adulthood and in advancing age.

  4. Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy

    Science.gov (United States)

    Smith, Jenessa B; Lanitis, Evripidis; Dangaj, Denarda; Buza, Elizabeth; Poussin, Mathilde; Stashwick, Caitlin; Scholler, Nathalie; Powell, Daniel J

    2016-01-01

    B7-H4 protein is frequently overexpressed in ovarian cancer. Here, we engineered T cells with novel B7-H4-specific chimeric antigen receptors (CARs) that recognized both human and murine B7-H4 to test the hypothesis that B7-H4 CAR T cell therapy can be applied safely in preclinical models. B7-H4 CAR T cells specifically secreted IFN-γ and lysed B7-H4(+) targets. In vivo, B7-H4 CAR T cells displayed antitumor reactivity against B7-H4(+) human ovarian tumor xenografts. Unexpectedly, B7-H4 CAR T cell treatment reproducibly showed delayed, lethal toxicity 6–8 weeks after therapy. Comprehensive assessment of murine B7-H4 protein distribution uncovered expression in ductal and mucosal epithelial cells in normal tissues. Postmortem analysis revealed the presence of widespread histologic lesions that correlated with B7-H4(+) expression, and were inconsistent with graft versus host disease. Lastly, expression patterns of B7-H4 protein in normal human tissue were comparable to distribution in mice, advancing our understanding of B7-H4. We conclude that B7-H4 CAR therapy mediates control of cancer outgrowth. However, long-term engraftment of B7-H4 CAR T cells mediates lethal, off-tumor toxicity that is likely due to wide expression of B7-H4 in healthy mouse organs. This model system provides a unique opportunity for preclinical evaluation of safety approaches that limit CAR-mediated toxicity after tumor destruction in vivo. PMID:27439899

  5. Carbonate fuel cell and components thereof for in-situ delayed addition of carbonate electrolyte

    Energy Technology Data Exchange (ETDEWEB)

    Johnsen, Richard [Waterbury, CT; Yuh, Chao-Yi [New Milford, CT; Farooque, Mohammad [Danbury, CT

    2011-05-10

    An apparatus and method in which a delayed carbonate electrolyte is stored in the storage areas of a non-electrolyte matrix fuel cell component and is of a preselected content so as to obtain a delayed time release of the electrolyte in the storage areas in the operating temperature range of the fuel cell.

  6. Mechanotransduction in cancer stem cells.

    Science.gov (United States)

    Hao, Jin; Zhang, Yueling; Ye, Rui; Zheng, Yingcheng; Zhao, Zhihe; Li, Juan

    2013-09-01

    The cancer stem cell (CSC) concept, which arose about a decade ago, proposes that tumor growth is sustained by a subpopulation of highly malignant cells. These cells, termed CSCs, are capable of extensive self-renewal that contributes to metastasis and treatment resistance. Therefore, therapeutic strategies that target CSCs should be developed for improving outcomes of cancer patients. Recent progress has highlighted the importance of physical properties of the extracellular matrix and mechanotransduction pathway in cancer cells during cancer development. On the other hand, the significance of CXCR1, an upstream signal of FAK/PI3K/Akt has been revealed in CSCs. FAK/PI3K/Akt is a key signal mediator in mechanotransduction pathway. Therefore, mechanotransduction could be a new target for CSCs, and would be an innovative way to treat cancer by inhibiting FAK/PI3K/Akt. © 2013 International Federation for Cell Biology.

  7. Pregnancy-associated breast cancer in Taiwanese women: potential treatment delay and impact on survival.

    Directory of Open Access Journals (Sweden)

    Ya-Ling Yang

    Full Text Available This study investigated the clinicopathologic characteristics and survival of women diagnosed with pregnancy-associated breast cancer (PABC in Taiwan. PABC is defined as breast cancer diagnosed during pregnancy or within 1 year after obstetric delivery. Our sample of PABC patients (N = 26 included all patients diagnosed at a major medical center in northern Taiwan from 1984 through 2009. Among these patients, 15 were diagnosed during pregnancy and 11 were diagnosed within 1 year after delivery. The comparison group included 104 patients within the same age range as the PABC patients and diagnosed with breast cancer not associated with pregnancy from 2004 through 2009 at the same hospital. Patients' initiating treatment delayed, 5-year and 10-year overall survival were delineated by stratified Kaplan-Meier estimates. Patients' characteristics were associated with initiating treatment delayed was evaluated with multivariate proportional hazards modeling. Antepartum PABC patients were younger and had longer time between diagnosis and treatment initiation than postpartum PABC patients. The predictor of treatment delayed was including birth parity, cancer stage, and pregnancy. The PABC group had larger tumors, more advanced cancer stage, and tumors with less progesterone receptor than the comparison group. The antepartum PABC patients had higher mortality than postpartum PABC and comparison groups within 5 years after diagnosis. Based on these results, we confirmed that pregnant women with breast cancer were more likely to delay treatment. Therefore, we recommend that breast cancer screening should be integrated into the prenatal and postnatal routine visits for early detection of the women's breast problems.

  8. Nanotechniques Inactivate Cancer Stem Cells

    Science.gov (United States)

    Goltsev, Anatoliy N.; Babenko, Natalya N.; Gaevskaya, Yulia A.; Bondarovich, Nikolay A.; Dubrava, Tatiana G.; Ostankov, Maksim V.; Chelombitko, Olga V.; Malyukin, Yuriy V.; Klochkov, Vladimir K.; Kavok, Nataliya S.

    2017-06-01

    One of the tasks of current oncology is identification of cancer stem cells and search of therapeutic means capable of their specific inhibition. The paper presents the data on phenotype characteristics of Ehrlich carcinoma cells as convenient and easy-to-follow model of tumor growth. The evidence of cancer stem cells as a part of Ehrlich carcinoma and significance of CD44+ and CD44- subpopulations in maintaining the growth of this type of tumor were demonstrated. A high (tenfold) tumorigenic activity of the Ehrlich carcinoma CD44+ cells if compared to CD44- cells was proven. In this pair of comparison, the CD44+ cells had a higher potential of generating in peritoneal cavity of CD44high, CD44+CD24-, CD44+CD24+ cell subpopulations, highlighting the presence of cancer stem cells in a pool of CD44+ cells.

  9. Distress, delay of gratification and preference for palliative care in men with prostate cancer.

    Science.gov (United States)

    Gerhart, James; Asvat, Yasmin; Lattie, Emily; O'Mahony, Sean; Duberstein, Paul; Hoerger, Michael

    2016-01-01

    Patient-centered cancer care standards include routine psychosocial distress screening and referral for supportive care services. Although many cancer patients report psychosocial distress that could be alleviated by supportive services including palliative care, patients often decline such services for reasons that are poorly understood. Research on decision-making suggests that during periods of acute distress, individuals have more difficulty prioritizing long-term over immediate gains. Thus, distressed cancer patients may prioritize immediate gains (e.g., avoidance of palliative care discussions in the moment) over longer-term gains (e.g., improved quality of life in the future). This study investigated the associations between psychosocial distress, difficulties with delay of gratification (tendency to prioritize short-term over longer-term gains), and preference for palliative care in a sample of 212 men with a history of prostate cancer (94% white men and 27% advanced stage, age M = 62, SD = 8). It was hypothesized that psychosocial distress would be associated with lower preferences for palliative care, and this association would be explained, in part, by difficulty delaying gratification. Self-report measures included the depression anxiety stress scales, delay of gratification inventory, and ratings on an item assessing preferences for palliative care. Consistent with the hypothesis, mediation models confirmed that the association of psychosocial distress with lower preference for palliative care was mediated by delay of gratification. Findings suggest that distressed prostate cancer patients may benefit from additional support managing the emotional aspects of medical decisions and weighing immediate versus delayed outcomes. Copyright © 2015 John Wiley & Sons, Ltd.

  10. Cancer stem cell markers in common cancers - therapeutic implications

    DEFF Research Database (Denmark)

    Klonisch, Thomas; Wiechec, Emilia; Hombach-Klonisch, Sabine

    2008-01-01

    Rapid advance in the cancer stem cell field warrants optimism for the development of more reliable cancer therapies within the next 2-3 decades. Below, we characterize and compare the specific markers that are present on stem cells, cancer cells and cancer stem cells (CSC) in selected tissues...

  11. Factors Responsible for the Diagnostic Delay in Oral Cancer Patients: A Hospital Based Sociodemographic Study in Kolkata

    Directory of Open Access Journals (Sweden)

    Pramitasri Bhattacharyya

    2016-12-01

    Full Text Available Introduction Oral cancer is a challenging health problem globally. Delay in diagnosis is an important factor in determining the outcome of the disease. It is a major determinant of mortality and morbidity of oral cancer patients. Present observational study was conducted with the objective of finding the factors responsible for delay in diagnosis of oral cancer in patients. Materials and Methods Hospital based observational study where patient register was used as data source from 15th Nov, 2013-15th Jan, 2014. Results Among the causes for delay in reporting to hospital, financial constraint (84% and illiteracy (56.5% have been found to contribute the most. The risk of primary delay is 3.53 times more among illiterate in comparison with literate. Age, gender, stage of cancer, religion, caste, tobacco use and delayed referral from the first physician were the other factors found to be significant in relation to primary delay. Discussion Early diagnosis is a major factor for favorable outcome of a disease and several factors hinder early diagnosis. Some of these factors can be easily modified through Information, Education and Communication (IEC. Conclusion Some important factors that lead to delay are identified and some of them are preventable. So, IEC regarding cancer among general population will not only provide knowledge to them, but also will break myths regarding cancer and reduce the burden of disease. These identified predictors of delay may be used for designing an educational intervention program for patients with oral cancers.

  12. Effect of diagnostic delay on survival in patients with colorectal cancer: a retrospective cohort study.

    Science.gov (United States)

    Pita-Fernández, Salvador; González-Sáez, Luis; López-Calviño, Beatriz; Seoane-Pillado, Teresa; Rodríguez-Camacho, Elena; Pazos-Sierra, Alejandro; González-Santamaría, Paloma; Pértega-Díaz, Sonia

    2016-08-22

    Disparate and contradictory results make studies necessary to investigate in more depth the relationship between diagnostic delay and survival in colorectal cancer (CRC) patients. The aim of this study is to analyse the relationship between the interval from first symptom to diagnosis (SDI) and survival in CRC. Retrospective study of n = 942 CRC patients. SDI was calculated as the time from the diagnosis of cancer and the first symptoms of CRC. Cox regression was used to estimate five-year mortality hazard ratios as a function of SDI, adjusting for age and gender. SDI was modelled according to SDI quartiles and as a continuous variable using penalized splines. Median SDI was 3.4 months. SDI was not associated with stage at diagnosis (Stage I = 3.6 months, Stage II-III = 3.4, Stage IV = 3.2; p = 0.728). Shorter SDIs corresponded to patients with abdominal pain (2.8 months), and longer SDIs to patients with muchorrhage (5.2 months) and rectal tenesmus (4.4 months). Adjusting for age and gender, in rectum cancers, patients within the first SDI quartile had lower survival (p = 0.003), while in colon cancer no significant differences were found (p = 0.282). These results do not change after adjusting for TNM stage. The splines regression analysis revealed that, for rectum cancer, 5-year mortality progressively increases for SDIs lower than the median (3.7 months) and decreases as the delay increases until approximately 8 months. In colon cancer, no significant relationship was found between SDI and survival. Short diagnostic intervals are significantly associated with higher mortality in rectal but not in colon cancers, even though a borderline significant effect is also observed in colon cancer. Longer diagnostic intervals seemed not to be associated with poorer survival. Other factors than diagnostic delay should be taken into account to explain this "waiting-time paradox".

  13. Impact of social and clinical factors on diagnostic delay of breast cancer

    Science.gov (United States)

    Dianatinasab, Mostafa; Fararouei, Mohammad; Mohammadianpanah, Mohammad; Zare-Bandamiri, Mohammad

    2016-01-01

    Abstract One of the reasons for high mortality of breast cancer is long delay in seeking medical care. This study was designed to measure the association of a wide range of socio-demographic and clinical factors with the diagnostic delay in breast cancer among Iranian patients. This study was conducted on 505 newly diagnosed patients with breast cancer from southern part of Iran. Medical files of the patients who were admitted to the hospital from November 2013 to May 2015 were examined and clinical and demographic information were extracted. According to the results, illiterate patients were diagnosed on average 87.42 days later compared with those with a college degree (95%CI: 29.68–145.16, P = 0.003) and those from rural area were diagnosed on average 72.48 days later (95%CI: 35.94–109.03, P = 0.001) compared with urban residences. Single women were diagnosed 65.99 days later (95%CI: 7.37–124.61, P = 0.02) compared with those married. Lobular or medullary types of cancer were diagnosed 65.19 days later (95%CI: 2.67–127.70, P = 0.04) compared with ductal type. On the other hand, those who were able to perform breast self-exam were diagnosed 49.07 days earlier compared with others (95%CI: 18.69–79.45, P = 0.002). Those felt lump as the initiating symptom were diagnosed 62.01 days earlier, (95%CI: 8.17–115.85, P = 0.02) compared with those with other initial symptoms. The only factor associated with doctors diagnosis delay was the place of residence as rural residences were diagnosed on average 87.42 days later compared with urban residences, (95%CI: 53.82–121.92, P = 0.001). Higher education, living in cities, ductal type of tumor, and noticing lump in breast were the most important demographic and clinical factors associated with shorter breast cancer diagnosis delay. Informing women and doctors, especially general physicians who are practicing in rural areas, of the common symptoms of breast cancer as well as training women to perform breast self

  14. Multifaceted Interpretation of Colon Cancer Stem Cells

    OpenAIRE

    Hatano, Yuichiro; Fukuda, Shinya; Hisamatsu, Kenji; Hirata, Akihiro; Hara, Akira; Tomita, Hiroyuki

    2017-01-01

    Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but...

  15. Characterising Castrate Tolerant Prostate Cancer Cells

    OpenAIRE

    ASHLEE KATE CLARK

    2017-01-01

    Prostate cancer is a prevalent disease in aging males. This thesis explores prostate cancer cells that escape current therapy and give rise to end-stage disease. Using sophisticated experimental approaches, this important cancer cell population was identified and characterised in human prostate cancer tissues.  Our discoveries will eventually lead to improved cancer treatments for men with prostate cancer.

  16. Diagnosis and treatment delays among elderly breast cancer patients with pre-existing mental illness.

    Science.gov (United States)

    Iglay, Kristy; Santorelli, Melissa L; Hirshfield, Kim M; Williams, Jill M; Rhoads, George G; Lin, Yong; Demissie, Kitaw

    2017-11-01

    This study aimed to compare diagnosis and treatment delays in elderly breast cancer patients with and without pre-existing mental illness. A retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results-Medicare data including 16,636 women 68+ years, who were diagnosed with stage I-IIIa breast cancer in the United States from 2005 to 2007. Mental illness was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes recorded on inpatient and outpatient claims during the 3 years prior to breast cancer diagnosis. Patients were classified as having no mental illness, anxiety, depression, anxiety and depression, or severe mental illness (bipolar disorder, schizophrenia, and other psychotic disorder). Multivariable binomial regression was used to assess the association between mental illness and delays of ≥60 and ≥90 days after adjustment for confounders. Patients with comorbid anxiety and depression had an increased risk for diagnosis delay of ≥90 days from symptom recognition (RR 1.11; 95% CI 1.00, 1.23), and those with severe mental illness had an increased risk for initial treatment delay of ≥60 days from diagnosis (RR 1.36; 95% CI 1.06, 1.74). Patients with any mental illness experienced an increased risk for adjuvant chemotherapy delay of ≥90 days from last operation (RR 1.13; 95% CI 1.01, 1.26) and each category of mental illness, except depression, showed a non-significant trend for this association. Breast cancer patients with mental illness should be closely managed by a cross-functional care team, including a psychiatrist, a primary care physician, and an oncologist, to ensure adequate care is received within an appropriate timeframe.

  17. Diagnosis delay and follow-up strategies in colorectal cancer. Prognosis implications: a study protocol.

    Science.gov (United States)

    Pita Fernández, Salvador; Pértega Díaz, Sonia; López Calviño, Beatriz; González Santamaría, Paloma; Seoane Pillado, Teresa; Arnal Monreal, Francisco; Maciá, Francesc; Sánchez Calavera, María Antonia; Espí Macías, Alejandro; Valladares Ayerbes, Manuel; Pazos, Alejandro; Reboredo López, Margarita; González Saez, Luis; Montserrat, María Ramos; Segura Noguera, Josep María; Monreal Aliaga, Isabel; González Luján, Luis; Martín Rabadán, María; Murta Nascimento, Cristiane; Pueyo, Olga; Boscá Watts, Marta Maia; Cabeza Irigoyen, Elena; Casmitjana Abella, Montserrat; Pinilla, Marina; Costa Alcaraz, Ana; Ruiz Torrejón, Amador; Burón Pust, Andrea; García Aranda, Concepción; de Lluc Bennasar, María; Lafita Mainz, Sergio; Novella, Maite; Manzano, Hermini; Vadell, Catalina; Falcó, Esther; Esteva, Magdalena

    2010-10-05

    Controversy exists with regard to the impact that the different components of diagnosis delay may have on the degree of invasion and prognosis in patients with colorectal cancer. The follow-up strategies after treatment also vary considerably. The aims of this study are: a) to determine if the symptoms-to-diagnosis interval and the treatment delay modify the survival of patients with colorectal cancer, and b) to determine if different follow-up strategies are associated with a higher survival rate. Multi-centre study with prospective follow-up in five regions in Spain (Galicia, Balearic Islands, Catalonia, Aragón and Valencia) during the period 2010-2012. Incident cases are included with anatomopathological confirmation of colorectal cancer (International Classification of Diseases 9th revision codes 153-154) that formed a part of a previous study (n = 953).At the time of diagnosis, each patient was given a structured interview. Their clinical records will be reviewed during the follow-up period in order to obtain information on the explorations and tests carried out after treatment, and the progress of these patients.Symptoms-to-diagnosis interval is defined as the time calculated from the diagnosis of cancer and the first symptoms attributed to cancer. Treatment delay is defined as the time elapsed between diagnosis and treatment. In non-metastatic patients treated with curative intention, information will be obtained during the follow-up period on consultations performed in the digestive, surgery and oncology departments, as well as the endoscopies, tumour markers and imaging procedures carried out.Local recurrence, development of metastases in the follow-up, appearance of a new tumour and mortality will be included as outcome variables.Actuarial survival analysis with Kaplan-Meier curves, Cox regression and competitive risk survival analysis will be performed. This study will make it possible to verify if the different components of delay have an impact on

  18. Diagnosis delay and follow-up strategies in colorectal cancer. Prognosis implications: a study protocol

    Directory of Open Access Journals (Sweden)

    Aranda Concepción

    2010-10-01

    Full Text Available Abstract Background Controversy exists with regard to the impact that the different components of diagnosis delay may have on the degree of invasion and prognosis in patients with colorectal cancer. The follow-up strategies after treatment also vary considerably. The aims of this study are: a to determine if the symptoms-to-diagnosis interval and the treatment delay modify the survival of patients with colorectal cancer, and b to determine if different follow-up strategies are associated with a higher survival rate. Methods/Design Multi-centre study with prospective follow-up in five regions in Spain (Galicia, Balearic Islands, Catalonia, Aragón and Valencia during the period 2010-2012. Incident cases are included with anatomopathological confirmation of colorectal cancer (International Classification of Diseases 9th revision codes 153-154 that formed a part of a previous study (n = 953. At the time of diagnosis, each patient was given a structured interview. Their clinical records will be reviewed during the follow-up period in order to obtain information on the explorations and tests carried out after treatment, and the progress of these patients. Symptoms-to-diagnosis interval is defined as the time calculated from the diagnosis of cancer and the first symptoms attributed to cancer. Treatment delay is defined as the time elapsed between diagnosis and treatment. In non-metastatic patients treated with curative intention, information will be obtained during the follow-up period on consultations performed in the digestive, surgery and oncology departments, as well as the endoscopies, tumour markers and imaging procedures carried out. Local recurrence, development of metastases in the follow-up, appearance of a new tumour and mortality will be included as outcome variables. Actuarial survival analysis with Kaplan-Meier curves, Cox regression and competitive risk survival analysis will be performed. Discussion This study will make it possible to

  19. Single cancer cell analysis on a chip

    NARCIS (Netherlands)

    Yang, Yoon Sun

    2016-01-01

    Cancer cells in blood may represent “a real time liquid biopsy” through the interrogation of single cancer cells thereby determining the outspread of their heterogeneity and guiding therapy. In this thesis, we focused on single cancer cell analysis downstream of the isolation of cancer cells from

  20. Changes from 1992 to 2002 in the pretreatment delay for patients with squamous cell carcinoma of larynx or pharynx: a Danish nationwide survey from DAHANCA

    DEFF Research Database (Denmark)

    Primdahl, Hanne; Nielsen, Anni Linnet; Larsen, Susanne

    2006-01-01

    In Denmark, a general impression of prolonged pretreatment delay for patients with head and neck cancer led to a nationwide study of time spans from symptom debut over first health care contact to start of treatment. Charts of consecutive new patients with squamous cell carcinoma of the pharynx...

  1. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    Science.gov (United States)

    2017-09-01

    chose to make new medulloblastoma models with oncogenic PIK3CA (PIK3CAH1047R). However, this change caused major delay in our progress since we have not...these tumors. 15. SUBJECT TERMS cancer stem cells, medulloblastoma, targeted therapy, therapy resistance , pediatric cancer, brain tumor, Notch1...Keywords……………………………………………………………. 4 3. Accomplishments………..………………………………………….. 4 4. Impact…………………………...…………………………………… 8 5. Changes /Problems

  2. Dynamics of a stochastic cell-to-cell HIV-1 model with distributed delay

    Science.gov (United States)

    Ji, Chunyan; Liu, Qun; Jiang, Daqing

    2018-02-01

    In this paper, we consider a stochastic cell-to-cell HIV-1 model with distributed delay. Firstly, we show that there is a global positive solution of this model before exploring its long-time behavior. Then sufficient conditions for extinction of the disease are established. Moreover, we obtain sufficient conditions for the existence of an ergodic stationary distribution of the model by constructing a suitable stochastic Lyapunov function. The stationary distribution implies that the disease is persistent in the mean. Finally, we provide some numerical examples to illustrate theoretical results.

  3. Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer

    NARCIS (Netherlands)

    Pore, Milind; Meijer, Coby; de Bock, Geertruida H.; Boersma-van Ek, Wytske; Terstappen, Leon W. M. M.; Groen, Harry J. M.; Timens, Wim; Kruyt, Frank A. E.; Hiltermann, T. Jeroen N.

    2016-01-01

    The prognostic value of markers of cancer stem cells and epithelial to mesenchymal transition in small cell lung cancer is not known. We retrospectively studied these markers in the biopsy tissue of patients with small cell lung cancer and correlated them with overall survival and the strongest

  4. Importance of cell damage causing growth delay for high pressure inactivation of Saccharomyces cerevisiae

    Science.gov (United States)

    Nanba, Masaru; Nomura, Kazuki; Nasuhara, Yusuke; Hayashi, Manabu; Kido, Miyuki; Hayashi, Mayumi; Iguchi, Akinori; Shigematsu, Toru; Hirayama, Masao; Ueno, Shigeaki; Fujii, Tomoyuki

    2013-06-01

    A high pressure (HP) tolerant (barotolerant) mutant a2568D8 and a variably barotolerant mutant a1210H12 were generated from Saccharomyces cerevisiae using ultra-violet mutagenesis. The two mutants, a barosensitive mutant a924E1 and the wild-type strain, were pressurized (225 MPa), and pressure inactivation behavior was analyzed. In the wild-type strain, a proportion of the growth-delayed cells were detected after exposure to HP. In a924E1, the proportion of growth-delayed cells significantly decreased compared with the wild-type. In a2568D8, the proportion of growth-delayed cells increased and the proportion of inactivated cells decreased compared with the wild-type. In a1210H12, the growth-delayed cells could not be detected within 120 s of exposure to HP. The proportion of growth-delayed cells, which incurred the damage, would affect the survival ratio by HP. These results suggested that cellular changes in barotolerance caused by mutations are remarkably affected by the ability to recover from cellular damage, which results in a growth delay.

  5. Laparoscopy mitigates adverse oncological effects of delayed adjuvant chemotherapy for colon cancer.

    Science.gov (United States)

    Gantt, Gerald A; Ashburn, Jean; Kiran, Ravi P; Khorana, Alok A; Kalady, Matthew F

    2015-02-01

    Delaying initiation of adjuvant chemotherapy more than 8 weeks after surgical resection for colorectal cancer adversely affects overall patient survival. The effect of a laparoscopic surgical approach on initiation of chemotherapy has not been studied. The goal of this study was to determine if a laparoscopic approach to colon cancer resection affects the timing of adjuvant chemotherapy and outcomes. Patients who underwent curative surgery for stage II or III colon cancer and received adjuvant chemotherapy between 2003 and 2010 were identified from a prospectively maintained database. Patients were categorized according to surgical approach: open or laparoscopic. Patient demographics, clinicopathologic variables, postoperative complications, time from surgery to initiation of chemotherapy, and long-term oncologic outcomes were compared. Age, gender, ASA class, BMI, tumor stage, and postoperative complications were similar for laparoscopic and open cases, while length of stay was 2 days shorter for laparoscopic cases (5.4 vs 7.6 days, p < 0.01). The proportion of patients who received adjuvant chemotherapy more than 8 weeks after surgery did not differ between the groups (35.6 % open vs 38.7 % laparoscopic, p = 0.77). In the open group, delay in chemotherapy after surgery was associated with decreased disease-free and overall survival (p = 0.01, 0.01, respectively). However, delay in chemotherapy more than 8 weeks did not affect disease-free or overall survival in the laparoscopy group (p = 0.93, 0.51, respectively). The benefits of quicker recovery after laparoscopic surgery did not translate into earlier initiation of adjuvant chemotherapy in this retrospective study. However, a laparoscopic approach negated the inferior oncologic outcomes of patients who received delayed initiation of chemotherapy.

  6. An investigation of dendritic delay in octopus cells of the mammalian cochlear nucleus

    Science.gov (United States)

    Spencer, Martin J.; Grayden, David B.; Bruce, Ian C.; Meffin, Hamish; Burkitt, Anthony N.

    2012-01-01

    Octopus cells, located in the mammalian auditory brainstem, receive their excitatory synaptic input exclusively from auditory nerve fibers (ANFs). They respond with accurately timed spikes but are broadly tuned for sound frequency. Since the representation of information in the auditory nerve is well understood, it is possible to pose a number of questions about the relationship between the intrinsic electrophysiology, dendritic morphology, synaptic connectivity, and the ultimate functional role of octopus cells in the brainstem. This study employed a multi-compartmental Hodgkin-Huxley model to determine whether dendritic delay in octopus cells improves synaptic input coincidence detection in octopus cells by compensating for the cochlear traveling wave delay. The propagation time of post-synaptic potentials from synapse to soma was investigated. We found that the total dendritic delay was approximately 0.275 ms. It was observed that low-threshold potassium channels in the dendrites reduce the amplitude dependence of the dendritic delay of post-synaptic potentials. As our hypothesis predicted, the model was most sensitive to acoustic onset events, such as the glottal pulses in speech when the synaptic inputs were arranged such that the model's dendritic delay compensated for the cochlear traveling wave delay across the ANFs. The range of sound frequency input from ANFs was also investigated. The results suggested that input to octopus cells is dominated by high frequency ANFs. PMID:23125831

  7. Role of Ku80-dependent end-joining in delayed genomic instability in mammalian cells surviving ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Keiji, E-mail: kzsuzuki@nagasaki-u.ac.jp [Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Kodama, Seiji [Research Institute for Advanced Science and Technology, Osaka Prefecture University, 1-2 Gakuen-machi, Sakai 599-8570 (Japan); Watanabe, Masami [Kyoto University Research Reactor Institute, Kumatori-cho Sennan-gun, Osaka 590-0494 (Japan)

    2010-01-05

    Ionizing radiation induces delayed destabilization of the genome in the progenies of surviving cells. This phenomenon, which is called radiation-induced genomic instability, is manifested by delayed induction of radiation effects, such as cell death, chromosome aberration, and mutation in the progeny of cells surviving radiation exposure. Previously, there was a report showing that delayed cell death was absent in Ku80-deficient Chinese hamster ovary (CHO) cells, however, the mechanism of their defect has not been determined. We found that delayed induction of DNA double strand breaks and chromosomal breaks were intact in Ku80-deficient cells surviving X-irradiation, whereas there was no sign for the production of chromosome bridges between divided daughter cells. Moreover, delayed induction of dicentric chromosomes was significantly compromised in those cells compared to the wild-type CHO cells. Reintroduction of the human Ku86 gene complimented the defective DNA repair and recovered delayed induction of dicentric chromosomes and delayed cell death, indicating that defective Ku80-dependent dicentric induction was the cause of the absence of delayed cell death. Since DNA-PKcs-defective cells showed delayed phenotypes, Ku80-dependent illegitimate rejoining is involved in delayed impairment of the integrity of the genome in radiation-survived cells.

  8. Montelukast Induces Apoptosis-Inducing Factor-Mediated Cell Death of Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ming-Ju Tsai

    2017-06-01

    Full Text Available Developing novel chemo-prevention techniques and advancing treatment are key elements to beating lung cancer, the most common cause of cancer mortality worldwide. Our previous cohort study showed that cysteinyl leukotriene receptor antagonists, mainly montelukast, decreased the lung cancer risk in asthma patients. In the current study, we conducted in vivo and in vitro experiments to demonstrate the inhibiting effect of montelukast on lung cancer and to investigate the underlying mechanisms. Using Lewis lung carcinoma-bearing mice, we showed that feeding montelukast significantly delayed the tumor growth in mice (p < 0.0001. Montelukast inhibited cell proliferation and colony formation and induced the cell death of lung cancer cells. Further investigation showed the down-regulation of B-cell lymphoma 2 (Bcl-2, up-regulation of Bcl-2 homologous antagonist/killer (Bak, and nuclear translocation of apoptosis-inducing factor (AIF in montelukast-treated lung cancer cells. Montelukast also markedly decreased the phosphorylation of several proteins, such as with no lysine 1 (WNK1, protein kinase B (Akt, extracellular signal-regulated kinase 1/2 (Erk1/2, MAPK/Erk kinase (MEK, and proline-rich Akt substrate of 40-kDa (PRAS40, which might contribute to cell death. In conclusion, montelukast induced lung cancer cell death via the nuclear translocation of AIF. This study confirmed the chemo-preventive effect of montelukast shown in our previous cohort study. The utility of montelukast in cancer prevention and treatment thus deserves further studies.

  9. Montelukast Induces Apoptosis-Inducing Factor-Mediated Cell Death of Lung Cancer Cells.

    Science.gov (United States)

    Tsai, Ming-Ju; Chang, Wei-An; Tsai, Pei-Hsun; Wu, Cheng-Ying; Ho, Ya-Wen; Yen, Meng-Chi; Lin, Yi-Shiuan; Kuo, Po-Lin; Hsu, Ya-Ling

    2017-06-24

    Developing novel chemo-prevention techniques and advancing treatment are key elements to beating lung cancer, the most common cause of cancer mortality worldwide. Our previous cohort study showed that cysteinyl leukotriene receptor antagonists, mainly montelukast, decreased the lung cancer risk in asthma patients. In the current study, we conducted in vivo and in vitro experiments to demonstrate the inhibiting effect of montelukast on lung cancer and to investigate the underlying mechanisms. Using Lewis lung carcinoma-bearing mice, we showed that feeding montelukast significantly delayed the tumor growth in mice (p Montelukast inhibited cell proliferation and colony formation and induced the cell death of lung cancer cells. Further investigation showed the down-regulation of B-cell lymphoma 2 (Bcl-2), up-regulation of Bcl-2 homologous antagonist/killer (Bak), and nuclear translocation of apoptosis-inducing factor (AIF) in montelukast-treated lung cancer cells. Montelukast also markedly decreased the phosphorylation of several proteins, such as with no lysine 1 (WNK1), protein kinase B (Akt), extracellular signal-regulated kinase 1/2 (Erk1/2), MAPK/Erk kinase (MEK), and proline-rich Akt substrate of 40-kDa (PRAS40), which might contribute to cell death. In conclusion, montelukast induced lung cancer cell death via the nuclear translocation of AIF. This study confirmed the chemo-preventive effect of montelukast shown in our previous cohort study. The utility of montelukast in cancer prevention and treatment thus deserves further studies.

  10. Socio-demographic factors, comorbidity and diagnostic delay among women diagnosed with cervical, endometrial or ovarian cancer: a nationwide survey in Denmark

    DEFF Research Database (Denmark)

    Robinson, Kirstine Magtengaard; Christensen, Karl Bang; Ottesen, Bent Smedegaard

    2011-01-01

    This study investigates the association between socio-demographic factors, comorbidity and diagnostic delay among gynaecological cancer patients. A questionnaire was sent to 1052 women diagnosed with cervical, endometrial or ovarian cancer between October 2006 and December 2007 in Denmark. Long...... patient delays were associated with diagnosis with a greater risk of experiencing long delays among women diagnosed with cervical and endometrial cancer as opposed to ovarian cancer. The risk of experiencing long GP referral delays was associated with residential area, with a greater risk of long delays...... diagnosed with cervical and endometrial cancer as opposed to ovarian cancer, and with working as opposed to being retired. In conclusion, this study found that socio-demographic factors and comorbidity play a role in the probability of experiencing long delays. If delays in diagnosis are to be reduced...

  11. A low-power DCO using inverter interlaced cascaded delay cell

    Science.gov (United States)

    Qiang, Huang; Tao, Fan; Xiangming, Dai; Guoshun, Yuan

    2014-11-01

    This paper presents a low-power small-area digitally controlled oscillator (DCO) using an inverters interlaced cascaded delay cell (IICDC). It uses a coarse-fine architecture with binary-weighted delay stages for the delay range and resolution. The coarse-tuning stage of the DCO uses IICDC, which is power and area efficient with low phase noise, as compared with conventional delay cells. The ADPLL with a DCO is fabricated in the UMC 180-nm CMOS process with an active area of 0.071 mm2. The output frequency range is 140-600 MHz at the power supply of 1.8 V. The power consumption is 2.34 mW @ a 200 MHz output.

  12. p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Amy Tarangelo

    2018-01-01

    Full Text Available How cancer cells respond to nutrient deprivation remains poorly understood. In certain cancer cells, deprivation of cystine induces a non-apoptotic, iron-dependent form of cell death termed ferroptosis. Recent evidence suggests that ferroptosis sensitivity may be modulated by the stress-responsive transcription factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome editing, small-molecule probes, and high-resolution, time-lapse imaging, we find that stabilization of wild-type p53 delays the onset of ferroptosis in response to cystine deprivation. This delay requires the p53 transcriptional target CDKN1A (encoding p21 and is associated with both slower depletion of intracellular glutathione and a reduced accumulation of toxic lipid-reactive oxygen species (ROS. Thus, the p53-p21 axis may help cancer cells cope with metabolic stress induced by cystine deprivation by delaying the onset of non-apoptotic cell death.

  13. Do Cell Phones Cause Cancer?

    CERN Document Server

    Leikind, Bernard

    2010-01-01

    Do cell phones, household electrical power wiring or appliance, or high voltage power lines cause cancer? Fuggedaboudit! No way! When pigs fly! When I'm the Pope! Don't text while you're driving, however, or eat your cell phone. All organisms absorb microwave radiation directly as thermal energy. In living organisms, the organisms' thermal control systems, including the blood flow, and various cooling mechanisms, such as sweating in humans, that work to maintain a stable body temperature rapidly transfer the absorbed energy to the environment. Any temperature rise is small or even unobserved. Any proposed mechanism by which cell phone radiation might cause cancer must begin with this fact. But the amount of radiation absorbed from a cell phone is less than that produced by normal metabolic processes, and much less than that produced by, for example, exercise. None of these normal metabolic processes cause cancer. Therefore, the much smaller amounts of energy from cell phones doesn't cause cancer either. All f...

  14. Delayed effects of cold atmospheric plasma on vascular cells

    NARCIS (Netherlands)

    Stoffels, Eva; Roks, Anton J. M.; Deelmm, Leo E.

    2008-01-01

    We investigated the long-term behaviour of vascular cells (endothelial and smooth muscle) after exposure to a cold atmospheric plasma source. The cells were treated through a gas-permeable membrane, in order to simulate intravenous treatment with a gas plasma-filled catheter. Such indirect treatment

  15. Factors influencing delay in the diagnosis of colorectal cancer: a study protocol

    Directory of Open Access Journals (Sweden)

    Segura Josep M

    2007-05-01

    Full Text Available Abstract Background Colorectal cancer (CRC is the second most frequent tumor in developed countries. Since survival from CRC depends mostly on disease stage at the time of diagnosis, individuals with symptoms or signs suspicious of CRC should be examined without delay. Many factors, however, intervene between symptom onset and diagnosis. This study was designed to: 1 Describe the diagnostic process of CRC from the onset of first symptoms to diagnosis and treatment. 2 Establish the time interval from initial symptoms to diagnosis and treatment, globally and considering patient's and doctors' delay, with the latter due to family physician and/or hospital services. 3 Identify the factors related to defined types of delay. 4 Assess the concordance between information included in primary health care and hospital clinical records regarding onset of first symptoms. Methods/Design Descriptive study, coordinated, with 5 participant groups of 5 different Spanish regions (Balearic Islands, Galicia, Catalunya, Aragón and Valencia Health Districts, with a total of 8 acute public hospitals and 140 primary care centers. Incident cases of CRC during the study period, as identified from pathology services at the involved hospitals. A sample size of 896 subjects has been estimated, 150 subjects for each participant group. Information will be collected through patient interviews and primary health care and hospital clinical records. Patient variables will include sociodemographic variables, family history of cancer, symptom perception, and confidence in the family physician; tumor variables will include tumor site, histological type, grade and stage; symptom variables will include date of onset, type and number of symptoms; health system variables will include number of patient contacts with family physician, type and content of the referral, hospital services attending the patient, diagnostic modalities and results; and delay intervals, including global delays

  16. Factors influencing delay in the diagnosis of colorectal cancer: a study protocol.

    Science.gov (United States)

    Esteva, Magdalena; Ramos, Maria; Cabeza, Elena; Llobera, Joan; Ruiz, Amador; Pita, Salvador; Segura, Josep M; Cortes, Jose M; Gonzalez-Lujan, Luis

    2007-05-21

    Colorectal cancer (CRC) is the second most frequent tumor in developed countries. Since survival from CRC depends mostly on disease stage at the time of diagnosis, individuals with symptoms or signs suspicious of CRC should be examined without delay. Many factors, however, intervene between symptom onset and diagnosis. This study was designed to: 1) Describe the diagnostic process of CRC from the onset of first symptoms to diagnosis and treatment. 2) Establish the time interval from initial symptoms to diagnosis and treatment, globally and considering patient's and doctors' delay, with the latter due to family physician and/or hospital services. 3) Identify the factors related to defined types of delay. 4) Assess the concordance between information included in primary health care and hospital clinical records regarding onset of first symptoms. Descriptive study, coordinated, with 5 participant groups of 5 different Spanish regions (Balearic Islands, Galicia, Catalunya, Aragon and Valencia Health Districts), with a total of 8 acute public hospitals and 140 primary care centers. Incident cases of CRC during the study period, as identified from pathology services at the involved hospitals. A sample size of 896 subjects has been estimated, 150 subjects for each participant group. Information will be collected through patient interviews and primary health care and hospital clinical records. Patient variables will include sociodemographic variables, family history of cancer, symptom perception, and confidence in the family physician; tumor variables will include tumor site, histological type, grade and stage; symptom variables will include date of onset, type and number of symptoms; health system variables will include number of patient contacts with family physician, type and content of the referral, hospital services attending the patient, diagnostic modalities and results; and delay intervals, including global delays and delays attributed to the patient, family

  17. Clinical characteristics and diagnostic delay of head and neck cancer : Results from a prospective study in Belgium

    NARCIS (Netherlands)

    Dhooge, IJ; Albers, FWJ; vanCauwenberge, PB

    A prospective study of head and neck cancer patients was started to gather information about topographic and clinical characteristics of head and neck cancer, alcohol and nicotine abuse and the delay in diagnosis. More than half of the patients consulted our institution with an advanced stage of

  18. Isosorbide delays gentamicin-induced vestibular sensory cell death.

    Science.gov (United States)

    Takumida, Masaya; Anniko, Matti

    2005-01-01

    The efficacy of isosorbide for protection from vestibular sensory cell damage was investigated. The effects of isosorbide on gentamicin-induced production of nitric oxide (NO) and reactive oxygen species (ROS) were studied by means of the fluorescence indicators 4,5-diaminofluorescein diacetate and dihydrotetramethylrosamine. The effect on gentamicin-induced vestibular sensory cell damage was examined by using an in vitro LIVE/DEAD system. Isosorbide inhibited the production of both NO and ROS. Isosorbide limited the vestibular sensory cell damage caused by gentamicin. It is, therefore, suggested that isosorbide may help to treat inner ear disorders.

  19. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  20. Breast cancer circulating tumor cells

    Directory of Open Access Journals (Sweden)

    Maria Joao Carvalho

    2011-12-01

    Full Text Available Metastasization of breast cancer involves various mechanisms responsible for progression from invasive lesion to dissemination in distant organs. Regional lymph node metastasization was considered an initial step in this process, but it is now recognized that hematogenous dissemination is a deviation from lymphatic circulation. The detection of circulating tumor cells (CTC is an aim in several oncology areas. For this purpose, several techniques have been used to detect CTC, including the use of antibodies and techniques with nucleic acids. This study reviews the published studies considering the detection of breast cancer CTC. There are focused the difficulties in identifying a CTC in a heterogeneous population, the handling of the sample, criteria of positivity, analytical techniques, and specific markers. There are systematized various specific markers of breast cancer cells also the problems with false positive results. Finally, we hypothesize clinical applications either as a prognostic marker or as a therapeutic response monitor.

  1. Colorectal Cancer Stem Cells and Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Catalano, Veronica [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Gaggianesi, Miriam [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Spina, Valentina; Iovino, Flora [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Dieli, Francesco [Departement of Biopathology and Medicine Biotechnologies, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Stassi, Giorgio, E-mail: giorgio.stassi@unipa.it [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Todaro, Matilde [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy)

    2011-04-11

    Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem–like cells (CSCs), which survive conventional anticancer treatments, thanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) autocrine production through upregulation of antiapoptotic mediators, including survivin. Consequently, IL-4 neutralization could deregulate survivin expression and localization inducing chemosensitivity of the colon CSCs pool.

  2. Predictors of preoperative delays before radical cystectomy for bladder cancer in Quebec, Canada: a population-based study.

    Science.gov (United States)

    Santos, Fabiano; Dragomir, Alice; Kassouf, Wassim; Franco, Eduardo L; Aprikian, Armen

    2015-03-01

    To characterise and measure different components of preoperative delays experienced by patients with bladder cancer before radical cystectomy (RC) in the province of Quebec, Canada and to identify the predictors of long waiting times. We conducted a retrospective cohort study using the data of patients who underwent RC for bladder cancer between 2000 and 2009 in Quebec. The cohort was obtained with the linkage of two provincial health databases: the Régie de l'assurance maladie du Québec database (data on medical services dispensed to Quebec residents), and the Fichier des évenements démographiques de l'Institut de la statistique du Québec database (demographic data on births and deaths). For the entire cohort, we determined several components of delay from first medical visit related to bladder cancer symptoms until RC. Predictors of long delays were analysed using logistic regression. We analysed a total of 2778 patients who met the inclusion criteria. The median urologist referral delay was 32 days. The median delays between first urologist visit and RC and between transurethral resection of bladder tumour (TURBT) to RC were 90 days and 46 days, respectively. The median overall delay was 116 days. All components of delay progressively increased from the decade of the 1990s to the decade of the 2000s. Male gender was a protective factor for several components of delay, which suggests that gender-related variations may exist in the course of care for bladder cancer (odds ratio 0.67, 95% CI 0.50-0.89 for overall delay). Patient age and gender were associated with delayed urologist referral, delayed time to TURBT, and long overall waiting time. Factors related to the health system were associated with long cystoscopy delays. Median preoperative delays among patients with bladder cancer have been increasing and remain unacceptably long. Patient's age, gender and type of hospital facility were associated with long waiting times. © 2014 The Authors. BJU

  3. Gene Delivery for Metastatic Prostate Cancer Cells

    National Research Council Canada - National Science Library

    Pang, Shen

    2001-01-01

    .... Enhanced by the bystander effect, the specific expression of the DTA gene causes significant cell death in prostate cancer cell cultures, with very low background cell eradication in control cell lines...

  4. Stem cells in prostate cancer.

    Science.gov (United States)

    Mateo, Francesca; Fernandez, Pedro L; Thomson, Timothy M

    2013-06-01

    Tumors constitute complex ecosystems with multiple interactions among neoplastic cells displaying various phenotypes and functions and where the tumoral niche is built with an active participation of the host environment that also impacts the malignant progression of the tumor cells. Irrespective of the cell of origin of prostate adenocarcinoma, mounting evidences support the existence of a hierarchy within neoplastic prostate cells that contributes to the heterogeneity of these tumors. At the origin of this hierarchy are small populations of tumor cells with high self-renewal potential and also capable of generating progeny tumor cells that lose self-renewal properties as they acquire more differentiated phenotypes. These cancer stem cells (CSC) depend on active gene networks that confer them with their self-renewal capacity through symmetrical divisions whereas they can also undergo asymmetrical division and differentiation either as stochastic events or in response to environmental cues. Although new experimental evidences indicate that this is can be a reversible process, thus blurring the distinction between CSCs and non-CSCs, the former are considered as the drivers of tumor growth and evolution, and thus a prime target for therapeutic intervention. Of particular importance in prostate cancer, CSCs may constitute the repository population of androgen-insensitive and chemotherapy-resistant tumor cells responsible for castration-resistant and chemotherapy-insensitive tumors, thus their identification and quantification in primary and metastatic neoplasms could play important roles in the management of this disease.

  5. Diagnostic delay of breast cancer - an analysis of claims to Swedish Board of Malpractice (LÖF).

    Science.gov (United States)

    Hafström, Larsolof; Johansson, Henry; Ahlberg, Jon

    2011-12-01

    Delay in the diagnosis of breast cancer may have important clinical and medico-legal implications. This study examined the decisions made by reviewers at the Swedish agency (LÖF) that handles claims of medical malpractice where claimants seek compensation for alleged suffering and/or negative clinical impacts of diagnostic delays. In 1995-2006 a total of 134 women filed claims for negative effects resulting from delays in the diagnosis of breast cancer. Review of the claims led to approval of delay in the primary diagnosis for 62 women and of recurrence for 28 women. The clinical symptoms that were overlooked and other causes of delay that had any relation to therapy, prognosis and economic compensation were identified. The verdicts reached were analysed. The median delay in the diagnosis of the primary disease was 11 months and for recurrent disease 3.5 months. Delay in diagnosis of the primary disease was considered to have an impact on the therapy in 23%. The prognosis was postulated to have been adversely affected 11% of the patients for whom the delay was longer than 12 months. Delay in diagnosing the recurrence was contributing to delay in starting therapy and to unnecessary suffering in 32%. The delay in diagnosis was mainly caused by incomplete clinical or radiological examination and by misinterpretations of the examination results. Economic compensation was given in 90%. There was a warning or admonition to the responsible doctor in a third of the cases referred to the judgement court. This study demonstrates that claims for compensation for delay in diagnosis of breast cancer in Sweden occur in about 1/1000 new patient. The delay in the diagnosis of the primary tumour was considered to have an impact on the magnitude of therapeutic measures in almost 25% of the women who filed claims. Economic compensation for the patients' injuries was given in ninety percent of the cases. In women for whom there was a delay in diagnosing the recurrence there was

  6. Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer

    NARCIS (Netherlands)

    Pore, M.M.; Meijer, C.; de Bock, G.H.; Boersma-van Ek, W.; Terstappen, Leonardus Wendelinus Mathias Marie; Groen, H.J.M.; Timens, W.; Kruyt, F.A.E.; Hiltermann, T.N.J.

    2016-01-01

    Background Small cell lung cancer (SCLC) has a poor prognosis, and even with localized (limited) disease, the 5-year survival has only been around 20%. Elevated levels of circulating tumor cells (CTCs) have been associated with a worse prognosis, and markers of cancer stem cells (CSCs) and

  7. Glutathione in Cancer Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, Angel L. [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain); Mena, Salvador [Green Molecular SL, Pol. Ind. La Coma-Parc Cientific, 46190 Paterna, Valencia (Spain); Estrela, Jose M., E-mail: jose.m.estrela@uv.es [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain)

    2011-03-11

    Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy.

  8. [Dendritic cells in cancer immunotherapy].

    Science.gov (United States)

    Gato, M; Liechtenstein, T; Blanco-Luquín, I; Zudaire, M I; Kochan, G; Escors, D

    2015-01-01

    Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are still first line treatments. Even so, there is a quantity of experimental evidence demonstrating that cancer cells are immunogenic. However, the effective activation of anti-cancer T cell responses closely depends on an efficient antigen presentation carried out by professional antigen presenting cells such as DC. Although there are a number of strategies to strengthen antigen presentation by DC, anti-cancer immunotherapy is not as effective as we would expect according to preclinical data accumulated in recent decades. We do not aim to make an exhaustive review of DC immunotherapy here, which is an extensive research subject already dealt with in many specialised reviews. Instead, we present the experimental approaches undertaken by our group over the last decade, by modifying DC to improve their anti-tumour capacities.

  9. Dynamics of an HBV/HCV infection model with intracellular delay and cell proliferation

    Science.gov (United States)

    Zhang, Fengqin; Li, Jianquan; Zheng, Chongwu; Wang, Lin

    2017-01-01

    A new mathematical model of hepatitis B/C virus (HBV/HCV) infection which incorporates the proliferation of healthy hepatocyte cells and the latent period of infected hepatocyte cells is proposed and studied. The dynamics is analyzed via Pontryagin's method and a newly proposed alternative geometric stability switch criterion. Sharp conditions ensuring stability of the infection persistent equilibrium are derived by applying Pontryagin's method. Using the intracellular delay as the bifurcation parameter and applying an alternative geometric stability switch criterion, we show that the HBV/HCV infection model undergoes stability switches. Furthermore, numerical simulations illustrate that the intracellular delay can induce complex dynamics such as persistence bubbles and chaos.

  10. Proteasome expression and activity in cancer and cancer stem cells.

    Science.gov (United States)

    Voutsadakis, Ioannis A

    2017-03-01

    Proteasome is a multi-protein organelle that participates in cellular proteostasis by destroying damaged or short-lived proteins in an organized manner guided by the ubiquitination signal. By being in a central place in the cellular protein complement homeostasis, proteasome is involved in virtually all cell processes including decisions on cell survival or death, cell cycle, and differentiation. These processes are important also in cancer, and thus, the proteasome is an important regulator of carcinogenesis. Cancers include a variety of cells which, according to the cancer stem cell theory, descend from a small percentage of cancer stem cells, alternatively termed tumor-initiating cells. These cells constitute the subsets that have the ability to propagate the whole variety of cancer and repopulate tumors after cytostatic therapies. Proteasome plays a role in cellular processes in cancer stem cells, but it has been found to have a decreased function in them compared to the rest of cancer cells. This article will discuss the transcriptional regulation of proteasome sub-unit proteins in cancer and in particular cancer stem cells and the relationship of the proteasome with the pluripotency that is the defining characteristic of stem cells. Therapeutic opportunities that present from the understanding of the proteasome role will also be discussed.

  11. Low-Dose Formaldehyde Delays DNA Damage Recognition and DNA Excision Repair in Human Cells

    Science.gov (United States)

    Luch, Andreas; Frey, Flurina C. Clement; Meier, Regula; Fei, Jia; Naegeli, Hanspeter

    2014-01-01

    Objective Formaldehyde is still widely employed as a universal crosslinking agent, preservative and disinfectant, despite its proven carcinogenicity in occupationally exposed workers. Therefore, it is of paramount importance to understand the possible impact of low-dose formaldehyde exposures in the general population. Due to the concomitant occurrence of multiple indoor and outdoor toxicants, we tested how formaldehyde, at micromolar concentrations, interferes with general DNA damage recognition and excision processes that remove some of the most frequently inflicted DNA lesions. Methodology/Principal Findings The overall mobility of the DNA damage sensors UV-DDB (ultraviolet-damaged DNA-binding) and XPC (xeroderma pigmentosum group C) was analyzed by assessing real-time protein dynamics in the nucleus of cultured human cells exposed to non-cytotoxic (formaldehyde concentrations. The DNA lesion-specific recruitment of these damage sensors was tested by monitoring their accumulation at local irradiation spots. DNA repair activity was determined in host-cell reactivation assays and, more directly, by measuring the excision of DNA lesions from chromosomes. Taken together, these assays demonstrated that formaldehyde obstructs the rapid nuclear trafficking of DNA damage sensors and, consequently, slows down their relocation to DNA damage sites thus delaying the excision repair of target lesions. A concentration-dependent effect relationship established a threshold concentration of as low as 25 micromolar for the inhibition of DNA excision repair. Conclusions/Significance A main implication of the retarded repair activity is that low-dose formaldehyde may exert an adjuvant role in carcinogenesis by impeding the excision of multiple mutagenic base lesions. In view of this generally disruptive effect on DNA repair, we propose that formaldehyde exposures in the general population should be further decreased to help reducing cancer risks. PMID:24722772

  12. Staphylococcus aureus Lpl Lipoproteins Delay G2/M Phase Transition in HeLa Cells.

    Science.gov (United States)

    Nguyen, Minh-Thu; Deplanche, Martine; Nega, Mulugeta; Le Loir, Yves; Peisl, Loulou; Götz, Friedrich; Berkova, Nadia

    2016-01-01

    The cell cycle is an ordered set of events, leading to cell growth and division into two daughter cells. The eukaryotic cell cycle consists of interphase (G1, S, and G2 phases), followed by the mitotic phase and G0 phase. Many bacterial pathogens secrete cyclomodulins that interfere with the host cell cycle. In Staphylococcus aureus four cyclomodulins have been described so far that all represent toxins and are secreted into the culture supernatant. Here we show that the membrane-anchored lipoprotein-like proteins (Lpl), encoded on a genomic island called νSaα, interact with the cell cycle of HeLa cells. By comparing wild type and lpl deletion mutant it turned out that the lpl cluster is causative for the G2/M phase transition delay and also contributes to increased invasion frequency. The lipoprotein Lpl1, a representative of the lpl cluster, also caused G2/M phase transition delay. Interestingly, the lipid modification, which is essential for TLR2 signaling and activation of the immune system, is not necessary for cyclomodulin activity. Unlike the other staphylococcal cyclomodulins Lpl1 shows no cytotoxicity even at high concentrations. As all Lpl proteins are highly conserved there might be a common function that is accentuated by their multiplicity in a tandem gene cluster. The cell surface localized Lpls' suggests a correlation between G2/M phase transition delay and host cell invasion.

  13. Prostate Cancer Stem Cells: Research Advances

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska

    2015-11-01

    Full Text Available Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  14. Silent Crooke's cell corticotroph adenoma of the pituitary gland presenting as delayed puberty.

    Science.gov (United States)

    Giri, Dinesh; Roncaroli, Federico; Sinha, Ajay; Didi, Mohammed; Senniappan, Senthil

    2017-01-01

    Corticotroph adenomas are extremely rare in children and adolescents. We present a 15-year-old boy who was investigated for delayed puberty (A1P2G1, bilateral testicular volumes of 3 mL each). There was no clinical or laboratory evidence suggestive of chronic illness, and the initial clinical impression was constitutional delay in puberty. Subsequently, MRI scan of the brain revealed the presence of a mixed cystic and solid pituitary lesion slightly displacing the optic chiasma. The lesion was removed by transphenoidal surgery and the biopsy confirmed the lesion to be pituitary adenoma. Furthermore, the adenoma cells also had Crooke's hyaline changes and were intensely positive for ACTH. However there was no clinical/biochemical evidence of ACTH excess. There was a spontaneous pubertal progression twelve months after the surgery (A2P4G4, with bilateral testicular volume of 8 mL). Crooke's cell adenoma is an extremely rare and aggressive variant of corticotroph adenoma that can uncommonly present as a silent corticotroph adenoma in adults. We report for the first time Crooke's cell adenoma in an adolescent boy presenting with delayed puberty. Constitutional delay of growth and puberty (CDGP) is a diagnosis of exclusion; hence a systematic and careful review should be undertaken while assessing boys with delayed puberty.Crooke's cell adenomas are a group of corticotroph adenomas that can rarely present in childhood and adolescence with delayed puberty.Crooke's cell adenomas can be clinically silent but are potentially aggressive tumours that require careful monitoring.

  15. Cancer Stem Cells and the Ontogeny of Lung Cancer

    OpenAIRE

    Peacock, Craig D.; Watkins, D. Neil

    2008-01-01

    Lung cancer is the leading cause of cancer death in the world today and is poised to claim approximately 1 billion lives during the 21st century. A major challenge in treating this and other cancers is the intrinsic resistance to conventional therapies demonstrated by the stem/progenitor cell that is responsible for the sustained growth, survival, and invasion of the tumor. Identifying these stem cells in lung cancer and defining the biologic processes necessary for their existence is paramou...

  16. Reprogramming cancer cells: overview & current progress.

    Science.gov (United States)

    Lim, Kian Lam; Teoh, Hoon Koon; Choong, Pei Feng; Teh, Hui Xin; Cheong, Soon Keng; Kamarul, Tunku

    2016-07-01

    Cancer is a disease with genetic and epigenetic origins, and the possible effects of reprogramming cancer cells using the defined sets of transcription factors remain largely uninvestigated. In the handful of publications available so far, findings have shown that reprogramming cancer cells changed the characteristics of the cells to differ from the parental cancer cells. These findings indicated the possibility of utilizing reprogramming technology to create a disease model in the laboratory to be used in studying the molecular pathogenesis or for drug screening of a particular cancer model. Despite numerous methods employed in generating induced pluripotent stem cells (iPSCs) from cancer cells only a few studies have successfully reprogrammed malignant human cells. In this review we will provide an overview on i) methods to reprogram cancer cells, ii) characterization of the reprogrammed cancer cells, and iii) the differential effects of reprogramming on malignancy, epigenetics and response of the cancer cells to chemotherapeutic agents. Continued technical progress in cancer cell reprogramming technology will be instrumental for more refined in vitro disease models and ultimately for the development of directed and personalized therapy for cancer patients in the future.

  17. Cancer stem cells: the theory and perspectives in cancer therapy.

    Science.gov (United States)

    Gil, Justyna; Stembalska, Agnieszka; Pesz, Karolina A; Sasiadek, Maria M

    2008-01-01

    The cancer stem cell theory elucidates not only the issue of tumour initiation and development, tumour's ability to metastasise and reoccur, but also the ineffectiveness of conventional cancer therapy. This review examines stem cell properties, such as self-renewal, heterogeneity, and resistance to apoptosis. The 'niche' hypothesis is presented, and mechanisms of division, differentiation, self-renewal and signalling pathway regulation are explained. Epigenetic alterations and mutations of genes responsible for signal transmission may promote the formation of cancer stem cells. We also present the history of development of the cancer stem cell theory and discuss the experiments that led to the discovery and confirmation of the existence of cancer stem cells. Potential clinical applications are also considered, including therapeutic models aimed at selective elimination of cancer stem cells or induction of their proper differentiation.

  18. Predictors of delayed failure of structural kyphoplasty for pathological compression fractures in cancer patients.

    Science.gov (United States)

    Rajah, Gary; Altshuler, David; Sadiq, Omar; Nyame, V Kwasi; Eltahawy, Hazem; Szerlip, Nicholas

    2015-08-01

    OBJECT Pathological compression fractures in cancer patients cause significant pain and disability. Spinal metastases affect quality of life near the end of life and may require multiple procedures, including medical palliative care and open surgical decompression and fixation. An increasingly popular minimally invasive technique to treat metastatic instabilities is kyphoplasty. Even though it may alleviate pain due to pathological fractures, it may fail. However, delayed kyphoplasty failures with retropulsed cement and neural element compression have not been well reported. Such failures necessitate open surgical decompression and stabilization, and cement inserted during the kyphoplasty complicates salvage surgeries in patients with a disease-burdened spine. The authors sought to examine the incidence of delayed failure of structural kyphoplasty in a series of cement augmentations for pathological compression fractures. The goal was to identify risk predictors by analyzing patient and disease characteristics to reduce kyphoplasty failure and to prevent excessive surgical procedures at the end of life. METHODS The authors retrospectively reviewed the records of all patients with metastatic cancer from 2010 to 2013 who had undergone a procedure involving cement augmentation for a pathological compression fracture at their institution. The authors examined the characteristics of the patients, diseases, and radiographic fractures. RESULTS In total, 37 patients underwent cement augmentation in 75 spinal levels during 45 surgeries. Four patients had delayed structural kyphoplasty failure necessitating surgical decompression and fusion. The mean time to kyphoplasty failure was 2.88 ± 1.24 months. The mean loss of vertebral body height was 16% in the patients in whom kyphoplasty failed and 32% in patients in whom kyphoplasty did not fail. No posterior intraoperative cement extravasation was observed in the patients in whom kyphoplasty had failed. The mean spinal

  19. Dynamic contrast-enhanced MR imaging of endometrial cancer. Optimizing the imaging delay for tumour-myometrium contrast

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Bin [Chung-Ang University Hospital, Chung-Ang University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Moon, Min Hoan; Sung, Chang Kyu [Seoul National University College of Medicine, 41, Department of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Oh, Sohee [Seoul National University College of Medicine, 41, Department of Biostatistics, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Lee, Young Ho [Kwandong University College of Medicine, Department of Radiology, Cheil General Hospital and Women' s Healthcare Center, Seoul (Korea, Republic of)

    2014-11-15

    To investigate the optimal imaging delay time of dynamic contrast-enhanced magnetic resonance (MR) imaging in women with endometrial cancer. This prospective single-institution study was approved by the institutional review board, and informed consent was obtained from the participants. Thirty-five women (mean age, 54 years; age range, 29-66 years) underwent dynamic contrast-enhanced MR imaging with a temporal resolution of 25-40 seconds. The signal intensity difference ratios between the myometrium and endometrial cancer were analyzed to investigate the optimal imaging delay time using single change-point analysis. The optimal imaging delay time for appropriate tumour-myometrium contrast ranged from 31.7 to 268.1 seconds. The median optimal imaging delay time was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. The median signal intensity difference ratios between the myometrium and endometrial cancer were 0.03, with an interquartile range of -0.01 to 0.06, on the pre-contrast MR imaging and 0.20, with an interquartile range of 0.15 to 0.25, on the post-contrast MR imaging. An imaging delay of approximately 90 seconds after initiating contrast material injection may be optimal for obtaining appropriate tumour-myometrium contrast in women with endometrial cancer. (orig.)

  20. A POX on Renal Cancer Cells | Center for Cancer Research

    Science.gov (United States)

    Proline oxidase, or POX, is an enzyme responsible for metabolizing the amino acid proline. POX contributes to the regulation of cell death that occurs when cellular systems malfunction, a process called apoptosis. Previous studies have determined that levels of POX are reduced in several types of human cancer. Likewise, many cancer cells become resistant to apoptosis, suggesting a link between POX and cancer cell survival.

  1. Generation of time delays: simplified models of intracellular signaling in cerebellar Purkinje cells

    NARCIS (Netherlands)

    Steuber, V.; Willshaw, D.; van Ooyen, A.

    2006-01-01

    In many neuronal systems, information is encoded in temporal spike patterns. The recognition and storage of temporal patterns requires the generation and modulation of time delays between inputs and outputs. In cerebellar Purkinje cells, stimulation of metabotropic glutamate receptors (mGluRs)

  2. Deficiency of CCN5/WISP-2-Driven Program in breast cancer Promotes Cancer Epithelial cells to mesenchymal stem cells and Breast Cancer growth.

    Science.gov (United States)

    Das, Amlan; Dhar, Kakali; Maity, Gargi; Sarkar, Sandipto; Ghosh, Arnab; Haque, Inamul; Dhar, Gopal; Banerjee, Snigdha; Banerjee, Sushanta K

    2017-04-27

    Breast cancer progression and relapse is conceivably due to tumor initiating cells (TICs)/cancer stem cells. EMT (epithelial-mesenchymal-transition)-signaling regulates TICs' turnover. However, the mechanisms associated with this episode are unclear. We show that, in triple-negative-breast cancer (TNBC) cells enriched with TICs, CCN5 significantly blocks cellular growth via apoptosis, reversing EMT-signaling and impairing mammosphere formation, thereby blocking the tumor-forming ability and invasive capacity of these cells. To corroborate these findings, we isolated tumor-initiating side populations (SP) and non-side population (NSP or main population) from MCF-7 cell line, and evaluated the impact of CCN5 on these subpopulations. CCN5 was overexpressed in the NSP but downregulated in the SP. Characteristically, NSP cells are ER-α positive and epithelial type with little tumorigenic potency, while SP cells are very similar to triple-negative ones that do not express ER-α- and Her-2 and are highly tumorigenic in xenograft models. The overexpression of CCN5 in SP results in EMT reversion, ER-α upregulation and delays in tumor growth in xenograft models. We reasoned that CCN5 distinguishes SP and NSP and could reprogram SP to NSP transition, thereby delaying tumor growth in the xenograft model. Collectively, we reveal how CCN5-signaling underlies the driving force to prevent TNBC growth and progression.

  3. O-antigen delays lipopolysaccharide recognition and impairs antibacterial host defense in murine intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Claudia U Duerr

    2009-09-01

    Full Text Available Although Toll-like receptor (TLR 4 signals from the cell surface of myeloid cells, it is restricted to an intracellular compartment and requires ligand internalization in intestinal epithelial cells (IECs. Yet, the functional consequence of cell-type specific receptor localization and uptake-dependent lipopolysaccharide (LPS recognition is unknown. Here, we demonstrate a strikingly delayed activation of IECs but not macrophages by wildtype Salmonella enterica subsp. enterica sv. (S. Typhimurium as compared to isogenic O-antigen deficient mutants. Delayed epithelial activation is associated with impaired LPS internalization and retarded TLR4-mediated immune recognition. The O-antigen-mediated evasion from early epithelial innate immune activation significantly enhances intraepithelial bacterial survival in vitro and in vivo following oral challenge. These data identify O-antigen expression as an innate immune evasion mechanism during apical intestinal epithelial invasion and illustrate the importance of early innate immune recognition for efficient host defense against invading Salmonella.

  4. Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma.

    Science.gov (United States)

    Liu, Hen-Yu; Huang, Chiung-Fang; Lin, Tzu-Chieh; Tsai, Ching-Yu; Tina Chen, Szu-Yu; Liu, Alice; Chen, Wei-Hong; Wei, Hong-Jian; Wang, Ming-Fu; Williams, David F; Deng, Win-Ping

    2014-12-01

    Aging is related to loss of functional stem cell accompanying loss of tissue and organ regeneration potentials. Previously, we demonstrated that the life span of ovariectomy-senescence accelerated mice (OVX-SAMP8) was significantly prolonged and similar to that of the congenic senescence-resistant strain of mice after platelet rich plasma (PRP)/embryonic fibroblast transplantation. The aim of this study is to investigate the potential of PRP for recovering cellular potential from senescence and then delaying animal aging. We first examined whether stem cells would be senescent in aged mice compared to young mice. Primary adipose derived stem cells (ADSCs) and bone marrow derived stem cells (BMSCs) were harvested from young and aged mice, and found that cell senescence was strongly correlated to animal aging. Subsequently, we demonstrated that PRP could recover cell potential from senescence, such as promote cell growth (cell proliferation and colony formation), increase osteogenesis, decrease adipogenesis, restore cell senescence related markers and resist the oxidative stress in stem cells from aged mice. The results also showed that PRP treatment in aged mice could delay mice aging as indicated by survival, body weight and aging phenotypes (behavior and gross morphology) in term of recovering the cellular potential of their stem cells compared to the results on aged control mice. In conclusion these findings showed that PRP has potential to delay aging through the recovery of stem cell senescence and could be used as an alternative medicine for tissue regeneration and future rejuvenation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Successful Treatment of T Cell-Mediated Acute Rejection with Delayed CTLA4-Ig in Mice

    Directory of Open Access Journals (Sweden)

    James S. Young

    2017-09-01

    Full Text Available Clinical observations that kidney transplant recipients receiving belatacept who experienced T cell-mediated acute rejection can be successfully treated and subsequently maintained on belatacept-based immunosuppression suggest that belatacept is able to control memory T cells. We recently reported that treatment with CTLA4-Ig from day 6 posttransplantation successfully rescues allografts from acute rejection in a BALB/c to C57BL/6 heart transplant model, in part, by abolishing B cell germinal centers and reducing alloantibody titers. Here, we show that CTLA4-Ig is additionally able to inhibit established T cell responses independently of B cells. CTLA4-Ig inhibited the in vivo cytolytic activity of donor-specific CD8+ T cells, and the production of IFNγ by graft-infiltrating T cells. Delayed CTLA4-Ig treatment did not reduce the numbers of graft-infiltrating T cells nor prevented the accumulation of antigen-experienced donor-specific memory T cells in the spleen. Nevertheless, delayed CTLA4-Ig treatment successfully maintained long-term graft acceptance in the majority of recipients that had experienced a rejection crisis, and enabled the acceptance of secondary BALB/c heart grafts transplanted 30 days after the first transplantation. In summary, we conclude that delayed CTLA4-Ig treatment is able to partially halt ongoing T cell-mediated acute rejection. These findings extend the functional efficacy of CTLA4-Ig therapy to effector T cells and provide an explanation for why CTLA4-Ig-based immunosuppression in the clinic successfully maintains long-term graft survival after T cell-mediated rejection.

  6. Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Luce, A.; Courtin, A.; Levalois, C.; Altmeyer-Morel, S.; Chevillard, S.; Lebeau, J. [CEA, DSV, iRCM, SREIT, Laboratoire de Cancerologie Experimentale, Fontenay-aux-Roses, F-92265 (France); Romeo, P.H. [CEA, DSV, iRCM, SCSR, Laboratoire de recherche sur la Reparation et la Transcription dans les cellules Souches, Fontenay-aux-Roses, F-92265 (France)

    2009-07-01

    Delayed cell death by mitotic catastrophe is a frequent mode of solid tumor cell death after {gamma}-irradiation, a widely used treatment of cancer. Whereas the mechanisms that underlie the early {gamma}-irradiation-induced cell death are well documented, those that drive the delayed cell death are largely unknown. Here we show that the Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor (TNF)-{alpha} death receptor pathways mediate the delayed cell death observed after {gamma}-irradiation of breast cancer cells. Early after irradiation, we observe the increased expression of Fas, TRAIL-R and TNF-R that first sensitizes cells to apoptosis. Later, the increased expression of FasL, TRAIL and TNF-{alpha} permit the apoptosis engagement linked to mitotic catastrophe. Treatments with TNF-{alpha}, TRAIL or anti-Fas antibody, early after radiation exposure, induce apoptosis, whereas the neutralization of the three death receptors pathways impairs the delayed cell death. We also show for the first time that irradiated breast cancer cells excrete soluble forms of the three ligands that can induce the death of sensitive bystander cells. Overall, these results define the molecular basis of the delayed cell death of irradiated cancer cells and identify the death receptors pathways as crucial actors in apoptosis induced by targeted as well as non-targeted effects of ionizing radiation. (authors)

  7. Colon Cancer Cell Separation by Dielectrophoresis

    Science.gov (United States)

    Yang, Fang; Yang, Xiaoming; Jiang, H.; Wood, P.; Hrushesky, W.; Wang, Guiren

    2009-11-01

    Separation of cancer cells from the other biological cells can be useful for clinical cancer diagnosis and cancer treatment. In this presentation, conventional dielectrophoresis (c-DEP) is used in a microfluidic chip to manipulate and collect colorectal cancer HCT116 cell, which is doped with Human Embryonic Kidney 293 cells (HEK 293). It is noticed that, the HCT116 cell are deflected to a side channel from a main channel clearly by apply electric field at particular AC frequency band. This motion caused by negative DEP can be used to separate the cancer cell from others. In this manuscript, chip design, flow condition, the DEP spectrum of the cancer cell are reported respectively, and the separation and collection efficiency are investigated as well. The sorter is microfabricated using plastic laminate technology. -/abstract- This work has been financially supported by the NSF RII funding (EP

  8. Induction of delayed-type hypersensitivity by the T cell line specific to bacterial peptidoglycans

    Energy Technology Data Exchange (ETDEWEB)

    Katsuki, M.; Kakimoto, K.; Kawata, S.; Kotani, S.; Koga, T.

    1987-12-01

    A T cell line specific for the chemically well-defined peptidoglycan of bacterial cell wall, disaccharide tetrapeptide, was established from Lewis rats immunized with the antigen covalently linked to the autologous rat serum albumin. The antigen specificity was examined with various analogues or derivatives of the peptidoglycan. The cell line was reactive to analogues with the COOH-terminal D-amino acid, but least reactive to those with L-amino acid as COOH terminus. Transferring of the T cell line into X-irradiated normal Lewis rats induced delayed-type hypersensitivity in an antigen specific manner.

  9. Identifying women at risk for delayed presentation of breast cancer: a cross-sectional study in Estonia.

    Science.gov (United States)

    Innos, Kaire; Padrik, Peeter; Valvere, Vahur; Eelma, Evelyn; Kütner, Riina; Lehtsaar, Jaak; Tekkel, Mare

    2013-10-09

    Survival from breast cancer remains lower in Estonia than in most other European countries. More advanced stage and larger tumors that have impact on survival may be a result of delay in seeking help for breast cancer symptoms. The aim of this study was to identify determinants of delayed presentation among breast cancer patients in Estonia. The study population included women with primary breast cancer diagnosed in Estonia in 2008-2010. All data were collected using structured personal interviews carried out by trained nurses in the hospital setting. Only patients with self-discovered symptoms were included in this analysis. Patient delay was measured as time elapsing from symptom self-discovery to first medical consultation. The effect of different factors on the likelihood of prolonged delay (>90 days) was evaluated using logistic regression. Among 703 eligible patients, median patient delay was 16 days (interquartile range 5-54 days). Seventeen percent of the patients had their first medical consultation more than three months after self-detection of symptoms. In multivariate analysis, the risk of prolonged delay was significantly associated with age 65 years and over (OR 2.27, 95% CI 1.23-4.20), current smoking (OR 2.09, 95% CI 1.21-3.61), symptoms other than painless breast lump or breast pain (OR 1.84, 95% CI 1.08-3.16), no history of mammograms (OR 1.83, 95% CI 1.13-2.95), having received no information on breast cancer during past year (OR 1.77, 95% CI 1.05-2.99), and previous benign breast problems (OR 1.65, 95% CI 1.01-2.67). Non-significant risk increase was seen with lower education. This study provides evidence that factors associated with delayed presentation of breast cancer in Eastern Europe are similar to those observed in Western countries. The results suggest that educational messages to general population should aim at increasing awareness of "non-lump" symptoms of breast cancer and encouraging women of all ages to present in a timely manner

  10. Project Zero Delay: a process for accelerating the activation of cancer clinical trials.

    Science.gov (United States)

    Kurzrock, Razelle; Pilat, Susan; Bartolazzi, Marcel; Sanders, Dwana; Van Wart Hood, Jill; Tucker, Stanley D; Webster, Kevin; Mallamaci, Michael A; Strand, Steven; Babcock, Eileen; Bast, Robert C

    2009-09-10

    Drug development in cancer research is lengthy and expensive. One of the rate-limiting steps is the initiation of first-in-human (phase I) trials. Three to 6 months can elapse between investigational new drug (IND) approval by the US Food and Drug Administration and the entry of a first patient. Issues related to patient participation have been well analyzed, but the administrative processes relevant to implementing clinical trials have received less attention. While industry and academia often partner for the performance of phase I studies, their administrative processes are generally performed independently, and their timelines driven by different priorities: safety reviews, clinical operations, regulatory submissions, and contracting of clinical delivery vendors for industry; contracts, budgets, and institutional review board approval for academia. Both processes converge on US Food and Drug Administration approval of an IND. In the context of a strategic alliance between M. D. Anderson Cancer Center and AstraZeneca Pharmaceuticals LP, a concerted effort has been made to eliminate delays in implementing clinical trials. These efforts focused on close communications, identifying and matching key timelines, alignment of priorities, and tackling administrative processes in parallel, rather than sequentially. In a recent, first-in-human trial, the study was activated and the first patient identified in 46 days from completion of the final study protocol and about 48 hours after final US Food and Drug Administration IND approval, reducing the overall timeline by about 3 months, while meeting all clinical good practice guidelines. Eliminating administrative delays can accelerate the evaluation of new drugs without compromising patient safety or the quality of clinical research.

  11. Prostate Cancer Stem-Like Cells | Center for Cancer Research

    Science.gov (United States)

    Prostate cancer is the third leading cause of cancer-related death among men, killing an estimated 27,000 men each year in the United States. Men with advanced prostate cancer often become resistant to conventional therapies. Many researchers speculate that the emergence of resistance is due to the presence of cancer stem cells, which are believed to be a small subpopulation of tumor cells that can self-renew and give rise to more differentiated tumor cells. It is thought that these stem cells survive initial therapies (such as chemotherapy and hormone therapy) and then generate new tumor cells that are resistant to these standard treatments. If prostate cancer stem cells could be identified and characterized, it might be possible to design treatments that prevent resistance.

  12. Preclinical evaluation of 4-methylthiobutyl isothiocyanate on liver cancer and cancer stem cells with different p53 status.

    Directory of Open Access Journals (Sweden)

    Evelyn Lamy

    Full Text Available Isothiocyanates from plants of the order Brassicales are considered promising cancer chemotherapeutic phytochemicals. However, their selective cytotoxicity on liver cancer has been barely researched. Therefore, in the present study, we systematically studied the chemotherapeutic potency of 4-methylthiobutyl isothiocyanate (MTBITC. Selective toxicity was investigated by comparing its effect on liver cancer cells and their chemoresistant subpopulations to normal primary hepatocytes and liver tissue slices. Additionally, in a first assessment, the in vivo tolerability of MTBITC was investigated in mice. Growth arrest at G2/M and apoptosis induction was evident in all in vitro cancer models treated with MTBITC, including populations with cancer initiating characteristics. This was found independent from TP53; however cell death was delayed in p53 compromised cells as compared to wt-p53 cells which was probably due to differential BH3 only gene regulation i. e. Noxa and its antagonist A1. In normal hepatocytes, no apoptosis or necrosis could be detected after repeated administration of up to 50 µM MTBITC. In mice, orally applied MTBITC was well tolerated over 18 days of treatment for up to 50 mg/kg/day, the highest dose tested. In conclusion, we could show here that the killing effect of MTBITC has a definite selectivity for cancer cells over normal liver cells and its cytotoxicity even applies for chemoresistant cancer initiating cells. Our study could serve for a better understanding of the chemotherapeutic properties of isothiocyanates on human liver-derived cancer cells.

  13. Stability and Hopf bifurcation in a delayed model for HIV infection of CD4{sup +}T cells

    Energy Technology Data Exchange (ETDEWEB)

    Cai Liming [Department of Mathematics, Xinyang Normal University, Xinyang, 464000 Henan (China); Beijing Institute of Information Control, Beijing 100037 (China)], E-mail: lmcai06@yahoo.com.cn; Li Xuezhi [Department of Mathematics, Xinyang Normal University, Xinyang, 464000 Henan (China)

    2009-10-15

    In this paper, we consider a delayed mathematical model for the interactions of HIV infection and CD4{sup +}T cells. We first investigate the existence and stability of the Equilibria. We then study the effect of the time delay on the stability of the infected equilibrium. Criteria are given to ensure that the infected equilibrium is asymptotically stable for all delay. Moreover, by applying Nyquist criterion, the length of delay is estimated for which stability continues to hold. Finally by using a delay {tau} as a bifurcation parameter, the existence of Hopf bifurcation is also investigated. Numerical simulations are presented to illustrate the analytical results.

  14. Transplantation of Bone Marrow-Derived Mesenchymal Stem Cells Promotes Delayed Wound Healing in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jiangbo Wan

    2013-01-01

    Full Text Available In this paper, we established a delayed wound healing model on diabetic rat to mimic the pathophysiology of clinical patients who suffered from diabetic foot ulcers. We also evaluated if transplantation of allogeneic bone marrow-derived mesenchymal stem cells could promote the delayed wound healing and investigated the possible underlying biological mechanisms and stem cell behavior involved in this process. The results showed that bone marrow-derived mesenchymal stem cells had a positive effect on delayed wound healing in diabetic rats. Intramuscular transplantation demonstrated the best efficacy. This effect is associated with granulation tissue formation, angiogenesis, cellular proliferation, and high vascular endothelial growth factor expression in wound tissues. In addition, bone marrow-derived mesenchymal stem cells have been shown to mobilize and find home for ischemic and wounded tissues to participate in the process of wound healing. Intramuscular transplantation of exogenous isogeneic stem cells may be suitable for clinical application in the treatment of diabetic foot ulcers although the safety of this therapy should be considered.

  15. Cancer Cell Fusion: Mechanisms Slowly Unravel

    Directory of Open Access Journals (Sweden)

    Felicite K. Noubissi

    2016-09-01

    Full Text Available Although molecular mechanisms and signaling pathways driving invasion and metastasis have been studied for many years, the origin of the population of metastatic cells within the primary tumor is still not well understood. About a century ago, Aichel proposed that cancer cell fusion was a mechanism of cancer metastasis. This hypothesis gained some support over the years, and recently became the focus of many studies that revealed increasing evidence pointing to the possibility that cancer cell fusion probably gives rise to the metastatic phenotype by generating widespread genetic and epigenetic diversity, leading to the emergence of critical populations needed to evolve resistance to the treatment and development of metastasis. In this review, we will discuss the clinical relevance of cancer cell fusion, describe emerging mechanisms of cancer cell fusion, address why inhibiting cancer cell fusion could represent a critical line of attack to limit drug resistance and to prevent metastasis, and suggest one new modality for doing so.

  16. A Comparison of Postoperative Early Enteral Nutrition with Delayed Enteral Nutrition in Patients with Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Gongchao Wang

    2015-06-01

    Full Text Available We examined esophageal cancer patients who received enteral nutrition (EN to evaluate the validity of early EN compared to delayed EN, and to determine the appropriate time to start EN. A total of 208 esophagectomy patients who received EN postoperatively were divided into three groups (Group 1, 2 and 3 based on whether they received EN within 48 h, 48 h–72 h or more than 72 h, respectively. The postoperative complications, length of hospital stay (LOH, days for first fecal passage, cost of hospitalization, and the difference in serum albumin values between pre-operation and post-operation were all recorded. The statistical analyses were performed using the t-test, the Mann-Whitney U test and the chi square test. Statistical significance was defined as p < 0.05. Group 1 had the lowest thoracic drainage volume, the earliest first fecal passage, and the lowest LOH and hospitalization expenses of the three groups. The incidence of pneumonia was by far the highest in Group 3 (p = 0.019. Finally, all the postoperative outcomes of nutritional conditions were the worst by a significant margin in Group 3. It is therefore safe and valid to start early enteral nutrition within 48 h for postoperative esophageal cancer patients.

  17. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

    OpenAIRE

    Yuan, Zhi-xiang; Mo, Jingxin; Zhao, Guixian; Shu, Gang; Fu, Hua-Lin; Wei ZHAO

    2016-01-01

    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rati...

  18. Peers without fears? Barriers to effective communication among primary care physicians and oncologists about diagnostic delays in cancer.

    Science.gov (United States)

    Lipitz-Snyderman, Allison; Kale, Minal; Robbins, Laura; Pfister, David; Fortier, Elizabeth; Pocus, Valerie; Chimonas, Susan; Weingart, Saul N

    2017-11-01

    Relatively little attention has been devoted to the role of communication between physicians as a mechanism for individual and organisational learning about diagnostic delays. This study's objective was to elicit physicians' perceptions about and experiences with communication among physicians regarding diagnostic delays in cancer. Qualitative analysis based on seven focus groups. Fifty-one physicians affiliated with three New York-based academic medical centres participated, with six to nine subjects per group. We used content analysis to identify commonalities among primary care physicians and specialists (ie, medical and surgical oncologists). Perceptions and experiences with physician-to-physician communication about delays in cancer diagnosis. Our analysis identified five major themes: openness to communication, benefits of communication, fears about giving and receiving feedback, infrastructure barriers to communication and overcoming barriers to communication. Subjects valued communication about cancer diagnostic delays, but they had many concerns and fears about providing and receiving feedback in practice. Subjects expressed reluctance to communicate if there was insufficient information to attribute responsibility, if it would have no direct benefit or if it would jeopardise their existing relationships. They supported sensitive approaches to conveying information, as they feared eliciting or being subject to feelings of incompetence or shame. Subjects also cited organisational barriers. They offered suggestions that might facilitate communication about delays. Addressing the barriers to communication among physicians about diagnostic delays is needed to promote a culture of learning across specialties and institutions. Supporting open and honest discussions about diagnostic delays may help build safer health systems. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use

  19. Tumor associated macrophage × cancer cell hybrids may acquire cancer stem cell properties in breast cancer.

    Directory of Open Access Journals (Sweden)

    Jingxian Ding

    Full Text Available Breast cancer is one of the most frequently diagnosed cancers among women, and metastasis makes it lethal. Tumor-associated macrophages (TAMs that acquire an alternatively activated macrophage (M2 phenotype may promote metastasis. However, the underlying mechanisms are still elusive. Here, we examined how TAMs interact with breast cancer cells to promote metastasis. Immunohistochemistry was used to examine the expression of the M2-specific antigen CD163 in paraffin-embedded mammary carcinoma blocks to explore fusion events in breast cancer patients. U937 cells were used as a substitute for human monocytes, and these cells differentiated into M2 macrophages following phorbol 12-myristate 13-acetate (PMA and M-CSF stimulation. M2 macrophages and the breast cancer cell lines MCF-7 and MDA-MB-231 fused in the presence of 50% polyethylene glycol. Hybrids were isolated by fluorescence-activated cell sorting, and the relevant cell biological properties were compared with their parental counterparts. Breast cancer stem cell (BCSC-related markers were quantified by immunofluorescence staining, RT-PCR, quantitative RT-PCR and/or western blotting. The tumor-initiating and metastatic capacities of the hybrids and their parental counterparts were assessed in NOD/SCID mice. We found that the CD163 expression rate in breast cancer tissues varied significantly and correlated with estrogen receptor status (p0.05. Characterization of the fusion hybrids revealed a more aggressive phenotype, including increased migration, invasion and tumorigenicity, but reduced proliferative ability, compared with the parental lines. The hybrids also gained a CD44(+CD24(-/low phenotype and over-expressed epithelial-mesenchymal transition-associated genes. These results indicate that TAMs may promote breast cancer metastasis through cell fusion, and the hybrids may gain a BCSC phenotype.

  20. An adenoviral cancer vaccine co-encoding a tumor associated antigen together with secreted 4-1BBL leads to delayed tumor progression

    DEFF Research Database (Denmark)

    Ragonnaud, Emeline; Andersson, Anne-Marie C; Pedersen, Anders Elm

    2016-01-01

    ) in a replicative deficient adenovirus vaccine expressing the invariant chain (Ii) adjuvant fused to a tumor associated antigen (TAA). The Ii adjuvant increases and prolongs TAA specific CD8+ T cells as previously shown and local expression of 4-1BBL was chosen to avoid the toxicity associated with systemic...... presenting cells, but it did not enhance T cell responses in mice towards the Ii linked antigen. In tumor-bearing mice, our vaccine was found to decrease the frequency of TAA specific CD8+ T cells, but this difference did not alter the therapeutic efficacy. In order to reconcile our findings...... with the previous reports of increased anti-cancer efficacy using systemically delivered 4-1BB agonists, we incorporated a secreted version of 4-1BBL (Fc-4-1BBL) in our vaccine and co-expressed it with the Ii linked to TAA. In tumor bearing mice, this vaccine initially delayed tumor growth and slightly increased...

  1. Molecular Characterization of Androgen Independence to Delay Progression to Hormone Refractory Prostate Cancer

    Science.gov (United States)

    2005-03-01

    repair that removes 8-oxoguanine, a highly mutagenic oxidative DNA adduct. This enzyme has been shown to undergo mutation during cancer progression...variant CLI cell line. The frequency of each MPSS signature was calculated for each sample and represented in tpm (transcripts per million). We...lase is an enzyme involved in DNA repair that removes blocking IL-6 expression may have no or minimal 8-oxoguanine, a highly mutagenic oxidative DNA

  2. Delay in diagnosis of cancer as a patient safety issue - a root cause analysis based on a representative case report

    Directory of Open Access Journals (Sweden)

    Mansour Paul

    2011-07-01

    Full Text Available Abstract Background It is well known in the literature that imaging has almost no value for diagnosis of superficial bladder cancer. However, wide gap exists between knowledge on diagnosis of bladder cancer and actual clinical practice. Case presentation Delay in diagnosis of bladder cancer in a male person with tetraplegia occurred because of reliance on negative flexible cystoscopy and single biopsy, negative ultrasound examination of urinary bladder, and computerised tomography of pelvis. Difficulties in scheduling cystoscopy also contributed to a delay of nearly ten months between the onset of haematuria and establishing a histological diagnosis of vesical malignancy in this patient. The time interval between transurethral resection and cystectomy was 42 days. This delay was mainly due to scheduling of surgery. Conclusion We learn from this case that doctors should be aware of the limitations of negative flexible cystoscopy and single biopsy, cytology of urine, ultrasound examination of urinary bladder, and computed tomography of pelvis for diagnosis of bladder cancer in spinal cord injury patients. Random bladder biopsies must be considered under general anaesthesia when there is high suspicion of bladder cancer. Spinal cord injury patients with lesions above T-6 may develop autonomic dysreflexia; therefore, one should be extremely well prepared to prevent or manage autonomic dysreflexia when performing cystoscopy and bladder biopsy. Spinal cord injury patients, who pass blood in urine, should be accorded top priority in scheduling of investigations and surgical procedures.

  3. Radiofrequency treatment alters cancer cell phenotype

    Science.gov (United States)

    Ware, Matthew J.; Tinger, Sophia; Colbert, Kevin L.; Corr, Stuart J.; Rees, Paul; Koshkina, Nadezhda; Curley, Steven; Summers, H. D.; Godin, Biana

    2015-07-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment.

  4. Ovarian Cancer Stem Cells: A New Target for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Qinglei Zhan

    2013-01-01

    Full Text Available Ovarian cancer is a highly lethal disease among all gynecologic malignancies and is the fifth leading cause of cancer-related death in women. Although the standard combination of surgery and chemotherapy was initially effective in patients with ovarian cancer, disease relapse commonly occurred due to the generation of chemoresistance. It has been reported that cancer stem cells (CSCs are involved in drug resistance and cancer recurrence. Over the past decades, increasing studies have been done to identify CSCs from human ovarian cancer cells. The present paper will summarize different investigations on ovarian CSCs, including isolation, mechanisms of chemoresistance, and therapeutic approaches. Although there are still numerous challenges to translate basic research to clinical applications, understanding the molecular details of CSCs is essential for developing effective strategies to prevent ovarian cancer and its recurrence.

  5. Cancer stem cell targeted therapy: progress amid controversies

    Science.gov (United States)

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  6. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  7. Treatment Option Overview (Small Cell Lung Cancer)

    Science.gov (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  8. General Information about Small Cell Lung Cancer

    Science.gov (United States)

    ... inside of the lungs. Enlarge Anatomy of the respiratory system, showing the trachea and both lungs and their ... Cell Lung Cancer Tobacco (includes help with quitting) Cigarette Smoking: Health Risks and How to Quit Secondhand Smoke and Cancer For general cancer information and other ...

  9. Random start ovarian stimulation for fertility preservation appears unlikely to delay initiation of neoadjuvant chemotherapy for breast cancer.

    Science.gov (United States)

    Letourneau, Joseph M; Sinha, Nikita; Wald, Kaitlyn; Harris, Eve; Quinn, Molly; Imbar, Tal; Mok-Lin, Evelyn; Chien, A Jo; Rosen, Mitchell

    2017-10-01

    Is random start ovarian stimulation associated with delays in initiation of neoadjuvant chemotherapy for breast cancer? Among women who complete fertility preservation (FP) consultation, random start ovarian stimulation is unlikely to delay time to initiation of neoadjuvant chemotherapy start. Neoadjuvant chemotherapy is now a widely accepted treatment modality for operable breast cancer and random start ovarian stimulation is an increasingly-utilized modality for FP. While conventional ovarian stimulation does not appear to delay starting adjuvant chemotherapy, the relationship between random start ovarian stimulation and neoadjuvant chemotherapy start is not well-understood. Cross-sectional study of all women seen between from January 2011 to April 2017 for FP consultation prior to starting neoadjuvant chemotherapy for breast cancer. A chart-review was performed. Study inclusion criteria were female sex; age 18-45; non-metastatic breast cancer diagnosis; underwent FP consultation; underwent neoadjuvant chemotherapy. Referrals for FP evaluation came from a regional referral base of oncology clinics. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. We compared time-points between those who underwent ovarian stimulation for FP versus those who did not using T-tests and linear modeling. A total of 89 women who had FP consultation prior to neoadjuvant chemotherapy were identified. Sixty-seven percent underwent ovarian stimulation prior to cancer treatment and 33% did not. Women who underwent ovarian stimulation were similar in parity and clinical cancer stage to those who did not. Overall, the average time from cancer diagnosis to chemotherapy start was similar between the group that did undergo ovarian stimulation and those who did not (38.1 ± 11.3 versus 39.4 ± 18.5 days, P = 0.672). Those that underwent ovarian stimulation were referred 9.4 ± 6.8 days after diagnosis versus 17.9 ± 15.3 days for those

  10. Deficiency in the 15 kDa Selenoprotein Inhibits Human Colon Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Ryuta Tobe

    2011-09-01

    Full Text Available Selenium is an essential micronutrient for humans and animals, and is thought to provide protection against some forms of cancer. These protective effects appear to be mediated, at least in part, through selenium-containing proteins (selenoproteins. Recent studies in a mouse colon cancer cell line have shown that the 15 kDa selenoprotein (Sep15 may also play a role in promoting colon cancer. The current study investigated whether the effects of reversing the cancer phenotype observed when Sep15 was removed in mouse colon cancer cells, were recapitulated in HCT116 and HT29 human colorectal carcinoma cells. Targeted down-regulation of Sep15 using RNAi technology in these human colon cancer cell lines resulted in similarly decreased growth under anchorage-dependent and anchorage-independent conditions. However, the magnitude of reduction in cell growth was much less than in the mouse colon cancer cell line investigated previously. Furthermore, changes in cell cycle distribution were observed, indicating a delayed release of Sep15 deficient cells from the G0/G1 phase after synchronization. The potential mechanism by which human colon cancer cells lacking Sep15 revert their cancer phenotype will need to be explored further.

  11. Cancer stem cells of the digestive system.

    Science.gov (United States)

    Colvin, Hugh S; Nishida, Naohiro; Koseki, Jun; Konno, Masamitsu; Kawamoto, Koichi; Tsunekuni, Kenta; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2014-12-01

    Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Molecular Biology of Liver Cancer Stem Cells

    National Research Council Canada - National Science Library

    Oishi, Naoki; Yamashita, Taro; Kaneko, Shuichi

    2014-01-01

    .... The concept of cancer stem cells (CSCs) is based primarily on the clinical and experimental observations that indicate the existence of a subpopulation of cells with the capacity to self-renew and differentiate as well as show increased...

  13. Cancer Stem Cells: Repair Gone Awry?

    Directory of Open Access Journals (Sweden)

    Fatima Rangwala

    2011-01-01

    Full Text Available Because cell turnover occurs in all adult organs, stem/progenitor cells within the stem-cell niche of each tissue must be appropriately mobilized and differentiated to maintain normal organ structure and function. Tissue injury increases the demands on this process, and thus may unmask defective regulation of pathways, such as Hedgehog (Hh, that modulate progenitor cell fate. Hh pathway dysregulation has been demonstrated in many types of cancer, including pancreatic and liver cancers, in which defective Hh signaling has been linked to outgrowth of Hh-responsive cancer stem-initiating cells and stromal elements. Hence, the Hh pathway might be a therapeutic target in such tumors.

  14. Silent Crooke’s cell corticotroph adenoma of the pituitary gland presenting as delayed puberty

    Directory of Open Access Journals (Sweden)

    Dinesh Giri

    2017-03-01

    Full Text Available Corticotroph adenomas are extremely rare in children and adolescents. We present a 15-year-old boy who was investigated for delayed puberty (A1P2G1, bilateral testicular volumes of 3 mL each. There was no clinical or laboratory evidence suggestive of chronic illness, and the initial clinical impression was constitutional delay in puberty. Subsequently, MRI scan of the brain revealed the presence of a mixed cystic and solid pituitary lesion slightly displacing the optic chiasma. The lesion was removed by transphenoidal surgery and the biopsy confirmed the lesion to be pituitary adenoma. Furthermore, the adenoma cells also had Crooke’s hyaline changes and were intensely positive for ACTH. However there was no clinical/biochemical evidence of ACTH excess. There was a spontaneous pubertal progression twelve months after the surgery (A2P4G4, with bilateral testicular volume of 8 mL. Crooke’s cell adenoma is an extremely rare and aggressive variant of corticotroph adenoma that can uncommonly present as a silent corticotroph adenoma in adults. We report for the first time Crooke’s cell adenoma in an adolescent boy presenting with delayed puberty.

  15. Impact of social and clinical factors on diagnostic delay of breast cancer: A Cross-sectional Study.

    Science.gov (United States)

    Dianatinasab, Mostafa; Fararouei, Mohammad; Mohammadianpanah, Mohammad; Zare-Bandamiri, Mohammad

    2016-09-01

    One of the reasons for high mortality of breast cancer is long delay in seeking medical care. This study was designed to measure the association of a wide range of socio-demographic and clinical factors with the diagnostic delay in breast cancer among Iranian patients.This study was conducted on 505 newly diagnosed patients with breast cancer from southern part of Iran. Medical files of the patients who were admitted to the hospital from November 2013 to May 2015 were examined and clinical and demographic information were extracted.According to the results, illiterate patients were diagnosed on average 87.42 days later compared with those with a college degree (95%CI: 29.68-145.16, P = 0.003) and those from rural area were diagnosed on average 72.48 days later (95%CI: 35.94-109.03, P = 0.001) compared with urban residences. Single women were diagnosed 65.99 days later (95%CI: 7.37-124.61, P = 0.02) compared with those married. Lobular or medullary types of cancer were diagnosed 65.19 days later (95%CI: 2.67-127.70, P = 0.04) compared with ductal type. On the other hand, those who were able to perform breast self-exam were diagnosed 49.07 days earlier compared with others (95%CI: 18.69-79.45, P = 0.002). Those felt lump as the initiating symptom were diagnosed 62.01 days earlier, (95%CI: 8.17-115.85, P = 0.02) compared with those with other initial symptoms. The only factor associated with doctors diagnosis delay was the place of residence as rural residences were diagnosed on average 87.42 days later compared with urban residences, (95%CI: 53.82-121.92, P = 0.001).Higher education, living in cities, ductal type of tumor, and noticing lump in breast were the most important demographic and clinical factors associated with shorter breast cancer diagnosis delay. Informing women and doctors, especially general physicians who are practicing in rural areas, of the common symptoms of breast cancer as well as training women to perform breast self-examination are effective

  16. Value of the Post-Operative CT in Predicting Delayed Flap Failures Following Head and Neck Cancer Surgery.

    Science.gov (United States)

    Kim, Bitna; Yoon, Dae Young; Seo, Young Lan; Park, Min Woo; Kwon, Kee Hwan; Rho, Young-Soo; Chung, Chul Hoon

    2017-01-01

    To identify post-operative computed tomography (CT) findings associated with delayed flap failures following head and neck cancer surgery. We retrospectively reviewed 60 patients who underwent flap reconstruction after head and neck cancer surgery and post-operative (3-14 days) contrast-enhanced CT scans for suspected complications. Patients were divided into two groups: delayed flap failure patients (patients required flap revision) (n = 18) and flap success patients (n = 42). Clinical data (age, sex, T-stage, type of flap, and time interval between reconstruction surgery and CT) and post-operative CT findings of flap status (maximum dimension of the flap, intra- or peri-flap fluid collection and intra- or peri-flap air collection, fat infiltration within the flap, fistula to adjacent aerodigestive tract or skin, and enhanced vascular pedicle) were assessed and compared between the two groups. CT findings showed that the following flap anomalies were observed more frequently in the delayed flap failure group than in the flap success group: intra- or peri-flap fluid collection > 4 cm (61.1% vs. 23.8%, p 2 cm (61.1% vs. 2.4%, p failures. A large amount of fluid or air collection and fistula are the CT findings that were associated with delayed flap failures in patients with suspected post-operative complications after head and neck cancer surgery.

  17. Help seeking behavior of women with self-discovered breast cancer symptoms: a meta-ethnographic synthesis of patient delay.

    Directory of Open Access Journals (Sweden)

    Zohreh Khakbazan

    Full Text Available BACKGROUND AND OBJECTIVE: Patient delay makes a critical contribution to late diagnosis and poor survival in cases of breast cancer. Identifying the factors that influence patient delay could provide information for adopting strategies that shorten this delay. The aim of this meta-ethnography was to synthesize existing qualitative evidence in order to gain a new understanding of help seeking behavior in women with self-discovered breast cancer symptoms and to determine the factors that influence patient delay. METHODS: The design was a meta-ethnography approach. A systematic search of the articles was performed in different databases including Elsevier, PubMed, ProQuest and SCOPUS. Qualitative studies with a focus on help seeking behaviors in women with self-discovered breast cancer symptoms and patient delay, published in the English language between 1990 and 2013 were included. The quality appraisal of the articles was carried out using the Critical Appraisal Skills Programme qualitative research checklist and 13 articles met the inclusion criteria. The synthesis was conducted according to Noblit and Hare's meta-ethnographic approach (1988, through reciprocal translational analysis and lines-of-argument. FINDINGS: The synthesis led to identification of eight repeated key concepts including: symptom detection, initial symptom interpretation, symptom monitoring, social interaction, emotional reaction, priority of medical help, appraisal of health services and personal-environmental factors. Symptom interpretation is identified as the important step of the help seeking process and which changed across the process through active monitoring of their symptoms, social interactions and emotional reactions. The perceived seriousness of the situation, priority to receive medical attention, perceived inaccessibility and unacceptability of the health care system influenced women's decision-making about utilizing health services. CONCLUSION: Help seeking

  18. NK Cells and Virus-Related Cancers

    OpenAIRE

    Mishra, Rabinarayan; Welsh, Raymond M.; Szomolanyi-Tsuda, Eva

    2014-01-01

    Natural killer (NK) cells become activated during viral infections and can play roles in such infections by attacking virus-infected cells or by regulating adaptive immune responses. Experimental models suggest that NK cells may also have the capacity to restrain virus-induced cancers. Here, we discuss the seven viruses linked to human cancers and the evidence of NK cell involvement in these systems.

  19. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics ......, help us both in the identification and characterization of cancer stem cells and in the further development of therapeutic strategies including tissue engineering...

  20. Small interfering RNA targeted to IGF-IR delays tumor growth and induces proinflammatory cytokines in a mouse breast cancer model.

    Directory of Open Access Journals (Sweden)

    Tiphanie Durfort

    Full Text Available Insulin-like growth factor I (IGF-I and its type I receptor (IGF-IR play significant roles in tumorigenesis and in immune response. Here, we wanted to know whether an RNA interference approach targeted to IGF-IR could be used for specific antitumor immunostimulation in a breast cancer model. For that, we evaluated short interfering RNA (siRNAs for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice. We designed 2'-O-methyl-modified siRNAs to inhibit expression of IGF-IR in two murine breast cancer cell lines (EMT6, C4HD. Cell transfection of IGF-IR siRNAs decreased proliferation, diminished phosphorylation of downstream signaling pathway proteins, AKT and ERK, and caused a G0/G1 cell cycle block. The IGF-IR silencing also induced secretion of two proinflammatory cytokines, TNF- α and IFN-γ. When we transfected C4HD cells with siRNAs targeting IGF-IR, mammary tumor growth was strongly delayed in syngenic mice. Histology of developing tumors in mice grafted with IGF-IR siRNA treated C4HD cells revealed a low mitotic index, and infiltration of lymphocytes and polymorphonuclear neutrophils, suggesting activation of an antitumor immune response. When we used C4HD cells treated with siRNA as an immunogen, we observed an increase in delayed-type hypersensitivity and the presence of cytotoxic splenocytes against wild-type C4HD cells, indicative of evolving immune response. Our findings show that silencing IGF-IR using synthetic siRNA bearing 2'-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF-IR. Interestingly, our work also suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines.

  1. Targeting the osteosarcoma cancer stem cell

    Directory of Open Access Journals (Sweden)

    Qin Ling

    2010-10-01

    Full Text Available Abstract Osteosarcoma is the most common type of solid bone cancer and the second leading cause of cancer-related death in pediatric patients. Many patients are not cured by the current osteosarcoma therapy consisting of combination chemotherapy along with surgery and thus new treatments are urgently needed. In the last decade, cancer stem cells have been identified in many tumors such as leukemia, brain, breast, head and neck, colon, skin, pancreatic, and prostate cancers and these cells are proposed to play major roles in drug resistance, tumor recurrence, and metastasis. Recent studies have shown evidence that osteosarcoma also possesses cancer stem cells. This review summarizes the current knowledge about the osteosarcoma cancer stem cell including the methods used for its isolation, its properties, and its potential as a new target for osteosarcoma treatment.

  2. Disrupting Na+,HCO3--cotransporter NBCn1 (Slc4a7) delays murine breast cancer development

    DEFF Research Database (Denmark)

    Lee, S.; Axelsen, T. V.; Andersen, Anne Poder

    2016-01-01

    . Genome-wide association studies have indicated a possible link between the Na(+),HCO3(-)-cotransporter NBCn1 (SLC4A7) and breast cancer. We tested the functional consequences of NBCn1 knockout (KO) for breast cancer development. NBCn1 protein expression increased 2.5-fold during breast carcinogenesis...... and was responsible for the increased net acid extrusion and alkaline intracellular pH of breast cancer compared with normal breast tissue. Genetic disruption of NBCn1 delayed breast cancer development: tumor latency was ~50% increased while tumor growth rate was ~65% reduced in NBCn1 KO compared with wild-type (WT......) mice. Breast cancer histopathology in NBCn1 KO mice differed from that in WT mice and included less aggressive tumor types. The extracellular tumor microenvironment in NBCn1 KO mice contained higher concentrations of glucose and lower concentrations of lactate than that in WT mice. Independently...

  3. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-01-26

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

  4. Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Aftab, Blake T. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rudin, Charles M. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K., E-mail: rhales1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-05-01

    Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras{sup G12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.

  5. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

    Science.gov (United States)

    2015-07-01

    dominant role over some oncogene function.In addition, we recently reported that cancer stem cells (CSCs)- stem cell like cells in tumors that have stem ... cell properties and tumor initiating ability- retain epigenetic memories of their cells of origin (Chow et al., 2014). We showed that CSCs derived from

  6. Targeting senescence cells in pancreatic cancer | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Targeting senescence cells in pancreatic cancer. Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination.

  7. Betulinic Acid Kills Colon Cancer Stem Cells

    NARCIS (Netherlands)

    Potze, Lisette; Di Franco, Simone; Kessler, Jan H.; Stassi, Giorgio; Medema, Jan Paul

    2016-01-01

    Cancer stem cells (CSCs) are considered to be the origin of cancer and it is suggested that they are resistant to chemotherapy. Current therapies fail to eradicate CSCs and therefore selecting a resistant cell subset that is able to facilitate tumor recurrences. Betulinic acid (BetA) is a broad

  8. Effect of ranitidine on postoperative suppression of natural killer cell activity and delayed hypersensitivity

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Pedersen, B K; Moesgaard, F

    1989-01-01

    In a randomized study of patients undergoing major elective abdominal surgery, 12 received i.v. ranitidine (50 mg every 6 hours for 72 hours from the skin incision) and 12 had no ranitidine. Cell-mediated immunity was assessed pre- and postoperatively by skin testing with seven common delayed type...... hypersensitivity (DTH) antigens, and blood drawn immediately before and 24 hours after skin incision was analyzed for spontaneous and in vitro stimulated (IL-2, IFN-alpha or indomethacin) natural killer (NK) cell activity and PHA and PPD-stimulated lymphocyte proliferation. Lymphocyte subsets (helper...

  9. A cancer cell-specific fluorescent probe for imaging Cu2 + in living cancer cells

    Science.gov (United States)

    Wang, Chao; Dong, Baoli; Kong, Xiuqi; Song, Xuezhen; Zhang, Nan; Lin, Weiying

    2017-07-01

    Monitoring copper level in cancer cells is important for the further understanding of its roles in the cell proliferation, and also could afford novel copper-based strategy for the cancer therapy. Herein, we have developed a novel cancer cell-specific fluorescent probe for the detecting Cu2 + in living cancer cells. The probe employed biotin as the cancer cell-specific group. Before the treatment of Cu2 +, the probe showed nearly no fluorescence. However, the probe can display strong fluorescence at 581 nm in response to Cu2 +. The probe exhibited excellent sensitivity and high selectivity for Cu2 + over the other relative species. Under the guidance of biotin group, could be successfully used for detecting Cu2 + in living cancer cells. We expect that this design strategy could be further applied for detection of the other important biomolecules in living cancer cells.

  10. Are cancer cells really softer than normal cells?

    Science.gov (United States)

    Alibert, Charlotte; Goud, Bruno; Manneville, Jean-Baptiste

    2017-05-01

    Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  11. Are Survivors Who Report Cancer-Related Financial Problems More Likely to Forgo or Delay Medical Care?

    Science.gov (United States)

    Kent, Erin E.; Forsythe, Laura P.; Yabroff, K. Robin; Weaver, Kathryn E.; de Moor, Janet S.; Rodriguez, Juan L.; Rowland, Julia H.

    2015-01-01

    BACKGROUND Financial problems caused by cancer and its treatment can substantially affect survivors and their families and create barriers to seeking health care. METHODS The authors identified cancer survivors diagnosed as adults (n = 1556) from the nationally representative 2010 National Health Interview Survey. Using multivariable logistic regression analyses, the authors report sociodemographic, clinical, and treatment-related factors associated with perceived cancer-related financial problems and the association between financial problems and forgoing or delaying health care because of cost. Adjusted percentages using the predictive marginals method are presented. RESULTS Cancer-related financial problems were reported by 31.8% (95% confidence interval, 29.3%–34.5%) of survivors. Factors found to be significantly associated with cancer-related financial problems in survivors included younger age at diagnosis, minority race/ethnicity, history of chemotherapy or radiation treatment, recurrence or multiple cancers, and shorter time from diagnosis. After adjustment for covariates, respondents who reported financial problems were more likely to report delaying (18.3% vs 7.4%) or forgoing overall medical care (13.8% vs 5.0%), prescription medications (14.2% vs 7.6%), dental care (19.8% vs 8.3%), eyeglasses (13.9% vs 5.8%), and mental health care (3.9% vs 1.6%) than their counterparts without financial problems (all Pfinancial problems are not only disproportionately represented in survivors who are younger, members of a minority group, and have a higher treatment burden, but may also contribute to survivors forgoing or delaying medical care after cancer. PMID:23907958

  12. Of germ cells, trophoblasts, and cancer stem cells.

    Science.gov (United States)

    Burleigh, Angela R

    2008-12-01

    The trophoblastic theory of cancer, proposed in the early 1900s by Dr John Beard, may not initially seem relevant to current cancer models and treatments. However, the underpinnings of this theory are remarkably similar to those of the cancer stem cell (CSC) theory. Beard noticed that a significant fraction of germ cells never reach their final destination as they migrate during embryonic development from the hindgut to the germinal ridge. In certain situations, upon aberrant stimulation, these vagrant germ cells are able to generate tumors. Simplistically, the CSC theory surmises that a small population of tumorigenic cells exists, which initiate and maintain tumors, and these cells have a likely origin in normal stem cells. Both these theories are based on the potential of a single primitive cell to form a tumor. This has a major implication for cancer therapy, in that only a small percentage of cells need to be targeted to ablate a tumor.

  13. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

    Energy Technology Data Exchange (ETDEWEB)

    Heravi, Mitra [Department of Human Genetics, McGill University, Montreal (Canada); Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Kumala, Slawomir [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada); Rachid, Zakaria; Jean-Claude, Bertrand J. [Cancer Drug Research Laboratory, McGill University Health Center, Montreal (Canada); Radzioch, Danuta [Department of Human Genetics, McGill University, Montreal (Canada); Muanza, Thierry M., E-mail: tmuanza@yahoo.com [Department of Radiation Oncology, McGill University, Montreal (Canada); Segal Cancer Center, Jewish General Hospital, Montreal (Canada)

    2015-06-01

    Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Western blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.

  14. Single Cell Characterization of Prostate Cancer Circulating Tumor Cells

    Science.gov (United States)

    2011-08-01

    CTCs from patient blood, a single T24 bladder and LNCaP prostate cancer cells, a pool of 8 prostate CTCs, and one leukocyte isolated from the blood...amplify 66% of mRNA pool from a single cell. Clustering analysis does differentiate CTCs from LNCaP and T24 bladder cell lines (Figure 4). At present we...profiles could distinguish a CTC from prostate cancer cell line LNCaP and T24 bladder cancer cell line.  There was intra and inter patient heterogeneity

  15. The use of artificial neural networks to predict delayed discharge and readmission in enhanced recovery following laparoscopic colorectal cancer surgery.

    Science.gov (United States)

    Francis, N K; Luther, A; Salib, E; Allanby, L; Messenger, D; Allison, A S; Smart, N J; Ockrim, J B

    2015-07-01

    Artificial neural networks (ANNs) can be used to develop predictive tools to enable the clinical decision-making process. This study aimed to investigate the use of an ANN in predicting the outcomes from enhanced recovery after colorectal cancer surgery. Data were obtained from consecutive colorectal cancer patients undergoing laparoscopic surgery within the enhanced recovery after surgery (ERAS) program between 2002 and 2009 in a single center. The primary outcomes assessed were delayed discharge and readmission within a 30-day period. The data were analyzed using a multilayered perceptron neural network (MLPNN), and a prediction tools were created for each outcome. The results were compared with a conventional statistical method using logistic regression analysis. A total of 275 cancer patients were included in the study. The median length of stay was 6 days (range 2-49 days) with 67 patients (24.4 %) staying longer than 7 days. Thirty-four patients (12.5 %) were readmitted within 30 days. Important factors predicting delayed discharge were related to failure in compliance with ERAS, particularly with the postoperative elements in the first 48 h. The MLPNN for delayed discharge had an area under a receiver operator characteristic curve (AUROC) of 0.817, compared with an AUROC of 0.807 for the predictive tool developed from logistic regression analysis. Factors predicting 30-day readmission included overall compliance with the ERAS pathway and receiving neoadjuvant treatment for rectal cancer. The MLPNN for readmission had an AUROC of 0.68. These results may plausibly suggest that ANN can be used to develop reliable outcome predictive tools in multifactorial intervention such as ERAS. Compliance with ERAS can reliably predict both delayed discharge and 30-day readmission following laparoscopic colorectal cancer surgery.

  16. Triiodothyronine regulates cell growth and survival in renal cell cancer.

    Science.gov (United States)

    Czarnecka, Anna M; Matak, Damian; Szymanski, Lukasz; Czarnecka, Karolina H; Lewicki, Slawomir; Zdanowski, Robert; Brzezianska-Lasota, Ewa; Szczylik, Cezary

    2016-10-01

    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle.

  17. Modeling a snap-action, variable-delay switch controlling extrinsic cell death.

    Directory of Open Access Journals (Sweden)

    John G Albeck

    2008-12-01

    Full Text Available When exposed to tumor necrosis factor (TNF or TNF-related apoptosis-inducing ligand (TRAIL, a closely related death ligand and investigational therapeutic, cells enter a protracted period of variable duration in which only upstream initiator caspases are active. A subsequent and sudden transition marks activation of the downstream effector caspases that rapidly dismantle the cell. Thus, extrinsic apoptosis is controlled by an unusual variable-delay, snap-action switch that enforces an unambiguous choice between life and death. To understand how the extrinsic apoptosis switch functions in quantitative terms, we constructed a mathematical model based on a mass-action representation of known reaction pathways. The model was trained against experimental data obtained by live-cell imaging, flow cytometry, and immunoblotting of cells perturbed by protein depletion and overexpression. The trained model accurately reproduces the behavior of normal and perturbed cells exposed to TRAIL, making it possible to study switching mechanisms in detail. Model analysis shows, and experiments confirm, that the duration of the delay prior to effector caspase activation is determined by initiator caspase-8 activity and the rates of other reactions lying immediately downstream of the TRAIL receptor. Sudden activation of effector caspases is achieved downstream by reactions involved in permeabilization of the mitochondrial membrane and relocalization of proteins such as Smac. We find that the pattern of interactions among Bcl-2 family members, the partitioning of Smac from its binding partner XIAP, and the mechanics of pore assembly are all critical for snap-action control.

  18. Delayed persistence of giant-nucleated cells induced by X-ray and proton irradiation in the progeny of replicating normal human f ibroblast cells

    Science.gov (United States)

    Almahwasi, A. A.; Jeynes, J. C.; Merchant, M. J.; Bradley, D. A.; Regan, P. H.

    2017-08-01

    Ionising radiation can induce giant-nucleated cells (GCs) in the progeny of irradiated populations, as demonstrated in various cellular systems. Most in vitro studies have utilised quiescent cancerous or normal cell lines but it is not clear whether radiation-induced GCs persist in the progeny of normal replicated cells. In the current work we show persistent induction of GCs in the progeny of normal human-diploid skin fibroblasts (AG1522). These cells were originally irradiated with a single equivalent clinical dose of 0.2, 1 or 2 Gy of either X-ray or proton irradiation and maintained in an active state for various post-irradiation incubation interval times before they were replated for GC analysis. The results demonstrate that the formation of GCs in the progeny of X-ray or proton irradiated cells was increased in a dose-dependent manner when measured 7 days after irradiation and this finding is in agreement with that reported for the AG1522 cells using other radiation qualities. For the 1 Gy X-ray doses it was found that the GC yield increased continually with time up to 21 days post-irradiation. These results can act as benchmark data for such work and may have important implications for studies aimed at evaluating the efficacy of radiation therapy and in determining the risk of delayed effects particularly when applying protons.

  19. Response of breast cancer cells and cancer stem cells to metformin and hyperthermia alone or combined.

    Directory of Open Access Journals (Sweden)

    Hyemi Lee

    Full Text Available Metformin, the most widely prescribed drug for treatment of type 2 diabetes, has been shown to exert significant anticancer effects. Hyperthermia has been known to kill cancer cells and enhance the efficacy of various anti-cancer drugs and radiotherapy. We investigated the combined effects of metformin and hyperthermia against MCF-7 and MDA-MB-231 human breast cancer cell, and MIA PaCa-2 human pancreatic cancer cells. Incubation of breast cancer cells with 0.5-10 mM metformin for 48 h caused significant clonogenic cell death. Culturing breast cancer cells with 30 µM metformin, clinically relevant plasma concentration of metformin, significantly reduced the survival of cancer cells. Importantly, metformin was preferentially cytotoxic to CD44(high/CD24(low cells of MCF-7 cells and, CD44(high/CD24(high cells of MIA PaCa-2 cells, which are known to be cancer stem cells (CSCs of MCF-7 cells and MIA PaCa-2 cells, respectively. Heating at 42°C for 1 h was slightly toxic to both cancer cells and CSCs, and it markedly enhanced the efficacy of metformin to kill cancer cells and CSCs. Metformin has been reported to activate AMPK, thereby suppressing mTOR, which plays an important role for protein synthesis, cell cycle progression, and cell survival. For the first time, we show that hyperthermia activates AMPK and inactivates mTOR and its downstream effector S6K. Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K. Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR. It is conclude that the effects of metformin against cancer cells including CSCs can be markedly enhanced by hyperthermia.

  20. Cancer stem cells in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Trapasso S

    2012-11-01

    Full Text Available Eugenia Allegra, Serena TrapassoOtolaryngology – Head and Neck Surgery, University Magna Graecia of Catanzaro, Catanzaro, ItalyAbstract: Cancer stem cells (CSCs, also called "cells that start the tumor," represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal, giving rise both to other tumor stem cells and most advanced cells in the line of differentiation (asymmetric division. A final characteristic is tumorigenicity, a fundamental property, which outlines the tumor stem cell as the only cell able to initiate the formation of a tumor when implanted in immune-deficient mice. The hypothesis of a hierarchical organization of tumor cells dates back more than 40 years, but only in 1997, thanks to the work of John Dick and Dominique Bonnet, was there the formal proof of such an organization in acute myeloid leukemia. Following this, many other research groups were able to isolate CSCs, by appropriate selection markers, in various malignancies, such as breast, brain, colon, pancreas, and liver cancers and in melanoma. To date, however, it is not possible to isolate stem cells from all types of neoplasia, particularly in solid tumors. From a therapeutic point of view, the concept of tumor stem cells implies a complete revision of conventional antineoplastic treatment. Conventional cytotoxic agents are designed to target actively proliferating cells. In the majority of cases, this is not sufficient to eliminate the CSCs, which thanks to their reduced proliferative activity and/or the presence of proteins capable of extruding chemotherapeutics from the cell are not targeted. Therefore, the theory of cancer stem cells can pose new paradigms in terms of cancer treatment. Potential approaches, even in the very early experimental stages, relate to the selective inhibition of pathways connected with self-renewal, or more specifically based on

  1. Anastomotic salvage after rectal cancer resection using the Turnbull-Cutait delayed anastomosis.

    Science.gov (United States)

    Hallet, Julie; Bouchard, Alexandre; Drolet, Sébastien; Milot, Hélène; Desrosiers, Emilie; Lebrun, Aude; Grégoire, Roger Charles

    2014-12-01

    Turnbull-Cutait abdominoperineal pull-through followed by delayed coloanal anastomosis (DCA) was first described in 1961. Studies have described its use for challenging colorectal conditions. We reviewed our experience with Turnbull-Cutait DCA as a salvage procedure for complex failure of colorectal anastomosis. We performed a retrospective cohort study from October 2010 to September 2011, with analysis of postoperative morbidity and mortality. Seven DCAs were performed for anastomotic complications (3 chronic leaks, 2 rectovaginal fistulas, 1 colovesical fistula, 1 colonic ischemia) following surgery for rectal cancer. Six patients had a diverting ileostomy constructed as part of previous treatment for anastomotic complications before the salvage procedure. No anastomotic leaks were observed. All procedures but 1 were completed successfully. One patient who underwent DCA subsequently required an abdominoperineal resection and a permanent colostomy for postoperative extensive colonic ischemia. No 30-day mortality occurred. Salvage Turnbull-Cutait DCA appears to be a safe procedure and could be offered to patients with complex anastomotic complications. This procedure could be added to the surgeon's armamentarium as an alternative to the creation of a permanent stoma.

  2. P38 delta MAPK promotes breast cancer progression and lung metastasis by enhancing cell proliferation and cell detachment.

    Science.gov (United States)

    Wada, M; Canals, D; Adada, M; Coant, N; Salama, M F; Helke, K L; Arthur, J S; Shroyer, K R; Kitatani, K; Obeid, L M; Hannun, Y A

    2017-11-23

    The protein p38 mitogen-activated protein kinase (MAPK) delta isoform (p38δ) is a poorly studied member of the MAPK family. Data analysis from The Cancer Genome Atlas database revealed that p38δ is highly expressed in all types of human breast cancers. Using a human breast cancer tissue array, we confirmed elevation in cancer tissue. The breast cancer mouse model, MMTV-PyMT (PyMT), developed breast tumors with lung metastasis; however, mice deleted in p38δ (PyMT/p38δ -/- ) exhibited delayed primary tumor formation and highly reduced lung metastatic burden. At the cellular level, we demonstrate that targeting of p38δ in breast cancer cells, MCF-7 and MDA-MB-231 resulted in a reduced rate of cell proliferation. In addition, cells lacking p38δ also displayed an increased cell-matrix adhesion and reduced cell detachment. This effect on cell adhesion was molecularly supported by the regulation of the focal adhesion kinase by p38δ in the human breast cell lines. These studies define a previously unappreciated role for p38δ in breast cancer development and evolution by regulating tumor growth and altering metastatic properties. This study proposes MAPK p38δ protein as a key factor in breast cancer. Lack of p38δ resulted in reduced primary tumor size and blocked the metastatic potential to the lungs.

  3. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    Directory of Open Access Journals (Sweden)

    Thomas W.J. Lennard

    2011-04-01

    Full Text Available In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP, have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC, combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis.

  4. Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Britton, Kelly M. [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); Kirby, John A. [Institute of Cellular Medicine, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Lennard, Thomas W.J. [Faculty of Medical Sciences, Newcastle University, 3rd Floor William Leech Building, Framlington Place, Newcastle-upon-Tyne, NE2 4HH (United Kingdom); Meeson, Annette P., E-mail: annette.meeson@ncl.ac.uk [Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom); North East England Stem Cell Institute, Bioscience Centre, International Centre for Life, Central Parkway, Newcastle-upon-Tyne, NE1 3BZ (United Kingdom)

    2011-04-19

    In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC), combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis.

  5. Correlation between induction of meiotic delay and aneuploidy in male mouse germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Adler, I.D.; Gassner, P.; Schriever-Schwemmer, G.; Min, Zhou Ru [Institut fuer Sauugetiergenetik, Neuherberg (Germany)

    1993-12-31

    No aneuploidy assays are prescribed in any international guidelines for chemical safety testing up to now. The CEC-sponsored Aneuploidy Project has the aim to validate test methods for aneuploidy induction which could be used as screening tests. Furthermore, one of the major goals is to develop an understanding of mechanisms by which aneuploidy is induced. The present paper describes the investigation of meiotic delay and aneuploidy induction with the drug diazepam (DZ), the environmentally important mutagen acrylamide (AA) and the spindle poison colchicine (COL), which is used as a positive control. The time course of events was investigated. It is concluded that the assessment of meiotic delay can be used to preselect chemicals which require evaluation of aneuploidy induction during MMI in male germ cells.

  6. Stability and bifurcation analysis in hematopoietic stem cell dynamics with multiple delays

    Science.gov (United States)

    Qu, Ying; Wei, Junjie; Ruan, Shigui

    2010-10-01

    This paper is devoted to the analysis of a maturity structured system of hematopoietic stem cell (HSC) populations in the bone marrow. The model is a system of differential equations with several time delays. We discuss the stability of equilibria and perform the analysis of Hopf bifurcation. More precisely, we first obtain a set of improved sufficient conditions ensuring the global asymptotical stability of the zero solution using the Lyapunov method and the embedding technique of asymptotically autonomous semiflows. Then we prove that there exists at least one positive periodic solution for the n-dimensional system as a time delay varies in some region. This result is established by combining Hopf bifurcation theory, the global Hopf bifurcation theorem due to Wu [J. Wu, Symmetric functional differential equations and neural networks with memory, Trans. Amer. Math. Soc. 350 (1998) 4799-4838], and a continuation theorem of coincidence degree theory. Some numerical simulations are also presented to illustrate the analytic results.

  7. Cisplatin induces differentiation of breast cancer cells.

    Science.gov (United States)

    Prabhakaran, Praseetha; Hassiotou, Foteini; Blancafort, Pilar; Filgueira, Luis

    2013-01-01

    Breast tumors are heterogeneous including cells with stem cell properties and more differentiated cells. This heterogeneity is reflected into the molecular breast cancer subtypes. Breast cancer stem cells are resistant to chemotherapy, thus recent efforts are focusing on identifying treatments that shift them toward a more differentiated phenotype, making them more susceptible to chemotherapy. We examined whether the drug cisplatin induces differentiation in breast cancer cell lines that represent different breast cancer subtypes. We used three cell lines representing triple-negative breast cancers, BT-549 and MDA-MB-231 (claudin-low), and MDA-MB-468 (basal-like), along with estrogen and progesterone receptor positive MCF-7 cells (luminal). Cisplatin was applied at 2.5, 5, 10, and 20 μM, and cell viability and proliferation were measured using MTS and BrdU assays, respectively. The effect of cisplatin on the cellular hierarchy was examined by flow cytometry, immunofluorescence and qRT-PCR. Cisplatin treatment of 10 and 20 μM reduced cell viability by 36-51% and proliferation capacity by 36-67%. Treatment with cisplatin resulted in 12-67% down-regulation of stem cell markers (CD49f, SSEA4) and 10-130% up-regulation of differentiation markers (CK18, SMA, β-tubulin). At the mRNA level, CD49f was down-regulated whilst β-tubulin was up-regulated in the claudin-low cell lines. SSEA4 protein expression decreased upon cisplatin treatment, but SSEA4 mRNA expression increased indicating a differential regulation of cisplatin at the post-transcriptional level. It is concluded that cisplatin reduces breast cancer cell survival and induces differentiation of stem/progenitor cell subpopulations within breast cancer cell lines. These effects indicate the potential of this drug to target specific chemotherapy-resistant cells within a tumor.

  8. Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly(I:C) leads to myeloid cell maturation and activates NK cells.

    Science.gov (United States)

    Kübler, Kirsten; tho Pesch, Carola; Gehrke, Nadine; Riemann, Soheila; Dassler, Juliane; Coch, Christoph; Landsberg, Jennifer; Wimmenauer, Vera; Pölcher, Martin; Rudlowski, Christian; Tüting, Thomas; Kuhn, Walther; Hartmann, Gunther; Barchet, Winfried

    2011-10-01

    Owing to high rates of tumor relapse, ovarian cancer remains a fatal disease for which new therapeutic approaches are urgently needed. Accumulating evidence indicates that immune stimulation may delay or even prevent disease recurrence in ovarian cancer. In order to elicit proinflammatory signals that induce or amplify antitumor immune reactivity, we mimicked viral infection in ascites-derived ovarian cancer cells. By transfection or electroporation we targeted the synthetic double-stranded RNA poly(I:C) intracellularly in order to activate melanoma differentiation-associated gene-5 (MDA-5), a sensor of viral RNA in the cytosol of somatic cells. Cancer cells reacted with enhanced expression of HLA-class I, release of CXCL10, IL-6, and type I IFN as well as tumor cell apoptosis. Monocytes and monocyte-derived DCs (MoDCs) engulfed MDA-5-activated cancer cells, and subsequently upregulated HLA-class I/II and costimulatory molecules, and secreted CXCL10 and IFN-α. Further, this proinflammatory milieu promoted cytolytic activity and IFN-γ secretion of NK cells. Thus, our data suggest that the engagement of MDA-5 in a whole tumor cell vaccine is a promising approach for the immunotherapy of ovarian cancer. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Cancer-associated fibroblasts promote proliferation of endometrial cancer cells.

    Directory of Open Access Journals (Sweden)

    Kavita S Subramaniam

    Full Text Available Endometrial cancer is the most commonly diagnosed gynecologic malignancy worldwide; yet the tumor microenvironment, especially the fibroblast cells surrounding the cancer cells, is poorly understood. We established four primary cultures of fibroblasts from human endometrial cancer tissues (cancer-associated fibroblasts, CAFs using antibody-conjugated magnetic bead isolation. These relatively homogenous fibroblast cultures expressed fibroblast markers (CD90, vimentin and alpha-smooth muscle actin and hormonal (estrogen and progesterone receptors. Conditioned media collected from CAFs induced a dose-dependent proliferation of both primary cultures and cell lines of endometrial cancer in vitro (175% when compared to non-treated cells, in contrast to those from normal endometrial fibroblast cell line (51% (P<0.0001. These effects were not observed in fibroblast culture derived from benign endometrial hyperplasia tissues, indicating the specificity of CAFs in affecting endometrial cancer cell proliferation. To determine the mechanism underlying the differential fibroblast effects, we compared the activation of PI3K/Akt and MAPK/Erk pathways in endometrial cancer cells following treatment with normal fibroblasts- and CAFs-conditioned media. Western blot analysis showed that the expression of both phosphorylated forms of Akt and Erk were significantly down-regulated in normal fibroblasts-treated cells, but were up-regulated/maintained in CAFs-treated cells. Treatment with specific inhibitors LY294002 and U0126 reversed the CAFs-mediated cell proliferation (P<0.0001, suggesting for a role of these pathways in modulating endometrial cancer cell proliferation. Rapamycin, which targets a downstream molecule in PI3K pathway (mTOR, also suppressed CAFs-induced cell proliferation by inducing apoptosis. Cytokine profiling analysis revealed that CAFs secrete higher levels of macrophage chemoattractant protein (MCP-1, interleukin (IL-6, IL-8, RANTES and vascular

  10. Value of the post-operative CT in predicting delayed flap failures following head and neck cancer surgery

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bitna; Yoon, Dae Young; Seo, Young Lan; Park, Min Woo; Kwon, Kee Hwan; Rho, Young Soo; Chung, Chul Hoon [Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

    2017-06-15

    To identify post-operative computed tomography (CT) findings associated with delayed flap failures following head and neck cancer surgery. We retrospectively reviewed 60 patients who underwent flap reconstruction after head and neck cancer surgery and post-operative (3–14 days) contrast-enhanced CT scans for suspected complications. Patients were divided into two groups: delayed flap failure patients (patients required flap revision) (n = 18) and flap success patients (n = 42). Clinical data (age, sex, T-stage, type of flap, and time interval between reconstruction surgery and CT) and post-operative CT findings of flap status (maximum dimension of the flap, intra- or peri-flap fluid collection and intra- or peri-flap air collection, fat infiltration within the flap, fistula to adjacent aerodigestive tract or skin, and enhanced vascular pedicle) were assessed and compared between the two groups. CT findings showed that the following flap anomalies were observed more frequently in the delayed flap failure group than in the flap success group: intra- or peri-flap fluid collection > 4 cm (61.1% vs. 23.8%, p < 0.05), intra- or peri-flap air collection > 2 cm (61.1% vs. 2.4%, p < 0.001), and fistula to adjacent aerodigestive tract or skin (44.4% vs. 0%, p < 0.001). The maximum dimension of the flap, fat infiltration within the flap, and enhanced vascular pedicle were not associated with delayed flap failures. A large amount of fluid or air collection and fistula are the CT findings that were associated with delayed flap failures in patients with suspected post-operative complications after head and neck cancer surgery.

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

    DEFF Research Database (Denmark)

    Bjerregaard, B; Holck, Susanne; Christensen, Ib Jarle

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer...... and inhibits fusions between breast cancer cells and endothelial cells. Moreover, a syncytin inhibitory peptide also inhibits fusions between cancer and endothelial cells. These results are the first to show that syncytin is expressed by human cancer cells and is involved in cancer-endothelial cell fusions....

  12. Targetless T cells in cancer immunotherapy

    DEFF Research Database (Denmark)

    thor Straten, Eivind Per; Garrido, Federico

    2016-01-01

    Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell...... transfer (ACT) using expanded tumor infiltrating lymphocytes (TIL) or genetically modified cytotoxic T cells. However, despite clear clinical responses, only a fraction of patients respond to treatment and there is an urgent call for characterization of predictive biomarkers. CD8 positive T cells can...... infiltrate tumor tissues and destroy HLA class I positive tumor cells expressing the specific antigen. In fact, current progress in the field of cancer immune therapy is based on the capacity of T cells to kill cancer cells that present tumor antigen in the context on an HLA class I molecule. However...

  13. A delayed-onset rectourethral fistula after intersphincteric resection for very low rectal cancer: a case report and literature review.

    Science.gov (United States)

    Komori, Koji; Kimura, Kenya; Kinoshita, Takashi; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuichi; Uemura, Norihisa; Natsume, Seiji; Kawakami, Jiro; Iwata, Yoshinori; Tsutsuyama, Masayuki; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Shimizu, Yasuhiro

    2015-01-01

    Rectourethral fistula is one of the complications that can occur after prostatectomy in the urologic discipline. However, a delayed-onset rectourethral fistula after intersphincteric resection (ISR) for low rectal cancer is extremely rare. Here, we report one such case in a 57-year-old man. After ISR for low rectal cancer with a diverting stoma (DS), the DS was closed. After approximately 1 year, frequent pneumaturia and right orchitis were observed. Results of contrast enemas and abdominal computed tomography examinations revealed a rectourethral fistula from an anastomosis to the urethra. The colonoscopic appearance revealed a pinhole fistula on the anastomotic line, with thick pus. We performed a transverse colostomy, and the pneumaturia and right orchitis were no longer observed. Two months later, colonoscopy, contrast enemas, and cystoscopy revealed no rectourethral fistula. To the best of our knowledge, our case is the first report of a delayed-onset rectourethral fistula after ISR.

  14. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hamada, Shin [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Hamada, Hirofumi [Laboratory of Oncology, Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji (Japan); Kobune, Masayoshi [Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo (Japan); Satoh, Kennichi [Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori (Japan); Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called 'cancer stem cells', within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the 'stemness' of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  15. Delayed Cystectomy for T1G3 Transitional Cell Carcinoma (TCC) of the Urinary Bladder, NCI Retrospective Case Series.

    Science.gov (United States)

    Fakhr, Ibrahim; El-Hossieny, Hesham; Salama, Asmaa

    2008-12-01

    We aim to evaluate the National Cancer Institute (NCI) treatment protocol and its outcome regarding recurrence, progression and survival in patients with T1G3 urinary bladder transitional cell carcinoma. In a retrospective study, between January 2001 and December 2007, all 34 patients with T1G3 bladder transitional cell carcinoma (TCC), after complete transurethral resection (TURBT), received intravesical BCG as adjuvant therapy. A conservative approach was adopted, whereby those with superficial recurrences were eligible to TURBT, with delayed cystectomy for progression to muscle invasion. Overall, recurrence, and progression-free survival were analyzed. Thirty-three patients were included, 29 were males and 4 were females. The mean age was 61 years (range 35-89 years). Final analysis was made at median follow-up of 15 months (Range of 3-68 months, mean 18 months) for survival. Eleven (33.3%) patients had multifocal tumors. Associated schistosomiasis was present in 12 (36.6%) patients. Twenty-two (66.67%) patients showed recurrence. Eleven out of these 22 (50.0%) patients progressed to muscle invasion and underwent radical cystectomy. Ten out of 34 (30.3%) patients received postcystectomy radiotherapy. Two (20.0%) of them, were staged as TNM stage II, 6 (60.0%) as TNM stage III and 2 (20.0%) patients were TNM stage IV. Eight (72.7%) of these 11 patients had post-cystectomy radiotherapy alone; while the 2 (6.0%) other patients with stage IV had adjuvant concomitant Cisplatin and Gemcitabine chemotherapy. Five (14%) patients of those cystectomy patients died of TCC. Three (60%) patients died from metastatic disease (to lung, liver and bone), one patient died from advanced locoregional disease and another patient died from postoperative complications. Among those patients who received radiotherapy alone, 62.5% are alive. Although, we report a biologically more aggressive behavior of T1G3 than that reported by some authors, for this conservative approach, the overall

  16. The Haiti Breast Cancer Initiative: Initial Findings and Analysis of Barriers-to-Care Delaying Patient Presentation

    Directory of Open Access Journals (Sweden)

    Ketan Sharma

    2013-01-01

    Full Text Available Background. In Haiti, breast cancer patients present at such advanced stages that even modern therapies offer modest survival benefit. Identifying the personal, sociocultural, and economic barriers-to-care delaying patient presentation is crucial to controlling disease. Methods. Patients presenting to the Hôpital Bon Sauveur in Cange were prospectively accrued. Delay was defined as 12 weeks or longer from initial sign/symptom discovery to presentation, as durations greater than this cutoff correlate with reduced survival. A matched case-control analysis with multivariate logistic regression was used to identify factors predicting delay. Results. Of N=123 patients accrued, 90 (73% reported symptom-presentation duration and formed the basis of this study: 52 patients presented within 12 weeks of symptoms, while 38 patients waited longer than 12 weeks. On logistic regression, lower education status (OR = 5.6, P=0.03, failure to initially recognize mass as important (OR = 13.0, P<0.01, and fear of treatment cost (OR = 8.3, P=0.03 were shown to independently predict delayed patient presentation. Conclusion. To reduce stage at presentation, future interventions must educate patients on the recognition of initial breast cancer signs and symptoms and address cost concerns by providing care free of charge and/or advertising that existing care is already free.

  17. Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer.

    Science.gov (United States)

    Shan, Naing Lin; Wahler, Joseph; Lee, Hong Jin; Bak, Min Ji; Gupta, Soumyasri Das; Maehr, Hubert; Suh, Nanjoo

    2017-10-01

    Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures. In the present study, the effects of vitamin D compounds in regulating breast cancer stem-like cells and differentiation in triple-negative breast cancer were assessed. Mammosphere cultures, which enriches for breast cancer cells with stem-like properties, were used to assess the effects of 1α,25(OH)2D3 and BXL0124 on cancer stem cell markers in the triple-negative breast cancer cell line, SUM159. Vitamin D compounds significantly reduced the mammosphere forming efficiency in primary, secondary and tertiary passages of mammospheres compared to control groups. Key markers of cancer stem-like phenotype and pluripotency were analyzed in mammospheres treated with 1α,25(OH)2D3 and BXL0124. As a result, OCT4, CD44 and LAMA5 levels were decreased. The vitamin D compounds also down-regulated the Notch signaling molecules, Notch1, Notch2, Notch3, JAG1, JAG2, HES1 and NFκB, which are involved in breast cancer stem cell maintenance. In addition, the vitamin D compounds up-regulated myoepithelial differentiating markers, cytokeratin 14 and smooth muscle actin, and down-regulated the luminal marker, cytokeratin 18. Cytokeratin 5, a biomarker associated with basal-like breast cancer, was found to be significantly down-regulated by the vitamin D compounds. These results suggest that

  18. Targeting Cancer Stem Cells with Natural Killer Cell Immunotherapy.

    Science.gov (United States)

    Luna, Jesus I; Grossenbacher, Steven K; Murphy, William J; Canter, Robert J

    2017-03-01

    Standard cytoreductive cancer therapy, such as chemotherapy and radiotherapy, are frequently resisted by a small portion of cancer cells with 'stem-cell' like properties including quiescence and repopulation. Immunotherapy represents a breakthrough modality for improving oncologic outcomes in cancer patients. Since the success of immunotherapy is not contingent on target cell proliferation, it may also be uniquely suited to address the problem of resistance and repopulation exerted by cancer stem cells (CSCs). Areas covered: Natural killer (NK) cells have long been known for their ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. The authors review the current knowledge of CSCs and NK cells and highlight recent studies that support the concept that NK cells are capable of targeting CSC in solid tumors, especially in the context of combination therapy simultaneously targeting non-CSCs and CSCs. Expert opinion: Unlike cytotoxic cancer treatments, NK cells can target and eliminate quiescent/non-proliferating cells such as CSCs, and these enigmatic cells are an important source of relapse and metastasis. NK targeting of CSCs represents a novel and potentially high impact method to capitalize on the intrinsic therapeutic potential of NK cells.

  19. Lipid degradation promotes prostate cancer cell survival

    Science.gov (United States)

    Itkonen, Harri M; Brown, Michael; Urbanucci, Alfonso; Tredwell, Gregory; Lau, Chung Ho; Barfeld, Stefan; Hart, Claire; Guldvik, Ingrid J.; Takhar, Mandeep; Heemers, Hannelore V.; Erho, Nicholas; Bloch, Katarzyna; Davicioni, Elai; Derua, Rita; Waelkens, Etienne; Mohler, James L.; Clarke, Noel; Swinnen, Johan V.; Keun, Hector C.; Rekvig, Ole P.; Mills, Ian G.

    2017-01-01

    Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential. PMID:28415728

  20. Characterization of cancer stem-like cells in the side population cells of human gastric cancer cell line MKN-45.

    Science.gov (United States)

    Zhang, Hai-hong; Cai, Ai-zhen; Wei, Xue-ming; Ding, Li; Li, Feng-zhi; Zheng, Ai-ming; Dai, Da-jiang; Huang, Rong-rong; Cao, Hou-jun; Zhou, Hai-yang; Wang, Jian-mei; Wang, Xue-jing; Shi, Wei; Zhu, Heng; Yuan, Xiao-ying; Chen, Lin

    2013-03-01

    Side population (SP) cells may play a crucial role in tumorigenesis and the recurrence of cancer. Many kinds of cell lines and tissues have demonstrated the presence of SP cells, including several gastric cancer cell lines. This study is aimed to identify the cancer stem-like cells in the SP of gastric cancer cell line MKN-45. We used fluorescence activated cell sorting (FACS) to sort SP cells in the human gastric carcinoma cell line MKN-45 (cells labeled with Hoechst 33342) and then characterized the cancer stem-like properties of SP cells. This study found that the SP cells had higher clone formation efficiency than major population (MP) cells. Five stemness-related gene expression profiles, including OCT-4, SOX-2, NANOG, CD44, and adenosine triphosphate (ATP)-binding cassette transporters gene ABCG2, were tested in SP and MP cells using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Western blot was used to show the difference of protein expression between SP and MP cells. Both results show that there was significantly higher protein expression in SP cells than in MP cells. When inoculated into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, SP cells show higher tumorigenesis tendency than MP cells. These results indicate that SP cells possess cancer stem cell properties and prove that SP cells from MKN-45 are gastric cancer stem-like cells.

  1. CHRNA5 Risk Variant Predicts Delayed Smoking Cessation and Earlier Lung Cancer Diagnosis—A Meta-Analysis

    Science.gov (United States)

    Hung, Rayjean J.; Baker, Timothy; Horton, Amy; Culverhouse, Rob; Saccone, Nancy; Cheng, Iona; Deng, Bo; Han, Younghun; Hansen, Helen M.; Horsman, Janet; Kim, Claire; Lutz, Sharon; Rosenberger, Albert; Aben, Katja K.; Andrew, Angeline S.; Breslau, Naomi; Chang, Shen-Chih; Dieffenbach, Aida Karina; Dienemann, Hendrik; Frederiksen, Brittni; Han, Jiali; Hatsukami, Dorothy K.; Johnson, Eric O.; Pande, Mala; Wrensch, Margaret R.; McLaughlin, John; Skaug, Vidar; van der Heijden, Henricus F.; Wampfler, Jason; Wenzlaff, Angela; Woll, Penella; Zienolddiny, Shanbeh; Bickeböller, Heike; Brenner, Hermann; Duell, Eric J.; Haugen, Aage; Heinrich, Joachim; Hokanson, John E.; Hunter, David J.; Kiemeney, Lambertus A.; Lazarus, Philip; Le Marchand, Loic; Liu, Geoffrey; Mayordomo, Jose; Risch, Angela; Schwartz, Ann G.; Teare, Dawn; Wu, Xifeng; Wiencke, John K.; Yang, Ping; Zhang, Zuo-Feng; Spitz, Margaret R.; Kraft, Peter; Amos, Christopher I.; Bierut, Laura J.

    2015-01-01

    Background: Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis. Methods: Meta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each dataset, we used Cox regression models to evaluate the association between rs16969968 and the two primary phenotypes (age of smoking cessation among ever smokers and age of lung cancer diagnosis among lung cancer case patients) and the secondary phenotype of smoking duration. Heterogeneity across studies was assessed with the Cochran Q test. All statistical tests were two-sided. Results: The rs16969968 allele (A) was associated with a lower likelihood of smoking cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98, P = .0042), and the AA genotype was associated with a four-year delay in median age of quitting compared with the GG genotype. Among smokers with lung cancer diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95% CI = 1.04 to 1.12, P = 1.1*10–5). Conclusion: These data support the clinical significance of the CHRNA5 variant rs16969968. It predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis. Given the existing evidence that this CHRNA5 variant predicts favorable response to cessation pharmacotherapy, these findings underscore the potential clinical and public health importance of rs16969968 in CHRNA5 in relation to smoking cessation success and lung cancer risk. PMID:25873736

  2. Liver Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Germana Castelli

    2017-09-01

    Full Text Available Liver cancer is the second most common cause of cancer-related death. The major forms of primary liver cancer are hepatocellular carcinoma (HCC and intrahepatic cholangiocarcinoma (iCCA. Both these tumors develop against a background of cirrhotic liver, non-alcoholic fatty liver disease, chronic liver damage and fibrosis. HCC is a heterogeneous disease which usually develops within liver cirrhosis related to various etiologies: hepatitis B virus (HBV infection (frequent in Asia and Africa, hepatitis C virus (HCV, chronic alcohol abuse, or metabolic syndrome (frequent in Western countries. In cirrhosis, hepatocarcinogenesis is a multi-step process where pre-cancerous dysplastic macronodules transform progressively into HCC. The patterns of genomic alterations observed in these tumors were recently identified and were instrumental for the identification of potential targeted therapies that could improve patient care. Liver cancer stem cells are a small subset of undifferentiated liver tumor cells, responsible for cancer initiation, metastasis, relapse and chemoresistance, enriched and isolated according to immunophenotypic and functional properties: cell surface proteins (CD133, CD90, CD44, EpCAM, OV-6, CD13, CD24, DLK1, α2δ1, ICAM-1 and CD47; the functional markers corresponding to side population, high aldehyde dehydrogenase (ALDH activity and autofluorescence. The identification and definition of liver cancer stem cells requires both immunophenotypic and functional properties.

  3. Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy

    DEFF Research Database (Denmark)

    Bruedigam, Claudia; Bagger, Frederik Otzen; Heidel, Florian H.

    2014-01-01

    priority. Here, we show that targeting telomerase activity eradicates AML LSCs. Genetic deletion of the telomerase subunit Terc in a retroviral mouse AML model induces cell-cycle arrest and apoptosis of LSCs, and depletion of telomerase-deficient LSCs is partially rescued by p53 knockdown. Murine Terc......(-/-) LSCs express a specific gene expression signature that can be identified in human AML patient cohorts and is positively correlated with patient survival following chemotherapy. In xenografts of primary human AML, genetic or pharmacological inhibition of telomerase targets LSCs, impairs leukemia...... progression, and delays relapse following chemotherapy. Altogether, these results establish telomerase inhibition as an effective strategy for eliminating AML LSCs....

  4. Loss of PACS-2 delays regeneration in DSS-induced colitis but does not affect the ApcMin model of colorectal cancer

    DEFF Research Database (Denmark)

    Dombernowsky, Sarah L.; Schwarz, Jeanette; Samsøe-Petersen, Jacob

    2017-01-01

    PACS-2 is a multifunctional sorting protein that mediates cell homeostasis. We recently identified PACS-2 in a functional genome-wide siRNA screen for novel regulators of the metalloproteinase ADAM17, the main sheddase for ligands of the ErbB receptor family. Of note, we showed that Pacs2-/- mice...... have significantly reduced EGFR activity and proliferative index in the intestinal epithelium. As EGFR signaling is highly mitogenic for intestinal epithelial stem cells, and plays essential roles in intestinal epithelial regeneration and tumor development, we have now examined the role of PACS-2...... in these processes. Specifically, we analyzed the role of Pacs2- deficiency in a DSS-induced colitis model as well as in the genetic ApcMin colon cancer model. We now report that loss of PACS-2 delays tissue regeneration after colonic injury with little effect on key inflammatory parameters. We did however...

  5. Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression.

    Science.gov (United States)

    Lopes-Coelho, Filipa; Gouveia-Fernandes, Sofia; Serpa, Jacinta

    2018-02-01

    The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

  6. c-Myc-Dependent Cell Competition in Human Cancer Cells.

    Science.gov (United States)

    Patel, Manish S; Shah, Heta S; Shrivastava, Neeta

    2017-07-01

    Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. The enteropathogenic Escherichia coli effector Cif induces delayed apoptosis in epithelial cells.

    Science.gov (United States)

    Samba-Louaka, Ascel; Nougayrède, Jean-Philippe; Watrin, Claude; Oswald, Eric; Taieb, Frédéric

    2009-12-01

    The cycle inhibiting factor (Cif) belongs to a family of bacterial toxins, the cyclomodulins, which modulate the host cell cycle. Upon injection into the host cell by the type III secretion system of enteropathogenic Escherichia coli (EPEC), Cif induces both G(2) and G(1) cell cycle arrests. The cell cycle arrests correlate with the accumulation of p21(waf1) and p27(kip1) proteins that inhibit CDK-cyclin complexes, whose activation is required for G(1)/S and G(2)/M transitions. Increases of p21 and p27 levels are independent of p53 transcriptional induction and result from protein stabilization through inhibition of the ubiquitin/proteasome degradation pathway. In this study, we show that Cif not only induces cell cycle arrest but also eventually provokes a delayed cell death. Indeed, 48 h after infection with EPEC expressing Cif, cultured IEC-6 intestinal cells were positive for extracellular binding of annexin V and exhibited high levels of cleaved caspase-3 and lactate dehydrogenase release, indicating evidence of apoptosis. Cif was necessary and sufficient for inducing this late apoptosis, and the cysteine residue of the catalytic site was required for Cif activity. These results highlight a more complex role of Cif than previously thought, as a cyclomodulin but also as an apoptosis inducer.

  8. Gene sensitizes cancer cells to chemotherapy drugs

    Science.gov (United States)

    NCI scientists have found that a gene, Schlafen-11 (SLFN11), sensitizes cells to substances known to cause irreparable damage to DNA.  As part of their study, the researchers used a repository of 60 cell types to identify predictors of cancer cell respons

  9. Effect of acute exercise on prostate cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Helene Rundqvist

    Full Text Available Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum and after completed exercise (exercise serum. The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.

  10. A Small Molecule Polyamine Oxidase Inhibitor Blocks Androgen-Induced Oxidative Stress and Delays Prostate Cancer Progression in the TRAMP Mouse Model

    Science.gov (United States)

    Basu, Hirak S.; Thompson, Todd A.; Church, Dawn R.; Clower, Cynthia C.; Mehraein-Ghomi, Farideh; Amlong, Corey A.; Martin, Christopher T.; Woster, Patrick M.; Lindstrom, Mary J.; Wilding, George

    2009-01-01

    High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiological factor in prostate cancer (CaP) occurrence, recurrence and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data demonstrate that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays prostate cancer progression. PMID:19773450

  11. Spindle Cell Metaplastic Breast Cancer: Case Report

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    Dursun Ozgur Karakas

    2013-08-01

    Conclusion: Spindle cell metaplastic breast cancer must be considered in differential diagnosis of breast cancers, and preoperative immunohistochemical examination, including cytokeratin and vimentin, must be added to pathological examination in intervening cases. [Arch Clin Exp Surg 2013; 2(4.000: 259-262

  12. Human umbilical cord blood mononuclear cell transplantation for delayed encephalopathy after carbon monoxide intoxication

    Directory of Open Access Journals (Sweden)

    Gong D

    2013-08-01

    Full Text Available Dianrong Gong,1 Haiyan Yu,1 Weihua Wang,2 Haixin Yang,1 Fabin Han1,21Department of Neurology, 2Centre for Stem Cells and Regenerative Medicine, Liaocheng People's Hospital, The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of ChinaAbstract: Stem cell transplantation is one of the potential treatments for neurological disorders. Since human umbilical cord stem cells have been shown to provide neuroprotection and promote neural regeneration, we have attempted to transplant the human umbilical cord blood mononuclear cells (hUCB-MNCs to treat patients with delayed encephalopathy after carbon monoxide intoxication (DEACOI. The hUCB-MNCs were isolated from fresh umbilical cord blood and were given to patients subarachnoidally. Physical examinations, mini-mental state examination scores, and computed tomography scans were used to evaluate the improvement of symptoms, signs, and pathological changes of the patient's brain before and after hUCB-MNC transplantation. A total of 12 patients with DEACOI were treated with hUCB-MNCs in this study. We found that most of the patients have shown significant improvements in movement, behavior, and cognitive function, and improved brain images in 1–4 months from the first transplantation of hUCB-MNCs. None of these patients have been observed to have any severe adverse effects. Our study suggests that the hUCB-MNC transplantation may be a safe and effective treatment for DEACOI. Further studies and clinical trials with more cases, using more systematic scoring methods, are needed to evaluate brain structural and functional improvements in patients with DEACOI after hUCB-MNC therapy.Keywords: human umbilical cord blood mononuclear cells, transplantation, delayed encephalopathy after carbon monoxide intoxication, MMSE

  13. Stem Cells and Cancer; Celulas madre y cancer

    Energy Technology Data Exchange (ETDEWEB)

    Segrelles, C.; Paraminio, J. M.; Lorz, C.

    2014-04-01

    Stem cell research has thrived over the last years due to their therapeutic and regenerative potential. Scientific breakthroughs in the field are immediately translated from the scientific journals to the mass media, which is not surprising as the characterisation of the molecular mechanisms that regulate the biology of stem cells is crucial for the treatment of degenerative and cardiovascular diseases, as well as cancer. In the Molecular Oncology Unit at Ciemat we work to unravel the role of cancer stem cells in tumour development, and to find new antitumor therapies. (Author)

  14. Improved tumor tissue penetration and tumor cell uptake achieved by delayed charge reversal nanoparticles.

    Science.gov (United States)

    Gou, Jingxin; Liang, Yuheng; Miao, Linlin; Guo, Wei; Chao, Yanhui; He, Haibing; Zhang, Yu; Yang, Jingyu; Wu, Chunfu; Yin, Tian; Wang, Yanjiao; Tang, Xing

    2017-10-15

    The high affinity of positively charged nanoparticles to biological interfaces makes them easily taken up by tumor cells but limits their tumor permeation due to non-specific electrostatic interactions. In this study, polyion complex coated nanoparticles with different charge reversal profiles were developed to study the influence of charge reversal profile on tumor penetration. The system was constructed by polyion complex coating using micelles composed of poly (lysine)-b-polycaprolactone (PLys-b-PCL) as the cationic core and poly (glutamic acid)-g- methoxyl poly (ethylene glycol) (PGlu-g-mPEG) as the anionic coating material. Manipulation of charge reversal profile was achieved by controlling the polymer chain entanglement and electrostatic interaction in the polyion complex layer through glutaraldehyde-induced shell-crosslinking. The delayed charge reversal nanoparticles (CTCL30) could maintain negatively charged in pH 6.5 PBS for at least 2h and exhibit pH-responsive cytotoxicity and cellular uptake in an extended time scale. Compared with a faster charge reversal counterpart (CTCL70) with similar pharmacokinetic profile, CTCL30 showed deeper penetration, higher in vivo tumor cell uptake and stronger antitumor activity in vivo (tumor inhibition rate: 72.3% vs 60.2%, compared with CTCL70). These results indicate that the delayed charge reversal strategy could improve therapeutic effect via facilitating tumor penetration. Here, the high tumor penetration capability of PEG-coated nanoparticles and the high cellular uptake of cationic nanoparticles were combined by a delayed charge reversal drug delivery system. This drug delivery system was composed of a drug-loading cationic inner core and a polyion complex coating. Manipulation of charge reversal profile was realized by varying the crosslinking degree of the shell of the cationic inner core, through which changed the strength of the polyion complex layer. Nanoparticles with delayed charge reversal profile

  15. Modeling protective anti-tumor immunity via preventative cancer vaccines using a hybrid agent-based and delay differential equation approach.

    Directory of Open Access Journals (Sweden)

    Peter S Kim

    Full Text Available A next generation approach to cancer envisions developing preventative vaccinations to stimulate a person's immune cells, particularly cytotoxic T lymphocytes (CTLs, to eliminate incipient tumors before clinical detection. The purpose of our study is to quantitatively assess whether such an approach would be feasible, and if so, how many anti-cancer CTLs would have to be primed against tumor antigen to provide significant protection. To understand the relevant dynamics, we develop a two-compartment model of tumor-immune interactions at the tumor site and the draining lymph node. We model interactions at the tumor site using an agent-based model (ABM and dynamics in the lymph node using a system of delay differential equations (DDEs. We combine the models into a hybrid ABM-DDE system and investigate dynamics over a wide range of parameters, including cell proliferation rates, tumor antigenicity, CTL recruitment times, and initial memory CTL populations. Our results indicate that an anti-cancer memory CTL pool of 3% or less can successfully eradicate a tumor population over a wide range of model parameters, implying that a vaccination approach is feasible. In addition, sensitivity analysis of our model reveals conditions that will result in rapid tumor destruction, oscillation, and polynomial rather than exponential decline in the tumor population due to tumor geometry.

  16. Red cell exchange to mitigate a delayed hemolytic transfusion reaction in a patient transfused with incompatible red blood cells.

    Science.gov (United States)

    Irani, Mehraboon S; Karafin, Matthew S; Ernster, Luke

    2017-02-01

    A red cell exchange was performed to prevent a potentially fatal hemolytic transfusion reaction in a patient with anti-e who was transfused with e-antigen unscreened red blood cells during liver transplant surgery. A 64-year-old woman with cirrhosis due to hepatitis C was scheduled to receive a liver transplant. She had a previously documented anti-e, an antibody to the Rh(e)-antigen that is known to cause delayed hemolytic transfusion reactions. Pre-operatively and intra-operatively, she had massive hemorrhage which required transfusion of 34 e-antigen unscreened red blood cells (RBCs) most of which were incompatible. The hemoglobin dropped from 9.1 g/dL on post-operative day (POD)1 to 6.6 g/dL on POD6, with no evidence of blood loss. The bilirubin also increased from 5.0 mg/dL on POD 1 to 11.0 mg/dL on POD 6. As she was also becoming more hemodynamically unstable, a red cell exchange with 10 units of e-negative RBCs was performed on POD 6. She improved clinically and was extubated the following day. A few residual transfused e-positive red cells were detected after the red cell exchange until POD 13. This case illustrates how a red cell exchange can mitigate the potentially harmful effects of a delayed hemolytic transfusion reaction caused by red cell antibodies. With massive intraoperative blood loss it may not be possible to have antigen-negative RBCs immediately available, particularly for the e-antigen, which is present in 98% of the donor population. The ability to perform such a procedure may be life-saving in such patients. J. Clin. Apheresis 32:59-61, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Alterations of calcium homeostasis in cancer cells.

    Science.gov (United States)

    Marchi, Saverio; Pinton, Paolo

    2016-08-01

    Typical hallmarks of cancer include programmed cell death evasion, uncontrolled cell growth, invasion, and metastasis. Changes in intracellular Ca(2+) levels can modulate signaling pathways that control a broad range of cellular events, including those important to tumorigenesis and cancer progression. Here we discuss how known molecular mediators of cellular Ca(2+) homeostasis impact tumor dynamics and how deregulation of major oncogenes and tumor suppressors is tightly associated with Ca(2+) signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Lgr5-Positive Cells are Cancer-Stem-Cell-Like Cells in Gastric Cancer

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    Zhongli Wang

    2015-07-01

    Full Text Available Background/Aims: Effective treatment of gastric cancer (GC requires better understanding of the molecular regulation of its carcinogenesis. Identification of cancer stem cells (CSCs in GC appears to be a critical question. Methods: We analyzed Lgr5 expression in GC specimen. We used an adeno-associated virus (AAV that carries diphtheria toxin fragment A (DTA under the control of Lgr5 promoter (AAV-pLgr5-DTA to transduce human GC cells. The growth of GC cells with/without depletion of Lgr5-positive cells was studied in vitro in an MTT assay, and in vivo by analyzing bioluminescence levels. Results: A portion of GC cells in the resected specimen expressed Lgr5. GC cells that formed tumor spheres expressed high Lgr5. Selective depletion of Lgr5-positive GC cells resulted in significant growth inhibition of GC cells in vitro and in vivo. Conclusion: Lgr5-positive cells may be CSCs-like cells in GC and may play a pivotal role in the tumorigenesis of GC. Treating Lgr5-positive GC cells may substantially improve the therapeutic outcome.

  19. Study characterizes how DNA-damaging anti-cancer drugs kill cancer cells | Center for Cancer Research

    Science.gov (United States)

    Patients whose cancer cells express the SLFN11 protein are more likely to respond to DNA-damaging anti-cancer drugs than those whose cancer cells don’t express SLFN11. In a new study, Center for Cancer Research investigators show how these drugs recruit SLFN11 to block replication and kill cancer cells. Read more…

  20. Delayed Diagnosis of Osteonecrosis of the Jaw (ONJ Associated with Bevacizumab Therapy in Colorectal Cancer Patients: Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Francesco Erovigni

    2016-10-01

    Full Text Available Medication-induced Osteonecrosis of the Jaw (MRONJ has been reported not only after use of antiresorptive agents (bisphosphonates and denosumab, but also in cancer patients receiving antiangiogenic agents, alone or combined with antiresorptive drugs. We report two cases of MRONJ observed in colorectal cancer patients after bevacizumab therapy only. MRONJ was diagnosed, respectively, two and seven months after a tooth extraction; both the patients had received two courses of bevacizumab infusions (for a total of 29 and 10 administrations, respectively. We discuss if tooth extraction during or after antiangiogenic therapy could be a potential trigger of MRONJ, but also if an underlying bone disease not evident before oral surgery might be a possible cause. A careful drug history has to be registered by dental specialists in cancer patients before oral surgery and adequate imaging might be obtained to avoid a delayed diagnosis.

  1. Epigenetics of solid cancer stem cells.

    Science.gov (United States)

    Mishra, Alok; Verma, Mukesh

    2012-01-01

    Epigenetics is an emerging science that can help to explain carcinogenesis. The possibility that carcinogenesis may originate in a stem cell process was proposed recently. Stem cells are generated and contribute to tumor formation during the process of tumor development. This chapter focuses on the role of epigenetics and genetics in stem cell formation, different theories about the origin of cancer stem cells (CSCs), and epigenetic mechanisms that occur in solid CSCs. Potential applications of knowledge gained through this field and future prospects for cancer treatment also are discussed.

  2. Human Cancer Classification: A Systems Biology- Based Model Integrating Morphology, Cancer Stem Cells, Proteomics, and Genomics

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    Halliday A Idikio

    2011-01-01

    Full Text Available Human cancer classification is currently based on the idea of cell of origin, light and electron microscopic attributes of the cancer. What is not yet integrated into cancer classification are the functional attributes of these cancer cells. Recent innovative techniques in biology have provided a wealth of information on the genomic, transcriptomic and proteomic changes in cancer cells. The emergence of the concept of cancer stem cells needs to be included in a classification model to capture the known attributes of cancer stem cells and their potential contribution to treatment response, and metastases. The integrated model of cancer classification presented here incorporates all morphology, cancer stem cell contributions, genetic, and functional attributes of cancer. Integrated cancer classification models could eliminate the unclassifiable cancers as used in current classifications. Future cancer treatment may be advanced by using an integrated model of cancer classification.

  3. Cell-of-Origin of Cancer versus Cancer Stem Cells: Assays and Interpretations.

    Science.gov (United States)

    Rycaj, Kiera; Tang, Dean G

    2015-10-01

    A tumor originates from a normal cell that has undergone tumorigenic transformation as a result of genetic mutations. This transformed cell is the cell-of-origin for the tumor. In contrast, an established clinical tumor is sustained by subpopulations of self-renewing cancer cells operationally called cancer stem cells (CSC) that can generate, intraclonally, both tumorigenic and nontumorigenic cells. Identifying and characterizing tumor cell-of-origin and CSCs should help elucidate tumor cell heterogeneity, which, in turn, should help understand tumor cell responses to clinical treatments, drug resistance, tumor relapse, and metastatic spread. Both tumor transplantation and lineage-tracing assays have been helpful in characterizing these cancer cell populations, although each system has its strengths and caveats. In this article, we briefly review and summarize advantages and limitations of both assays in support of a combinatorial approach to accurately define the roles of both cancer-initiating and cancer-propagating cells. As an aside, we also wish to clarify the definitions of cancer cell-of-origin and CSCs, which are often interchangeably used by mistake. ©2015 American Association for Cancer Research.

  4. Ectopic expression of Capsicum-specific cell wall protein Capsicum annuum senescence-delaying 1 (CaSD1) delays senescence and induces trichome formation in Nicotiana benthamiana.

    Science.gov (United States)

    Seo, Eunyoung; Yeom, Seon-In; Jo, Sunghwan; Jeong, Heejin; Kang, Byoung-Cheorl; Choi, Doil

    2012-04-01

    Secreted proteins are known to have multiple roles in plant development, metabolism, and stress response. In a previous study to understand the roles of secreted proteins, Capsicum annuum secreted proteins (CaS) were isolated by yeast secretion trap. Among the secreted proteins, we further characterized Capsicum annuum senescence-delaying 1 (CaSD1), a gene encoding a novel secreted protein that is present only in the genus Capsicum. The deduced CaSD1 contains multiple repeats of the amino acid sequence KPPIHNHKPTDYDRS. Interestingly, the number of repeats varied among cultivars and species in the Capsicum genus. CaSD1 is constitutively expressed in roots, and Agrobacterium-mediated transient overexpression of CaSD1 in Nicotiana benthamiana leaves resulted in delayed senescence with a dramatically increased number of trichomes and enlarged epidermal cells. Furthermore, senescence- and cell division-related genes were differentially regulated by CaSD1-overexpressing plants. These observations imply that the pepper-specific cell wall protein CaSD1 plays roles in plant growth and development by regulating cell division and differentiation.

  5. Delayed Activation Kinetics of Th2- and Th17 Cells Compared to Th1 Cells.

    Science.gov (United States)

    Duechting, Andrea; Przybyla, Anna; Kuerten, Stefanie; Lehmann, Paul V

    2017-09-12

    During immune responses, different classes of T cells arise: Th1, Th2, and Th17. Mobilizing the right class plays a critical role in successful host defense and therefore defining the ratios of Th1/Th2/Th17 cells within the antigen-specific T cell repertoire is critical for immune monitoring purposes. Antigen-specific Th1, Th2, and Th17 cells can be detected by challenging peripheral blood mononuclear cells (PBMC) with antigen, and establishing the numbers of T cells producing the respective lead cytokine, IFN-γ and IL-2 for Th1 cells, IL-4 and IL-5 for Th2, and IL-17 for Th-17 cells, respectively. Traditionally, these cytokines are measured within 6 h in flow cytometry. We show here that 6 h of stimulation is sufficient to detect peptide-induced production of IFN-γ, but 24 h are required to reveal the full frequency of protein antigen-specific Th1 cells. Also the detection of IL-2 producing Th1 cells requires 24 h stimulation cultures. Measurements of IL-4 producing Th2 cells requires 48-h cultures and 96 h are required for frequency measurements of IL-5 and IL-17 secreting T cells. Therefore, accounting for the differential secretion kinetics of these cytokines is critical for the accurate determination of the frequencies and ratios of antigen-specific Th1, Th2, and Th17 cells.

  6. Patient delay among Colombian women with breast cancer Demora en pacientes colombianas con cáncer de mama

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    Marion Piñeros

    2009-10-01

    Full Text Available OBJECTIVE: Characterize diagnosis and treatment of breast cancer in Bogota, Colombia and examine the extent and determinants of patient delay. MATERIAL AND METHODS: Using a census approach we identified 1 106 women with breast cancer. Information was gathered through personal interviews and the review of medical records. Patient delay was defined as the time elapsed from first symptoms to initial consultation. RESULTS: More than 80% of the women (902 consulted due to symptoms; the majority had advanced-stage disease. Patient delay was established in 20.3% and the main related factors were older age, lack of social security and advanced clinical stage. Higher education in patients was associated with reduced delays. DISCUSSION: Women do not recognize breast cancer symptoms. Patient delay and related factors are similar to those found in other studies. There is an urgent need to develop communication and education strategies regarding breast cancer symptoms and early detection.OBJETIVO: Caracterizar el diagnóstico y tratamiento de mujeres con cáncer de mama en Bogotá, Colombia; establecer la demora de pacientes en la asistencia a consulta y los factores relacionados. MATERIAL Y MÉTODOS: A través de una aproximación censal se identificaron 1 106 mujeres con cáncer de mama. La recolección de información se hizo mediante entrevistas y revisión de historias clínicas. Se consideró demora de la paciente el tiempo entre la percepción del síntoma y la primera consulta. RESULTADOS: Más de 80% de las mujeres consultaron por síntomas; la mayoría eran estados avanzados. Los factores que se relacionaron con la demora fueron una mayor edad, no tener afiliación al sistema de salud y la enfermedad avanzada. Una mayor educación se relacionó con menor demora. DISCUSIÓN: Las mujeres no reconocen los síntomas del cáncer de mama; es necesario diseñar estrategias de comunicación y educación para estimular el reconocimiento de los síntomas y

  7. Fatty acids and breast cancer cell proliferation.

    Science.gov (United States)

    Hardy, R W; Wickramasinghe, N S; Ke, S C; Wells, A

    1997-01-01

    We and others have shown that fatty acids are important regulators of breast cancer cell proliferation. In particular individual fatty acids specifically alter EGF-induced cell proliferation in very different ways. This regulation is mediated by an EGFR/G-protein signaling pathway. Understanding the molecular mechanisms of how this signaling pathway functions and how fatty acids regulate it will provide important information on the cellular and molecular basis for the association of dietary fat and cancer. Furthermore these in vitro studies may explain data previously obtained from in vivo animal studies and identify "good" as well as "bad" fatty acids with respect to the development of cancer.

  8. Delayed cutaneous wound healing and aberrant expression of hair follicle stem cell markers in mice selectively lacking Ctip2 in epidermis.

    Directory of Open Access Journals (Sweden)

    Xiaobo Liang

    Full Text Available COUP-TF interacting protein 2 [(Ctip2, also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2(ep-/- mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB establishment during development, similar to what was observed in Ctip2 null (Ctip2(-/- mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing.Full thickness excisional wound healing experiments were performed on Ctip2(L2/L2 and Ctip2(ep-/- animals per time point and used for harvesting samples for histology, immunohistochemistry (IHC and immunoblotting. Results demonstrated inherent defects in proliferation and migration of Ctip2 lacking keratinocytes during re-epithelialization. Mutant mice exhibited reduced epidermal proliferation, delayed keratinocyte activation, altered cell-cell adhesion and impaired ECM development. Post wounding, Ctip2(ep-/- mice wounds displayed lack of E-Cadherin suppression in the migratory tongue, insufficient expression of alpha smooth muscle actin (alpha SMA in the dermis, and robust induction of K8. Importantly, dysregulated expression of several hair follicle (HF stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in mutant skin during wound repair.Results confirm a cell autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation and/or differentiation, and to maintain HF stem cells during cutaneous wounding. Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue formation and tissue contraction during wound closure.

  9. Expression of periostin in breast cancer cells.

    Science.gov (United States)

    Ratajczak-Wielgomas, Katarzyna; Grzegrzolka, Jedrzej; Piotrowska, Aleksandra; Matkowski, Rafal; Wojnar, Andrzej; Rys, Janusz; Ugorski, Maciej; Dziegiel, Piotr

    2017-10-01

    Periostin (POSTN) is a protein involved in multiple processes important for cancer development, both at the stage of cancer initiation and progression, as well as metastasis. The aim of this study was to determine the expression of POSTN in the cells of non-invasive ductal breast carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to correlate it with clinicopathological data. Immunohistochemical studies (IHC) were conducted on 21 cases of fibrocystic breast change (FC), 44 cases of DCIS and 92 cases of IDC. POSTN expression at mRNA (real-time PCR) and protein level (western blot analysis) was also confirmed in selected breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231 and BO2). Statistically significant higher level of POSTN expression in IDC and DCIS cancer cells compared to FC was noted. Also, the level of POSTN expression in the cytoplasm of IDC cells was shown to increase with the increasing degree of tumour malignancy (G) and significantly higher expression of POSTN was observed in each degree of tumour malignancy (G) relative to FC. Statistically significant higher POSTN expression was observed in tumours with estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) phenotypes in comparison to estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) cases, as well as significant negative correlation between POSTN expression in cancer cells and expression of ER and PR (p<0.05). Additionally, statistically significant differences in POSTN expression were shown between particular breast cancer cell lines, both at mRNA and protein level. Observed POSTN expression was the lowest in the case of MCF-7, and the highest in MDA-MB-231 and BO2 of the most aggressive potential clinically corresponding to G3 tumours. POSTN expression in the cytoplasm of IDC cancer cells may play an important role in cancer transformation mechanism.

  10. Exercise regulates breast cancer cell viability

    DEFF Research Database (Denmark)

    Dethlefsen, Christine; Lillelund, Christian; Midtgaard, Julie

    2016-01-01

    Purpose: Exercise decreases breast cancer risk and disease recurrence, but the underlying mechanisms are unknown. Training adaptations in systemic factors have been suggested as mediating causes. We aimed to examine if systemic adaptations to training over time, or acute exercise responses......, in breast cancer survivors could regulate breast cancer cell viability in vitro. Methods: Blood samples were collected from breast cancer survivors, partaking in either a 6-month training intervention or across a 2 h acute exercise session. Changes in training parameters and systemic factors were evaluated...... and pre/post exercise-conditioned sera from both studies were used to stimulate breast cancer cell lines (MCF-7, MDA-MB-231) in vitro. Results: Six months of training increased VO2peak (16.4 %, p

  11. Cancer stem cells, the ultimate targets in cancer therapy

    OpenAIRE

    Shabbir A; Esfandyari T; Farassati F

    2018-01-01

    Ahmed Shabbir,1 Tuba Esfandyari,2 Faris Farassati1,3,4 1Midwest Biomedical Research Foundation, Kansas City Veterans Affairs Medical Center, 2Department of Medicine, School of Medicine, The University of Kansas, 3Saint Luke’s Cancer Institute, 4Saint Luke’s Marion Bloch Neuroscience Institute, Saint Luke’s Health System, Kansas City, MO, USAThe concept of cancer stem cells (CSCs) is currently of significant interest due to its important implications in our under...

  12. Cancer stem cells, the ultimate targets in cancer therapy

    OpenAIRE

    Shabbir A; Esfandyari T; Farassati F

    2018-01-01

    Ahmed Shabbir,1 Tuba Esfandyari,2 Faris Farassati1,3,4 1Midwest Biomedical Research Foundation, Kansas City Veterans Affairs Medical Center, 2Department of Medicine, School of Medicine, The University of Kansas, 3Saint Luke’s Cancer Institute, 4Saint Luke’s Marion Bloch Neuroscience Institute, Saint Luke’s Health System, Kansas City, MO, USAThe concept of cancer stem cells (CSCs) is currently of significant interest due to its important implications in our understanding of ...

  13. Overcoming Multidrug Resistance in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Karobi Moitra

    2015-01-01

    Full Text Available The principle mechanism of protection of stem cells is through the expression of ATP-binding cassette (ABC transporters. These transporters serve as the guardians of the stem cell population in the body. Unfortunately these very same ABC efflux pumps afford protection to cancer stem cells in tumors, shielding them from the adverse effects of chemotherapy. A number of strategies to circumvent the function of these transporters in cancer stem cells are currently under investigation. These strategies include the development of competitive and allosteric modulators, nanoparticle mediated delivery of inhibitors, targeted transcriptional regulation of ABC transporters, miRNA mediated inhibition, and targeting of signaling pathways that modulate ABC transporters. The role of ABC transporters in cancer stem cells will be explored in this paper and strategies aimed at overcoming drug resistance caused by these particular transporters will also be discussed.

  14. Availability of stage at diagnosis, cancer treatment delay and compliance with cancer guidelines as cancer registry indicators for cancer care in Europe: Results of EUROCHIP-3 survey

    NARCIS (Netherlands)

    Siesling, Sabine; Kwast, A.; Gavin, A.; Baili, P.; Otter, R.

    2013-01-01

    EUROCHIP (European Cancer Health Indicators Project) focuses on understanding inequalities in the cancer burden, care and survival by the indicators “stage at diagnosis,” “cancer treatment delay” and “compliance with cancer guidelines” as the most important indicators. Our study aims at providing

  15. Socioeconomic Factors, Health Behavior, and Late-Stage Diagnosis of Breast Cancer: Considering the Impact of Delay in Diagnosis.

    Science.gov (United States)

    Dianatinasab, Mostafa; Mohammadianpanah, Mohammad; Daneshi, Nima; Zare-Bandamiri, Mohammad; Rezaeianzadeh, Abbas; Fararouei, Mohammad

    2017-09-19

    Stage of cancer at diagnosis is one of the most important factors in patient prognosis. By controlling for diagnostic delay, this study aimed to identify factors associated with late-stage breast cancer (BC). From November 2014 to January 2017, required information on 497 patients who were newly diagnosed with BC was obtained from patients' medical records. Logistic regression was used to measure the association between cancer stage and study variables. Only 18.3% of patients were diagnosed at stage I. The rest were diagnosed at stage II (45.5%) or higher (36.2%). Among those with ≤ 3 months' diagnostic delay, age (odds ratio [OR] = 0.96; 95% confidence interval [CI], 0.93-0.99), place of residence (OR urban/rural = 1.72; 95% CI, 1.42-1.93), income (OR high/low = 0.27; 95% CI, 0.10-0.72), performing breast self-examination (OR yes/no = 0.51; 95% CI, 0.0.26 -0.98), smoking (OR yes/no = 2.23; 95% CI, 1.37-3.62), history of chest X-ray (OR yes/no = 1.40; 95% CI, 1.16-1.98), presence of chronic diseases (OR yes/no = 1.73; 95% CI, 1.36-5.48), and, for those with a delay of > 3 months, marriage age (OR = 0.83; 95% CI, 0.73-0.94), income (OR high/low = 0.07; 95% CI, 0.008-0.63), family history of BC (OR = 3.82; 95% CI, 1.05-5.05), daily exercise (OR < 10/10-20 = 0.10; 95% CI, 0.01-0.67), and presence of chronic diseases (OR yes/no = 1.77; 95% CI, 1.73-5.07), were associated with late-stage of cancer. Shortening the diagnostic delay can help patients receive medical treatment at an earlier disease stage, resulting in better prognosis. Smokers, younger women, and those with chronic conditions or a family history of BC should take extra caution, as they may have worse prognosis if diagnosed with cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Identification of cancer stem-like side population cells in ovarian cancer cell line OVCAR-3.

    Science.gov (United States)

    Gao, Quanli; Geng, Li; Kvalheim, Gunnar; Gaudernack, Gustav; Suo, Zhenhe

    2009-01-01

    Side population (SP) cells may enrich stem-like cells in many normal and malignant tissues. However, SP method application has drawn special attention to the field of stem cell research, and the existence of SP cells in cell culture is being debated, most probably because different cell lines require different technical modifications, especially when cell staining is considered. In this study, the authors aimed to disclose whether the hoechst33342 staining required extensive optimization for identifying SP cells in the human ovarian cancer cell line OVCAR-3. After systematic evaluations, it was found that only 2.5 microg/mL hoechst33342 staining of the cells for 60 min could get an ideal SP population, which accounted for 0.9% of the whole cell population. The sorted SP cells showed significantly higher colony formation efficiency than the non-side population (NSP) cells, and only the SP cells could form holoclones. Real-time PCR disclosed that SP cells expressed higher levels of "stemness" gene Oct3/4 than the NSP cells did, indicating that the SP cells might harbor cancer stem cells in this cell line. The results highlight the necessity of SP method optimization in cell studies, and the SP cells in this cell line merit further studies when cancer stem cell identification and isolation are considered.

  17. Cancer stem cells and their implication in breast cancer.

    Science.gov (United States)

    Carrasco, E; Alvarez, Pablo J; Prados, José; Melguizo, Consolación; Rama, Ana R; Aránega, Antonia; Rodríguez-Serrano, Fernando

    2014-07-01

    The cancer stem cell (CSC) hypothesis on the origin of cancer has recently gained considerable support. CSCs are tumour cells with the capacity for self-renewal and differentiation that direct the origin and progression of the disease and may be responsible for relapse, metastasis and treatment failures. This article reviews breast CSCs (BCSCs) phenotyping, clinical implications and clinical trials focused on BCSCs in breast cancer. Relevant studies were found through PubMed and Clinicaltrials.gov databases. Cancer stem cells are identified and isolated using membrane and cell activity markers; in the case of BCSCs, these are CD44(+) /CD24(low/-) and show aldehyde dehydrogenase activity, alongside their capacity to grow and form mammospheres. The presence of stem cell properties is associated with a worse outcome. Hence, these cells have important clinical implications, and elucidation of the mechanisms underlying their activity will allow the development of novel effective therapies and diagnostic instruments, improving the prognosis of these patients. Standard treatments are directed against the tumour mass and do not eliminate CSCs. There is therefore a need for specific anti-CSC therapies, and numerous authors are investigating new targets to this end, as reported in this review. It is also necessary for clinical trials to be undertaken to allow this new knowledge to be applied in the clinical setting. However, there have been few trials on anti-BCSCs therapies to date. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  18. Human Cancer Classification: A Systems Biology- Based Model Integrating Morphology, Cancer Stem Cells, Proteomics, and Genomics

    OpenAIRE

    Halliday A Idikio

    2011-01-01

    Human cancer classification is currently based on the idea of cell of origin, light and electron microscopic attributes of the cancer. What is not yet integrated into cancer classification are the functional attributes of these cancer cells. Recent innovative techniques in biology have provided a wealth of information on the genomic, transcriptomic and proteomic changes in cancer cells. The emergence of the concept of cancer stem cells needs to be included in a classification model to capture...

  19. Cell Phones and Cancer Risk

    Science.gov (United States)

    ... Español 1-800-4-CANCER Live Chat Publications Dictionary Menu Contact Dictionary Search About Cancer Causes and Prevention Risk Factors ... interagency program headquartered at the National Institute of Environmental Health Sciences (NIEHS), which is part of the ...

  20. Game theory in the death galaxy: interaction of cancer and stromal cells in tumour microenvironment.

    Science.gov (United States)

    Wu, Amy; Liao, David; Tlsty, Thea D; Sturm, James C; Austin, Robert H

    2014-08-06

    Preventing relapse is the major challenge to effective therapy in cancer. Within the tumour, stromal (ST) cells play an important role in cancer progression and the emergence of drug resistance. During cancer treatment, the fitness of cancer cells can be enhanced by ST cells because their molecular signalling interaction delays the drug-induced apoptosis of cancer cells. On the other hand, competition among cancer and ST cells for space or resources should not be ignored. We explore the population dynamics of multiple myeloma (MM) versus bone marrow ST cells by using an experimental microecology that we call the death galaxy, with a stable drug gradient and connected microhabitats. Evolutionary game theory is a quantitative way to capture the frequency-dependent nature of interactive populations. Therefore, we use evolutionary game theory to model the populations in the death galaxy with the gradients of pay-offs and successfully predict the future densities of MM and ST cells. We discuss the possible clinical use of such analysis for predicting cancer progression.

  1. Induction of cancer stem cell properties in colon cancer cells by defined factors.

    Directory of Open Access Journals (Sweden)

    Nobu Oshima

    Full Text Available Cancer stem cells (CSCs are considered to be responsible for the dismal prognosis of cancer patients. However, little is known about the molecular mechanisms underlying the acquisition and maintenance of CSC properties in cancer cells because of their rarity in clinical samples. We herein induced CSC properties in cancer cells using defined factors. We retrovirally introduced a set of defined factors (OCT3/4, SOX2 and KLF4 into human colon cancer cells, followed by culture with conventional serum-containing medium, not human embryonic stem cell medium. We then evaluated the CSC properties in the cells. The colon cancer cells transduced with the three factors showed significantly enhanced CSC properties in terms of the marker gene expression, sphere formation, chemoresistance and tumorigenicity. We designated the cells with CSC properties induced by the factors, a subset of the transduced cells, as induced CSCs (iCSCs. Moreover, we established a novel technology to isolate and collect the iCSCs based on the differences in the degree of the dye-effluxing activity enhancement. The xenografts derived from our iCSCs were not teratomas. Notably, in contrast to the tumors from the parental cancer cells, the iCSC-based tumors mimicked actual human colon cancer tissues in terms of their immunohistological findings, which showed colonic lineage differentiation. In addition, we confirmed that the phenotypes of our iCSCs were reproducible in serial transplantation experiments. By introducing defined factors, we generated iCSCs with lineage specificity directly from cancer cells, not via an induced pluripotent stem cell state. The novel method enables us to obtain abundant materials of CSCs that not only have enhanced tumorigenicity, but also the ability to differentiate to recapitulate a specific type of cancer tissues. Our method can be of great value to fully understand CSCs and develop new therapies targeting CSCs.

  2. The therapeutic promise of the cancer stem cell concept

    National Research Council Canada - National Science Library

    Frank, Natasha Y; Schatton, Tobias; Frank, Markus H

    2010-01-01

    Cancer stem cells (CSCs) are a subpopulation of tumor cells that selectively possess tumor initiation and self-renewal capacity and the ability to give rise to bulk populations of nontumorigenic cancer cell progeny through differentiation...

  3. The telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines.

    Science.gov (United States)

    Joseph, Immanual; Tressler, Robert; Bassett, Ekaterina; Harley, Calvin; Buseman, Christen M; Pattamatta, Preeti; Wright, Woodring E; Shay, Jerry W; Go, Ning F

    2010-11-15

    Cancer stem cells (CSC) are rare drug-resistant cancer cell subsets proposed to be responsible for the maintenance and recurrence of cancer and metastasis. Telomerase is constitutively active in both bulk tumor cell and CSC populations but has only limited expression in normal tissues. Thus, inhibition of telomerase has been shown to be a viable approach in controlling cancer growth in nonclinical studies and is currently in phase II clinical trials. In this study, we investigated the effects of imetelstat (GRN163L), a potent telomerase inhibitor, on both the bulk cancer cells and putative CSCs. When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited. Additionally, imetelstat treatment reduced the CSC fractions present in the breast and pancreatic cell lines. In vitro treatment with imetelstat, but not control oligonucleotides, also reduced the proliferation and self-renewal potential of MCF7 mammospheres and resulted in cell death after telomerase activity expression levels or telomere length of CSCs and bulk tumor cells in these cell lines did not correlate with the increased sensitivity of CSCs to imetelstat, suggesting a mechanism of action independent of telomere shortening for the effects of imetelstat on the CSC subpopulations. Our results suggest that imetelstat-mediated depletion of CSCs may offer an alternative mechanism by which telomerase inhibition may be exploited for cancer therapy. Copyright © 2010 AACR.

  4. Liver cancer stem cells as an important target in liver cancer therapies.

    Science.gov (United States)

    Zou, Gang-Ming

    2010-02-01

    Hepatic cancer is one of most common cause of cancer-related death. Hepato-epithelial cancers are believed to originate from the malignant transformation of liver-resident stem/progenitor cells. Liver cancer stem cells have been characterized recently and the phenotype of liver cancer stem cells has been defined as CD133+ CD44+ cancer cells. Recently, it has been also demonstrated about the relevance of targeting liver cancer stem cells, due to cancer stem cells are related to cancer metastasis. These advances no doubt to bring the new strategy in liver cancer treatment and control in this disease. This review describes the current status and progress about cancer stem cell research in liver and discuss of the implications of these studies in new liver cancer treatment strategies.

  5. Cells as delivery vehicles for cancer therapeutics.

    Science.gov (United States)

    Basel, Matthew T; Shrestha, Tej B; Bossmann, Stefan H; Troyer, Deryl L

    2014-05-01

    Cell-based therapeutics have advanced significantly over the past decade and are poised to become a major pillar of modern medicine. Three cell types in particular have been studied in detail for their ability to home to tumors and to deliver a variety of different payloads. Neural stem cells, mesenchymal stem cells and monocytes have each been shown to have great potential as future delivery systems for cancer therapy. A variety of other cell types have also been studied. These results demonstrate that the field of cell-based therapeutics will only continue to grow.

  6. Delayed cell cycle pathway modulation facilitates recovery after spinal cord injury

    Science.gov (United States)

    Wu, Junfang; Stoica, Bogdan A.; Dinizo, Michael; Pajoohesh-Ganji, Ahdeah; Piao, Chunshu; Faden, Alan I.

    2012-01-01

    Traumatic spinal cord injury (SCI) causes tissue loss and associated neurological dysfunction through mechanical damage and secondary biochemical and physiological responses. We have previously described the pathobiological role of cell cycle pathways following rat contusion SCI by examining the effects of early intrathecal cell cycle inhibitor treatment initiation or gene knockout on secondary injury. Here, we delineate changes in cell cycle pathway activation following SCI and examine the effects of delayed (24 h) systemic administration of flavopiridol, an inhibitor of major cyclin-dependent kinases (CDKs), on functional recovery and histopathology in a rat SCI contusion model. Immunoblot analysis demonstrated a marked upregulation of cell cycle-related proteins, including pRb, cyclin D1, CDK4, E2F1 and PCNA, at various time points following SCI, along with downregulation of the endogenous CDK inhibitor p27. Treatment with flavopiridol reduced induction of cell cycle proteins and increased p27 expression in the injured spinal cord. Functional recovery was significantly improved after SCI from day 7 through day 28. Treatment significantly reduced lesion volume and the number of Iba-1+ microglia in the preserved tissue and increased the myelinated area of spared white matter as well as the number of CC1+ oligodendrocytes. Furthermore, flavopiridol attenuated expression of Iba-1 and glactin-3, associated with microglial activation and astrocytic reactivity by reduction of GFAP, NG2, and CHL1 expression. Our current study supports the role of cell cycle activation in the pathophysiology of SCI and by using a clinically relevant treatment model, provides further support for the therapeutic potential of cell cycle inhibitors in the treatment of human SCI. PMID:22510563

  7. NSAIDs and Cell Proliferation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Raj Ettarh

    2010-06-01

    Full Text Available Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration, could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.

  8. Phenotype heterogeneity in cancer cell populations

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luis [CNRS UMR 7598, LJLL, & INRIA MAMBA team, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, luis@ann.jussieu.fr (France); Chisholm, Rebecca [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia, rebecca.chisholm@gmail.com (Australia); Clairambault, Jean [INRIA MAMBA team & LJLL, UMR 7598, Sorbonne Universités, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, jean.clairambault@inria.fr, Corresponding author (France); Escargueil, Alexandre [INSERM “Cancer Biology and Therapeutics”, Sorbonne Universités, UPMC Univ Paris 06, UMR-S 938, CDR St Antoine, Hôpital St Antoine, 184 Fbg. St Antoine, 75571 Paris cedex 12, France, alexandre.escargueil@upmc.fr (France); Lorenzi, Tommaso [CMLA, ENS Cachan, 61, Av. du Président Wilson, 94230 Cachan cedex & INRIA MAMBA team, & LJLL, UMR 7598, UPMC Univ Paris 06, Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, tommaso.lorenzi@gmail.com (France); Lorz, Alexander [Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598 & INRIA Boîte courrier 187, 4 Pl. Jussieu, 75252 Paris cedex 05, France, alex.lorz@ann.jussieu.fr (France); Trélat, Emmanuel [Institut Universitaire de France, Sorbonne Universités, UPMC Univ Paris 06, LJLL, UMR 7598, Boîte courrier 187, UPMC Univ Paris 06, 4 Pl. Jussieu, 75252 Paris cedex 05, France, emmanuel.trelat@upmc.fr (France)

    2016-06-08

    Phenotype heterogeneity in cancer cell populations, be it of genetic, epigenetic or stochastic origin, has been identified as a main source of resistance to drug treatments and a major source of therapeutic failures in cancers. The molecular mechanisms of drug resistance are partly understood at the single cell level (e.g., overexpression of ABC transporters or of detoxication enzymes), but poorly predictable in tumours, where they are hypothesised to rely on heterogeneity at the cell population scale, which is thus the right level to describe cancer growth and optimise its control by therapeutic strategies in the clinic. We review a few results from the biological literature on the subject, and from mathematical models that have been published to predict and control evolution towards drug resistance in cancer cell populations. We propose, based on the latter, optimisation strategies of combined treatments to limit emergence of drug resistance to cytotoxic drugs in cancer cell populations, in the monoclonal situation, which limited as it is still retains consistent features of cell population heterogeneity. The polyclonal situation, that may be understood as “bet hedging” of the tumour, thus protecting itself from different sources of drug insults, may lie beyond such strategies and will need further developments. In the monoclonal situation, we have designed an optimised therapeutic strategy relying on a scheduled combination of cytotoxic and cytostatic treatments that can be adapted to different situations of cancer treatments. Finally, we review arguments for biological theoretical frameworks proposed at different time and development scales, the so-called atavistic model (diachronic view relying on Darwinian genotype selection in the coursof billions of years) and the Waddington-like epigenetic landscape endowed with evolutionary quasi-potential (synchronic view relying on Lamarckian phenotype instruction of a given genome by reversible mechanisms), to

  9. The singlet-oxygen-sensitized delayed fluorescence in mammalian cells: a time-resolved microscopy approach.

    Science.gov (United States)

    Scholz, Marek; Biehl, Anna-Louisa; Dědic, Roman; Hála, Jan

    2015-04-01

    The present work provides a proof-of-concept that the singlet oxygen-sensitized delayed fluorescence (SOSDF) can be detected from individual living mammalian cells in a time-resolved microscopy experiment. To this end, 3T3 mouse fibroblasts incubated with 100 μM TPPS4 or TMPyP were used and the microsecond kinetics of the delayed fluorescence (DF) were recorded. The analysis revealed that SOSDF is the major component of the overall DF signal. The microscopy approach enables precise control of experimental conditions - the DF kinetics are clearly influenced by the presence of the (1)O2 quencher (sodium azide), H2O/D2O exchange, and the oxygen concentration. Analysis of SOSDF kinetics, which was reconstructed as a difference DF kinetics between the unquenched and the NaN3-quenched samples, provides a cellular (1)O2 lifetime of τΔ = 1-2 μs and a TPPS4 triplet lifetime of τT = 22 ± 5 μs in agreement with previously published values. The short SOSDF acquisition times, typically in the range of tens of seconds, enable us to study the dynamic cellular processes. It is shown that SOSDF lifetimes increase during PDT-like treatment, which may provide valuable information about changes of the intracellular microenvironment. SOSDF is proposed and evaluated as an alternative tool for (1)O2 detection in biological systems.

  10. Impaired immune evasion in HIV through intracellular delays and multiple infection of cells

    Science.gov (United States)

    Althaus, Christian L.; De Boer, Rob J.

    2012-01-01

    With its high mutation rate, HIV is capable of escape from recognition, suppression and/or killing by CD8+ cytotoxic T lymphocytes (CTLs). The rate at which escape variants replace each other can give insights into the selective pressure imposed by single CTL clones. We investigate the effects of specific characteristics of the HIV life cycle on the dynamics of immune escape. First, it has been found that cells in HIV-infected patients can carry multiple copies of proviruses. To investigate how this process affects the emergence of immune escape, we develop a mathematical model of HIV dynamics with multiple infections of cells. Increasing the frequency of multiple-infected cells delays the appearance of immune escape variants, slows down the rate at which they replace the wild-type variant and can even prevent escape variants from taking over the quasi-species. Second, we study the effect of the intracellular eclipse phase on the rate of escape and show that escape rates are expected to be slower than previously anticipated. In summary, slow escape rates do not necessarily imply inefficient CTL-mediated killing of HIV-infected cells, but are at least partly a result of the specific characteristics of the viral life cycle. PMID:22492063

  11. IL-4-mediated drug resistance in colon cancer stem cells

    NARCIS (Netherlands)

    Todaro, Matilde; Perez Alea, Mileidys; Scopelliti, Alessandro; Medema, Jan Paul; Stassi, Giorgio

    2008-01-01

    Cancer stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Cancer stem cells are thus likely to be responsible for maintaining or spreading a cancer, and may be the most relevant targets for cancer therapy. The CD133 glycoprotein was recently

  12. Stem Cell Transplants in Cancer Treatment

    Science.gov (United States)

    Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

  13. Harnessing the apoptotic programs in cancer stem-like cells.

    Science.gov (United States)

    Wang, Ying-Hua; Scadden, David T

    2015-09-01

    Elimination of malignant cells is an unmet challenge for most human cancer types even with therapies targeting specific driver mutations. Therefore, a multi-pronged strategy to alter cancer cell biology on multiple levels is increasingly recognized as essential for cancer cure. One such aspect of cancer cell biology is the relative apoptosis resistance of tumor-initiating cells. Here, we provide an overview of the mechanisms affecting the apoptotic process in tumor cells emphasizing the differences in the tumor-initiating or stem-like cells of cancer. Further, we summarize efforts to exploit these differences to design therapies targeting that important cancer cell population. © 2015 The Authors.

  14. Epithelial cell polarity, stem cells and cancer

    DEFF Research Database (Denmark)

    Martin-Belmonte, Fernando; Perez-Moreno, Mirna

    2011-01-01

    , deregulation of adhesion and polarity proteins can cause misoriented cell divisions and increased self-renewal of adult epithelial stem cells. In this Review, we highlight some advances in the understanding of how loss of epithelial cell polarity contributes to tumorigenesis.......After years of extensive scientific discovery much has been learned about the networks that regulate epithelial homeostasis. Loss of expression or functional activity of cell adhesion and cell polarity proteins (including the PAR, crumbs (CRB) and scribble (SCRIB) complexes) is intricately related...

  15. Does pyogenic liver abscess increase the risk of delayed-onset primary liver cancer?: Evidence from a nationwide cohort study.

    Science.gov (United States)

    Chu, Chia-Sheng; Lin, Che-Chen; Peng, Cheng-Yuan; Chuang, Po-Heng; Su, Wen-Pang; Lai, Shih-Wei; Chen, Hsuan-Ju; Chung, Chi-Jung; Lai, Hsueh-Chou

    2017-08-01

    Delayed-onset primary liver cancer (PLC) including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in patients with pyogenic liver abscess (PLA) is not common. The relationship between PLA and delayed-onset PLC is unclear. We investigated the association in a nationwide cohort study.From Taiwan National Health Insurance claims data, a cohort of 17,531 patients with PLA was generated after excluding patients with a history of cancer (n = 2034) and those diagnosed with PLC (n = 572) and other cancers (n = 627) within 1 year of a diagnosis of PLA. An age-, sex-, index year-, and diabetes mellitus (DM)-matched control cohort of 70,124 persons without PLA was selected from the same dataset. Both cohorts were followed up until the end of 2011. The risk of PLC was estimated for both cohorts.The incidence of PLC was nearly 2-fold greater in the PLA group than in the control cohort (29.3 per 10,000 person-years vs. 16.2 per 10,000 person-years). The incidences of HCC and ICC were 1.5- (22.1 per 10,000 person-years vs. 15.0 per 10,000 person-years) and 11-fold greater (6.73 per 10,000 person-years vs. 0.62 per 10,000 person-years), respectively, in the PLA group than in the control cohort. The PLA cohort also had high risks of PLC (adjusted hazard ratio [aHR] = 1.56; 95% confidence interval [CI] = 1.35-1.81), HCC (aHR = 1.34; 95% CI = 1.15-1.57), and ICC (aHR = 6.94; 95% CI = 4.23-11.57).In conclusion, in this nationwide cohort study, PLA increased the risk of delayed-onset PLC.

  16. T cell recognition of breast cancer antigens

    DEFF Research Database (Denmark)

    Petersen, Nadia Viborg; Andersen, Sofie Ramskov; Andersen, Rikke Sick

    Recent studies are encouraging research of breast cancer immunogenicity to evaluate the applicability ofimmunotherapy as a treatment strategy. The epitope landscape in breast cancer is minimally described, thus it is necessary to identify T cell targets to develop immune mediated therapies.......This project investigates four proteins commonly upregulated in breast cancer and thus probable tumor associated antigens (TAAs). Aromatase, prolactin, NEK3, and PIAS3 contribute to increase growth, survival, and motility of malignant cells. Aspiring to uncover novel epitopes for cytotoxic T cells, a reverse...... immunology approach is applied. Via in silico screening of the protein sequences, 415 peptides were predicted as HLA-A*0201 and HLA-B*0702 binders. Subsequent in vitro binding analysis in a MHC ELISA platform confirmed binding for 147 of the 415 predicted binders. The 147 peptides were evaluated for T cell...

  17. Delaying Renal Transplant after Radical Prostatectomy for Low-Risk Prostate Cancer.

    Science.gov (United States)

    Özçelik, Ümit; Bircan, Hüseyin Yüce; Karakayalı, Feza; Moray, Gökhan; Demirağ, Alp

    2015-11-01

    To minimize the recurrence of a previously treated neoplasm in organ recipients, a period of 2 to 5 years without recurrence is advocated for most malignancies. However, prostate cancer is different because of its biological properties, diagnosis, and treatment. Most prostate cancers are detected at a low stage and demonstrate slow growth after detection. Definitive treatment with radical prostatectomy affords excellent results. Renal transplant candidates with early-stage prostate cancer have a higher risk of dying on dialysis than dying from prostate cancer; therefore, renal transplant candidates with organ-confined prostate cancer should be immediately considered for transplant.

  18. Equine herpesvirus type 1 replication is delayed in CD172a+ monocytic cells and controlled by histone deacetylases.

    Science.gov (United States)

    Laval, Kathlyn; Favoreel, Herman W; Nauwynck, Hans J

    2015-01-01

    Equine herpesvirus type 1 (EHV-1) replicates in the epithelial cells of the upper respiratory tract and disseminates through the body via a cell-associated viraemia in monocytic cells, despite the presence of neutralizing antibodies. However, the mechanism by which EHV-1 hijacks immune cells and uses them as 'Trojan horses' in order to disseminate inside its host is still unclear. Here, we hypothesize that EHV-1 delays its replication in monocytic cells in order to avoid recognition by the immune system. We compared replication kinetics in vitro of EHV-1 in RK-13, a cell line fully susceptible to EHV-1 infection, and primary horse cells from the myeloid lineage (CD172a(+)). We found that EHV-1 replication was restricted to 4 % of CD172a(+) cells compared with 100 % in RK-13 cells. In susceptible CD172a(+) cells, the expression of immediate-early (IEP) and early (EICP22) proteins was delayed in the cell nuclei by 2-3 h post-infection (p.i.) compared with RK-13, and the formation of replicative compartments by 15 h p.i. Virus production in CD172a(+) cells was significantly lower (from 10(1.7) to 10(3.1) TCID50 per 10(5) inoculated cells) than in RK-13 (from 10(5) to 10(5.7) TCID50 per 10(5) inoculated cells). Less than 0.02 % of inoculated CD172a(+) cells produced and transmitted infectious virus to neighbouring cells. Pre-treatment of CD172a(+) cells with inhibitors of histone deacetylase activity increased and accelerated viral protein expression at very early times of infection and induced productive infection in CD172a(+) cells. Our results demonstrated that the restriction and delay of EHV-1 replication in CD172a(+) cells are part of an immune evasive strategy and involve silencing of EHV-1 gene expression associated with histone deacetylases. © 2015 The Authors.

  19. Phenotypic Heterogeneity of Breast Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Aurelio Lorico

    2011-01-01

    Full Text Available Many types of tumors are organized in a hierarchy of heterogeneous cell populations, with only a small proportion of cancer stem cells (CSCs capable of sustaining tumor formation and growth, giving rise to differentiated cells, which form the bulk of the tumor. Proof of the existence of CSC comes from clinical experience with germ-cell cancers, where the elimination of a subset of undifferentiated cells can cure patients (Horwich et al., 2006, and from the study of leukemic cells (Bonnet and Dick, 1997; Lapidot et al., 1994; and Yilmaz et al., 2006. The discovery of CSC in leukemias as well as in many solid malignancies, including breast carcinoma (Al-Hajj et al. 2003; Fang et al., 2005; Hemmati et al., 2003; Kim et al., 2005; Lawson et al., 2007; Li et al., 2007; Ricci-Vitiani et al., 2007; Singh et al., 2003; and Xin et al., 2005, has suggested a unifying CSC theory of cancer development. The reported general insensitivity of CSC to chemotherapy and radiation treatment (Bao et al., 2006 has suggested that current anticancer drugs, which inhibit bulk replicating cancer cells, may not effectively inhibit CSC. The clinical relevance of targeting CSC-associated genes is supported by several recent studies, including CD44 targeting for treatment of acute myeloid leukemia (Jin et al., 2006, CD24 targeting for treatment of colon and pancreatic cancer (Sagiv et al., 2008, and CD133 targeting for hepatocellular and gastric cancer (Smith et al., 2008. One promising approach is to target CSC survival signaling pathways, where leukemia stem cell research has already made some progress (Mikkola et al., 2010.

  20. Small margin (2 mm) excision of peri-ocular basal cell carcinoma with delayed repair.

    Science.gov (United States)

    David, D B.; Gimblett, M L.; Potts, M J.; Harrad, R A.

    1999-03-01

    Successful surgical treatment of peri-ocular basal cell carcinomas requires complete excision. Mohs' micrographic surgery achieves this, but is not readily available in all hospitals. The standard 3-4 mm margin does not guarantee complete excision and histology is often not available until after a repair has been undertaken. The 3-4 mm margin has evolved to deal with all forms of BCC. In our opinion, this margin is unnecessarily large for nodular/ulcerative BCC. We report our interim results of excision of localised BCCs using a 2 mm margin in conjunction with a delayed repair following confirmation of histological clearance. Thirty-one patients were treated in this manner; there have been no recurrences after an average follow-up period of 36 months (range 24-57 months).

  1. Coronatine inhibits stomatal closure and delays hypersensitive response cell death induced by nonhost bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Seonghee Lee

    2013-02-01

    Full Text Available Pseudomonas syringae is the most widespread bacterial pathogen in plants. Several strains of P. syringae produce a phytotoxin, coronatine (COR, which acts as a jasmonic acid mimic and inhibits plant defense responses and contributes to disease symptom development. In this study, we found that COR inhibits early defense responses during nonhost disease resistance. Stomatal closure induced by a nonhost pathogen, P. syringae pv. tabaci, was disrupted by COR in tomato epidermal peels. In addition, nonhost HR cell death triggered by P. syringae pv. tabaci on tomato was remarkably delayed when COR was supplemented along with P. syringae pv. tabaci inoculation. Using isochorismate synthase (ICS-silenced tomato plants and transcript profiles of genes in SA- and JA-related defense pathways, we show that COR suppresses SA-mediated defense during nonhost resistance.

  2. Can Full Duplex Boost Throughput and Delay of 5G Ultra-Dense Small Cell Networks?

    DEFF Research Database (Denmark)

    Gatnau, Marta; Berardinelli, Gilberto; Mahmood, Nurul Huda

    2016-01-01

    Given the recent advances in system and antenna design, practical implementation of full duplex (FD) communication is becoming increasingly feasible. In this paper, the potential of FD in enhancing the performance of 5th generation (5G) ultra-dense small cell networks is investigated. The goal...... is to understand whether FD is able to boost the system performance from a throughput and delay perspective. The impact of having symmetric and asymmetric finite buffer traffic is studied for two types of FD: when only the base station is FD capable, and when both the user equipment and base station are FD nodes....... System level results indicate that there is a trade-off between multiple-input multiple-output (MIMO) spatial multiplexing and FD in achieving the optimal system performance. Moreover, results show that FD may be useful for asymmetric traffic applications where the lightly loaded link requires high level...

  3. CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.

    Science.gov (United States)

    Chen, Li-Shiun; Hung, Rayjean J; Baker, Timothy; Horton, Amy; Culverhouse, Rob; Saccone, Nancy; Cheng, Iona; Deng, Bo; Han, Younghun; Hansen, Helen M; Horsman, Janet; Kim, Claire; Lutz, Sharon; Rosenberger, Albert; Aben, Katja K; Andrew, Angeline S; Breslau, Naomi; Chang, Shen-Chih; Dieffenbach, Aida Karina; Dienemann, Hendrik; Frederiksen, Brittni; Han, Jiali; Hatsukami, Dorothy K; Johnson, Eric O; Pande, Mala; Wrensch, Margaret R; McLaughlin, John; Skaug, Vidar; van der Heijden, Henricus F; Wampfler, Jason; Wenzlaff, Angela; Woll, Penella; Zienolddiny, Shanbeh; Bickeböller, Heike; Brenner, Hermann; Duell, Eric J; Haugen, Aage; Heinrich, Joachim; Hokanson, John E; Hunter, David J; Kiemeney, Lambertus A; Lazarus, Philip; Le Marchand, Loic; Liu, Geoffrey; Mayordomo, Jose; Risch, Angela; Schwartz, Ann G; Teare, Dawn; Wu, Xifeng; Wiencke, John K; Yang, Ping; Zhang, Zuo-Feng; Spitz, Margaret R; Kraft, Peter; Amos, Christopher I; Bierut, Laura J

    2015-05-01

    Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis. Meta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each dataset, we used Cox regression models to evaluate the association between rs16969968 and the two primary phenotypes (age of smoking cessation among ever smokers and age of lung cancer diagnosis among lung cancer case patients) and the secondary phenotype of smoking duration. Heterogeneity across studies was assessed with the Cochran Q test. All statistical tests were two-sided. The rs16969968 allele (A) was associated with a lower likelihood of smoking cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98, P = .0042), and the AA genotype was associated with a four-year delay in median age of quitting compared with the GG genotype. Among smokers with lung cancer diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95% CI = 1.04 to 1.12, P = 1.1*10(-5)). These data support the clinical significance of the CHRNA5 variant rs16969968. It predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis. Given the existing evidence that this CHRNA5 variant predicts favorable response to cessation pharmacotherapy, these findings underscore the potential clinical and public health importance of rs16969968 in CHRNA5 in relation to smoking cessation success and lung cancer risk. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Targeting regulatory T cells in cancer.

    LENUS (Irish Health Repository)

    Byrne, William L

    2012-01-31

    Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.

  5. Cancer stem cells in the development of liver cancer

    Science.gov (United States)

    Yamashita, Taro; Wang, Xin Wei

    2013-01-01

    Liver cancer is an aggressive disease with a poor outcome. Several hepatic stem/progenitor markers are useful for isolating a subset of liver cells with stem cell features, known as cancer stem cells (CSCs). These cells are responsible for tumor relapse, metastasis, and chemoresistance. Liver CSCs dictate a hierarchical organization that is shared in both organogenesis and tumorigenesis. An increased understanding of the molecular signaling events that regulate cellular hierarchy and stemness, and success in defining key CSC-specific genes, have opened up new avenues to accelerate the development of novel diagnostic and treatment strategies. This Review highlights recent advances in understanding the pathogenesis of liver CSCs and discusses unanswered questions about the concept of liver CSCs. PMID:23635789

  6. Luteal cell steroidogenesis in relation to delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Meenakumari, Karukayil J; Banerjee, Arnab; Krishna, Amitabh

    2009-01-01

    The primary aim of this study was to determine the possible cause of slow or delayed embryonic development in Cynopterus sphinx by investigating morphological and steroidogenic changes in the corpus luteum (CL) and circulating hormone concentrations during two pregnancies of a year. This species showed delayed post-implantational embryonic development during gastrulation of the first pregnancy. Morphological features of the CL showed normal luteinization during both pregnancies. The CL did not change significantly in luteal cell size during the delay period of the first pregnancy as compared with the second pregnancy. The circulating progesterone and 17beta-estradiol concentrations were significantly lower during the period of delayed embryonic development as compared with the same stage of embryonic development during the second pregnancy. We also showed a marked decline in the activity of 3beta-hydroxysteroid dehydrogenase, P450 side chain cleavage enzyme, and steroidogenic acute regulatory peptide in the CL during the delay period. This may cause low circulating progesterone and estradiol synthesis and consequently delay embryonic development. What causes the decrease in steroidogenic factors in the CL during the period of delayed development in C. sphinx is under investigation.

  7. Sunitinib for advanced renal cell cancer

    Directory of Open Access Journals (Sweden)

    Chris Coppin

    2008-03-01

    Full Text Available Chris CoppinBC Cancer Agency and University of British Columbia, Vancouver, CanadaAbstract: Renal cell cancer has been refractory to drug therapy in the large majority of patients. Targeted agents including sunitinib have been intensively evaluated in renal cell cancer over the past 5 years. Sunitinib is an oral small molecule inhibitor of several targets including multiple tyrosine kinase receptors of the angiogenesis pathway. This review surveys the rationale, development, validation, and clinical use of sunitinib that received conditional approval for use in North America and Europe in 2006. In patients with the clear-cell subtype of renal cell cancer and metastatic disease with good or moderate prognostic factors for survival, sunitinib 50 mg for 4 weeks of a 6-week cycle provides superior surrogate and patient-reported outcomes when compared with interferon-alfa, the previous commonly used first-line drug. Overall survival has not yet shown improvement over interferon and is problematic because of patient crossover from the control arm to sunitinib at disease progression. Toxicity is significant but manageable with experienced monitoring. Sunitinib therapy is an important step forward for this condition. High cost and limited efficacy support the ongoing search for further improved therapy.Keywords: renal cell cancer, targeted therapy, sunitinib

  8. with esophageal squamous cell cancer

    Directory of Open Access Journals (Sweden)

    Tao Li

    2017-02-01

    Full Text Available Purpose: The aim of this study was to retrospectively observe and analyze the long-term treatment outcomes of 191 elderly patients with esophageal squamous cell cancer (ESCC who were treated with californium-252 (252Cf neutron brachytherapy (NBT in combination with external beam radiotherapy (EBRT. Material and methods : From January 2002 to November 2012, 191 patients with ESCC underwent NBT in combination with EBRT. The total radiation dose to the reference point via NBT was 8-25 Gy-eq in two to five fractions with one fraction per week. The total dose via EBRT was 50-60 Gy, which was delivered over a period of 5 to 6 weeks with normal fractionation. Results : The median survival time for the 191 patients was 23.6 months, and the 5-year rates for overall survival (OS and local-regional control (LRC were 28.7% and 54.2%, respectively. The patients’ age was a factor that was significantly associated with OS (p = 0.010, according to univariate analysis. The 5-year OS (LRC was 37.3% (58.6% for patients aged 70-74 years and 14.5% (47.9% for patients aged > 74 years (p = 0.010 and p = 0.038. In multivariate analysis, age and clinical N stage were associated with OS and LRC (p = 0.011 [0.041] and p = 0.005 [0.005]. From the time of treatment completion to the development of local-regional recurrence or death, 5 (2.6% patients experienced fistula and 15 (7.9% experienced massive bleeding. The incidence of severe late complications was related to older age (p = 0.027, higher NBT dose/fraction (20-25 Gy/5 fractions, and higher total dose (> 66 Gy. Conclusions : The clinical data indicated that NBT in combination with EBRT produced favorable local control and long-term survival rates for elderly patients with ESCC, and that the side effects were tolerable. Patient’s age, clinical stage N status, and radiation dose could be used to select the appropriate treatment for elderly patients.

  9. Gastric cancer stem cells: A novel therapeutic target

    Science.gov (United States)

    Singh, Shree Ram

    2013-01-01

    Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

  10. Altered calcium signaling in cancer cells.

    Science.gov (United States)

    Stewart, Teneale A; Yapa, Kunsala T D S; Monteith, Gregory R

    2015-10-01

    It is the nature of the calcium signal, as determined by the coordinated activity of a suite of calcium channels, pumps, exchangers and binding proteins that ultimately guides a cell's fate. Deregulation of the calcium signal is often deleterious and has been linked to each of the 'cancer hallmarks'. Despite this, we do not yet have a full understanding of the remodeling of the calcium signal associated with cancer. Such an understanding could aid in guiding the development of therapies specifically targeting altered calcium signaling in cancer cells during tumorigenic progression. Findings from some of the studies that have assessed the remodeling of the calcium signal associated with tumorigenesis and/or processes important in invasion and metastasis are presented in this review. The potential of new methodologies is also discussed. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Cellular radiosensitivity of small-cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Krarup, M; Poulsen, H S; Spang-Thomsen, M

    1997-01-01

    PURPOSE: The objective of this study was to determine the radiobiological characteristics of a panel of small-cell lung cancer (SCLC) cell lines by use of a clonogenic assay. In addition, we tested whether comparable results could be obtained by employing a growth extrapolation method based...

  12. Dendritic cell immunotherapy in uterine cancer.

    Science.gov (United States)

    Coosemans, An; Tuyaerts, Sandra; Vanderstraeten, Anke; Vergote, Ignace; Amant, Frédéric; Van Gool, Stefaan W

    2014-01-01

    Uterine cancer is the most common pelvic gynecological malignancy. Uterine sarcomas and relapsed uterine carcinomas have limited treatment options. The search for new therapies is urgent. Dendritic cell (DC) immunotherapy holds much promise, though has been poorly explored in uterine cancer. This commentary gives an insight in existing DC immunotherapy studies in uterine cancer and summarizes the possibilities and the importance of the loading of tumor antigens onto DC and their subsequent maturation. However, the sole application of DC immunotherapy to target uterine cancer will be insufficient because of tumor-induced immunosuppression, which will hamper the establishment of an effective anti-tumor immune response. The authors give an overview on the limited existing immunosuppressive data and propose a novel approach on DC immunotherapy in uterine cancer.

  13. Dormancy activation mechanism of oral cavity cancer stem cells.

    Science.gov (United States)

    Chen, Xiang; Li, Xin; Zhao, Baohong; Shang, Dehao; Zhong, Ming; Deng, Chunfu; Jia, Xinshan

    2015-07-01

    Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase. Thus, these treatments cannot prevent the recurrence and metastasis of cancer. Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies. The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase. Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2. This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell.

  14. Cells of Origin of Epithelial Ovarian Cancers

    Science.gov (United States)

    2015-09-01

    lethal malignancy of the female reproductive system, largely due to the fact that most EOCs are diagnosed only after the cancer has metastasized into the...Epithelial ovarian cancer (EOC) is the most lethal malignancy of the female reproductive system, largely due to the fact that most EOCs are diagnosed only...experience in ovary research (ovarian physiology , oogonial stem cells) to work on this project. We also ! 5! obtained approval of our animal

  15. Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Felthaus, O. [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany); Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Ettl, T.; Gosau, M.; Driemel, O. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Brockhoff, G. [Department of Gynecology and Obstetrics, University of Regensburg (Germany); Reck, A. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Zeitler, K. [Institute of Pathology, University of Regensburg (Germany); Hautmann, M. [Department of Radiotherapy, University of Regensburg (Germany); Reichert, T.E. [Department of Oral and Maxillofacial Surgery, University of Regensburg (Germany); Schmalz, G. [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany); Morsczeck, C., E-mail: christian.morsczeck@klinik.uni-regensburg.de [Department of Operative Dentistry and Periodontology, University of Regensburg (Germany)

    2011-04-01

    Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simple method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.

  16. Increased Arf/p53 activity in stem cells, aging and cancer.

    Science.gov (United States)

    Carrasco-Garcia, Estefania; Moreno, Manuel; Moreno-Cugnon, Leire; Matheu, Ander

    2017-04-01

    Arf/p53 pathway protects the cells against DNA damage induced by acute stress. This characteristic is the responsible for its tumor suppressor activity. Moreover, it regulates the chronic type of stress associated with aging. This is the basis of its anti-aging activity. Indeed, increased gene dosage of Arf/p53 displays elongated longevity and delayed aging. At a cellular level, it has been recently shown that increased dosage of Arf/p53 delays age-associated stem cell exhaustion and the subsequent decline in tissue homeostasis and regeneration. However, p53 can also promote aging if constitutively activated. In this context, p53 reduces tissue regeneration, which correlates with premature exhaustion of stem cells. We discuss here the current evidence linking the Arf/p53 pathway to the processes of aging and cancer through stem cell regulation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  17. The evolving cancer stem cell paradigm: implications in veterinary oncology.

    Science.gov (United States)

    Pang, Lisa Y; Argyle, David J

    2015-08-01

    The existence of subpopulations of cells in cancer with increased tumour-initiating ability, self-renewal potential, and intrinsic resistance to conventional therapeutics formed the basis of the cancer stem cell model. Some tumours have since been viewed as aberrant tissues with a unidirectional hierarchical structure consisting of cancer stem cells at the apex, driving tumour growth, metastasis and relapse after therapy. Here, recent developments in cancer stem cell research are reviewed with a focus on tumour heterogeneity, cellular plasticity and cancer stem cell reprogramming. The impact of these findings on the cancer stem cell model is discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Side population cells isolated from KATO III human gastric cancer cell line have cancer stem cell-like characteristics.

    Science.gov (United States)

    She, Jun-Jun; Zhang, Peng-Ge; Wang, Xuan; Che, Xiang-Ming; Wang, Zi-Ming

    2012-09-07

    To investigate whether the side population (SP) cells possess cancer stem cell-like characteristics in vitro and the role of SP cells in tumorigenic process in gastric cancer. We analyzed the presence of SP cells in different human gastric carcinoma cell lines, and then isolated and identified the SP cells from the KATO III human gastric cancer cell line by flow cytometry. The clonogenic ability and self-renewal were evaluated by clone and sphere formation assays. The related genes were determined by reverse transcription polymerase chain reaction. To compare tumorigenic ability, SP and non-side population (NSP) cells from the KATO III human gastric cancer cell line were subcutaneously injected into nude mice. SP cells from the total population accounted for 0.57% in KATO III, 1.04% in Hs-746T, and 0.02% in AGS (CRL-1739). SP cells could grow clonally and have self-renewal capability in conditioned media. The expression of ABCG2, MDRI, Bmi-1 and Oct-4 was different between SP and NSP cells. However, there was no apparent difference between SP and NSP cells when they were injected into nude mice. SP cells have some cancer stem cell-like characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer.

  19. Characterizing cancer cells with cancer stem cell-like features in 293T human embryonic kidney cells.

    Science.gov (United States)

    Debeb, Bisrat G; Zhang, Xiaomei; Krishnamurthy, Savitri; Gao, Hui; Cohen, Evan; Li, Li; Rodriguez, Angel A; Landis, Melissa D; Lucci, Anthony; Ueno, Naoto T; Robertson, Fredika; Xu, Wei; Lacerda, Lara; Buchholz, Thomas A; Cristofanilli, Massimo; Reuben, James M; Lewis, Michael T; Woodward, Wendy A

    2010-07-08

    Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced by serial xenograft passages through transplantation. Herein we fully characterize cancer stem cell-like features in 293T human embryonic kidney cells. 293T cells can be readily cultured and passaged as spheres in serum-free stem cell promoting culture conditions. Cells cultured in vitro as three-dimensional spheres (3D) were shown to contain higher ALDH1 and CD44+/CD24- population compared to monolayer cells. These cells were also resistant to radiation and upregulate stem cell survival signaling including beta-catenin, Notch1 and Survivin in response to radiation. Moreover, 3D spheres generated from the 293T cells have increased expression of mesenchymal genes including vimentin, n-cadherin, zeb1, snail and slug as well as pro-metastatic genes RhoC, Tenascin C and MTA1. In addition, microRNAs implicated in self-renewal and metastases were markedly reduced in 3D spheres. 293T cells exhibit a cancer stem cell-like phenotype when cultured as 3D spheres and represent an important research tool for studying the molecular and biological mechanisms of cancer stem cells and for testing and developing novel targets for cancer therapy.

  20. Stemness is Derived from Thyroid Cancer Cells

    Science.gov (United States)

    Ma, Risheng; Bonnefond, Simon; Morshed, Syed A.; Latif, Rauf; Davies, Terry F.

    2014-01-01

    Background: One hypothesis for thyroid cancer development is its derivation from thyroid cancer stem cells (CSCs). Such cells could arise via different paths including from mutated resident stem cells within the thyroid gland or via epithelial to mesenchymal transition (EMT) from malignant cells since EMT is known to confer stem-like characteristics. Furthermore, EMT is a critical process for epithelial tumor progression, local invasion, and metastasis formation. In addition, stemness provides cells with therapeutic resistance and is the likely cause of tumor recurrence. However, the relevance of EMT and stemness in thyroid cancer progression has not been extensively studied. Methods: To examine the status of stemness in thyroid papillary cancer, we employed a murine model of thyroid papillary carcinoma and examined the expression of stemness and EMT using qPCR and histochemistry in mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf(V600E)/TPO-Cre). This construct is only activated at the time of thyroid peroxidase (TPO) expression in differentiating thyroid cells and cannot be activated by undifferentiated stem cells, which do not express TPO. Results: There was decreased expression of thyroid-specific genes such as Tg and NIS and increased expression of stemness markers, such as Oct4, Rex1, CD15, and Sox2 in the thyroid carcinoma tissue from 6-week-old BRAFV600E mice indicating the dedifferentiated status of the cells and the fact that stemness was derived in this model from differentiated thyroid cells. The decreased expression of the epithelial marker E-cadherin and increased EMT regulators including Snail, Slug, and TGF-β1 and TGF-β3, and the mesenchymal marker vimentin demonstrated the simultaneous progression of EMT and the CSC-like phenotype. Stemness was also found in a cancer thyroid cell line (named Marca cells) derived from one of the murine tumors. In this cell line, we also found that overexpression of Snail caused up-regulation of

  1. Getting to the heart of the matter in cancer: Novel approaches to targeting cancer stem cells.

    Science.gov (United States)

    Colvin, Hugh; Mori, Masaki

    2017-01-01

    Cancer is one of the leading causes of deaths worldwide. While cancers may initially show good response to chemotherapy or radiotherapy, it is not uncommon for them to recur at a later date. This phenomenon may be explained by the existence of a small population of cancer stem cells, which are inherently resistant to anti-cancer treatment as well as being capable of self-renewal. Therefore, while most of the tumour bulk consisting of cells that are not cancer stem cells respond to treatment, the cancer stem cells remain, leading to disease recurrence. Following this logic, the effective targeting of cancer stem cells holds promise for providing long-term cure in individuals with cancer. Cancer stem cells, like normal stem cells are endowed with mechanisms to protect themselves against a wide range of insults including anti-cancer treatments, such as the enhancement of the DNA damage response and the ability to extrude drugs. It is therefore important to develop new strategies if cancer stem cells are to be eradicated. In this review, we describe the strategies that we have developed to target cancer stem cells. These strategies include the targeting of the histone demethylase jumonji, AT rich interactive domain 1B (JARID1B), which we found to be functionally significant in the maintenance of cancer stem cells. Other strategies being pursued include reprogramming of cancer stem cells and the targeting of a functional cell surface marker of liver cancer stem cells, the aminopeptidase CD13.

  2. Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness.

    Science.gov (United States)

    Xue, Jianguo; Zhu, Yuan; Sun, Zixuan; Ji, Runbi; Zhang, Xu; Xu, Wenrong; Yuan, Xiao; Zhang, Bin; Yan, Yongmin; Yin, Lei; Xu, Huijuan; Zhang, Leilei; Zhu, Wei; Qian, Hui

    2015-10-24

    Emerging evidence indicates that inappropriate cell-cell fusion might contribute to cancer progression. Similarly, mesenchymal stem cells (MSCs) can also fuse with other cells spontaneously and capable of adopting the phenotype of other cells. The aim of our study was to investigate the role of MSCs participated cell fusion in the tumorigenesis of gastric cancer. We fused human umbilical cord mesenchymal stem cells (hucMSCs) with gastric cancer cells in vitro by polyethylene glycol (PEG), the hybrid cells were sorted by flow cytometer. The growth and migration of hybrids were assessed by cell counting, cell colony formation and transwell assays. The proteins and genes related to epithelial- mesenchymal transition and stemness were tested by western blot, immunocytochemistry and real-time RT-PCR. The expression of CD44 and CD133 was examined by immunocytochemistry and flow cytometry. The xenograft assay was used to evaluation the tumorigenesis of the hybrids. The obtained hybrids exhibited epithelial- mesenchymal transition (EMT) change with down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, α-smooth muscle actin (α-SMA), and fibroblast activation protein (FAP). The hybrids also increased expression of stemness factors Oct4, Nanog, Sox2 and Lin28. The expression of CD44 and CD133 on hybrid cells was stronger than parental gastric cancer cells. Moreover, the migration and proliferation of heterotypic hybrids were enhanced. In addition, the heterotypic hybrids promoted the growth abilities of gastric xenograft tumor in vivo. Taken together, our results suggest that cell fusion between hucMSCs and gastric cancer cells could contribute to tumorigenic hybrids with EMT and stem cell-like properties, which may provide a flexible tool for investigating the roles of MSCs in gastric cancer.

  3. Staphylococcus aureus-induced G2/M phase transition delay in host epithelial cells increases bacterial infective efficiency.

    Directory of Open Access Journals (Sweden)

    Ludmila Alekseeva

    Full Text Available Staphylococcus aureus is a highly versatile, opportunistic pathogen and the etiological agent of a wide range of infections in humans and warm-blooded animals. The epithelial surface is its principal site of colonization and infection. In this work, we investigated the cytopathic effect of S. aureus strains from human and animal origins and their ability to affect the host cell cycle in human HeLa and bovine MAC-T epithelial cell lines. S. aureus invasion slowed down cell proliferation and induced a cytopathic effect, resulting in the enlargement of host cells. A dramatic decrease in the number of mitotic cells was observed in the infected cultures. Flow cytometry analysis revealed an S. aureus-induced delay in the G2/M phase transition in synchronous HeLa cells. This delay required the presence of live S. aureus since the addition of the heat-killed bacteria did not alter the cell cycle. The results of Western blot experiments showed that the G2/M transition delay was associated with the accumulation of inactive cyclin-dependent kinase Cdk1, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3, which was correlated with a reduction of the mitotic cell number. Analysis of S. aureus proliferation in asynchronous, G1- and G2-phase-enriched HeLa cells showed that the G2 phase was preferential for bacterial infective efficiency, suggesting that the G2 phase delay may be used by S. aureus for propagation within the host. Taken together, our results divulge the potential of S. aureus in the subversion of key cellular processes such as cell cycle progression, and shed light on the biological significance of S. aureus-induced host cell cycle alteration.

  4. Cancer stem cells and field cancerization of oral squamous cell carcinoma.

    Science.gov (United States)

    Simple, M; Suresh, Amritha; Das, Debashish; Kuriakose, Moni A

    2015-07-01

    Oral squamous cell carcinoma (OSCC) has a high propensity for local failure, which is attributed to recurrence at the primary site or the development of second primary tumors (SPT). Field cancerization that refers to the existence of transformed cells in areas adjacent to the primary tumor, has been attributed to be one of the probable reasons underlying disease relapse. The carcinogenic process necessitates multiple molecular events for the transformation of a normal cell into a cancer cell. This implies that only the long-time residents of the epithelium, such as the stem cells, might be the candidates capable of accumulating these genetic hits. These transformed stem cells- the 'Cancer stem cells' (CSCs), are further known to be equipped with the properties of tumor initiation and migration, both of which are essential for orchestrating field cancerization. The concept that the CSCs might be responsible for field cancerization in OSCC has not been explored extensively. If the role of CSCs as the primary units of field cancerization process is established, their presence in the mucosa adjacent to the tumor may be an indicator for local recurrence and/or development of second primary tumors. In this review, we examine the available evidence in literature exploring the possibilities of CSCs driving the process of field cancerization and thereby being the underlying mechanism for disease recurrence and development of SPT. Published by Elsevier Ltd.

  5. A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model.

    Science.gov (United States)

    Basu, Hirak S; Thompson, Todd A; Church, Dawn R; Clower, Cynthia C; Mehraein-Ghomi, Farideh; Amlong, Corey A; Martin, Christopher T; Woster, Patrick M; Lindstrom, Mary J; Wilding, George

    2009-10-01

    High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression.

  6. Targeting Lung Cancer Stem Cells: Research and Clinical Impacts

    Directory of Open Access Journals (Sweden)

    Norashikin Zakaria

    2017-05-01

    Full Text Available Lung cancer is the most common cancer worldwide, accounting for 1.8 million new cases and 1.6 million deaths in 2012. Non-small cell lung cancer (NSCLC, which is one of two types of lung cancer, accounts for 85–90% of all lung cancers. Despite advances in therapy, lung cancer still remains a leading cause of death. Cancer relapse and dissemination after treatment indicates the existence of a niche of cancer cells that are not fully eradicated by current therapies. These chemoresistant populations of cancer cells are called cancer stem cells (CSCs because they possess the self-renewal and differentiation capabilities similar to those of normal stem cells. Targeting the niche of CSCs in combination with chemotherapy might provide a promising strategy to eradicate these cells. Thus, understanding the characteristics of CSCs has become a focus of studies of NSCLC therapies.

  7. Cancer Cell Colonisation in the Bone Microenvironment

    Directory of Open Access Journals (Sweden)

    Casina Kan

    2016-10-01

    Full Text Available Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts. Cross-talk with the bone may alter tumour cell properties and, conversely, tumour cells may also acquire characteristics of the surrounding microenvironment, in a process known as osteomimicry. Alternatively, these cells may also express osteomimetic genes that allow cell survival or favour seeding to the bone marrow. The seeding of tumour cells in the bone disrupts bone-forming and bone-resorbing activities, which can lead to macrometastasis in bone. At present, bone macrometastases are incurable with only palliative treatment available. A better understanding of how these processes influence the early onset of bone metastasis may give insight into potential therapies. This review will focus on the early steps of bone colonisation, once disseminated tumour cells enter the bone marrow.

  8. Single cell sequencing reveals heterogeneity within ovarian cancer epithelium and cancer associated stromal cells.

    Science.gov (United States)

    Winterhoff, Boris J; Maile, Makayla; Mitra, Amit Kumar; Sebe, Attila; Bazzaro, Martina; Geller, Melissa A; Abrahante, Juan E; Klein, Molly; Hellweg, Raffaele; Mullany, Sally A; Beckman, Kenneth; Daniel, Jerry; Starr, Timothy K

    2017-03-01

    The purpose of this study was to determine the level of heterogeneity in high grade serous ovarian cancer (HGSOC) by analyzing RNA expression in single epithelial and cancer associated stromal cells. In addition, we explored the possibility of identifying subgroups based on pathway activation and pre-defined signatures from cancer stem cells and chemo-resistant cells. A fresh, HGSOC tumor specimen derived from ovary was enzymatically digested and depleted of immune infiltrating cells. RNA sequencing was performed on 92 single cells and 66 of these single cell datasets passed quality control checks. Sequences were analyzed using multiple bioinformatics tools, including clustering, principle components analysis, and geneset enrichment analysis to identify subgroups and activated pathways. Immunohistochemistry for ovarian cancer, stem cell and stromal markers was performed on adjacent tumor sections. Analysis of the gene expression patterns identified two major subsets of cells characterized by epithelial and stromal gene expression patterns. The epithelial group was characterized by proliferative genes including genes associated with oxidative phosphorylation and MYC activity, while the stromal group was characterized by increased expression of extracellular matrix (ECM) genes and genes associated with epithelial-to-mesenchymal transition (EMT). Neither group expressed a signature correlating with published chemo-resistant gene signatures, but many cells, predominantly in the stromal subgroup, expressed markers associated with cancer stem cells. Single cell sequencing provides a means of identifying subpopulations of cancer cells within a single patient. Single cell sequence analysis may prove to be critical for understanding the etiology, progression and drug resistance in ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Innate immune cells in inflammation and cancer.

    Science.gov (United States)

    Nowarski, Roni; Gagliani, Nicola; Huber, Samuel; Flavell, Richard A

    2013-08-01

    The innate immune system has evolved in multicellular organisms to detect and respond to situations that compromise tissue homeostasis. It comprises a set of tissue-resident and circulating leukocytes primarily designed to sense pathogens and tissue damage through hardwired receptors and eliminate noxious sources by mediating inflammatory processes. While indispensable to immunity, the inflammatory mediators produced in situ by activated innate cells during injury or infection are also associated with increased cancer risk and tumorigenesis. Here, we outline basic principles of innate immune cell functions in inflammation and discuss how these functions converge upon cancer development. ©2013 AACR.

  10. Does diagnostic delay of colorectal cancer result in malpractice claims? A retrospective analysis of the Swedish board of malpractice from 1995-2008.

    Science.gov (United States)

    Hafström, Larsolof; Johansson, Henry; Ahlberg, Jon

    2012-06-18

    Delay in the diagnosis of colorectal cancer (CRC) may have important clinical and medico-legal implications. This study identifies the claims made on the basis of delay in the diagnosis of CRC to the Swedish insurance agency (whose English name is The County Council´s Mutual Insurance Company) and the impact and consequences of the delay on prognosis, treatment and survival for patients who reported the claims. The Company handles claims of medical malpractice where claimants seek compensation for alleged suffering and/or negative clinical impacts of diagnostic delays. Between January 1, 1995 and December 31, 2008, a total of 80 patients filed claims for negative effects resulting from delays in the diagnosis of CRC. Review of the claims led to identification of delay for 62 patients. The clinical symptoms that were overlooked and other causes of delay that had any relation to therapy, prognosis and economic compensation were evaluated. The median delay in the diagnosis of CRC was six months. This delay was considered to have had an impact on the therapy in 20 % of the cases. The prognosis was postulated to have been adversely affected for 15 % of the patients. The delay was mainly caused by incomplete consideration of the symptoms hematoschisis or anaemia, changed bowel routine, or incomplete clinical or radiological examination and by misinterpretations of the results. No impact of duration of delay on survival was identified. The importance of identifying concomitant metastatic disease at diagnosis was overwhelming. Economic compensation was given in 79 % of the cases. This study found that claims for compensation for delay in diagnosis of CRC are rare. The delay in the diagnosis of the primary tumour was considered to have had an impact on the magnitude of therapeutic measures for a fifth of the patients who filed claims. Economic compensation for the patients´ injuries was given in almost 80 % of the cases.

  11. Delayed IFN response differentiates replication of West Nile virus and Japanese encephalitis virus in human neuroblastoma and glioblastoma cells.

    Science.gov (United States)

    Takamatsu, Yuki; Uchida, Leo; Morita, Kouichi

    2015-08-01

    West Nile virus (WNV) and Japanese encephalitis virus (JEV) are important causes of human encephalitis cases, which result in a high mortality ratio and neurological sequelae after recovery. Understanding the mechanism of neuropathogenicity in these viral infections is important for the development of specific antiviral therapy. Here, we focused on human-derived neuronal and glial cells to understand the cellular responses against WNV and JEV infection. It was demonstrated that early IFN-β induction regulated virus replication in glioblastoma tbl98G cells, whereas delayed IFN-β induction resulted in efficient virus replication in neuroblastoma SK-N-SH cells. Moreover, the concealing of viral dsRNA in the intracellular membrane resulted in the delayed IFN response in SK-N-SH cells. These results, which showed different IFN responses between human neuronal and glial cells after WNV or JEV infection, are expected to contribute to our understanding of the molecular mechanisms for neuropathology in these viral infections.

  12. Cancer stem cells: a minor cancer subpopulation that redefines global cancer features

    Directory of Open Access Journals (Sweden)

    Heiko eEnderling

    2013-04-01

    Full Text Available In recent years cancer stem cells (CSCs have been hypothesized to comprise only a minor subpopulation in solid tumors that drives tumor initiation, development and metastasis; the so-called cancer stem cell hypothesis. While a seemingly trivial statement about numbers, much is put at stake. If true, the conclusions of many studies of cancer cell populations could be challenged, as the bulk assay methods upon which they depend have, by and large, taken for granted the notion that a ‘typical’ cell of the population possesses the attributes of a cell capable of perpetuating the cancer, i.e., a CSC. In support of the CSC hypothesis, populations enriched for so-called ‘tumor-initiating’ cells have demonstrated a corresponding increase in tumorigenicity as measured by dilution assay, although estimates have varied widely as to what the fractional contribution of tumor-initiating cells is in any given population. Some have taken this variability to suggest the CSC fraction may be nearly 100% after all, countering the CSC hypothesis, and that there are simply assay-dependent error rates in our ability to ‘reconfirm’ CSC status at the cell level. To explore this controversy more quantitatively, we developed a simple theoretical model of cancer stem cell-driven tumor growth dynamics. Assuming CSC and non-stem cancer cell subpopulations coexist to some degree, we evaluated the impact of an environmentally-dependent cancer stem cell symmetric division probability and a non-stem cancer cell proliferation capacity on tumor progression and morphology. Our model predicts, as expected, that the frequency of CSC divisions that are symmetric highly influences the frequency of CSCs in the population, but goes on to predict the two frequencies can be widely divergent, and that spatial constraints will tend to increase the CSC fraction over time.

  13. Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells

    Science.gov (United States)

    Pelosi, Elvira; Castelli, Germana

    2017-01-01

    Pancreatic Ductal Adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death and is the most lethal of common malignancies with a five-year survival rate of pancreatic intraepithelial neoplasia. The genetic landscape of PDAC is characterized by the presence of four frequently-mutated genes: KRAS, CDKN2A, TP53 and SMAD4. The development of mouse models of PDAC has greatly contributed to the understanding of the molecular and cellular mechanisms through which driver genes contribute to pancreatic cancer development. Particularly, oncogenic KRAS-driven genetically-engineered mouse models that phenotypically and genetically recapitulate human pancreatic cancer have clarified the mechanisms through which various mutated genes act in neoplasia induction and progression and have led to identifying the possible cellular origin of these neoplasias. Patient-derived xenografts are increasingly used for preclinical studies and for the development of personalized medicine strategies. The studies of the purification and characterization of pancreatic cancer stem cells have suggested that a minority cell population is responsible for initiation and maintenance of pancreatic adenocarcinomas. The study of these cells could contribute to the identification and clinical development of more efficacious drug treatments. PMID:29156578

  14. Sphingosine 1-Phosphate and Cancer: Lessons from Thyroid Cancer Cells

    Directory of Open Access Journals (Sweden)

    Kid Törnquist

    2013-05-01

    Full Text Available Sphingomyelin is found in the cell membrane of all eukaryotic cells, and was for a long time considered merely as a structural component. However, during the last two decades, metabolites of sphingomyelin, especially sphingosine 1-phosphate (S1P, have proven to be physiologically significant regulators of cell function. Through its five different G protein-coupled receptors, S1P regulates a wide array of cellular processes, ranging from stimulating cellular proliferation and migration, to the inhibition of apoptosis and induction of angiogenesis and modulation of cellular calcium homeostasis. Many of the processes regulated by S1P are important for normal cell physiology, but may also induce severe pathological conditions, especially in malignancies like cancer. Thus, understanding S1P signaling mechanisms has been the aim of a multitude of investigations. Great interest has also been shown in understanding the action of sphingosine kinase (SphK, i.e., the kinase phosphorylating sphingosine to S1P, and the interactions between S1P and growth factor signaling. In the present review, we will discuss recent findings regarding the possible importance of S1P and SphK in the etiology of thyroid cancer. Although clinical data is still scarce, our in vitro findings suggest that S1P may function as a “double-edged sword”, as the receptor profile of thyroid cancer cells largely determines whether S1P stimulates or blocks cellular migration. We will also discuss the interactions between S1P- and VEGF-evoked signaling, and the importance of a S1P1-VEGF receptor 2 complex in thyroid cancer cells.

  15. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-15

    Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Fallopian Tube Cancer; Gastrointestinal Stromal Tumor; Localized Extrahepatic Bile Duct Cancer; Localized Gallbladder Cancer; Localized Gastrointestinal Carcinoid Tumor; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Primary Peritoneal Cavity Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Adult Soft Tissue Sarcoma; Recurrent Colon Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Small Intestine Cancer; Recurrent Uterine Sarcoma; Regional Gastrointestinal Carcinoid Tumor; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage 0 Non-small Cell Lung Cancer; Stage I Adult Soft Tissue Sarcoma; Stage I Colon Cancer; Stage I Gastric Cancer; Stage I Non-small Cell Lung Cancer; Stage I Ovarian Epithelial Cancer; Stage I Ovarian Germ Cell Tumor; Stage I Pancreatic Cancer; Stage I Rectal Cancer; Stage I Uterine Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage II Colon Cancer; Stage II Gastric Cancer; Stage II Non-small Cell Lung Cancer; Stage II Ovarian Epithelial Cancer; Stage II Ovarian Germ Cell Tumor; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage II Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Uterine Sarcoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Adult Soft Tissue Sarcoma; Stage IV Colon Cancer; Stage

  16. Delayed neuronal cell death in brainstem after transient brainstem ischemia in gerbils

    Directory of Open Access Journals (Sweden)

    Hakuba Nobuhiro

    2010-09-01

    Full Text Available Abstract Background Because of the lack of reproducible brainstem ischemia models in rodents, the temporal profile of ischemic lesions in the brainstem after transient brainstem ischemia has not been evaluated intensively. Previously, we produced a reproducible brainstem ischemia model of Mongolian gerbils. Here, we showed the temporal profile of ischemic lesions after transient brainstem ischemia. Results Brainstem ischemia was produced by occlusion of the bilateral vertebral arteries just before their entry into the transverse foramina of the cervical vertebrae of Mongolian gerbils. Animals were subjected to brainstem ischemia for 15 min, and then reperfused for 0 d (just after ischemia, 1 d, 3 d and 7 d (n = 4 in each group. Sham-operated animals (n = 4 were used as control. After deep anesthesia, the gerbils were perfused with fixative for immunohistochemical investigation. Ischemic lesions were detected by immunostaining for microtubule-associated protein 2 (MAP2. Just after 15-min brainstem ischemia, ischemic lesions were detected in the lateral vestibular nucleus and the ventral part of the spinal trigeminal nucleus, and these ischemic lesions disappeared one day after reperfusion in all animals examined. However, 3 days and 7 days after reperfusion, ischemic lesions appeared again and clusters of ionized calcium-binding adapter molecule-1(IBA-1-positive cells were detected in the same areas in all animals. Conclusion These results suggest that delayed neuronal cell death took place in the brainstem after transient brainstem ischemia in gerbils.

  17. Chronological changes of delayed-type hypersensitivity in mice immunised with testicular germ cells alone.

    Science.gov (United States)

    Qu, N; Naito, M; Terayama, H; Hirai, S; Musha, M; Itoh, M

    2014-06-01

    Experimental autoimmune orchitis (EAO), comprising a breakdown of the testicular immune privilege, is one of the models of immunological male infertility. EAO is characterised by CD4 + T-cell-dependent lymphocytic inflammation and augmented delayed-type hypersensitivity (DTH) against testicular antigens. We previously established an EAO model in mice by immunisation with viable syngeneic testicular germ cells (TGC) alone. However, the sequential change of DTH during development of this EAO has not been analysed yet. In this study, the DTH response during TGC-induced EAO was investigated by the injection of syngeneic TGC protein into the ears of mice. The results showed that a significant DTH response was observed on injection of 20 μg TGC protein, but not on that of 0.2 or 2 μg TGC protein. Also, the level of the DTH response to 20 μg TGC protein was highly relevant to the pathology of EAO development. These results indicate that the DTH response on injection of 20 μg TGC protein into the ears of mice is effective for predicting the pathology of EAO development. © 2013 Blackwell Verlag GmbH.

  18. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  19. Population genetics of cancer cell clones: possible implications of cancer stem cells

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    Naugler Christopher T

    2010-11-01

    Full Text Available Abstract Background The population dynamics of the various clones of cancer cells existing within a tumour is complex and still poorly understood. Cancer cell clones can be conceptualized as sympatric asexual species, and as such, the application of theoretical population genetics as it pertains to asexual species may provide additional insights. Results The number of generations of tumour cells within a cancer has been estimated at a minimum of 40, but high cancer cell mortality rates suggest that the number of cell generations may actually be in the hundreds. Such a large number of generations would easily allow natural selection to drive clonal evolution assuming that selective advantages of individual clones are within the range reported for free-living animal species. Tumour cell clonal evolution could also be driven by variation in the intrinsic rates of increase of different clones or by genetic drift. In every scenario examined, the presence of cancer stem cells would require lower selection pressure or less variation in intrinsic rates of increase. Conclusions The presence of cancer stem cells may result in more rapid clonal evolution. Specific predictions from theoretical population genetics may lead to a greater understanding of this process.

  20. The influence of spirituality and religiosity on breast cancer screening delay in African American women: application of the Theory of Reasoned Action and Planned Behavior (TRA/TPB).

    Science.gov (United States)

    Gullate, Mary

    2006-01-01

    African American women (AAW) are 25% more likely to present with late stage breast cancer and 20% more likely to die from their disease than Caucasian women. Researchers report that a treatment delay of 3 months is a significant factor in breast cancer mortality. Socioeconomic factors, lack of access and knowledge, spiritual and religious beliefs, fear and fatalism are reported as contributing factors to screening delays. Studies have primarily applied the Health Belief Model (HBM) and modified versions like the Champion HBM to preventive health practices. Neither have significant inclusion of spirituality or religiosity. The TRA/TPB focus on beliefs, intent and attitude as individual determinants of the likelihood of performing a specific behavior; but have not had wide utility in studies related to screening delays among AAW. This paper explores the utility of applying the TRA/TPB as the theoretical framework for determining cultural relevance of spirituality and religiosity to screening delays among AAW.

  1. Distinct metabolic responses of an ovarian cancer stem cell line.

    Science.gov (United States)

    Vermeersch, Kathleen A; Wang, Lijuan; McDonald, John F; Styczynski, Mark P

    2014-12-18

    Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to be a major cause of cancer recurrence, respond to these variations. Here, in vitro environmental perturbations designed to mimic different aspects of the in vivo environment were used to characterize how an ovarian cancer cell line and its derived, isogenic cancer stem cells metabolically respond to environmental cues. Mass spectrometry was used to profile metabolite levels in response to in vitro environmental perturbations. Docetaxel, the chemotherapeutic used for this experiment, caused significant metabolic changes in amino acid and carbohydrate metabolism in ovarian cancer cells, but had virtually no metabolic effect on isogenic ovarian cancer stem cells. Glucose deprivation, hypoxia, and the combination thereof altered ovarian cancer cell and cancer stem cell metabolism to varying extents for the two cell types. Hypoxia had a much larger effect on ovarian cancer cell metabolism, while glucose deprivation had a greater effect on ovarian cancer stem cell metabolism. Core metabolites and pathways affected by these perturbations were identified, along with pathways that were unique to cell types or perturbations. The metabolic responses of an ovarian cancer cell line and its derived isogenic cancer stem cells differ greatly under most conditions, suggesting that these two cell types may behave quite differently in an in vivo tumor microenvironment. While cancer metabolism and cancer stem cells are each promising potential therapeutic targets, such varied behaviors in vivo would need to

  2. Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish

    OpenAIRE

    Kanada, Masamitsu; Zhang, Jinyan; Libo YAN; Sakurai, Takashi; Terakawa, Susumu

    2014-01-01

    The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility re...

  3. Reduced delay in diagnosis of cancer after implementation of ‘fast track’

    DEFF Research Database (Denmark)

    Jensen, Henry; Tørring, Marie Louise; Vedsted, Peter

    In Denmark, the National Integrated Cancer Pathways (“fast track”) was introduced in 2008 as a response to the long waiting times. We performed a natural experiment of 14,023 cancer patients to compare the length of time intervals before and after the introduction of “fast-track”. We saw a decrease...... in time intervals, but the difference in treatment interval was not statistically significant. The reduction in time intervals seemed to occur before the implementation of ‘fast track’ – indicating that other factors may also have influenced the length of the cancer diagnostic pathways....

  4. Stability and Hopf bifurcation on a model for HIV infection of CD4{sup +} T cells with delay

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xia [College of Mathematics and Information Science, Xinyang Normal University, Xinyang, Henan 464000 (China)], E-mail: xywangxia@163.com; Tao Youde [College of Mathematics and Information Science, Xinyang Normal University, Xinyang, Henan 464000 (China); Beijing Institute of Information Control, Beijing 100037 (China); Song Xinyu [College of Mathematics and Information Science, Xinyang Normal University, Xinyang, Henan 464000 (China) and Research Institute of Forest Resource Information Techniques, Chinese Academy of Forestry, Beijing 100091 (China)], E-mail: xysong88@163.com

    2009-11-15

    In this paper, a delayed differential equation model that describes HIV infection of CD4{sup +} T cells is considered. The stability of the positive equilibrium and the existence of Hopf bifurcation are investigated. In succession, using the normal form theory and center manifold argument, we derive the explicit formulas which determine the stability, direction and other properties of bifurcating periodic solutions.

  5. Diet, Stem Cells, and Breast Cancer Prevention

    Science.gov (United States)

    2011-01-01

    abrogated by small interfering RNA to PTEN, indicating PTEN-dependence. Using FACS analysis , we showed that GEN induced cell cycle arrest at G0-G1 phase...isolated from WT (PND 100) and Tg (PND75) mice. The percentage of mammary SCs was quantified by Fluorescence activated cell sorting analysis of...fruits and vegetables in breast cancer prevention due to their phytochemical components, yet mechanisms underlying their presumed anti-tumor activities

  6. Scheduling delay in suspected cases of oral cancer Atraso de agendamento em casos suspeitos de câncer bucal

    Directory of Open Access Journals (Sweden)

    Luciana Meneses Souza

    2011-12-01

    Full Text Available The objective of the study was to evaluate scheduling delay of dental exams in the city of São Paulo of patients suspected of having oral cancer. A cross-sectional study was performed in which telephone conversations simulated clinical situations that represented two types of patients: one presenting symptoms suggestive of oral cancer (CA, and another one suggesting the need for prostheses (PR. The scheduling delay was evaluated by the days until an appointment for care; and among public offices, by type of schedule (emergency or routine. Negative binomial regression was used (95% statistical significance. Five hundred and seventy-five public and private dental offices participated in the study. The mean scheduling delay for the CA group was 2.88 days, and for the PR group, 4.34 days (p = 0.01. The mean scheduling delay was shorter in private dental offices (2.59 days than in offices that accepted health insurance (2.74 days (p = 0.01; the delay was shorter when performed by the dentist rather than by the dental assistant, 2.45 versus 4.21 days (p = 0.01. In public services, 69% of patients in the cancer group were sent to the emergency service. Dental services were accessible for scheduling clinical examinations among patients suspected of having oral cancer.O objetivo do estudo foi avaliar o atraso de agendamento de pacientes com suspeita de câncer bucal aos exames odontológicos na cidade de São Paulo. Realizou-se estudo transversal, em que conversações telefônicas simularam situações clínicas, representando dois tipos de pacientes-padrão: um com sintomas sugestivos de câncer bucal e outro com necessidade de prótese. O atraso do agendamento foi avaliado pelo tempo de agendamento para a consulta e, no caso de estabelecimentos públicos, pelo tipo de agendamento (rotina ou urgência. Utilizou-se regressão binomial negativa (95% de nível de significância. Participaram do estudo 575 estabelecimentos públicos e privados. O tempo m

  7. Circulating Tumor Cells in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Brian Hu

    2013-12-01

    Full Text Available Circulating tumor cells (CTCs can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management.

  8. Metformin Induces Growth Inhibition and Cell Cycle Arrest by Upregulating MicroRNA34a in Renal Cancer Cells.

    Science.gov (United States)

    Xie, Wei; Wang, Lei; Sheng, Halei; Qiu, Jing; Zhang, Di; Zhang, Le; Yang, Fan; Tang, Dahai; Zhang, Kebin

    2017-01-03

    BACKGROUND Metformin is a widely used biguanide drug for the treatment of type 2 diabetes. It has been revaluated as a potential anti-cancer drug with promising activity in various tumors. However, the precise mechanisms underlying the suppression of cancer cells by metformin remain not well understood. MATERIAL AND METHODS In this study, human renal cell carcinoma cell line ACHN was used to investigate the anti-proliferation effect of metformin. A cell counting kit-8 assay was used to detect the cell viability. The cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression of cyclin D1 and p27KIP1 was detected by Western blot. The underlying mechanism involving miRNA34a was further investigated by quantitative RT-PCR and transfection with miRNA inhibitor specific for miRNA34a in ACHN, 769-P, and A498 cells. RESULTS Metformin could significantly inhibit the proliferation of ACHN cells in a dose- and time-dependent manner. In addition, the results showed that metformin induced G0/G1 phase arrest and delayed entry into S phase in ACHN cells. It was shown that metformin downregulates the expression of cyclin D1 and increases the p27KIP1 level. Furthermore, metformin increased ACHN cell death. Lastly, miRNA34a was found to be upregulated by metformin in ACHN, 769-P, and A498 cells. Subsequently, it was demonstrated that inhibition of miRNA34a could partially attenuate the suppressive effect of metformin on renal cancer cell proliferation. CONCLUSIONS The study data revealed that metformin induced cell growth inhibition and cell cycle arrest partially by upregulating miRNA34a in renal cancer cells.

  9. Fraction against Human Cancer Cell Lines

    African Journals Online (AJOL)

    Purpose: To investigate the anti-proliferative and apoptotic activity of crude and dichloromethane fraction of A. sieberi against seven cancer cell lines (Colo20, HCT116, DLD, MCF7, Jurkat, HepG2 and. L929). Methods: A. sieberi was extracted with methanol and further purification was carried out using liquid-.

  10. Germ cell cancer and disorders of spermatogenesis

    DEFF Research Database (Denmark)

    Skakkebaek, N E; Rajpert-De Meyts, E; Jørgensen, N

    1998-01-01

    Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads...

  11. Cancer stem cells: the challenges ahead

    NARCIS (Netherlands)

    Medema, Jan Paul

    2013-01-01

    Cancer stem cells (CSCs) have been proposed as the driving force of tumorigenesis and the seeds of metastases. However, their existence and role remain a topic of intense debate. Recently, the identification of CSCs in endogenously developing mouse tumours has provided further support for this

  12. Current therapy of small cell lung cancer

    DEFF Research Database (Denmark)

    Sorensen, M; Lassen, U; Hansen, H H

    1998-01-01

    This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated...

  13. DNA repair of cancer stem cells

    National Research Council Canada - National Science Library

    Mathews, Lesley A; Cabarcas, Stephanie M; Hurt, Elaine M

    2013-01-01

    ... leukemia by John E. Dick from the University of Toronto. The heterogeneity of human leukemia and the presence of stem cells in cancer was further translated into solid tumors by Al-Hajj et al. when they published a provocative paper in Proceedings of the National Academy of Sciences discussing the ability to distinguish tumorigenic (tumor-initi...

  14. Optical imaging of cancer and cell death

    NARCIS (Netherlands)

    Xie, Bangwen

    2013-01-01

    The aim of the work included in this PhD thesis was to explore the diverse application possibility of using NIR fluorescent probes with specific properties to visualize and characterize cancer and cell death. In this thesis, we mainly focus on optical imaging and its application, both at microscopic

  15. Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism.

    Science.gov (United States)

    Phiboonchaiyanan, Preeyaporn Plaimee; Kiratipaiboon, Chayanin; Chanvorachote, Pithi

    2016-04-25

    Cancer stem cells (CSCs), a subpopulation of cancer cells with high aggressive behaviors, have been identified in many types of cancer including lung cancer as one of the key mediators driving cancer progression and metastasis. Here, we have reported for the first time that ciprofloxacin (CIP), a widely used anti-microbial drug, has a potentiating effect on CSC-like features in human non-small cell lung cancer (NSCLC) cells. CIP treatment promoted CSC-like phenotypes, including enhanced anchorage-independent growth and spheroid formation. The known lung CSC markers: CD133, CD44, ABCG2 and ALDH1A1 were found to be significantly increased, while the factors involving in epithelial to mesenchymal transition (EMT): Slug and Snail, were depleted. Also, self-renewal transcription factors Oct-4 and Nanog were found to be up-regulated in CIP-treated cells. The treatment of CIP on CSC-rich populations obtained from secondary spheroids resulted in the further increase of CSC markers. In addition, we have proven that the mechanistic insight of the CIP induced stemness is through Caveolin-1 (Cav-1)-dependent mechanism. The specific suppression of Cav-1 by stably transfected Cav-1 shRNA plasmid dramatically reduced the effect of CIP on CSC markers as well as the CIP-induced spheroid formation ability. Cav-1 was shown to activate protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) pathways in CSC-rich population; however, such an effect was rarely found in the main lung cancer cells population. These findings reveal a novel effect of CIP in positively regulating CSCs in lung cancer cells via the activation of Cav-1, Akt and ERK, and may provoke the awareness of appropriate therapeutic strategy in cancer patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Inhibition of Bim enhances replication of varicella-zoster virus and delays plaque formation in virus-infected cells.

    Science.gov (United States)

    Liu, Xueqiao; Cohen, Jeffrey I

    2014-01-01

    Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication.

  17. Selected Activities of Citrus Maxima Merr. Fruits on Human Endothelial Cells: Enhancing Cell Migration and Delaying Cellular Aging

    Directory of Open Access Journals (Sweden)

    Paiwan Buachan

    2014-04-01

    Full Text Available Endothelial injury and damage as well as accumulated reactive oxygen species (ROS in aging play a significant role in the development of cardiovascular disease (CVD. Recent studies show an association of high citrus fruit intake with a lower risk of CVD and stroke but the mechanisms involved are not fully understood. This study investigated the effects of pummelo (Citrus maxima Merr. var. Tubtim Siam, CM fruit extract on human umbilical vein endothelial cell (HUVECs migration and aging. The freeze-dried powder of fruit extract was characterized for antioxidant capacity (FRAP assay and certain natural antioxidants, including ascorbic acid, gallic acid, hesperidin, and naringin (HPLC. Short-term (48 h co-cultivation of HUVECs with CM enhanced cell migration as evaluated by a scratch wound assay and Boyden chamber assay. A long-term treatment with CM for 35 days significantly increased HUVEC proliferation capability as indicated by population doubling level (PDL. CM also delayed the onset of aging phenotype shown by senescence-associated β-galactosidase (SA-β-gal staining. Furthermore, CM was able to attenuate increased ROS levels in aged cells when determined by 2′,7′-dichlorodihydrofluorescein diacetate (DCDHF while eNOS mRNA expression was increased but the eNOS protein level was not changed. Thus, further in vivo and clinical studies are warranted to support the use of pummelo as a functional fruit for endothelial health and CVD risk reduction.

  18. Stemness is derived from thyroid cancer cells

    Directory of Open Access Journals (Sweden)

    Risheng eMa

    2014-07-01

    Full Text Available Background: One hypothesis for thyroid cancer development is its derivation from thyroid cancer stem cells (CSCs. Such cells could arise via different paths including from mutated resident stem cells within the thyroid gland or via epithelial to mesenchymal transition (EMT from malignant cells since EMT is known to confer stem-like characteristics. Methods: To examine the status of stemness in thyroid papillary cancer we employed a murine model of thyroid papillary carcinoma and examined the expression of stemness and EMT using qPCR and histochemistry in mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf(V600E/TPO-Cre. This construct is only activated at the time of thyroid peroxidase (TPO expression in differentiating thyroid cells and cannot be activated by undifferentiated stem cells which do not express TPO.Results: There was decreased expression of thyroid specific genes such as Tg and NIS and increased expression of stemness markers such as Oct4, Rex1, CD15 and Sox2 in the thyroid carcinoma tissue from 6 week old BRAFV600E mice. The decreased expression of the epithelial marker E-cadherin and increased EMT regulators including Snail, Slug, and TGF-β1 and TGF-β3, and the mesenchymal marker vimentin demonstrated the simultaneous progression of EMT and the CSC-like phenotype. Stemness was also found in a derived cancer thyroid cell line in which overexpression of Snail caused up-regulation of vimentin expression and up regulation of stemness markers Oct4, Rex1, CD15 with enhanced migration ability of the cells. Conclusions: Our findings support our earlier hypothesis that stemness in thyroid cancer is derived via EMT rather than from resident thyroid stem cells. In mice with a thyroid-specific knock-in of oncogenic Braf (LSL-Braf(V600E/TPO-Cre the neoplastic changes were dependent on thyroid cell differentiation and the onset of stemness must have been derived from differentiated thyroid epithelial cells.

  19. Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Narumol Bhummaphan

    2015-01-01

    Full Text Available As cancer stem cells (CSCs contribute to malignancy, metastasis, and relapse of cancers, potential of compound in inhibition of CSCs has garnered most attention in the cancer research as well as drug development fields recently. Herein, we have demonstrated for the first time that gigantol, a pure compound isolated from Dendrobium draconis, dramatically suppressed stem-like phenotypes of human lung cancer cells. Gigantol at nontoxic concentrations significantly reduced anchorage-independent growth and survival of the cancer cells. Importantly, gigantol significantly reduced the ability of the cancer cells to form tumor spheroids, a critical hallmark of CSCs. Concomitantly, the treatment of the compound was shown to reduce well-known lung CSCs markers, including CD133 and ALDH1A1. Moreover, we revealed that gigantol decreased stemness in the cancer cells by suppressing the activation of protein kinase B (Akt signal which in turn decreased the cellular levels of pluripotency and self-renewal factors Oct4 and Nanog. In conclusion, gigantol possesses CSCs suppressing activity which may facilitate the development of this compound for therapeutic approaches by targeting CSCs.

  20. The origin of stroma surrounding epithelial ovarian cancer cells.

    Science.gov (United States)

    Akahane, Tomoko; Hirasawa, Akira; Tsuda, Hiroshi; Kataoka, Fumio; Nishimura, Sadako; Tanaka, Hideo; Tominaga, Eiichiro; Nomura, Hiroyuki; Chiyoda, Tatsuyuki; Iguchi, Yoko; Yamagami, Wataru; Susumu, Nobuyuki; Aoki, Daisuke

    2013-01-01

    Cancer stroma is thought to play an important role in tumor behavior, including invasion or metastasis and response to therapy. Cancer stroma is generally thought either to be non-neoplastic cells, including tissue-marrow or bone-marrow-derived fibroblasts, or to originate in epithelial mesenchymal transition of cancer cells. In this study, we evaluated the status of the p53 gene in both the cancer cells and the cancer stroma in epithelial ovarian cancer (EOC) to elucidate the origin of the stroma. Samples from 16 EOC patients were included in this study. Tumor cells and adjacent nontumor stromal cells were microdissected and DNA was extracted separately. We analyzed p53 sequences (exons 5-8) of both cancer and stromal tissues in all cases. Furthermore, we examined p53 protein expression in all cases. Mutations in p53 were detected in 9 of the 16 EOCs: in 8 of these cases, the mutations were detected only in cancer cells. In 1 case, the same mutation (R248Q) was detected in both cancer and stromal tissues, and p53 protein expression was detected in both the cancer cells and the cancer stroma. Most cancer stroma in EOC is thought to originate from non-neoplastic cells, but some parts of the cancer stroma might originate from cancer cells.

  1. Understanding delayed T-cell priming, lung recruitment, and airway luminal T-cell responses in host defense against pulmonary tuberculosis.

    Science.gov (United States)

    Shaler, Christopher R; Horvath, Carly; Lai, Rocky; Xing, Zhou

    2012-01-01

    Mycobacterium tuberculosis (M.tb), the causative bacterium of pulmonary tuberculosis (TB), is a serious global health concern. Central to M.tb effective immune avoidance is its ability to modulate the early innate inflammatory response and prevent the establishment of adaptive T-cell immunity for nearly three weeks. When compared with other intracellular bacterial lung pathogens, such as Legionella pneumophila, or even closely related mycobacterial species such as M. smegmatis, this delay is astonishing. Customarily, the alveolar macrophage (AM) acts as a sentinel, detecting and alerting surrounding cells to the presence of an invader. However, in the case of M.tb, this may be impaired, thus delaying the recruitment of antigen-presenting cells (APCs) to the lung. Upon uptake by APC populations, M.tb is able to subvert and delay the processing of antigen, MHC class II loading, and the priming of effector T cell populations. This delay ultimately results in the deferred recruitment of effector T cells to not only the lung interstitium but also the airway lumen. Therefore, it is of upmost importance to dissect the mechanisms that contribute to the delayed onset of immune responses following M.tb infection. Such knowledge will help design the most effective vaccination strategies against pulmonary TB.

  2. Production of endocannabinoids by activated T cells and B cells modulates inflammation associated with delayed-type hypersensitivity.

    Science.gov (United States)

    Sido, Jessica M; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2016-06-01

    Endocannabinoids are endogenous ligands for the cannabinoid (CB) receptors which include anandamide (AEA) and 2-arachidonyl glycerol (2-AG). 2-AG has been linked to inflammation due to its elevated expression in animal models of autoimmunity and hypersensitivity. However, administration of exogenous 2-AG has been shown to suppress inflammation making its precise role unclear. In the current study, we investigated the role of 2-AG following immunization of C57BL/6 (BL6) mice with methylated BSA (mBSA) antigen, which triggers both delayed-type hypersensitivity (DTH) and antibody response. We found that while naïve T cells and B cells expressed low levels of 2-AG, expression significantly increased upon activation. Furthermore, mBSA-immunized mice exhibited higher 2-AG concentration than naïve mice. Exogenous 2-AG treatment (40 mg/kg) in mBSA-immunized mice led to reduced DTH response, and decreased Th1 and Th17-associated cytokines including IL-6, IL-2, TNF-α, and the IgG response. Addition of 2-AG to activated popliteal lymph node (PopLN) cell cultures also inhibited lymphocyte proliferation. Together, these data show for the first time that activated T and B cells produce 2-AG, which plays a negative regulatory role to decrease DTH via inhibition of T-cell activation and proliferation. Moreover, these findings suggest that exogenous 2-AG treatment can be used therapeutically in Th1- or Th17-driven disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Science.gov (United States)

    Choi, Yun-Jung; Park, Jung-Hyun; Han, Jae Woong; Kim, Eunsu; Jae-Wook, Oh; Lee, Seung Yoon; Kim, Jin-Hoi; Gurunathan, Sangiliyandi

    2016-01-01

    The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs). In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells) and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH) and CD133 by fluorescence-activated cell sorting (FACS). The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and mitochondrial membrane potential (mt-MP). The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells) and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells). These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells. PMID:27973444

  4. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi

    2016-12-01

    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  5. Levobuipivacaine-Induced Dissemination of A549 Lung Cancer Cells.

    Science.gov (United States)

    Chan, Shun-Ming; Lin, Bo-Feng; Wong, Chih-Shung; Chuang, Wen-Ting; Chou, Yu-Ting; Wu, Zhi-Fu

    2017-08-17

    While anaesthetics are frequently used on cancer patients during surgical procedures, their consequence on cancer progression remains to be elucidated. In this study, we sought to investigate the influence of local anesthetics on lung cancer cell dissemination in vitro and in vivo. A549 human non-small lung cancer cells were treated with various local anaesthetics including ropivacaine, lidocaine, levobupivacaine and bupivacaine. Cell barrier property was assessed using an electric cell-substrate impedance sensing (ECIS) system. The epithelial-to-mesenchymal transition (EMT) of treated cells was studied by immunofluorescence staining. In vitro and in vivo cancer cell dissemination were investigated.Gene expression microarray and quantitative real-time PCR (qrt-PCR) assays were used to identify the genes responsible for levobupivacaine-mediated cancer cell dissemination.The results illustrated that only levobupivacaine induced EMT in the treated cells and also caused the dissemination of cancer cells in vitro. In addition, after intravenous injection, levobupivacaine encouraged cancer cell dissemination in vivo. Gene expression microarray, qrt-PCR and immunoblotting revealed that after levobupivacaine treatment, the hypoxia-inducible factor (HIF)- 2α gene was upregulated in cancer cells. Our findings suggest that levobupivacaine may induce A549 lung cancer cell dissemination both in vitro and in vivo. More specifically, HIF-2α signaling possibly contributes to levobupivacaine-mediated A549 lung cancer cell dissemination.

  6. Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ®)—Health Professional Version

    Science.gov (United States)

    Hereditary kidney cancer (renal cell cancer) syndromes include von Hippel-Lindau disease, hereditary leiomyomatosis and renal cell cancer, Birt-Hogg-Dubé syndrome, and hereditary papillary renal carcinoma. Learn about the genetics, clinical manifestations, and management of these hereditary cancer syndromes in this expert-reviewed summary.

  7. Probiotics, dendritic cells and bladder cancer.

    Science.gov (United States)

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  8. Complementary and alternative medicine (CAM) use and delays in presentation and diagnosis of breast cancer patients in public hospitals in Malaysia.

    Science.gov (United States)

    Mohd Mujar, Noor Mastura; Dahlui, Maznah; Emran, Nor Aina; Abdul Hadi, Imisairi; Wai, Yan Yang; Arulanantham, Sarojah; Hooi, Chea Chan; Mohd Taib, Nur Aishah

    2017-01-01

    Complementary and alternative medicine (CAM) is widely used among the breast cancer patients in Malaysia. Delays in presentation, diagnosis and treatment have been shown to impact the disease prognosis. There is considerable use of CAM amongst breast cancer patients. CAM use has been cited as a cause of delay in diagnosis and treatments in qualitative studies, however there had not been any confirmatory study that confirms its impact on delays. The purpose of this study was to evaluate whether the use of CAM among newly diagnosed breast cancer patients was associated with delays in presentation, diagnosis or treatment of breast cancer. This multi-centre cross-sectional study evaluating the time points of the individual breast cancer patients' journey from first visit, resolution of diagnosis and treatments was conducted in six public hospitals in Malaysia. All newly diagnosed breast cancer patients from 1st January to 31st December 2012 were recruited. Data were collected through medical records review and patient interview by using a structured questionnaire. Complementary and alternative medicine (CAM) was defined as the use of any methods and products not included in conventional allopathic medicine before commencement of treatments. Presentation delay was defined as time taken from symptom discovery to first presentation of more than 3 months. The time points were categorised to diagnosis delay was defined as time taken from first presentation to diagnosis of more than 1 month and treatment delay was defined as time taken from diagnosis to initial treatment of more than 1 month. Multiple logistic regression was used for analysis. A total number of 340 patients participated in this study. The prevalence of CAM use was 46.5% (n = 158). Malay ethnicity (OR 3.32; 95% CI: 1.85, 5.97) and not interpreting symptom as cancerous (OR 1.79; 95% CI: 1.10, 2.92) were significantly associated with CAM use. The use of CAM was associated with delays in presentation (OR 1

  9. Delayed fertilization of anuran amphibian (Xenopus) eggs leads to reduced numbers of primordial germ cells

    Science.gov (United States)

    Wakahara, M.; Neff, A. W.; Malacinski, G. M.

    1984-01-01

    Several media were tested for the extent to which they promoted high fertilization efficiencies in ovulated, stripped Xenopus eggs. One medium was selected for maintaining eggs in a 'delayed fertilization' (DelF) condition. DelF eggs displayed several unusual characteristics, including shift of the center of gravity, prominent sperm entrance site, and occasional polyspermy. The frequency of normal pattern formation varied according to the length of time eggs were maintained in the DelF condition. Various developmental abnormalities were observed during gastrulation, neurulation, and organogenesis. Most abnormalities appeared, however, to be related to morphogenesis of the endoderm. Primordial germ cell (PGC) development was examined in DelF eggs which displayed normal external morphological features at the swimming tadpole stage. PGC counts were usually normal in short-duration (eg, 5 hr) DelF eggs, but frequently substantially reduced or completely diminished in longer-duration (eg, 25h) tadpoles. Six spawnings were compared and shown to exhibit considerable variability in fertility, morphogenesis, and PGC development. Yolk platelet shifts and developmental parameters were examined in two additional spawnings. The subcortical cytoplasm in which the germ plasm is normally localized appeared to be disrupted in longer duration DelF eggs. That observation may account for low PGC counts in DelF tadpoles.

  10. American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators.

    Science.gov (United States)

    Déziel, Bob; MacPhee, James; Patel, Kunal; Catalli, Adriana; Kulka, Marianna; Neto, Catherine; Gottschall-Pass, Katherine; Hurta, Robert

    2012-05-01

    Prostate cancer is one of the most common cancers in the world, and its prevalence is expected to increase appreciably in the coming decades. As such, more research is necessary to understand the etiology, progression and possible preventative measures to delay or to stop the development of this disease. Recently, there has been interest in examining the effects of whole extracts from commonly harvested crops on the behaviour and progression of cancer. Here, we describe the effects of whole cranberry extract (WCE) on the behaviour of DU145 human prostate cancer cells in vitro. Following treatment of DU145 human prostate cancer cells with 10, 25 and 50 μg ml⁻¹ of WCE, respectively for 6 h, WCE significantly decreased the cellular viability of DU145 cells. WCE also decreased the proportion of cells in the G2-M phase of the cell cycle and increased the proportion of cells in the G1 phase of the cell cycle following treatment of cells with 25 and 50 μg ml⁻¹ treatment of WCE for 6 h. These alterations in cell cycle were associated with changes in cell cycle regulatory proteins and other cell cycle associated proteins. WCE decreased the expression of CDK4, cyclin A, cyclin B1, cyclin D1 and cyclin E, and increased the expression of p27. Changes in p16(INK4a) and pRBp107 protein expression levels also were evident, however, the changes noted in p16(INK4a) and pRBp107 protein expression levels were not statistically significant. These findings demonstrate that phytochemical extracts from the American cranberry (Vaccinium macrocarpon) can affect the behaviour of human prostate cancer cells in vitro and further support the potential health benefits associated with cranberries.

  11. Dendritic Cells in the Cancer Microenvironment

    Directory of Open Access Journals (Sweden)

    Yang Ma, Galina V. Shurin, Zhu Peiyuan, Michael R. Shurin

    2013-01-01

    Full Text Available The complexity of the tumor immunoenvironment is underscored by the emergence and discovery of different subsets of immune effectors and regulatory cells. Tumor-induced polarization of immune cell differentiation and function makes this unique environment even more intricate and variable. Dendritic cells (DCs represent a special group of cells that display different phenotype and activity at the tumor site and exhibit differential pro-tumorigenic and anti-tumorigenic functions. DCs play a key role in inducing and maintaining the antitumor immunity, but in the tumor environment their antigen-presenting function may be lost or inefficient. DCs might be also polarized into immunosuppressive/tolerogenic regulatory DCs, which limit activity of effector T cells and support tumor growth and progression. Although various factors and signaling pathways have been described to be responsible for abnormal functioning of DCs in cancer, there are still no feasible therapeutic modalities available for preventing or reversing DC malfunction in tumor-bearing hosts. Thus, better understanding of DC immunobiology in cancer is pivotal for designing novel or improved therapeutic approaches that will allow proper functioning of DCs in patients with cancer.

  12. Are All Highly Malignant Cancer Cells Identical?

    Science.gov (United States)

    1979-01-01

    ADA3665 ARE AL HIGHL MAGNANTCANCER CELLS DENOIALU) PENNSYLVANIA HOSPITAL PHILADELPHIA DEPT OF MOLECULAR BIOLOGY G NIGET AL 199 N00014-ACA026 UNCLASFE...embryo cells or even the original fertilized ovum . If this speculation has validity, the carcinogenesis and differentiation have the same destinies but...F/G /5 N 1111 2Z111117 1 125iiI 1 1. 1111_L6. -11 O=M 1 MrCROCOP RErSOLUTICN TEST CHART N, APoP SN A’ ,- ARE ALL HIGHLY MALIGNANT CANCER CELLS

  13. Gastrin releasing peptide GRP(14-27) in human breast cancer cells and in small cell lung cancer

    DEFF Research Database (Denmark)

    Vangsted, A J; Andersen, E V; Nedergaard, L

    1991-01-01

    Immunoreactivity related to the gastrin-releasing peptide (GRP) precursor was detected in four different human breast cancer cell lines. The amounts and the characteristics in extracts from different breast carcinoma cells were compared with cell extracts from small cell lung cancer (SCLC) cells...

  14. Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer

    Science.gov (United States)

    2013-03-25

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

  15. Myc mediates cancer stem-like cells and EMT changes in triple negative breast cancers cells.

    Directory of Open Access Journals (Sweden)

    Shuping Yin

    Full Text Available Women with triple negative breast cancer (TNBC have poor prognosis compared to other breast cancer subtypes. There were several reports indicating racial disparity in breast cancer outcomes between African American (AA and European American (EA women. For example, the mortality rates of AA breast cancer patients were three times higher than of EA patients, even though, the incidence is lower in AA women. Our in vitro studies indicate that cancer stem-like cells (CSCs derived from AA TNBC cell lines have significantly higher self-renewal potential (mammosphere formation than CSCs derived from EA cell lines. TNBC tumors express high levels of Myc compared to luminal A or HER2 expressing breast cancers. We studied the effects of c-Myc overexpression on CSCs and chemotherapy in AA, and EA derived TNBC cell line(s. Overexpression of c-Myc in AA derived MDA-MB-468 (Myc/MDA-468 cells resulted in a significant increase in CSCs and with minimal changes in epithelial-to-mesenchymal transition (EMT compared to the control group. In contrast, overexpression of c-Myc in EA derived MDA-MB-231(Myc/MDA-231 cells led to increased epithelial-to-mesenchymal transition (EMT, with a minimal increase in CSCs compared to the control group. Myc/MDA-468 cells were resistant to standard chemotherapeutic treatments such as iniparib (PARP inhibitor plus cisplatin, / iniparib, cisplatin, paclitaxel and docetaxel. However, Myc/MDA-231 cells, which showed EMT changes responded to iniparib with cisplatin, but were resistant to other drugs, such as iniparib, cisplatin, paclitaxel and docetaxel. Collectively, our results indicate that intrinsic differences in the tumor biology may contribute to the breast cancer disparities.

  16. Adipose-derived stromal cells inhibit prostate cancer cell proliferation inducing apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Takahara, Kiyoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Ii, Masaaki, E-mail: masaii@art.osaka-med.ac.jp [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Inamoto, Teruo; Komura, Kazumasa; Ibuki, Naokazu; Minami, Koichiro; Uehara, Hirofumi; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Asahi, Michio [Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka (Japan); Azuma, Haruhito [Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka (Japan)

    2014-04-18

    Highlights: • AdSC transplantation exhibits inhibitory effect on tumor progressions of PCa cells. • AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway. • High expression of the TGF-β1 gene in AdSCs. - Abstract: Mesenchymal stem cells (MSCs) have generated a great deal of interest in the field of regenerative medicine. Adipose-derived stromal cells (AdSCs) are known to exhibit extensive proliferation potential and can undergo multilineage differentiation, sharing similar characteristics to bone marrow-derived MSCs. However, as the effect of AdSCs on tumor growth has not been studied sufficiently, we assessed the degree to which AdSCs affect the proliferation of prostate cancer (PCa) cell. Human AdSCs exerted an inhibitory effect on the proliferation of androgen-responsive (LNCaP) and androgen-nonresponsive (PC3) human PCa cells, while normal human dermal fibroblasts (NHDFs) did not, and in fact promoted PCa cell proliferation to a degree. Moreover, AdSCs induced apoptosis of LNCaP cells and PC3 cells, activating the caspase3/7 signaling pathway. cDNA microarray analysis suggested that AdSC-induced apoptosis in both LNCaP and PC3 cells was related to the TGF-β signaling pathway. Consistent with our in vitro observations, local transplantation of AdSCs delayed the growth of tumors derived from both LNCaP- and PC3-xenografts in immunodeficient mice. This is the first preclinical study to have directly demonstrated that AdSC-induced PCa cell apoptosis may occur via the TGF-β signaling pathway, irrespective of androgen-responsiveness. Since autologous AdSCs can be easily isolated from adipose tissue without any ethical concerns, we suggest that therapy with these cells could be a novel approach for patients with PCa.

  17. Guidelines on renal cell cancer

    NARCIS (Netherlands)

    Mickisch, G; Carballido, J; Hellsten, S; Schuize, H; Mensink, H

    Objectives., On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and. Follow Up of Renal. Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost-effectiveness and clinical feasibility. Method: A

  18. Decreased Iron in Cancer Cells and Their Microenvironment Improves Cytolysis of Breast Cancer Cells by Natural Killer Cells.

    Science.gov (United States)

    Jiang, Xian-Peng; Elliott, Robert L

    2017-05-01

    The association of iron with anticancer immunity is unclear. In order to determine the role of iron in anticancer immunity, we manipulated intracellular iron levels of the human MCF-7 and MDA-MB-231 breast cancer cell lines, and measured cytolysis of breast cancer cells by the natural killer cell line NK-92MI, nitric oxide (NO) production, tumor necrosis factor alpha (TNFα) production and gene expression of ferritin heavy chain (FTH1). We found that NK-92MI increased synthesis and release of NO and TNFα into the medium during co-culturing of NK-92MI cells with MCF-7 or MDA-MB-231 cells. Addition of iron inhibited the cytolysis of the breast cancer cell lines. The iron chelator deferoxamine (DFOM) increased NK-92MI cytolysis to MCF-7 or MDA-MB-231 cells. Iron reversed cytotoxicity to breast cancer cells induced by NO, released from S-nitroso-N-acetyl-penicillamine (NO donor). Real time quantitative polymerase chain reaction showed that iron up-regulated the expression of FTH1 and iron chelator DFOM reduced FTH1 expression of MCF-7 and MDA-MB-231 cells. In conclusion, increased iron in cancer cells and their microenvironment protects cancer cells from natural killer cell cytolysis by antagonizing NO- and TNFα-associated cytotoxicity and by up-regulation of ferritin expression in breast cancer cells. Conversely, a decrease in iron concentration caused by DFOM improves natural killer cytolysis of tumor cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. Immediate and delayed effects of mammographic screening on breast cancer mortality and incidence in birth cohorts.

    Science.gov (United States)

    Ripping, T M; Verbeek, A L M; van der Waal, D; Otten, J D M; den Heeten, G J; Fracheboud, J; de Koning, H J; Broeders, M J M

    2013-10-29

    Trend studies investigating the impact of mammographic screening usually display age-specific mortality and incidence rates over time, resulting in an underestimate of the benefit of screening, that is, mortality reduction, and an overestimate of its major harmful effect, that is, overdiagnosis. This study proposes a more appropriate way of analysing trends. Breast cancer mortality (1950-2009) and incidence data (1975-2009) were obtained from Statistics Netherlands, 'Stg. Medische registratie' and the National Cancer Registry in the Netherlands for women aged 25-85 years. Data were visualised in age-birth cohort and age-period figures. Birth cohorts invited to participate in the mammographic screening programme showed a deflection in the breast cancer mortality rates within the first 5 years after invitation. Thereafter, the mortality rate increased, although less rapidly than in uninvited birth cohorts. Furthermore, invited birth cohorts showed a sharp increase in invasive breast cancer incidence rate during the first 5 years of invitation, followed by a moderate increase during the following screening years and a decline after passing the upper age limit. When applying a trend study to estimate the impact of mammographic screening, we recommend using a birth cohort approach.

  20. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    Science.gov (United States)

    2017-09-14

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Renal Cell Cancer

  1. Induction of iPS cells and of cancer stem cells: the stem cell or reprogramming hypothesis of cancer?

    Science.gov (United States)

    Trosko, James E

    2014-01-01

    This article as designed to examine whether the "stoichiometric" or "elite models" of the origin of the "induced pluripotent stem" (iPS) cells fits some experiment facts from the developmental biology of adult stem cells and from the field of cancer research. In brief, since the evidence presented to support the stoichiometric model failed to recognize the factual existence of adult organ specific stem cells, the model has not been rigorously tested. In addition, the demonstration of a subset of cells (MUSE cells) in normal primary in vitro cultures of human fibroblasts (the usual source of iPS cells) seems to be the origin of the iPS cells. Moreover, from the field of carcinogenesis, the "stem cell" versus "de-differentiation" or "reprogramming" hypotheses were examined. Again, using the role of glycolysis, known to be associated with the Warburg effect in cancer cells, a list of experiments showing that (a) normal stem cells, which have few mitochondria, metabolize via glycolysis; (b) the stem cells are targets for "initiation" or "immortalization" or the blockage of differentiation and apoptosis of the stem cells by "immortalizing viruses"; (c) Lactate dehydrogenase A (LDHA), when expressed, is associated with glycolysis and therefore, must be expressed in normal adult stem cells, as well as in cancer cells; and (d) p53, depleted or rendered dysfunctional by SV40 Large T antigen, is associated with the reduction of mitochondrial function and mass and is associated with the Warburg effect. Together, these observations from the iPS and "cancer stem cell" fields support the idea that both iPS cells and cancer stem cell are derived from adult organ-specific stem cells that do not restore or switch their metabolism of glucose from oxidative metabolism to glycolysis but, rather, in both cases, the adult stem cell, which metabolizes by glycolysis, is prevented from differentiation or from metabolizing by oxidative phosphorylation. Copyright © 2013 Wiley Periodicals

  2. The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Ahmed Abdal Dayem

    2016-09-01

    Full Text Available The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The interplay between autophagy and apoptosis in the anti-cancer activity of polyphenols will also be highlighted. In addition, the potential of polyphenols to target cancer stem cells (CSCs via various mechanisms will be explained. Recently, the use of natural products as chemotherapeutics and chemopreventive drugs to overcome the side effects and resistance that arise from using chemical-based agents has garnered the attention of the scientific community. Polyphenol research is considered a promising field in the treatment and prevention of breast cancer.

  3. Calcium wave signaling in cancer cells

    Science.gov (United States)

    PARKASH, JAI; ASOTRA, KAMLESH

    2010-01-01

    Ca2+ functions as an important signaling messenger right from beginning of the life to final moment of the end of the life. Ca2+ is needed at several steps of the cell cycle such as early G1, at the G1/S, and G2/M transitions. The Ca2+ signals in the form of time-dependent changes in intracellular Ca2+ concentrations, [Ca2+]i, are presented as brief spikes organized into regenerative Ca2+ waves. Ca2+-mediated signaling pathways have also been shown to play important roles in carcinogenesis such as transformation of normal cells to cancerous cells, tumor formation and growth, invasion, angiogenesis and metastasis. Since the global Ca2+ oscillations arise from Ca2+ waves initiated locally, it results in stochastic oscillations because although each cell has many IP3Rs and Ca2+ ions, the law of large numbers does not apply to the initiating event which is restricted to very few IP3Rs due to steep Ca2+ concentration gradients. The specific Ca2+ signaling information is likely to be encoded in a calcium code as the amplitude, duration, frequency, waveform or timing of Ca2+ oscillations and decoded again at a later stage. Since Ca2+ channels or pumps involved in regulating Ca2+ signaling pathways show altered expression in cancer, one can target these Ca2+ channels and pumps as therapeutic options to decrease proliferation of cancer cells and to promote their apoptosis. These studies can provide novel insights into alterations in Ca2+ wave patterns in carcinogenesis and lead to development of newer technologies based on Ca2+ waves for the diagnosis and therapy of cancer. PMID:20875431

  4. Recognising symptoms of breast cancer as a reason for delayed presentation in Asian women--the psycho-socio-cultural model for breast symptom appraisal: opportunities for intervention.

    Science.gov (United States)

    Taib, Nur Aishah; Yip, Cheng-Har; Low, Wah-Yun

    2011-01-01

    Advanced presentation of breast cancer and the problem of late diagnosis is well documented. Patient delay beyond three months has been shown to reduce survival. This paper aims to explore the experience of Malaysian women presenting with advanced breast cancer with regards to their interpretation of breast symptoms. Purposive sampling of 19 breast cancer patients presenting with delayed treatment and/ or advanced cancer diagnosed within two years at the University Malaya Medical Centre, Kuala Lumpur were carried out. In-depth interviews were conducted using a self-devised interview guide. The interview guide covered the journey of the patient from discovering of symptoms to their present state. The audiotaped interviews were transcribed verbatim. NVivo 8 qualitative software was utilised for data management. Grounded theory with thematic analysis was utilised. Nine women delayed seeking diagnosis although recognizing the symptom, five did not recognize symptom, three delayed treatment and two did not delay health attention. Themes that emerged with regards to triggering help seeking behavior were: a) poor symptom knowledge and recognition; b) importance of knowledge of the disease and its' outcomes; c) role of coping mechanisms and affect; and lastly d) role of significant others in appraising a breast symptom. Symptom recognition remains an important public health issue in Malaysia. Educating women, their significant others and primary health and primary care providers in detecting early staged breast cancer are needed. Supporting and sanctioning women with breast symptoms are important. The psycho-social-cultural model of symptom appraisal may serve as an important addition to the fight against cancer in countries that do not have the resources for population based screening mammogram programmes.

  5. JUNB promotes the survival of Flavopiridol treated human breast cancer cells.

    Science.gov (United States)

    Hicks, Mellissa; Hu, Qiuping; Macrae, Erin; DeWille, James

    2014-07-18

    Chemotherapy resistance is a major obstacle to achieving durable progression-free-survival in breast cancer patients. Identifying resistance mechanisms is crucial to the development of effective breast cancer therapies. Immediate early genes (IEGs) function in the initial cellular reprogramming response to alterations in the extracellular environment and IEGs have been implicated in cancer cell development and progression. The purpose of this study was to investigate the influence of kinase inhibitors on IEG expression in breast cancer cells. The results demonstrated that Flavopiridol (FP), a CDK9 inhibitor, effectively reduced gene expression. FP treatment, however, consistently produced a delayed induction of JUNB gene expression in multiple breast cancer cell lines. Similar results were obtained with Sorafenib, a multi-kinase inhibitor and U0126, a MEK1 inhibitor. Functional studies revealed that JUNB plays a pro-survival role in kinase inhibitor treated breast cancer cells. These results demonstrate a unique induction of JUNB in response to kinase inhibitor therapies that may be among the earliest events in the progression to treatment resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy

    Directory of Open Access Journals (Sweden)

    Lisa Y. Pang

    2016-01-01

    Full Text Available Cyclooxygenase-2 (COX-2 is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE2, a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE2 release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

  7. Breast-conserving therapy for breast cancer: Cosmetic results and options for delayed reconstruction.

    Science.gov (United States)

    Negenborn, Vera L; Volders, José H; Krekel, Nicole M A; Haloua, Max H; Bouman, Mark-Bram; Buncamper, Marlon E; Niessen, Frank B; Winters, Hay A H; Terwee, Caroline B; Meijer, Sybren; van den Tol, M Petrousjka

    2017-10-01

    Optimisation of the cosmetic outcome after breast-conserving therapy (BCT) is important. We aimed to determine the cosmetic outcome following BCT and factors influencing this cosmesis and identify the most favourable options for delayed breast reconstruction. Four reconstructive surgeons evaluated the cosmetic outcome of 109 patients after BCT. Additionally, the surgeons indicated which patients were amenable for delayed reconstruction and the preferred type of reconstruction. The inter- and intra-observer agreement of the surgeons was rated. The mean overall cosmetic outcome was rated as fair (2.7/4.0, SD 0.9, 1.0-4.0). Risk factors for a poor cosmesis were larger breast size (OR 3.81, p = 0.040), larger tumour (OR 1.63, p = 0.028) and axillary lymph node dissection (ALND) (OR 3.09, p = 0.013). Reconstruction of the ipsilateral side was recommended in 55.6% and 94.5% and contralateral reconstruction in 16.7% and 73.3% of patients with good and poor cosmesis, respectively. Flap reconstruction and lipofilling were most commonly reported for the ipsilateral, and breast reduction for the contralateral breast, with reasonable improvement expected (2.2/4.0, SD 0.5, 1.08-3.3). The inter- (0.5-0.7) and intra-observer (0.63-0.79) agreement of the cosmesis was moderate to good, however, poor regarding the recommended reconstruction techniques (mainly Cosmetic outcome after BCT is influenced by breast and tumour size and ALND. Although several reconstructive options are available, the optimal method for revision surgery has not yet been determined. Future studies are necessary to obtain evidence-based guidelines for reconstructive surgery after BCT. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Advances in Lung Stem Cells and Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Huijing YIN

    2015-10-01

    Full Text Available Cancer stem cells (CSCs are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs, including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH and ATP-binding cassette sub-family G member 2 (ABCG2. Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR, signal transducer and activator of transcription 3 (STAT3 and phosphatidylinositol 3 kinase (PI3K pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients.

  9. Heat induces gene amplification in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Bin, E-mail: yanbin@mercyhealth.com [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Mercy Cancer Center, Mercy Medical Center-North Iowa, Mason City, IA 50401 (United States); Ouyang, Ruoyun [Department of Respiratory Medicine, The Second Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410011 (China); Huang, Chenghui [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Department of Oncology, The Third Xiangya Hospital, Xinagya School of Medicine, Central South University, Changsha 410013 (China); Liu, Franklin [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States); Neill, Daniel [Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39213 (United States); Li, Chuanyuan [Dermatology, Duke University Medical Center, Durham, NC 27710 (United States); Dewhirst, Mark [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. Black-Right-Pointing-Pointer Hyperthermia induces DNA double strand breaks. Black-Right-Pointing-Pointer DNA double strand breaks are considered to be required for the initiation of gene amplification. Black-Right-Pointing-Pointer The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 Degree-Sign C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) {gamma}H2AX immunostaining to detect {gamma}H2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 Degree-Sign C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 Degree-Sign C for 30 min induces DNA double strand breaks in HCT116 cells as shown by {gamma}H2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and

  10. Induction of artificial cancer stem cells from tongue cancer cells by defined reprogramming factors.

    Science.gov (United States)

    Harada, Koji; Ferdous, Tarannum; Cui, Dan; Kuramitsu, Yasuhiro; Matsumoto, Takuya; Ikeda, Eiji; Okano, Hideyuki; Ueyama, Yoshiya

    2016-07-27

    The cancer stem cells (CSCs), a small subpopulation of cells in tumor are responsible for the tumor initiation, growth, recurrence and metastasis of cancer, as well as resistance of cancers to drugs or radiotherapy. CSCs are an important target for the development of novel strategies in cancer treatment. However, CSCs-targeted new anti-cancer drug discovery is currently hindered by the lack of easy and reliable methods for isolating, collecting and maintaining sufficient number of CSCs. Here, we examined whether introduction of defined reprogramming factors (Oct4, shp53, Sox2, Klf4, l-Myc and Lin28) into HSC2 tongue cancer cells could transform the HSC2 into HSC2 with CSCs properties. We introduced the defined reprogramming factors into HSC2 tongue cancer cells via episomal vectors by electroporation method to generate transfectant cells. We investigated the malignant properties of the transfectant cells by cell proliferation assay, migration assay, wound healing assay, sphere formation assay, chemosensitivity and radiosensitivity assay in vitro; and also examined the tumorigenic potential of the transfectants in vivo. The transfectant cells (HSC2/hOCT3/4-shp53-F, HSC2/hSK, HSC2/hUL, HSC2/hOCT3/4-shp53-F + hSK, HSC2/hOCT3/4-shp53-F + hUL, HSC2/hSK + hUL, HSC2/hOCT3/4-shp53-F + hSK + hUL) displayed a malignant phenotype in culture and form tumors on the back of nude mice more efficiently than parental HSC2 and control HSC2/EGFP transfectant cells. They exhibited increased resistance to chemotherapeutic agents; 5-fluorouracil, cisplatin, docetaxel, trifluorothymidine, zoledronic acid, cetuximab, bortezomib and radiation when compared with HSC2 and HSC2/EGFP. Among all the transfected cells, HSC2/hOCT3/4-shp53-F + hSK + hUL cell containing all of the reprogramming factors showed the most aggressive and malignant properties and presented the highest number of spheres in the culture medium containing human recombinant fibroblast Growth Factor

  11. Transcription profiles of non-immortalized breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Holland James F

    2006-04-01

    Full Text Available Abstract Background Searches for differentially expressed genes in tumours have made extensive use of array technology. Most samples have been obtained from tumour biopsies or from established tumour-derived cell lines. Here we compare cultures of non-immortalized breast cancer cells, normal non-immortalized breast cells and immortalized normal and breast cancer cells to identify which elements of a defined set of well-known cancer-related genes are differentially expressed. Methods Cultures of cells from pleural effusions or ascitic fluids from breast cancer patients (MSSMs were used in addition to commercially-available normal breast epithelial cells (HMECs, established breast cancer cell lines (T-est and established normal breast cells (N-est. The Atlas Human Cancer 1.2 cDNA expression array was employed. The data obtained were analysed using widely-available statistical and clustering software and further validated through real-time PCR. Results According to Significance Analysis of Microarray (SAM and AtlasImage software, 48 genes differed at least 2-fold in adjusted intensities between HMECs and MSSMs (p Conclusion The expression profiles of 1176 genes were determined in finite life-span cultures of metastatic breast cancer cells and of normal breast cells. Significant differences were detected between the finite life-span breast cancer cell cultures and the established breast cancer cell lines. These data suggest caution in extrapolating information from established lines for application to clinical cancer research.

  12. FACT prevents the accumulation of free histones evicted from transcribed chromatin and a subsequent cell cycle delay in G1.

    Directory of Open Access Journals (Sweden)

    Macarena Morillo-Huesca

    2010-05-01

    Full Text Available The FACT complex participates in chromatin assembly and disassembly during transcription elongation. The yeast mutants affected in the SPT16 gene, which encodes one of the FACT subunits, alter the expression of G1 cyclins and exhibit defects in the G1/S transition. Here we show that the dysfunction of chromatin reassembly factors, like FACT or Spt6, down-regulates the expression of the gene encoding the cyclin that modulates the G1 length (CLN3 in START by specifically triggering the repression of its promoter. The G1 delay undergone by spt16 mutants is not mediated by the DNA-damage checkpoint, although the mutation of RAD53, which is otherwise involved in histone degradation, enhances the cell-cycle defects of spt16-197. We reveal how FACT dysfunction triggers an accumulation of free histones evicted from transcribed chromatin. This accumulation is enhanced in a rad53 background and leads to a delay in G1. Consistently, we show that the overexpression of histones in wild-type cells down-regulates CLN3 in START and causes a delay in G1. Our work shows that chromatin reassembly factors are essential players in controlling the free histones potentially released from transcribed chromatin and describes a new cell cycle phenomenon that allows cells to respond to excess histones before starting DNA replication.

  13. Natural killer cells enhance the immune surveillance of cancer

    African Journals Online (AJOL)

    Faisal Nouroz

    2015-09-11

    Sep 11, 2015 ... All the cells of the immune sys- tem cooperatively work against infectious agents and cancerous cells but Natural killer (NK) cells ..... Cancer stem cells (CSCs) retain the growth of tumor and resist chemotherapy [25]. ... radiation therapy and mushroom beta glucans showed only 1 nodule. The experiments ...

  14. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  15. Impact of treatment delay in Radium-223 therapy of metastatic castration-resistant prostate cancer patients

    DEFF Research Database (Denmark)

    Fosbøl, Marie Øbro; Petersen, Peter Meidahl; Daugaard, Gedske

    2018-01-01

    BACKGROUND: Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities...... to non-disease related reasons on OS, rPFS or number of completed treatment cycles....

  16. Hazard function for cancer patients and cancer cell dynamics.

    Science.gov (United States)

    Horová, Ivana; Pospísil, Zdenek; Zelinka, Jirí

    2009-06-07

    The aim of the paper is to develop a procedure for an estimate of an analytical form of a hazard function for cancer patients. Although a deterministic approach based on cancer cell population dynamics yields the analytical expression, it depends on several parameters which should be estimated. On the other hand, a kernel estimate is an effective nonparametric method for estimating hazard functions. This method provides the pointwise estimate of the hazard function. Our procedure consists of two steps: in the first step we find the kernel estimate of the hazard function and in the second step the parameters in the deterministic model are obtained by the least squares method. A simulation study with different types of censorship is carried out and the developed procedure is applied to real data.

  17. A stochastic model for cancer stem cell origin in metastatic colon cancer.

    Science.gov (United States)

    Odoux, Christine; Fohrer, Helene; Hoppo, Toshitaka; Guzik, Lynda; Stolz, Donna Beer; Lewis, Dale W; Gollin, Susanne M; Gamblin, T Clark; Geller, David A; Lagasse, Eric

    2008-09-01

    Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here, we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally derived tumor cells expressed many consistent (clonal) along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability.

  18. Surgery for nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Loïc Lang-Lazdunski

    2013-09-01

    Full Text Available Surgery remains the best curative option in patients with early stage lung cancer (stage I and II. Developments in minimally invasive techniques now allow surgeons to perform lung resections on elderly patients, patients with poor pulmonary function or significant cardiopulmonary comorbidities. New techniques, such as stereotactic radiotherapy and ablative procedures, are being evaluated in early-stage lung cancer and may represent an alternative to surgery in patients unfit for lung resection. Perioperative mortality rates have dropped significantly at most institutions in the past two decades and complications are managed more efficiently. Progress in imaging and staging techniques have helped cut futile thoracotomy rates and offer patients the most adequate treatment options. Large randomised trials have helped clarify the role of neoadjuvant, induction and adjuvant chemotherapy, as well as radiotherapy. Surgery remains an essential step in the multimodality therapy of selected patients with advanced-stage lung cancer (stage III and IV. Interventional and endoscopic techniques have reduced the role of surgery in the diagnosis and staging of nonsmall cell lung cancer, but surgery remains an important tool in the palliation of advanced-stage lung cancer. Large national/international surgical databases have been developed and predictive risk-models for surgical mortality/morbidity published by learned surgical societies. Nonetheless, lung cancer overall survival rates remain deceptively low and it is hoped that early detection/screening, better understanding of tumour biology and development of biomarkers, and development of efficient targeted therapies will help improve the prognosis of lung cancer patients in the next decade.

  19. Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis

    NARCIS (Netherlands)

    Chen, L.S.; Baker, T.; Hung, R.J.; Horton, A.; Culverhouse, R.; Hartz, S.; Saccone, N.; Cheng, I.; Deng, B.; Han, Y.; Hansen, H.M.; Horsman, J.; Kim, C.; Rosenberger, A.; Aben, K.K.H.; Andrew, A.S.; Chang, S.C.; Saum, K.U.; Dienemann, H.; Hatsukami, D.K.; Johnson, E.O.; Pande, M.; Wrensch, M.R.; McLaughlin, J.; Skaug, V.; Heijden, E.H.F.M. van der; Wampfler, J.; Wenzlaff, A.; Woll, P.; Zienolddiny, S.; Bickeboller, H.; Brenner, H.; Duell, E.J.; Haugen, A.; Bruske, I.; Kiemeney, L.A.L.M.; Lazarus, P.; Marchand, L. Le; Liu, G.; Mayordomo, J.; Risch, A.; Schwartz, A.G.; Teare, M.D.; Wu, X.; Wiencke, J.K.; Yang, P.; Zhang, Z.F.; Spitz, M.R.; Amos, C.I.; Bierut, L.J.

    2016-01-01

    BACKGROUND: Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear

  20. Early and Delayed Antiretroviral Therapy Results in Comparable Reductions in CD8+T Cell Exhaustion Marker Expression.

    Science.gov (United States)

    Rutishauser, Rachel Lena; Hartogensis, Wendy; Deguit, Christian Deo; Krone, Melissa; Hoh, Rebecca; Hecht, Frederick M; Pilcher, Christopher D; Bacchetti, Peter; Deeks, Steven G; Hunt, Peter W; McCune, Joseph M

    2017-07-01

    In untreated HIV infection, CD8 + T cell exhaustion (i.e., decreased proliferative and effector capacity) is associated with high levels of expression of coinhibitory receptors, including PD-1, T cell immunoreceptor with Ig and ITIM domains (TIGIT), CD160, and 2B4. This is evident for both HIV-specific and non-HIV-specific CD8 + T cells. Antiretroviral therapy (ART) initiated during chronic infection decreases but may not completely normalize the expression of such "exhaustion markers." Compared to initiation of ART later in the course of disease, initiation soon after infection reduces some parameters of chronic inflammation and adaptive immune dysfunction. However, it is not known if Early ART (e.g., initiated within the first 6 months after HIV infection) versus Delayed ART (e.g., initiated during chronic infection) preferentially reduces expression of exhaustion markers. We evaluated exhaustion marker expression on subsets of circulating effector and memory CD8 + T cells at longitudinal pre- and post-ART (2 and 5 years on ART) time points from n = 19 (Early ART) and n = 23 (Delayed ART) individuals. Before ART, TIGIT and CD160 were expressed on a statistically significantly higher proportion of effector and transitional memory cells from individuals in the Delayed ART group: the timing of ART initiation, however, did not consistently affect the expression of the exhaustion markers once viral suppression was achieved. Understanding which factors do and do not regulate aspects of CD8 + T cell exhaustion, including the expression of exhaustion markers, is critical to inform the rational design of CD8 + T cell-based therapies to treat HIV, for which CD8 + T cell exhaustion remains an important barrier to efficacy.

  1. Uptake of DNA by cancer cells without a transfection reagent.

    Science.gov (United States)

    Kong, Yanping; Zhang, Xianbo; Zhao, Yongliang; Xue, Yanfang; Zhang, Ye

    2017-01-21

    Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis. Their uptake of DNAs might be different from normal cells; they may take in DNAs directly from the environment. In this report, we studied the uptake of DNAs in cancer cells without a transfection reagent. A group of DNA fragments were prepared with PCR and labeled with isotope phosphorous-32 to test their uptake by Huh 7 (liver cancer) and THLE3 (normal liver cells) after incubation overnight by counting radioactivity of the cells' genomic DNA. Multiple cell lines including breast cancer and lung cancer were tested with the same method. DNA molecules were also labeled with fluorescence to test the location in the cells using a kit of "label it fluorescence in situ hybridization (FISH)" from Mirus (USA). The data demonstrated that hepatocellular carcinoma cells possess the ability to take in large DNA fragments directly without a transfection reagent whereas normal liver cells cannot. Huh7 and MDA-MB231 cells displayed a significantly higher Rhodamine density in the cytoplasmic phagosomes and this suggests that the mechanism of uptake of large DNA by cancer cells is likely endocytosis. The efficacy of uptake is related to the DNA's size. Some cell lines of lung cancer and breast cancer also showed similar uptake of DNA. In the present study, we have revealed the evidence that some cancer cells, but not nontumorigenic cells, can take DNA fragments directly from the environment without the aid of the transfecting

  2. Calcium, cancer and killing: the role of calcium in killing cancer cells by cytotoxic T lymphocytes and natural killer cells.

    Science.gov (United States)

    Schwarz, Eva C; Qu, Bin; Hoth, Markus

    2013-07-01

    Killing cancer cells by cytotoxic T lymphocytes (CTL) and by natural killer (NK) cells is of vital importance. Cancer cell proliferation and apoptosis depend on the intracellular Ca(2+) concentration, and the expression of numerous ion channels with the ability to control intracellular Ca(2+) concentrations has been correlated with cancer. A rise of intracellular Ca(2+) concentrations is also required for efficient CTL and NK cell function and thus for killing their targets, in this case cancer cells. Here, we review the data on Ca(2+)-dependent killing of cancer cells by CTL and NK cells. In addition, we discuss emerging ideas and present a model how Ca(2+) may be used by CTL and NK cells to optimize their cancer cell killing efficiency. This article is part of a Special Issue entitled: 12th European Symposium on Calcium. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

    Directory of Open Access Journals (Sweden)

    G-Andre Banat

    Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

  4. Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy

    Science.gov (United States)

    Lee, Changhan; Raffaghello, Lizzia; Brandhorst, Sebastian; Safdie, Fernando M.; Bianchi, Giovanna; Martin-Montalvo, Alejandro; Pistoia, Vito; Wei, Min; Hwang, Saewon; Merlino, Annalisa; Emionite, Laura; de Cabo, Rafael; Longo, Valter D.

    2013-01-01

    Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2val19 to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs—but not either treatment alone—resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers. PMID:22323820

  5. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy.

    Science.gov (United States)

    Lee, Changhan; Raffaghello, Lizzia; Brandhorst, Sebastian; Safdie, Fernando M; Bianchi, Giovanna; Martin-Montalvo, Alejandro; Pistoia, Vito; Wei, Min; Hwang, Saewon; Merlino, Annalisa; Emionite, Laura; de Cabo, Rafael; Longo, Valter D

    2012-03-07

    Short-term starvation (or fasting) protects normal cells, mice, and potentially humans from the harmful side effects of a variety of chemotherapy drugs. Here, we show that treatment with starvation conditions sensitized yeast cells (Saccharomyces cerevisiae) expressing the oncogene-like RAS2(val19) to oxidative stress and 15 of 17 mammalian cancer cell lines to chemotherapeutic agents. Cycles of starvation were as effective as chemotherapeutic agents in delaying progression of different tumors and increased the effectiveness of these drugs against melanoma, glioma, and breast cancer cells. In mouse models of neuroblastoma, fasting cycles plus chemotherapy drugs--but not either treatment alone--resulted in long-term cancer-free survival. In 4T1 breast cancer cells, short-term starvation resulted in increased phosphorylation of the stress-sensitizing Akt and S6 kinases, increased oxidative stress, caspase-3 cleavage, DNA damage, and apoptosis. These studies suggest that multiple cycles of fasting promote differential stress sensitization in a wide range of tumors and could potentially replace or augment the efficacy of certain chemotherapy drugs in the treatment of various cancers.

  6. Optical imaging of cancer and cell death

    OpenAIRE

    Xie, Bangwen

    2013-01-01

    The aim of the work included in this PhD thesis was to explore the diverse application possibility of using NIR fluorescent probes with specific properties to visualize and characterize cancer and cell death. In this thesis, we mainly focus on optical imaging and its application, both at microscopic and macroscopic level. Because we believe optical imaging in particular represents a technology that has unique potential to exploit further our knowledge in preclinical research. First, we imaged...

  7. Mesenchymal Stem Cell Based Therapy for Prostate Cancer

    Science.gov (United States)

    2015-11-01

    14 4 1. Introduction Prostate cancer (PCa) is the second most common cancer and the second leading cause of cancer- related deaths in American men...internalization by MSCs (red (DiI) - MPs, green ( cholera toxin) - cell membrane, blue (Hoechst) - cell nucleus). (d) To assess drug release from G114 MP-loaded

  8. Therapeutic Effectiveness of Anticancer Phytochemicals on Cancer Stem Cells.

    Science.gov (United States)

    Oh, Jisun; Hlatky, Lynn; Jeong, Yong-Seob; Kim, Dohoon

    2016-06-30

    Understanding how to target cancer stem cells (CSCs) may provide helpful insights for the development of therapeutic or preventive strategies against cancers. Dietary phytochemicals with anticancer properties are promising candidates and have selective impact on CSCs. This review summarizes the influence of phytochemicals on heterogeneous cancer cell populations as well as on specific targeting of CSCs.

  9. Novel regulators of prostate cancer stem cells and tumor aggressiveness

    NARCIS (Netherlands)

    Zoni, E.

    2016-01-01

    In the past decade it became increasingly clear that tumor heterogeneity represents one of the major problems for cancer treatment, also in prostate cancer. The identification of the molecular properties of highly aggressive cells (Cancer Stem Cells, CSCs) dispersed within the tumor represents a

  10. Differentiation of Prostate Cancer Cells by Using Flexible Fluorescent Polymers

    Science.gov (United States)

    Scott, Michael D.; Dutta, Rinku; Haldar, Manas K.; Guo, Bin; Friesner, Daniel L.; Mallik, Sanku

    2011-01-01

    Using water soluble, fluorescent, flexible polymers, we have devised a novel methodology for identification and differentiation of prostate cancer cells. By using a step-wise linear discriminant analysis we demonstrate that the differential modulations of the polymer emission intensities in the presence of conditioned cell culture media can be used to distinguish between prostate cancer subtypes and between cancerous and non-cancer cells. The differences in the compositions of the conditioned cell culture media are likely contributing to different fluorescence spectral patterns of the polymers. This in vitro approach may provide a novel platform for the development of an alternative prostate cancer diagnostic and subtyping technique. PMID:22148518

  11. Breast Cancer Stem Cells and Tumor Suppressor Genes

    Directory of Open Access Journals (Sweden)

    Wendy W. Hwang-Verslues

    2008-10-01

    Full Text Available Studies of breast cancer stem cells are in their infancy and many fundamental questions have yet to be fully addressed. The molecular distinction between normal and cancerous breast stem cells is not clear. While there have been recent breakthroughs in mouse mammary stem cells and lineage determination in mammary glands, little has been determined in human cells. Microarray analyses have provided molecular categorization of breast cancer. However, the cellular origin of different types of breast cancer is largely unknown. In addition, the relationship between breast cancer stem cells and mammary progenitor cells has yet to be clarified. One of the key questions is how a normal mammary stem cell becomes a breast cancer stem cell. Importantly, the existence of different types of human breast cancers with distinct pathologic and molecular signatures suggests the possibility that different types of breast cancer stem cells may exist. Here, we aim to review the current evidence for the existence of different subtypes of breast cancer stem cells and provide further insight into how tumor suppressors might be involved in the initiation of breast cancer stem cells.

  12. Telmisartan inhibits human urological cancer cell growth through early apoptosis

    Science.gov (United States)

    MATSUYAMA, MASAHIDE; FUNAO, KIYOAKI; KURATSUKURI, KATSUYUKI; TANAKA, TOMOAKI; KAWAHITO, YUTAKA; SANO, HAJIME; CHARGUI, JAMEL; TOURAINE, JEAN-LOUIS; YOSHIMURA, NORIO; YOSHIMURA, RIKIO

    2010-01-01

    Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agents. In addition, studies have provided evidence that ARBs have the potential to inhibit the growth of several types of cancer cells. It was reported that telmisartan (a type of ARB) has peroxisome proliferator-activated receptor (PPAR)-γ activation activity. We previously reported that the PPAR-γ ligand induces growth arrest in human urological cancer cells through apoptosis. In this study, we evaluated the effects of telmisartan and other ARBs on cell proliferation in renal cell carcinoma (RCC), bladder cancer (BC), prostate cancer (PC) and testicular cancer (TC) cell lines. The inhibitory effects of telmisartan and other ARBs (candesartan, valsartan, irbesartan and losartan) on the growth of the RCC, BC, PC and TC cell lines was investigated using an MTT assay. Flow cytometry and Hoechst staining were used to determine whether the ARBs induced apoptosis. Telmisartan caused marked growth inhibition in the urological cancer cells in a dose- and time-dependent manner. Urological cancer cells treated with 100 μM telmisartan underwent early apoptosis and DNA fragmentation. However, the other ARBs had no effect on cell proliferation in any of the urological cancer cell lines. Telmisartan may mediate potent anti-proliferative effects in urological cancer cells through PPAR-γ. Thus, telmisartan is a potent target for the prevention and treatment of human urological cancer. PMID:22993542

  13. {sup 68}Ga-PSMA I and T PET/CT for assessment of prostate cancer: evaluation of image quality after forced diuresis and delayed imaging

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten; Weiberg, Desiree; Ross, Tobias L.; Bengel, Frank M. [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Klot, Christoph von [Hannover Medical School, Department of Urology and Urologic Oncology, Hannover (Germany); Wester, Hans-Juergen [Technische Universitaet Muenchen, Pharmaceutical Radiochemistry, Garching (Germany); Henkenberens, Christoph; Christiansen, Hans [Hannover Medical School, Department of Radiation Oncology, Hannover (Germany); Merseburger, Axel S. [University Hospital Schleswig-Holstein, Department of Urology, Campus Luebeck, Luebeck (Germany)

    2016-12-15

    Urinary radiotracer excretion of {sup 68}Ga-Labelled prostate-specific membrane antigen (PSMA) ligands may complicate the assessment of the prostate region and differentiation of lymph nodes from ureteral activity. The aim of this study was to assess the value of delayed imaging after forced diuresis. Sixty-six patients underwent {sup 68}Ga-PSMA I and T PET/CT for evaluation of prostate cancer at 60 min post-injection. In subgroups of patients, this was amended by delayed imaging after 180 min post-injection, preceded by furosemide and oral hydration early, at the time of tracer injection, or delayed, at 100 min post-injection. Urinary tracer activity within the bladder and focal ureteral activity was analyzed. After forced diuresis, linear and focal visualization of ureters was significantly reduced. After delayed furosemide, mean and peak bladder activity decreased (p < 0.001), and image quality of the prostate region improved on delayed images (p < 0.001). Early furosemide co-injection with tracer resulted in increased mean and peak bladder activity (p < 0.001) and in deteriorated image quality of the prostate region on delayed images (p = 0.008). Ga-PSMA I and T PET/CT delayed imaging after forced diuresis can improve the assessment of prostate region and pelvic lymph nodes by removing excreted tracer from the lower urinary tract. (orig.)

  14. Cell-ECM Interactions During Cancer Invasion

    Science.gov (United States)

    Jiang, Yi

    The extracellular matrix (ECM), a fibrous material that forms a network in a tissue, significantly affects many aspects of cellular behavior, including cell movement and proliferation. Transgenic mouse tumor studies indicate that excess collagen, a major component of ECM, enhances tumor formation and invasiveness. Clinically, tumor associated collagen signatures are strong markers for breast cancer survival. However, the underlying mechanisms are unclear since the properties of ECM are complex, with diverse structural and mechanical properties depending on various biophysical parameters. We have developed a three-dimensional elastic fiber network model, and parameterized it with in vitro collagen mechanics. Using this model, we study ECM remodeling as a result of local deformation and cell migration through the ECM as a network percolation problem. We have also developed a three-dimensional, multiscale model of cell migration and interaction with ECM. Our model reproduces quantitative single cell migration experiments. This model is a first step toward a fully biomechanical cell-matrix interaction model and may shed light on tumor associated collagen signatures in breast cancer. This work was partially supported by NIH-U01CA143069.

  15. Mechanistic exploration of cancer stem cell marker voltage-dependent calcium channel α2δ1 subunit-mediated chemotherapy resistance in small cell lung cancer.

    Science.gov (United States)

    Yu, Jiangyong; Wang, Shuhang; Zhao, Wei; Duan, Jianchun; Wang, Zhijie; Chen, Hanxiao; Tian, Yanhua; Wang, Di; Zhao, Jun; An, Tongtong; Bai, Hua; Wu, Meina; Wang, Jie

    2018-02-06

    Chemo-resistance in small cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSCs). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. The current study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemo-resistant SCLC, and explored the potential mechanisms of α2δ1-mediated chemo-resistance and strategies of overcoming the resistance. α2δ1 positive cells were identified and isolated from SCLC cell lines and patient derived xenografts (PDXs) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western Blotting were carried out to identify pathways involved in α2δ1-mediated chemo-resistance in SCLC. Additionally, possible interventions to overcome ɑ2δ1 mediated chemo-resistance were examined. Different proportions of α2δ1+ cells were identified in SCLC cell lines and PDX models. ɑ2δ1 positive cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential and high-expression of genes related to CSCs and drug-resistance). Chemotherapy induced the enrichment of α2δ1+ cells instead of CD133+ cells in PDXs, and an increased proportion of α2δ1+ cells corresponded to increased chemo-resistance. Activation and over-expression of Erk in the ɑ2δ1 positive H1048 cell line was identified at the protein level. 1B50-1 mAb was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models. SCLC cells expressing α2δ1 demonstrated CSC-like properties, and may contribute to chemo-resistance. Erk may play a key role in α2δ1 mediated chemo-resistance. 1B50-1 inhibitors may serve as potential anti-SCLC drugs. Copyright ©2018, American Association for Cancer Research.

  16. CGGBP1 regulates cell cycle in cancer cells

    Directory of Open Access Journals (Sweden)

    Uhrbom Lene

    2011-07-01

    Full Text Available Abstract Background CGGBP1 is a CGG-triplet repeat binding protein, which affects transcription from CGG-triplet-rich promoters such as the FMR1 gene and the ribosomal RNA gene clusters. Earlier, we reported some previously unknown functions of CGGBP1 in gene expression during heat shock stress response. Recently we had found CGGBP1 to be a cell cycle regulatory midbody protein required for normal cytokinetic abscission in normal human fibroblasts, which have all the cell cycle regulatory mechanisms intact. Results In this study we explored the role of CGGBP1 in the cell cycle in various cancer cell lines. CGGBP1 depletion by RNA interference in tumor-derived cells caused an increase in the cell population at G0/G1 phase and reduced the number of cells in the S phase. CGGBP1 depletion also increased the expression of cell cycle regulatory genes CDKN1A and GAS1, associated with reductions in histone H3 lysine 9 trimethylation in their promoters. By combining RNA interference and genetic mutations, we found that the role of CGGBP1 in cell cycle involves multiple mechanisms, as single deficiencies of CDKN1A, GAS1 as well as TP53, INK4A or ARF failed to rescue the G0/G1 arrest caused by CGGBP1 depletion. Conclusions Our results show that CGGBP1 expression is important for cell cycle progression through multiple parallel mechanisms including the regulation of CDKN1A and GAS1 levels.

  17. Delayed effects of accelerated heavy ions on the induction of HPRT mutations in V79 hamster cells.

    Science.gov (United States)

    Bláha, Pavel; Koshlan, Nataliya A; Koshlan, Igor V; Petrova, Daria V; Bogdanova, Yulia V; Govorun, Raisa D; Múčka, Viliam; Krasavin, Evgeny A

    2017-10-01

    Fundamental research on the harmful effects of ionizing radiation on living cells continues to be of great interest. Recently, priority has been given to the study of high-charge and high-energy (HZE) ions that comprise a substantial part of the galactic cosmic ray (GCR) spectra that would be encountered during long-term space flights. Moreover, predictions of the delayed genetic effects of high linear energy transfer (LET) exposure is becoming more important as heavy ion therapy use is increasing. This work focuses mainly on the basic research on the delayed effects of HZE ions on V79 Chinese hamster cells, with emphasis on the induction of HPRT mutations after prolonged expression times (ET). The research was conducted under various irradiation conditions with accelerated ions 18 O (E=35.2MeV/n), 20 Ne (E=47.7MeV/n and 51.8MeV/n), and 11 B (E=32.4MeV/n), with LET in the range from 49 to 149 keV/μm and with 60 Co γ-rays. The HPRT mutant fractions (MF) were detected in irradiated cells in regular intervals during every cell culture recultivation (every 3days) up to approximately 40days (70-80 generations) after irradiation. The MF maximum was reached at different ET depending on ionizing radiation characteristics. The position of the maximum was shifting towards longer ET with increasing LET. We speculate that the delayed mutations are created de novo and that they are the manifestation of genomic instability. Although the exact mechanisms involved in genomic instability initiation are yet to be identified, we hypothesize that differences in induction of delayed mutations by radiations with various LET values are related to variations in energy deposition along the particle track. A dose dependence of mutation yield is discussed as well. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Breast cancer stem cells, cytokine networks, and the tumor microenvironment

    National Research Council Canada - National Science Library

    Korkaya, Hasan; Liu, Suling; Wicha, Max S

    2011-01-01

    .... These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment - including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune...

  19. Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment.

    Science.gov (United States)

    Aponte, Pedro M; Caicedo, Andrés

    2017-01-01

    Stemness combines the ability of a cell to perpetuate its lineage, to give rise to differentiated cells, and to interact with its environment to maintain a balance between quiescence, proliferation, and regeneration. While adult Stem Cells display these properties when participating in tissue homeostasis, Cancer Stem Cells (CSCs) behave as their malignant equivalents. CSCs display stemness in various circumstances, including the sustaining of cancer progression, and the interaction with their environment in search for key survival factors. As a result, CSCs can recurrently persist after therapy. In order to understand how the concept of stemness applies to cancer, this review will explore properties shared between normal and malignant Stem Cells. First, we provide an overview of properties of normal adult Stem Cells. We thereafter elaborate on how these features operate in CSCs. We then review the organization of microenvironment components, which enables CSCs hosting. We subsequently discuss Mesenchymal Stem/Stromal Cells (MSCs), which, although their stemness properties are limited, represent essential components of the Stem Cell niche and tumor microenvironment. We next provide insights of the therapeutic strategies targeting Stem Cell properties in tumors and the use of state-of-the-art techniques in future research. Increasing our knowledge of the CSCs microenvironment is key to identifying new therapeutic solutions.

  20. Colorectal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  1. Esophageal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  2. Stages of Gallbladder Cancer

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  3. NCI Designated Cancer Centers

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  4. Small Intestine Cancer Treatment

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  5. Esophageal Cancer Prevention

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  6. Stages of Vulvar Cancer

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  7. Effect of lycopene on cell viability and cell cycle progression in human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Teodoro Anderson

    2012-08-01

    Full Text Available Abstract Background Lycopene, a major carotenoid component of tomato, has a potential anticancer activity in many types of cancer. Epidemiological and clinical trials rarely provide evidence for mechanisms of the compound’s action, and studies on its effect on cancer of different cell origins are now being done. The aim of the present study was to determine the effect of lycopene on cell cycle and cell viability in eight human cancer cell lines. Methods Human cell lines were treated with lycopene (1–5 μM for 48 and 96 h. Cell viability was monitored using the method of MTT. The cell cycle was analyzed by flow cytometry, and apoptotic cells were identified by terminal deoxynucleotidyl transferase-mediated dUTP nick labeling (TUNEL and by DAPI. Results Our data showed a significant decrease in the number of viable cells in three cancer cells lines (HT-29, T84 and MCF-7 after 48 h treatment with lycopene, and changes in the fraction of cells retained in different cell cycle phases. Lycopene promoted also cell cycle arrest followed by decreased cell viability in majority of cell lines after 96 h, as compared to controls. Furthermore, an increase in apoptosis was observed in four cell lines (T-84, HT-29, MCF-7 and DU145 when cells were treated with lycopene. Conclusions Our findings show the capacity of lycopene to inhibit cell proliferation, arrest cell cycle in different phases and increase apoptosis, mainly in breast, colon and prostate lines after 96 h. These observations suggest that lycopene may alter cell cycle regulatory proteins depending on the type of cancer and the dose of lycopene administration. Taken together, these data indicated that the antiproliferative effect of lycopene was cellular type, time and dose-dependent.

  8. Reprogramming of human cancer cells to pluripotency for models of cancer progression

    Science.gov (United States)

    Kim, Jungsun; Zaret, Kenneth S

    2015-01-01

    The ability to study live cells as they progress through the stages of cancer provides the opportunity to discover dynamic networks underlying pathology, markers of early stages, and ways to assess therapeutics. Genetically engineered animal models of cancer, where it is possible to study the consequences of temporal-specific induction of oncogenes or deletion of tumor suppressors, have yielded major insights into cancer progression. Yet differences exist between animal and human cancers, such as in markers of progression and response to therapeutics. Thus, there is a need for human cell models of cancer progression. Most human cell models of cancer are based on tumor cell lines and xenografts of primary tumor cells that resemble the advanced tumor state, from which the cells were derived, and thus do not recapitulate disease progression. Yet a subset of cancer types have been reprogrammed to pluripotency or near-pluripotency by blastocyst injection, by somatic cell nuclear transfer and by induced pluripotent stem cell (iPS) technology. The reprogrammed cancer cells show that pluripotency can transiently dominate over the cancer phenotype. Diverse studies show that reprogrammed cancer cells can, in some cases, exhibit early-stage phenotypes reflective of only partial expression of the cancer genome. In one case, reprogrammed human pancreatic cancer cells have been shown to recapitulate stages of cancer progression, from early to late stages, thus providing a model for studying pancreatic cancer development in human cells where previously such could only be discerned from mouse models. We discuss these findings, the challenges in developing such models and their current limitations, and ways that iPS reprogramming may be enhanced to develop human cell models of cancer progression. PMID:25712212

  9. Spheroid body-forming cells in the human gastric cancer cell line MKN-45 possess cancer stem cell properties.

    Science.gov (United States)

    Liu, Jianming; Ma, Lilin; Xu, Junfei; Liu, Chun; Zhang, Jianguo; Liu, Jie; Chen, Ruixin; Zhou, Youlang

    2013-02-01

    The cancer stem cell theory hypothesizes that cancer stem cells (CSCs), which possess self-renewal and other stem cell properties, are regarded as the cause of tumor formation, recurrence and metastasis. The isolation and identification of CSCs could help to develop novel therapeutic strategies specifically targeting CSCs. In this study, we enriched gastric cancer stem cells through spheroid body formation by cultivating the human gastric cancer cell line MKN-45 in defined serum-free medium. The stemness characteristics of spheroid body-forming cells, including self-renewal, proliferation, chemoresistance, tumorigenicity of the MKN-45 spheroid body-forming cells were evaluated, and the expression levels of stemness genes and related proteins in the MKN-45 spheroid body-forming cells were assessed. Furthermore, immunofluorescence staining for the stem cell markers on spheroid body-forming cells was examined to evaluate the association between stemness factors (Oct4, Sox2, Nanog) and the proposed CSC marker CD44. Our data demonstrated that non-adherent spheroid body-forming cells from the gastric cancer cell line MKN-45 cultured in stem cell-conditioned medium possessed gastric CSC properties, such as persistent self-renewal, extensive proliferation, drug resistance, high tumorigenic capacity and overexpression of CSC-related genes and proteins (Oct4, Sox2, Nanog and CD44), compared with the parental cells. More importantly, CD44-positive cells co-expressing the pluripotency genes Oct4, Sox2 and Nanog may represent gastric CSCs. Further experiments using more refined selection criteria such as a combination of two or multiple markers would be useful to specifically identify and purify CSCs.

  10. Cancer stem cell-like side population cells in clear cell renal cell carcinoma cell line 769P.

    Science.gov (United States)

    Huang, Bin; Huang, Yi Jun; Yao, Zhi Jun; Chen, Xu; Guo, Sheng Jie; Mao, Xiao Peng; Wang, Dao Hu; Chen, Jun Xing; Qiu, Shao Peng

    2013-01-01

    Although cancers are widely considered to be maintained by stem cells, the existence of stem cells in renal cell carcinoma (RCC) has seldom been reported, in part due to the lack of unique surface markers. We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line, contained the largest amount of SP cells as compared with other four cell lines. These 769P SP cells possessed characteristics of proliferation, self-renewal, and differentiation, as well as strong resistance to chemotherapy and radiotherapy that were possibly related to the ABCB1 transporter. In vivo experiments with serial tumor transplantation in mice also showed that 769P SP cells formed tumors in NOD/SCID mice. Taken together, these results indicate that 769P SP cells have the properties of cancer stem cells, which may play important roles in tumorigenesis and therapy-resistance of RCC.

  11. Nonequilibrium population dynamics of phenotype conversion of cancer cells.

    Directory of Open Access Journals (Sweden)

    Joseph Xu Zhou

    Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.

  12. Omega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells.

    Science.gov (United States)

    Pizato, Nathalia; Luzete, Beatriz Christina; Kiffer, Larissa Fernanda Melo Vasconcelos; Corrêa, Luís Henrique; de Oliveira Santos, Igor; Assumpção, José Antônio Fagundes; Ito, Marina Kiyomi; Magalhães, Kelly Grace

    2018-01-31

    The implication of inflammation in pathophysiology of several type of cancers has been under intense investigation. Omega-3 fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. Pyroptosis is an inflammation related cell death and so far, the function of docosahexaenoic acid (DHA) in pyroptosis cell death has not been described. This study investigated the role of DHA in triggering pyroptosis activation in breast cancer cells. MDA-MB-231 breast cancer cells were supplemented with DHA and inflammation cell death was analyzed. DHA-treated breast cancer cells triggered increased caspase-1and gasdermin D activation, enhanced IL-1β secretion, translocated HMGB1 towards the cytoplasm, and membrane pore formation when compared to untreated cells, suggesting DHA induces pyroptosis programmed cell death in breast cancer cells. Moreover, caspase-1 inhibitor (YVAD) could protect breast cancer cells from DHA-induced pyroptotic cell death. In addition, membrane pore formation showed to be a lysosomal damage and ROS formation-depended event in breast cancer cells. DHA triggered pyroptosis cell death in MDA-MB-231by activating several pyroptosis markers in these cells. This is the first study that shows the effect of DHA triggering pyroptosis programmed cell death in breast cancer cells and it could improve the understanding of the omega-3 supplementation during breast cancer treatment.

  13. Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Tae Hun Kim

    2014-01-01

    Full Text Available Ovarian cancer is the most lethal gynecologic malignancy among women worldwide and is presumed to result from the presence of ovarian cancer stem cells. To overcome the limitation of current anticancer agents, another anticancer strategy is necessary to effectively target cancer stem cells in ovarian cancer. In many types of malignancies, including ovarian cancer, metformin, one of the most popular antidiabetic drugs, has been demonstrated to exhibit chemopreventive and anticancer efficacy with respect to incidence and overall survival rates. Thus, the metabolic reprogramming of cancer and cancer stem cells driven by genetic alterations during carcinogenesis and cancer progression could be therapeutically targeted. In this review, the potential efficacy and anticancer mechanisms of metformin against ovarian cancer stem cells will be discussed.

  14. Renal cell cancer among African Americans: an epidemiologic review

    National Research Council Canada - National Science Library

    Lipworth, Loren; Tarone, Robert E; McLaughlin, Joseph K

    2011-01-01

    Incidence rates for renal cell cancer, which accounts for 85% of kidney cancers, have been rising more rapidly among blacks than whites, almost entirely accounted for by an excess of localized disease...

  15. Integrins in mammary-stem-cell biology and breast-cancer progression – a role in cancer stem cells?

    Science.gov (United States)

    Pontier, Stephanie M.; Muller, William J.

    2009-01-01

    Summary Cancer cells with stem cell-like properties (cancer stem cells) are believed to drive cancer and are associated with poor prognosis. Data from mouse models have demonstrated that integrins, the major cellular receptors for extracellular-matrix components, have essential roles both during cancer initiation and progression, and during cell differentiation in normal development. By presenting an overview of the role of integrins in stem-cell biology and in cancer progression, this Commentary aims to present evidence for a role of integrins in the biology of cancer stem cells. Given the recent interest in the role of integrins in breast-cancer initiation and progression, we focus on the role of the members of the integrin family and their coupled signaling pathways in mammary-gland development and tumorigenesis. PMID:19118213

  16. Integrins in mammary-stem-cell biology and breast-cancer progression--a role in cancer stem cells?

    Science.gov (United States)

    Pontier, Stephanie M; Muller, William J

    2009-01-15

    Cancer cells with stem cell-like properties (cancer stem cells) are believed to drive cancer and are associated with poor prognosis. Data from mouse models have demonstrated that integrins, the major cellular receptors for extracellular-matrix components, have essential roles both during cancer initiation and progression, and during cell differentiation in normal development. By presenting an overview of the role of integrins in stem-cell biology and in cancer progression, this Commentary aims to present evidence for a role of integrins in the biology of cancer stem cells. Given the recent interest in the role of integrins in breast-cancer initiation and progression, we focus on the role of the members of the integrin family and their coupled signaling pathways in mammary-gland development and tumorigenesis.

  17. Immuno Nanoparticles Integrated Electrical Control of Targeted Cancer Cell Development Using Whole Cell Bioelectronic Device

    Science.gov (United States)

    Hondroulis, Evangelia; Zhang, Rui; Zhang, Chengxiao; Chen, Chunying; Ino, Kosuke; Matsue, Tomokazu; Li, Chen-Zhong

    2014-01-01

    Electrical properties of cells determine most of the cellular functions, particularly ones which occur in the cell's membrane. Manipulation of these electrical properties may provide a powerful electrotherapy option for the treatment of cancer as cancerous cells have been shown to be more electronegative than normal proliferating cells. Previously, we used an electrical impedance sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal HUVEC cells to low intensity (electrotherapy for clinical and drug delivery applications. PMID:25057316

  18. Association of Knowledge and Cultural Perceptions of Malaysian Women with Delay in Diagnosis and Treatment of Breast Cancer: a Systematic Review.

    Science.gov (United States)

    Khan, Tahir Mehmood; Leong, Jamie Pik Yan; Ming, Long Chiau; Khan, Amer Hayat

    2015-01-01

    Breast cancer is the most common cancer and the leading cause of cancer mortality among women of all ethnic and age groups in Malaysia. Delay in seeking help for breast cancer symptoms is preventable and by identifying possible factors for delayed diagnosis, patient prognosis and survival rates could be improved. This narrative review aimed to understand and evaluate the level of in-depth breast cancer knowledge in terms of clinical breast examination and breast self-examination, and other important aspects such as side-effects and risk factors in Malaysian females. Since Malaysia is multicultural, this review assessed social perceptions, cultural beliefs and help-seeking behaviour in respect to breast cancer among different ethnic groups, since these may impinge on efforts to 'avoid' the disease. A comprehensive literature search of seven databases was performed from December 2015 to January 2015. Screening of relevant published journals was also undertaken to identify available information related to the knowledge, perception and help-seeking behaviour of Malaysian women in relation to breast cancer. A total of 42 articles were appraised and included in this review. Generally, women in Malaysia had good awareness of breast cancer and its screening tools, particularly breast self-examination, but only superficial in-depth knowledge about the disease. Women in rural areas had lower levels of knowledge than those in urban areas. It was also shown that books, magazines, brochures and television were among the most common sources of breast cancer information. Delay in presentation was attributed mainly to a negative social perception of the disease, poverty, cultural and religion practices, and a strong influence of complementary and alternative medicine, rather than a lack of knowledge. This review highlighted the need for an intensive and in-depth breast cancer education campaigns using media and community health programmes, even with the existing good awareness of

  19. Multiple Time-Point 68Ga-PSMA I&T PET/CT for Characterization of Primary Prostate Cancer: Value of Early Dynamic and Delayed Imaging.

    Science.gov (United States)

    Schmuck, Sebastian; Mamach, Martin; Wilke, Florian; von Klot, Christoph A; Henkenberens, Christoph; Thackeray, James T; Sohns, Jan M; Geworski, Lilli; Ross, Tobias L; Wester, Hans-Juergen; Christiansen, Hans; Bengel, Frank M; Derlin, Thorsten

    2017-06-01

    The aims of this study were to gain mechanistic insights into prostate cancer biology using dynamic imaging and to evaluate the usefulness of multiple time-point Ga-prostate-specific membrane antigen (PSMA) I&T PET/CT for the assessment of primary prostate cancer before prostatectomy. Twenty patients with prostate cancer underwent Ga-PSMA I&T PET/CT before prostatectomy. The PET protocol consisted of early dynamic pelvic imaging, followed by static scans at 60 and 180 minutes postinjection (p.i.). SUVs, time-activity curves, quantitative analysis based on a 2-tissue compartment model, Patlak analysis, histopathology, and Gleason grading were compared between prostate cancer and benign prostate gland. Primary tumors were identified on both early dynamic and delayed imaging in 95% of patients. Tracer uptake was significantly higher in prostate cancer compared with benign prostate tissue at any time point (P ≤ 0.0003) and increased over time. Consequently, the tumor-to-nontumor ratio within the prostate gland improved over time (2.8 at 10 minutes vs 17.1 at 180 minutes p.i.). Tracer uptake at both 60 and 180 minutes p.i. was significantly higher in patients with higher Gleason scores (P < 0.01). The influx rate (Ki) was higher in prostate cancer than in reference prostate gland (0.055 [r = 0.998] vs 0.017 [r = 0.996]). Primary prostate cancer is readily identified on early dynamic and static delayed Ga-PSMA ligand PET images. The tumor-to-nontumor ratio in the prostate gland improves over time, supporting a role of delayed imaging for optimal visualization of prostate cancer.

  20. [Mechanisms of delay endothelial cell replicative senescence by extracts from Panax ginseng, Panax notoginseng and Ligusticum chuanxiong].

    Science.gov (United States)

    Yang, Jing; Lei, Yan; Cui, Wei; Fang, Suping; Chen, Keji

    2009-06-01

    To explore effect of extracts from Panax ginseng, P. notoginseng and Ligusticum chuanxiong on human umbilical endothelial cells (HUVECs) replicative senescence. HUVECs were induced to aging by generation cultivating to the eighth cells in order to establish a model of endothelial cells replicative senescence. The cultured HUVECs in vitro were divided into 4 groups, the eighth generation cell-senescence untreated group, Vitamin E group, herbal treated high dose and low dose groups. Changes of HUVECs aging were observed by method of SA-beta-gal stained HUVECs and cells cycle were analyzed. Contents of ROS in cells, the levels of anti-superoxide (O2-) and nitric oxide (NO) in cell mediums were examined. Western blot were used to analyse protein expression of NADPH oxidase p47phox, angiotensin type 1 and 2 receptor (AT1R, AT2R). Compared with Vitamin E group, the positive cell numbers of beta-gal stained HUVECs were enhanced, cell proliferation was depressed, and the fluorescence intensity of ROS was increased, at the same time, less NO and more O2- in cells were produced in the eighth generation cell-senescence untreated group. Protein expression of p47phox, AT1R and AT2R in cells increased compared with Vit E group. Chinese herbs of high dose and low dose could improve condutions of HUVECs aging. Chinese herbs of high dose and low dose could reduce the positive cell numbers of beta-gal stained HUVEC, increase cell proliferation and decrease fluorescence intensity of ROS in cells, at the same time, cells secreting more NO and less O2-. Protein expression of p47phox, AT1R and AT2R in cells treated with Chinese herbs of high dose and low dose were decreased compared with Vit E group. The study indicated that extracts from P. ginseng, P. notoginseng and L. chuanxiong could delay endothelial cell replicative senescence. Herbal extracts downregulate the expression of NAD (P) H oxidase subunit-p47phox by means of ROS, hence decrease O2- production and ultimately delay

  1. Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Alvero, Ayesha B; Yang, Yingkui

    2011-01-01

    Epithelial ovarian cancer stem cells (EOC stem cells) have been associated with recurrence and chemoresistance. CD44 and CK18 are highly expressed in cancer stem cells and function as tools for their identification and characterization. We investigated the association between the number of CD44......+ EOC stem cells in ovarian cancer tumors and progression-free survival. EOC stem cells exist as clusters located close to the stroma forming the cancer stem cell "niche". 17.1% of the samples reveled high number of CD44+ EOC stem cells (>20% positive cells). In addition, the number of CD44+ EOC stem...... cells was significantly higher in patients with early-stage ovarian cancer (FIGO I/II), and it was associated with shorter progression-free survival (P = 0.026). This study suggests that quantification of the number of EOC stem cells in the tumor can be used as a predictor of disease and could...

  2. Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E

    2007-01-01

    with parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment....... for future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells...

  3. Breast cancer stem cell-like cells are more sensitive to ionizing radiation than non-stem cells: role of ATM.

    Directory of Open Access Journals (Sweden)

    Seog-Young Kim

    Full Text Available There are contradictory observations about the different radiosensitivities of cancer stem cells and cancer non-stem cells. To resolve these contradictory observations, we studied radiosensitivities by employing breast cancer stem cell (CSC-like MDA-MB231 and MDA-MB453 cells as well as their corresponding non-stem cells. CSC-like cells proliferate without differentiating and have characteristics of tumor-initiating cells [1]. These cells were exposed to γ-rays (1.25-8.75 Gy and survival curves were determined by colony formation. A final slope, D(0, of the survival curve for each cell line was determined to measure radiosensitivity. The D(0 of CSC-like and non-stem MDA-MB-453 cells were 1.16 Gy and 1.55 Gy, respectively. Similar results were observed in MDA-MB-231 cells (0.94 Gy vs. 1.56 Gy. After determination of radiosensitivity, we investigated intrinsic cellular determinants which influence radiosensitivity including cell cycle distribution, free-radical scavengers and DNA repair. We observed that even though cell cycle status and antioxidant content may contribute to differential radiosensitivity, differential DNA repair capacity may be a greater determinant of radiosensitivity. Unlike non-stem cells, CSC-like cells have little/no sublethal damage repair, a low intracellular level of ataxia telangiectasia mutated (ATM and delay of γ-H2AX foci removal (DNA strand break repair. These results suggest that low DNA repair capacity is responsible for the high radiosensitivity of these CSC-like cells.

  4. Translational potential of cancer stem cells: A review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment.

    Science.gov (United States)

    Islam, Farhadul; Gopalan, Vinod; Smith, Robert A; Lam, Alfred K-Y

    2015-07-01

    Cancer stem cells (CSCs) are a subpopulation of cancer cells with many clinical implications in most cancer types. One important clinical implication of CSCs is their role in cancer metastases, as reflected by their ability to initiate and drive micro and macro-metastases. The other important contributing factor for CSCs in cancer management is their function in causing treatment resistance and recurrence in cancer via their activation of different signalling pathways such as Notch, Wnt/β-catenin, TGF-β, Hedgehog, PI3K/Akt/mTOR and JAK/STAT pathways. Thus, many different therapeutic approaches are being tested for prevention and treatment of cancer recurrence. These may include treatment strategies targeting altered genetic signalling pathways by blocking specific cell surface molecules, altering the cancer microenvironments that nurture cancer stem cells, inducing differentiation of CSCs, immunotherapy based on CSCs associated antigens, exploiting metabolites to kill CSCs, and designing small interfering RNA/DNA molecules that especially target CSCs. Because of the huge potential of these approaches to improve cancer management, it is important to identify and isolate cancer stem cells for precise study and application of prior the research on their role in cancer. Commonly used methodologies for detection and isolation of CSCs include functional, image-based, molecular, cytological sorting and filtration approaches, the use of different surface markers and xenotransplantation. Overall, given their significance in cancer biology, refining the isolation and targeting of CSCs will play an important role in future management of cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Reasons for diagnostic delay in gynecological malignancies

    DEFF Research Database (Denmark)

    Vandborg, Mai Partridge; Christensen, René dePont Christensen; Kragstrup, Jakob

    2011-01-01

    Aim The primary aim of this study was to identify and describe different delay types in women with gynecologic cancer, and to analyze the relationship between diagnostic delay and a number of characteristics for patients, cancers and the health care system. Setting A cohort study of women newly......) and The Danish Gynecological Cancer Database (DGCD). 161 women were included; ovarian cancer: 63, endometrial cancer: 50, cervical cancer: 34 and vulvar cancer: 14. Outcome measures were different delay types counted in days and the influence of four clinical important variables: Presence of alarm symptoms, age...... (≤ or > 60 years), performance of gynecological examination by the GP and notification of cancer suspicion on first referral from GP’s on the diagnostic delay (short delay ≤90 days and long delay >90 days). Results Across cancer type a median total delay of 101 days was observed. The 10% of women...

  6. [Case of heterochronous triple urogenital cancer (renal cell carcinoma, bladder cancer, prostatic cancer)].

    Science.gov (United States)

    Okumura, Akiou; Tsuritani, Shinji; Takagawa, Kiyoshi; Fuse, Hideki

    2013-11-01

    We report a case of a 73-year-old male with heterochronous triple urogenital cancer. The patient was referred to our hospital because serum PSA was elevated (7.0 ng/ml) in 1998. Prostatic needle biopsy revealed prostatic cancer in the right lobe, and total prostatectomy was performed. The histopathological diagnosis was moderately differentiated adenocarcinoma (TlcNOMO). Non-muscle invasive bladder cancer (NMIBC) was detected during an examination for microhematuria in 2002. Transurethral resection of the bladder tumor (TURBT) procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). A right renal mass was detected incidentally on follow-up CT for bladder cancer in 2008. Renal enucleation was performed in 2009. The histopathological diagnosis was grade 2 clear cell renal cell carcinoma (pTlaNXMO). NMIBC was detected on follow-up urethrocystoscopy in 2011. The TURBT procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). On follow-up for urogenital cancer patients, it is important to investigate recurrence of the primary cancer and also heterochronous canceration of other urogenital organs.

  7. EAMJ Delayed April 10.indd

    African Journals Online (AJOL)

    2010-04-04

    Apr 4, 2010 ... INTRODUCTION. Breast cancer remains a leading cause of death of ... ABSTRACT. Objective: To determine the extent and nature of delayed presentation of patients .... symptomatic breast cancer: a systematic review. Lancet.

  8. From gametogenesis and stem cells to cancer: common metabolic themes.

    Science.gov (United States)

    Pereira, Sandro L; Rodrigues, Ana Sofia; Sousa, Maria Inês; Correia, Marcelo; Perestrelo, Tânia; Ramalho-Santos, João

    2014-01-01

    Both pluripotent stem cells (PSCs) and cancer cells have been described as having similar metabolic pathways, most notably a penchant for favoring glycolysis even under aerobiosis, suggesting common themes that might be explored for both stem cell differentiation and anti-oncogenic purposes. A search of the scientific literature available in the PubMed/Medline was conducted for studies on metabolism and mitochondrial function related to gametogenesis, early development, stem cells and cancers in the reproductive system, notably breast, prostate, ovarian and testicular cancers. Both PSCs and some types of cancer cells, particularly reproductive cancers, were found to obtain energy mostly by glycolysis, often reducing mitochondrial activity and oxidative phosphorylation. This strategy links proliferating cells, allowing for the biosynthesis reactions necessary for cell division. Interventions that affect metabolic pathways, and force cells to change their preferences, can lead to shifts in cell status, increasing either pluripotency or differentiation of stem cells, and causing cancer cells to become more or less aggressive. Interestingly metabolic changes in many cases seemed to lead to cell transformation, not necessarily follow it, suggesting a direct role of metabolic choices in influencing the (epi)genetic program of different cell types. There are uncanny similarities between PSCs and cancer cells at the metabolic level. Furthermore, metabolism may also play a direct role in cell status and targeting metabolic pathways could therefore be a promising strategy for both the control of cancer cell proliferation and the regulation of stem cell physiology, in terms of manipulating stem cells toward relevant phenotypes that may be important for tissue engineering, or making cancer cells become less tumorigenic. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For

  9. Measuring density and compressibility of white blood cells and prostate cancer cells by microchannel acoustophoresis

    DEFF Research Database (Denmark)

    Barnkob, Rune; Augustsson, Per; Magnusson, Cecilia

    2011-01-01

    to determine the density and compressibility of individual cells enables the prediction and alteration of the separation outcome for a given cell mixture. We apply the method on white blood cells (WBCs) and DU145 prostate cancer cells (DUCs) aiming to improve isolation of circulating tumor cells from blood......, an emerging tool in the monitoring and characterizing of metastatic cancer....

  10. Oct-4 expression maintained stem cell properties in prostate cancer ...

    African Journals Online (AJOL)

    The purpose of the present study is to isolate cancerous stem-like cells from normal healthy volunteers and prostate cancer patients (CD133+) which also express MDR1 and to ascertain the influence of Oct-4 on 'stem-ness' and differentiation of these CD133+ cells towards epithelium. Methods: CD133+ cells were isolated ...

  11. Cytotoxicity of Sambucus ebulus on cancer cell lines and protective ...

    African Journals Online (AJOL)

    Cytotoxicity of Sambucus ebulus on cancer cell lines and protective effects of vitamins C and E against its cytotoxicity on normal cell lines. ... Cytotoxicity of SEE on cancer (HepG2 and CT26) and normal (CHO and rat fibroblast) cell lines was evaluated by MTT assay. IC50 of SEE on ... African Journal of Biotechnology Vol.

  12. Targeting Apoptotic Activity Against Prostate Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska

    2017-07-01

    Full Text Available Numerous data suggest that an increase of cancer stem cells (CSCs in tumor mass can be the reason for failure of conventional therapies because of their resistance. CD44+/CD24− cells are a putative cancer stem cells subpopulation in prostate cancer. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand is an activator of apoptosis in tumor cells. However, some tumors are TRAIL-resistant. Cancer cells can be re-sensitized to TRAIL induced apoptosis by a combination of TRAIL and taxanes. The aim of this work was to analyze the enhancement of the anticancer effect of TRAIL by paclitaxel, cabazitaxel and docetaxel in the whole population of PC3 and DU145 prostate cancer cells, but also in CD44+/CD24− prostate cancer stem cells. We examined the apoptotic effect of TRAIL and taxanes using flow cytometry and Annexin-V-PE staining. The co-treatment with taxanes and TRAIL enhanced significantly the apoptosis in CD44+/CD24− cells only in PC3 cell line but not in DU145 cells. We discovered also that taxanes can increase the expression of death receptor TRAIL-R2 in PC3 prostate cancer cells. The results of our study show that treatment with paclitaxel, cabazitaxel and docetaxel is able to enhance the apoptosis induced by TRAIL even in prostate cancer stem cells.

  13. Milk stimulates growth of prostate cancer cells in culture.

    Science.gov (United States)

    Tate, Patricia L; Bibb, Robert; Larcom, Lyndon L

    2011-11-01

    Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes.

  14. Therapeutic Approaches to Target Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Arlhee, E-mail: arlhee@cim.sld.cu; Leon, Kalet [Department of Systems Biology, Center of Molecular Immunology, 216 Street, PO Box 16040, Atabey, Havana 11600 (Cuba)

    2011-08-15

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC.

  15. Advanced Merkel cell cancer and the elderly.

    LENUS (Irish Health Repository)

    Bird, B R

    2012-02-03

    BACKGROUND: Merkel cell cancer (MCC) is an uncommon neuroendocrine skin cancer occurring predominantly in elderly Caucasians. It tends to metastasize to regional lymph nodes and viscera and is sensitive to chemotherapy but recurs rapidly. AIM: To report one such case, its response to chemotherapy and briefly review the literature. METHODS: A 73-year-old male with a fungating primary lesion on his left knee and ulcerated inguinal lymph nodes was diagnosed with MCC and treated with chemotherapy. The two largest case series and reviews of case reports were summarised. RESULTS: His ulcer healed after two cycles of carboplatin and etoposide with improvement in quality of life. Overall response rates of nearly 60% to chemotherapy are reported but median survival is only nine months with metastatic disease. CONCLUSIONS: Chemotherapy should be considered for fit elderly patients with MCC who have recurrent or advanced disease.

  16. Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.

    Science.gov (United States)

    Chen, Li-Shiun; Baker, Timothy; Hung, Rayjean J; Horton, Amy; Culverhouse, Robert; Hartz, Sarah; Saccone, Nancy; Cheng, Iona; Deng, Bo; Han, Younghun; Hansen, Helen M; Horsman, Janet; Kim, Claire; Rosenberger, Albert; Aben, Katja K; Andrew, Angeline S; Chang, Shen-Chih; Saum, Kai-Uwe; Dienemann, Hendrik; Hatsukami, Dorothy K; Johnson, Eric O; Pande, Mala; Wrensch, Margaret R; McLaughlin, John; Skaug, Vidar; van der Heijden, Erik H; Wampfler, Jason; Wenzlaff, Angela; Woll, Penella; Zienolddiny, Shanbeh; Bickeböller, Heike; Brenner, Hermann; Duell, Eric J; Haugen, Aage; Brüske, Irene; Kiemeney, Lambertus A; Lazarus, Philip; Le Marchand, Loic; Liu, Geoffrey; Mayordomo, Jose; Risch, Angela; Schwartz, Ann G; Teare, M Dawn; Wu, Xifeng; Wiencke, John K; Yang, Ping; Zhang, Zuo-Feng; Spitz, Margaret R; Amos, Christopher I; Bierut, Laura J

    2016-09-01

    Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not. Meta-analyses examined the association between smoking cessation and lung cancer risk in 15 studies of individuals with European ancestry who possessed varying rs16969968 genotypes (N=12,690 ever smokers, including 6988 cases of lung cancer and 5702 controls) in the International Lung Cancer Consortium. Smoking cessation (former vs. current smokers) was associated with a lower likelihood of lung cancer (OR=0.48, 95%CI=0.30-0.75, p=0.0015). Among lung cancer patients, smoking cessation was associated with a 7-year delay in median age of lung cancer diagnosis (HR=0.68, 95%CI=0.61-0.77, p=4.9∗10 -10 ). The CHRNA5 rs16969968 risk genotype (AA) was associated with increased risk and earlier diagnosis for lung cancer, but the beneficial effects of smoking cessation were very similar in those with and without the risk genotype. We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7years for those who develop it. These results: 1) underscore the potential value of smoking cessation for all smokers, 2) suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3) have potential value for framing preventive interventions for those who smoke. Copyright © 2016

  17. Increased susceptibility to delayed genetic effects of low dose X-irradiation in DNA repair deficient cells.

    Science.gov (United States)

    Kashino, Genro; Suzuki, Keiji; Kodama, Seiji; Watanabe, Masami; Prise, Kevin M

    2013-04-01

    To examine whether the levels of micronuclei induction, as a marker for genomic instability in the progeny of X-irradiated cells, correlates with DNA repair function. Two repair deficient cell lines (X-ray repair cross-complementing 1 [XRCC1] deficient cell line [EM9] and X-ray repair cross complementing 5 [XRCC5; Ku80] deficient X-ray sensitive Chinese hamster ovary [CHO] cell line [xrs5]) were used in addition to wild-type CHO cells. These cells were irradiated with low doses of X-rays (up to 1 Gy). Seven days after irradiation, micronuclei formed in binucleated cells were counted. To assess the contribution of the bystander effect micronuclei induction was measured in progeny of non-irradiated cells co-cultured with cells that had been irradiated with 1Gy. The delayed induction of micronuclei in 1 Gy-irradiated cells was observed in normal CHO and EM9 but not in xrs5. In the clone analysis, progenies of xrs5 under bystander conditions showed significantly higher levels of micronuclei, while CHO and EM9 did not. Genomic instability induced by X-irradiation is associated with DSB (double-strand break) repair, even at low doses. It is also suggested that bystander signals, which lead to genomic instability, may be enhanced when DSB repair is compromised.

  18. Complete androgen blockade safely allows for delay of cytotoxic chemotherapy in castration refractory prostate cancer

    Directory of Open Access Journals (Sweden)

    Rafael A. Kaliks

    2010-06-01

    Full Text Available PURPOSE: Complete androgen blockade (CAB does not prolong overall survival (OS in patients with castration refractory prostate cancer (CRPC. Although there is variable clinical benefit with second-line hormone manipulation, we do not know which patients might benefit the most. OBJECTIVES: To identify clinical predictors of benefit of complete androgen blockade. MATERIALS AND METHODS: We reviewed the records for 54 patients who received treatment with CAB in the setting of disease progression despite castration. We evaluated progression-free survival (PFS and OS according to PSA at diagnosis, Gleason scores, age, testosterone level, and duration of prior disease control during castration in first line treatment. RESULTS: Among 54 patients who received CAB, the median PFS was 9 months (CI 4.3-13.7 and OS was 36 months (CI 24-48. We did not find an effect of PSA at diagnosis (p = 0.32, Gleason score (p = 0.91, age (p = 0.69 or disease control during castration (p = 0.87 on PFS or OS. Thirty-four patients subsequently received chemotherapy, with a mean OS of 21 months (CI 16.4-25.5, median not reached. CONCLUSION: Age, Gleason score, PSA at diagnosis and length of disease control with castration did not affect PFS or OS. In the absence of predictors of benefit, CAB should still be considered in CRPC.

  19. Amygdalin Influences Bladder Cancer Cell Adhesion and Invasion In Vitro

    OpenAIRE

    Jasmina Makarević; Jochen Rutz; Eva Juengel; Silke Kaulfuss; Igor Tsaur; Karen Nelson; Jesco Pfitzenmaier; Axel Haferkamp; Blaheta, Roman A

    2014-01-01

    The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as...

  20. Spheroid Cultures of Primary Urothelial Cancer Cells: Cancer Tissue-Originated Spheroid (CTOS) Method.

    Science.gov (United States)

    Yoshida, Takahiro; Okuyama, Hiroaki; Endo, Hiroko; Inoue, Masahiro

    2018-01-01

    Increasingly, it has been recognized that studying cancer samples from individual patients is important for the development of effective therapeutic strategies and in endeavors to overcome therapy resistance. Primary cultures of cancer cells acutely dissected from individual patients can provide a platform that enables the study and characterization of individual tumors. To that end, we have developed a method for preparing cancer cells in the form of multi-cellular spheroids. The cells can be derived from patient tumors (primary cells), from patient-derived xenografts, or from genetically- or chemically induced animal tumors. This method of culturing spheroids composed of cells derived from cancer tissues can be applied to various types of cancer, including urothelial cancer. The method is based on the principle of retaining cell-cell contact throughout cancer cell preparation and culturing. The first step is a partial digestion of the tumor specimen into small fragments; these fragments spontaneously form spheroidal shapes within several hours. The spheroid is referred to as a cancer tissue-originated spheroid (CTOS). The advantage of the CTOS method is that it allows one to prepare pure cancer cells at high yield. CTOSs can be stably cultured in serum-free conditions. The CTOS method can be applied to drug sensitivity assays, drug screening, and analyses of intracellular signaling. Moreover, the CTOS method provides a platform for studying the nature of cancer cell clusters.

  1. Doxycycline inhibits the cancer stem cell phenotype and epithelial-to-mesenchymal transition in breast cancer.

    Science.gov (United States)

    Zhang, Le; Xu, Liang; Zhang, Fengchun; Vlashi, Erina

    2017-04-18

    Experimental evidence suggest that breast tumors originate from breast cancer stem cells (BCSCs), and that mitochondrial biogenesis is essential for the anchorage-independent clonal expansion and survival of CSCs, thus rendering mitochondria a significant target for novel treatment approaches. One of the recognized side effects of the FDA-approved drug, doxycycline is the inhibition of mitochondrial biogenesis. Here we investigate the mechanism by which doxycycline exerts its inhibitory effects on the properties of breast cancer cells and BCSCs, such as mammosphere forming efficiency, invasion, migration, apoptosis, the expression of stem cell markers and epithelial-to-mesenchymal transition (EMT) related markers of breast cancer cells. In addition, we explored whether autophagy plays a role in the inhibitory effect of doxycycline on breast cancer cells. We find that doxycyline can inhibit the viability and proliferation of breast cancer cells and BCSCs, decrease mammosphere forming efficiency, migration and invasion, and EMT of breast cancer cells. Expression of stem cell factors Oct4, Sox2, Nanog and CD44 were also significantly downregulated after doxycycline treatment. Moreover, doxycycline could down-regulate the expression of the autophagy marker LC-3BI and LC-3BII, suggesting that inhibiting autophagy may be responsible in part for the observed effects on proliferation, EMT and stem cell markers. The potent inhibition of EMT and cancer stem-like characteristics in breast cancer cells by doxycycline treatment suggests that this drug can be repurposed as an anti-cancer drug in the treatment of breast cancer patients in the clinic.

  2. Implications of Cancer Stem Cell Theory for Cancer Chemoprevention by Natural Dietary Compounds

    Science.gov (United States)

    Li, Yanyan; Wicha, Max S.; Schwartz, Steven J.; Sun, Duxin

    2011-01-01

    The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anti-cancer drugs targeting cancer stem cells. Naturally-occurring dietary compounds have received increasing attention in cancer chemoprevention. The anti-cancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog, and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine, and vitamin D3, are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival. PMID:21295962

  3. Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells.

    Science.gov (United States)

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Siddiqui, Imtiaz Ahmad; Verma, Ajit Kumar; Mukhtar, Hasan

    2016-12-01

    Although treatment of prostate cancer has improved over the past several years, taxanes, such as cabazitaxel, remain the only form of effective chemotherapy that improves survival in patients with metastatic castration-resistant prostate cancer. However, the effectiveness of this class of drugs has been associated with various side effects and drug resistance. We previously reported that fisetin, a hydroxyflavone, is a microtubule-stabilizing agent and inhibits prostate cancer cell proliferation, migration, and invasion and suggested its use as an adjuvant for treatment of prostate and other cancer types. In this study, we investigated the effect of fisetin in combination with cabazitaxel with the objective to achieve maximum therapeutic benefit, reduce dose and toxicity, and minimize or delay the induction of drug resistance and metastasis. Our data show for the first time that a combination of fisetin (20 μmol/L) enhances cabazitaxel (5 nmol/L) and synergistically reduces 22Rν1, PC-3M-luc-6, and C4-2 cell viability and metastatic properties with minimal adverse effects on normal prostate epithelial cells. In addition, the combination of fisetin with cabazitaxel was associated with inhibition of proliferation and enhancement of apoptosis. Furthermore, combination treatment resulted in the inhibition of tumor growth, invasion, and metastasis when assessed in two in vivo xenograft mouse models. These results provide evidence that fisetin may have therapeutic benefit for patients with advanced prostate cancer through enhancing the efficacy of cabazitaxel under both androgen-dependent and androgen-independent conditions. This study underscores the benefit of the combination of fisetin with cabazitaxel fo