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  1. Columnar cell lesions and subsequent breast cancer risk: a nested case-control study

    OpenAIRE

    Aroner, Sarah A.; Collins, Laura Christine; Schnitt, Stuart Jay; Connolly, James Leo; Colditz, Graham A; Tamimi, Rulla May

    2010-01-01

    Introduction: Histologic and genetic evidence suggests that at least some columnar cell lesions (CCL) of the breast represent precursor lesions in the low-grade breast neoplasia pathway. However, the risk of subsequent breast cancer associated with the presence of CCL in a benign breast biopsy is poorly understood.Methods The authors examined the association between the presence of CCL and subsequent breast cancer risk in a nested case-control study of benign breast disease (BBD) and breast c...

  2. Epithelial cells in nipple aspirate fluid and subsequent breast cancer risk: A historic prospective study

    International Nuclear Information System (INIS)

    Past studies have shown that women with abnormal cytology or epithelial cells in nipple aspirate fluid (NAF) have an increased relative risk (RR) of breast cancer when compared to women from whom NAF was attempted but not obtained (non-yielders). This study analyzed NAF results from a group of women seen in a breast clinic between 1970–1991 (N = 2480). Our analysis presented here is an aggregate of two sub-groups: women with questionnaire data (n = 712) and those with NAF visits beginning in 1988 (n = 238), the year in which cancer case information was uniformly collected in California. Cytological classification was determined for a group of 946 women using the most abnormal epithelial cytology observed in fluid specimens. Breast cancer incidence and mortality status was determined through June 2006 using data from the California Cancer Registry, California Vital Statistics and self-report. We estimated odd ratios (ORs) for breast cancer using logistic regression analysis, adjusting for age. We analyzed breast cancer risk related to abnormality of NAF cytology using non-yielders as the referent group and breast cancer risk related to the presence or absence of epithelial cells in NAF, using non-yielders/fluid without epithelial cells as the referent group. Overall, 10% (93) of the 946 women developed breast cancer during the follow-up period. Age-adjusted ORs and 95% confidence intervals (C.I.) compared to non-yielders were 1.4 (0.3 to 6.4), 1.7 (0.9 to 3.5), and 2.0 (1.1 to 3.6) for women with fluid without epithelial cells, normal epithelial cells and hyperplasia/atypia, respectively. Comparing the presence or absence of epithelial cells in NAF, women with epithelial cells present in NAF were more likely to develop breast cancer than non-yielders or women with fluid without epithelial cells (RR = 1.9, 1.2 to 3.1). These results support previous findings that 1) women with abnormal epithelial cells in NAF have an increased risk of breast cancer when compared to

  3. Modulation of oxidative stress and subsequent induction of apoptosis and endoplasmic reticulum stress allows citral to decrease cancer cell proliferation.

    Science.gov (United States)

    Kapur, Arvinder; Felder, Mildred; Fass, Lucas; Kaur, Justanjot; Czarnecki, Austin; Rathi, Kavya; Zeng, San; Osowski, Kathryn Kalady; Howell, Colin; Xiong, May P; Whelan, Rebecca J; Patankar, Manish S

    2016-01-01

    The monoterpenoid, citral, when delivered through PEG-b-PCL nanoparticles inhibits in vivo growth of 4T1 breast tumors. Here, we show that citral inhibits proliferation of multiple human cancer cell lines. In p53 expressing ECC-1 and OVCAR-3 but not in p53-deficient SKOV-3 cells, citral induces G1/S cell cycle arrest and apoptosis as determined by Annexin V staining and increased cleaved caspase3 and Bax and decreased Bcl-2. In SKOV-3 cells, citral induces the ER stress markers CHOP, GADD45, EDEM, ATF4, Hsp90, ATG5, and phospho-eIF2α. The molecular chaperone 4-phenylbutyric acid attenuates citral activity in SKOV-3 but not in ECC-1 and OVCAR-3 cells. In p53-expressing cells, citral increases phosphorylation of serine-15 of p53. Activation of p53 increases Bax, PUMA, and NOXA expression. Inhibition of p53 by pifithrin-α, attenuates citral-mediated apoptosis. Citral increases intracellular oxygen radicals and this leads to activation of p53. Inhibition of glutathione synthesis by L-buthionine sulfoxamine increases potency of citral. Pretreatment with N-acetylcysteine decreases phosphorylation of p53 in citral-treated ECC-1 and OVCAR-3. These results define a p53-dependent, and in the absence of p53, ER stress-dependent mode of action of citral. This study indicates that citral in PEG-b-PCL nanoparticle formulation should be considered for treatment of breast and other tumors. PMID:27270209

  4. ING5 suppresses proliferation, apoptosis, migration and invasion, and induces autophagy and differentiation of gastric cancer cells: a good marker for carcinogenesis and subsequent progression

    Science.gov (United States)

    Gou, Wen-feng; Shen, Dao-fu; Yang, Xue-feng; Zhao, Shuang; Liu, Yun-peng; Sun, Hong-zhi; Su, Rong-jian; Luo, Jun-sheng; Zheng, Hua-chuan

    2015-01-01

    Here, we found that ING5 overexpression increased autophagy, differentiation, and decreased proliferation, apoptosis, migration, invasion and lamellipodia formation in gastric cancer cells, while ING5 knockdown had the opposite effects. In SGC-7901 transfectants, ING5 overexpression caused G1 arrest, which was positively associated with 14-3-3 overexpression, Cdk4 and c-jun hypoexpression. The induction of Bax hypoexpression, Bcl-2, survivin, 14-3-3, PI3K, p-Akt and p70S6K overexpression by ING5 decreased apoptosis in SGC-7901 cells. The hypoexpression of MMP-9, MAP1B and flotillin 2 contributed to the inhibitory effects of ING5 on migration and invasion of SGC-7901 cells. ING5 overexpression might activate both β-catenin and NF-κB pathways in SGC-7901 cells, and promote the expression of down-stream genes (c-myc, VEGF, Cyclin D1, survivin, and interleukins). Compared with the control, ING5 transfectants displayed drug resistance to triciribine, paclitaxel, cisplatin, SAHA, MG132 and parthenolide, which was positively related to their apoptotic induction and the overexpression of chemoresistance-related genes (MDR1, GRP78, GRP94, IRE, CD147, FBXW7, TOP1, TOP2, MLH1, MRP1, BRCP1 and GST-π). ING5 expression was higher in gastric cancer than matched mucosa. It was inversely associated with tumor size, dedifferentiation, lymph node metastasis and clinicopathological staging of cancer. ING5 overexpression suppressed growth, blood supply and lung metastasis of SGC-7901 cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that ING5 expression might be employed as a good marker for gastric carcinogenesis and subsequent progression by inhibiting proliferation, growth, migration, invasion and metastasis. ING5 might induce apoptotic and chemotherapeutic resistances of gastric cancer cells by activating β-catenin, NF-κB and Akt pathways. PMID:25980581

  5. Effects of irradiation for cervical cancer on subsequent breast cancer

    International Nuclear Information System (INIS)

    Previous research suggests that cervical cancer patients have a lower risk of breast cancer than women in the general population. Possible explanations include opposing risk factors for cervical cancer and breast cancer, the effect of irradiation used to treat cervical cancer, or both. The purpose of this study was to explore the relationship between irradiation for cervical cancer and the subsequent development of breast cancer. There was no statistically significant relationship between radiation to the ovarian area and the risk of breast cancer in this study. However, the results were consistent with a 19% reduction in risk for women irradiated for cervical cancer when compared to nonirradiated women. In a dose-response analysis, there was a nonsignificant trend of decreased risk of breast cancer with increased radiation up to 1800 rad. There was no consistent pattern for higher doses. The trend, although nonsignificant, differed by age. Women <60 years of age at irradiation were generally at a lower risk of breast cancer than nonirradiated women. Women over 59 years were at an increased risk. There are some potentially important findings from this study which might influence medical care. These should be examined in the larger International Radiation Study

  6. Unpasteurized Milk Consumption and Subsequent Risk of Cancer

    OpenAIRE

    Sellers, Thomas A.; Robert A Vierkant; Djeu, Julie; Celis, Esteban; Wang, Alice H.; Kumar, Nagi; Cerhan, James R.

    2008-01-01

    Concerns have been raised regarding the possible adverse health effects of consumption of unpasteurized milk and risk of cancer. We examined the association of self-reported intake of unpasteurized milk with subsequent risk of cancer in a large population-based cohort study. The Iowa Women's Health Study is a prospective cohort study of 55-69 year old women at baseline in 1986. Of the 41,836 women in the cohort at baseline, 22,808 cancer-free women completed the fourth follow-up questionnaire...

  7. Silencing of ribosomal protein S9 elicits a multitude of cellular responses inhibiting the growth of cancer cells subsequent to p53 activation.

    Directory of Open Access Journals (Sweden)

    Mikael S Lindström

    Full Text Available BACKGROUND: Disruption of the nucleolus often leads to activation of the p53 tumor suppressor pathway through inhibition of MDM2 that is mediated by a limited set of ribosomal proteins including RPL11 and RPL5. The effects of ribosomal protein loss in cultured mammalian cells have not been thoroughly investigated. Here we characterize the cellular stress response caused by depletion of ribosomal protein S9 (RPS9. METHODOLOGY/PRINCIPAL FINDINGS: Depletion of RPS9 impaired production of 18S ribosomal RNA and induced p53 activity. It promoted p53-dependent morphological differentiation of U343MGa Cl2:6 glioma cells as evidenced by intensified expression of glial fibrillary acidic protein and profound changes in cell shape. U2OS osteosarcoma cells displayed a limited senescence response with increased expression of DNA damage response markers, whereas HeLa cervical carcinoma cells underwent cell death by apoptosis. Knockdown of RPL11 impaired p53-dependent phenotypes in the different RPS9 depleted cell cultures. Importantly, knockdown of RPS9 or RPL11 also markedly inhibited cell proliferation through p53-independent mechanisms. RPL11 binding to MDM2 was retained despite decreased levels of RPL11 protein following nucleolar stress. In these settings, RPL11 was critical for maintaining p53 protein stability but was not strictly required for p53 protein synthesis. CONCLUSIONS: p53 plays an important role in the initial restriction of cell proliferation that occurs in response to decreased level of RPS9. Our results do not exclude the possibility that other nucleolar stress sensing molecules act upstream or in parallel to RPL11 to activate p53. Inhibiting the expression of certain ribosomal proteins, such as RPS9, could be one efficient way to reinitiate differentiation processes or to induce senescence or apoptosis in rapidly proliferating tumor cells.

  8. SchA-p85-FAK complex dictates isoform-specific activation of Akt2 and subsequent PCBP1-mediated post-transcriptional regulation of TGFβ-mediated epithelial to mesenchymal transition in human lung cancer cell line A549.

    Science.gov (United States)

    Xue, Xinying; Wang, Xin; Liu, Yuxia; Teng, Guigen; Wang, Yong; Zang, Xuefeng; Wang, Kaifei; Zhang, Jinghui; Xu, Yali; Wang, Jianxin; Pan, Lei

    2014-08-01

    A post-transcriptional pathway by which TGF-β modulates expression of specific proteins, Disabled-2 (Dab2) and Interleukin-like EMT Inducer (ILEI), inherent to epithelial to mesenchymal transition (EMT) in murine epithelial cells through Akt2-mediated phosphorylation of poly r(C) binding protein (PCBP1), has been previously elucidated. The aims of the current study were to determine if the same mechanism is operative in the non-small cell lung cancer (NSCLC) cell line, A549, and to delineate the underlying mechanism. Steady-state transcript and protein expression levels of Dab2 and ILEI were examined in A549 cells treated with TGF-β for up to 48 h. Induction of translational de-repression in this model was quantified by polysomal fractionation followed by qRT-PCR. The underlying mechanism of isoform-specific activation of Akt2 was elucidated through a combination of co-immunoprecipitation studies. TGF-β induced EMT in A549 cells concomitant with translational upregulation of Dab2 and ILEI proteins through isoform-specific activation of Akt2 followed by phosphorylation of PCBP1 at serine-43. Our experiments further elucidated that the adaptor protein SchA is phosphorylated at tyrosine residues following TGF-β treatment, which initiated a signaling cascade resulting in the sequential recruitment of p85 subunit of PI3K and focal adhesion kinase (FAK). The SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1. Inhibition of the p85 subunit through phosphorylated 1257 peptide completely attenuated EMT in these cells. We have defined the underlying mechanism responsible for isoform-specific recruitment and activation of Akt2, not Akt1, during TGF-β-mediated EMT in A549 cells. Inhibition of the formation of this complex thus represents an important and novel therapeutic target in metastatic lung carcinoma. PMID:24819169

  9. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC ...

  10. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  11. Squamous cell skin cancer

    Science.gov (United States)

    ... earliest form of squamous cell cancer is called Bowen disease (or squamous cell carcinoma in situ). This type ... cancer; Squamous cell carcinoma of the skin Images Bowen's disease on the hand Keratoacanthoma Keratoacanthoma Skin cancer, squamous ...

  12. Childhood indicators of susceptibility to subsequent cervical cancer

    OpenAIRE

    Montgomery, S M; Ehlin, A G C; Sparén, P.; Björkstén, B; Ekbom, A.

    2002-01-01

    Common warts could indicate cervical cancer susceptibility, as both are caused by human papillomavirus (HPV). Eczema was also investigated, as atopic eczema has been negatively associated with warts, but non-atopic eczema may be associated with compromised host defences, as observed in patients with HIV, suggesting increased susceptibility to HPV infection and cervical cancer. ‘Cervical cancer’ was self-reported during an interview by 87 of 7594 women members of two longitudinal British birth...

  13. Gastrectomy and subsequent risk of oesophageal cancer in Milan.

    OpenAIRE

    La Vecchia, C; D'Avanzo, B; Negri, E; Franceschi, S.; Boyle, P.

    1994-01-01

    STUDY OBJECTIVE--To analyse quantitatively the relationship between gastrectomy and oesophageal cancer risk. DESIGN--This was a case-control study, based on a structured questionnaire that included a problem-oriented medical history. SETTING--A network of hospitals in the Greater Milan area between 1984 and 1992. SUBJECTS--Subjects were 316 incident, histologically confirmed cases of oesophageal cancer (258 males and 58 females), and 1408 controls (1031 males, 377 females), admitted to hospit...

  14. Metabolic syndrome and risk of subsequent colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Raluca Pais; Horatiu Silaghi; Alina Cristina Silaghi; Mihai Lucian Rusu; Dan Lucian Dumitrascu

    2009-01-01

    The metabolic syndrome and visceral obesity have an increasing prevalence and incidence in the general population. The actual prevalence of the metabolic syndrome is 24% in US population and between 24.6% and 30.9% in Europe. As demonstrated by many clinical trials (NAHANES Ⅲ, INTERHART) the metabolic syndrome is associated with an increased risk of both diabetes and cardiovascular disease. In addition to cardiovascular disease, individual components of the metabolic syndrome have been linked to the development of cancer, particularly to colorectal cancer.Colorectal cancer is an important public health problem; in the year 2000 there was an estimated total of 944 717 incident cases of colorectal cancer diagnosed world-wide. This association is sustained by many epidemiological studies. Recent reports suggest that individuals with metabolic syndrome have a higher risk of colon or rectal cancer. Moreover, the clusters of metabolic syndrome components increase the risk of associated cancer. The physiopathological mechanism that links metabolic syndrome and colorectal cancer is mostly related to abdominal obesity and insulin resistance. Population and experimental studies demonstrated that hyperinsulinemia, elevated C-peptide, elevated body mass index, high levels of insulin growth factor-1, low levels of insulin growth factor binding protein-3, high leptin levels and low adiponectin levels are all involved in carcinogenesis. Understanding the pathological mechanism that links metabolic syndrome and its components to carcinogenesis has a major clinical significance and may have profound health benefits on a number of diseases including cancer, which represents a major cause of mortality and morbidity in our societies.

  15. Radiotherapy and subsequent thyroid cancer in German childhood cancer survivors: a nested case–control study

    International Nuclear Information System (INIS)

    Radiotherapy is associated with a risk of subsequent neoplasms (SN) in childhood cancer survivors. It has been shown that children’s thyroid glands are especially susceptible. The aim is to quantify the risk of a second neck neoplasm after primary cancer radiotherapy with emphasis on thyroid cancer. We performed a nested case–control study: 29 individuals, diagnosed with a solid SN in the neck region, including 17 with thyroid cancer, in 1980–2002 and 57 matched controls with single neoplasms were selected from the database of the German Childhood Cancer Registry. We investigated the risk associated with radiotherapy exposure given per body region, adjusted for chemotherapy. 16/17 (94.1 %) thyroid SN cases, 9/12 (75 %) other neck SN cases and 34/57 (59.6 %) controls received radiotherapy, with median doses of 27.8, 25 and 24 Gy, respectively. Radiotherapy exposure to the neck region increased the risk of the other neck SNs by 4.2 % (OR = 1.042/Gy (95 %-CI 0.980-1.109)) and of thyroid SN by 5.1 % (OR = 1.051/Gy (95 %-CI 0.984-1.123)), and radiotherapy to the neck or spine region increased the thyroid risk by 6.6 % (OR = 1.066/Gy (95 %-CI 1.010-1.125)). Chemotherapy was not a confounder. Exposure to other body regions was not associated with increased risk. Radiotherapy in the neck or spine region increases the risk of thyroid cancer, while neck exposure increases the risk of any other solid SN to a similar extent. Other studies showed a decreasing risk of subsequent thyroid cancer for very high doses; we cannot confirm this

  16. Diet and subsequent survival in women with breast cancer.

    OpenAIRE

    Ingram, D

    1994-01-01

    Our findings from a previous study, that increased consumption of beta-carotene and vitamin C is associated with favourable prognostic indices in patients with breast cancer, have been borne out by our current study of patient survival over a 6-year period. The results of the current study point to beta-carotene consumption as the dietary variable most significantly associated with improved survival. Only one death occurred in the group with the highest consumption of beta-carotene, while the...

  17. Sperm Cryopreservation before Testicular Cancer Treatment and Its Subsequent Utilization for the Treatment of Infertility

    Directory of Open Access Journals (Sweden)

    Jana Žáková

    2014-01-01

    Full Text Available Aims. In this study we report our results with storage of cryopreserved semen intended for preservation and subsequent infertility treatment in men with testicular cancer during the last 18 years. Methods. Cryopreserved semen of 523 men with testicular cancer was collected between October 1995 and the end of December 2012. Semen of 34 men (6.5% was used for fertilization of their partners. They underwent 57 treatment cycles with cryopreserved, fresh, and/or donor sperm. Results. A total of 557 men have decided to freeze their semen before cancer treatment. Azoospermia was diagnosed in 34 men (6.1%, and semen was cryopreserved in 532 patients. Seminoma was diagnosed in 283 men (54.1% and nonseminomatous germ cell tumors in 240 men (45.9%. 34 patients who returned for infertility treatment underwent 46 treatment cycles with cryopreserved sperm. Totally 16 pregnancies were achieved, that is, 34.8% pregnancy rate. Conclusion. The testicular cancer survivors have a good chance of fathering a child by using sperm cryopreserved prior to the oncology treatment, even when it contains only limited number of spermatozoa.

  18. Is a Cancer Diagnosis Associated with Subsequent Risk of Transient Global Amnesia?

    OpenAIRE

    Zhu, Jianwei; Lu, DongHao; Sveinsson, Olafur; Wirdefeldt, Karin; Fall, Katja; Piehl, Fredrik; Valdimarsdóttir, Unnur; Fang, Fang

    2015-01-01

    Background Psychological stress has been associated with transient global amnesia (TGA). Whether a cancer diagnosis, a severely stressful life event, is associated with subsequent risk of TGA has not been studied. Methods Based on the Swedish Cancer Register and Patient Register, we conducted a prospective cohort study including 5,365,608 Swedes at age 30 and above during 2001–2009 to examine the relative risk of TGA among cancer patients, as compared to cancer-free individuals. Incidence rat...

  19. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil, E-mail: hyunil74@hotmail.com; Lee, Zang Hee, E-mail: zang1959@snu.ac.kr

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  20. Ultrasonic cell disruption of stabilised sludge with subsequent anaerobic digestion.

    Science.gov (United States)

    Onyeche, T I; Schläfer, O; Bormann, H; Schröder, C; Sievers, M

    2002-05-01

    The world-wide increasing environmental awareness and its subsequent regulations have led to the application of improved technologies in wastewater purification plants. This has resulted in higher wastewater and sludge productions. Sludge is the by-product of such plants and it is not only rich in organic carbon and pathogens but also in heavy metals and other environmental pollutants. In Europe, agricultural application of dried sludge (bio-solids) is confronted with negative reactions from the citizens, governmental organisations, farmers and the food industry. Ultrasonic disruption of sludge is a popular mechanical disruption process in sludge treatment. During ultrasonic treatment, high frequency acoustic signals are used to initiate the cavitation process. The applied ultrasonic field leads to a breakdown of cohesive forces of the liquid molecules resulting in the generation of cavitation bubbles. A shock wave is released by the collapse of the cavitation bubbles and propagates in the surrounding medium forming jet streams that cause the disruption of cells in sludge. Disruption of sludge cells enables the release of light organic substances into the sludge water thereby exposing them for further anaerobic digestion. This paper presents results on the disruption of conventionally stabilised sludge through the application of the ultrasonic field. In order to reduce the specific energy input (i.e. ratio of the consumed energy during ultrasonic disruption to the input sludge mass) and improve biogas production, the total solids content of the stabilised sludge was increased before disruption. The anaerobic digestion of sludge samples was carried out in a set of specially constructed laboratory anaerobic digesters. Results showed that subsequent anaerobic digestion of the ultrasonically disrupted sludge could improve biogas production with reduced sludge quantity that is vital to the economic consideration of the wastewater treatment plants. This process

  1. Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Sharon R. Pine

    2008-01-01

    Full Text Available Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

  2. 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 ...

  3. Radiation dose and subsequent risk for stomach cancer in long-term survivors of cervical cancer

    DEFF Research Database (Denmark)

    Kleinerman, Ruth A; Smith, Susan A; Holowaty, Eric;

    2013-01-01

    To assess the dose-response relationship for stomach cancer after radiation therapy for cervical cancer.......To assess the dose-response relationship for stomach cancer after radiation therapy for cervical cancer....

  4. Cancer Stem Cells

    OpenAIRE

    Katarzyna Wieczorek; Jolanta Niewiarowska

    2008-01-01

    Cancer stem cell theory gains increasingly greater significance in the world of medicine. Numerous findings of scientific research in vivo and in vitro indicate that it is the population of undifferentiated, self-renewing cells which is responsible for recurrence of cancer and metastasis. Similarly to normal stem cells, cancer stem cells (CSC) function in the environment of the other cells of the organism, called the niche, where they receive signals for differentiation and proliferation proc...

  5. Stemming Cancer: Functional Genomics of Cancer Stem Cells in Solid Tumors

    OpenAIRE

    Regenbrecht, C. R. A.; Lehrach, H; Adjaye, J.

    2008-01-01

    Cancer stem cells (CSCs) were discovered about 15 years ago in hematopoietic cancers. Subsequently, cancer stem cells were discovered in various solid tumors. Based on parallels with normal stem cells, a developmental process of cancer stem cells follows paths of organized, hierarchical structure of cells with different degrees of maturity. While some investigators have reported particular markers as identification of cancer stem cells, these markers require further research. In this review, ...

  6. Lung Cancer Stem Cells

    OpenAIRE

    Pine, Sharon R.; Blair Marshall; Lyuba Varticovski

    2008-01-01

    Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation p...

  7. Breast cancer stem cells

    OpenAIRE

    Owens, Thomas W.; Naylor, Matthew J.

    2013-01-01

    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 tumors 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 th...

  8. Efficacy of a touchscreen computer based family cancer history questionnaire and subsequent cancer risk assessment

    OpenAIRE

    Westman, J; Hampel, H.; Bradley, T.

    2000-01-01

    OBJECTIVE—A computer based touchscreen family cancer history questionnaire was developed and implemented to facilitate the provision of cancer risk assessments for the ambulatory and outpatient populations of a free standing cancer hospital.
METHODS—A questionnaire consisting of a series of branched point decision making screens was developed which enables the participant to enter demographic data, personal cancer history, and cancer histories for first and second degree relatives. A freestan...

  9. Subsequent malignancies in patients treated with 131-iodine for thyroid cancer

    International Nuclear Information System (INIS)

    I-131 was administered to 298 patients with thyroid cancer, and there has been a follow-up of at least two years. Follow-up periods were: 2.5 to 30 years (median 14.5) in living patients, 2.5 to 15 years (median 5.5) in patients dead of tumour ≥ 2 years after first treatment and 2.5 to 23 years (median nine) in patients dead without tumour. Person-years at risk were (total applied activity of I-131): 1119 (3 to 21 GBq), 1477 (22 to 65 GBq), 521 (61 to 170 Gbq). 33 subsequent malignancies in 31 patients were observed, compared to an expected number of 17. The relative risk of subsequent malignancies is therefore 1.94 with a 95% confidence intervall of 1.15 to 3.05. This increase in the incidence of subsequent malignancies after I-131 treatments is largely due to the significantly increased incidence of leukemia and bladder cancer. Estimated radiation doses to the bone marrow in the patients with leukemia were 301 cGy to 792 cGy and the doses to the bladder in patients with bladder cancer were 2250 cGy to 10, 350 cGy. After a total activity of less than 37 GBq I-131, no cases of bladder cancer or leukemia were observed. The observed number of subsequent malignancies are compared with the expected number according to several dose-effect estimations. (orig.)

  10. Stages of Renal Cell Cancer

    Science.gov (United States)

    ... cell cancer is a disease in which malignant (cancer) cells form in tubules of the kidney. Renal cell ... diagnosed, tests are done to find out if cancer cells have spread within the kidney or to other ...

  11. Gastric Cancer Stem Cells

    OpenAIRE

    Takaishi, Shigeo; Okumura, Tomoyuki; Timothy C Wang

    2008-01-01

    Cancer stem cells are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. Accumulating evidence in recent years strongly indicate the existence of cancer stem cells in solid tumors of a wide variety of organs. In this review, we will discuss the possible existence of a gastric cancer stem cell. Our recent data suggest that a subpopulation with a defined marker shows spheroid colony format...

  12. Cancer stem cell metabolism

    OpenAIRE

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

    2016-01-01

    Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. 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. Deter...

  13. 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...

  14. TRICHOMONOSIS AND SUBSEQUENT RISK OF PROSTATE CANCER IN THE PROSTATE CANCER PREVENTION TRIAL

    OpenAIRE

    Sutcliffe, Siobhan; Alderete, John F.; Till, Cathee; Goodman, Phyllis J.; Hsing, Ann W.; Zenilman, Jonathan M; De Marzo, Angelo M.; Platz, Elizabeth A.

    2009-01-01

    We previously observed a positive association between a history of trichomonosis, a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis, and prostate cancer risk in the Health Professionals Follow-up Study. To determine the reproducibility of this finding, we conducted a second, prospective investigation of trichomonosis and prostate cancer in the Prostate Cancer Prevention Trial. Participants were men ≥55 years of age with no evidence of prostate cancer at enrollmen...

  15. Serum beta-carotene and subsequent risk of cancer: results from the BUPA Study.

    OpenAIRE

    Wald, N J; Thompson, S G; Densem, J W; Boreham, J.; Bailey, A

    1988-01-01

    In the BUPA Study, a prospective study of 22,000 men attending a screening centre in London, serum samples were collected and stored. The concentration of beta-carotene was measured in the stored serum samples from 271 men who were subsequently notified as having cancer and from 533 unaffected controls, matched for age, smoking history and duration of storage of the serum samples. The mean beta-carotene level of the cancer subjects was significantly lower than that of their matched controls (...

  16. Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study

    DEFF Research Database (Denmark)

    Frederiksen, Henrik Kronholm; Farkas, Dóra Körmendiné; Christiansen, Christian Fynbo;

    2011-01-01

    Patients with chronic myeloproliferative neoplasms, including essential thrombocythemia (ET), polycythemia vera (PV), and chronic myeloid leukemia (CML), are at increased risk of new hematologic malignancies, but their risk of nonhematologic malignancies remains unknown. In the present study, we...... diagnosed with a chronic myeloproliferative neoplasm during 1977-2008. We compared the incidence of subsequent cancer in this cohort with that expected on the basis of cancer incidence in the general population (standardized incidence ratio). Overall, ET, PV, and CML patients were at increased risk of...... conclude that patients with chronic myeloproliferative neoplasms are at increased risk of developing a new malignant disease. © 2011 by The American Society of Hematology....

  17. Risk factors for subsequent endocrine-related cancer in childhood cancer survivors.

    Science.gov (United States)

    Wijnen, M; van den Heuvel-Eibrink, M M; Medici, M; Peeters, R P; van der Lely, A J; Neggers, S J C M M

    2016-06-01

    Long-term adverse health conditions, including secondary malignant neoplasms, are common in childhood cancer survivors. Although mortality attributable to secondary malignancies declined over the past decades, the risk for developing a solid secondary malignant neoplasm did not. Endocrine-related malignancies are among the most common secondary malignant neoplasms observed in childhood cancer survivors. In this systematic review, we describe risk factors for secondary malignant neoplasms of the breast and thyroid, since these are the most common secondary endocrine-related malignancies in childhood cancer survivors. Radiotherapy is the most important risk factor for secondary breast and thyroid cancer in childhood cancer survivors. Breast cancer risk is especially increased in survivors of Hodgkin lymphoma who received moderate- to high-dosed mantle field irradiation. Recent studies also demonstrated an increased risk after lower-dose irradiation in other radiation fields for other childhood cancer subtypes. Premature ovarian insufficiency may protect against radiation-induced breast cancer. Although evidence is weak, estrogen-progestin replacement therapy does not seem to be associated with an increased breast cancer risk in premature ovarian-insufficient childhood cancer survivors. Radiotherapy involving the thyroid gland increases the risk for secondary differentiated thyroid carcinoma, as well as benign thyroid nodules. Currently available studies on secondary malignant neoplasms in childhood cancer survivors are limited by short follow-up durations and assessed before treatment regimens. In addition, studies on risk-modifying effects of environmental and lifestyle factors are lacking. Risk-modifying effects of premature ovarian insufficiency and estrogen-progestin replacement therapy on radiation-induced breast cancer require further study. PMID:27229933

  18. The impact of induction chemotherapy on the dosimetric parameters of subsequent radiotherapy: an investigation of 30 consecutive patients with locally-advanced non-small cell lung cancer and modern radiation planning techniques

    International Nuclear Information System (INIS)

    To investigate the influence of induction chemotherapy (ICT) on dosimetric outcomes in patients with inoperable non-small cell lung cancer (NSCLC) treated with definitive chemoradiation (CRT). 30 patients with inoperable stage II-III NSCLC treated with 2–4 cycles of ICT followed by definitive CRT to ≥ 60 Gy were selected. Tumor response to chemotherapy was scored by RECIST criteria. Treatment plans based on tumor extent prior to chemotherapy were generated based on equivalent planning constraints and techniques as the original post-chemotherapy plans. Dosimetric parameters predictive of toxicity for lung, esophagus, heart, and spinal cord were compared amongst the pre- and post-ICT plans. The majority of patients (70%) experienced an overall reduction in GTV size between the pre-ICT imaging and the time of simulation. Comparing pre-and post-ICT diagnostic imaging, 5 patients met the RECIST criteria for response, 23 were classified as stable, and 2 experienced disease progression on diagnostic imaging. Despite a significantly reduced GTV size in the post-ICT group, no systematic improvements in normal tissue doses were seen amongst the entire cohort. This result persisted amongst the subgroup of patients with larger pre-ICT GTV tumor volumes (>100 cc3). Among patients with RECIST-defined response, a significant reduction in lung mean dose (1.9 Gy absolute, median 18.2 Gy to 16.4 Gy, p = 0.04) and V20, the percentage of lung receiving 20 Gy (3.1% absolute, median 29.3% to 26.3%, p = 0.04) was observed. In the non-responding group of patients, an increased esophageal V50 was found post-chemotherapy (median 28.9% vs 30.1%, p = 0.02). For patients classified as having a response by RECIST to ICT, modest improvements in V20 and mean lung dose were found. However, these benefits were not realized for the cohort as a whole or for patients with larger tumors upfront. Given the variability of tumor response to ICT, the a priori impact of induction chemotherapy to reduce

  19. Clinical Stages in Patients with Primary and Subsequent Cancers Based on the Czech Cancer Registry 1976–2005

    Science.gov (United States)

    Štampach, Radim; Dítě, Petr; Kozel, Jiří; Horváth, Teodor; Kubíček, Petr

    2013-01-01

    Of 1,486,984 new cancers registered in the Czech Cancer Registry in 1976-2005, 290,312 (19.5%) were multiple malignant neoplasms (MMNs), of which there were 65,292 primary and 89,796 subsequent cases in men and 59,970 primary and 75,254 subsequent cases in women. The duplicities were higher in women, and the triplicities and others (3–6 MMNs) were higher in men. The most frequent diagnoses were the primary cancers of skin, gastrointestinal and urinary tract, male genital organs, respiratory tract in men, and cancers of skin, breast, female genital organs, and gastrointestinal tract in women. The analysis of the early and advanced clinical stages shows that the number of subsequent advanced stages increased after primary advanced stages. Their time-age-space distributions visualized maps of MMNs in 14 Czech regions. These results support the improvement of algorithms of dispensary care for the early detection of the subsequent neoplasms. PMID:23936674

  20. Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term Survivors of Cervical Cancer

    International Nuclear Information System (INIS)

    Purpose: To assess the dose–response relationship for stomach cancer after radiation therapy for cervical cancer. Methods and Materials: We conducted a nested, matched case–control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63 Gy, range 0.12-6.3). Results: More than 90% of women received radiation therapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses ≥5 Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, Ptrend=.047) compared with nonirradiated women. A highly significant radiation dose–response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (Ptrend=.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (Ptrend=.23). Conclusions: Our findings show for the first time a significant linear dose–response relationship for risk of stomach cancer in long-term survivors of cervical cancer

  1. Independent Association of Postdoctoral Training with Subsequent Careers in Cancer Prevention.

    Directory of Open Access Journals (Sweden)

    Jessica M Faupel-Badger

    Full Text Available The purpose of this study was to examine the career paths of alumni from the National Cancer Institute (NCI Cancer Prevention Fellowship Program (CPFP, a structured in-house postdoctoral training program of 3-4 years duration, and specifically what proportion of the alumni were currently performing cancer prevention-related activities. The analyses here included 119 CPFP alumni and 85 unsuccessful CPFP applicants, all of whom completed postdoctoral training between 1987-2011 and are currently employed. Postdoctoral training experiences and current career outcomes data were collected via online surveys. Differences between groups were assessed using chi-square and Fisher's exact test p-values and subsequent regression analyses adjusted for differences between the groups. Compared to 15.3% of unsuccessful CPFP applicants, 52.1% of CPFP alumni (odds ratio [OR] = 4.99, 95% confidence interval [95% CI: 1.91-13.0 were currently spending the majority of their time working in cancer prevention. Among those doing any cancer prevention-focused work, 54.3% of CPFP alumni spent the majority of their time performing cancer prevention research activities when compared to 25.5% of unsuccessful applicants (OR = 4.26, 95% CI: 1.38-13.2. In addition to the independent effect of the NCI CPFP, scientific discipline, and employment sector were also associated with currently working in cancer prevention and involvement in cancer prevention research-related activities. These results from a structured postdoctoral training program are relevant not only to the cancer prevention community but also to those interested in evaluating alignment of postdoctoral training programs with available and desired career paths more broadly.

  2. Independent Association of Postdoctoral Training with Subsequent Careers in Cancer Prevention

    Science.gov (United States)

    Faupel-Badger, Jessica M.; Nelson, David E.; Izmirlian, Grant; Ross, Katherine H.; Raue, Kimberley; Tsakraklides, Sophia; Miyaoka, Atsushi; Spiegelman, Maura

    2015-01-01

    The purpose of this study was to examine the career paths of alumni from the National Cancer Institute (NCI) Cancer Prevention Fellowship Program (CPFP), a structured in-house postdoctoral training program of 3–4 years duration, and specifically what proportion of the alumni were currently performing cancer prevention-related activities. The analyses here included 119 CPFP alumni and 85 unsuccessful CPFP applicants, all of whom completed postdoctoral training between 1987–2011 and are currently employed. Postdoctoral training experiences and current career outcomes data were collected via online surveys. Differences between groups were assessed using chi-square and Fisher’s exact test p-values and subsequent regression analyses adjusted for differences between the groups. Compared to 15.3% of unsuccessful CPFP applicants, 52.1% of CPFP alumni (odds ratio [OR] = 4.99, 95% confidence interval [95% CI): 1.91–13.0) were currently spending the majority of their time working in cancer prevention. Among those doing any cancer prevention-focused work, 54.3% of CPFP alumni spent the majority of their time performing cancer prevention research activities when compared to 25.5% of unsuccessful applicants (OR = 4.26, 95% CI: 1.38–13.2). In addition to the independent effect of the NCI CPFP, scientific discipline, and employment sector were also associated with currently working in cancer prevention and involvement in cancer prevention research-related activities. These results from a structured postdoctoral training program are relevant not only to the cancer prevention community but also to those interested in evaluating alignment of postdoctoral training programs with available and desired career paths more broadly. PMID:26659381

  3. Systemic therapy for breast cancer and risk of subsequent contralateral breast cancer in the WECARE Study

    OpenAIRE

    Langballe, Rikke; Mellemkjær, Lene; Malone, Kathleen E.; Lynch, Charles F.; John, Esther M.; Julia A. Knight; Bernstein, Leslie; Brooks, Jennifer; Andersson, Michael; Reiner, Anne S.; Liang, Xiaolin; Woods, Meghan; Concannon, Patrick J.; ,; Bernstein, Jonine L.

    2016-01-01

    Background Treatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment characteristics. Methods The population-based WECARE Study included 1521 cases with CBC and 2212 age- and year of first diagnosis-matched controls with unilateral breast cancer recruited during two phases in the USA, Canada, and Denmark. Women were diagnose...

  4. Breast cancer stem-like cells and breast cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Niansong Qian; Nobuko Kawaguchi-Sakita; Masakazu Toi

    2010-01-01

    @@ Until the early 1990s, human cancers were considered a morphologically heterogeneous population of cells. In 1997, Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone was organized as a hierarchy; this was subsequently denoted as cancer stem like cells (CSCs). CSCs are cancer cells that possess characteristics associated with normal stem cells and have the specific ability to give rise to all cell types found in a particular cancer. One reason for the failure of traditional anti tumor therapies might be their inability to eradicate CSCs. Therefore, therapies must identify and destroy CSCs in both primary and metastatic tumors.

  5. Cancer Stem Cells, Cancer Cell Plasticity and Radiation Therapy

    OpenAIRE

    Vlashi, Erina; Pajonk, Frank

    2014-01-01

    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 ...

  6. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    MatthewJNaylor

    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.

  7. First and subsequent asbestos exposures in relation to mesothelioma and lung cancer mortality.

    Science.gov (United States)

    Pira, E; Pelucchi, C; Piolatto, P G; Negri, E; Discalzi, G; La Vecchia, C

    2007-11-01

    We analysed data from a cohort of 1966 subjects (889 men and 1,077 women) employed by an Italian asbestos (mainly textile) company in the period 1946-1984, who were followed-up to 2004. A total of 62,025 person-years of observation were recorded. We computed standardised mortality ratios (SMR) for all causes and selected cancer sites using national death rates for each 5-year calendar period and age group. There were 68 deaths from mesothelioma (25 men and 43 women, 39 pleural and 29 peritoneal) vs 1.6 expected (SMR=4,159), and 109 from lung cancer vs 35.1 expected (SMR=310). The SMRs of pleural/peritoneal cancer were 6661 for subjects exposed only before 30 years of age, 8,019 for those first exposed before 30 and still employed at 30-39 years of age and 5,786 for those first exposed before 30 and still employed at 40 or more years of age. The corresponding SMRs for lung cancer were 227, 446 and 562. The SMR of mesothelioma was strongly related to time since first exposure. The SMR of lung cancer, but not of mesothelioma, appeared to be related to subsequent exposures. PMID:17895892

  8. Memory and effector T cells modulate subsequently primed immune responses to unrelated antigens

    OpenAIRE

    Tian, Jide D; LU, Y. X.; Hanssen, L.; Dang, H.; Kaufman, D L

    2003-01-01

    Memory and effector T cells modulate subsequently primed T cell responses to the same antigen. However, little is known about the impact of pre-existing memory and effector T cell immunity on subsequently primed immune responses to unrelated antigens. Here, we show that an antigen-primed first wave of Th1 and Th2 immunity enhanced or inhibited the subsequently primed T cell immunity to an unrelated Antigen, depending on whether the second antigen was administered in the same or opposite type ...

  9. Fingerprints in cancer cells

    International Nuclear Information System (INIS)

    Gene research has shown that factors causing cancer, or carcinogens, may leave marks typical of each particular carcinogen (fingerprints) in the genotype of the cell. Radiation, for instance, may leave such fingerprints in a cancer cell. In particular, the discovery of a gene called p53 has yielded much new information on fingerprints. It has been discovered, for example, that toxic fungus and UV-radiation each leave fingerprints in the p53 gene. Based on the detection of fingerprints, it may be possible in the future to tell a cancer patient what factor had trigged the maglinancy

  10. Prostate cancer stem cells

    OpenAIRE

    Tu, Shi-Ming; Lin, Sue-Hwa

    2011-01-01

    Stem cells have long been implicated in prostate glandular 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 AR− status of prostate stem cells renders them inherently insensitive to androgen blockade ther...

  11. A novel microfluidic platform for size and deformability based separation and the subsequent molecular characterization of viable circulating tumor cells.

    Science.gov (United States)

    Hvichia, G E; Parveen, Z; Wagner, C; Janning, M; Quidde, J; Stein, A; Müller, V; Loges, S; Neves, R P L; Stoecklein, N H; Wikman, H; Riethdorf, S; Pantel, K; Gorges, T M

    2016-06-15

    Circulating tumor cells (CTCs) were introduced as biomarkers more than 10 years ago, but capture of viable CTCs at high purity from peripheral blood of cancer patients is still a major technical challenge. Here, we report a novel microfluidic platform designed for marker independent capture of CTCs. The Parsortix™ cell separation system provides size and deformability-based enrichment with automated staining for cell identification, and subsequent recovery (harvesting) of cells from the device. Using the Parsortix™ system, average cell capture inside the device ranged between 42% and 70%. Subsequent harvest of cells from the device ranged between 54% and 69% of cells captured. Most importantly, 99% of the isolated tumor cells were viable after processing in spiking experiments as well as after harvesting from patient samples and still functional for downstream molecular analysis as demonstrated by mRNA characterization and array-based comparative genomic hybridization. Analyzing clinical blood samples from metastatic (n = 20) and nonmetastatic (n = 6) cancer patients in parallel with CellSearch(®) system, we found that there was no statistically significant difference between the quantitative behavior of the two systems in this set of twenty six paired separations. In conclusion, the epitope independent Parsortix™ system enables the isolation of viable CTCs at a very high purity. Using this system, viable tumor cells are easily accessible and ready for molecular and functional analysis. The system's ability for enumeration and molecular characterization of EpCAM-negative CTCs will help to broaden research into the mechanisms of cancer as well as facilitating the use of CTCs as "liquid biopsies." PMID:26789903

  12. Stem Cells and Cancer

    International Nuclear Information System (INIS)

    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)

  13. Cancer Stem Cells in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer

  14. Cancer Stem Cells

    OpenAIRE

    Aurelio Lorico; Eric Deutsch; Bo Lu; Shih-Hwa Chiou

    2011-01-01

    Cancer Stem Cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity when transplanted into an animal host. A number of cell surface markers such as CD44, CD24, and CD133 are often used to identify and enrich CSCs. A regulatory network consisting of microRNAs and Wnt/β-catenin, Notch, and Hedgehog signaling pathways controls the CSC properties. The clinical relevance of CSCs has been strengthened by emerging evidence,...

  15. Cancer Stem Cells in Breast Cancer

    OpenAIRE

    Fumitaka Takeshita; Tomohiro Fujiwara; Takahiro Ochiya; Makiko Ono; Ryou-u Takahashi

    2011-01-01

    The cancer stem cell (CSC) theory is generally acknowledged as an important field of cancer research, not only as an academic matter but also as a crucial aspect of clinical practice. CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche. However, CSCs differ from normal stem cel...

  16. Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

    Science.gov (United States)

    Mierke, Claudia T.

    There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

  17. Extragonadal Germ Cell Cancer (EGC)

    Science.gov (United States)

    ... Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell ... seen in young adults. Patients with mediastinal nonseminomatous EGC are typically classed as poor risk patients because ...

  18. Translocation of Magnaporthe oryzae effectors into rice cells and their subsequent cell-to-cell movement.

    Science.gov (United States)

    Khang, Chang Hyun; Berruyer, Romain; Giraldo, Martha C; Kankanala, Prasanna; Park, Sook-Young; Czymmek, Kirk; Kang, Seogchan; Valent, Barbara

    2010-04-01

    Knowledge remains limited about how fungal pathogens that colonize living plant cells translocate effector proteins inside host cells to regulate cellular processes and neutralize defense responses. To cause the globally important rice blast disease, specialized invasive hyphae (IH) invade successive living rice (Oryza sativa) cells while enclosed in host-derived extrainvasive hyphal membrane. Using live-cell imaging, we identified a highly localized structure, the biotrophic interfacial complex (BIC), which accumulates fluorescently labeled effectors secreted by IH. In each newly entered rice cell, effectors were first secreted into BICs at the tips of the initially filamentous hyphae in the cell. These tip BICs were left behind beside the first-differentiated bulbous IH cells as the fungus continued to colonize the host cell. Fluorescence recovery after photobleaching experiments showed that the effector protein PWL2 (for prevents pathogenicity toward weeping lovegrass [Eragrostis curvula]) continued to accumulate in BICs after IH were growing elsewhere. PWL2 and BAS1 (for biotrophy-associated secreted protein 1), BIC-localized secreted proteins, were translocated into the rice cytoplasm. By contrast, BAS4, which uniformly outlines the IH, was not translocated into the host cytoplasm. Fluorescent PWL2 and BAS1 proteins that reached the rice cytoplasm moved into uninvaded neighbors, presumably preparing host cells before invasion. We report robust assays for elucidating the molecular mechanisms that underpin effector secretion into BICs, translocation to the rice cytoplasm, and cell-to-cell movement in rice. PMID:20435900

  19. Cancer stem cells in prostate cancer

    OpenAIRE

    Moltzahn, Felix; Thalmann, George N

    2013-01-01

    Prostate cancer (P-Ca) remains a leading cause of cancer-related death in men. Lately, increasing evidence for a hierarchically organized cancer stem cell (CSC) model emerged for different tumors entities, including P-Ca. CSCs are defined by several characteristics including self-renewal, pluripotency and tumorigenicity and are thought to be responsible for tumor recurrence, metastasis and cancer related death. In this review we discuss the recent research in the field of CSCs, its limitation...

  20. Cancer Stem Cells in Pancreatic Cancer

    OpenAIRE

    Karl-Walter Jauch; Hendrik Seeliger; Hanno Niess; Qi Bao; Andrea Renner; Yue Zhao; Bruns, Christiane J.

    2010-01-01

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC t...

  1. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    , vinculin and FAK synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Finally, the knowledge of the mechanical properties of invasive and non-invasive cells could provide a source for future drug developments to inhibit formation of metastases. This special section also includes two papers from the group of Martin Herrmann, a research paper and a review paper. The research paper by Janko et al deals with the cooperative binding of Annexin A5 to phosphatidylserines on apoptotic cell membranes [6]. This could not alone serve as an 'eat me' signal for macrophages as healthy cells also express Annexin A5 on their cell surface. The authors suggest that the cooperative binding is altered and subsequently the fluidity of Annexin A5 on the membrane. Together this may serve as a signal for phagocytic cells to eat apoptotic cells and leave healthy ones untouched. The paper by Biermann et al reviews the role of biophysical signals in the clearance of apoptotic cells [7]. In addition to the acto-myosin cytoskeleton, the keratin network seems to play a role in cancer research. The paper from the Beil and the Marti group demonstrates that microrheology is a valuable tool to determine the viscoelastic properties of polymer networks such as the keratin network in cells and an arbitrary in vitro network [8]. They describe how the topology of the keratin network affects the overall mechanical behavior of cells. It seems that the field of physical oncology will continue to grow in the future and more research will address the mechanical properties of cancer cells and whole tissues. Biophysical methods will need to be further improved and adapted to the needs of cancer research. References [1] Coughlin M F and Fredberg J J 2013 Phys. Biol. 10 065001 [2] Krause M, te Riet J and Wolf K 2013 Phys. Biol. 10 065002 [3] Munn L L 2013 Phys. Biol. 10 065003 [4] Bordeleau F, Tang L N and Reinhart-King C A 2013 Phys. Biol. 10 065004 [5

  2. Population Based Screening for Prostate Cancer: prognostic findings of two subsequent screening rounds

    OpenAIRE

    Postma, Renske

    2006-01-01

    textabstractProstate cancer is nowadays the most common non-cutaneous cancer in men in the Western world. Since the introduction of Prostate Specific Antigen (PSA) testing in the last decade, prostate cancer incidence increased dramatically. In addition, the population is aging, and prostate cancer incidence increases with higher age. The dilemma of prostate cancer is that more men die with prostate cancer than from prostate cancer, as reflected by the observation that in 70% of men who are 8...

  3. Breast cancer stem cells and radiation

    Science.gov (United States)

    Phillips, Tiffany Marie

    2007-12-01

    ligand, Jagged-1, and this was complemented by radiation induced Notch-1 activation. Studies also linked hypoxia and BCSC renewal through Epo signaling. Treatment with rhEpo induced an increase in BCSC's, which again was due to rhEpo induced Jagged-1 expression and subsequent Notch-1 activation. This thesis suggests that radiation and rhEpo induce Jagged-1 expression in non-stem cells, which then induce Notch-1 activation in adjacent stem cells, and results in symmetric cancer stem cell self-renewal.

  4. Cancer stem cell subsets and their relationships

    OpenAIRE

    Pan Yi-Fei; Yang Han; Chen Chong; Liu Hai-Guang; Zhang Xiao-Hua

    2011-01-01

    Abstract Emerging evidence suggests that cancer stem cells account for the initiation and progression of cancer. While many types of cancer stem cells with specific markers have been isolated and identified, a variety of differences among them began to be appreciated. Cancer stem cells are hierarchical populations that consist of precancerous stem cells, primary cancer stem cells, migrating cancer stem cells and chemoradioresistant cancer stem cells, playing different roles in cancer initiati...

  5. Renal cell cancer without a renal primary

    OpenAIRE

    Cumani B; Bratcher J; Wang W.; Wayne M.; Kasmin F; Cooperman A

    2010-01-01

    Abstract Renal cell carcinoma has been increasing in incidence over the past two decades. Men are affected more than women and metastatic disease at presentation occurs in up to one third of patients. Metastasis can occur to virtually any organ, and involvement of multiple organs is not uncommon. To date, no reports have been found of metastatic disease without a renal primary. We present a case of renal cell cancer initially presenting as a subcutaneous mass with subsequent pancreatic and pa...

  6. Urothelial Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Irena Dimov

    2010-01-01

    Full Text Available There is mounting evidence supporting the idea that tumors, similar to normal adult tissues, arise from a specific stem-like cell population, the cancer stem cells (CSCs, which are considered as the real driving force behind tumor growth, the ability to metastasize, as well as resistance to conventional antitumor therapy. The concept that cancer growth recapitulates normal proliferative and/or regenerative processes, even though in very dysfunctional ways, has tremendous implications for cancer therapy. The rapid development of the CSC field, shoulder to shoulder with powerful genome-wide screening techniques, has provided cause for optimism for the development of more reliable therapies in the future. However, several important issues still lie ahead. Recent identification of a highly tumorigenic stem-like compartment and existence of urothelial differentiation programs in urothelial cell carcinomas (UCCs raised important questions about UCC initiation and development. This review examines the present knowledge on CSCs in UCCs regarding the similarities between CSCs and the adult urothelial stem cells, potential origin of urothelial CSCs, main regulatory pathways, surface markers expression, and the current state of CSC-targeting therapeutic strategies.

  7. Population Based Screening for Prostate Cancer: prognostic findings of two subsequent screening rounds

    NARCIS (Netherlands)

    R. Postma (Renske)

    2006-01-01

    textabstractProstate cancer is nowadays the most common non-cutaneous cancer in men in the Western world. Since the introduction of Prostate Specific Antigen (PSA) testing in the last decade, prostate cancer incidence increased dramatically. In addition, the population is aging, and prostate cancer

  8. Mobilization of regulatory T cells in response to carotid injury does not influence subsequent neointima formation.

    Directory of Open Access Journals (Sweden)

    Amit Saxena

    Full Text Available AIM: T cells have been attributed an important role in modulating repair responses following vascular injury. The aim of this study was to investigate the role of different T cell subsets in this context. METHODS AND RESULTS: A non-obstructive collar was introduced to inflict carotid artery injury in mice and subsequent activation of immune cells in draining lymph nodes and spleen were studied by flow cytometry. Carotid artery injury of wild type mice was associated with mobilization of both Th1 type CD4(+IFNγ(+ and regulatory CD4(+CD25(+FoxP3(+ T cells in draining lymph nodes. Studies using FoxP3-green fluorescent protein (GFP transgenic C57/Bl6 mice demonstrated scattered presence of regulatory T cells in the adventitial tissue of injured arteries as well as a massive emigration of regulatory T cells from the spleen in response to carotid injury. However, deletion of antigen presentation to CD4+ T cells (H2(0 mice, as well as deletion of regulatory T cells (through treatment with blocking anti-CD25 antibodies, did not affect neointima formation. Also deletion of antigen presentation to CD8(+ T cells (Tap1(0 mice was without effect on carotid collar-induced neointima formation. CONCLUSION: The results demonstrate that carotid artery injury is associated with mobilization of regulatory T cells. Depletion of regulatory T cells does not, however, influence the subsequent repair processes leading to the formation of a neointima. The results also demonstrate that lack of CD8(+ T cells does not influence neointima formation in presence of functional CD4(+ T cells and B cells.

  9. Comprehensive copy number profiles of breast cancer cell model genomes

    OpenAIRE

    Shadeo, Ashleen; Lam, Wan L.

    2006-01-01

    Introduction Breast cancer is the most commonly diagnosed cancer in women worldwide and consequently has been extensively investigated in terms of histopathology, immunochemistry and familial history. Advances in genome-wide approaches have contributed to molecular classification with respect to genomic changes and their subsequent effects on gene expression. Cell lines have provided a renewable resource that is readily used as model systems for breast cancer cell biology. A thorough characte...

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

    OpenAIRE

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

    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 resea...

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

    Institute of Scientific and Technical Information of China (English)

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

    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.

  12. Immunotargeting of cancer stem cells

    OpenAIRE

    Kwiatkowska-Borowczyk, Eliza P.; Gąbka-Buszek, Agnieszka; Jankowski, Jakub; Mackiewicz, Andrzej

    2015-01-01

    Cancer stem cells (CSCs) represent a distinctive population of tumour cells that control tumour initiation, progression, and maintenance. Their influence is great enough to risk the statement that successful therapeutic strategy must target CSCs in order to eradicate the disease. Because cancer stem cells are highly resistant to chemo- and radiotherapy, new tools to fight against cancer have to be developed. Expression of antigens such as ALDH, CD44, EpCAM, or CD133, which distinguish CSCs fr...

  13. Optimization of tumor cell culture conditions in soft agar for subsequent immunohistochemical analysis

    Directory of Open Access Journals (Sweden)

    Khoruzhenko A. I.

    2012-07-01

    Full Text Available Aim. The aim of this work is to optimize conditions of malignant cells cultivation in soft agar for subsequent immunohistochemical analysis of formed three-dimensional colonies. Methods. Cultivation of breast carcinoma cell line MCF-7 in soft agar, immunohistochemical and im- munofluorescence detection of epithelial antigen and mTOR kinase in cultured cells. Results. We describe a methodical approach to the cultivation of cells in soft agar, which allows to carry out morphological, morphometric and immunochemical analysis of the studied cells. Conclusions. The proposed method provides an additional characteriza tion of cells growing in soft agar, which will be useful in basic research and in evaluation of the effectiveness of anticancer drugs.

  14. Prostate stem cells and cancer

    OpenAIRE

    Nikitin, Alexander Y.; Matoso, A; Roy-Burman, P

    2007-01-01

    Properties shared by neoplastic and stem cells indicate a possibility that somatic stem cells or transit-amplifying cells that have reacquired stem cell properties, particularly the ability for self-renewal, represent favorable targets for malignant transformation. In this review we discuss significance of the stem cell model for understanding prostate cancer pathogenesis and describe relevant studies in animals. It is proposed that dissemination of rare cancer stem ce...

  15. General Information about Small Cell Lung Cancer

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  16. Stages of Small Cell Lung Cancer

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  17. Treatment Option Overview (Small Cell Lung Cancer)

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  18. Familial aggregation of breast/ovarian cancer: age of onset along subsequent generations in Brazil

    Directory of Open Access Journals (Sweden)

    Koifman Rosalina Jorge

    1998-01-01

    Full Text Available Antecedents of familial aggregation of breast and ovarian cancer are observed in only 5-8% of all breast cancer cases. Nevertheless, this variable displays one of the highest risk ratios associated to breast cancer outcome. Despite recent identification of genetic mutations associated with familial aggregation of these tumors, mainly at BRCA1 and BRCA2 genes, knowledge on the interaction between environmental agents in these families remains quite unclear. In this paper we ascertained the correlation among ages of the onset of breast/ovarian cancer in 260 Brazilian families with those cancer aggregation. Further we estimated the median age of the onset of breast cancer among four generations. We observed that the higher the number of family cancer cases, the highest is the correlation of ages for the onset of breast cancer. We also observed a 8-10 year decline in the mean age-of-onset of breast/ovarian cancer from one generation to another in the studied families. If these results could be confirmed elsewhere, we believe that the hypothesis of interaction between environmental risks factors in families indeed showing breast/ovarian cancer aggregation is reinforced.

  19. Ovarian cancer: emerging concept on cancer stem cells

    OpenAIRE

    Ponnusamy Moorthy P; Batra Surinder K

    2008-01-01

    Abstract Emerging evidence suggests that the capacity of a tumor to grow and propagate is dependent on a small subset of cells within a tumor, termed cancer stem cells. In fact, cancer cells, like stem cells, can proliferate indefinitely through a dysregulated cellular self-renewal capacity. Cancer stem cells may originate due to the distribution into self-renewal and differentiation pathways occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells and cancer cell...

  20. Joint and independent effect of alcohol and tobacco use on the risk of subsequent cancer incidence among cancer survivors: A cohort study using cancer registries.

    Science.gov (United States)

    Tabuchi, Takahiro; Ozaki, Koken; Ioka, Akiko; Miyashiro, Isao

    2015-11-01

    Drinking alcohol and smoking tobacco are major modifiable risk factors for cancer. However, little is known about whether these modifiable factors of cancer survivors are associated with subsequent primary cancer (SPC) incidence, regardless of the first cancer sites. 27,762 eligible cancer survivors diagnosed between 1985 and 2007 were investigated for SPC until the end of 2008, using hospital-based and population-based cancer registries. The association between drinking, smoking and combined drinking and smoking (interaction) at the time of the first cancer diagnosis and incidence of SPCs (i.e., all SPCs, alcohol-related, smoking-related and specific SPCs) was estimated by Poisson regression. Compared with never-drinker/never-smoker, the categories ever-drinker/ever-smoker, current-drinker/current-smoker and heavy-drinker/heavy-smoker had 43-108%, 51-126% and 167-299% higher risk for all, alcohol-related and tobacco-related SPCs, respectively. The interaction of drinking and smoking had significantly high incidence rate ratios (IRRs) for SPCs among ever-drinker/ever-smoker and current-drinker/current-smoker, although ever drinking did not show a significant risk. Ever-drinker/ever-smoker had also significantly higher IRRs for esophageal and lung SPCs than never-drinker/never-smoker. Among comprehensive cancer survivors, ever and current drinkers only had a SPC risk when combined with smoking, while ever and current smokers had a SPC risk regardless of drinking status. Heavy drinking and heavy smoking were considered to be independent additive SPC risk factors. To reduce SPC incidence, it may be necessary (i) to reduce or stop alcohol use, (ii) to stop tobacco smoking and (iii) dual users, especially heavy users, should be treated as a high-risk population for behavioral-change intervention. PMID:25904109

  1. Hypertensive disorders of pregnancy and subsequent risk of solid cancer-A nationwide cohort study.

    Science.gov (United States)

    Behrens, Ida; Basit, Saima; Jensen, Allan; Lykke, Jacob Alexander; Nielsen, Lars Peter; Wohlfahrt, Jan; Kjaer, Susanne K; Melbye, Mads; Boyd, Heather Allison

    2016-07-01

    Women with hypertensive disorders of pregnancy (HDP) have higher levels of antiangiogenic growth factors during pregnancy than women with normotensive pregnancies. Since angiogenesis is necessary for solid cancer growth and spread, we hypothesized that women with a history of HDP might have a reduced risk of solid cancers (cancers other than lymphomas, hematologic cancers and nonmelanoma skin cancers) later in life. In a register-based cohort study of 1.08 million women giving birth at least once between 1978 and 2011, we used Cox regression to estimate hazard ratios (HRs) comparing solid cancer rates for women with and without a history of HDP. In this cohort, 68,236 women (6.3%) had ≥1 pregnancy complicated by HDP and 42,236 women (3.9%) developed solid tumors during follow-up. A history of HDP was not associated with a clinically meaningful reduction in the overall rate of solid cancer (HR 0.96, 95% confidence interval 0.92-1.00), regardless of HDP severity or time since HDP, nor was there a general tendency toward reduced solid cancer rates across organ sites. A history of HDP was only significantly associated with decreased rates of breast and lung cancers and with increased rates of endometrial and urinary tract cancers. Overall, our results do not support the hypothesis that women with a history of HDP have a reduced overall risk of solid cancer due to a persistent post-HDP antiangiogenic state or an innate tendency toward antiangiogenesis. Observed associations with specific cancers may instead be due to other pregnancy-related mechanisms or to residual/unmeasured confounding. PMID:26919086

  2. Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women

    OpenAIRE

    Eliassen, A. Heather; Spiegelman, Donna; Xu, Xia; Keefer, Larry K; Veenstra, Timothy D.; Barbieri, Robert L.; Willett, Walter C; Hankinson, Susan E.; Ziegler, Regina G.

    2011-01-01

    Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites (EM) and breast cancer risk among premenopausal women in a case-control study nested within the Nurses’ Health Study II (NHSII). In 1996–1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N=247) diagnosed between collection and June 2005 were match...

  3. Natural killer cells in baboons and humans subjected to total lymphoid irradiation and subsequent renal transplantation

    International Nuclear Information System (INIS)

    This study investigates the functional ability and numbers of natural killer (NK) cells in peripheral blood of the chacma baboon and humans which were subjected to varying doses of total lymphoid irradiation (TLI) and subsequent renal transplantation. NK cell activity was determined by measuring the amount of 51Cr release from K562 target cells when placed in contact with baboon or human peripheral blood lymphocytes. The anti-human antibody Leu11b was shown to cross-react with determinants on baboon effector cells. Concomitant measurements of large granular lymphocytes (LGL) were also made. Normal values for NK cell activity Leu11b+ cells and LGL in the baboon were 73.4+-39.6 Vmax units, 6.8+-3.8% and 6.0+-3.2% respectively. After TLI, NK cell activity was elevated 3 to 4 fold of pre-TLI values and remained at these supranormal levels. The effects of surgery caused a transient depression of activity. Normal values for NK cell activity, Leu11b+ cells and LGL in humans were 280+-212 Vmax units, 6.7+-2.5% and 7.6+-2.5% respectively. A significant depression of NK cell activity was observed in renal allograft patients receiving combination doses of immunosuppressive drugs. Those patients that received tolerogenic doses of TLI prior to transplant followed by immunosuppressive drug regimens had a significant and persistent elevation of NK cell activity. Baboons and humans showed no relationship between NK cell function and Leu11b+ cells or LGL. The latter two parameters did not significantly change in response to TLI or transplantation. It was concluded that TLI gives rise to activated NK cells which results in elevated function unrelated to cell numbers. This dissertation has demonstrated that one advantage of TLI lies in the selective suppression of immunity - while graft tolerance is easily induced

  4. 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 ...

  5. Prostate cancer stem cell biology

    OpenAIRE

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of s...

  6. Redirecting neutrophils against bladder cancer cells by BCG and Smac mimetic combination

    OpenAIRE

    Jinesh G, Goodwin; Kamat, Ashish M

    2012-01-01

    Intravesical bacillus Calmette-Guérin (BCG) immunotherapy results in neutrophil recruitment and subsequent secretion of cytokines to eliminate non-muscle invasive bladder cancer cells. However, bladder cancer cells often resist BCG immunotherapy. Thus, understanding the mechanism of action of BCG, and designing appropriate combination therapies might help to overcome BCG resistance and redirect neutrophils against bladder cancer cells.

  7. CD133 is a temporary marker of cancer stem cells in small cell lung cancer, but not in non-small cell lung cancer.

    Science.gov (United States)

    Cui, Fei; Wang, Jian; Chen, Duan; Chen, Yi-Jiang

    2011-03-01

    Lung cancer is the most common cause of cancer-related death worldwide. Current investigations in the field of cancer research have intensively focused on the 'cancer stem cell' or 'tumor-initiating cell'. While CD133 was initially considered as a stem cell marker only in the hematopoietic system and the nervous system, the membrane antigen also identifies tumorigenic cells in certain solid tumors. In this study, we investigated the human lung cancer cell lines A549, H157, H226, Calu-1, H292 and H446. The results of real-time PCR analysis after chemotherapy drug selection and the fluorescence-activated cell sorting analysis showed that CD133 only functioned as a marker in the small cell lung cancer line H446. The sorted CD133+ subset presented stem cell-like features, including self-renewal, differentiation, proliferation and tumorigenic capacity in subsequent assays. Furthermore, a proportion of the CD133+ cells had a tendency to remain stable, which may explain the controversies arising from previous studies. Therefore, the CD133+ subset should provide an enriched source of tumor-initiating cells among H446 cells. Moreover, the antigen could be used as an investigative marker of the tumorigenic process and an effective treatment for small cell lung cancer. PMID:21174061

  8. Breast cancer surface receptors predict risk for developing brain metastasis and subsequent prognosis

    OpenAIRE

    Grewal, Jai; Kesari, Santosh

    2008-01-01

    Determining the status of breast cancer surface receptors (estrogen receptor, progesterone receptor, HER2/neu) has become routine in the care of patients with this disease and has proven to be helpful in guiding treatment. For this reason, breast cancer has become a model for molecularly guided therapy in solid tumors. Emerging data support that these receptors are associated with risk for developing brain metastases. Additionally, once brain metastases have occurred these receptors may also ...

  9. Mouse models for cancer stem cell research

    OpenAIRE

    Cheng, Le; Ramesh, Anirudh V.; Flesken-Nikitin, Andrea; Choi, Jinhyang; Nikitin, Alexander Yu.

    2009-01-01

    Cancer stem cell concept assumes that cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumor initiating cells, which are able to reproduce themselves and produce phenotypically heterogeneous cells with lesser tumorigenic potential. Cancer stem cells represent an appealing target for development of more selective and efficient therapies. However, direct testing of the cancer stem cell concept and assessment of its therapeutic implications in human...

  10. Venous thromboembolism and subsequent risk of cancer in patients with liver disease

    DEFF Research Database (Denmark)

    Montomoli, Jonathan; Erichsen, Rune; Søgaard, Kirstine Kobberøe;

    2015-01-01

    OBJECTIVE: Venous thromboembolism (VTE) may be a marker of occult cancer in the general population. While liver disease is known to increase the risk of VTE and cancer, it is unclear whether VTE in patients with liver disease is also a marker of occult cancer. DESIGN: A population-based cohort...... and patients with liver cirrhosis were followed as two separate cohorts from the date of their VTE. MEASURES: For each cohort, we computed the absolute and relative risk (standardised incidence ratio; SIR) of cancer after VTE. RESULTS: During the study period, 1867 patients with non-cirrhotic liver disease...... and 888 with liver cirrhosis were diagnosed with incident VTE. In the first year following VTE, the absolute risk of cancer was 2.7% among patients with non-cirrhotic liver disease and 4.3% among those with liver cirrhosis. The SIR for the first 90 days of follow-up was 9.96 (95% CI 6.85 to 13.99) among...

  11. Eradicating cancer cells: struggle with a chameleon

    OpenAIRE

    Di, Jiabo; Boer, Tjitske Duiveman-de; Figdor, Carl G.; Torensma, Ruurd

    2011-01-01

    Eradication of cancer stem cells to abrogate tumor growth is a new treatment modality. However, like normal cells cancer cells show plasticity. Differentiated tumor stem cells can acquire stem cell properties when they gain access to the stem cell niche. This indicates that eradicating of stem cells (emptying of the niche) alone will not lead to eradication of the tumor. Treatment should be directed to cancer stem cells ànd more mature cancer cells.

  12. Acetaminophen Changes Intestinal Epithelial Cell Membrane Properties, Subsequently Affecting Absorption Processes

    Directory of Open Access Journals (Sweden)

    Christine Schäfer

    2013-08-01

    Full Text Available Background/Aims: Acetaminophen (APAP effects on intestinal barrier properties are less investigated. APAP may lead to a changed bioavailability of a subsequently administered drug or diet in the body. We investigated the influence of APAP on enterocytic cell membrane properties that are able to modify the net intestinal absorption of administered substances across the Caco-2 barrier model. Methods: The effect of APAP on cytotoxicity was measured by LDH assay, TER value and cell capacitance label-free using impedance monitoring, membrane permeability by FITC-dextrans, and efflux transporter MDR1 activity by Rh123. APAP levels were determined by HPLC analysis. Cell membrane topography and microvilli were investigated using SEM and intestinal alkaline phosphatase (Alpi and tight junction protein 1 (TJP1 expression by western blot analysis. Results: APAP changed the apical cell surface, reduced the number of microvilli and protein expression of Alpi as a brush border marker and TJP1, increased the membrane integrity and concurrently decreased cell capacitance over time. In addition, APAP decreased the permeability to small molecules and increased the efflux transporter activity, MDR1. Conclusion: APAP alters the Caco-2 cell membrane properties by different mechanisms and reduces the permeability to administered substances. These findings may help to optimize therapeutic implications.

  13. Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines

    OpenAIRE

    Wang, Jian-Lin; Yu, Jing-Ping; Zhi-qiang SUN; Sun, Su-Ping

    2014-01-01

    AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics.

  14. Chemotherapy targeting cancer stem cells

    OpenAIRE

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cance...

  15. Single cancer cell analysis on a chip

    OpenAIRE

    Yang, Yoonsun

    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 blood. We designed and developed various microfluidic devices for genetic and phenotypic characterization of single cancer cells. The limited DNA content in a single cell requires DNA amplification t...

  16. Cell of origin of lung cancer

    OpenAIRE

    Hanna, Jennifer M.; Onaitis, Mark W.

    2013-01-01

    Lung cancer is the leading cause of cancer deaths worldwide, and current therapies are disappointing. Elucidation of the cell(s) of origin of lung cancer may lead to new therapeutics. In addition, the discovery of putative cancer-initiating cells with stem cell properties in solid tumors has emerged as an important area of cancer research that may explain the resistance of these tumors to currently available therapeutics. Progress in our understanding of normal tissue stem cells, tumor cell o...

  17. Head and Neck Cancer Stem Cells

    OpenAIRE

    Krishnamurthy, S.; Nör, J.E.

    2012-01-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signalin...

  18. Inhibition of subsequent nodal metastasis by low dose of elective neck irradiation for tongue cancers

    International Nuclear Information System (INIS)

    To study the influence of elective neck irradiation (ENI) with a dose of ≤30 Gy on subsequent nodal metastasis for tongue carcinomas. Forty-nine patients controlled at the primary site were evaluated. They were treated with interstitial irradiation and ENI of ≤30 Gy from 1979 to 1991. Subsequent nodal metastases developed in 14 patients (29%) 1 to 23 months after radiotherapy. The nodal recurrence rates were 4/10 (40%) for 0 Gy, 4/9 (44%) for 10-15 Gy, 6/22 (27%) for 16-20 Gy, and 0/8 (0%) for 21-30 Gy. The rates according to tumor thickness were 5/28 (18%) for superficial tumors and 9/21 (41%) for deeply invasive tumors. These factors were shown to be significant by multivariate analysis. The nodal recurrence from irradiated fields developed late compared with that from outside the fields. Successful salvage was obtained in 11/14 (79%), depending on the recurrent nodal stage. The five-year survival rate was significantly better in patients with irradiation of >15 Gy (96%) than those with 15 Gy or less (79%). ENI of low dose (15-30 Gy) significantly reduced nodal recurrence rate and prolonged survival. An elective dose of 30 Gy including the upper and middle neck was able to reduce subsequent nodal metastases about 10% (from 37% to 27% in our review). (author)

  19. Limited small cell lung cancer

    International Nuclear Information System (INIS)

    This paper assesses the prognosis of patients with limited small cell lung cancer (LSCLC) not achieving complete response (CR) to induction combination chemotherapy (ICC) but who achieve CR after thoracic irradiation (TI). Twenty-four patients had CRs to ICC (CR- ICC) of two cycles of cytoxan, Adriamycin, and vincristine alternating with two cycles of cisplatin with VP-16. Another 24 had CR after consolidation with subsequent T1 (CR-T1): 45 Gy in daily fractions of 2.5 Gy or twice-daily fractions of 1.5 Gy. The CR-ICC and CR-TI patients had similar prognostic factors and treatment. Comparing CR-ICC and CR-TI, survival was 40% versus 26% at 2 years and 35% versus 4% at 5 years (P < .05). There were eight (33%) long-term survivors (≥3 years) in the CR-ICC group versus three (13%) in the CR-TI group. Local control for CR-ICC patients was 59% at 5 years versus 21% for the CR-TI patients (not significant). Freedom from DM for the CR-ICC patients was 41% at 5 years versus 8% for the CR-TI patients (P < .05)

  20. Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer.

    Science.gov (United States)

    Rybicki, Benjamin A; Rundle, Andrew; Kryvenko, Oleksandr N; Mitrache, Nicoleta; Do, Kieu C; Jankowski, Michelle; Chitale, Dhananjay A; Trudeau, Sheri; Belinsky, Steven A; Tang, Deliang

    2016-06-15

    In DNA from prostate tumors, methylation patterns in gene promoter regions can be a biomarker for disease progression. It remains unclear whether methylation patterns in benign prostate tissue-prior to malignant transformation-may provide similar prognostic information. To determine whether early methylation events predict prostate cancer outcomes, we evaluated histologically benign prostate specimens from 353 men who eventually developed prostate cancer and received "definitive" treatment [radical prostatectomy (58%) or radiation therapy (42%)]. Cases were drawn from a large hospital-based cohort of men with benign prostate biopsy specimens collected between 1990 and 2002. Risk of disease progression associated with methylation was estimated using time-to-event analyses. Average follow-up was over 5 years; biochemical recurrence (BCR) occurred in 91 cases (26%). In White men, methylation of the APC gene was associated with increased risk of BCR, even after adjusting for standard clinical risk factors for prostate cancer progression (adjusted hazard ratio (aHR) = 2.26; 95%CI 1.23-4.16). APC methylation was most strongly associated with a significant increased risk of BCR in White men with low prostate specific antigen at cohort entry (HR = 3.66; 95%CI 1.51-8.85). In additional stratified analyses, we found that methylation of the RARB gene significantly increased risk of BCR in African American cases who demonstrated methylation of at least one of the other four genes under study (HR = 3.80; 95%CI 1.07-13.53). These findings may have implications in the early identification of aggressive prostate cancer as well as reducing unnecessary medical procedures and emotional distress for men who present with markers of indolent disease. PMID:26860439

  1. The thioredoxin system in breast cancer cell invasion and migration

    OpenAIRE

    Maneet Bhatia; Kelly L. McGrath; Giovanna Di Trapani; Pornpimol Charoentong; Fenil Shah; Mallory M. King; Clarke, Frank M.; Tonissen, Kathryn F

    2016-01-01

    Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1) in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1) expression with breast cancer patient ...

  2. Cancer Stem Cell Hypothesis: Implication for Cancer Prevention and Treatment

    OpenAIRE

    Anna Meiliana; Nurrani Mustika Dewi; Andi Wijaya

    2016-01-01

    BACKGROUND: Cancer is a disease of genomic instability, evasion of immune cells, and adaptation of the tumor cells to the changing environment. Genetic heterogeneity caused by tumors and tumor microenvironmental factors forms the basis of aggressive behavior of some cancer cell populations. CONTENT: Cancers arise in self-renewing cell populations and that the resulting cancers, like their normal organ counterparts, are composed of hierarchically organized cell populations. Self–renewing “...

  3. Prostate Cancer Stem Cells: Research Advances

    OpenAIRE

    Dagmara Jaworska; Wojciech Król; Ewelina Szliszka

    2015-01-01

    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 th...

  4. A Population-Based Study of Subsequent Primary Malignancies After Endometrial Cancer: Genetic, Environmental, and Treatment-Related Associations

    International Nuclear Information System (INIS)

    Purpose: To examine the risk of subsequent primary malignancies (SPMs) in women diagnosed with endometrial cancer. Methods and Materials: The National Cancer Institute's Survival, Epidemiology, and End Results database was used to determine the risk of SPM after endometrial cancer in 69,739 women diagnosed between 1973 and 2005. Standardized incidence ratios were calculated (observed/expected [O/E]) for SPM sites. Results: Median follow-up was 11.2 years, representing 757,567 person-years of follow-up. The risk of SPM was significantly increased for small intestine (O/E = 1.48; 99% confidence interval [CI], 1.03-2.05), colon (O/E = 1.16; CI, 1.09-1.24), vagina (O/E = 2.71; CI, 1.86-3.8), and urinary bladder (O/E = 1.41; CI, 1.25-1.59) SPMs and decreased for oral cavity and pharynx (O/E = 0.75; CI, 0.6-0.93), lung and bronchus (O/E = 0.78; CI, 0.72-0.84), and esophagus (O/E = 0.58; CI, 0.37-0.86) SPMs. Patients receiving external-beam radiotherapy for endometrial cancer had an increased risk of colon (p < 0.001), bladder (p < 0.001), vagina (p = 0.04), and soft-tissue (p = 0.014) SPMs. Patients treated with brachytherapy had an increased risk of bladder SPM (p = 0.006). A positive bidirectional association with endometrial cancer was observed for colorectal cancer, with a negative bidirectional association for oropharyngeal and lung cancers. Conclusions: Genetic, environmental, and treatment-related factors influence SPM risk. Genetic factors may contribute to the increased risk of colorectal cancer. Smoking's negative effect on endometrial cancer risk factors might explain the decreased risk of lung and oropharyngeal cancer. Patients treated with radiotherapy likely have a small but significantly increased risk of bladder, vagina, colon, and soft-tissue SPM.

  5. Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women.

    Science.gov (United States)

    Eliassen, A Heather; Spiegelman, Donna; Xu, Xia; Keefer, Larry K; Veenstra, Timothy D; Barbieri, Robert L; Willett, Walter C; Hankinson, Susan E; Ziegler, Regina G

    2012-02-01

    Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99-2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio

  6. Results of Breast Conserving Surgery and Subsequent Postoperative Radiotherapy for Cases of Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chie, Eui Kyu; Kim, Kyu Bo; Choi, Jin Hwa [Seoul National University College of Medicine, Seoul (Korea, Republic of)] (and others)

    2008-09-15

    We analyzed the treatment outcomes and prognostic factors of breast conserving surgery, followed by postoperative radiotherapy. Materials and Methods: A total of 424 breast cancer patients treated with breast conserving surgery and postoperative radiotherapy between February 1992 and January 2001 were retrospectively analyzed. A quadrantectomy and axillary lymph node dissection was performed in 396 patients. A total of 302 patients had T1 disease, and 122 patients had T2 disease. Lymph node involvement was confirmed in 107 patients. Whole breast irradiation was administered at up to 50.4 Gy in 28 fractions, followed by a 10 Gy boost in 5 fractions to the tumor bed. In addition, 57 patients underwent regional lymph node irradiation. Moreover, chemotherapy was administered in 231 patients. A regimen consisting of cyclophosphamide, methotrexate, and 5-fluorouracil was most frequently used with 170 patients. The median follow-up time was 64 months. Results: The 5-year local control rate was 95.6%. During the follow-up period, local tumor recurrence was observed in 15 patients. The 5-year overall and disease-free survival rates were 93.1% and 88.7%, respectively. The 5-year overall survival rates, by stage, were 94.8% for stage I, 95.0% for stage IIA, 91.1% for stage IIB, 75.9% for stage IIIA, and 57.1% for stage IIIC. As for disease-free survival, the corresponding figures, by stage (in the same order), were 93.1%, 89.4%, 82.8%, 62.0%, and 28.6%, respectively. The advanced N stage (p=0.0483) was found to be a significant prognostic factor in predicting poor overall survival, while the N stage (p=0.0284) and age at diagnosis (p=0.0001) were associated with disease-free survival. Conclusion: This study has shown that breast conserving surgery and postoperative radiotherapy for early breast cancer results was excellent for local control and survival.

  7. Stem cells in human breast cancer

    OpenAIRE

    Roberto Oliveira, Lucinei; Jeffrey, Stefanie S; Ribeiro Silva, Alfredo

    2010-01-01

    Increasing data support cancer as a stem cell-based disease. Cancer stem cells (CSCs) have beenfound in different human cancers, and recent evidenceindicates that breast cancer originates from and ismaintained by its own CSCs, as well as the normalmammary gland. Mammary stem cells and breast CSCshave been identified and purified in in vitroculturesystems, transplantation assays and/or by cell surfaceantigen identification. Cell surface markers enable thefunctional isolation of stem cells that...

  8. 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......, the last part of the review discusses future directions of this intriguing new research field in the context of new diagnostic and therapeutic opportunities....

  9. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells

    OpenAIRE

    Chang W. Song; Hyemi Lee; Dings, Ruud P. M.; Brent Williams; John Powers; Troy Dos Santos; Bo-Hwa Choi; Heon Joo Park

    2012-01-01

    The anti-cancer effects of metformin, the most widely used drug for type 2 diabetes, alone or in combination with ionizing radiation were studied with MCF-7 human breast cancer cells and FSaII mouse fibrosarcoma cells. Clinically achievable concentrations of metformin caused significant clonogenic death in cancer cells. Importantly, metformin was preferentially cytotoxic to cancer stem cells relative to non-cancer stem cells. Metformin increased the radiosensitivity of cancer cells in vitro, ...

  10. Subsequent fertility and birth histories of children and adolescents treated with 131I for thyroid cancer

    International Nuclear Information System (INIS)

    Forty patients aged 20 years or less who had been treated with 131I after surgery for papillary-follicular thyroid carcinoma were contacted for followup study. Five had died and two were unmarried; the remaining 33 were studied with respect to their subsequent reproductive histories and the health of the offspring. The mean age at the time of the first 131I therapeutic dose was 14.6 years (range 6 to 20), and the average followup interval, from that first dose until followup, was 18.7 years (range 14 to 25). The mean total dose of 131I was 196 mCi (range 80 to 691). The incidences of infertility (12 percent), miscarriage (1.4 percent), prematurity (8 percent), and major congenital anomaly (1.4 percent) found in this series are not significantly different from those in the general population. Thus, our study offers no overt evidence of genetic damage in children and adolescents treated with high doses of 131I for thyroid carcinoma

  11. Cancer stem cells, metabolism, and therapeutic significance.

    Science.gov (United States)

    Yang, Mengqi; Liu, Panpan; Huang, Peng

    2016-05-01

    Cancer stem cells (CSCs) have attracted much attention of the research community in the recent years. Due to their highly tumorigenic and drug-resistant properties, CSCs represent important targets for developing novel anticancer agents and therapeutic strategies. CSCs were first described in hematopoietic malignancies and subsequently identified in various types of solid tumors including brain, breast, lung, colon, melanoma, and ovarian cancer. CSCs possess special biological properties including long-term self-renewal capacity, multi-lineage differentiation, and resistance to conventional chemotherapy and radiotherapy. As such, CSCs are considered as a major source of residual disease after therapy leading to disease occurrence. Thus, it is very important to understand the cellular survival mechanisms specific to CSCs and accordingly develop effective therapeutic approaches to eliminate this subpopulation of cancer cells in order to improve the treatment outcome of cancer patients. Possible therapeutic strategies against CSCs include targeting the self-renewal pathways of CSCs, interrupting the interaction between CSCs and their microenvironment, and exploiting the unique metabolic properties of CSCs. In this review article, we will provide an overview of the biological characteristics of CSCs, with a particular focus on their metabolic properties and potential therapeutic strategies to eliminate CSCs. PMID:26864589

  12. The cell birth marker BrdU does not affect recruitment of subsequent cell divisions in the adult avian brain.

    Science.gov (United States)

    Cattan, Anat; Ayali, Amir; Barnea, Anat

    2015-01-01

    BrdU is commonly used to quantify neurogenesis but also causes mutation and has mitogenic, transcriptional, and translational effects. In mammalian studies, attention had been given to its dosage, but in birds such examination was not conducted. Our previous study suggested that BrdU might affect subsequent cell divisions and neuronal recruitment in the brain. Furthermore, this effect seemed to increase with time from treatment. Accordingly, we examined whether BrdU might alter neurogenesis in the adult avian brain. We compared recruitment of [(3)H]-thymidine(+) neurons in brains of zebra finches (Taeniopygia guttata) when no BrdU was involved and when BrdU was given 1 or 3 months prior to [(3)H]-thymidine. In nidopallium caudale, HVC, and hippocampus, no differences were found between groups in densities and percentages of [(3)H]-thymidine(+) neurons. The number of silver grains per [(3)H]-thymidine(+) neuronal nucleus and their distribution were similar across groups. Additionally, time did not affect the results. The results indicate that the commonly used dosage of BrdU in birds has no long-term effects on subsequent cell divisions and neuronal recruitment. This conclusion is also important in neuronal replacement experiments, where BrdU and another cell birth marker are given, with relatively long intervals between them. PMID:25759813

  13. Nanomechanical analysis of cells from cancer patients

    Science.gov (United States)

    Cross, Sarah E.; Jin, Yu-Sheng; Rao, Jianyu; Gimzewski, James K.

    2007-12-01

    Change in cell stiffness is a new characteristic of cancer cells that affects the way they spread. Despite several studies on architectural changes in cultured cell lines, no ex vivo mechanical analyses of cancer cells obtained from patients have been reported. Using atomic force microscopy, we report the stiffness of live metastatic cancer cells taken from the body (pleural) fluids of patients with suspected lung, breast and pancreas cancer. Within the same sample, we find that the cell stiffness of metastatic cancer cells is more than 70% softer, with a standard deviation over five times narrower, than the benign cells that line the body cavity. Different cancer types were found to display a common stiffness. Our work shows that mechanical analysis can distinguish cancerous cells from normal ones even when they show similar shapes. These results show that nanomechanical analysis correlates well with immunohistochemical testing currently used for detecting cancer.

  14. Dexamethasone acutely regulates endocrine parameters in stallions and subsequently affects gene expression in testicular germ cells.

    Science.gov (United States)

    Ing, N H; Brinsko, S P; Curley, K O; Forrest, D W; Love, C C; Hinrichs, K; Vogelsang, M M; Varner, D D; Welsh, T H

    2015-01-01

    Testicular steroidogenesis and spermatogenesis are negatively impacted by stress-related hormones such as glucocorticoids. The effects of two injections of a therapeutic dose of dexamethasone (a synthetic glucocorticoid, 0.1mg/kg; i.v.) given 24h apart to each of three stallions were investigated and compared to three saline-injected control stallions. Dexamethasone decreased circulating concentrations of cortisol by 50% at 24h after the initial injection. Serum testosterone decreased by a maximum of 94% from 4 to 20h after the initial injection of dexamethasone. Semen parameters of the dexamethasone-treated stallions were unchanged in the subsequent two weeks. Two weeks after treatment, stallions were castrated. Functional genomic analyses of the testes revealed that, of eight gene products analyzed, dexamethasone depressed concentrations of heat shock protein DNAJC4 and sperm-specific calcium channel CATSPER1 mRNAs by more than 60%. Both genes are expressed in germ cells during spermiogenesis and have been related to male fertility in other species, including humans. This is the first report of decreased DNAJC4 and CATSPER1 mRNA concentrations in testes weeks after dexamethasone treatment. Concentrations of these mRNAs in sperm may be useful as novel markers of fertility in stallions. PMID:25487569

  15. Role of cancer stem cells in hepatocarcinogenesis

    OpenAIRE

    Wang, Bo; Jacob, Samson T.

    2011-01-01

    There has been considerable interest in cancer stem cells (CSCs) among cancer biologists and clinicians, most likely because of their role in the heterogeneity of cancer and their potential application in cancer therapeutics. Recent studies suggest that CSCs play a key role in liver carcinogenesis. A small subpopulation of cancer cells with CSC properties has been identified and characterized from hepatocellular carcinoma (HCC) cell lines, animal models and human primary HCCs. Considering the...

  16. 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...

  17. The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-β and IL-10

    OpenAIRE

    Wang, Yuzhou; Yi, Jun; CHEN, XINGGUI; Zhang, Ying; Xu, Meng; Yang, Zhixiong

    2015-01-01

    Tumorigenesis has been considered to be as a result of abnormal cell-cell communication. It has been proposed that exosomes act as communicators between tumors and their microenvironment and have been demonstrated to be involved in tumorigenesis and subsequent metastasis. However, the mechanisms underlying the role of exosomes in these processes remains elusive. The present study sought to determine the underlying mechanisms. Using two lung cancer cell lines, it was demonstrated that exosomes...

  18. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  19. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

    ... Genetics of Kidney Cancer Research Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  20. PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation

    KAUST Repository

    Hou, Xu

    2015-03-12

    Glioma relies on glycolysis to obtain energy and sustain its survival under low glucose microenvironment in vivo. The mechanisms on glioma cell glycolysis regulation are still unclear. Signaling mediated by Double-stranded RNA-activated protein kinase (PKR) - like ER kinase (PERK) is one of the important pathways of unfolded protein response (UPR) which is comprehensively activated in cancer cells upon the hypoxic and low glucose stress. Here we show that PERK is significantly activated in human glioma tissues. PERK silencing results in decreased glioma cell viability and ATP/lactate production upon low glucose stress, which is mediated by partially blocked AKT activation and subsequent inhibition of Hexokinase II (HK2)\\'s mitochondria translocation. More importantly, PERK silenced glioma cells show decreased tumor formation capacity. Our results reveal that PERK activation is involved in glioma glycolysis regulation and may be a potential molecular target for glioma treatment.

  1. Colon cancer stem cells: implications in carcinogenesis

    OpenAIRE

    Sanders, Matthew A.; Majumdar, Adhip P. N.

    2011-01-01

    The cancer stem cell model was described for hematologic malignancies in 1997 and since then evidence has emerged to support it for many solid tumors as well, including colon cancer. This model proposes that certain cells within the tumor mass are pluripotent and capable of self-renewal and have an enhanced ability to initiate distant metastasis. The cancer stem cell model has important implications for cancer treatment, since most current therapies target actively proliferating cells and may...

  2. Expression of Stem Cell and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells of Breast Cancer Patients

    OpenAIRE

    Natalia Krawczyk; Franziska Meier-Stiegen; Malgorzata Banys; Hans Neubauer; Eugen Ruckhaeberle; Tanja Fehm

    2014-01-01

    Evaluation and characterization of circulating tumor cells (CTCs) have become a major focus of translational cancer research. Presence of CTCs predicts worse clinical outcome in early and metastatic breast cancer. Whether all cells from the primary tumor have potential to disseminate and form subsequent metastasis remains unclear. As part of the metastatic cascade, tumor cells lose their cell-to-cell adhesion and undergo epithelial-mesenchymal transition (EMT) in order to enter blood circulat...

  3. What makes cancer stem cell markers different?

    OpenAIRE

    Karsten, Uwe; Goletz, Steffen

    2013-01-01

    Since the cancer stem cell concept has been widely accepted, several strategies have been proposed to attack cancer stem cells (CSC). Accordingly, stem cell markers are now preferred therapeutic targets. However, the problem of tumor specificity has not disappeared but shifted to another question: how can cancer stem cells be distinguished from normal stem cells, or more specifically, how do CSC markers differ from normal stem cell markers? A hypothesis is proposed which might help to solve t...

  4. Screen detection of ductal carcinoma in situ and subsequent incidence of invasive interval breast cancers: a retrospective population-based study

    OpenAIRE

    Duffy, Stephen W; Dibden, Amanda; Michalopoulos, Dimitrios; Offman, Judith; Parmar, Dharmishta; Jenkins, Jacquie; Collins, Beverley; Robson, Tony; Scorfield, Suzanne; Green, Kathryn; Hall, Clare; Liao, Xiao-Hui; Ryan, Michael; Johnson, Fiona; Stevens, Guy

    2016-01-01

    Summary Background The value of screen detection and treatment of ductal carcinoma in situ (DCIS) is a matter of controversy. At present, the extent to which the diagnosis and treatment of DCIS could prevent the occurrence of invasive breast cancer in the future is not clear. We sought to estimate the association between detection of DCIS at screening and invasive interval cancers subsequent to the relevant screen. Methods We obtained aggregate data for screen-detected cancers from 84 local s...

  5. 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 ... Smoking causes most cases (around 90%) of lung cancer. The risk ... day and for how long you have smoked. Being around the smoke ...

  6. Colorectal Cancer Stem Cells and Cell Death

    International Nuclear Information System (INIS)

    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

  7. The relationship of cancer stem cells in urological cancers

    OpenAIRE

    Marta Pokrywczyńska; Jan Adamowicz; Jakub Tworkiewicz; Zbigniew Wolski; Tomasz Drewa

    2013-01-01

    Numerous studies are ongoing to identify and isolate cancer stem cells from cancers of genito-urinary tracts. Better understanding of their role in prostate, urothelial and kidney cancer origin, growth and progression opens new pathways in development of more effective treatment methods. However there are still many issues before advances in this field can be introduced for clinical application. This review addresses current achievements in cancer stem cells research in uro-oncology.

  8. The relationship of cancer stem cells in urological cancers

    Directory of Open Access Journals (Sweden)

    Marta Pokrywczyńska

    2013-08-01

    Full Text Available Numerous studies are ongoing to identify and isolate cancer stem cells from cancers of genito-urinary tracts. Better understanding of their role in prostate, urothelial and kidney cancer origin, growth and progression opens new pathways in development of more effective treatment methods. However there are still many issues before advances in this field can be introduced for clinical application. This review addresses current achievements in cancer stem cells research in uro-oncology.

  9. Glutathione in Cancer Cell Death

    International Nuclear Information System (INIS)

    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

  10. 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.

  11. [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. PMID:26486534

  12. Understanding the cancer stem cell

    OpenAIRE

    Bomken, S; Fišer, K; Heidenreich, O; Vormoor, J

    2010-01-01

    The last 15 years has seen an explosion of interest in the cancer stem cell (CSC). Although it was initially believed that only a rare population of stem cells are able to undergo self-renewing divisions and differentiate to form all populations within a malignancy, a recent work has shown that these cells may not be as rare as thought first, at least in some malignancies. Improved experimental models are beginning to uncover a less rigid structure to CSC biology, in which the concepts of fun...

  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. 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

    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 epitheli

  15. Extinction Models for Cancer Stem Cell Therapy

    OpenAIRE

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet ,; Lange, Kenneth

    2009-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tool...

  16. Cancer stem cells: the lessons from pre-cancerous stem cells

    OpenAIRE

    Gao, Jian-Xin

    2007-01-01

    Abstract How a cancer is initiated and established remains elusive despite all the advances in decades of cancer research. Recently the cancer stem cell (CSC) hypothesis has been revived, challenging the long-standing model of ‘clonal evolution’ for cancer development and implicating the dawning of a potential cure for cancer [1]. The recent identification of pre-cancerous stem cells (pCSCs) in cancer, an early stage of CSC development, however, implicates that the clonal evolution is not con...

  17. The thioredoxin system in breast cancer cell invasion and migration.

    Science.gov (United States)

    Bhatia, Maneet; McGrath, Kelly L; Di Trapani, Giovanna; Charoentong, Pornpimol; Shah, Fenil; King, Mallory M; Clarke, Frank M; Tonissen, Kathryn F

    2016-08-01

    Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1) in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1) expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS) or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS) levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration. PMID:26760912

  18. The thioredoxin system in breast cancer cell invasion and migration

    Directory of Open Access Journals (Sweden)

    Maneet Bhatia

    2016-08-01

    Full Text Available Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1 in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1 expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration.

  19. FR901228 in Treating Patients With Refractory or Progressive Small Cell Lung Cancer or Non-small Cell Lung Cancer

    Science.gov (United States)

    2013-08-14

    Extensive Stage Small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer

  20. Breast cancer stem cells: implications for therapy of breast cancer

    OpenAIRE

    Morrison, Brian J.; Schmidt, Chris W.; Lakhani, Sunil R; Reynolds, Brent A.; Lopez, J. Alejandro

    2008-01-01

    The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to...

  1. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models......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...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...

  2. Cancer Stem Cells Converted from Pluripotent Stem Cells and the Cancerous Niche

    OpenAIRE

    Kasai, T; Chen, L.; Mizutani, AZ; Kudoh, T.; Murakami, H; Fu, L.; Seno, M

    2014-01-01

    Nowadays, the cancer stem cells are considered to be significantly responsible for growth, metastasis, invasion and recurrence of all cancer. Cancer stem cells are typically characterized by continuous proliferation and self-renewal as well as by differentiation potential, while stem cells are considered to differentiate into tissue- specific phenotype of mature cells under the influence of micro-environment. Cancer stem cells should be traced to the stem cells under the influence of a micro-...

  3. Cancer stem cells in head and neck cancer

    OpenAIRE

    Trapasso S; Allegra E

    2012-01-01

    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 differe...

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

    OpenAIRE

    Lennard, Thomas W.J.; Meeson, Annette P; Britton, Kelly M.; Kirby, John A.

    2011-01-01

    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....

  5. Cancer stem cells, tumor dormancy, and metastasis

    OpenAIRE

    EmilyChen

    2012-01-01

    Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs) in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignanc...

  6. Cancer stem cells and brain tumors

    OpenAIRE

    Pérez Castillo, Ana; Aguilar Morante, Diana; Morales-García, José A.; Dorado, Jorge

    2008-01-01

    Besides the role of normal stem cells in organogenesis, cancer stem cells are thought to be crucial for tumorigenesis. Most current research on human tumors is focused on molecular and cellular analysis of the bulk tumor mass. However, evidence in leukemia and, more recently, in solid tumors suggests that the tumor cell population is heterogeneous. In recent years, several groups have described the existence of a cancer stem cell population in different brain tumors. These neural cancer stem ...

  7. Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells

    OpenAIRE

    Gschweng, Eric Hans

    2015-01-01

    Engineering the immune system against cancer ideally provides surgical precision against the antigen bearing target cell while avoiding the systemic, off-target toxicity of chemotherapy. Successful treatment of patients in the clinic has been achieved by the expression of anti-cancer T-cell receptors (TCR) and chimeric antigen receptors (CAR) in T cells followed by infusion of these cells into cancer patients. Unfortunately, while many patients initially respond showing anti-tumor efficacy, t...

  8. Metastasis-Initiating Cells in Renal Cancer

    OpenAIRE

    Khan, Mohammed I.; Czarnecka, Anna M; Duchnowska, Renata; Kukwa, Wojciech; Szczylik, Cezary

    2013-01-01

    Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of rena...

  9. Mitotic Control of Cancer Stem Cells

    OpenAIRE

    Venere, Monica; Miller, Tyler E.; Rich, Jeremy N.

    2013-01-01

    Cancer stem cells are self-renewing, tumorigenic cells at the apex of tumor hierarchies, and postulated to be quiescent in many tumor types. This issue of Cancer Discovery highlights a study that links the presentation of kinetochores within mitosis to an essential requirement for BUB1B/BubR1, broadening our understanding of the cell-cycle machinery in cancer stem cells.

  10. Head and neck cancer stem cells.

    Science.gov (United States)

    Krishnamurthy, S; Nör, J E

    2012-04-01

    Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the "drivers" of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy. PMID:21933937

  11. Implications of Stem Cells and Cancer Stem Cells for Understanding Fomation and Therapy of Cancer

    Institute of Scientific and Technical Information of China (English)

    Guanghui Li; Donglin Wang

    2005-01-01

    Most cancers are heterogeneous with respect to proliferation and differentiation. There is increasing evidence suggesting that only a minority of cancer cells, tumorigenic or tumor initiating cells, possess the capacity to proliferate extensively and form new hematopoietic cancer or solid tumors. Tumor initiating cells share characteristics required for normal stem cells. The dysregulation of self-renewal and proliferation of stem cells is a likely requirement for cancer development. This review formulates a model for the origin of cancer stem cells and regulating self-renewal which influences the way we study and treat cancer.

  12. Gefitinib in Non Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Raffaele Costanzo

    2011-01-01

    Full Text Available Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR that plays a key role in the biology of non small cell lung cancer (NSCLC. Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations.

  13. Gossypol Induced Cell Death in DU 145 Prostate Cancer Cells

    OpenAIRE

    Kennelly, Susan

    2010-01-01

    Cancer Biology Tumourigenesis is a multistep process which includes the transformation of healthy cells into extremely malignant cells, caused by the disruption of normal tissue homeostasis. Hanahan and Weinberg propose that there are a common set of 'acquired capabilities' that most if not all cancers posses's in order to survive and proliferate despite changes in their normal cell physiology during cancer development (Hanahan and Weinberg, 2000). These "Hallmarks of Cancer", according to...

  14. Advances in Research on Circulating Tumor Cells in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yingjian SONG

    2012-10-01

    Full Text Available Metastatic and recurrent tumors have been identified as the leading attribute to the lung cancer deaths. Cancer research has demonstrated the critical role circulating tumor cells (CTCs play in the metastatic spread of carcinomas and the recurrence of lung cancer. The rapid advancement of technology in targeted therapy resolves the embarrassing situation for those late-stage patients whose tumor tissues cannot be obtained. CTCs, as a substitute for the tumor tissues, represent a decisive tool to the cancer treatment strategy. Thus, CTCs exert a fundamental role in the early detection of micro-metastasis, assisting in diagnosis, prognosis and monitoring of the recurrent tumors, and subsequently choosing an individualized approach for the therapeutic treatment. This article will review the advances, which have been made in the research area of CTCs with the aid of its applications in cancer therapy.

  15. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

    OpenAIRE

    MOMOZONO, HIROYUKI; Miyake, Hideaki; TEI, HIROMOTO; Harada, Ken-ichi; Fujisawa, Masato

    2016-01-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With...

  16. Dendritic cell-based cancer immunotherapy for colorectal cancer

    OpenAIRE

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are curr...

  17. Targeted therapies in small cell lung cancer

    OpenAIRE

    LU, HONG-YANG; Wang, Xiao-Jia; Mao, Wei-Min

    2012-01-01

    Lung cancer is the leading cause of cancer-related mortality. Small cell lung cancer (SCLC) accounted for 12.95% of all lung cancer histological types in 2002. Despite trends toward modest improvement in survival, the outcome remains extremely poor. Chemotherapy is the cornerstone of treatment in SCLC. More than two-thirds of patients who succumb to lung cancer in the United States are over 65 years old. Elderly patients tolerate chemotherapy poorly and need novel therapeutic agents. Targeted...

  18. Mitochondria, cholesterol and cancer cell metabolism.

    Science.gov (United States)

    Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C

    2016-12-01

    Given the role of mitochondria in oxygen consumption, metabolism and cell death regulation, alterations in mitochondrial function or dysregulation of cell death pathways contribute to the genesis and progression of cancer. Cancer cells exhibit an array of metabolic transformations induced by mutations leading to gain-of-function of oncogenes and loss-of-function of tumor suppressor genes that include increased glucose consumption, reduced mitochondrial respiration, increased reactive oxygen species generation and cell death resistance, all of which ensure cancer progression. Cholesterol metabolism is disturbed in cancer cells and supports uncontrolled cell growth. In particular, the accumulation of cholesterol in mitochondria emerges as a molecular component that orchestrates some of these metabolic alterations in cancer cells by impairing mitochondrial function. As a consequence, mitochondrial cholesterol loading in cancer cells may contribute, in part, to the Warburg effect stimulating aerobic glycolysis to meet the energetic demand of proliferating cells, while protecting cancer cells against mitochondrial apoptosis due to changes in mitochondrial membrane dynamics. Further understanding the complexity in the metabolic alterations of cancer cells, mediated largely through alterations in mitochondrial function, may pave the way to identify more efficient strategies for cancer treatment involving the use of small molecules targeting mitochondria, cholesterol homeostasis/trafficking and specific metabolic pathways. PMID:27455839

  19. Cell of origin of lung cancer

    Directory of Open Access Journals (Sweden)

    Jennifer M Hanna

    2013-01-01

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide, and current therapies are disappointing. Elucidation of the cell(s of origin of lung cancer may lead to new therapeutics. In addition, the discovery of putative cancer-initiating cells with stem cell properties in solid tumors has emerged as an important area of cancer research that may explain the resistance of these tumors to currently available therapeutics. Progress in our understanding of normal tissue stem cells, tumor cell of origin, and cancer stem cells has been hampered by the heterogeneity of the disease, the lack of good in vivo transplantation models to assess stem cell behavior, and an overall incomplete understanding of the epithelial stem cell hierarchy. As such, a systematic computerized literature search of the MEDLINE database was used to identify articles discussing current knowledge about normal lung and lung cancer stem cells or progenitor cells. In this review, we discuss what is currently known about the role of cancer-initiating cells and normal stem cells in the development of lung tumors.

  20. CD24 negative lung cancer cells, possessing partial cancer stem cell properties, cannot be considered as cancer stem cells

    OpenAIRE

    Xu, Haineng; Mu, Jiasheng; Xiao, Jing; Wu, Xiangsong; Li, Maolan; Liu, Tianrun; Liu, Xinyuan

    2015-01-01

    Cancer stem cells (CSCs) play vital role in lung cancer progression, resistance, metastasis and relapse. Identifying lung CSCs makers for lung CSCs targeting researches are critical for lung cancer therapy. In this study, utilizing previous identified lung CSCs as model, we compared the expression of CD24, CD133 and CD44 between CSCs and non-stem cancer cells. Increased ratio of CD24- cells were found in CSCs. CD24- cells were then sorted by flow cytometry and their proliferative ability, che...

  1. Sensitivity of mononuclear cells to UV radiation; effect on subsequent stimulation with phytohemagglutinin

    International Nuclear Information System (INIS)

    The ability of peripheral blood mononuclear cells to incorporate 3[H] thymidine into nuclear DNA following stimulation by phytohemagglutinin is reduced by prior exposure to UV radiation in vitro; the reduction is dose and wavelength dependent. The doses required to affect this function of mononuclear cells are higher than the doses required to reduce trypan blue dye exclusion, so that following exposure to radiation populations of cells that are unable to exclude trypan blue dye are still capable of responding to phytohemagglutinin. This finding indicates that trypan blue dye exclusion may not accurately reflect the viability of cells after exposure to UV radiation. (author)

  2. Mechanisms of Therapeutic Resistance in Cancer (Stem) Cells with Emphasis on Thyroid Cancer Cells

    OpenAIRE

    Hombach-Klonisch, Sabine; Natarajan, Suchitra; Thanasupawat, Thatchawan; Medapati, Manoj; PATHAK, ALOK; Ghavami, Saeid; Klonisch, Thomas

    2014-01-01

    The two main reasons for death of cancer patients, tumor recurrence and metastasis, are multi-stage cellular processes that involve increased cell plasticity and coincide with elevated resistance to anti-cancer treatments. Epithelial-to-mesenchymal transition (EMT) is a key contributor to metastasis in many cancer types, including thyroid cancer and is known to confer stem cell-like properties onto cancer cells. This review provides an overview of molecular mechanisms and factors known to con...

  3. Fluoropyrimidine sensitivity of human MCF-7 breast cancer cells stably transfected with human uridinehosphorylase

    OpenAIRE

    Cuq, P; Rouquet, C; Evrard, A.; Ciccolini, J; Vian, L; Cano, J-P

    2001-01-01

    The relationship between uridine phosphorylase (UP) expression level in cancer cells and the tumour sensitivity to fluoropyrimidines is unclear. In this study, we found that UP overexpression by gene transfer, and the subsequent efficient metabolic activation of 5-fluorouracil (5-FU) by the ribonucleotide pathway, does not increase the fluoropyrimidine sensitivity of MCF-7 human cancer cells. © 2001 Cancer Research Campaign http://www.bjcancer.com

  4. The biology of cancer stem cells.

    Science.gov (United States)

    Lobo, Neethan A; Shimono, Yohei; Qian, Dalong; Clarke, Michael F

    2007-01-01

    Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies. PMID:17645413

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

    OpenAIRE

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

    2010-01-01

    Abstract Background 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 b...

  6. Small cell cervical cancer: an unusual finding at cholecystectomy.

    LENUS (Irish Health Repository)

    Boyle, Emily

    2012-02-01

    BACKGROUND: Small cell carcinoma of the cervix is a rare cancer, comprising less than 3% of all cervical neoplasms. It uniformly has a poor prognosis, and has a high mortality even with early stage disease. It can metastasise rapidly and metastatic sites include lung, liver, brain, bone, pancreas and lymph nodes. CASE: Here, we report the case of a 60-year-old woman with no symptoms of cervical pathology who developed post-renal failure following a laparoscopic cholecystectomy. The cause was bilateral ureteric obstruction from metastatic small cell cervical cancer and metastases were subsequently found on her gallbladder specimen. CONCLUSION: This is an unusual presentation of small cell cervical cancer and demonstrates the aggressive nature of this disease.

  7. Prognostic Effects of Adjuvant Chemotherapy-Induced Amenorrhea and Subsequent Resumption of Menstruation for Premenopausal Breast Cancer Patients.

    Science.gov (United States)

    Jeon, Se Jeong; Lee, Jae Il; Jeon, Myung Jae; Lee, Maria

    2016-04-01

    Chemotherapy-induced amenorrhea (CIA) is a side effect that occurs in patients with breast cancer (BC) as a result of chemotherapy. These patients require special treatments to avoid infertility and menopause. However, the factors controlling CIA, resumption of menstruation (RM), and persistence of menstruation after chemotherapy are unknown. The long-term prognosis for premenopausal patients with BC and the prognostic factors associated with CIA and RM are subject to debate. We performed a retrospective study by reviewing the medical records of 249 patients with BC (stage I to stage III) who were treated with cytotoxic chemotherapy. The median patient age was 43 (range, 26-55 years) and the median duration of follow-up was 64 months (range, 28-100 months). The medical records indicated that 219 patients (88.0%) scored as positive for the hormone receptor (HR); the majority of these patients completed chemotherapy and then received additional therapy of tamoxifen. Our analyses revealed that 88.0% (n = 219) of patients experienced CIA, and the percentage of RM during follow-up was 48.6% (n = 121). A total of 30 patients (12.0%) did not experience CIA. Disease-free survival (DFS) was affected by several factors, including tumour size ≥2 cm, node positivity, HR negative status, and body mass index ≥23 kg/m. Multivariate analysis indicated that tumour size ≥2 cm remained as a significant factor for DFS (hazard ratio = 3.3, P = 0.034). In summary, this study finds that the majority of premenopausal patients with BC (stage I to stage III) who receive chemotherapy experience CIA and subsequent RM. Although tumour size ≥2 cm is negatively associated with DFS, RM after CIA is not associated with poor prognosis. PMID:27057900

  8. Cancer Stem Cells: From Bench to Bedside

    OpenAIRE

    Jones, Richard J.; Matsui, William

    2007-01-01

    Objective clinical responses to anticancer treatments often do not translate into substantial improvements in overall survival. Recent data suggesting many cancers arise from rare self-renewing cells (cancer stem cells) that are biologically distinct from their more numerous differentiated progeny, may explain this paradox. Current anticancer therapies have been developed to target the bulk of the tumor mass (i.e., the differentiated cancer cells). Although treatments directed against the bul...

  9. Dielectrophoretic separation of colorectal cancer cells

    OpenAIRE

    Yang, Fang; Yang, Xiaoming; Jiang, Hong; Bulkhaults, Phillip; Wood, Patricia; Hrushesky, William; Wang, Guiren

    2010-01-01

    Separation of colorectal cancer cells from other biological materials is important for stool-based diagnosis of colorectal cancer. In this paper, we use conventional dielectrophoresis in a microfluidic chip to manipulate and isolate HCT116 colorectal cancer cells. It is noticed that at a particular alternating current frequency band, the HCT116 cells are clearly deflected to a side channel from the main channel after the electric activation of an electrode pair. This motion caused by negative...

  10. The Implications of Cancer Stem Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wenjing Jiang

    2012-12-01

    Full Text Available Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Recent studies have showed that cancer stem cells (CSCs, a small subpopulation of tumor cells, can generate bulk populations of nontumorigenic cancer cell progeny through the self-renewal and differentiation processes. As CSCs are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors, development of CSC-targeted therapeutic strategies holds new hope for improving survival and quality of life in patients with cancer. Therapeutic innovations will emerge from a better understanding of the biology and environment of CSCs, which, however, are largely unexplored. This review summarizes the characteristics, evidences and development of CSCs, as well as implications and challenges for cancer treatment.

  11. ATM-deficient human fibroblast cells are resistant to low levels of DNA double-strand break induced apoptosis and subsequently undergo drug-induced premature senescence

    International Nuclear Information System (INIS)

    Highlights: ► A-T cells were not hypersensitive to low levels of DNA DSBs. ► A-T cells have enhanced Akt but defect in activation of p53 and apoptotic proteins. ► A-T cells underwent premature senescence after DNA damage accumulated. ► Chemotherapeutic effect in cancer therapy may be associated with premature senescence. -- Abstract: DNA DSBs are induced by IR or radiomimetic drugs such as doxorubicin. It has been indicated that cells from ataxia-telangiectasia patients are highly sensitive to radiation due to defects in DNA repair, but whether they have impairment in apoptosis has not been fully elucidated. A-T cells showed increased sensitivity to high levels of DNA damage, however, they were more resistant to low doses. Normal cells treated with combination of KU55933, a specific ATM kinase inhibitor, and doxorubicin showed increased resistance as they do in a similar manner to A-T cells. A-T cells have higher viability but more DNA breaks, in addition, the activations of p53 and apoptotic proteins (Bax and caspase-3) were deficient, but Akt expression was enhanced. A-T cells subsequently underwent premature senescence after treatment with a low dose of doxorubicin, which was confirmed by G2 accumulation, senescent morphology, and SA-β-gal positive until 15 days repair incubation. Finally, A-T cells are radio-resistant at low doses due to its defectiveness in detecting DNA damage and apoptosis, but the accumulation of DNA damage leads cells to premature senescence.

  12. ATM-deficient human fibroblast cells are resistant to low levels of DNA double-strand break induced apoptosis and subsequently undergo drug-induced premature senescence

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun; Jo, Yong Hwa; Cho, Chang Hoon; Choe, Wonchae; Kang, Insug; Baik, Hyung Hwan [Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, 26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Yoon, Kyung-Sik, E-mail: sky9999@khu.ac.kr [Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, 26 Kyunghee-daero, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer A-T cells were not hypersensitive to low levels of DNA DSBs. Black-Right-Pointing-Pointer A-T cells have enhanced Akt but defect in activation of p53 and apoptotic proteins. Black-Right-Pointing-Pointer A-T cells underwent premature senescence after DNA damage accumulated. Black-Right-Pointing-Pointer Chemotherapeutic effect in cancer therapy may be associated with premature senescence. -- Abstract: DNA DSBs are induced by IR or radiomimetic drugs such as doxorubicin. It has been indicated that cells from ataxia-telangiectasia patients are highly sensitive to radiation due to defects in DNA repair, but whether they have impairment in apoptosis has not been fully elucidated. A-T cells showed increased sensitivity to high levels of DNA damage, however, they were more resistant to low doses. Normal cells treated with combination of KU55933, a specific ATM kinase inhibitor, and doxorubicin showed increased resistance as they do in a similar manner to A-T cells. A-T cells have higher viability but more DNA breaks, in addition, the activations of p53 and apoptotic proteins (Bax and caspase-3) were deficient, but Akt expression was enhanced. A-T cells subsequently underwent premature senescence after treatment with a low dose of doxorubicin, which was confirmed by G2 accumulation, senescent morphology, and SA-{beta}-gal positive until 15 days repair incubation. Finally, A-T cells are radio-resistant at low doses due to its defectiveness in detecting DNA damage and apoptosis, but the accumulation of DNA damage leads cells to premature senescence.

  13. Cancer Stem Cells in Lung Tumorigenesis

    OpenAIRE

    Kratz, Johannes R.; Yagui-Beltrán, Adam; Jablons, David M.

    2010-01-01

    Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continue...

  14. Role of stem cells in cancer therapy and cancer stem cells: a review

    OpenAIRE

    Sales Kevin; Chaib Boussad; Sagar Jayesh; Winslet Marc; Seifalian Alexander

    2007-01-01

    Abstract For over 30 years, stem cells have been used in the replenishment of blood and immune systems damaged by the cancer cells or during treatment of cancer by chemotherapy or radiotherapy. Apart from their use in the immuno-reconstitution, the stem cells have been reported to contribute in the tissue regeneration and as delivery vehicles in the cancer treatments. The recent concept of 'cancer stem cells' has directed scientific communities towards a different wide new area of research fi...

  15. Treatment Options by Stage (Small Cell Lung Cancer)

    Science.gov (United States)

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

  16. Adipocyte activation of cancer stem cell signaling in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2015-01-01

    Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

  17. Interleukin 1 beta initially sensitizes and subsequently protects murine intestinal stem cells exposed to photon radiation

    International Nuclear Information System (INIS)

    Interleukin 1 (IL-1) has been shown to prevent early bone marrow-related death following total-body irradiation, by protecting hematopoietic stem cells and speeding marrow repopulation. This study assesses the effect of IL-1 on the radiation response of the intestinal mucosal stem cell, a nonhematopoietic normal cell relevant to clinical radiation therapy. As observed with bone marrow, administration of human recombinant IL-1 beta (4 micrograms/kg) to C3H/Km mice 20 h prior to total-body irradiation modestly protected duodenal crypt cells. In contrast to bone marrow, IL-1 given 4 or 8 h before radiation sensitized intestinal crypt cells. IL-1 exposure did not substantially alter the slope of the crypt cell survival curve but did affect the shoulder: the X-ray survival curve was offset to the right by 1.01 +/- 0.06 Gy when IL-1 was given 20 h earlier and by 1.28 +/- 0.08 Gy to the left at the 4-h interval. Protection was greatest when IL-1 was administered 20 h before irradiation, but minimal effects persisted as long as 7 days after a single injection. The magnitude of radioprotection at 20 h or of radiosensitization at 4 h increased rapidly as IL-1 dose increased from 0 to 4 micrograms/kg. However, doses ranging from 10 to 100 micrograms/kg produced no further difference in radiation response. Animals treated with saline or IL-1 had similar core temperatures from 4 to 24 h after administration, suggesting that thermal changes were not responsible for either sensitization or protection. Mice irradiated 20 h after IL-1 had significantly greater crypt cell survival than saline-treated irradiated controls at all assay times, which ranged from 54 to 126 h following irradiation. The intervals to maximum crypt depopulation and initiation of repopulation were identical in both saline- and IL-1-treated groups

  18. Confocal Raman imaging for cancer cell classification

    Science.gov (United States)

    Mathieu, Evelien; Van Dorpe, Pol; Stakenborg, Tim; Liu, Chengxun; Lagae, Liesbet

    2014-05-01

    We propose confocal Raman imaging as a label-free single cell characterization method that can be used as an alternative for conventional cell identification techniques that typically require labels, long incubation times and complex sample preparation. In this study it is investigated whether cancer and blood cells can be distinguished based on their Raman spectra. 2D Raman scans are recorded of 114 single cells, i.e. 60 breast (MCF-7), 5 cervix (HeLa) and 39 prostate (LNCaP) cancer cells and 10 monocytes (from healthy donors). For each cell an average spectrum is calculated and principal component analysis is performed on all average cell spectra. The main features of these principal components indicate that the information for cell identification based on Raman spectra mainly comes from the fatty acid composition in the cell. Based on the second and third principal component, blood cells could be distinguished from cancer cells; and prostate cancer cells could be distinguished from breast and cervix cancer cells. However, it was not possible to distinguish breast and cervix cancer cells. The results obtained in this study, demonstrate the potential of confocal Raman imaging for cell type classification and identification purposes.

  19. Epigenetic targeting of ovarian cancer stem cells.

    Science.gov (United States)

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P; Matei, Daniela

    2014-09-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH(+) ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH(+) cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem-like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  20. 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.

  1. Breathless cancer cells get fat on glutamine

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Anastasiou; Lewis C Cantley

    2012-01-01

    Many cancer cells depend on glutamine as a fuel for proliferation,yet the mechanisms by which glutamine supports cancer metabolism are not fully understood.Two recent studies highlight an important role for glutamine in the synthesis of lipids and provide novel insights into how glutamine metabolism could be targeted for cancer therapy.

  2. Cancer stem cell targeted therapy: progress amid controversies

    OpenAIRE

    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 illu...

  3. Relationship between somatic cell count status and subsequent clinical mastitis in Dutch dairy cows

    NARCIS (Netherlands)

    Borne, van den B.H.P.; Vernooij, J.C.M.; Lupindu, A.M.; Schaik, van G.; Frankena, K.; Lam, T.J.G.M.; Nielen, M.

    2011-01-01

    High composite somatic cell counts (CSCC) in dairy cows may develop into clinical mastitis (CM), suggesting that prevention or intervention of high CSCC may prevent CM later in lactation. The objective of this study was to quantify the relationship between high CSCC in dairy cows and the first subse

  4. Iron induces cancer stem cells and aggressive phenotypes in human lung cancer cells.

    Science.gov (United States)

    Chanvorachote, Pithi; Luanpitpong, Sudjit

    2016-05-01

    Evidence has accumulated in support of the critical impact of cancer stem cells (CSCs) behind the chemotherapeutic failure, cancer metastasis, and subsequent disease recurrence and relapse, but knowledge of how CSCs are regulated is still limited. Redox status of the cells has been shown to dramatically influence cell signaling and CSC-like aggressive behaviors. Here, we investigated how subtoxic concentrations of iron, which have been found to specifically induce cellular hydroxyl radical, affected CSC-like subpopulations of human non-small cell lung carcinoma (NSCLC). We reveal for the first time that subchronic iron exposure and higher levels of hydroxyl radical correlated well with increased CSC-like phenotypes. The iron-exposed NSCLC H460 and H292 cells exhibited a remarkable increase in propensities to form CSC spheroids and to proliferate, migrate, and invade in parallel with an increase in level of a well-known CSC marker, ABCG2. We further observed that such phenotypic changes induced by iron were not related to an epithelial-to-mesenchymal transition (EMT). Instead, the sex-determining region Y (SRY)-box 9 protein (SOX9) was substantially linked to iron treatment and hydroxyl radical level. Using gene manipulations, including ectopic SOX9 overexpression and SOX9 short hairpin RNA knockdown, we have verified that SOX9 is responsible for CSC enrichment mediated by iron. These findings indicate a novel role of iron via hydroxyl radical in CSC regulation and its importance in aggressive cancer behaviors and likely metastasis through SOX9 upregulation. PMID:26911281

  5. 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

    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...... 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...... SED, P < 0.0001), and when reduced to 1 SED, the median delays were 18 days (2 SED, P = 0.0469) and 33 days (4 SED, P < 0.0001). The median delay to the third tumor was after UV reduction 47 days (4 SED, P < 0.0001) and 35 days (2 SED, P = 0.151), and after UV discontinuation 49 days (4 SED, P < 0...

  6. Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration.

    Science.gov (United States)

    Wang, Hui-Chen; Lee, Wen-Sen

    2016-01-01

    Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation, and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration, and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells. PMID:27510838

  7. Resveratrol induces apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jia-hua; CHENG Hai-yan; YU Ze-qian; HE Dao-wei; PAN Zheng; YANG De-tong

    2011-01-01

    Background Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years.Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer.The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells.Methods Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines.Results In the screened pancreatic cancer cell lines, capan-2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells,capan-2 and colo357, the activation of caspase-3 was detected and showed significant caspase-3 activation upon resveratrol treatment; p53 and p21 were also detected up-regulated upon resveratrol treatment.Conclusion Resveratrol provides a promising anti-tumor stratagy to fight against pancreatic cancer.

  8. Markers of small cell lung cancer

    OpenAIRE

    Sharma SK; Taneja Tarvinder

    2004-01-01

    Abstract Lung cancer is the number one cause of cancer death; however, no specific serum biomarker is available till date for detection of early lung cancer. Despite good initial response to chemotherapy, small-cell lung cancer (SCLC) has a poor prognosis. Therefore, it is important to identify molecular markers that might influence survival and may serve as potential therapeutic targets. The review aims to summarize the current knowledge of serum biomarkers in SCLC to improve diagnostic effi...

  9. Chlorpromazine inhibits store-operated calcium entry and subsequent noradrenaline secretion in PC12 cells

    OpenAIRE

    Choi, Se-Young; Kim, Yong-Hyun; Lee, Yong-kyu; Kim, Kyong-Tai

    2001-01-01

    The effect of chlorpromazine on the store-operated Ca2+ entry activated via the phospholipase C signalling pathway was investigated in PC12 cells.Chlorpromazine inhibited the sustained increase after the initial peak in the intracellular Ca2+ concentration produced by bradykinin while having no effect on the initial transient response. The inhibition was lowered by the removal of extracellular free Ca2+. However, chlorpromazine did not inhibit bradykinin-induced inositol 1,4,5-trisphosphate p...

  10. 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.

  11. Targeting prostate cancer stem cells for cancer therapy

    OpenAIRE

    Wang, Guocan; Wang, Zhiwei; Sarkar, Fazlul H; Wei, Wenyi

    2012-01-01

    Prostate cancer (PCa) is the most common malignant neoplasm in men and the second most frequent cause of cancer death for males in the United States. Recently, emerging evidence suggests that prostate cancer stem cells (CSCs) may play a critical role in the development and progression of PCa. Therefore, targeting prostate CSCs for the prevention of tumor progression and treatment of PCa could become a novel strategy for better treatment of patients diagnosed with PCa. In this review article, ...

  12. Metastatic renal cell cancer treatments.

    Science.gov (United States)

    Sternberg, C N

    2003-01-01

    Metastatic renal cell carcinoma has been considered to be resistant to chemotherapy, with responses observed in only limited numbers of patients. For this reason, therapeutic options have ranged from no treatment, to immunotherapy with cytokines such as IL-2 and interferon-alpha, chemotherapy alone or in combination with cytokines, and to a variety of new investigational approaches. Interferon and interleukin-2 (IL-2) have led to long-term survival in selected patients. Immunotherapy with cytokines, monoclonal antibodies, new agents, dendritic cell therapy, and allotransplantation offer promise. Novel therapeutic strategies include combining cytokines, and antiangiogenic approaches such as thalidomide and antivascular endothelial growth factor therapy. Pathologic, cytogenic and molecular studies have proven that renal cell carcinoma is not a single tumor entity. Efforts to improve results also include the identification of prognostic factors, which allow treatment to be better directed towards those patients most likely to benefit. Increasing understanding of cancer biology is beginning to allow for a more targeted approach to the therapy of metastatic renal cell carcinoma. Adequate positioning of known treatments is essential and many trials of new targeted therapies are underway. PMID:14988745

  13. Multiple skin cancers in a single patient: Multiple pigmented Bowen′s disease, giant basal cell carcinoma, squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ravi Saini

    2015-01-01

    Full Text Available Basal cell carcinoma (BCC and squamous cell carcinoma are the most common type of nonmelanoma skin cancers (NMSCs. Bowen′s disease (BD, a premalignant condition, has a marginal potential (3-5% to progress to invasive carcinoma. We report here a rarest of a rare case of multiple pigmented BD with overlying squamous cell cancer along with a giant neglected BCC on the scalp of a 76-year-old man. The occurrence of multiple BD and NMSC in a single patient compelled us to explore the following hypothesis: (1 The multiple precancerous and cancerous lesions can be due to common etiopathogenesis. Chronic ultraviolet exposure, immunosupresssion, human papillomavirus infection, dietary factors, and environmental factors including arsenic exposure were probed in to. (2 There is evolution of precancerous lesions into a different type of cancers in different time frame. (3 The new cancerous lesions are subsequent cancers that developed after neglected untreated primary cancer.

  14. 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

  15. Tracheal metastasis of small cell lung cancer

    OpenAIRE

    De, Sajal

    2009-01-01

    Endotracheal metastases of primary lung cancer are rare. Only one case of tracheal metastasis from small cell lung cancer has been reported in literature. Here, we report a rare case of a 45-year-old woman who was admitted for sudden-onset breathlessness with respiratory failure and required ventilatory support. Endotracheal growth was identified during bronchoscopy, and biopsy revealed endotracheal metastasis of small cell lung cancer.

  16. Repopulation of Ovarian Cancer Cells After Chemotherapy

    OpenAIRE

    Telleria, Carlos M.

    2013-01-01

    The high mortality rate caused by ovarian cancer has not changed for the past thirty years. Although most patients diagnosed with this disease respond to cytoreductive surgery and platinum-based chemotherapy and undergo remission, foci of cells almost always escape therapy, manage to survive, and acquire the capacity to repopulate the tumor. Repopulation of ovarian cancer cells that escape front-line chemotherapy, however, is a poorly understood phenomenon. Here I analyze cancer-initiating ce...

  17. Cell phones - do they cause cancer?

    Science.gov (United States)

    ... cancer URL of this page: //medlineplus.gov/ency/article/007151.htm Cell phones and cancer To use the sharing features ... adults. For this reason, some agencies and government organizations recommend that children avoid prolonged use of cell phones. REDUCING RISKS Although health problems related to ...

  18. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    OpenAIRE

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-01-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and sup...

  19. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    OpenAIRE

    Wenke YUE; JIAO, FENG; Liu, Bin; Jiacong YOU; Zhou, Qinghua

    2011-01-01

    Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung can...

  20. Personalized Therapy of Non-small Cell Lung Cancer (NSCLC).

    Science.gov (United States)

    Gadgeel, Shirish M

    2016-01-01

    Lung cancer remains the most common cause of cancer related deaths in both men and women in the United States and non-small cell lung cancer (NSCLC) accounts for over 85 % of all lung cancers. Survival of these patients has not significantly altered in over 30 years. This chapter initially discusses the clinical presentation of lung cancer patients. Most patients diagnosed with lung cancer due to symptoms have advanced stage cancer. Once diagnosed, lung cancer patients need imaging studies to assess the stage of the disease before decisions regarding therapy are finalized. The most important prognostic factors are stage of the disease and performance status and these factors also determine therapy. The chapter subsequently discusses management of each stage of the disease and the impact of several pathologic, clinical factors in personalizing therapy for each individual patient. Transition from chemotherapy for every patient to a more personalized approach based on histology and molecular markers has occurred in the management of advanced stage NSCLC. It is expected that such a personalized approach will extend to all stages of NSCLC and will likely improve the outcomes of all NSCLC patients. PMID:26703806

  1. In vitro cytotoxicity evaluation of HDAC inhibitor Apicidin in pancreatic carcinoma cells subsequent time and dose dependent treatment.

    Science.gov (United States)

    Bauden, Monika; Tassidis, Helena; Ansari, Daniel

    2015-07-01

    Apicidin is a potent histone deacetylase inhibitor (HDACI) that selectively binds to histone deacetylases (HDACs) class I and interferes with the deacetylation process, which results in modification of acetylation level of cellular proteins. The aim of the study was to investigate the potential time and dose dependent cytotoxicity of the test compound, Apicidin, in pancreatic cancer cells Capan-1 and Panc-1 as well as estimate maximal tolerable dose (MTD) of the test agent and determine EC50 using four complementary colorimetric cytotoxicity or viability assays. The cells were treated with increasing concentrations of Apicidin (0-5000nM) for 2, 4 and 6h (short term exposure) or 24, 48 and 72h (long term exposure) before conducting cytotoxic analyses with lactate dehydrogenase assay or viability analyses with sulforhodamine B (SRB), methyl tetrazolium (MTT) and crystal violet (CV) assays. In order to investigate whether Apicidin irreversibly affects the cells already during the short term exposure, the medium containing Apicidin was removed and replaced with fresh culturing medium after 6h of treatment. The cells were then incubated for additional 24, 48 or 72h before carrying out the analysis. The results obtained from cytotoxicity and viability assays indicated, that Apicidin was well tolerated by both cell lines at concentrations below 100nM at any given time point and at all applied concentrations during the short term (6h or less) treatment. Continuous prolonged term exposures (48h or greater) of the cells to Apicidin with concentration exceeding 100nM resulted in significantly increasing cytotoxicity and sustained significant loss of cell viability. Moreover, long term exposure of pancreatic cancer cells Capan-1 and Panc-1 to Apicidin concentrations exceeding 100nM showed an initial anti-proliferative effect before cytotoxicity onset. In summary, MTD was exposure time dependent and estimated to 100nM for long term treatment and to at least 5000nM for treatment

  2. 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.

  3. H. pylori seropositivity before age 40 and subsequent risk of stomach cancer: a glimpse of the true relationship?

    Directory of Open Access Journals (Sweden)

    Christina Persson

    Full Text Available Stomach carcinogenesis involves mucosal and luminal changes that favor spontaneous disappearance of Helicobacter pylori. Therefore, the association between the infection and cancer risk might typically be underestimated. As acquisition of the infection almost invariably occurs before adulthood, the serostatus at age 16-40 should best reflect the lifetime occurrence of the infection. We therefore conducted a case-control study nested within a historic cohort of about 400,000 individuals who donated sera before age 40 to either of two large Swedish Biobanks between 1968 and 2006, and whose records were linked to complete nationwide registers. For each stomach adenocarcinoma case occurring at least 5 years after serum donation 2 controls were selected matched on age, sex and year of donation and biobank. Serum immunoglobulin G antibodies against H. pylori cell-surface antigens (Hp-CSAs were measured with an enzyme-linked immunosorbent assay and antibodies against CagA with an immunoblot assay. Conditional logistic regression models were used to estimate odds ratios (ORs for stomach adenocarcinoma among H. pylori infected relative to uninfected. We confirmed 59 incident cases of stomach adenocarcinoma (41 non-cardia tumors during follow-up. ORs for non-cardia stomach adenocarcinoma among subjects with Hp-CSA antibodies (regardless of CagA serostatus, antibodies against CagA (regardless of Hp-CSA serostatus, and antibodies to both, relative to those who were seronegative to both, were 17.1 (95% confidence interval [CI] 4.0-72.9, 10.9 (95% CI 3.2-36.9, and 48.5 (95% CI 5.8-407.4, respectively. H. pylori infection is a much stronger risk factor for non-cardia stomach adenocarcinoma than initially realized. However, further studies are needed to answer whether it is a necessary cause, as the possibility of misclassification of H. pylori status could not be ruled out in our study.

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

    International Nuclear Information System (INIS)

    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

  6. Wnt Signaling in Cancer Stem Cell Biology

    Science.gov (United States)

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  7. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells

    DEFF Research Database (Denmark)

    Collombat, Patrick; Xu, Xiaobo; Ravassard, Philippe;

    2009-01-01

    We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-spec...... cell mass and curing diabetes in animals that have been chemically depleted of beta cells....

  8. Fentanyl inhibits cell viability in human pancreatic cancer cell line and tumor growth in pancreatic cancer cell-transplanted mice

    OpenAIRE

    Miao, Jianxia; Wang, Liangrong; Chen, Lei; Yang, Tao; Jin, Lida; Lin, Lina

    2015-01-01

    Pancreatic cancer is a kind of devastating disease with a high mortality rate. Fentanyl has been widely applied to anesthesia and analgesia in pancreatic cancer therapy, and is also demonstrated to inhibit the growth of some kinds of cancer cells in existed studies. To investigate the functions of fentanyl in pancreatic cancer, we conducted a series of in vivo and in vitro experiments using human pancreatic cancer cells SW1990 and fentanyl treatment. The cells were transplanted to BALB/c nude...

  9. Dendritic cell-based cancer immunotherapy for colorectal cancer

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. PMID:27158196

  10. Circulating cancer stem cells: the importance to select.

    Science.gov (United States)

    Yang, Ming-Hsin; Imrali, Ahmet; Heeschen, Christopher

    2015-10-01

    It has been demonstrated that even localized tumors without clinically apparent metastasis give rise to circulating tumor cells (CTCs). A growing number of technically diverse platforms are being developed for detecting/isolating CTCs in the circulating blood. Despite the technical challenges of isolating rare CTCs from blood, recent studies have already shown the predictive value of CTCs enumeration. Thus, it is becoming increasingly accepted that CTC numbers are linked to patients' outcome and may also be used to monitor treatment response and disease relapse, respectively. Further CTCs provide a non-invasive source for tumor material, 'liquid biopsy', which is particularly important for patients, where no biopsy material can be obtained or where serial biopsies of the tumor, e.g., following treatment, are practically impossible. On the other hand the molecular and biological characterization of CTCs has still remained at a rather experimental stage. Future studies are necessary to define CTC heterogeneity to establish the crucial role of circulating cancer stem cells for driving metastasis, which represent a distinct subpopulation of CTCs that bear metastasis-initiating capabilities based on their stemness properties and invasiveness and thus are critical for the patients' clinical outcome. As compared to non-tumorigenic/metastatic bulk CTCs, circulating cancer stem cells may not only be capable of evading from the primary tumor, but also escape from immune surveillance, survive in the circulating blood and subsequently form metastases in distant organs. Thus, circulating cancer stem cells represent a subset of exclusively tumorigenic cancer stem cells characterized by their invasive characteristics and are potential therapeutic targets for preventing disease progression. To date, only a few original reports and reviews have been published focusing on circulating cancer stem cells. This review discusses the potential importance of isolating and characterizing

  11. Cancer Stem Cells in the Thyroid

    Science.gov (United States)

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

    The cancer stem cell (CSC) model posits that CSCs are a small, biologically distinct subpopulation of cancer cells in each tumor that have self-renewal and multi-lineage potential, and are critical for cancer initiation, metastasis, recurrence, and therapy-resistance. Numerous studies have linked CSCs to thyroid biology, but the candidate markers and signal transduction pathways that drive thyroid CSC growth are controversial, the origin(s) of thyroid CSCs remain elusive, and it is unclear whether thyroid CSC biology is consistent with the original hierarchical CSC model or the more recent dynamic CSC model. Here, we critically review the thyroid CSC literature with an emphasis on research that confirmed the presence of thyroid CSCs by in vitro sphere formation or in vivo tumor formation assays with dispersed cells from thyroid cancer tissues or bona fide thyroid cancer cell lines. Future perspectives of thyroid CSC research are also discussed. PMID:26973599

  12. Therapeutic strategies targeting cancer stem cells.

    Science.gov (United States)

    Ning, Xiaoyan; Shu, Jianchang; Du, Yiqi; Ben, Qiwen; Li, Zhaoshen

    2013-04-01

    Increasing studies have demonstrated a small proportion of cancer stem cells (CSCs) exist in the cancer cell population. CSCs have powerful self-renewal capacity and tumor-initiating ability and are resistant to chemotherapy and radiation. Conventional anticancer therapies kill the rapidly proliferating bulk cancer cells but spare the relatively quiescent CSCs, which cause cancer recurrence. So it is necessary to develop therapeutic strategies acting specifically on CSCs. In recent years, studies have shown that therapeutic agents such as metformin, salinomycin, DECA-14, rapamycin, oncostatin M (OSM), some natural compounds, oncolytic viruses, microRNAs, cell signaling pathway inhibitors, TNF-related apoptosis inducing ligand (TRAIL), interferon (IFN), telomerase inhibitors, all-trans retinoic acid (ATRA) and monoclonal antibodies can suppress the self-renewal of CSCs in vitro and in vivo. A combination of these agents and conventional chemotherapy drugs can significantly inhibit tumor growth, metastasis and recurrence. These strategies targeting CSCs may bring new hopes to cancer therapy. PMID:23358473

  13. Ultrasound Effect on Cancerous versus Non-Cancerous Cells.

    Science.gov (United States)

    Azagury, Aharon; Amar-Lewis, Eliz; Yudilevitch, Yana; Isaacson, Carol; Laster, Brenda; Kost, Joseph

    2016-07-01

    Previous studies have found that cancer cells whose metastatic potential is low are more vulnerable to mechanical stress-induced trauma to their cytoskeleton compared with benign cells. Because ultrasound induces mechanical stresses on cells and tissues, it is postulated that there may be a way to apply ultrasound to tumors to reduce their ability to metastasize. The difference between low-malignant-potential cancer cells and benign cells could be a result of their different responses to the mechanical stress insonation induced. This hypothesis was tested in vitro and in vivo. Low-malignant-potential cells were found to be more sensitive to insonation, resulting in a significantly higher mortality rate compared with that of benign cells, 89% versus 21%, respectively. This effect can be controlled by varying ultrasound parameters: intensity, duration, and duty cycle. Thus, the results presented in this study suggest the application of ultrasound to discriminate between benign and malignant cells. PMID:27067417

  14. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

    OpenAIRE

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T.; Peng, Lifeng; Davis, Paul F.; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is ...

  15. Dietary arsenic intake and subsequent risk of cancer: the Japan Public Health Center-based (JPHC) Prospective Study

    OpenAIRE

    Sawada, Norie; Iwasaki, Motoki; Inoue, Manami; Takachi, Ribeka; Sasazuki, Shizuka; Yamaji, Taiki; Shimazu, Taichi; Tsugane, Shoichiro

    2013-01-01

    Purpose Arsenic is a known human carcinogen and has been linked to adverse health outcomes, including cancer. However, the effects of arsenic exposure from food on health are still unknown. We researched to examine the association between arsenic exposure from food and incidence of cancer in a Japanese population. Methods We conducted a population-based prospective study in 90,378 Japanese men and women aged 45–74 years. Participants responded to a validated questionnaire that included 138 fo...

  16. Hallmarks of cancer stem cell metabolism.

    Science.gov (United States)

    Sancho, Patricia; Barneda, David; Heeschen, Christopher

    2016-06-14

    Cancer cells adapt cellular metabolism to cope with their high proliferation rate. Instead of primarily using oxidative phosphorylation (OXPHOS), cancer cells use less efficient glycolysis for the production of ATP and building blocks (Warburg effect). However, tumours are not uniform, but rather functionally heterogeneous and harbour a subset of cancer cells with stemness features. Such cancer cells have the ability to repopulate the entire tumour and thus have been termed cancer stem cells (CSCs) or tumour-initiating cells (TICs). As opposed to differentiated bulk tumour cells relying on glycolysis, CSCs show a distinct metabolic phenotype that, depending on the cancer type, can be highly glycolytic or OXPHOS dependent. In either case, mitochondrial function is critical and takes centre stage in CSC functionality. Remaining controversies in this young and emerging research field may be related to CSC isolation techniques and/or the use of less suitable model systems. Still, the apparent dependence of CSCs on mitochondrial function, regardless of their primary metabolic phenotype, represents a previously unrecognised Achilles heel amendable for therapeutic intervention. Elimination of highly chemoresistant CSCs as the root of many cancers via inhibition of mitochondrial function bears the potential to prevent relapse from disease and thus improve patients' long-term outcome. PMID:27219018

  17. Every Single Cell Clones from Cancer Cell Lines Growing Tumors In Vivo May Not Invalidate the Cancer Stem Cell Concept

    OpenAIRE

    Li, Fengzhi

    2009-01-01

    We present the result of our research on the tumorigenic ability of single cell clones isolated from an aggressive murine breast cancer cell line in a matched allografting mouse model. Tumor formation is basically dependent on the cell numbers injected per location. We argue that in vivo tumor formation from single cell clones, isolated in vitro from cancer cell lines, may not provide conclusive evidence to disprove the cancer stem cell (CSC) theory without additional data.

  18. Cancer stem cells in head and neck cancer.

    Science.gov (United States)

    Allegra, Eugenia; Trapasso, Serena

    2012-01-01

    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 the presence of specific surface markers for selective cytotoxic agent vehicles. Finally, some research groups are trying to induce these cells to

  19. Gigantol Suppresses Cancer Stem Cell-Like Phenotypes in Lung Cancer Cells

    OpenAIRE

    Narumol Bhummaphan; Pithi Chanvorachote

    2015-01-01

    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 ...

  20. Nonlinear Growth Kinetics of Breast Cancer Stem Cells: Implications for Cancer Stem Cell Targeted Therapy

    Science.gov (United States)

    Liu, Xinfeng; Johnson, Sara; Liu, Shou; Kanojia, Deepak; Yue, Wei; Singn, Udai; Wang, Qian; Wang, Qi; Nie, Qing; Chen, Hexin

    2013-08-01

    Cancer stem cells (CSCs) have been identified in primary breast cancer tissues and cell lines. The CSC population varies widely among cancerous tissues and cell lines, and is often associated with aggressive breast cancers. Despite of intensive research, how the CSC population is regulated within a tumor is still not well understood so far. In this paper, we present a mathematical model to explore the growth kinetics of CSC population both in vitro and in vivo. Our mathematical models and supporting experiments suggest that there exist non-linear growth kinetics of CSCs and negative feedback mechanisms to control the balance between the population of CSCs and that of non-stem cancer cells. The model predictions can help us explain a few long-standing questions in the field of cancer stem cell research, and can be potentially used to predict the efficicacy of anti-cancer therapy.

  1. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

    Androgen refractory prostate cancer metastasis is a major clinical challenge.Mechanism-based approaches to treating prostate cancer metastasis require an understanding of the developmental origin of the metastasis-initiating cell.Properties of prostate cancer metastases such as plasticity with respect to differentiated phenotype and androgen independence are consistent with the transformation of a prostate epithelial progenitor or stem cell leading to metastasis.This review focuses upon current evidence and concepts addressing the identification and properties of normal prostate stem or progenitor cells and their transformed counterparts.

  2. Metformin induces apoptosis of pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To assess the role and mechanism of mefformin in inducing apoptosis of pancreatic cancer cells. METHODS: The human pancreatic cancer cell lines ASPC-1, BxPc-3, PANC-1 and SW1990 were exposed to mefformin. The inhibition of cell proliferation and colony formation via apoptosis induction and S phase arrest in pancreatic cancer cell lines of mefformin was tested.RESULTS: In each pancreatic cancer cell line tested, metformin inhibited cell proliferation in a dose dependent manner in MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays). Flow cytometric analysis showed that metformin reduced the number of cells in G1 and increased the percentage of cells in S phase as well as the apoptotic fraction. Enzymelinked immunosorbent assay (EUSA) showed that metformin induced apaptosis in all pancreatic cancer cell lines. In Western blot studies, metformin induced oly-ADP-ribose polymerase(PARP) cleavage (an indicator of aspase activation) in all pancreatic cancer cell lines. The general caspase inhibitor (VAD-fmk) completely abolished metformin-induced PARP cleavage and apoptosis in ASPC-1 BxPc-3 and PANC-1, the caspase-8 specific inhibitor (IETD-fmk) and the caspase-9 specific inhibitor (LEHD-fmk) only partially abrogated metformin-induced apoptosis and PARP cleavage in BxPc-3 and PANC-1 cells. We also observed that metformin treatment ramatically reduced epidermal growth factor receptor (EGFR) and phosphorylated mitogen activated protein kinase (P-MAPK) in both a time- and dose-dependent manner in all cell lines tested.CONCLUSION: Metformin significantly inhibits cell proliferation and apoptosis in all pancreatic cell lines. And the metformin-induced apoptosis is associated with PARP leavage, activation of caspase-3, -8, and -9 in a time- and dose-dependent manner. Hence, both caspase-8 and -9-initiated apoptotic signaling pathways contribute to metforrnin-induced apoptosis in pancreatic cell lines.

  3. AKT Inhibition Promotes Nonautonomous Cancer Cell Survival.

    Science.gov (United States)

    Salony; Solé, Xavier; Alves, Cleidson P; Dey-Guha, Ipsita; Ritsma, Laila; Boukhali, Myriam; Lee, Ju H; Chowdhury, Joeeta; Ross, Kenneth N; Haas, Wilhelm; Vasudevan, Shobha; Ramaswamy, Sridhar

    2016-01-01

    Small molecule inhibitors of AKT (v-akt murine thymoma viral oncogene homolog) signaling are being evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with subtherapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multiscale, molecular snapshot of this "AKT(low)" cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously upregulate a host of other proteins and metabolites posttranscriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. PMID:26637368

  4. 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)

  5. Identifying cancer origin using circulating tumor cells.

    Science.gov (United States)

    Lu, Si-Hong; Tsai, Wen-Sy; Chang, Ying-Hsu; Chou, Teh-Ying; Pang, See-Tong; Lin, Po-Hung; Tsai, Chun-Ming; Chang, Ying-Chih

    2016-04-01

    Circulating tumor cells (CTCs) have become an established clinical evaluation biomarker. CTC count provides a good correlation with the prognosis of cancer patients, but has only been used with known cancer patients, and has been unable to predict the origin of the CTCs. This study demonstrates the analysis of CTCs for the identification of their primary cancer source. Twelve mL blood samples were equally dispensed on 6 CMx chips, microfluidic chips coated with an anti-EpCAM-conjugated supported lipid bilayer, for CTC capture and isolation. Captured CTCs were eluted to an immunofluorescence (IF) staining panel consisting of 6 groups of antibodies: anti-panCK, anti-CK18, anti-CK7, anti-TTF-1, anti-CK20/anti-CDX2, and anti-PSA/anti-PSMA. Cancer cell lines of lung (H1975), colorectal (DLD-1, HCT-116), and prostate (PC3, DU145, LNCaP) were selected to establish the sensitivity and specificity for distinguishing CTCs from lung, colorectal, and prostate cancer. Spiking experiments performed in 2mL of culture medium or whole blood proved the CMx platform can enumerate cancer cells of lung, colorectal, and prostate. The IF panel was tested on blood samples from lung cancer patients (n = 3), colorectal cancer patients (n = 5), prostate cancer patients (n = 5), and healthy individuals (n = 12). Peripheral blood samples found panCK(+) and CK18(+) CTCs in lung, colorectal, and prostate cancers. CTCs expressing CK7(+) or TTF-1(+), (CK20/ CDX2)(+), or (PSA/ PSMA)(+) corresponded to lung, colorectal, or prostate cancer, respectively. In conclusion, we have designed an immunofluorescence staining panel to identify CTCs in peripheral blood to correctly identify cancer cell origin. PMID:26828696

  6. 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.

  7. Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

    Energy Technology Data Exchange (ETDEWEB)

    Carrasco A, H.; Cardona, W. [Universidad Andres Bello, Vina del Mar (Chile). Dept. de Ciencias Quimicas]. E-mail: hcarrasco@unab.cl; Espinoza C, L.; Gallardo, C.; Catalan M, K. [Universidad Tecnica Federico Santa Maria, Valparaiso (Chile). Dept. de Quimica; Cardile, V.; Lombardo, L. [University of Catania (Italy). Dept. of Physiological Sciences; Cuellar F, M. [Universidad de Valparaiso (Chile). Facultad de Farmacia; Russo, A. [University of Catania (Italy). Dept. of Biological Chemistry, Medical Chemistry and Molecular Biology

    2008-07-01

    Eugenol (4-allyl-2-methoxyphenol) (1) has been reported to possess antioxidant and anticancer properties. In an attempt to enhance intrinsic activity of this natural compound, some derivatives were synthesized. Eugenol was extracted from cloves oil and further, the eugenol analogues (2-6) were obtained through acetylation and nitration reactions. Eugenol (1) and its analogues (2-6) were examined by in vitro model of cancer using two human cancer cell lines: DU-145 (androgeninsensitive prostate cancer cells) and KB (oral squamous carcinoma cells). Cell viability, by tetrazolium salts assay, was measured. Lactic dehydrogenase (LDH) release was also investigated to evaluate the presence of cell toxicity as a result of cell disruption, subsequent to membrane rupture. In the examined cancer cells, all compounds showed cell-growth inhibition activity. The obtained results demonstrate that the compounds 5-allyl-3-nitrobenzene-1,2-diol (3) and 4-allyl- 2-methoxy-5-nitrophenyl acetate (5) were significantly (p < 0,001) more active than eugenol, with IC{sub 50} values in DU-145 cells of 19.02 x 10{sup -6} and 21.5 x 10{sup -6} mol L{sup -1}, respectively, and in KB cells of 18.11 x 10{sup -6} and 21.26 x 10{sup -6} mol L{sup -1}, respectively, suggesting that the presence of nitro and hydroxyl groups could be important in the activity of these compounds. In addition, our results seem to indicate that apoptotic cell demise appears to be induced in KB and DU-145 cells. In fact, in our experimental conditions, no statistically significant increase in LDH release was observed in cancer cells treated with eugenol and its analogues. (author)

  8. Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

    International Nuclear Information System (INIS)

    Eugenol (4-allyl-2-methoxyphenol) (1) has been reported to possess antioxidant and anticancer properties. In an attempt to enhance intrinsic activity of this natural compound, some derivatives were synthesized. Eugenol was extracted from cloves oil and further, the eugenol analogues (2-6) were obtained through acetylation and nitration reactions. Eugenol (1) and its analogues (2-6) were examined by in vitro model of cancer using two human cancer cell lines: DU-145 (androgeninsensitive prostate cancer cells) and KB (oral squamous carcinoma cells). Cell viability, by tetrazolium salts assay, was measured. Lactic dehydrogenase (LDH) release was also investigated to evaluate the presence of cell toxicity as a result of cell disruption, subsequent to membrane rupture. In the examined cancer cells, all compounds showed cell-growth inhibition activity. The obtained results demonstrate that the compounds 5-allyl-3-nitrobenzene-1,2-diol (3) and 4-allyl- 2-methoxy-5-nitrophenyl acetate (5) were significantly (p 50 values in DU-145 cells of 19.02 x 10-6 and 21.5 x 10-6 mol L-1, respectively, and in KB cells of 18.11 x 10-6 and 21.26 x 10-6 mol L-1, respectively, suggesting that the presence of nitro and hydroxyl groups could be important in the activity of these compounds. In addition, our results seem to indicate that apoptotic cell demise appears to be induced in KB and DU-145 cells. In fact, in our experimental conditions, no statistically significant increase in LDH release was observed in cancer cells treated with eugenol and its analogues. (author)

  9. Treatment Option Overview (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  10. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  11. General Information about Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

  12. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Prevention Lung Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small Cell Lung Cancer Go to Health Professional Version Key Points Non- ...

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

    International Nuclear Information System (INIS)

    Highlights: ► Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. ► Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. ► Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. ► Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. ► 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.

  14. 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

  15. Measuring the metastatic potential of cancer cells

    Science.gov (United States)

    Morrison, Dennis R.; Gratzner, Howard; Atassi, M. Z.

    1993-01-01

    Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

  16. Dietary fat intake and subsequent weight change in adults: results from the European Prospective Investigation into Cancer and Nutrition cohorts

    DEFF Research Database (Denmark)

    Forouhi, Nita G; Sharp, Stephen J; Du, Huaidong; van der A, Daphne L; Halkjaer, Jytte; Schulze, Matthias B; Tjønneland, Anne; Overvad, Kim; Jakobsen, Marianne Uhre; Boeing, Heiner; Buijsse, Brian; Palli, Domenico; Masala, Giovanna; Feskens, Edith J M; Sørensen, Thorkild I A; Wareham, Nicholas J

    2009-01-01

    weight divided by duration of follow-up). DESIGN: We analyzed data from 89,432 men and women from 6 cohorts of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Using country-specific food-frequency questionnaires, we examined the association between baseline fat intake...

  17. T Cells in Gastric Cancer: Friends or Foes

    OpenAIRE

    Mario M. D'Elios; Elena Silvestri; Chiara Della Bella; Amedeo Amedei; Domenico Prisco

    2012-01-01

    Gastric cancer is the second cause of cancer-related deaths worldwide. Helicobacter pylori is the major risk factor for gastric cancer. As for any type of cancer, T cells are crucial for recognition and elimination of gastric tumor cells. Unfortunately T cells, instead of protecting from the onset of cancer, can contribute to oncogenesis. Herein we review the different types, “friend or foe”, of T-cell response in gastric cancer.

  18. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme.

    Science.gov (United States)

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T; Peng, Lifeng; Davis, Paul F; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM's cancer biology. PMID:27148537

  19. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

    Science.gov (United States)

    Bradshaw, Amy; Wickremsekera, Agadha; Tan, Swee T.; Peng, Lifeng; Davis, Paul F.; Itinteang, Tinte

    2016-01-01

    Glioblastoma multiforme (GBM), an aggressive tumor that typically exhibits treatment failure with high mortality rates, is associated with the presence of cancer stem cells (CSCs) within the tumor. CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells that drive tumor growth. Studies of many cancer types have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple GBM and glioblastoma cancer stem cell subtypes, making investigation and establishment of a universal treatment difficult. This review examines the current knowledge on the CSC markers SALL4, OCT-4, SOX2, STAT3, NANOG, c-Myc, KLF4, CD133, CD44, nestin, and glial fibrillary acidic protein, specifically focusing on their use and validity in GBM research and how they may be utilized for investigations into GBM’s cancer biology.

  20. Learning about Cancer by Studying Stem Cells

    Science.gov (United States)

    ... View All Articles | Inside Life Science Home Page Learning About Cancer by Studying Stem Cells By Sharon ... culture. Credit: Anne Weston, London Research Institute, CRUK (image available under a Creative Commons Attribution, Non-Commercial, ...

  1. Cancer: repositioned to kill stem cells

    OpenAIRE

    Holyoake, Tessa; Vetrie, David

    2015-01-01

    Chemotherapy-resistant cancer stem cells make it hard to cure many forms of the disease. Repositioning an existing drug to tackle this problem could significantly improve treatment for one form of leukaemia.

  2. 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)

    2016-05-05

    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 Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  3. Biochanin A Modulates Cell Viability, Invasion, and Growth Promoting Signaling Pathways in HER-2-Positive Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Vikas Sehdev

    2009-01-01

    Full Text Available Overexpression of HER-2 receptor is associated with poor prognosis and aggressive forms of breast cancer. Scientific literature indicates a preventive role of isoflavones in cancer. Since activation of HER-2 receptor initiates growth-promoting events in cancer cells, we studied the effect of biochanin A (an isoflavone on associated signaling events like receptor activation, downstream signaling, and invasive pathways. HER-2-positive SK-BR-3 breast cancer cells, MCF-10A normal breast epithelial cells, and NIH-3T3 normal fibroblast cells were treated with biochanin A (2–100 μM for 72 hours. Subsequently cell viability assay, western blotting and zymography were carried out. The data indicate that biochanin A inhibits cell viability, signaling pathways, and invasive enzyme expression and activity in SK-BR-3 cancer cells. Biochanin A did not inhibit MCF-10A and NIH-3T3 cell viability. Therefore, biochanin A could be a unique natural anticancer agent which can selectively target cancer cells and inhibit multiple signaling pathways in HER-2-positive breast cancer cells.

  4. The proteasomal and apoptotic phenotype determine bortezomib sensitivity of non-small cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Chęcińska Agnieszka

    2007-11-01

    Full Text Available Abstract Bortezomib is a novel anti-cancer agent which has shown promising activity in non-small lung cancer (NSCLC patients. However, only a subset of patients respond to this treatment. We show that NSCLC cell lines are differentially sensitive to bortezomib, IC50 values ranging from 5 to 83 nM. The apoptosis-inducing potential of bortezomib in NSCLC cells was found to be dependent not only on the apoptotic phenotype but also on the proteasomal phenotype of individual cell lines. Upon effective proteasome inhibition, H460 cells were more susceptible to apoptosis induction by bortezomib than SW1573 cells, indicating a different apoptotic phenotype. However, exposure to a low dose of bortezomib did only result in SW1573 cells, and not in H460 cells, in inhibition of proteasome activity and subsequent apoptosis. This suggests a different proteasomal phenotype as well. Additionally, overexpression of anti-apoptotic protein Bcl-2 in H460 cells did not affect the proteasomal phenotype of H460 cells but did result in decreased bortezomib-induced apoptosis. In conclusion, successful proteasome-inhibitor based treatment strategies in NSCLC face the challenge of having to overcome apoptosis resistance as well as proteasomal resistance of individual lung cancer cells. Further studies in NSCLC are warranted to elucidate underlying mechanisms.

  5. Noncoding RNAs in cancer and cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Tianzhi Huang; Angel Alvarez; Bo Hu; Shi-Yuan Cheng

    2013-01-01

    In recent years, it has become increasingly apparent that noncoding RNAs (ncRNA) are of crucial importance for human cancer. The functional relevance of ncRNAs is particularly evident for microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). miRNAs are endogenously expressed small RNA sequences that act as post-transcriptional regulators of gene expression and have been extensively studied for their roles in cancers, whereas lncRNAs are emerging as important players in the cancer paradigm in recent years. These noncoding genes are often aberrantly expressed in a variety of human cancers. However, the biological functions of most ncRNAs remain largely unknown. Recently, evidence has begun to accumulate describing how ncRNAs are dysregulated in cancer and cancer stem cells, a subset of cancer cells harboring self-renewal and differentiation capacities. These studies provide insight into the functional roles that ncRNAs play in tumor initiation, progression, and resistance to therapies, and they suggest ncRNAs as attractive therapeutic targets and potential y useful diagnostic tools.

  6. Redox Regulation in Cancer Stem Cells

    OpenAIRE

    Shijie Ding; Chunbao Li; Ninghui Cheng; Xiaojiang Cui; Xinglian Xu; Guanghong Zhou

    2015-01-01

    Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of can...

  7. Prostate cancer stem cells: The case for model systems

    Directory of Open Access Journals (Sweden)

    Paul G Hynes

    2012-01-01

    Full Text Available Advanced prostate cancers are treated with androgen deprivation therapy, which usually leads to a rapid and significant reduction in tumor burden but subsequent development of castration-resistant and metastatic disease almost always occurs. The source of tumor heterogeneity and the accompanying mechanisms leading to treatment resistance are major areas of prostate cancer research. Although our understanding of tumor heterogeneity is evolving, the functional isolation of tumor propagating populations, also known as cancer stem cells (CSCs, is fundamental to the identification and molecular characterization of castration-resistant prostate cancer cells. Of clinical importance, knowledge of prostate CSCs has implications for design of next generation-targeted therapies aimed at both eradicating primary tumor mass and preventing castration-resistant disease. The inability to routinely transplant fractionated primary human prostate tumors has prevented progress in analyzing the source of heterogeneous and treatment-resistant populations in prostate cancer. Here, we briefly overview the mechanisms of castration resistance, including the hypothesis for the existence of androgen-independent prostate CSCs. Finally, we discuss the interpretation of preclinical models and their utility for characterizing prostate CSCs in androgen-replete and androgen-deprived conditions.

  8. CD133: A cancer stem cells marker, is used in colorectal cancers

    OpenAIRE

    Fei Ren; Wei-Qi Sheng; Xiang Du

    2013-01-01

    Colorectal cancer is one of the most common malignant tumors worldwide. A model of cancer development involving cancer stem cells has been put forward because it provides a possible explanation of tumor hierarchy. Cancer stem cells are characterized by their proliferation, tumorigenesis, differentiation, and self-renewal capacities, and chemoradiotherapy resistance. Due to the role of cancer stem cells in tumor initiation and treatment failure, studies of cancer stem cell markers, such as CD1...

  9. 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...

  10. Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

    Science.gov (United States)

    Abrao, Emiliana Pereira; da Fonseca, Benedito Antônio Lopes

    2016-02-01

    Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice-versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs. PMID:26808727

  11. Markers of small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Sharma SK

    2004-05-01

    Full Text Available Abstract Lung cancer is the number one cause of cancer death; however, no specific serum biomarker is available till date for detection of early lung cancer. Despite good initial response to chemotherapy, small-cell lung cancer (SCLC has a poor prognosis. Therefore, it is important to identify molecular markers that might influence survival and may serve as potential therapeutic targets. The review aims to summarize the current knowledge of serum biomarkers in SCLC to improve diagnostic efficiency in the detection of tumor progression in lung cancer. The current knowledge on the known serum cytokines and tumor biomarkers of SCLC is emphasized. Recent findings in the search for novel diagnostic and therapeutic molecular markers using the emerging genomic technology for detecting lung cancer are also described. It is believed that implementing these new research techniques will facilitate and improve early detection, prognostication and better treatment of SCLC.

  12. 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.

  13. Biomechanical investigation of colorectal cancer cells

    Science.gov (United States)

    Palmieri, Valentina; Lucchetti, Donatella; Maiorana, Alessandro; Papi, Massimiliano; Maulucci, Giuseppe; Ciasca, Gabriele; Svelto, Maria; De Spirito, Marco; Sgambato, Alessandro

    2014-09-01

    The nanomechanical properties of SW480 colon cancer cells were investigated using Atomic Force Microscopy. SW480 cells are composed of two sub-populations with different shape and invasiveness. These two cells populations showed similar adhesion properties while appeared significantly different in term of cells stiffness. Since cell stiffness is related to invasiveness and growth, we suggest elasticity as a useful parameter to distinguish invasive cells inside the colorectal tumor bulk and the high-resolution mechanical mapping as a promising diagnostic tool for the identification of malignant cells.

  14. 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......, including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress...... in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which...

  15. Cancer stem cells and chemoradiation resistance

    International Nuclear Information System (INIS)

    Cancer is a disease of genetic and epigenetic alterations, which are emphasized as the central mechanisms of tumor progression in the multistepwise model. Discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. The heterogeneity of tumors can be explained with the help of CSCs supported by antiapoptotic signaling. CSCs mimic normal adult stem cells by demonstrating resistance to toxic injuries and chemoradiation therapy. Moreover, they might be responsible for tumor relapse following apparent beneficial treatments. Compared with hematopoietic malignancies, conventional therapy regimes in solid tumors have improved the overall survival marginally, illustrating the profound impact of treatment resistance. This implies that the present therapies, which follow total elimination of rapidly dividing and differentiated tumor cells, need to be modified to target CSCs that repopulate the tumor. In this review article, we report on recent findings regarding the involvement of CSCs in chemoradiation resistance and provide new insights into their therapeutic implications in cancer. (author)

  16. Laser Direct-Write Onto Live Tissues: A Novel Model for Studying Cancer Cell Migration.

    Science.gov (United States)

    Burks, Hope E; Phamduy, Theresa B; Azimi, Mohammad S; Saksena, Jayant; Burow, Matthew E; Collins-Burow, Bridgette M; Chrisey, Douglas B; Murfee, Walter L

    2016-11-01

    Investigation into the mechanisms driving cancer cell behavior and the subsequent development of novel targeted therapeutics requires comprehensive experimental models that mimic the complexity of the tumor microenvironment. Recently, our laboratories have combined a novel tissue culture model and laser direct-write, a form of bioprinting, to spatially position single or clustered cancer cells onto ex vivo microvascular networks containing blood vessels, lymphatic vessels, and interstitial cell populations. Herein, we highlight this new model as a tool for quantifying cancer cell motility and effects on angiogenesis and lymphangiogenesis in an intact network that matches the complexity of a real tissue. Application of our proposed methodology offers an innovative ex vivo tissue perspective for evaluating the effects of gene expression and targeted molecular therapies on cancer cell migration and invasion. J. Cell. Physiol. 231: 2333-2338, 2016. © 2016 Wiley Periodicals, Inc. PMID:26923437

  17. Alteration of pancreatic cancer cell functions by tumor-stromal cell interaction

    OpenAIRE

    Shin eHamada; Atsushi eMasamune; Tooru eShimosegawa

    2013-01-01

    Pancreatic cancer shows a characteristic tissue structure called desmoplasia, which consists of dense fibrotic stroma surrounding cancer cells. Interactions between pancreatic cancer cells and stromal cells promote invasive growth of cancer cells and establish a specific microenvironment such as hypoxia which further aggravates the malignant behavior of cancer cells. Pancreatic stellate cells (PSCs) play pivotal role in the development of fibrosis within the pancreatic cancer tissue, and also...

  18. Alteration of pancreatic cancer cell functions by tumor-stromal cell interaction

    OpenAIRE

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2013-01-01

    Pancreatic cancer shows a characteristic tissue structure called desmoplasia, which consists of dense fibrotic stroma surrounding cancer cells. Interactions between pancreatic cancer cells and stromal cells promote invasive growth of cancer cells and establish a specific microenvironment such as hypoxia which further aggravates the malignant behavior of cancer cells. Pancreatic stellate cells (PSCs) play a pivotal role in the development of fibrosis within the pancreatic cancer tissue, and al...

  19. Case of cytomegalovirus retinitis aggravated by sub-Tenon injection of triamcinolone acetonide with subsequent metastatic liver cancer

    Directory of Open Access Journals (Sweden)

    Yamamoto Y

    2013-03-01

    Full Text Available Yumiko Yamamoto,1 Yoshitake Kato,2 Hitoshi Tabuchi,2 Atsuki Fukushima11Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi, Japan; 2Department of Ophthalmology, Tsukazaki Hospital, Hyogo, JapanAbstract: We report a case of cytomegalovirus (CMV retinitis in an immunocompetent patient who was resistant to antiviral treatment, and in whom fatal metastatic liver cancer was later detected. A 74-year-old Japanese man visited our ophthalmology clinic in May 2011. He had a history of well controlled type 2 diabetes and colon cancer, and underwent successful surgical treatment in 2008. In April 2011, he was diagnosed with uveitis affecting his left eye and received posterior sub-Tenon injection of triamcinolone acetonide. He was referred to us because of aggravation of the retinal lesion. Funduscopic examination of the left eye revealed arcuate, whitish, necrotizing retinitis with hemorrhage along the temporal arcade of the retina. Polymerase chain reaction of the aqueous fluid was positive for CMV DNA. Because of diagnosis of CMV retinitis in his left eye, he was referred to an internist and investigated for systemic CMV infection or any serious disease which could cause immunocompromise, but neither was detected. Despite an intensive course of intravitreous ganciclovir and oral valganciclovir, the retinitis did not resolve. In June 2012, 14 months after the initial ocular symptoms, metastatic liver cancer was found and the patient passed away. When CMV retinitis is resistant to antiviral treatment or recurs in an immunocompetent patient, it is important that ophthalmologists undertake systemic investigation for occult malignancy.Keywords: cytomegalovirus, retinitis, uveitis, immunocompromised, immunocompetent, triamcinolone acetonide, diabetes, ganciclovir, valganciclovir

  20. DNA From Dead Cancer Cells Induces TLR9-Mediated Invasion and Inflammation In Living Cancer Cells

    Science.gov (United States)

    Tuomela, Johanna; Sandholm, Jouko; Kaakinen, Mika; Patel, Ankita; Kauppila, Joonas H.; Ilvesaro, Joanna; Chen, Dongquan; Harris, Kevin W.; Graves, David; Selander, Katri S.

    2014-01-01

    TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR9- and cathepsin-mediated invasion in living cancer cells. To study whether this phenomenon contributes to treatment responses, triple negative, human MDA-MB-231 breast cancer cells stably expressing control or TLR9 siRNA were inoculated orthotopically into nude mice. The mice were treated with vehicle or doxorubicin. The tumor groups exhibited equal decreases in size in response to doxorubicin. However, while the weights of vehicle-treated mice were similar, mice bearing control siRNA tumors became significantly more cachectic in response to doxorubicin, as compared with similarly treated mice bearing TLR9 siRNA tumors, suggesting a TLR9-mediated inflammation at the site of the tumor. In conclusion, our findings propose that DNA released from chemotherapy-killed cancer cells has significant influence on TLR9-mediated biological effects in living cancer cells. Through these mechanisms, tumor TLR9 expression may affect treatment responses to chemotherapy. PMID:24212717

  1. Gap Junctions: The Claymore for Cancerous Cells

    Directory of Open Access Journals (Sweden)

    Ailar Nakhlband

    2011-07-01

    Full Text Available Introduction: Gap junctions play an important role in the cell proliferation in mammalian cells as well as carcinogenesis. However, there are controversial issues about their role in cancer pathogenesis. This study was designed to evaluate genotoxicity and cytotoxicity of Carbenoxolone (CBX as a prototype of inter-cellular gap junction blocker in MCF7 and BT20 human breast cancer cells. Methods: The MCF7and BT20 human breast cancer cell lines were cultivated, and treated at designated confluency with different doses of CBX. Cellular cytotoxicity was examined using standard colorimetric assay associated with cell viability tests. Gene expression evaluation was carried out using real time polymerase chain reaction (PCR. Results: MCF7 and BT20 cells were significantly affected by CBX in a dose dependent manner in cell viability assays. Despite varying expression of genes, down regulation of pro- and anti-apoptotic genes was observed in these cells. Conclusion: Based upon this investigation, it can be concluded that CBX could affect both low and high proliferative types of breast cancer cell lines and disproportionate down regulation of both pre- and anti-apoptotic genes may be related to interacting biomolecules, perhaps via gap junctions.

  2. 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.

  3. Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jie, E-mail: jie.wang2@osumc.edu [Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH (United States); Osei, Kwame [Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH (United States)

    2011-07-22

    Highlights: {yields} Primary proinsulin maturation disorder is inherent in Ins2{sup +/Akita} islets/{beta}-cells. {yields} A consequence is the inefficient conversion of proinsulin to insulin. {yields} Post-translational defects occur as well in the involved PC1/3 and PC2 convertases. {yields} Proinsulin maturation chaos results in defects in the following conversion process. {yields} A link of the proinsulin maturation disorder and hyperproinsulinemia is suggested. -- Abstract: Disproportionate hyperproinsulinemia is an indicator of {beta}-cell dysfunction in diabetes and the basis underlying this abnormality remains obscure. Recently, we have found proinsulin is an aggregation-prone molecule inherent with a low relative folding rate and maintains a homeostatic balance of natively and plentiful non-natively folded states (i.e., proinsulin homeostasis, PIHO) in normal {beta}-cells as a result of the integration of maturation and disposal processes. PIHO is susceptible to environmental and genetic influences. Perturbation of PIHO produces a number of toxic consequences with known association to {beta}-cell failure in diabetes. To explore whether the perturbation of PIHO has a link to disproportionate hyperproinsulinemia, we investigated proinsulin conversion and the involved prohormone convertase 1/3 (PC1/3) and 2 (PC2) in mouse Ins2{sup +/Akita} islets/{beta}-cells that preserve a primary PIHO disorder due to a mutation (C96Y) in the insulin 2 (Ins2) gene. Our metabolic-labeling studies found an increased ratio of proinsulin to insulin in the cellular or released proteins of Ins2{sup +/Akita} islets. Histological, metabolic-labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2 immunoreactivities in the {beta}-cells of Ins2{sup +/Akita} islets in spite of no declines of these two convertases at the transcriptional and translational levels. Immunoblot analyses in cloned Ins2{sup +/Akita} {beta}-cells further confirmed the increased ratio of proinsulin

  4. Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in β-cells

    International Nuclear Information System (INIS)

    Highlights: → Primary proinsulin maturation disorder is inherent in Ins2+/Akita islets/β-cells. → A consequence is the inefficient conversion of proinsulin to insulin. → Post-translational defects occur as well in the involved PC1/3 and PC2 convertases. → Proinsulin maturation chaos results in defects in the following conversion process. → A link of the proinsulin maturation disorder and hyperproinsulinemia is suggested. -- Abstract: Disproportionate hyperproinsulinemia is an indicator of β-cell dysfunction in diabetes and the basis underlying this abnormality remains obscure. Recently, we have found proinsulin is an aggregation-prone molecule inherent with a low relative folding rate and maintains a homeostatic balance of natively and plentiful non-natively folded states (i.e., proinsulin homeostasis, PIHO) in normal β-cells as a result of the integration of maturation and disposal processes. PIHO is susceptible to environmental and genetic influences. Perturbation of PIHO produces a number of toxic consequences with known association to β-cell failure in diabetes. To explore whether the perturbation of PIHO has a link to disproportionate hyperproinsulinemia, we investigated proinsulin conversion and the involved prohormone convertase 1/3 (PC1/3) and 2 (PC2) in mouse Ins2+/Akita islets/β-cells that preserve a primary PIHO disorder due to a mutation (C96Y) in the insulin 2 (Ins2) gene. Our metabolic-labeling studies found an increased ratio of proinsulin to insulin in the cellular or released proteins of Ins2+/Akita islets. Histological, metabolic-labeling, and RT-PCR analyses revealed decreases of the PC1/3 and PC2 immunoreactivities in the β-cells of Ins2+/Akita islets in spite of no declines of these two convertases at the transcriptional and translational levels. Immunoblot analyses in cloned Ins2+/Akita β-cells further confirmed the increased ratio of proinsulin to insulin despite the levels of PC1/3 and PC2 proteins were not reduced somehow

  5. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  6. Phenotype heterogeneity in cancer cell populations

    Science.gov (United States)

    Almeida, Luis; Chisholm, Rebecca; Clairambault, Jean; Escargueil, Alexandre; Lorenzi, Tommaso; Lorz, Alexander; Trélat, Emmanuel

    2016-06-01

    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

  7. Squamous cell cancer of the rectum

    Institute of Scientific and Technical Information of China (English)

    Tara Dyson; Peter V Draganov

    2009-01-01

    Squamous cell carcinoma of the rectum is a rare malignancy. It appears to be associated with chronic inflammatory conditions and infections. The clear association seen between Human Papilloma Virus and various squamous cancers has not been firmly established for the squamous cell cancer of the rectum. The presentation is nonspecific and patients tend to present with advanced stage disease. Diagnosis relies on endoscopic examination with biopsy of the lesion. Distinction from squamous cell cancer of the anus can be difficult, but can be facilitated by immunohistochemical staining for cytokeratins. Staging of the cancer with endoscopic ultrasound and computed tomography provides essential information on prognosis and can guide therapy. At present, surgery remains the main therapeutic option; however recent advances have made chemoradiation a valuable therapeutic addition. Squamous cell carcinoma of the rectum is a distinct entity and it is of crucial importance for the practicing Gastroenterologist to be thoroughly familiar with this disease. Compared to adenocarcinoma of the rectum and squamous cell cancer of the anal canal, squamous cell carcinoma of the rectum has different epidemiology, etiology, pathogenesis, and prognosis but, most importantly, requires a different therapeutic approach. This review will examine and summarize the available information regarding this disease from the perspective of the practicing gastroenterologist.

  8. A genomics approach to identify susceptibilities of breast cancer cells to “fever-range” hyperthermia

    International Nuclear Information System (INIS)

    Preclinical and clinical studies have shown for decades that tumor cells demonstrate significantly enhanced sensitivity to “fever range” hyperthermia (increasing the intratumoral temperature to 42-45°C) than normal cells, although it is unknown why cancer cells exhibit this distinctive susceptibility. To address this issue, mammary epithelial cells and three malignant breast cancer lines were subjected to hyperthermic shock and microarray, bioinformatics, and network analysis of the global transcription changes was subsequently performed. Bioinformatics analysis differentiated the gene expression patterns that distinguish the heat shock response of normal cells from malignant breast cancer cells, revealing that the gene expression profiles of mammary epithelial cells are completely distinct from malignant breast cancer lines following this treatment. Using gene network analysis, we identified altered expression of transcripts involved in mitotic regulators, histones, and non-protein coding RNAs as the significant processes that differed between the hyperthermic response of mammary epithelial cells and breast cancer cells. We confirmed our data via qPCR and flow cytometric analysis to demonstrate that hyperthermia specifically disrupts the expression of key mitotic regulators and G2/M phase progression in the breast cancer cells. These data have identified molecular mechanisms by which breast cancer lines may exhibit enhanced susceptibility to hyperthermic shock

  9. High prevalence of side population in human cancer cell lines

    OpenAIRE

    Boesch, Maximilian; Zeimet, Alain G; Fiegl, Heidi; Wolf, Barbara; Huber, Julia; Klocker, Helmut; Gastl, Guenther; Sopper, Sieghart; Wolf, Dominik

    2016-01-01

    Cancer cell lines are essential platforms for performing cancer research on human cells. We here demonstrate that, across tumor entities, human cancer cell lines harbor minority populations of putative stem-like cells, molecularly defined by dye extrusion resulting in the side population phenotype. These findings establish a heterogeneous nature of human cancer cell lines and argue for their stem cell origin. This should be considered when interpreting research involving these model systems.

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

    OpenAIRE

    Bjerregaard, Bolette; Holck, S.; Christensen, I. J.; Larsson, Lars-Inge

    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 specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to ex...

  11. Cancer Stem Cells: From Identification To Eradication

    International Nuclear Information System (INIS)

    A fundamental problem in cancer research is identification of the cells within a tumor that sustain the growth of the neoplastic clone. The concept that only a subpopulation of rare cancer stem cells (CSCs) is responsible for maintenance of the neoplasm emerged nearly 50 years ago: however, conclusive proof for the existence of a CSC was obtained only relatively recently. As definition, cancer stem cells (CSCs) are a sub-population of cancer cells (found within solid tumors or hematological malignancies) that possess characteristics normally associated with stem cells as high self-renewal potential. These cells are believed to be tumorige forming) in contrast to the bulk of cancer cells, which are thought to be non-tumorigenic. The first conclusive evidence for CSCs was published in 1997 in Nature Medicine by Bonnet and Dick who isolated a subpopulation of leukemic cells in AML that express a specific surface marker CD34 but lacks the CD38 marker. The authors established that the CD34+/CD38– subpopulation is capable of initiating leukemia in NOD/SCID mice that is histologically similar to the donor [1]. This subpopulation of cells is termed SCID Leukemia-initiating cells (SLIC). A theory suggests that such cells act as a reservoir for disease recurrence, are the origin of metastasis and exert resistance towards classical antitumor regimens. This resistance was attributed to a combination of several factors [2], suggesting that conventional antitumor regimens are targeting the bulk of the tumor not the dormant stubborn CSCs. Purpose Better understanding of the leukemogenic process and the biology of CSCS to define the most applicable procedures for their identification and isolation in order to design specific targeted therapies aiming at reducing disease burden to very low levels .. up to eradication of the tumor

  12. Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Fangfang Lang

    Full Text Available Resveratrol (trans-3,4,5'-trihydroxystilbene is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3 was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.

  13. Electrodynamic activity of healthy and cancer cells

    Czech Academy of Sciences Publication Activity Database

    Pokorný, Jiří

    Vol. 329. Bristol : IOP, 2011 - (Cifra, M.; Pokorny, J.; Kučera, O.), 012007 ISSN 1742-6588. [9th International Frohlich's Symposium on Electrodynamic Activity of Living Cells - Including Microtubule Coherent Modes and Cancer Cell Physics. Praha (CZ), 01.07.2011-03.07.2011] R&D Projects: GA ČR(CZ) GAP102/11/0649 Institutional research plan: CEZ:AV0Z20670512 Keywords : Boundary elements * Cancer cells * Electric dipole Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  14. Targeted therapy for squamous cell lung cancer

    OpenAIRE

    Liao, Rachel G.; Watanabe, Hideo; Meyerson, Matthew; Hammerman, Peter S.

    2012-01-01

    Lung squamous cell carcinoma (SqCC) is the second most common subtype of non-small-cell lung cancer and leads to 40,000–50,000 deaths per year in the USA. Management of non-small-cell lung cancer has dramatically changed over the past decade with the introduction of targeted therapeutic agents for genotypically selected individuals with lung adenocarcinoma. These agents lead to improved outcomes, and it has now become the standard of care to perform routine molecular genotyping of lung adenoc...

  15. The Activity of Sirtuin 1 in MCF-7 Breast Cancer Cell Line: The Effects of Visfatin

    Directory of Open Access Journals (Sweden)

    kiarash behrouzfar

    2015-11-01

    Full Text Available Background & Objectives: Breast cancer is the most common cancer and the second leading cause of cancer deaths among women. Obesity, hormones, and growth factors are the risk factors for this kind of cancer. One of the changes observed in patients suffering from breast cancer is the elevated Visfatin or nicotinamide phosphoribosyl transferase (NAMPT in their tumor tissues and blood. The increased activity of Visfatin and SIRT1 (Sirtuin 1 in breast cancer and many other cancers has been determined, and its value is correlated with cancer prognosis. The aim of the present study is to investigate the effects of Visfatin on SIRT1 activity in MCF-7 breast cancer cell line. Materials & Methods: In this study, in order to investigate the effects of Visfatin on SIRT1 activity in MCF-7 cells, cells were treated after cell culture by Visfatin for 12, 24, and 48 hours. Subsequently, the cells were lysed by nuclear extraction kit, and their total protein concentrations were measured by Bradford assay. Finally, we estimated the general activity of SIRT1 by measuring the SIRT1 activity with the assay kit via spectrofluorometric device. Results: The findings of this research show that SIRT1 activity is not significantly changed following Visfatin treatments for 12 and 24 hours. However, after 48 hour, Visfatin increases SIRT1 activity about 2 times more than control group. Conclusion: The antiapoptotic effects of Visfatin are exerted by increasing SIRT1 activity in MCF-7 cells, and these effects happen after 24 hours. 

  16. 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

  17. Cancer Stem Cells, Tumor Dormancy, And Metastasis

    Directory of Open Access Journals (Sweden)

    Purvi ePatel

    2012-10-01

    Full Text Available Tumor cells can persist undetectably for an extended period of time in primary tumors and in disseminated cancer cells. Very little is known about why and how these tumors persist for extended periods of time and then evolve to malignancy. The discovery of cancer stem cells (CSCs in human tumors challenges our current understanding of tumor recurrence, drug resistance, and metastasis, and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Although overlapping molecules and pathways have been reported to regulate the stem-like phenotype of CSCs and metastasis, accumulated evidence has suggested additional clonal diversity within the stem-like cancer cell subpopulation. This review will describe the current hypothesis linking CSCs and metastasis and summarize mechanisms important for metastatic CSCs to re-initiate tumors in the secondary sites. A better understanding of CSCs’ contribution to clinical tumor dormancy and metastasis will provide new therapeutic revenues to eradicate metastatic tumors and significantly reduce the mortality of cancer patients.

  18. 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

  19. 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.

  20. Molecular mechanisms of pharmacological doses of ascorbate on cancer cells.

    Science.gov (United States)

    Venturelli, Sascha; Sinnberg, Tobias W; Niessner, Heike; Busch, Christian

    2015-06-01

    Intravenous application of high-dose ascorbate (vitamin C) has been used in complementary medicine since the 1970s to treat cancer patients. In recent years it became evident that high-dose ascorbate in the millimolar range bears selective cytotoxic effects on cancer cells in vitro and in vivo. This anticancer effect is dose dependent, catalyzed by serum components and mediated by reactive oxygen species and ascorbyl radicals, making ascorbate a pro-oxidative pro-drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. It further depends on HIF-1 signaling and oxygen pressure, and shows a strong epigenetic signature (alteration of DNA-methylation and induction of tumor-suppressing microRNAs in cancer cells). The detailed understanding of ascorbate-induced antiproliferative molecular mechanisms warrants in-depth preclinical evaluation in cancer-bearing animal models for the optimization of an efficacious therapy regimen (e.g., combination with hyperbaric oxygen or O2-sensitizers) that subsequently need to be evaluated in clinical trials. PMID:26065536

  1. Noble Hybrid Nanostructures as Efficient Anti-Proliferative Platforms for Human Breast Cancer Cell.

    Science.gov (United States)

    Tavangar, Amirhossein; Premnath, Priyatha; Tan, Bo; Venkatakrishnan, Krishnan

    2016-04-27

    Nanomaterials have proven to possess great potential in biomaterials research. Recently, they have suggested considerable promise in cancer diagnosis and therapy. Among others, silicon (Si) nanomaterials have been extensively employed for various biomedical applications; however, the utilization of Si for cancer therapy has been limited to nanoparticles, and its potential as anticancer substrates has not been fully explored. Noble nanoparticles have also received considerable attention owing to unique anticancer properties to improve the efficiency of biomaterials for numerous biological applications. Nevertheless, immobilization and control over delivery of the nanoparticles have been challenge. Here, we develop hybrid nanoplatforms to efficiently hamper breast cancer cell adhesion and proliferation. Platforms are synthesized by femtosecond laser processing of Si into multiphase nanostructures, followed by sputter-coating with gold (Au)/gold-palladium (Au-Pd) nanoparticles. The performance of the developed platforms was then examined by exploring the response of normal fibroblast and metastatic breast cancer cells. Our results from the quantitative and qualitative analyses show a dramatic decrease in the number of breast cancer cells on the hybrid platform compared to untreated substrates. Whereas, fibroblast cells form stable adhesion with stretched and elongated cytoskeleton and actin filaments. The hybrid platforms perform as dual-acting cytophobic/cytostatic stages where Si nanostructures depress breast cancer cell adhesion while immobilized Au/Au-Pd nanoparticles are gradually released to affect any surviving cell on the nanostructures. The nanoparticles are believed to be taken up by breast cancer cells via endocytosis, which subsequently alter the cell nucleus and may cause cell death. The findings suggest that the density of nanostructures and concentration of coated nanoparticles play critical roles on cytophobic/cytostatic properties of the platforms on

  2. High aldehyde dehydrogenase activity identifies cancer stem cells in human cervical cancer

    OpenAIRE

    Liu, Shu-Yan; Zheng, Peng-Sheng

    2013-01-01

    High aldehyde dehydrogenase (ALDH) activity characterizes a subpopulation of cells with cancer stem cell (CSC) properties in several malignancies. To clarify whether ALDH can be used as a marker of cervical cancer stem cells (CCSCs), ALDHhigh and ALDHlow cells were sorted from 4 cervical cancer cell lines and 5 primary tumor xenografts and examined for CSC characteristics. Here, we demonstrate that cervical cancer cells with high ALDH activity fulfill the functional criteria for CSCs: (1) ALD...

  3. Chemokine receptors in cancer metastasis and cancer cell-derived chemokines in host immune response.

    Science.gov (United States)

    Koizumi, Keiichi; Hojo, Shozo; Akashi, Takuya; Yasumoto, Kazuo; Saiki, Ikuo

    2007-11-01

    The chemotactic cytokines called chemokines are a superfamily of small secreted cytokines that were initially characterized through their ability to prompt the migration of leukocytes. Attention has been focused on the chemokine receptors expressed on cancer cells because cancer cell migration and metastasis show similarities to leukocyte trafficking. CXC chemokine receptor 4 (CXCR4) was first investigated as a chemokine receptor that is associated with lung metastasis of breast cancers. Recently, CXCR4 was reported to be a key molecule in the formation of peritoneal carcinomatosis in gastric cancer. In the present review, we highlight current knowledge about the role of CXCR4 in cancer metastases. In contrast to chemokine receptors expressed on cancer cells, little is known about the roles of cancer cell-derived chemokines. Cancer tissue consists of both cancer cells and various stromal cells, and leukocytes that infiltrate into cancer are of particular importance in cancer progression. Although colorectal cancer invasion is regulated by the chemokine CCL9-induced infiltration of immature myeloid cells into cancer, high-level expression of cancer cell-derived chemokine CXCL16 increases infiltrating CD8(+) and CD4(+) T cells into cancer tissues, and correlates with a good prognosis. We discuss the conflicting biological effects of cancer cell-derived chemokines on cancer progression, using CCL9 and CXCL16 as examples. PMID:17894551

  4. Surgery for small cell lung cancer.

    Science.gov (United States)

    de Hoyos, Alberto; DeCamp, Malcolm M

    2014-11-01

    Small-cell lung cancer (SCLC) comprises approximately 14% of all lung cancer cases. Most patients present with locally advanced or metastatic disease and are therefore treated nonoperatively with chemotherapy, radiotherapy, or both. A small subset of patients with SCLC present with early-stage disease and will benefit from surgical resection plus chemotherapy. The rationale for radiotherapy in these patients remains controversial. PMID:25441133

  5. Targeting cancer stem cells in hepatocellular carcinoma

    OpenAIRE

    MISHRA, LOPA

    2014-01-01

    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 fun...

  6. How Taxol/paclitaxel kills cancer cells

    OpenAIRE

    Weaver, Beth A

    2014-01-01

    Taxol (generic name paclitaxel) is a microtubule-stabilizing drug that is approved by the Food and Drug Administration for the treatment of ovarian, breast, and lung cancer, as well as Kaposi's sarcoma. It is used off-label to treat gastroesophageal, endometrial, cervical, prostate, and head and neck cancers, in addition to sarcoma, lymphoma, and leukemia. Paclitaxel has long been recognized to induce mitotic arrest, which leads to cell death in a subset of the arrested population. However, r...

  7. Cell Membrane Softening in Cancer Cells

    Science.gov (United States)

    Schmidt, Sebastian; Händel, Chris; Käs, Josef

    Biomechanical properties are useful characteristics and regulators of the cell's state. Current research connects mechanical properties of the cytoskeleton to many cellular processes but does not investigate the biomechanics of the plasma membrane. We evaluated thermal fluctuations of giant plasma membrane vesicles, directly derived from the plasma membranes of primary breast and cervical cells and observed a lowered rigidity in the plasma membrane of malignant cells compared to non-malignant cells. To investigate the specific role of membrane rigidity changes, we treated two cell lines with the Acetyl-CoA carboxylase inhibitor Soraphen A. It changed the lipidome of cells and drastically increased membrane stiffness by up regulating short chained membrane lipids. These altered cells had a decreased motility in Boyden chamber assays. Our results indicate that the thermal fluctuations of the membrane, which are much smaller than the fluctuations driven by the cytoskeleton, can be modulated by the cell and have an impact on adhesion and motility.

  8. Reversibility of apoptosis in cancer cells

    OpenAIRE

    Tang, H. L.; Yuen, K L; Tang, H M; Fung, M C

    2008-01-01

    Apoptosis is a cell suicide programme characterised by unique cellular events such as mitochondrial fragmentation and dysfunction, nuclear condensation, cytoplasmic shrinkage and activation of apoptotic protease caspases, and these serve as the noticeable apoptotic markers for the commitment of cell demise. Here, we show that, however, the characterised apoptotic dying cancer cells can regain their normal morphology and proliferate after removal of apoptotic inducers. In addition, we demonstr...

  9. Lung cancer-initiating cells: a novel target for cancer therapy

    OpenAIRE

    Morrison, Brian J.; Morris, John C.; Steel, Jason C

    2013-01-01

    Lung cancer is a major public health problem causing more deaths than any other cancer. A better understanding of the biology of this disease and improvements in treatment are greatly needed. Increasing evidence supports the concept that a rare and specialized population of cancer cells, so-called cancer-initiating cells with stem cell-like characteristics, is responsible for tumor growth, maintenance, and recurrence. Cancer-initiating cells also exhibit characteristics that render them resis...

  10. Immunology of Stem Cells and Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Yang

    2007-01-01

    The capacity of pluri-potent stem cells to repair the tissues in which stem cells reside holds great promise in development of novel cell replacement therapeutics for treating chronic and degenerative diseases. However,numerous reports show that stem cell therapy, even in an autologous setting, triggers lymphocyte infiltration and inflammation. Therefore, an important question to be answered is how the host immune system responds to engrafted autologous stem cells or allogeneous stem cells. In this brief review, we summarize the progress in several related areas in this field, including some of our data, in four sections: (1) immunogenicity of stem cells; (2)strategies to inhibit immune rejection to allograft stem cells; (3) immune responses to cancer stem cells; and (4)mesenchymal stem cells in immune regulation. Improvement of our understanding on these and other aspects of immune system-stem cell interplay would greatly facilitate the development of stem cell-based therapeutics for regenerative purposes.

  11. Chemotherapy in heterogeneous cultures of cancer cells with interconversion

    International Nuclear Information System (INIS)

    Recently, the interconversion between differentiated and stem-like cancer cells has been observed. Here, we model the in vitro growth of heterogeneous cell cultures in the presence of interconversion from differentiated cancer cells to cancer stem cells (CSCs), showing that, by targeting only CSC with cytotoxic agents, it is not always possible to eradicate cancer. We have determined the kinetic conditions under which cytotoxic agents in in vitro heterogeneous cultures of cancer cells eradicate cancer. In particular, we have shown that the chemotherapeutic elimination of in vitro cultures of heterogeneous cancer cells is effective only if it targets all cancer cell types, and if the induced death rates for the different subpopulations of cancer cell types are large enough. The quantitative results of the model are compared and validated with experimental data. (paper)

  12. Mapping proteolytic cancer cell-extracellular matrix interfaces.

    NARCIS (Netherlands)

    Wolf, K.A.; Friedl, P.H.A.

    2009-01-01

    For cancer progression and metastatic dissemination, cancer cells migrate and penetrate through extracellular tissues. Cancer invasion is frequently facilitated by proteolytic processing of components of the extracellular matrix (ECM). The cellular regions mediating proteolysis are diverse and depen

  13. The metabolic landscape of cancer stem cells.

    Science.gov (United States)

    Dando, Ilaria; Dalla Pozza, Elisa; Biondani, Giulia; Cordani, Marco; Palmieri, Marta; Donadelli, Massimo

    2015-09-01

    Cancer stem cells (CSCs) are a sub-population of quiescent cells endowed with self-renewal properties that can sustain the malignant behavior of the tumor mass giving rise to more differentiated cancer cells. For this reason, the specific killing of CSCs represents one of the most important challenges of the modern molecular oncology. However, their particular resistance to traditional chemotherapy and radiotherapy imposes a thorough understanding of their biological and biochemical features. The metabolic peculiarities of CSCs may be a therapeutic and diagnostic opportunity in cancer research. In this review, we summarize the most significant discoveries on the metabolism of CSCs describing and critically analyzing the studies supporting either glycolysis or mitochondrial oxidative phosphorylation as a primary source of energy for CSCs. PMID:26337609

  14. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    Energy Technology Data Exchange (ETDEWEB)

    Berman, Abigail T., E-mail: abigail.berman@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104 (United States); James, Sara St.; Rengan, Ramesh [Department of Radiation Oncology, University of Washington Medical Center, Seattle, WA 98195 (United States)

    2015-07-02

    Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

  15. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    International Nuclear Information System (INIS)

    Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning

  16. Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

    Directory of Open Access Journals (Sweden)

    Abigail T. Berman

    2015-07-01

    Full Text Available Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT, through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC, as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

  17. Stem cell technology and engineering for cancer treatment

    OpenAIRE

    Sinh Truong Nguyen; Phuc Van Pham

    2015-01-01

    Stem cells are not only widely used for regenerative medicine, but are also considered as a useful tool for cancer treatment. For a long time, stem cells have been utilized to renew the immune system for radiation or chemotherapy treated patients. Recently, stem cells are being engineered to carry therapeutic reagents to target tumor sites. Cancer vaccines based on the knowledge of cancer stem cells have been studied and applied for cancer treatment. Induced pluripotent stem cells have been u...

  18. Interactome analysis of myeloid-derived suppressor cells in murine models of colon and breast cancer

    OpenAIRE

    Aliper, Alexander M.; FRIEDEN-KOROVKINA, VICTORIA P.; Buzdin, Anton; Roumiantsev, Sergey A.; Zhavoronkov, Alex

    2014-01-01

    In solid cancers, myeloid derived suppressor cells (MDSC) infiltrate (peri)tumoral tissues to induce immune tolerance and hence to establish a microenvironment permissive to tumor growth. Importantly, the mechanisms that facilitate such infiltration or a subsequent immune suppression are not fully understood. Hence, in this study, we aimed to delineate disparate molecular pathways which MDSC utilize in murine models of colon or breast cancer. Using pathways enrichment analysis, we completed i...

  19. Biological characteristics of side population cells in a self-established human ovarian cancer cell line

    Science.gov (United States)

    WEI, ZHENTONG; LV, SHUANG; WANG, YISHU; SUN, MEIYU; CHI, GUANGFAN; GUO, JUN; SONG, PEIYE; FU, XIAOYU; ZHANG, SONGLING; LI, YULIN

    2016-01-01

    The aim of the present study was to establish an ovarian cancer (OC) cell line from ascites of an ovarian serous cystadenocarcinoma patient and investigate the biological characteristics of its side population (SP) cells. The OC cell line was established by isolating, purifying and subculturing primary cells from ascites of an ovarian serous cystadenocarcinoma patient (stage IIIc; grade 3). SP and non-SP (NSP) cells were isolated by fluorescence-activated cell sorting and cultured in serum-free medium and soft agar to compare the tumorsphere and colony formation capacities. Furthermore, SP and NSP cell tumorigenesis was examined by subcutaneous and intraperitoneal injection of the cells to non-obese diabetic/severe combined immune deficiency (NOD/SCID) mice. Drug resistance to cisplatin was examined by cell counting kit-8. The OC cell line was successfully established from ascites of an ovarian serous cystadenocarcinoma patient, which exhibited properties similar to primary tumors subsequent to >50 passages and >2 years of culture. The SP cell ratio was 0.38% in the OC cell line, and a similar SP cell ratio (0.39%) was observed when sorted SP cells were cultured for 3 weeks. Compared with NSP cells, SP cells exhibited increased abilities in differentiation and tumorsphere and colony formation, in addition to the formation of xenografted tumors and ascites and metastasis of the tumors in NOD/SCID mice, even at low cell numbers (3.0×103 cells). The xenografted tumors demonstrated histological features similar to primary tumors and expressed the ovarian serous cystadenocarcinoma marker CA125. In addition, SP cells demonstrated a significantly stronger drug resistance to cisplatin compared with NSP and unsorted cells, while treatment with verapamil, an inhibitor of ATP-binding cassette transporters, potently abrogated SP cell drug resistance. In conclusion, the present study verified SP cells from an established OC cell line and characterized the cells with self

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

    Institute of Scientific and Technical Information of China (English)

    Hai-hong ZHANG; Ai-zhen CAI; Xue-ming WEI; Li DING; Feng-zhi LI; Ai-ming ZHENG; Da-jiang DAI

    2013-01-01

    Objective: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.Methods: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.Results: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.Conclusions: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. Cancer Stem Cells and Pediatric Solid Tumors

    International Nuclear Information System (INIS)

    Recently, a subpopulation of cells, termed tumor-initiating cells or tumor stem cells (TSC), has been identified in many different types of solid tumors. These TSC, which are typically more resistant to chemotherapy and radiation compared to other tumor cells, have properties similar to normal stem cells including multipotency and the ability to self-renew, proliferate, and maintain the neoplastic clone. Much of the research on TSC has focused on adult cancers. With considerable differences in tumor biology between adult and pediatric cancers, there may be significant differences in the presence, function and behavior of TSC in pediatric malignancies. We discuss what is currently known about pediatric solid TSC with specific focus on TSC markers, tumor microenvironment, signaling pathways, therapeutic resistance and potential future therapies to target pediatric TSC

  2. 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 on the...

  3. Cancer Stem Cells in Breast: Current Opinion and Future Challenges

    OpenAIRE

    Charafe-Jauffret, Emmanuelle; Monville, Florence; Ginestier, Christophe; Dontu, Gabriela; Birnbaum, Daniel; Wicha, Max S.

    2008-01-01

    There is increasing evidence for the cancer stem cell hypothesis, which holds that cancers are driven by a cellular subcomponent that has stem cell properties, that is, self-renewal, tumorigenicity and multilineage differentiation capacity. The cancer stem cell hypothesis modifies our conceptual approach of oncogenesis and shall have implications in breast cancer prevention, detection and treatment, especially in metastatic breast cancer for which no curative treatment exists. Given the speci...

  4. Epirubicin-Adsorbed Nanodiamonds Kill Chemoresistant Hepatic Cancer Stem Cells

    OpenAIRE

    Wang, Xin; Low, Xinyi Casuarine; Hou, Weixin; Abdullah, Lissa Nurrul; Toh, Tan Boon; Mohd Abdul Rashid, Masturah; Ho, Dean; Chow, Edward Kai-Hua

    2014-01-01

    Chemoresistance is a primary cause of treatment failure in cancer and a common property of tumor-initiating cancer stem cells. Overcoming mechanisms of chemoresistance, particularly in cancer stem cells, can markedly enhance cancer therapy and prevent recurrence and metastasis. This study demonstrates that the delivery of Epirubicin by nanodiamonds is a highly effective nanomedicine-based approach to overcoming chemoresistance in hepatic cancer stem cells. The potent physical adsorption of Ep...

  5. Understanding cancer stem cell heterogeneity and plasticity

    Institute of Scientific and Technical Information of China (English)

    Dean G Tang

    2012-01-01

    Heterogeneity is an omnipresent feature of mammalian cells in vitro and in vivo.It has been recently realized that even mouse and human embryonic stem cells under the best culture conditions are heterogeneous containing pluripotent as well as partially committed cells.Somatic stem cells in adult organs are also heterogeneous,containing many subpopulations of self-renewing cells with distinct regenerative capacity.The differentiated progeny of adult stem cells also retain significant developmental plasticity that can be induced by a wide variety of experimental approaches.Like normal stem cells,recent data suggest that cancer stem cells(CSCs)similarly display significant phenotypic and functional heterogeneity,and that the CSC progeny can manifest diverse plasticity.Here,I discuss CSC heterogeneity and plasticity in the context of tumor development and progression,and by comparing with normal stem cell development.Appreciation of cancer cell plasticity entails a revision to the earlier concept that only the tumorigenic subset in the tumor needs to be targeted.By understanding the interrelationship between CSCs and their differentiated progeny,we can hope to develop better therapeutic regimens that can prevent the emergence of tumor cell variants that are able to found a new tumor and distant metastases.

  6. Metformin targets the metabolic achilles heel of human pancreatic cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Enza Lonardo

    Full Text Available Pancreatic ductal adenocarcinomas contain a subset of exclusively tumorigenic cancer stem cells (CSCs, which are capable of repopulating the entire heterogeneous cancer cell populations and are highly resistant to standard chemotherapy. Here we demonstrate that metformin selectively ablated pancreatic CSCs as evidenced by diminished expression of pluripotency-associated genes and CSC-associated surface markers. Subsequently, the ability of metformin-treated CSCs to clonally expand in vitro was irreversibly abrogated by inducing apoptosis. In contrast, non-CSCs preferentially responded by cell cycle arrest, but were not eliminated by metformin treatment. Mechanistically, metformin increased reactive oxygen species production in CSC and reduced their mitochondrial transmembrane potential. The subsequent induction of lethal energy crisis in CSCs was independent of AMPK/mTOR. Finally, in primary cancer tissue xenograft models metformin effectively reduced tumor burden and prevented disease progression; if combined with a stroma-targeting smoothened inhibitor for enhanced tissue penetration, while gemcitabine actually appeared dispensable.

  7. 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

  8. Molecular Pathways: Reactive Oxygen Species Homeostasis in Cancer Cells and Implications for Cancer Therapy

    OpenAIRE

    Nogueira, Veronique; Hay, Nissim

    2013-01-01

    Reactive oxygen species (ROS) are important in regulating normal cellular processes, but deregulated ROS contribute to the development of various human diseases including cancers. Cancer cells have increased ROS levels compared to normal cells, because of their accelerated metabolism. The high ROS levels in cancer cells, which distinguish them from normal cells, could be pro-tumorigenic, but are also their Achilles’ heel. The high ROS content in cancer cells renders them more susceptible to o...

  9. Evaluation of Enrichment Techniques for Mass Spectrometry : Identification of Tyrosine Phosphoproteins in Cancer Cells

    OpenAIRE

    Schumacher, Jonathan A.; Crockett, David K.; Elenitoba-Johnson, Kojo S.J.; Lim, Megan S.

    2007-01-01

    Phosphorylation of tyrosine residues by protein tyrosine kinases mediates numerous cellular processes. Deregulated tyrosine phosphorylation underlies constitutive activation of signaling pathways leading to oncogenesis. Analytical techniques for evaluation of the global phosphoproteome level are challenging and can be improved on to enhance yields. Here, we evaluated several approaches to enrich for tyrosine phosphoproteins in cancer cells for subsequent liquid chromatography-tandem mass spec...

  10. 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

  11. Foxp3 expression in human cancer cells

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos I

    2008-04-01

    Full Text Available Abstract Objective Transcription factor forkhead box protein 3 (Foxp3 specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs. Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types. Materials and methods Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones. Results Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1. Conclusion We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.

  12. Quantitative analysis of cell-free DNA in ovarian cancer

    Science.gov (United States)

    SHAO, XUEFENG; He, YAN; JI, MIN; CHEN, XIAOFANG; QI, JING; SHI, WEI; HAO, TIANBO; JU, SHAOQING

    2015-01-01

    The aim of the present study was to investigate the association between cell-free DNA (cf-DNA) levels and clinicopathological characteristics of patients with ovarian cancer using a branched DNA (bDNA) technique, and to determine the value of quantitative cf-DNA detection in assisting with the diagnosis of ovarian cancer. Serum specimens were collected from 36 patients with ovarian cancer on days 1, 3 and 7 following surgery, and additional serum samples were also collected from 22 benign ovarian tumor cases, and 19 healthy, non-cancerous ovaries. bDNA techniques were used to detect serum cf-DNA concentrations. All data were analyzed using SPSS version 18.0. The cf-DNA levels were significantly increased in the ovarian cancer group compared with those of the benign ovarian tumor group and healthy ovarian group (P<0.01). Furthermore, cf-DNA levels were significantly increased in stage III and IV ovarian cancer compared with those of stages I and II (P<0.01). In addition, cf-DNA levels were significantly increased on the first day post-surgery (P<0.01), and subsequently demonstrated a gradual decrease. In the ovarian cancer group, the area under the receiver operating characteristic curve of cf-DNA and the sensitivity were 0.917 and 88.9%, respectively, which was higher than those of cancer antigen 125 (0.724, 75%) and human epididymis protein 4 (0.743, 80.6%). There was a correlation between the levels of serum cf-DNA and the occurrence and development of ovarian cancer in the patients evaluated. bDNA techniques possessed higher sensitivity and specificity than other methods for the detection of serum cf-DNA in patients exhibiting ovarian cancer, and bDNA techniques are more useful for detecting cf-DNA than other factors. Thus, the present study demonstrated the potential value for the use of bDNA as an adjuvant diagnostic method for ovarian cancer. PMID:26788153

  13. Cell membrane softening in human breast and cervical cancer cells

    Science.gov (United States)

    Händel, Chris; Schmidt, B. U. Sebastian; Schiller, Jürgen; Dietrich, Undine; Möhn, Till; Kießling, Tobias R.; Pawlizak, Steve; Fritsch, Anatol W.; Horn, Lars-Christian; Briest, Susanne; Höckel, Michael; Zink, Mareike; Käs, Josef A.

    2015-08-01

    Biomechanical properties are key to many cellular functions such as cell division and cell motility and thus are crucial in the development and understanding of several diseases, for instance cancer. The mechanics of the cellular cytoskeleton have been extensively characterized in cells and artificial systems. The rigidity of the plasma membrane, with the exception of red blood cells, is unknown and membrane rigidity measurements only exist for vesicles composed of a few synthetic lipids. In this study, thermal fluctuations of giant plasma membrane vesicles (GPMVs) directly derived from the plasma membranes of primary breast and cervical cells, as well as breast cell lines, are analyzed. Cell blebs or GPMVs were studied via thermal membrane fluctuations and mass spectrometry. It will be shown that cancer cell membranes are significantly softer than their non-malignant counterparts. This can be attributed to a loss of fluid raft forming lipids in malignant cells. These results indicate that the reduction of membrane rigidity promotes aggressive blebbing motion in invasive cancer cells.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    AIM: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.METHODS: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.RESULTS: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.CONCLUSION:SP cells have some cancer stem celllike characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer.

  15. Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?

    Energy Technology Data Exchange (ETDEWEB)

    Chiodi, Ilaria; Belgiovine, Cristina; Donà, Francesca; Scovassi, A. Ivana; Mondello, Chiara, E-mail: mondello@igm.cnr.it [Institute of Molecular Genetics, CNR, via Abbiategrasso 207, 27100 Pavia (Italy)

    2011-03-04

    Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs.

  16. Drug Treatment of Cancer Cell Lines: A Way to Select for Cancer Stem Cells?

    International Nuclear Information System (INIS)

    Tumors are generally composed of different cell types. In recent years, it has been shown that in many types of cancers a subset of cells show peculiar characteristics, such as the ability to induce tumors when engrafted into host animals, self-renew and being immortal, and give rise to a differentiated progeny. These cells have been defined as cancer stem cells (CSCs) or tumor initiating cells. CSCs can be isolated both from tumor specimens and established cancer cell lines on the basis of their ability to exclude fluorescent dyes, express specific cell surface markers or grow in particular culture conditions. A key feature of CSCs is their resistance to chemotherapeutic agents, which could contribute to the remaining of residual cancer cells after therapeutic treatments. It has been shown that CSC-like cells can be isolated after drug treatment of cancer cell lines; in this review, we will describe the strategies so far applied to identify and isolate CSCs. Furthermore, we will discuss the possible use of these selected populations to investigate CSC biology and develop new anticancer drugs

  17. Circulating tumor cells in lung cancer.

    Science.gov (United States)

    Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

    2012-01-01

    Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. PMID:23207444

  18. Interleukin-1β induces fibroblast growth factor 2 expression and subsequently promotes endothelial progenitor cell angiogenesis in chondrocytes.

    Science.gov (United States)

    Chien, Szu-Yu; Huang, Chun-Yin; Tsai, Chun-Hao; Wang, Shih-Wei; Lin, Yu-Min; Tang, Chih-Hsin

    2016-05-01

    Arthritis is a process of chronic inflammation that results in joint damage. IL (interleukin)-1β is an inflammatory cytokine that acts as a key mediator of cartilage degradation, and is abundantly expressed in arthritis. Neovascularization is one of the pathological characteristics of arthritis. However, the role of IL-1β in the angiogenesis of chondrocytes remains unknown. In the present study, we demonstrate that stimulating chondrocytes (ATDC5) with IL-1β increased the expression of FGF (fibroblast growth factor)-2, a potent angiogenic inducer, and then promoted EPC (endothelial progenitor cell) tube formation and migration. In addition, FGF-2-neutralizing antibody abolished ATDC5-conditional medium-mediated angiogenesis in vitro, as well as its angiogenic effects in the CAM (chick chorioallantoic membrane) assay and Matrigel plug nude mice model in vivo. IHC (immunohistochemistry) staining from a CIA (collagen-induced arthritis) mouse model also demonstrates that arthritis increased the expression of IL-1β and FGF-2, as well as EPC homing in articular cartilage. Moreover, IL-1β-induced FGF-2 expression via IL-1RI (type-1 IL-1 receptor), ROS (reactive oxygen species) generation, AMPK (AMP-activated protein kinase), p38 and NF-κB (nuclear factor κB) pathway has been demonstrated. On the basis of these findings, we conclude that IL-1β promotes FGF-2 expression in chondrocytes through the ROS/AMPK/p38/NF-κB signalling pathway and subsequently increases EPC angiogenesis. Therefore IL-1β serves as a link between inflammation and angiogenesis during arthritis. PMID:26811540

  19. Sunitinib activates Axl signaling in renal cell cancer.

    Science.gov (United States)

    van der Mijn, Johannes C; Broxterman, Henk J; Knol, Jaco C; Piersma, Sander R; De Haas, Richard R; Dekker, Henk; Pham, Thang V; Van Beusechem, Victor W; Halmos, Balazs; Mier, James W; Jiménez, Connie R; Verheul, Henk M W

    2016-06-15

    Mass spectrometry-based phosphoproteomics provides a unique unbiased approach to evaluate signaling network in cancer cells. The tyrosine kinase inhibitor sunitinib is registered as treatment for patients with renal cell cancer (RCC). We investigated the effect of sunitinib on tyrosine phosphorylation in RCC tumor cells to get more insight in its mechanism of action and thereby to find potential leads for combination treatment strategies. Sunitinib inhibitory concentrations of proliferation (IC50) of 786-O, 769-p and A498 RCC cells were determined by MTT-assays. Global tyrosine phosphorylation was measured by LC-MS/MS after immunoprecipitation with the antiphosphotyrosine antibody p-TYR-100. Phosphoproteomic profiling of 786-O cells yielded 1519 phosphopeptides, corresponding to 675 unique proteins including 57 different phosphorylated protein kinases. Compared to control, incubation with sunitinib at its IC50 of 2 µM resulted in downregulation of 86 phosphopeptides including CDK5, DYRK3, DYRK4, G6PD, PKM and LDH-A, while 94 phosphopeptides including Axl, FAK, EPHA2 and p38α were upregulated. Axl- (y702), FAK- (y576) and p38α (y182) upregulation was confirmed by Western Blot in 786-O and A498 cells. Subsequent proliferation assays revealed that inhibition of Axl with a small molecule inhibitor (R428) sensitized 786-O RCC cells and immortalized endothelial cells to sunitinib up to 3 fold. In conclusion, incubation with sunitinib of RCC cells causes significant upregulation of multiple phosphopeptides including Axl. Simultaneous inhibition of Axl improves the antitumor activity of sunitinib. We envision that evaluation of phosphoproteomic changes by TKI treatment enables identification of new targets for combination treatment strategies. PMID:26815723

  20. Circulating Tumor Cells in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Brian [Institute of Urology, University of Southern California, 1441 Eastlake Avenue, Suite 7416, Los Angeles, CA 90033 (United States); Rochefort, Holly [Department of Surgery, University of Southern California, 1520 San Pablo Street, HCT 4300, Los Angeles, CA 90033 (United States); Goldkorn, Amir, E-mail: agoldkor@usc.edu [Department of Internal Medicine and Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Suite 3440, Los Angeles, CA 90033 (United States)

    2013-12-04

    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.

  1. Circulating Tumor Cells in Prostate Cancer

    International Nuclear Information System (INIS)

    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

  2. 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.

  3. 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.

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

    International Nuclear Information System (INIS)

    Research highlights: → Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). → Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. → Monoclonal cell lines showed reduced sensitivity for Paclitaxel. → In situ CD133+ cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. → CD133+ 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+ 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.

  5. Human Colon Cancer Cells Cultivated in Space

    Science.gov (United States)

    1995-01-01

    Within five days, bioreactor cultivated human colon cancer cells (shown) grown in Microgravity on the STS-70 mission in 1995, had grown 30 times the volume of the control specimens on Earth. The samples grown in space had a higher level of cellular organization and specialization. Because they more closely resemble tumors found in the body, microgravity grown cell cultures are ideal for research purposes.

  6. Orthotopic Injection of Pancreatic Cancer Cells.

    Science.gov (United States)

    Aiello, Nicole M; Rhim, Andrew D; Stanger, Ben Z

    2016-01-01

    Pancreatic ductal adenocarcinoma is an aggressive disease with a 5-yr survival rate of only 5%. The location of the pancreas in the abdomen, where it is obscured by other organs, makes it a difficult tissue to study and manipulate. This protocol describes in detail how to orthotopically inject cancer cells into the pancreas in mice. This technique is particularly useful when the cells must be manipulated in ways that cannot be modeled genetically. PMID:26729902

  7. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  8. Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Li, Yingrui; Xu, Xun; Song, Luting;

    2012-01-01

    sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading to...... two distinct tumor cell subpopulations. By analyzing recurrently mutant genes in an additional cohort of 99 TCC tumors, we identified genes that might play roles in the maintenance of the ancestral clone and in the muscle-invasive capability of subclones of this bladder cancer, respectively...

  9. 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.

  10. Cancer Stem Cells: Cell Culture, Markers and Targets for New Therapies

    OpenAIRE

    Gilbert, Candace A.; Ross, Alonzo H.

    2009-01-01

    A cancer stem cell is defined as an undifferentiated cell with the ability to self-renew, differentiate to multiple lineages and initiate tumors that mimic the parent tumor. In this review, we focus on glioblastomas, describing recent progress and problems in characterizing these cells. There have been advances in cancer stem cell culture, but tumor cell heterogeneity has made purification of cancer stem cells difficult. Indeed, it may be that cancer stem cells significantly vary from tumor t...

  11. Membrane proteomic analysis of pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Liu Xiaojun

    2010-09-01

    Full Text Available Abstract Background Pancreatic cancer is one of the most aggressive human tumors due to its high potential of local invasion and metastasis. The aim of this study was to characterize the membrane proteomes of pancreatic ductal adenocarcinoma (PDAC cells of primary and metastatic origins, and to identify potential target proteins related to metastasis of pancreatic cancer. Methods Membrane/membrane-associated proteins were isolated from AsPC-1 and BxPC-3 cells and identified with a proteomic approach based on SDS-PAGE, in-gel tryptic digestion and liquid chromatography with tandem mass spectrometry (LC-MS/MS. X! Tandem was used for database searching against the SwissProt human protein database. Results We identified 221 & 208 proteins from AsPC-1 and BxPC-3 cells, respectively, most of which are membrane or membrane-associated proteins. A hundred and nine proteins were found in both cell lines while the others were present in either AsPC-1 or BxPC-3 cells. Differentially expressed proteins between two cell lines include modulators of cell adhesion, cell motility or tumor invasion as well as metabolic enzymes involved in glycolysis, tricarboxylic acid cycle, or nucleotide/lipid metabolism. Conclusion Membrane proteomes of AsPC-1 (metastatic and BxPC-3 (primary cells are remarkably different. The differentially expressed membrane proteins may serve as potential targets for diagnostic and therapeutic interventions.

  12. Heme oxygenase-1 determines the differential response of breast cancer and normal cells to piperlongumine.

    Science.gov (United States)

    Lee, Ha-Na; Jin, Hyeon-Ok; Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, BoRa; Kim, Wonki; Hong, Sung-Eun; Lee, Yun-Han; Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun; Park, In-Chul; Surh, Young-Joon; Lee, Jin Kyung

    2015-04-01

    Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic α,β-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine. PMID:25813625

  13. Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles

    Directory of Open Access Journals (Sweden)

    Hu C

    2015-03-01

    Full Text Available Chenxia Hu,1 Martin Niestroj,2,3 Daniel Yuan,4 Steven Chang,5 Jie Chen5,6 1Faculty of Chinese Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Canadian Light Source, Saskatoon, SK, Canada; 3Physics Department, Bonn University, Bonn, Germany; 4Biomedical Engineering Department, Johns Hopkins University, Baltimore, MD, USA; 5Faculty of Engineering, University of Alberta, Edmonton, AB, Canada; 6Canadian National Research Council/National Institute for Nanotechnology, Edmonton, AB, Canada Abstract: Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain. Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs with thio-PEG (polyethylene glycol and thio-glucose, the resulting functionalized GNPs (Glu-GNPs were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption

  14. Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression

    International Nuclear Information System (INIS)

    Circulating tumor cells (CTCs) are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e.g., a range of 0–54 CTCs per 5 min). These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients

  15. Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression

    Energy Technology Data Exchange (ETDEWEB)

    Juratli, Mazen A.; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A. [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Melerzanov, Alexander V. [Moscow Institute of Physics and Technology (MIPT), Moscow Region, 141700 (Russian Federation); Zharov, Vladimir P. [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States); Moscow Institute of Physics and Technology (MIPT), Moscow Region, 141700 (Russian Federation); Galanzha, Ekaterina I., E-mail: egalanzha@uams.edu [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2014-01-15

    Circulating tumor cells (CTCs) are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e.g., a range of 0–54 CTCs per 5 min). These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients.

  16. Dynamic Fluctuation of Circulating Tumor Cells during Cancer Progression

    Directory of Open Access Journals (Sweden)

    Mazen A. Juratli

    2014-01-01

    Full Text Available Circulating tumor cells (CTCs are a promising diagnostic and prognostic biomarker for metastatic tumors. We demonstrate that CTCs’ diagnostic value might be increased through real-time monitoring of CTC dynamics. Using preclinical animal models of breast cancer and melanoma and in vivo flow cytometry with photoacoustic and fluorescence detection schematics, we show that CTC count does not always correlate with the primary tumor size. Individual analysis elucidated many cases where the highest level of CTCs was detected before the primary tumor starts progressing. This phenomenon could be attributed to aggressive tumors developing from cancer stem cells. Furthermore, real-time continuous monitoring of CTCs reveals that they occur at highly variable rates in a detection point over a period of time (e.g., a range of 0–54 CTCs per 5 min. These same fluctuations in CTC numbers were observed in vivo in epithelial and non-epithelial metastatic tumors, in different stages of tumor progression, and in different vessels. These temporal CTC fluctuations can explain false negative results of a one-time snapshot test in humans. Indeed, we observed wide variations in the number of CTCs in subsequent blood samples taken from the same metastatic melanoma patient, with some samples being CTC-free. If these phenomena are confirmed in our ongoing in vivo clinical trials, this could support a personalized strategy of CTC monitoring for cancer patients.

  17. Stemness is derived from thyroid cancer cells

    Directory of Open Access Journals (Sweden)

    RishengMa

    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.

  18. Enrichment and Function Research of Large Cell Lung Cancer Stem Cell-like Cells

    Directory of Open Access Journals (Sweden)

    Wenke YUE

    2011-06-01

    Full Text Available Background and objective There are no universal method to recognize and screen for lung cancer stem cell markers and indicators. Commonly used methods are flow Cytometry and learning from other cancer stem cell sorting tags to sort lung cancer stem cells. But this method has low specificity screening, the workload is huge. In this study, Serum-free suspension culture was used to enrich lung cancer stem cells, and explore method for lung cancer stem cell screening. Methods Human large lung cancer cell line-L9981 was cultured in serum-free and growth factors added medium, and spheres were obtained. Then the morphological differences of sphere cells and adherent L9981 cells cultured in serum-containing mediums are observed. Cell proliferation was analyzed by Vi-cell viability analyzer; invasion ability was tested by transwell assay; and in vivo tumorigenicity of the two groups of cells was studied in nude mouse. Results Compared with adherent L9981 cells cultured in serum-containing mediums, cells cultured in serum-free medium display sphere appearance. Doubling time of adherent cells and sphere cells are (56.05±1.95 h and (33.00±1.44 h respectively; Spheroid cells had higher invasion and tumorigenicity ability, 5 times and 20 times respectively, than adherent cells. Conclusion Suspension cultured L9981 in Serum-free medium could form spheroid populations. Cells in spheres had higher ability of invasion and Tumorigenicity than adherent L9981 cells. These results indicated spheroid L9981 cells contained enriched lung cancer stem cells, and Serum-free suspension culture can be a candidate method for enriching lung cancer stem cell.

  19. Alpha lipoic acid inhibits proliferation and epithelial mesenchymal transition of thyroid cancer cells.

    Science.gov (United States)

    Jeon, Min Ji; Kim, Won Gu; Lim, Seonhee; Choi, Hyun-Jeung; Sim, Soyoung; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

    2016-01-01

    The naturally occurring short-chain fatty acid, α-lipoic acid (ALA) is a powerful antioxidant which is clinically used for treatment of diabetic neuropathy. Recent studies suggested the possibility of ALA as a potential anti-cancer agent, because it could activate adenosine monophosphate activated protein kinase (AMPK) and inhibit transforming growth factor-β (TGFβ) pathway. In this study, we evaluate the effects of ALA on thyroid cancer cell proliferation, migration and invasion. We performed in vitro cell proliferation analysis using BCPAP, HTH-83, CAL-62 and FTC-133 cells. ALA suppressed thyroid cancer cell proliferation through activation of AMPK and subsequent down-regulation of mammalian target of rapamycin (mTOR)-S6 signaling pathway. Low-dose ALA, which had minimal effects on cell proliferation, also decreased cell migration and invasion of BCPAP, CAL-62 and HTH-83 cells. ALA inhibited epithelial mesenchymal transition (EMT) evidently by increase of E-cadherin and decreases of activated β-catenin, vimentin, snail, and twist in these cells. ALA suppressed TGFβ production and inhibited induction of p-Smad2 and twist by TGFβ1 or TGFβ2. These findings indicate that ALA reduces cancer cell migration and invasion through suppression of TGFβ production and inhibition of TGFβ signaling pathways in thyroid cancer cells. ALA also significantly suppressed tumor growth in mouse xenograft model using BCPAP and FTC-133 cells. This is the first study to show anti-cancer effect of ALA on thyroid cancer cells. ALA could be a potential therapeutic agent for treatment of advanced thyroid cancer, possibly as an adjuvant therapy with other systemic therapeutic agents. PMID:26463583

  20. Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer

    OpenAIRE

    Roh, Jong-Lyel; Kim, Eun Hye; Park, Jin Young; Kim, Ji Won; Kwon, Minsu; Lee, Byung-Heon

    2014-01-01

    Adaptation to cellular stress is not a vital function of normal cells but is required of cancer cells, and as such might be a sensible target in cancer therapy. Piperlongumine is a naturally occurring small molecule selectively toxic to cancer cells. This study assesses the cytotoxicity of piperlongumine and its combination with cisplatin in head-and-neck cancer (HNC) cells in vitro and in vivo. The effect of piperlongumine, alone and in combination with cisplatin, was assessed in human HNC c...

  1. Non-Small Cell Lung Cancer: Screening, Diagnosis, and Staging

    OpenAIRE

    Ferreira, J; Magalhães, M; Rocha, E; Marques, F

    2012-01-01

    Lung cancer is the leading cause of cancer deaths worldwide. Tobacco consumption is the primary cause of lung cancer, accounting for more than 85% 90% of all lung cancer deaths. Non-small cell lung cancer accounts for about 85% of all lung cancers. Several studies have shown that low-dose helical CT of the lung detects more nodules and lung cancers, including early-stage cancers, than does chest radiography. The National Lung Cancer Screening Trial results show that three annual roun...

  2. New insights into pancreatic cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Chinthalapally V Rao; Altaf Mohammed

    2015-01-01

    Pancreatic cancer (PC) has been one of the deadliest of allcancers, with almost uniform lethality despite aggressivetreatment. Recently, there have been important advancesin the molecular, pathological and biological understandingof pancreatic cancer. Even after the emergence of recentnew targeted agents and the use of multiple therapeuticcombinations, no treatment option is viable in patients withadvanced cancer. Developing novel strategies to targetprogression of PC is of intense interest. A small populationof pancreatic cancer stem cells (CSCs) has been foundto be resistant to chemotherapy and radiation therapy.CSCs are believed to be responsible for tumor initiation,progression and metastasis. The CSC research has recentlyachieved much progress in a variety of solid tumors,including pancreatic cancer to some extent. This leads tofocus on understanding the role of pancreatic CSCs. Thefocus on CSCs may offer new targets for prevention andtreatment of this deadly cancer. We review the most salientdevelopments in important areas of pancreatic CSCs. Here,we provide a review of current updates and new insightson the role of CSCs in pancreatic tumor progression withspecial emphasis on DclK1 and Lgr5, signaling pathwaysaltered by CSCs, and the role of CSCs in prevention andtreatment of PC.

  3. Advanced research on separating prostate cancer stem cells

    International Nuclear Information System (INIS)

    Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

  4. Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction

    OpenAIRE

    Shabo, Ivan; Midtbö, Kristine Maria; Andersson, Henrik; Åkerlund, Emma; Olsson, Hans; Wegman, Pia; Gunnarsson, Cecilia; Lindström, Annelie

    2015-01-01

    Background: Cell fusion is a natural process in normal development and tissue regeneration. Fusion between cancer cells and macrophages generates metastatic hybrids with genetic and phenotypic characteristics from both maternal cells. However, there are no clinical markers for detecting cell fusion in clinical context. Macrophage-specific antigen CD163 expression in tumor cells is reported in breast and colorectal cancers and proposed being caused by macrophages-cancer cell fusion in tumor st...

  5. Types of Stem Cell Transplants for Treating Cancer

    Science.gov (United States)

    ... Sources of stem cells for transplant Types of stem cell transplants for treating cancer In a typical stem ... come from your identical twin or triplet Autologous stem cell transplants These stem cells come from you alone. ...

  6. 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.

  7. Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells

    International Nuclear Information System (INIS)

    Mechanisms of digitoxin-inhibited cell growth and induced apoptosis in human non-small cell lung cancer (NCI-H460) cells remain unclear. Understanding how digitoxin or derivate analogs induce their cytotoxic effect below therapeutically relevant concentrations will help in designing and developing novel, safer and more effective anti-cancer drugs. In this study, NCI-H460 cells were treated with digitoxin and a synthetic analog D6-MA to determine their anti-cancer activity. Different concentrations of digitoxin and D6-MA were used and the subsequent changes in cell morphology, viability, cell cycle, and protein expressions were determined. Digitoxin and D6-MA induced dose-dependent apoptotic morphologic changes in NCI-H460 cells via caspase-9 cleavage, with D6-MA possessing 5-fold greater potency than digitoxin. In comparison, non-tumorigenic immortalized bronchial and small airway epithelial cells displayed significantly less apoptotic sensitivity compared to NCI-H460 cells suggesting that both digitoxin and D6-MA were selective for NSCLC. Furthermore, NCI-H460 cells arrested in G(2)/M phase following digitoxin and D6-MA treatment. Post-treatment evaluation of key G2/M checkpoint regulatory proteins identified down-regulation of cyclin B1/cdc2 complex and survivin. Additionally, Chk1/2 and p53 related proteins experienced down-regulation suggesting a p53-independent cell cycle arrest mechanism. In summary, digitoxin and D6-MA exert anti-cancer effects on NCI-H460 cells through apoptosis or cell cycle arrest, with D6-MA showing at least 5-fold greater potency relative to digitoxin. -- Highlights: ► Digitoxin and synthetic analog D6-MA induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. ► Apoptotic cell death induced by analog was 5-fold more potent when compared to digitoxin. ► NCI-H460 cells arrested in G(2)/M phase following digitoxin (≥ 5 nM) and analog (≥ 1 nM) treatment. ► Digitoxin inhibited the expression of cyclin

  8. Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Elbaz, Hosam A. [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Stueckle, Todd A. [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); National Institute for Occupational Safety and Health, Morgantown, WV26506 (United States); Wang, Hua-Yu Leo; O' Doherty, George A. [Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115 (United States); Lowry, David T.; Sargent, Linda M.; Wang, Liying [National Institute for Occupational Safety and Health, Morgantown, WV26506 (United States); Dinu, Cerasela Zoica, E-mail: cerasela-zoica.dinu@mail.wvu.edu [Department of Chemical Engineering, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-01-01

    Mechanisms of digitoxin-inhibited cell growth and induced apoptosis in human non-small cell lung cancer (NCI-H460) cells remain unclear. Understanding how digitoxin or derivate analogs induce their cytotoxic effect below therapeutically relevant concentrations will help in designing and developing novel, safer and more effective anti-cancer drugs. In this study, NCI-H460 cells were treated with digitoxin and a synthetic analog D6-MA to determine their anti-cancer activity. Different concentrations of digitoxin and D6-MA were used and the subsequent changes in cell morphology, viability, cell cycle, and protein expressions were determined. Digitoxin and D6-MA induced dose-dependent apoptotic morphologic changes in NCI-H460 cells via caspase-9 cleavage, with D6-MA possessing 5-fold greater potency than digitoxin. In comparison, non-tumorigenic immortalized bronchial and small airway epithelial cells displayed significantly less apoptotic sensitivity compared to NCI-H460 cells suggesting that both digitoxin and D6-MA were selective for NSCLC. Furthermore, NCI-H460 cells arrested in G(2)/M phase following digitoxin and D6-MA treatment. Post-treatment evaluation of key G2/M checkpoint regulatory proteins identified down-regulation of cyclin B1/cdc2 complex and survivin. Additionally, Chk1/2 and p53 related proteins experienced down-regulation suggesting a p53-independent cell cycle arrest mechanism. In summary, digitoxin and D6-MA exert anti-cancer effects on NCI-H460 cells through apoptosis or cell cycle arrest, with D6-MA showing at least 5-fold greater potency relative to digitoxin. -- Highlights: ► Digitoxin and synthetic analog D6-MA induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. ► Apoptotic cell death induced by analog was 5-fold more potent when compared to digitoxin. ► NCI-H460 cells arrested in G(2)/M phase following digitoxin (≥ 5 nM) and analog (≥ 1 nM) treatment. ► Digitoxin inhibited the expression of cyclin

  9. Tamoxifen-resistant breast cancer cells possess cancer stem-like cell properties

    Institute of Scientific and Technical Information of China (English)

    LIU Hui; ZHANG Heng-wei; SUN Xian-fu; GUO Xu-hui; HE Ya-ning; CUI Shu-de; FAN Qing-xia

    2013-01-01

    Background Cancer stem cells (CSCs) are the cause of cancer recurrence because they are resistant to conventional therapy and contribute to cancer growth and metastasis.Endocrinotherapy is the most common breast cancer therapy and acquired tamoxifen (TAM) resistance is the main reason for endocrinotherapy failure during such therapy.Although acquired resistance to endocrine treatment has been extensively studied,the underlying mechanisms are unclear.We hypothesized that breast CSCs played an important role in TAM-induced resistance during breast cancer therapy.Therefore,we investigated the biological characteristics of TAM-resistant (TAM-R) breast cancer cells.Methods Mammosphere formation and tumorigenicity of wild-type (WT) and TAM-R MCF7 cells were tested by a mammosphere assay and mouse tumor xenografts respectively.Stem-cell markers (SOX-2,OCT-4,and CD133) and epithelial-mesenchymal transition (EMT) markers were tested by quantitative real-time (qRT)-PCR.Morphological observation was performed to characterize EMT.Results After induction of TAM resistance,TAM-R MCF7 cells exhibited increased proliferation in the presence of TAM compared to that of WT MCF7 cells (P <0.05),indicating enhanced TAM resistance of TAM-R MCF7 cells compared to that of WT MCF7 cells.TAM-R MCF7 cells showed enhanced mammosphere formation and tumorigenicity in nude mice compared to that of WT MCF7 cells (P <0.01),demonstrating the elevated CSC properties of TAM-R MCF7 cells.Consistently,qRT-PCR revealed that TAM-R MCF7 cells expressed increased mRNA levels of stem cell markers including SOX-2,OCT-4,and CD133,compared to those of WT MCF7 cells (P <0.05).Morphologically,TAM-R MCF7 cells showed a fibroblastic phenotype,but WT MCF7 cells were epithelial-like.After induction of TAM resistance,qRT-PCR indicated that MCF7 cells expressed increased mRNA levels of Snail,vimentin,and N-cadherin and decreased levels of E-cadherin,which are considered as EMT characteristics (P <0

  10. Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation.

    Science.gov (United States)

    Zhang, Wenwen; Cao, Lulu; Sun, Zijia; Xu, Jing; Tang, Lin; Chen, Weiwei; Luo, Jiayan; Yang, Fang; Wang, Yucai; Guan, Xiaoxiang

    2016-05-18

    The F box protein Skp2 is oncogenic. Skp2 and Skp2B, an isoform of Skp2 are overexpressed in breast cancer. However, little is known regarding the mechanism by which Skp2B promotes the occurrence and development of breast cancer. Here, we determined the expression and clinical outcomes of Skp2 in breast cancer samples and cell lines using breast cancer database, and investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest. We obtained Skp2 is significantly overexpressed in breast cancer samples and cell lines, and high Skp2 expression positively correlated with poor prognosis of breast cancer. Both Skp2 and Skp2B could promote breast cancer cell proliferation, inhibit cell apoptosis, change the cell cycle distribution and induce the increased S phase cells and therefore induce cell proliferation in breast cancer cells. Moreover, the 2 isoforms could both suppress PIG3 expression via independent pathways in the breast cancer cells. Skp2 suppressed p53 and inhibited PIG3-induced apoptosis, while Skp2B attenuated the function of PIG3 by inhibiting PHB. Our results indicate that Skp2 and Skp2B induce breast cancer cell development and progression, making Skp2 and Skp2B potential molecular targets for breast cancer therapy. PMID:27111245

  11. Use of subsequent PET/CT in diffuse large B-cell lymphoma patients in complete remission following primary therapy

    Institute of Scientific and Technical Information of China (English)

    Xu Zhang; Wei Fan; Zhong-Jun Xia; Ying-Ying Hu; Xiao-Ping Lin; Ya-Rui Zhang; Zhi-Ming Li; Pei-Yan Liang; Yuan-Hua Li

    2015-01-01

    Interim 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (I-PET/CT) is a powerful tool for monitoring the response to therapy in diffuse large B-cell lymphoma (DLBCL). This retrospective study aimed to determine when and how to use I-PET/CT in DLBCL. A total of 197 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were enrolled between October 2005 and July 2011; PET/CT was performed at the time of diagnosis (PET/CT0), after 2 and 4 cycles of chemotherapy (PET/CT2 and PET/CT4, respectively), and at the end of treatment (F-PET/CT). According to the International Harmonization Project for Response Criteria in Lymphoma, 110 patients had negative PET/CT2 scans, and 87 had positive PET/CT2 scans. The PET/CT2-negative patients had significantly higher 3-year progression-free survival rate (75.8% vs. 38.2%) and 3-year overal survival rate (93.5%vs. 55.6%) than PET/CT2-positive patients. Al PET/CT2-negative patients remained negative at PET/CT4, but 3 were positive at F-PET/CT. Among the 87 PET/CT2-positive patients, 57 remained positive at F-PET/CT, and 32 progressed during chemotherapy (15 at PET/CT4 and 17 at F-PET/CT). Comparing PET/CT4 with PET/CT0, 7 patients exhibited progression, and 8 achieved partial remission. Comparing F-PET/CT with PET/CT0, 10 patients exhibited progression, and 7 achieved partial remission. In conclusion, our results indicate that I-PET/CT should be performed after 2 rather than 4 cycles of immunochemotherapy in DLBCL patients. There is a limited role for subsequent PET/CT in the detection of relapse in PET/CT2-negative patients, but repeat PET/CT is required if the PET/CT2 findings are positive.

  12. Role of Oxidative Stress in Stem, Cancer, and Cancer Stem Cells

    International Nuclear Information System (INIS)

    The term ‘‘oxidative stress” refers to a cell’s state characterized by excessive production of reactive oxygen species (ROS) and oxidative stress is one of the most important regulatory mechanisms for stem, cancer, and cancer stem cells. The concept of cancer stem cells arose from observations of similarities between the self-renewal mechanism of stem cells and that of cancer stem cells, but compared to normal stem cells, they are believed to have no control over the cell number. ROS have been implicated in diverse processes in various cancers, and generally the increase of ROS in cancer cells is known to play an important role in the initiation and progression of cancer. Additionally, ROS have been considered as the most significant mutagens in stem cells; when elevated, blocking self-renewal and at the same time, serving as a signal stimulating stem cell differentiation. Several signaling pathways enhanced by oxidative stress are suggested to have important roles in tumorigenesis of cancer or cancer stem cells and the self-renewal ability of stem or cancer stem cells. It is now well established that mitochondria play a prominent role in apoptosis and increasing evidence supports that apoptosis and autophagy are physiological phenomena closely linked with oxidative stress. This review elucidates the effect and the mechanism of the oxidative stress on the regulation of stem, cancer, and cancer stem cells and focuses on the cell signaling cascades stimulated by oxidative stress and their mechanism in cancer stem cell formation, as very little is known about the redox status in cancer stem cells. Moreover, we explain the link between ROS and both of apoptosis and autophagy and the impact on cancer development and treatment. Better understanding of this intricate link may shed light on mechanisms that lead to better modes of cancer treatment

  13. Immune cell interplay in colorectal cancer prognosis

    Institute of Scientific and Technical Information of China (English)

    Samuel; E; Norton; Kirsten; A; Ward-Hartstonge; Edward; S; Taylor; Roslyn; A; Kemp

    2015-01-01

    The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, par-ticularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship betweencancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment.

  14. Radiation response in prostate cancer stem cells

    International Nuclear Information System (INIS)

    The full text of the publication follows. Introduction: Currently, there is no successful treatment for secondary prostate cancer. Resistance of secondary tumours and metastases to radiotherapy and chemotherapy might be explained by cancer stem cells (CSCs). Prostate (P) CSCs are rare cells defined by cell surface markers, CD133+, a2b1integrinhi and CD44+, and are capable of self-renewal, differentiation and invasion in vitro and tumour initiation in vivo. Hypothesis: PCSCs have an alternative DNA damage response following radiation and are resistant to radiation treatment. Methods: Primary prostate (benign and cancer) epithelial stem (SC) transit amplifying (TA, CD133-/a2b1integrinhi/CD44+) and committed basal (CB, CD133-/a2b1integrinlo/CD44+) cells were exposed to 2 Gy of radiation (IR) to induce a DNA damage response. Immunofluorescence was used to quantify nuclear foci, representative of DNA damage response proteins (g-H2AX, 53BP1, phosphorylated ATM/ATR substrates, phospho-Chk2Th68). Immunofluorescence was also used to co-stain for heterochromatin and DNA damage markers. Comet assays (neutral and alkaline) were used to directly assess DNA damage. Results: In benign and cancer cells, the SCs had a lower percentage of cells containing initial foci (30 min post-IR), compared to the TA and CB cells. At 24 h post-IR there was a reduced percentage of cells positive for foci in TA and CB cells suggesting repair. Whilst there were also signs of repair in benign SCs, in the PCSCs there was an increase in percentage of cells positive for foci at 24 h, indicative of a delayed damage response. Comet assays indicated that SCs sustain different kinds of DNA damage to TA and CB cells. Heterochromatin staining indicated that DNA damage foci preferentially formed in euchromatin. Future work: Further studies will include apoptosis and clonogenic assays to measure PCSC survival. In addition, PCSC chromatin status will be examined to elucidate DNA repair kinetics. If we are able

  15. Highly parallel identification of essential genes in cancer cells

    OpenAIRE

    Luo, Biao; Cheung, Hiu Wing; Subramanian, Aravind; Sharifnia, Tanaz; Okamoto, Michael; Yang, Xiaoping; Hinkle, Greg; Boehm, Jesse S.; Beroukhim, Rameen; Weir, Barbara A.; Mermel, Craig; Barbie, David A; Awad, Tarif; Zhou, Xiaochuan; Nguyen, Tuyen Van

    2008-01-01

    More complete knowledge of the molecular mechanisms underlying cancer will improve prevention, diagnosis and treatment. Efforts such as The Cancer Genome Atlas are systematically characterizing the structural basis of cancer, by identifying the genomic mutations associated with each cancer type. A powerful complementary approach is to systematically characterize the functional basis of cancer, by identifying the genes essential for growth and related phenotypes in different cancer cells. Such...

  16. FBXL5 targets cortactin for ubiquitination-mediated destruction to regulate gastric cancer cell migration.

    Science.gov (United States)

    Cen, Gang; Ding, Hong-Hua; Liu, Bin; Wu, Wei-Dong

    2014-09-01

    Cortactin, an actin-interacting protein, is implicated in cytoskeletal architecture and often amplified in several types of cancer including gastric adenocarcinomas. Downregulation of cortactin decreases cell migration and invasion. However, how to regulate cortactin in gastric cancer remains largely unknown. Here, we report that FBXL5 interacts with and targets cortactin for ubiquitylation and subsequent proteasomal degradation. Furthermore, we showed that FBXL5-induced cortactin degradation is mediated by extracellular regulated signal kinase (ERK). Serine phosphorylation sites mutant, cortactinS405A/S418A, prevent FBXL5-induced cortactin degradation. Moreover, CortactinS405A/S418A exhibited stronger effects in promoting gastric cancer cell migration when compared to wild-type cortactin. Taken together, our data suggested a novel molecular mechanism for the negative regulation of cortactin by FBXL5 in gastric cancer cells migration. PMID:24867096

  17. 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

  18. Lymphocyte Infusion in Treating Patients With Relapsed Cancer After Bone Marrow or Peripheral Stem Cell Transplantation

    Science.gov (United States)

    2011-11-28

    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

  19. Cancer Stem Cells: Distinct Entities or Dynamically Regulated Phenotypes?

    OpenAIRE

    Li, Yunqing; Laterra, John

    2012-01-01

    The origins of tumor propagating neoplastic stem-like cells (cancer stem cells, CSCs) and their relationship to the bulk population of tumor cells that lack stem-like tumor-propagating features(i.e. transit-amplifying cancer progenitor cells) remain unclear. Recent findings from multiple laboratories show that cancer progenitor cells have the capacity to dedifferentiate and acquire a stem-like phenotype in response to either genetic manipulation or environmental cues. These findings suggest t...

  20. Thyroid stem cells: lessons from normal development and thyroid cancer

    OpenAIRE

    Thomas, Dolly; Friedman, Susan; Lin, Reigh-Yi

    2008-01-01

    Ongoing advances in stem cell research have opened new avenues for therapy for many human disorders. Until recently, however, thyroid stem cells have been relatively understudied. Here, we review what is known about thyroid stem cells and explore their utility as models of normal and malignant biological development. We also discuss the cellular origin of thyroid cancer stem cells and explore the clinical implications of cancer stem cells in the thyroid gland. Since thyroid cancer is the most...

  1. Selective killing of cancer cells by nanoparticle-assisted ultrasound

    OpenAIRE

    Kosheleva, Olga K.; Lai, Tsung-Ching; Chen, Nelson G.; Hsiao, Michael; Chen, Chung-Hsuan

    2016-01-01

    Background Intense ultrasound, such as that used for tumor ablation, does not differentiate between cancerous and normal cells. A method combining ultrasound and biocompatible gold or magnetic nanoparticles (NPs) was developed under in vitro conditions using human breast and lung epithelial cells, which causes ultrasound to preferentially destroy cancerous cells. Results Co-cultures of BEAS-2B normal lung cells and A549 cancerous lung cells labeled with green and red fluorescent proteins, res...

  2. Regulation of cell death in cancer - possible implications for immunotherapy

    OpenAIRE

    Simone eFulda

    2013-01-01

    Since most anticancer therapies including immunotherapy trigger programmed cell death in cancer cells, defective cell death programs can lead to treatment resistance and tumor immune escape. Therefore, evasion of programmed cell death may provide one possible explanation as to why cancer immunotherapy has so far only shown modest clinical benefits for children with cancer. A better understanding of the molecular mechanisms that regulate sensitivity and resistance to programmed cell death is e...

  3. Galiellalactone Inhibits Stem Cell-Like ALDH-Positive Prostate Cancer Cells

    OpenAIRE

    Hellsten, Rebecka; Johansson, Martin; Dahlman, Anna; Sterner, Olov; Bjartell, Anders

    2011-01-01

    Galiellalactone is a potent and specific inhibitor of STAT3 signaling which has been shown to possess growth inhibitory effects on prostate cancer cells expressing active STAT3. In this study we aimed to investigate the effect of galiellalactone on prostate cancer stem cell-like cells. We explored the expression of aldehyde dehydrogenase (ALDH) as a marker for cancer stem cell-like cells in different human prostate cancer cell lines and the effects of galiellalactone on ALDH expressing (ALDH+...

  4. Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate.

    Science.gov (United States)

    Orth, James D; Tang, Yangzhong; Shi, Jade; Loy, Clement T; Amendt, Christiane; Wilm, Claudia; Zenke, Frank T; Mitchison, Timothy J

    2008-11-01

    Kinesin-5 inhibitors (K5I) are promising antimitotic cancer drug candidates. They cause prolonged mitotic arrest and death of cancer cells, but their full range of phenotypic effects in different cell types has been unclear. Using time-lapse microscopy of cancer and normal cell lines, we find that a novel K5I causes several different cancer and noncancer cell types to undergo prolonged arrest in monopolar mitosis. Subsequent events, however, differed greatly between cell types. Normal diploid cells mostly slipped from mitosis and arrested in tetraploid G(1), with little cell death. Several cancer cell lines died either during mitotic arrest or following slippage. Contrary to prevailing views, mitotic slippage was not required for death, and the duration of mitotic arrest correlated poorly with the probability of death in most cell lines. We also assayed drug reversibility and long-term responses after transient drug exposure in MCF7 breast cancer cells. Although many cells divided after drug washout during mitosis, this treatment resulted in lower survival compared with washout after spontaneous slippage likely due to chromosome segregation errors in the cells that divided. Our analysis shows that K5Is cause cancer-selective cell killing, provides important kinetic information for understanding clinical responses, and elucidates mechanisms of drug sensitivity versus resistance at the level of phenotype. PMID:18974392

  5. Gastric cancer stem cells: A novel therapeutic target

    OpenAIRE

    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, ...

  6. T-helper-1-cell cytokines drive cancer into senescence

    OpenAIRE

    Braumüller, Heidi; Wieder, Thomas; Brenner, Ellen; Aßmann, Sonja; Hahn, Matthias; Alkhaled, Mohammed; Schilbach, Karin; Essmann, Frank; Kneilling, Manfred; Griessinger, Christoph; Ranta, Felicia; Ullrich, Susanne; Mocikat, Ralph; Braungart, Kilian; Mehra, Tarun

    2013-01-01

    Cancer control by adaptive immunity involves a number of defined death and clearance mechanisms. However, efficient inhibition of exponential cancer growth by T cells and interferon-γ (IFN-γ) requires additional undefined mechanisms that arrest cancer cell proliferation. Here we show that the combined action of the T-helper-1-cell cytokines IFN-γ and tumour necrosis factor (TNF) directly induces permanent growth arrest in cancers. To safely separate senescence induced by tumour immunity from ...

  7. Albendazole sensitizes cancer cells to ionizing radiation

    International Nuclear Information System (INIS)

    Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells. Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage. ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours. Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted

  8. Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer

    OpenAIRE

    Tae Hun Kim; Dong Hoon Suh; Mi-Kyung Kim; Yong Sang Song

    2014-01-01

    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 wi...

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

    International Nuclear Information System (INIS)

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

  10. Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival

    Directory of Open Access Journals (Sweden)

    Hsieh Fu-Chuan

    2008-10-01

    Full Text Available Abstract Background Constitutive activation of signal transducer and activator of transcription 3 (Stat3 signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer. Results We found that elevated Stat3 phosphorylation in 19 of 100 (19% bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC. The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin and a cell cycle regulating gene (cyclin D1 was associated with the cell growth inhibition and apoptosis. Conclusion These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.

  11. Vapor of volatile oils from Litsea cubeba seed induces apoptosis and causes cell cycle arrest in lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Soma Seal

    Full Text Available Non-small cell lung carcinoma (NSCLC is a major killer in cancer related human death. Its therapeutic intervention requires superior efficient molecule(s as it often becomes resistant to present chemotherapy options. Here we report that vapor of volatile oil compounds obtained from Litsea cubeba seeds killed human NSCLC cells, A549, through the induction of apoptosis and cell cycle arrest. Vapor generated from the combined oils (VCO deactivated Akt, a key player in cancer cell survival and proliferation. Interestingly VCO dephosphorylated Akt at both Ser(473 and Thr(308; through the suppression of mTOR and pPDK1 respectively. As a consequence of this, diminished phosphorylation of Bad occurred along with the decreased Bcl-xL expression. This subsequently enhanced Bax levels permitting the release of mitochondrial cytochrome c into the cytosol which concomitantly activated caspase 9 and caspase 3 resulting apoptotic cell death. Impairment of Akt activation by VCO also deactivated Mdm2 that effected overexpression of p53 which in turn upregulated p21 expression. This causes enhanced p21 binding to cyclin D1 that halted G1 to S phase progression. Taken together, VCO produces two prong effects on lung cancer cells, it induces apoptosis and blocked cancer cell proliferation, both occurred due to the deactivation of Akt. In addition, it has another crucial advantage: VCO could be directly delivered to lung cancer tissue through inhalation.

  12. 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.

  13. Impact of High-Dose Chemotherapy on the Ability to Deliver Subsequent Local-Regional Radiotherapy for Breast Cancer: Analysis of Cancer and Leukemia Group B Protocol 9082

    International Nuclear Information System (INIS)

    Purpose: To report, from Cancer and Leukemia Group B Protocol 9082, the impact of high-dose cyclophosphamide, cisplatin, and BCNU (HD-CPB) vs. intermediate-dose CPB (ID-CPB) on the ability to start and complete the planned course of local-regional radiotherapy (RT) for women with breast cancer involving ≥10 axillary nodes. Methods and Materials: From 1991 to 1998, 785 patients were randomized. The HD-CPB and ID-CPB arms were balanced regarding patient characteristics. The HD-CPB and ID-CPB arms were compared on the probability of RT initiation, interruption, modification, or incompleteness. The impact of clinical variables and interactions between variables were also assessed. Results: Radiotherapy was initiated in 82% (325 of 394) of HD-CPB vs. 92% (360 of 391) of ID-CPB patients (p = 0.001). On multivariate analyses, RT was less likely given to patients who were randomized to HD treatment (odds ratio [OR] = 0 .38, p < 0.001), older (p = 0.005), African American (p = 0.003), postmastectomy (p = 0.02), or estrogen receptor positive (p = 0.03). High-dose treatment had a higher rate of RT interruption (21% vs. 12%, p = 0.001, OR = 2.05), modification (29% vs. 14%, p = 0.001, OR = 2.46), and early termination of RT (9% vs. 2%, p = 0.0001, OR = 5.35), compared with ID. Conclusion: Treatment arm significantly related to initiation, interruption, modification, and early termination of RT. Patients randomized to HD-CPB were less likely to initiate RT, and of those who did, they were more likely to have RT interrupted, modified, and terminated earlier than those randomized to ID-CPB. The observed lower incidence of RT usage in African Americans vs. non-African Americans warrants further study.

  14. Sialylation: an Avenue to Target Cancer Cells.

    Science.gov (United States)

    Vajaria, Bhairavi N; Patel, Kinjal R; Begum, Rasheedunnisa; Patel, Prabhudas S

    2016-07-01

    Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoproteins and glycolipids. The expression of sialylated glycoconjugates has been shown to change during development, differentiation, disease and oncogenic transformation. Abnormal sialylation in cancer cell is a distinctive feature associated with malignant properties including invasiveness and metastatic potential. The alterations in sialylation is accompanied by changes in sialic acid, sialidase activity, sialyltransferase (ST) activity or sialoproteins. The present review summarizes the reports on alterations of sialic acid, linkage specific STs and sialoproteins, sialidase activity together with different subtypes of ST and sialidases mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is governed by levels of sialidases and STs. Various types of STs are also involved in formation of different types sialylated tumor associated carbohydrate antigens which plays important role in metastasis. The alterations associated with sialylation aids in early diagnosis, prognosis and post treatment monitoring in various cancers. Recently newer drugs targeting different interplays of sialylation have been developed, which might have profound effect in inhibiting sialylation and thus cancer metastasis and infiltration. PMID:26685886

  15. Heat induces gene amplification in cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. ► Hyperthermia induces DNA double strand breaks. ► DNA double strand breaks are considered to be required for the initiation of gene amplification. ► 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 °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) γH2AX immunostaining to detect γH2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 °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 °C for 30 min induces DNA double strand breaks in HCT116 cells as shown by γH2AX 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 telomere functions are denatured. To our knowledge, this is the first study to provide direct evidence of hyperthermia induced gene amplification.

  16. 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

  17. Electrodynamic activity of healthy and cancer cells

    International Nuclear Information System (INIS)

    Microtubules in the cell form a structure capable of generating electrodynamic field and mitochondria form their supporting system for physical processes including energy supply. Mitochondria transfer protons from their matrix space into cytosol, create strong static field around them that causes ordering of water and altering it into quasi-elastic medium with reduced viscous damping. Microtubules are composed of heterodimers that are electric dipoles. Microtubule oscillations generate an electrodynamic field. The greatest energy supply may be provided by liberation of non-utilized energy from mitochondria. Microtubules and mitochondria form a unique cooperating system in the cell. Mitochondria form a boundary element whose function depends on chemical-genetic control but their output is essential for physical processes in the cell. Mitochondrial dysfunction in cancer cells results in diminished intensity of the static electric field, disturbed water ordering, increased damping of microtubule oscillations and their shift towards linear region, and decreased energy supply. Power and coherence of oscillations and generated electrodynamic field is weakened. Malignant properties of cancer cell, in particular local invasion and metastasis, may depend on disturbed electrodynamic field. Nanotechnology is promising for investigation of electrodynamic activity in living cells.

  18. Cancer, stem cells and cancer stem cells: old ideas, new developments

    OpenAIRE

    Ghaffari, Saghi

    2011-01-01

    It has been suggested that, at least in some forms of cancer, a sub-population of slow-cycling, therapy-resistant cancer stem cells exists that has the ability to reconstitute the tumor in its entirety. If true, this model implies that conventional therapies based on targeting highly cycling cells within the tumor will leave the slow-cycling stem cell population intact, giving them the opportunity to reinitiate the tumor at a later date. This review discusses the evidence for this model and t...

  19. Clinical significance of T cell metabolic reprogramming in cancer.

    Science.gov (United States)

    Herbel, Christoph; Patsoukis, Nikolaos; Bardhan, Kankana; Seth, Pankaj; Weaver, Jessica D; Boussiotis, Vassiliki A

    2016-12-01

    Conversion of normal cells to cancer is accompanied with changes in their metabolism. During this conversion, cell metabolism undergoes a shift from oxidative phosphorylation to aerobic glycolysis, also known as Warburg effect, which is a hallmark for cancer cell metabolism. In cancer cells, glycolysis functions in parallel with the TCA cycle and other metabolic pathways to enhance biosynthetic processes and thus support proliferation and growth. Similar metabolic features are observed in T cells during activation but, in contrast to cancer, metabolic transitions in T cells are part of a physiological process. Currently, there is intense interest in understanding the cause and effect relationship between metabolic reprogramming and T cell differentiation. After the recent success of cancer immunotherapy, the crosstalk between immune system and cancer has come to the forefront of clinical and basic research. One of the key goals is to delineate how metabolic alterations of cancer influence metabolism-regulated function and differentiation of tumor resident T cells and how such effects might be altered by immunotherapy. Here, we review the unique metabolic features of cancer, the implications of cancer metabolism on T cell metabolic reprogramming during antigen encounters, and the translational prospective of harnessing metabolism in cancer and T cells for cancer therapy. PMID:27510264

  20. Experience of ReCell in Skin Cancer Reconstruction

    OpenAIRE

    Onur Gilleard; Nicholas Segaren; Ciaran Healy

    2013-01-01

    The ReCell system (Avita Medical) is a cell culture product that allows the immediate processing of a small split-thickness skin biopsy to produce a complete population of cells including keratinocytes, melanocytes, Langerhans cells and fibroblasts. This series is the first to highlight the reconstructive applications of ReCell following ablative skin cancer surgery. The ReCell system was utilized for three patients following skin cancer excision. In two cases, the cells were applied to foreh...

  1. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    Science.gov (United States)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  2. An optimization study on unprogrammed cryopreservation of human CD34+ bone marrow cells and their subsequent storage in an -80 degrees C mechanical freezer.

    Science.gov (United States)

    Ratajczak, M Z; Ratajczak, J; Kregenow, D A; Marlicz, W; Machalinski, B; Simon, M; Luger, S; Gewirtz, A M

    1997-01-01

    Among the factors which enable successful bone marrow transplantation, the ability to store and subsequently recover sufficient viable marrow cells to reestablish hematopoiesis is crucial. In most centers, marrow is typically prepared for long term storage by programmed, controlled rate freezing with subsequent placement into the vapor phase of liquid nitrogen. Though clearly effective, this procedure is time consuming and equipment intensive. Since cost containment is an important issue for all medical procedures, we evaluated the utility of a faster and less costly method to accomplish the same purpose. We found that when CD34+ bone marrow cells are immediately frozen and stored at -80 degrees C, the number and quality of stem/progenitor cells recovered after thawing was comparable to those reported recovered after conventional processing. Herein we report optimized conditions for cryopreserving and storing CD34+ bone marrow cells at -80 degrees C and for subsequent thawing of the stored product. With these methods post-thaw recovery of CFU-Mix, for example, equaled or exceeded 80% of predicted numbers, even after six months of storage. Further, though progenitor cell recovery does not necessarily correlate with speed of engraftment, these results nonetheless suggest that storage of human CD34+ cells at -80 degrees C in a mechanical freezer is a convenient, inexpensive, and reliable method for storing marrow for transplantation. PMID:9869847

  3. Left behind? Drug discovery in extensive-stage small-cell lung cancer.

    Science.gov (United States)

    Riess, Jonathan W; Lara, Primo N

    2014-03-01

    Systemic therapy and subsequent survival for patients with extensive-stage small-cell lung cancer (SCLC) are poor and have remained unchanged in the past quarter century. To improve outcomes in these patients, a new drug development paradigm must be adopted that moves away from empiricism and instead focuses on tumor biology and heterogeneity as a means to increase target and drug class diversity. By incorporating tools that have led to new diagnostic and treatment options in non-small-cell lung cancer, there could be hope yet for the future of SCLC therapeutics. PMID:24529447

  4. Molecular imaging of hypoxia in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Connie [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); St Thomas' Hospital, Imaging 2, London (United Kingdom); Blower, Philip J. [King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Goh, Vicky [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Clinical Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J.R. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Clinical PET Imaging Centre, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2015-05-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  5. Molecular imaging of hypoxia in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  6. NK cells, pregnancy, cancer. A short review

    Czech Academy of Sciences Publication Activity Database

    Vannucci, Luca; Pospíšil, Miloslav; Fišerová, Anna

    2005-01-01

    Roč. 8, č. 4 (2005), s. 147-152. ISSN 1506-4794 R&D Projects: GA AV ČR IAA500200509; GA AV ČR IAA5020403; GA ČR GA524/04/0102; GA AV ČR IAA500200510 Institutional research plan: CEZ:AV0Z50200510 Keywords : natural killer cells * immune tolerance * cancer Subject RIV: EE - Microbiology, Virology

  7. Neuroendocrine differentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois; Souček, Karel

    Budapest, 2008. s. 194. [ISAC XXIV International Congress, Cytometry in the Age of Systems Biology. 17.05.2008-21.05.2008, Budapest] R&D Projects: GA ČR(CZ) GA204/07/0834 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * neuroendocrine-like cells * prostate cancer Subject RIV: BO - Biophysics

  8. (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

    Science.gov (United States)

    Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

  9. The Use of Mild Trypsinization Conditions in the Detachment of Endothelial Cells to Promote Subsequent Endothelialization on Synthetic Surfaces

    OpenAIRE

    Brown, Melissa A.; Wallace, Charles S.; Anamelechi, Charles C.; Clermont, Edward; Reichert, William M.; Truskey, George A.

    2007-01-01

    A necessary condition for endothelialization of small diameter grafts is rapid and firm adhesion of endothelial cells upon exposure to flow. To retain integrins on the cell surface, we assessed the effects of trypsin concentration, the duration of trypsin incubation, and trypsin neutralization methods on endothelial cell adhesion. Human umbilical vein endothelial cells which were detached using 0.025% trypsin for five minutes and seeded onto glass pretreated with fibronectin had close to 100%...

  10. Deformability and size-based cancer cell separation using an integrated microfluidic device.

    Science.gov (United States)

    Pang, Long; Shen, Shaofei; Ma, Chao; Ma, Tongtong; Zhang, Rui; Tian, Chang; Zhao, Lei; Liu, Wenming; Wang, Jinyi

    2015-11-01

    Cell sorting by filtration techniques offers a label-free approach for cell separation on the basis of size and deformability. However, filtration is always limited by the unpredictable variation of the filter hydrodynamic resistance due to cell accumulation and clogging in the microstructures. In this study, we present a new integrated microfluidic device for cell separation based on the cell size and deformability by combining the microstructure-constricted filtration and pneumatic microvalves. Using this device, the cell populations sorted by the microstructures can be easily released in real time for subsequent analysis. Moreover, the periodical sort and release of cells greatly avoided cell accumulation and clogging and improved the selectivity. Separation of cancer cells (MCF-7, MDA-MB-231 and MDA231-LM2) with different deformability showed that the mixture of the less flexible cells (MCF-7) and the flexible cells (MDA-MB-231 and MDA231-LM2) can be well separated with more than 75% purity. Moreover, the device can be used to separate cancer cells from the blood samples with more than 90% cell recovery and more than 80% purity. Compared with the current filtration methods, the device provides a new approach for cancer cell separation with high collection recovery and purity, and also, possesses practical potential to be applied as a sample preparation platform for fundamental studies and clinical applications. PMID:26366443

  11. 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.

  12. Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro.

    Science.gov (United States)

    Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan; Lei, Xiao-Fei; Zhang, Ji-Xiang; Dong, Wei-Guo

    2012-05-11

    Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC(50)=75 μM). This cytotoxicity was reflected by cell cycle arrest at G(2)/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer. PMID:22546556

  13. Re-programming tumour cell metabolism to treat cancer: no lone target for lonidamine.

    Science.gov (United States)

    Bhutia, Yangzom D; Babu, Ellappan; Ganapathy, Vadivel

    2016-06-01

    Tumour cell metabolism is very different from normal cell metabolism; cancer cells re-programme the metabolic pathways that occur in normal cells in such a manner that it optimizes their proliferation, growth and survival. Although this metabolic re-programming obviously operates to the advantage of the tumour, it also offers unique opportunities for effective cancer therapy. Molecules that target the tumour cell-specific metabolic pathways have potential as novel anti-cancer drugs. Lonidamine belongs to this group of molecules and is already in use in some countries for cancer treatment. It has been known for a long time that lonidamine interferes with energy production in tumour cells by inhibiting hexokinase II (HKII), a glycolytic enzyme. However, subsequent studies have uncovered additional pharmacological targets for the drug, which include the electron transport chain and the mitochondrial permeability transition pore, thus expanding the pharmacological effects of the drug on tumour cell metabolism. A study by Nancolas et al. in a recent issue of the Biochemical Journal identifies two additional new targets for lonidamine: the pyruvate transporter in the mitochondria and the H(+)-coupled monocarboxylate transporters in the plasma membrane (PM). It is thus becoming increasingly apparent that the anti-cancer effects of lonidamine do not occur through a single target; the drug works at multiple sites. Irrespective of the molecular targets, what lonidamine does in the end is to undo what the tumour cells have done in terms of re-programming cellular metabolism and mitochondrial function. PMID:27234586

  14. Imprinted survival genes preclude loss of heterozygosity of chromosome 7 in cancer cells.

    Science.gov (United States)

    Boot, Arnoud; Oosting, Jan; de Miranda, Noel Fcc; Zhang, Yinghui; Corver, Willem E; van de Water, Bob; Morreau, Hans; van Wezel, Tom

    2016-09-01

    The genomes of a wide range of cancers, including colon, breast, and thyroid cancers, frequently show copy number gains of chromosome 7 and rarely show loss of heterozygosity. The molecular basis for this phenomenon is unknown. Strikingly, oncocytic follicular thyroid carcinomas can display an extreme genomic profile, with homozygosity of all chromosomes except for chromosome 7. The observation that homozygosity of chromosome 7 is never observed suggests that retention of heterozygosity is essential for cells. We hypothesized that cell survival genes are genetically imprinted on either of two copies of chromosome 7, which thwarts loss of heterozygosity at this chromosome in cancer cells. By employing a DNA methylation screen and gene expression analysis, we identified six imprinted genes that force retention of heterozygosity on chromosome 7. Subsequent knockdown of gene expression showed that CALCR, COPG2, GRB10, KLF14, MEST, and PEG10 were essential for cancer cell survival, resulting in reduced cell proliferation, G1 -phase arrest, and increased apoptosis. We propose that imprinted cell survival genes provide a genetic basis for retention of chromosome 7 heterozygosity in cancer cells. The monoallelically expressed cell survival genes identified in this study, and the cellular pathways that they are involved in, offer new therapeutic targets for the treatment of tumours showing retention of heterozygosity on chromosome 7. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27265324

  15. Can a Cancer Cell Turn into a Normal Cell?

    Directory of Open Access Journals (Sweden)

    Ranan Gülhan Aktas

    2014-09-01

    Full Text Available HepG2 cells, a human liver cancer cell line (hepatocellular carcinoma, are being considered as a future model for bioartificial liver studies. They have the ability to differentiate and demonstrate some features of normal liver cells. Our previous studies focused on examination of the morphological and functional properties of these cells under different extracellular environmental conditions. We have created a culture model that these cells demonstrate remarkable changes after 30 days. These changes include an increase in the cytoplasmic organelles, formation of bile canaliculi, occurrence of junctional complexes between the adjacent cells, existence of microvilli on the apical surfaces, accumulation of glycogen particles in the cytoplasm, an increase at the density of albumin labeled areas and a rise at the Na-K ATPase level on cellular membranes.

  16. 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.

  17. 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.

  18. Stromal-cell and cancer-cell exosomes leading the metastatic exodus for the promised niche

    OpenAIRE

    Hoffman, Robert M.

    2013-01-01

    Exosomes are thought to play an important role in metastasis. Luga and colleagues have described the production of exosomes by stromal cells such as cancer-associated fibroblasts that are taken up by breast cancer cells and are then loaded with Wnt 11, which is associated with stimulation of the invasiveness and metastasis of the breast cancer cells. Previous studies have shown that exosomes produced by breast cancer cells are taken up by stromal fibroblasts and other stromal cells, suggestin...

  19. Lack of correlation of stem cell markers in breast cancer stem cells

    OpenAIRE

    Liu, Y; Nenutil, R; Appleyard, M V; Murray, K; Boylan, M; Thompson, A. M.; Coates, P J

    2014-01-01

    Background: Various markers are used to identify the unique sub-population of breast cancer cells with stem cell properties. Whether these markers are expressed in all breast cancers, identify the same population of cells, or equate to therapeutic response is controversial. Methods: We investigated the expression of multiple cancer stem cell markers in human breast cancer samples and cell lines in vitro and in vivo, comparing across and within samples and relating expression with growth and t...

  20. Comparative anticancer potential of clove (Syzygium aromaticum)--an Indian spice--against cancer cell lines of various anatomical origin.

    Science.gov (United States)

    Dwivedi, Vinay; Shrivastava, Richa; Hussain, Showket; Ganguly, Chaiti; Bharadwaj, Mausumi

    2011-01-01

    Spices, active ingredients of Indian cooking, may play important roles in prevention and treatment of various cancers. The objective of the present study is to compare the in vitro anticancer activities of three different extracts of Clove (Syzygium aromaticum L), a commonly used spice and food flavouring agent, against different kinds of cancer cell lines of various anatomical derivations. Water, ethanol and oil extracts were screened for anti proliferative activity against HeLa (cervical cancer), MCF-7 (ER + ve) and MDA-MB-231 (ER - ve) breast cancer, DU-145 prostate cancer and TE-13 esophageal cancer cell lines, along with normal human peripheral blood lymphocytes. Inhibition of cell proliferation was assessed using MTT assay as a vital stain. In the examined five cancer cell lines, the extracts showed different patterns of cell growth inhibition activity, with the oil extract having maximal cytotoxic activity. Morphological analysis and DAPI staining showed cytotoxicity to be a result of cell disruption with subsequent membrane rupture. Maximum cell death and apoptotic cell demise occurred in TE-13 cells within 24 hours by clove oil at 300 μl/ml with 80% cell death whereas DU-145 cells showed minimal cell death. At the same time, no significant cytotoxicity was found in human PBMC's at the same dose. PMID:22292639

  1. Transformation-associated changes in sphingolipid metabolism sensitize cells to lysosomal cell death induced by inhibitors of acid sphingomyelinase

    DEFF Research Database (Denmark)

    Petersen, Nikolaj H T; Olsen, Ole D; Groth-Pedersen, Line;

    2013-01-01

    Lysosomal membrane permeabilization and subsequent cell death may prove useful in cancer treatment, provided that cancer cell lysosomes can be specifically targeted. Here, we identify acid sphingomyelinase (ASM) inhibition as a selective means to destabilize cancer cell lysosomes. Lysosome...

  2. Cancer stem cells in haematological malignancies

    OpenAIRE

    Zagozdzon, Radoslaw; Golab, Jakub

    2015-01-01

    At least several types of human haematological malignancies can now be seen as ‘stem-cell diseases’. The best-studied in this context is acute myeloid leukaemia (AML). It has been shown that these diseases are driven by a pool of ‘leukaemia stem cells (LSC)’, which remain in the quiescent state, have the capacity to survive and self-renew, and are responsible for the recurrence of cancer after classical chemotherapy. It has been understood that LSC must be eliminated in order to cure patients...

  3. Microrheology of keratin networks in cancer cells

    International Nuclear Information System (INIS)

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a deceasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior. (paper)

  4. Microrheology of keratin networks in cancer cells.

    Science.gov (United States)

    Paust, T; Paschke, S; Beil, M; Marti, O

    2013-12-01

    Microrheology is a valuable tool to determine viscoelastic properties of polymer networks. For this purpose measurements with embedded tracer beads inside the extracted network of pancreatic cancer cells were performed. Observing the beads motion with a CCD-high-speed-camera leads to the dynamic shear modulus. The complex shear modulus is divided into real and imaginary parts which give insight into the mechanical properties of the cell. The dependency on the distance of the embedded beads to the rim of the nucleus shows a tendency for a decreasing storage modulus. We draw conclusions on the network topology of the keratin network types based on the mechanical behavior. PMID:24305115

  5. Wnt/β-catenin signaling regulates cancer stem cells in lung cancer A549 cells

    International Nuclear Information System (INIS)

    Wnt/β-catenin signaling plays an important role not only in cancer, but also in cancer stem cells. In this study, we found that β-catenin and OCT-4 was highly expressed in cisplatin (DDP) selected A549 cells. Stimulating A549 cells with lithium chloride (LiCl) resulted in accumulation of β-catenin and up-regulation of a typical Wnt target gene cyclin D1. This stimulation also significantly enhanced proliferation, clone formation, migration and drug resistance abilities in A549 cells. Moreover, the up-regulation of OCT-4, a stem cell marker, was observed through real-time PCR and Western blotting. In a reverse approach, we inhibited Wnt signaling by knocking down the expression of β-catenin using RNA interference technology. This inhibition resulted in down-regulation of the Wnt target gene cyclin D1 as well as the proliferation, clone formation, migration and drug resistance abilities. Meanwhile, the expression of OCT-4 was reduced after the inhibition of Wnt/β-catenin signaling. Taken together, our study provides strong evidence that canonical Wnt signaling plays an important role in lung cancer stem cell properties, and it also regulates OCT-4, a lung cancer stem cell marker.

  6. Ovarian Cancer Stem Cell Markers: Prognostic and Therapeutic Implications

    OpenAIRE

    Burgos-Ojeda, Daniela; Rueda, Bo R.; Buckanovich, Ronald J.

    2012-01-01

    Cancer stem cells are rare chemotherapy resistant cells within a tumor which can serve to populate the bulk of a tumor with more differentiated daughter cells and potentially contribute to recurrent disease. Ovarian cancer is a disease for which at the time of initial treatment we can obtain complete clinical remission in the majority of patients. Unfortunately, most will relapse and succumb to their disease. This clinical course is in line with the cancer stem cell model. In the past five ye...

  7. Cancer Stem Cells in Brain Tumors and Their Lineage Hierarchy

    OpenAIRE

    Kong, Doo-Sik

    2012-01-01

    Despite recent advances in the development of novel targeted chemotherapies, the prognosis of malignant glioma remains dismal. The chemo-resistance of this tumor is attributed to tumor heterogeneity. To explain this unique chemo- resistance, the concept of cancer stem cells has been evoked. Cancer stem cells, a subpopulation of whole tumor cells, are now regarded as candidate therapeutic targets. Here, the author reviews and discusses the cancer stem cell concept.

  8. Risk Factors for Renal Cell Cancer in a Japanese Population

    OpenAIRE

    Washio, Masakazu; Mori, Mitsuru

    2009-01-01

    The incidence of renal cell cancer has been increasing worldwide. Although the incidence of renal cell cancer in Japan is lower than the rates in the other industrialized countries, there is no doubt that it is increasing. In this paper, we would like to introduce the result of our studies, which evaluate the risk factors for renal cell cancer in Japan. Hypertension, diabetes mellitus, kidney diseases, fondness for fatty food and black tea showed an increased risk of renal cell carcinoma whil...

  9. Cancer stem cell plasticity and tumor hierarchy

    Institute of Scientific and Technical Information of China (English)

    Marina Carla Cabrera; Robert E Hollingsworth; Elaine M Hurt

    2015-01-01

    The origins of the complex process of intratumoralheterogeneity have been highly debated and differentcellular mechanisms have been hypothesized to accountfor the diversity within a tumor. The clonal evolution andcancer stem cell (CSC) models have been proposed asdrivers of this heterogeneity. However, the concept ofcancer stem cell plasticity and bidirectional conversionbetween stem and non-stem cells has added additionalcomplexity to these highly studied paradigms and may helpexplain the tumor heterogeneity observed in solid tumors.The process of cancer stem cell plasticity in which cancercells harbor the dynamic ability of shifting from a non-CSCstate to a CSC state and vice versa may be modulated byspecific microenvironmental signals and cellular interactionsarising in the tumor niche. In addition to promoting CSCplasticity, these interactions may contribute to the cellulartransformation of tumor cells and affect response tochemotherapeutic and radiation treatments by providingCSCs protection from these agents. Herein, we review theliterature in support of this dynamic CSC state, discussthe effectors of plasticity, and examine their role in thedevelopment and treatment of cancer.

  10. Scanning the cell surface proteome of cancer cells and identification of metastasis-associated proteins using a subtractive immunization strategy

    DEFF Research Database (Denmark)

    Rasmussen, Nicolaj; Ditzel, Henrik J

    2009-01-01

    and technologically challenging, and no ideal method is currently available. Here, we describe a strategy that allows scanning of the entire cell surface and identification of molecules that exhibit altered expression between two cell types. Concurrently, this method gives rise to valuable reagents...... for further characterization of the identified proteins. The strategy is based on subtractive immunization of mice, and we used the two isogenic cell lines, NM-2C5 and M-4A4, derived from the MDA-MB-435 cancer cell line, as a model system. Although the two cell lines are equally tumorigenic, only M-4A...... neuroendocrine tumors while exhibiting no or very weak reactivity with normal tissues. mAb 15C7 stained a variety of cancers as well as some normal lymphoid organs and was subsequently identified to react with HLA-DR-beta. A third mAb, 31D7, that also specifically recognized HLA-DR-beta was capable of inhibiting...

  11. Cancer Stem Cells: Foe or Reprogrammable Cells for Efficient Cancer Therapy?

    Directory of Open Access Journals (Sweden)

    Carlo Ventura

    2015-11-01

    Full Text Available Embryonic development and carcinogenesis share many molecular pathways and regulatory molecules. While the induction of a pluripotent state involves a significant oncogenic risk, as in induced pluripotent stem cells (iPSCs, the embryonic environment in vivo has been shown to suppress tumor development. In this review, we discuss the subtle equilibrium between the nanotopography (niche of the hosting tissue resident stem cells and their biological dynamics, including the transformation in cancer stem cells. We review consistent findings indicating the potential for modulating the biology of human cancer stem cells by the aid of naturally occurring or synthetic molecules, including developmental stage zebrafish embryo extracts, hyaluronan, butyric acid (BA and retinoic acid (RA, hyaluronan mixed esters of BA and RA, melatonin, vitamin D3, and endorphin peptides. Within this context, we dissect the multifaceted mechanisms orchestrated by endorphinergic systems, including paracrine cellto- cell communication, as well as the establishment of autocrine and intracrine (intracellular peptide actions driving transcriptional responses and self-sustaining loops that behave as long-lived signals imparting features characteristic of differentiation, growth regulation and cell memory. Based upon the remarkable action of electromagnetic fields and mechanical vibration on (stem cell signaling, differentiation, and senescence, we also consider the potential for using these physical energies as a tool to afford a fine tuning of cancer stem cell fate. On the whole, we forecast future deployment of the physical and/or chemical approaches described herein aiming at reprogramming, rather than destroying cancer stem cells, eventually placing cancer therapy within the context of Regenerative Medicine.

  12. Prevalence of Epithelial Ovarian Cancer Stem Cells Correlates with Recurrence in Early-Stage Ovarian Cancer

    OpenAIRE

    Gil Mor; Anders Jakobsen; Thomas Rutherford; Dan-Arin Silasi; Holmberg, Jennie C.; Pei Hui; Marianne Waldstrøm; Karina Dahl Steffensen; Alvero, Ayesha B.; Yang Yang

    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 h...

  13. Role of Oxidative Stress in Stem, Cancer, and Cancer Stem Cells

    OpenAIRE

    Ahmed Abdal Dayem; Hye-Yeon Choi; Jung-Hyun Kim; Ssang-Goo Cho

    2010-01-01

    The term ‘‘oxidative stress” refers to a cell’s state characterized by excessive production of reactive oxygen species (ROS) and oxidative stress is one of the most important regulatory mechanisms for stem, cancer, and cancer stem cells. The concept of cancer stem cells arose from observations of similarities between the self-renewal mechanism of stem cells and that of cancer stem cells, but compared to normal stem cells, they are believed to have no control over the cell number. ROS have bee...

  14. Targeting Negative Surface Charges of Cancer Cells by Multifunctional Nanoprobes.

    Science.gov (United States)

    Chen, Bingdi; Le, Wenjun; Wang, Yilong; Li, Zhuoquan; Wang, Dong; Ren, Lei; Lin, Ling; Cui, Shaobin; Hu, Jennifer J; Hu, Yihui; Yang, Pengyuan; Ewing, Rodney C; Shi, Donglu; Cui, Zheng

    2016-01-01

    A set of electrostatically charged, fluorescent, and superparamagnetic nanoprobes was developed for targeting cancer cells without using any molecular biomarkers. The surface electrostatic properties of the established cancer cell lines and primary normal cells were characterized by using these nanoprobes with various electrostatic signs and amplitudes. All twenty two randomly selected cancer cell lines of different organs, but not normal control cells, bound specifically to the positively charged nanoprobes. The relative surface charges of cancer cells could be quantified by the percentage of cells captured magnetically. The activities of glucose metabolism had a profound impact on the surface charge level of cancer cells. The data indicate that an elevated glycolysis in the cancer cells led to a higher level secretion of lactate. The secreted lactate anions are known to remove the positive ions, leaving behind the negative changes on the cell surfaces. This unique metabolic behavior is responsible for generating negative cancer surface charges in a perpetuating fashion. The metabolically active cancer cells are shown to a unique surface electrostatic pattern that can be used for recovering cancer cells from the circulating blood and other solutions. PMID:27570558

  15. Targeting Negative Surface Charges of Cancer Cells by Multifunctional Nanoprobes

    Science.gov (United States)

    Chen, Bingdi; Le, Wenjun; Wang, Yilong; Li, Zhuoquan; Wang, Dong; Ren, Lei; Lin, Ling; Cui, Shaobin; Hu, Jennifer J.; Hu, Yihui; Yang, Pengyuan; Ewing, Rodney C.; Shi, Donglu; Cui, Zheng

    2016-01-01

    A set of electrostatically charged, fluorescent, and superparamagnetic nanoprobes was developed for targeting cancer cells without using any molecular biomarkers. The surface electrostatic properties of the established cancer cell lines and primary normal cells were characterized by using these nanoprobes with various electrostatic signs and amplitudes. All twenty two randomly selected cancer cell lines of different organs, but not normal control cells, bound specifically to the positively charged nanoprobes. The relative surface charges of cancer cells could be quantified by the percentage of cells captured magnetically. The activities of glucose metabolism had a profound impact on the surface charge level of cancer cells. The data indicate that an elevated glycolysis in the cancer cells led to a higher level secretion of lactate. The secreted lactate anions are known to remove the positive ions, leaving behind the negative changes on the cell surfaces. This unique metabolic behavior is responsible for generating negative cancer surface charges in a perpetuating fashion. The metabolically active cancer cells are shown to a unique surface electrostatic pattern that can be used for recovering cancer cells from the circulating blood and other solutions. PMID:27570558

  16. Cavitary Lung Cancer Lined with Normal Bronchial Epithelium and Cancer Cells

    OpenAIRE

    Goto, Taichiro; Maeshima, Arafumi; Oyamada, Yoshitaka; Kato, Ryoichi

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells.

  17. Direct targeting of cancer cells: a multiparameter approach.

    Science.gov (United States)

    Heinrich, Eileen L; Welty, Lily Anne Y; Banner, Lisa R; Oppenheimer, Steven B

    2005-01-01

    Lectins have been widely used in cell surface studies and in the development of potential anticancer drugs. Many past studies that have examined lectin toxicity have only evaluated the effects on cancer cells, not their non-cancer counterparts. In addition, few past studies have evaluated the relationship between lectin-cell binding and lectin toxicity on both cell types. Here we examine these parameters in one study: lectin-cell binding and lectin toxicity with both cancer cells and their normal counterparts. We found that the human colon cancer cell line CCL-220/Colo320DM bound to agarose beads derivatized with Phaseolus vulgaris agglutinin (PHA-L) and wheat germ agglutinin (WGA), while the non-cancer human colon cell line CRL-1459/CCD-18Co did not. When these lectins were tested for their effects on cell viability in culture, both cell lines were affected by the lectins but at 6, 48 and 72 h incubation times, PHA-L was most toxic to the cancer cell line in a concentration dependent manner. At 48 h incubation, WGA was more toxic to the cancer cell line. The results suggest that it may be possible to develop lectin protocols that selectively target cancer cells for death. In any case, examination of both malignant cells and their non-malignant counterparts, analysis of their binding characteristics to immobilized lectins, and examination of the toxicity of free lectins in culture, provides a multiparameter model for obtaining more comprehensive information than from more limited approaches. PMID:16181664

  18. Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate

    Directory of Open Access Journals (Sweden)

    Yumi Kawazoe, Shinichi Katoh, Yuichiro Onodera, Takao Kohgo, Masanobu Shindoh, Toshikazu Shiba

    2008-01-01

    Full Text Available Inorganic polyphosphate [poly(P] is a biopolymer existing in almost all cells and tissues, although its biological functions in higher eukaryotes have not been completely elucidated. We previously demonstrated that poly(P enhances the function of fibroblast growth factors (FGFs by stabilizing them and strengthening the affinity between FGFs and their cell surface receptors. Since FGFs play crucial roles in bone regeneration, we further investigated the effect of poly(P on the cell differentiation of human stem cells via FGF signaling systems. Human dental pulp cells (HDPCs isolated from human dental pulp show the characteristics of multipotent mesenchymal stem cells (MSCs. HDPCs secreted FGFs and the proliferation of HDPCs was shown to be enhanced by treatment with poly(P. Cell surface receptor-bound FGF-2 was stably maintained for more than 40 hours in the presence of poly(P. The phosphorylation of ERK1/2 was also enhanced by poly(P. The effect of poly(P on the osteogenic differentiation of HDPCs and human MSCs (hMSCs were also investigated. After 5 days of treatment with poly(P, type-I collagen expression of both cell types was enhanced. The C-terminal peptide of type-I collagen was also released at higher levels in poly(P-treated HDPCs. Microarray analysis showed that expression of matrix metalloproteinase-1 (MMP1, osteopontin (OPN, osteocalcin (OC and osteoprotegerin was induced in both cell types by poly(P. Furthermore, induced expression of MMP1, OPN and OC genes in both cells was confirmed by real-time PCR. Calcification of both cell types was clearly observed by alizarin red staining following treatment with poly(P. The results suggest that the activation of the FGF signaling pathway by poly(P induces both proliferation and mineralization of stem cells.

  19. Murine Lung Cancer Induces Generalized T Cell Exhaustion

    Science.gov (United States)

    Mittal, Rohit; Chen, Ching-Wen; Lyons, John D; Margoles, Lindsay M; Liang, Zhe; Coopersmith, Craig M; Ford, Mandy L

    2015-01-01

    Background Cancer is known to modulate tumor-specific immune responses by establishing a micro-environment that leads to the upregulation of T cell inhibitory receptors, resulting in the progressive loss of function and eventual death of tumor-specific T cells. However, the ability of cancer to impact the functionality of the immune system on a systemic level is much less well characterized. Because cancer is known to predispose patients to infectious complications including sepsis, we hypothesized that the presence of cancer alters pathogen-directed immune responses on a systemic level. Materials and Methods We assessed systemic T cell coinhibitory receptor expression, cytokine production, and apoptosis in mice with established subcutaneous lung cancer tumors and in unmanipulated mice without cancer. Results Results indicated that the frequencies of PD-1+, BTLA+, and 2B4+ cells in both the CD4+ and CD8+ T cell compartments were increased in mice with localized cancer relative to non-cancer controls, and the frequencies of both CD4+ and CD8+ T cells expressing multiple different inhibitory receptors was increased in cancer animals relative to non-cancer controls. Additionally, 2B4+CD8+ T cells in cancer mice exhibited reduced IL-2 and IFN-γ, while BTLA+CD8+ T cells in cancer mice exhibited reduced IL-2 and TNF. Conversely, CD4+ T cells in cancer animals demonstrated an increase in the frequency of Annexin V+ apoptotic cells. Conclusion Taken together, these data suggest that the presence of cancer induces systemic T cell exhaustion and generalized immune suppression. PMID:25748104

  20. 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 be...

  1. Effects of Recombinant Erythropoietin on Breast Cancer-Initiating Cells

    OpenAIRE

    Tiffany M. Phillips; Kwanghee Kim; Erina Vlashi; McBride, William H.; Frank Pajonk

    2007-01-01

    BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs). In breast can...

  2. Breast cancer stem cells, cytokine networks, and the tumor microenvironment

    OpenAIRE

    Korkaya, Hasan; Liu, Suling; Wicha, Max S.

    2011-01-01

    Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. 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 cells — through networks of cytokines and growth factors. Since these components have a direct...

  3. Overexpression of cyclin Y in non-small cell lung cancer is associated with cancer cell proliferation

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Cyclin Y (CCNY) is a key cell cycle regulator that acts as a growth factor sensor to integrate extracellular signals with the cell cycle machinery. The expression status of CCNY in lung cancer and its clinical significance remain unknown. The data indicates that CCNY may be deregulated in non-small cell lung cancer, where it may act to promote cell proliferation. These studies suggest that CCNY may be a candidate biomarker of NSCLC and a possible therapeutic target for lung cancer treatment.

  4. Enrichment of prostate cancer stem cells from primary prostate cancer cultures of biopsy samples

    OpenAIRE

    Wang, Shunqi; Huang, Shengsong; Zhao, Xin; Zhang, Qimin; Wu, Min; Sun, Feng; Han, Gang; Wu, Denglong

    2013-01-01

    This study was to enrich prostate cancer stem cells (PrCSC) from primary prostate cancer cultures (PPrCC). Primary prostate cancer cells were amplified in keratinocyte serum-free medium with epidermal growth factor (EGF) and bovine pituitary extract (BPE), supplemented with leukemia inhibitory factor (LIF), stem cell factor (SCF) and cholera toxin. After amplification, cells were transferred into ultra-low attachment dishes with serum-free DMEM/F12 medium, supplemented with EGF, basic fibrobl...

  5. Niche construction game cancer cells play

    Science.gov (United States)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology.

  6. Identification of genes involved in breast cancer and breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Apostolou P

    2015-07-01

    Full Text Available Panagiotis Apostolou, Maria Toloudi, Ioannis Papasotiriou Research and Development Department, Research Genetic Cancer Centre Ltd, Florina, Greece Abstract: Breast cancer is the most frequent type of cancer in women. Great progress has been made in its treatment but relapse is common. One hypothesis to account for the high recurrence rates is the presence of cancer stem cells (CSCs, which have the ability to self-renew and differentiate into multiple malignant cell types. This study aimed to determine genes that are expressed in breast cancer and breast CSCs and to investigate their correlation with stemness. RNA was extracted from established breast cancer cell lines and from CSCs derived from five different breast cancer patients. DNA microarray analysis was performed and any upregulated genes were also studied in other cancer types, including colorectal and lung cancer. For genes that were expressed only in breast cancer, knockdown-based experiments were performed. Finally, the gene expression levels of stemness transcription factors were measured. The outcome of the analysis indicated a group of genes that were aberrantly expressed mainly in breast cancer cells with stemness properties. Knockdown experiments confirmed the impact of several of these on NANOG, OCT3/4, and SOX2 transcription factors. It seems that several genes that are not directly related with hormone metabolism and basic signal transduction pathways might have an important role in relapse and disease progression and, thus, can be targeted for new treatment approaches for breast cancer. Keywords: breast cancer, cancer stem cells, stemness, DNA microarray

  7. Metformin inhibits cell growth by upregulating microRNA-26a in renal cancer cells

    OpenAIRE

    Yang, Feng-Qiang; Wang, Ji-Jiao; Yan, Jia-Sheng; Huang, Jian-Hua; Li, Wei; Che, Jian-Ping; Wang, Guang-Chun; Liu, Min; Zheng, Jun-Hua

    2014-01-01

    Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the ef...

  8. Metabolic alterations in cancer cells and therapeutic implications

    Institute of Scientific and Technical Information of China (English)

    Naima Hammoudi; Kausar Begam Riaz Ahmed; Celia Garcia-Prieto; Peng Huang

    2011-01-01

    Cancer metabolism has emerged as an important area of research in recent years. Elucidation of the metabolic differences between cancer and normal cells and the underlying mechanisms will not only advance our understanding of fundamental cancer cell biology but also provide an important basis for the development of new therapeutic strategies and novel compounds to selectively eliminate cancer cells by targeting their unique metabolism. This article reviews several important metabolic alterations in cancer cells, with an emphasis on increased aerobic glycolysis (the Warburg effect) and glutamine addiction, and discusses the mechanisms that may contribute to such metabolic changes. In addition, metabolic alterations in cancer stem cells, mitochondrial metabolism and its influence on drug sensitivity, and potential therapeutic strategies and agents that target cancer metabolism are also discussed.

  9. Sensitization of human pancreatic cancer cells harboring mutated K-ras to apoptosis.

    Directory of Open Access Journals (Sweden)

    Ling Shen

    Full Text Available Pancreatic cancer is a devastating human malignancy and gain of functional mutations in K-ras oncogene is observed in 75%-90% of the patients. Studies have shown that oncogenic ras is not only able to promote cell growth or survival, but also apoptosis, depending upon circumstances. Using pancreatic cancer cell lines with or without expressing mutated K-ras, we demonstrated that the inhibition of endogenous PKC activity sensitized human pancreatic cancer cells (MIA and PANC-1 expressing mutated K-ras to apoptosis, which had no apoptotic effect on BxPC-3 pancreatic cancer cells that contain a normal Ras as well as human lung epithelial BAES-2B cells. In this apoptotic process, the level of ROS was increased and PUMA was upregulated in a p73-dependent fashion in MIA and PANC-1 cells. Subsequently, caspase-3 was cleaved. A full induction of apoptosis required the activation of both ROS- and p73-mediated pathways. The data suggest that PKC is a crucial factor that copes with aberrant K-ras to maintain the homeostasis of the pancreatic cancer cells harboring mutated K-ras. However, the suppression or loss of PKC disrupts the balance and initiates an apoptotic crisis, in which ROS and p73 appear the potential, key targets.

  10. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    Science.gov (United States)

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  11. CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Chae Young; Lee, Seung-Min; Park, Sung Sup [Laboratory of Cell Signaling, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahangno, Yusong, Daejeon 305-806 (Korea, Republic of); Kwon, Ki-Sun, E-mail: kwonks@kribb.re.kr [Laboratory of Cell Signaling, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahangno, Yusong, Daejeon 305-806 (Korea, Republic of)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer H{sub 2}O{sub 2} differently adjusted senescence and proliferation in normal and cancer cells. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} exposure transiently decreased PCNA levels in normal cells. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} exposure transiently increased CDK2 activity in cancer cells. Black-Right-Pointing-Pointer p21{sup Cip1} is likely dispensable when H{sub 2}O{sub 2} induces senescence in normal cells. Black-Right-Pointing-Pointer Suggestively, CDK2 and PCNA play critical roles in H{sub 2}O{sub 2}-induced cell fate decision. -- Abstract: Reactive oxygen species modulate cell fate in a context-dependent manner. Sublethal doses of H{sub 2}O{sub 2} decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence. In contrast, exposure of cancer cells (such as HeLa and MCF7 cells) to H{sub 2}O{sub 2} increased CDK2 activity with no accompanying change in the PCNA level, leading to cell proliferation. A CDK2 inhibitor, CVT-313, prevented H{sub 2}O{sub 2}-induced cancer cell proliferation. These results support the notion that the cyclin/CDK2/p21{sup Cip1}/PCNA complex plays an important role as a regulator of cell fate decisions.

  12. Dendrimer-curcumin conjugate: a water soluble and effective cytotoxic agent against breast cancer cell lines.

    Science.gov (United States)

    Debnath, Shawon; Saloum, Darin; Dolai, Sukanta; Sun, Chong; Averick, Saadyah; Raja, Krishnaswami; Fata, Jimmie E

    2013-12-01

    Curcumin, which is derived from the plant Curcuma longa, has received considerable attention as a possible anti-cancer agent. In cell culture, curcumin is capable of inducing apoptosis in cancer cells at concentrations that do not affect normal cells. One draw-back holding curcumin back from being an effective anti-cancer agent in humans is that it is almost completely insoluble in water and therefore has poor absorption and subsequently poor bioavailability. Here we have generated a number of curcumin derivatives (tetrahydro-curcumin, curcumin mono-carboxylic acid, curcumin mono-galactose, curcumin mono-alkyne and dendrimer-curcumin conjugate) to test whether any of them display both cytotoxicity and water solubility. Of those tested only dendrimer-curcumin conjugate exhibited both water solubility and cytotoxicity against SKBr3 and BT549 breast cancer cells. When compared to curcumin dissolved in DMSO, dendrimer-curcumin conjugate dissolved in water was significantly more effective in inducing cytotoxicity, as measured by the MTT assay and effectively induced cellular apoptosis measured by caspase-3 activation. Since dendrimer-curcumin conjugate is water soluble and capable of inducing potent cytotoxic effects on breast cancer cell lines, it may prove to be an effective anti-cancer therapy to be used in humans. PMID:23387971

  13. Aptamer-based isolation and subsequent imaging of mesenchymal stem cells in ischemic myocard by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, R.; Hermanutz-Klein, U.; Northoff, H. [Universitaetsklinikum Tuebingen (Germany). Inst. fuer Klinische und Experimentelle Transfusionsmedizin; Wiskirchen, J.; Kehlbach, R.; Pintaske, J. [Universitaetsklinikum Tuebingen (Germany). Abt. fuer Radiologische Diagnostik; Guo, K.; Neumann, B.; Voth, V.; Walker, T.; Scheule, A.M.; Greiner, T.O.; Ziemer, G.; Wendel, H.P. [Universitaetsklinikum Tuebingen (Germany). Abt. fuer Thorax-, Herz- und Gefaesschirurgie; Claussen, C.D. [Universitaetsklinikum Tuebingen (Germany). Radiologische Universitaetsklinik

    2007-10-15

    Purpose: Mesenchymal stem cells (MSC) seem to be a promising cell source for cellular cardiomyoplasty. We recently developed a new aptamer-based specific selection of MSC to provide ''ready to transplant'' cells directly after isolation. We evaluated MRI tracking of newly isolated and freshly transplanted MSC in the heart using one short ex vivo selection step combining specific aptamer-based isolation and labeling of the cells. Materials and Methods: Bone marrow (BM) was collected from healthy pigs. The animals were euthanized and the heart was placed in a perfusion model. During cold ischemia, immunomagnetic isolation of MSC from the BM by MSC-specific aptamers labeled with Dynabeads {sup registered} was performed within 2 h. For histological identification the cells were additionally stained with PKH26. Approx. 3 x 10{sup 6} of the freshly aptamer-isolated cells were injected into the ramus interventricularis anterior (RIVA) and 5 x 10{sup 5} cells were injected directly into myocardial tissue after damaging the respective area by freezing (cryo-scar). 3 x 10{sup 6} of the aptamer-isolated cells were kept for further characterization (FACS and differentiation assays). 20 h after cell transplantation, MRI of the heart using a clinical 3.0 Tesla whole body scanner (Magnetom Trio, Siemens, Germany) was performed followed by histological examinations. Results: The average yield of sorted cells from 120 ml BM was 7 x 10{sup 6} cells. The cells were cultured and showed MSC-like properties. MRI showed reproducible artifacts within the RIVA-perfusion area and the cryo-scar with surprisingly excellent quality. The histological examination of the biopsies showed PKH26-positive cells within the areas which were positive in the MRI in contrast to the control biopsies. Conclusion: Immunomagnetic separation of MSC by specific aptamers linked to magnetic particles is feasible, effective and combines a specific separation and labeling technique to a &apos

  14. Targeted Elimination of Breast Cancer Cells with Low Proteasome Activity is Sufficient for Tumor Regression

    OpenAIRE

    Vlashi, Erina; Lagadec, Chann; Chan, Mabel; Frohnen, Patricia; Jean McDonald, Alexandra; Pajonk, Frank

    2013-01-01

    Breast cancers are thought to be organized hierarchically with a small number of breast cancer stem cells, able to regrow a tumor after sublethal treatment while their progeny lack this feature. Furthermore, breast cancer stem cells are highly resistant to conventional anti-cancer treatments. According to the cancer stem cell hypothesis, all cancer stem cells in a tumor have to be eliminated to achieve cancer cure. In this study we tested if targeted elimination of breast cancer stem cells le...

  15. Does the use of induction chemotherapy in oral cavity cancer compromise subsequent loco-regional treatment delivery: Results from a matched pair analysis

    Directory of Open Access Journals (Sweden)

    V M Patil

    2015-01-01

    Full Text Available BACKGROUND: Neoadjuvant chemotherapy is being increasingly used in patients with unresectable oral cavity cancers to make them resectable. However, its impact on locoregional treatment delivery in such setting remains poorly studied. AIMS: To evaluate the impact of neoadjuvant chemotherapy on delivery of further locoregional treatment. SETTINGS AND DESIGN: Mono institutional retrospective audit of patients with oral cavity squamous cell cancers treated with neoadjuvant triplet chemotherapy in India. MATERIALS AND METHODS: Patients receiving neoadjuvant chemotherapy (n = 14 from May 2012 to April 2014 were matched 1:2 to patients undergoing upfront surgery (n = 28 based on age (>60 or 60 and less, gender (male or female and subsite site (tongue and floor of mouth or buccoalveolar complex. Data regarding factors related to the delivery of locoregional treatment and toxicities were compiled. STATISTICAL ANALYSIS: Descriptive analysis in the form of median (range for continuous variables and frequencies for categorical variables. RESULTS: Patients undergoing neoadjuvant chemotherapy required more extensive resections and had greater operative time (460 vs. 415 min, P < 0.001. A greater incidence of locoregional wound complications was seen as a consequence (57.1% vs. 14.3%, P, 0.01. However, toxicities during radiotherapy were not substantially different between the two groups and compliance to radiation was also similar. Total package time of 100 days or less, was maintained in 90% of patients in both groups. CONCLUSIONS: Delivery of neoadjuvant chemotherapy does not impair the ability to deliver locoregional treatment.

  16. Chrysin enhances doxorubicin-induced cytotoxicity in human lung epithelial cancer cell lines: The role of glutathione

    Energy Technology Data Exchange (ETDEWEB)

    Brechbuhl, Heather M. [Pediatrics, National Jewish Health, Denver, Colorado (United States); Kachadourian, Remy; Min, Elysia [Department of Medicine, National Jewish Health, Denver, Colorado (United States); Chan, Daniel [Medical Oncology, University of Colorado Denver Health Sciences Center (United States); Day, Brian J., E-mail: dayb@njhealth.org [Department of Medicine, University of Colorado Denver Health Sciences Center (United States); Immunology, University of Colorado Denver Health Sciences Center (United States); Pharmaceutical Sciences, University of Colorado Denver Health Sciences Center (United States); Department of Medicine, National Jewish Health, Denver, Colorado (United States)

    2012-01-01

    We hypothesized that flavonoid-induced glutathione (GSH) efflux through multi-drug resistance proteins (MRPs) and subsequent intracellular GSH depletion is a viable mechanism to sensitize cancer cells to chemotherapies. This concept was demonstrated using chrysin (5–25 μM) induced GSH efflux in human non-small cell lung cancer lines exposed to the chemotherapeutic agent, doxorubicin (DOX). Treatment with chrysin resulted in significant and sustained intracellular GSH depletion and the GSH enzyme network in the four cancer cell types was predictive of the severity of chrysin induced intracellular GSH depletion. Gene expression data indicated a positive correlation between basal MRP1, MRP3 and MRP5 expression and total GSH efflux before and after chrysin exposure. Co-treating the cells for 72 h with chrysin (5–30 μM) and DOX (0.025–3.0 μM) significantly enhanced the sensitivity of the cells to DOX as compared to 72-hour DOX alone treatment in all four cell lines. The maximum decrease in the IC{sub 50} values of cells treated with DOX alone compared to co-treatment with chrysin and DOX was 43% in A549 cells, 47% in H157 and H1975 cells and 78% in H460 cells. Chrysin worked synergistically with DOX to induce cancer cell death. This approach could allow for use of lower concentrations and/or sensitize cancer cells to drugs that are typically resistant to therapy. -- Graphical abstract: Possible mechanisms by which chrysin enhances doxorubicin-induced toxicity in cancer cells. Highlights: ► Chyrsin sustains a significant depletion of GSH levels in lung cancer cells. ► Chyrsin synergistically potentiates doxorubicin-induced cancer cell cytotoxicity. ► Cancer cell sensitivity correlated with GSH and MRP gene network expression. ► This approach could allow for lower side effects and targeting resistant tumors.

  17. DUAL ROLES OF CANCER CELL-EXPRESSED IMMUNOGLOBULINS IN CANCER IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    Gregory Lee

    2014-01-01

    Full Text Available While the expression of immunoglobulins and T cell receptors on cancer cells has been well-established for decades, the potential roles and mechanisms of action of these cancerous antigen receptors have not been fully elucidated. A monoclonal antibody designated as RP215, which reacts specifically with the carbohydrate-associated epitope located on the heavy chain region of cancerous immunoglobulins and T cell receptors, was used as a unique probe to study the roles of antigen receptors in the immunology of cancer cells. Through extensive cell-based biological and immunological studies, it was found that both anti-antigen receptors and RP215 demonstrated similar actions on the gene regulations involved in the growth/proliferation of cancer cells, as well as on toll-like receptors involved in innate immunity. In addition, RP215-specific cancerous immunoglobulins are believed to capture or neutralize circulating antigen/antibodies which may be harmful to cancer cells within the human body. In contrast to normal B and T cells and their respective receptors in the conventional immune system, cancer cells co-express both immunoglobulins and T cell receptors and immune protection is exercised by unique mechanisms. For example, these cancer cell-expressed antigen receptors display a lack of class switching, limited hyper-mutation, aberrant glycosylations and a strong influence on the toll-like receptors of cancer cells. Therefore, it is hypothesized that both normal and cancerous immune systems may co-exist and operate simultaneously within the human body. The balance of these two immune factors for respective surveillance and protection may be relevant to the outcome of cancer immunotherapy in humans. A potential therapeutic strategy is being developed by using RP215 as a drug candidate to target cancer cells based on these observations.

  18. Transcription profiles of non-immortalized breast cancer cell lines

    International Nuclear Information System (INIS)

    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. 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. 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 < 0.01). Some of these genes have already been directly linked with breast cancer, metastasis and malignant progression, whilst others encode receptors linked to signal transduction pathways or are otherwise related to cell proliferation. Fifty genes showed at least a 2.5-fold difference between MSSMs and T-est cells according to AtlasImage, 2-fold according to SAM. Most of these classified as genes related to metabolism and cell communication. 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

  19. 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.

  20. Convergence of normal stem cell and cancer stem cell developmental stage: Implication for differential therapies

    OpenAIRE

    Shengwen Calvin Li; Lee, Katherine L.; Jane Luo; Jiang F. Zhong; William G Loudon

    2011-01-01

    Increased evidence shows that normal stem cells may contribute to cancer development and progression by acting as cancer-initiating cells through their interactions with abnormal environmental elements. We postulate that normal stem cells and cancer stem cells (CSC) possess similar mechanisms of self-renewal and differentiation. CSC can be the key to the elaboration of anti-cancer-based therapy. In this article, we focus on a controversial new theme relating to CSC. Tumorigenesis may have a c...

  1. Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation

    OpenAIRE

    Cheng, Kunrong; Samimi, Roxana; Xie, Guofeng; Shant, Jasleen; Drachenberg, Cinthia; Wade, Mark; Davis, Richard J.; Nomikos, George; Raufman, Jean-Pierre

    2008-01-01

    Most colon cancers overexpress M3 muscarinic receptors (M3R), and post-M3R signaling stimulates human colon cancer cell proliferation. Acetylcholine (ACh), a muscarinic receptor ligand traditionally regarded as a neurotransmitter, may be produced by nonneuronal cells. We hypothesized that ACh release by human colon cancer cells results in autocrine stimulation of proliferation. H508 human colon cancer cells, which have robust M3R expression, were used to examine effects of muscarinic receptor...

  2. Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

    Science.gov (United States)

    2016-02-08

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  3. Derivation and characterization of matched cell lines from primary and recurrent serous ovarian cancer

    Directory of Open Access Journals (Sweden)

    Létourneau Isabelle J

    2012-08-01

    Full Text Available Abstract Background Cell line models have proven to be effective tools to investigate a variety of ovarian cancer features. Due to the limited number of cell lines, particularly of the serous subtype, the heterogeneity of the disease, and the lack of cell lines that model disease progression, there is a need to further develop cell line resources available for research. This study describes nine cell lines derived from three ovarian cancer cases that were established at initial diagnosis and at subsequent relapse after chemotherapy. Methods The cell lines from three women diagnosed with high-grade serous ovarian cancer (1369, 2295 and 3133 were derived from solid tumor (TOV and ascites (OV, at specific time points at diagnosis and relapse (R. Primary treatment was a combination of paclitaxel/carboplatin (1369, 3133, or cisplatin/topotecan (2295. Second line treatment included doxorubicin, gemcitabine and topotecan. In addition to molecular characterization (p53, HER2, the cell lines were characterized based on cell growth characteristics including spheroid growth, migration potential, and anchorage independence. The in vivo tumorigenicity potential of the cell lines was measured. Response to paclitaxel and carboplatin was assessed using a clonogenic assay. Results All cell lines had either a nonsense or missense TP53 mutations. The ability to form compact spheroids or aggregates was observed in six of nine cell lines. Limited ability for migration and anchorage independence was observed. The OV3133(R cell line, formed tumors at subcutaneous sites in SCID mice. Based on IC50 values and dose response curves, there was clear evidence of acquired resistance to carboplatin for TOV2295(R and OV2295(R2 cell lines. Conclusion The study identified nine new high-grade serous ovarian cancer cell lines, derived before and after chemotherapy that provides a unique resource for investigating the evolution of this common histopathological subtype of ovarian

  4. Immunotherapy of Metastases Enhances Subsequent Chemotherapy

    Science.gov (United States)

    Hanna, Michael G.; Key, Marc E.

    1982-07-01

    In many multimodal therapies of cancer, postsurgical chemotherapy is administered before immunotherapy for treatment of micrometastatic disease. This sequence may not be the most efficacious. Experiments in which strain 2 guinea pigs bearing syngeneic L10 hepatocarcinomas were given immunotherapy showed that infiltrating immune effector cells not only were tumoricidal but disrupted the characteristically compact structure of metastatic foci. When cytotoxic drugs were administered at the peak of this inflammatory response, the survival rate of the guinea pigs increased significantly. We conclude that postsurgical immunotherapy can enhance the effect of cytotoxic drugs administered subsequently.

  5. Targeting the cancer cell cycle by cold atmospheric plasma

    Science.gov (United States)

    Volotskova, O.; Hawley, T. S.; Stepp, M. A.; Keidar, M.

    2012-09-01

    Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating S-phase damage, is enhanced specifically within CAP treated cells in the S phase of the cell cycle. Together with a significant decrease in EdU-incorporation after CAP, these data suggest that tumorigenic cancer cells are more susceptible to CAP treatment.

  6. Mitochondria as therapeutic targets for cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    In Sung Song; Jeong Yu Jeong; Seung Hun Jeong; Hyoung Kyu Kim; Kyung Soo Ko; Byoung Doo Rhee; Nari Kim; Jin Han

    2015-01-01

    Cancer stem cells (CSCs) are maintained by theirsomatic stem cells and are responsible for tumorinitiation, chemoresistance, and metastasis. Evidencefor the CSCs existence has been reported for a numberof human cancers. The CSC mitochondria have beenshown recently to be an important target for cancertreatment, but clinical significance of CSCs and theirmitochondria properties remain unclear. Mitochondriatargetedagents are considerably more effectivecompared to other agents in triggering apoptosis ofCSCs, as well as general cancer cells, via mitochondrialdysfunction. Mitochondrial metabolism is altered incancer cells because of their reliance on glycolyticintermediates, which are normally destined for oxidativephosphorylation. Therefore, inhibiting cancer-specificmodifications in mitochondrial metabolism, increasingreactive oxygen species production, or stimulatingmitochondrial permeabilization transition could bepromising new therapeutic strategies to activate celldeath in CSCs as well, as in general cancer cells. Thisreview analyzed mitochondrial function and its potentialas a therapeutic target to induce cell death in CSCs.Furthermore, combined treatment with mitochondriatargeteddrugs will be a promising strategy for thetreatment of relapsed and refractory cancer.

  7. 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. PMID:22043817

  8. Cancer Stem Cells: A Novel Paradigm for Cancer Prevention and Treatment

    OpenAIRE

    Subramaniam, D; Ramalingam, S; Houchen, C.W.; Anant, S

    2010-01-01

    Cancer is the second leading cause for mortality in US only after heart disease and lacks a good or effective therapeutic paradigm. Despite the emergence of new, targeted agents and the use of various therapeutic combinations, none of the treatment options available is curative in patients with advanced cancer. A growing body of evidence is supporting the idea that human cancers can be considered as a stem cell disease. Malignancies are believed to originate from a fraction of cancer cells th...

  9. Identification of genes involved in breast cancer and breast cancer stem cells

    OpenAIRE

    Apostolou P; Toloudi M; Papasotiriou I

    2015-01-01

    Panagiotis Apostolou, Maria Toloudi, Ioannis Papasotiriou Research and Development Department, Research Genetic Cancer Centre Ltd, Florina, Greece Abstract: Breast cancer is the most frequent type of cancer in women. Great progress has been made in its treatment but relapse is common. One hypothesis to account for the high recurrence rates is the presence of cancer stem cells (CSCs), which have the ability to self-renew and differentiate into multiple malignant cell types. This study aimed t...

  10. Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for enhanced cancer cell apoptosis.

    Science.gov (United States)

    Shah, Birju P; Pasquale, Nicholas; De, Gejing; Tan, Tao; Ma, Jianjie; Lee, Ki-Bum

    2014-09-23

    Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core-shell nanoparticle (MCNP)-mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail-anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis. PMID:25133971

  11. Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells.

    Science.gov (United States)

    Yongsanguanchai, Nuttida; Pongrakhananon, Varisa; Mutirangura, Apiwat; Rojanasakul, Yon; Chanvorachote, Pithi

    2015-01-15

    Even though tremendous advances have been made in the treatment of cancers during the past decades, the success rate among patients with cancer is still dismal, largely because of problems associated with chemo/radioresistance and relapse. Emerging evidence has indicated that cancer stem cells (CSCs) are behind the resistance and recurrence problems, but our understanding of their regulation is limited. Rapid reversible changes of CSC-like cells within tumors may result from the effect of biological mediators found in the tumor microenvironment. Here we show how nitric oxide (NO), a key cellular modulator whose level is elevated in many tumors, affects CSC-like phenotypes of human non-small cell lung carcinoma H292 and H460 cells. Exposure of NO gradually altered the cell morphology toward mesenchymal stem-like shape. NO exposure promoted CSC-like phenotype, indicated by increased expression of known CSC markers, CD133 and ALDH1A1, in the exposed cells. These effects of NO on stemness were reversible after cessation of the NO treatment for 7 days. Furthermore, such effect was reproducible using another NO donor, S-nitroso-N-acetylpenicillamine. Importantly, inhibition of NO by the known NO scavenger 2-(4-carboxy-phenyl)-4,4,5,5 tetramethylimidazoline-1-oxy-3-oxide strongly inhibited CSC-like aggressive cellular behavior and marker expression. Last, we unveiled the underlying mechanism of NO action through the activation of caveolin-1 (Cav-1), which is upregulated by NO and is responsible for the aggressive behavior of the cells, including anoikis resistance, anchorage-independent cell growth, and increased cell migration and invasion. These findings indicate a novel role of NO in CSC regulation and its importance in aggressive cancer behaviors through Cav-1 upregulation. PMID:25411331

  12. Transparent, biocompatible nanostructured surfaces for cancer cell capture and culture

    Directory of Open Access Journals (Sweden)

    Cheng BR

    2014-05-01

    Full Text Available Boran Cheng,1,* Zhaobo He,2,* Libo Zhao,2,* Yuan Fang,1 Yuanyuan Chen,1 Rongxiang He,2 Fangfang Chen,1 Haibin Song,1 Yuliang Deng,2 Xingzhong Zhao,2 Bin Xiong1 1Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan, Hubei, People’s Republic of China; 2Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Abstract: Circulating tumor cells (CTCs in the blood which have detached from both the primary tumor and any metastases may be considered as a “liquid biopsy” and are expected to replace tumor biopsies in the monitoring of treatment response and determining patient prognosis. Here, we introduce a facile and efficient CTC detection material made of hydroxyapatite/chitosan (HA/CTS, which is beneficial because of its transparency and excellent biological compatibility. Atomic force microscopy images show that the roughness of the HA/CTS nanofilm (HA/CTSNF substrates can be controlled by changing the HA:CTS ratio. Enhanced local topographic interactions between nano-components on cancer cell membranes, and the antibody coated nanostructured substrate lead to improved CTC capture and separation. This remarkable nanostructured substrate has the potential for CTC culture in situ and merits further analysis. CTCs captured from artificial blood samples were observed in culture on HA/CTSNF substrates over a period of 14 days by using conventional staining methods (hematoxylin eosin and Wright’s stain. We conclude that these substrates are multifunctional materials capable of isolating and culturing CTCs for subsequent studies. Keywords: cell capture, cell culture, nanofilms, hydroxyapatite/chitosan

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

    OpenAIRE

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

    2014-01-01

    Background 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 b...

  14. 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...

  15. Vaccination with embryonic stem cells protects against lung cancer: is a broad-spectrum prophylactic vaccine against cancer possible?

    Directory of Open Access Journals (Sweden)

    Kavitha Yaddanapudi

    Full Text Available The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine embryonic stem cells (ESC. Naïve C57BL/6 mice were vaccinated with ESC along with a source of granulocyte macrophage-colony stimulating factor (GM-CSF in order to provide immunostimulatory adjuvant activity. Vaccinated mice were protected against subsequent challenge with implantable Lewis lung carcinoma (LLC. ESC-induced anti-tumor immunity was not due to a non-specific "allo-response" as vaccination with allogeneic murine embryonic fibroblasts did not protect against tumor outgrowth. Vaccine efficacy was associated with robust tumor-reactive primary and memory CD8(+ T effector responses, Th1 cytokine response, higher intratumoral CD8(+ T effector/CD4(+CD25(+Foxp3(+ T regulatory cell ratio, and reduced myeloid derived suppressor cells in the spleen. Prevention of tumorigenesis was found to require a CD8-mediated cytotoxic T lymphocyte (CTL response because in vivo depletion of CD8(+ T lymphocytes completely abrogated the protective effect of vaccination. Importantly, this vaccination strategy also suppressed the development of lung cancer induced by the combination of carcinogen administration and chronic pulmonary inflammation. Further refinement of this novel vaccine strategy and identification of shared ESC/tumor antigens may lead to immunotherapeutic options for lung cancer patients and, perhaps more importantly, could represent a first step toward the development of prophylactic cancer vaccines.

  16. Feedback from each retinal neuron population drives expression of subsequent fate determinant genes without influencing the cell cycle exit timing.

    Science.gov (United States)

    Kei, Jeremy Ng Chi; Dudczig, Stefanie; Currie, Peter D; Jusuf, Patricia R

    2016-09-01

    During neurogenesis, progenitors balance proliferation and cell cycle exit together with expression of fate determinant genes to ensure that the correct number of each of these neuron types is generated. Although intrinsic gene expression acting cell autonomously within each progenitor drives these processes, the final number of neurons generated is also influenced by extrinsic cues, representing a potential avenue to direct neurogenesis in developmental disorders or regenerative settings without the requirement to change intrinsic gene expression. Thus, it is important to understand which of these stages of neurogenesis are amenable to such extrinsic influences. Additionally, all types of neurons are specified in a highly conserved histogenic order, although its significance is unknown. This study makes use of conserved patterns of neurogenesis in the relatively simple yet highly organized zebrafish retina model, in which such histogenic birth order is well characterized. We directly visualize and quantify birth dates and cell fate determinant expression in WT vs. environments lacking different neuronal populations. This study shows that extrinsic feedback from developing retinal neurons is important for the temporal expression of intrinsic fate determinants but not for the timing of birth dates. We found no changes in cell cycle exit timing but did find a significant delay in the expression of genes driving the generation only of later- but not earlier-born cells, suggesting that the robustness of this process depends on continuous feedback from earlier-formed cell types. Thus, extrinsic cues selectively influence cell fate determinant progression, which may explain the function of the retinal histogenic order observed. J. Comp. Neurol. 524:2553-2566, 2016. © 2016 Wiley Periodicals, Inc. PMID:26850379

  17. The role of myeloid cells in cancer therapies.

    Science.gov (United States)

    Engblom, Camilla; Pfirschke, Christina; Pittet, Mikael J

    2016-07-01

    Recent clinical trials have demonstrated the ability to durably control cancer in some patients by manipulating T lymphocytes. These immunotherapies are revolutionizing cancer treatment but benefit only a minority of patients. It is thus a crucial time for clinicians, cancer scientists and immunologists to determine the next steps in shifting cancer treatment towards better cancer control. This Review describes recent advances in our understanding of tumour-associated myeloid cells. These cells remain less studied than T lymphocytes but have attracted particular attention because their presence in tumours is often linked to altered patient survival. Also, experimental studies indicate that myeloid cells modulate key cancer-associated activities, including immune evasion, and affect virtually all types of cancer therapy. Consequently, targeting myeloid cells could overcome limitations of current treatment options. PMID:27339708

  18. Natural Products That Target Cancer Stem Cells.

    Science.gov (United States)

    Moselhy, Jim; Srinivasan, Sowmyalakshmi; Ankem, Murali K; Damodaran, Chendil

    2015-11-01

    The cancer stem cell model suggests that tumor initiation is governed by a small subset of distinct cells with stem-like character termed cancer stem cells (CSCs). CSCs possess properties of self-renewal and intrinsic survival mechanisms that contribute to resistance of tumors to most chemotherapeutic drugs. The failure to eradicate CSCs during the course of therapy is postulated to be the driving force for tumor recurrence and metastasis. Recent studies have focused on understanding the unique phenotypic properties of CSCs from various tumor types, as well as the signaling pathways that underlie self-renewal and drug resistance. Natural products (NPs) such as those derived from botanicals and food sources may modulate vital signaling pathways involved in the maintenance of CSC phenotype. The Wingless/Integrated (WNT), Hedgehog, Notch and PI3K/AKT/mTOR pathways have all been associated with quiescence and self-renewal of CSCs, as well as execution of CSC function including differentiation, multidrug resistance and metastasis. Recent studies evaluating NPs against CSC support the epidemiological evidence linking plant-based diets with reduced malignancy rates. This review covers the key aspects of NPs as modulators of CSC fate. PMID:26503998

  19. HS-4, a highly potent inhibitor of cell proliferation of human cancer cell

    Institute of Scientific and Technical Information of China (English)

    Gui-Lan Xing; Shu-Hong Tian; Xue-Li Xie; Jian Fu

    2015-01-01

    Objective:To investigate the antitumor activity of the compound HS-4 and the action mechanism.Methods:MTT method was used to testin vitroantitumor activity of the compound HS-4. Orthotopic xenotransplantation tumor model of liver cancer was established in nude mice, and,in vivoantitumor activity of compound HS-4 was tested with a small animal in-vivo imaging system. Sequencing of small RNA library and RNA library was performed in HS-4 treated tumor cell group and control group to investigate the anti-cancer mechanism of HS-4 at level of functional genomics, using high-throughput sequencing technology. Results:HS-4 was found to have relatively highin-vitro antitumor activity against liver cancer cells, gastric cancer cells, renal cancer cells, lung cancer cells, breast cancer cells and colon cancer cells. The IC50 values against SMMC-7721 and Bel-7402 of liver cancer cells were 0.14 and 0.13 nmol/L respectively, while the IC50 values against MGC-803 and SGC-7901 of gastric cancer cells were 0.19 and 0.21 nmol/L, respectively. It was demonstrated that HS- 4 possessed a better therapeutic effect in liver cancer.Conclusions: A new reliable orthotopic xenotransplantation tumor model of liver cancer in nude mice is established. The new compounds HS-4 was found to possess relatively highin vivo andin vitroantitumor activity against liver cancer cells.

  20. HS-4,a highly potent inhibitor of cell proliferation of human cancer cell

    Institute of Scientific and Technical Information of China (English)

    Gui-Lan; Xing; Shu-Hong; Tian; Xue-Li; Xie; Jian; Fu

    2015-01-01

    Objective:To investigate the antitumor activity of the compound HS-4 and the action mechanism.Methods:MTT method was used to test in vitro antitumor activity of the compound HS-4.Orthotopic xenotransplantation tumor model of liver cancer was established in nude mice,and.in vivo antitumor activity of compound HS-4 was tested with a small animal in-vivo imaging system.Sequencing of small RNA library and RNA library was performed in HS-4 treated tumor cell group and control group to investigate the anti-cancer mechanism of HS-4 at level of functional genomics,using high-throughput sequencing technology.Results:HS-4 was found to have relatively high in-vitro antitumor activity against liver cancer cells,gastric cancer cells,renal cancer cells,lung cancer cells,breast cancer cells and colon cancer cells.The IC50 values against SMMC-7721 and Bel-7402 of liver cancer cells were 0.14 and 0.13 nmol/L respectively,while the IC50 values against MGC-803 and SGC-7901 of gastric cancer cells were 0.19 and 0.21 nmol/L,respectively.It was demonstrated that HS- 4 possessed a betler therapeutic effect in liver cancer.Conclusions:A new reliable orthotopicxenotransplantation tumor model of liver cancer in nude mice is established.The new compounds HS-4 was found to possess relatively high in vivo and in vitro antitumor activity against liver cancer cells.

  1. Heat shock protein 70 antisense oligonucleotide inhibits cell growth and induces apoptosis in human gastric cancer cell line SGC-7901

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Zhao; Wen-Lu Shen

    2005-01-01

    AIM: Heat shock protein (HSP)70 is over-expressed in human gastric cancer and plays an important role in the progression of this cancer. We investigated the effects of antisense HSP70 oligomer on human gastric cancer cell line SGC-7901, and its potential role in gene therapy for this cancer.METHODS: Human gastric cancer cell line SGC-7901 was treated in vitro with various concentrations of antisense HSP70 oligonucleotides at different intervals. Growth inhibition was determined as percentage by trypan blue dye exclusion test. Extracted DNA was electrophoresed on agarose gel, and distribution of cell cycle and kinetics of apoptosis induction were analyzed by propidium iodide DNA incorporation using flow cytometry, which was also used to detect the effects of antisense oligomer pretreatment on the subsequent apoptosis induced by heat shock in SGC-7901 cells. Proteins were extracted for simultaneous measurement of HSP70 expression level by SDS-PAGE Western blotting.RESULTS: The number of viable cells decreased in a doseand time-dependent manner, and ladder-like patterns of DNA fragments were observed in SGC-7901 cells treated with antisense HSP70 oligomers at a concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h, which were consistent with inter-nucleosomal DNA fragmentation. Flow cytometric analysis showed a dose- and time-dependent increase in apoptotic rate by HSP70 antisense oligomers. This response was accompanied with a decrease in the percentage of cells in the G1 and S phases of the cell cycle, suggesting inhibition of cell proliferation. In addition, flow cytometry also showed that pretreatment of SGC-7901 cells with HSP70 antisense oligomers enhanced the subsequent apoptosis induced by heat shock treatment. Western blotting demonstrated that HSP70 antisense oligomers inhibited HSP70 expression, which preceded apoptosis, and HSP70 was undetectable at the concentration of 10 μmol/L for 48 h or 8 μmol/L for 72 h.CONCLUSION: Antisense HSP70 oligomers

  2. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer

    International Nuclear Information System (INIS)

    Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC) in the bone marrow and circulating tumor cells (CTC) from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer

  3. Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oakman, Catherine; Pestrin, Marta [‘Sandro Pitigliani’ Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, 59100, Prato (Italy); Bessi, Silvia; Galardi, Francesca [Translational Research Unit, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, 59100, Prato (Italy); Di Leo, Angelo, E-mail: adileo@usl4.toscana.it [‘Sandro Pitigliani’ Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, 59100, Prato (Italy)

    2010-06-08

    Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC) in the bone marrow and circulating tumor cells (CTC) from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer.

  4. Low Doses of Gamma Rays Reduce the Sensitivity of Cervical Carcinoma Cells to Subsequent Treatment with Cisplatin

    International Nuclear Information System (INIS)

    One of the major challenges of modern genetics is to apply recent advances in mutation research to improve the accuracy of the estimates of the genetic risk for humans. Because of the important implications for radiation protection, biological effects of low-dose radiation have been a focus of research in recent years. Previously we have found that human cervical carcinoma HeLa cells irradiated repeatedly with low doses of gamma rays (HeLa1500 cells) became resistant to cisplatin. In this study we examine whether this effect was caused by inhibition of apoptosis. In HeLa and HeLa1500 cells we determined the induction of apoptosis following the treatment with cisplatin (i) by counting apoptotic cells with characteristic morphological changes, (ii) by analysing the expression of apoptotic genes involved in cytochrome c/Apaf-1/caspase-9 and in Fas/FasL pathways by Western blot method, and (iii) by estimating the activities of caspases by commercial caspase detection kits. Our results show that low doses of gamma rays induced alterations in human cervical carcinoma cells that were reflected in inhibition of p53-independent cisplatin-induced apoptosis due to reduced activity of caspase 3. (author)

  5. Sodium hypochlorite decontamination of split-thickness cadaveric skin infected with bacteria and yeast with subsequent isolation and growth of basal cells to confluency in tissue culture.

    OpenAIRE

    Fader, R C; Maurer, A.; Stein, M D; Abston, S; Herndon, D N

    1983-01-01

    The ability of sodium hypochlorite to decontaminate skin while leaving sufficient epidermal cell viability for growth in tissue culture was investigated with an in vitro system. Split-thickness cadaveric skin was infected with Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans and subsequently treated with various concentrations of sodium hypochlorite for various time intervals. Exposure to a 0.5% solution of sodium hypochlorite for 6 min effectively decontaminated the skin w...

  6. Helicobacter pylori infection and stem cells at the origin of gastric cancer.

    Science.gov (United States)

    Bessède, E; Dubus, P; Mégraud, F; Varon, C

    2015-05-14

    Helicobacter pylori infection is now recognized as the main and specific infectious cause of cancer in the world. It is responsible for gastric adenocarcinomas of both intestinal and diffuse types, which are the long-term consequences of the chronic infection of the gastric mucosa. Case-control studies have shown an association between the two, recognized as early as 1994 and further substantiated by interventional studies in which H. pylori eradication has led to the prevention of at least part of the gastric cancers. Experimental studies have highlighted the role of bone marrow-derived cells (BMDCs) and particularly mesenchymal stem cells, in the neoplastic process in about a quarter of the cases and possibly an epithelial-mesenchymal transition (EMT) in the other cases. Different studies have confirmed that chronic infection with H. pylori induces a chronic inflammation and subsequent damage of the gastric epithelial mucosa, leading to BMDC recruitment. Once recruited, these cells home and differentiate by cell-cell fusion with local gastric epithelial cells, bearing local stem cell failure and participating in tissue regeneration. The context of chronic infection and inflammation leads to an EMT and altered tissue regeneration and differentiation from both local epithelial stem cells and BMDC. EMT induces the emergence of CD44+ cells possessing mesenchymal and stem cell properties, resulting in metaplastic and dysplastic lesions to give rise, after additional epigenetic and mutational events, to the emergence of cancer stem cells (CSCs) and adenocarcinoma. PMID:25043305

  7. Cancer Stem Cells: The Final Frontier for Glioma Virotherapy

    OpenAIRE

    Dey, Mahua; Ulasov, Ilya V.; Tyler, Matthew A.; Sonabend, Adam M.; Lesniak, Maciej S.

    2011-01-01

    Cancer stem cells (CSC) are a very small subset of all cancer cells and possess characteristics very similar to normal stem cells, in particular, the capacity for self-renewal, multipotency and relative quiescence. These chemo- and radiation resistant cells are responsible for maintaining tumor volume leading to therapy failure and recurrence. In glioblastoma multiforme (GBM), the most common primary intracranial malignancy, glioma stem cells have been implicated as one of the key players in ...

  8. Cancer Stem Cells – Basics, Progress and Future Potential

    OpenAIRE

    Bapat S.A

    2010-01-01

    The primary characteristics of adult stem cells are maintaining prolonged quiescence, ability to self-renew and plasticity to differentiate into multiple cell types. These properties are evolutionarily conserved from fruit fly to humans. Similar to normal tissue repair in organs, the stem cell concept is inherently impregnated in the etiology of cancer. Tumors contain a minor population of tumor-initiating cells, called "cancer stem cells" that maintain some similarities in self-renewal and d...

  9. Dynamic Switch Between Two Adhesion Phenotypes in Colorectal Cancer Cells

    OpenAIRE

    Geng, Yue; Chandrasekaran, Siddarth; Agastin, Sivaprakash; Li, Jiahe; King, Michael R.

    2013-01-01

    The hematogenous metastatic cascade is mediated by the interaction of cancer cells and the endothelial cell lining of blood vessels. In this work, we examine the colon cancer cell line COLO 205, which grows simultaneously in both adherent and suspended states in culture and can serve as a good model for studying tumor heterogeneity. The two subpopulations of cells have different molecular characteristics despite being from the same parent cell line. We found that the ratio of adherent to susp...

  10. TRANSCRIPTIONAL LANDSCAPE OF NEURONAL and CANCER STEM CELLS

    OpenAIRE

    Miele, Evelina

    2013-01-01

    Tumor mass is composed by heterogeneous cell population including a subset of “cancer stem cells” (CSC). Oncogenic signals foster CSC by transforming tissue stem cells or by reprogramming progenitor/differentiated cells towards stemness. Thus, CSC share features with cancer and stem cells (e.g. self-renewal, hierarchical developmental program leading to differentiated cells, epithelial/mesenchimal transition) and these latter are maintained by the constitutive activation of stemne...

  11. Human prostate cancer stem cells: new features unveiled

    Institute of Scientific and Technical Information of China (English)

    Yuting Sun; Wei-Qiang Gao

    2011-01-01

    @@ Cancer stem cells (CSCs) are a rare sub-population of phenotypically distinct cancer cells exhibiting stem cell characteristics.They are tumourigenic, meanwhile capable of self-renewal and forming differentiated progenies.CSCs are believed to be resistant to the standard therapeutics, and provide the cell reservoir for tumour initiation.1 Understanding CSCs or in another word, tumour-initiating cells, is of critical therapeutic importance.

  12. Adaptation of BHK-21 cells to growth in shaker culture and subsequent challenge by Japanese encephalitis virus.

    Science.gov (United States)

    Guskey, L E; Jenkin, H M

    1975-09-01

    Baby hamster kidney (BHK-21) cells were adapted to grow in shaker culture using Waymouth medium 752/1 containing 20 mM N-2-hydroxyethyl-piperazine-N'-2'-ethanesulfonic acid buffer and supplemented with 2.5% (vol/vol) calf serum, 0.002% (wt/vol) sodium oleate, and 0.2% fatty acid-free bovine serum albumin (WO2.5). Infectivity of Japanese encephalitis virus grown in the cells adapted to WO2.5 approached 2 x 10(8) plaque-forming units per ml. The culture volume of infected cells was reduced fivefold 12 h after infection. This step resulted in a 10-fold increase in infectivity over that obtained from infected cultures not subjected to volume reduction. PMID:1237269

  13. The cancer-germline antigen SSX2 causes cell cycle arrest and DNA damage in cancer cells

    DEFF Research Database (Denmark)

    Greve, Katrine Buch Vidén; Lindgreen, Jonas; Terp, Mikkel Green;

    2011-01-01

    increase in the number of gamma-H2AX ‘DNA damage foci’, indicating replicative stress, which may lead to genomic instability. As the p53 tumor suppressor is an inducer of G1 arrest after DNA damage and often deregulated in cancer cells, we investigated if the growth reduction due to SSX2 expression was p53...... dependent. The growth reduction was similar in isogenic colon cancer cells with and without p53, indicating that SSX2 is able to inhibit the growth of cancer cells, even in absence of functional p53. Our results show that SSX2 acts as an inhibitor of cancer cell proliferation, possibly through replicative......The SSX family of cancer and germline antigens is mainly expressed in the germ cells of healthy individuals as well as wide range of cancers and is therefore potential targets for immunotherapy. However, little is known about the role of SSX proteins in tumorigenesis and normal cell function. Here...

  14. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo

    2011-04-01

    Full Text Available In mammals, silencing of one of the two X chromosomes is necessary to achieve dosage compensation. The 17 kb non-coding RNA called Xist triggers X inactivation. Gene silencing by Xist can only be achieved in certain contexts such as in cells of the early embryo and in certain hematopoietic progenitors where silencing factors are present. Moreover, these epigenetic contexts are maintained in cancer progenitors in which SATB1 has been identified as a factor related to Xist-mediated chromosome silencing.

  15. MEMBRANE LEc EXPRESSION IN BREAST CANCER CELLS

    Directory of Open Access Journals (Sweden)

    Ya. A. Udalova

    2014-09-01

    Full Text Available Affine chromatography was used to isolate Lec antibodies from the sera of a healthy female donor with the high titers of these anti- bodies, which were labeled with biotin. The study enrolled 51 patients with primary breast cancer (BC. Antigen expression was found by immunohistochemistry and flow cytometry. With these two techniques being used, the detection rate of Lec expression in BC cells was 65% (33/51; the antigen was most frequently found by flow cytometry as compared with immunohistochemistry: 72 and 58% of cases, respectively.

  16. Neuroendocrine differentiation of prostate cancer cells

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Pernicová, Zuzana; Lincová, Eva; Staršíchová, Andrea; Kozubík, Alois

    2008-01-01

    Roč. 102, č. 5 (2008), s. 393. ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků. Konference Sigma-Aldrich /8./. 10.06.2008-13.06.2008, Devět skal - Žďárské vrchy] R&D Projects: GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA310/07/0961 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : neuroendocrine differentiation * prostate cancer * neuroendocrine-like cells Subject RIV: BO - Biophysics

  17. Adhesion between peptides/antibodies and breast cancer cells

    Science.gov (United States)

    Meng, J.; Paetzell, E.; Bogorad, A.; Soboyejo, W. O.

    2010-06-01

    Atomic force microscopy (AFM) techniques were used to measure the adhesion forces between the receptors on breast cancer cells specific to human luteinizing hormone-releasing hormone (LHRH) peptides and antibodies specific to the EphA2 receptor. The adhesion forces between LHRH-coated AFM tips and human MDA-MB-231 cells (breast cancer cells) were shown to be about five times greater than those between LHRH-coated AFM tips and normal Hs578Bst breast cells. Similarly, those between EphA2 antibody-coated AFM tips and breast cancer cells were over five times greater than those between EphA2 antibody-coated AFM tips and normal breast cells. The results suggest that AFM can be used for the detection of breast cancer cells in biopsies. The implications of the results are also discussed for the early detection and localized treatment of cancer.

  18. Cancer Stem Cells: Biological Functions and Therapeutically Targeting

    Directory of Open Access Journals (Sweden)

    Marius Eugen Ciurea

    2014-05-01

    Full Text Available Almost all tumors are composed of a heterogeneous cell population, making them difficult to treat. A small cancer stem cell population with a low proliferation rate and a high tumorigenic potential is thought to be responsible for cancer development, metastasis and resistance to therapy. Stem cells were reported to be involved in both normal development and carcinogenesis, some molecular mechanisms being common in both processes. No less controversial, stem cells are considered to be important in treatment of malignant diseases both as targets and drug carriers. The efforts to understand the role of different signalling in cancer stem cells requires in depth knowledge about the mechanisms that control their self-renewal, differentiation and malignant potential. The aim of this paper is to discuss insights into cancer stem cells historical background and to provide a brief review of the new therapeutic strategies for targeting cancer stem cells.

  19. Capture and release of cancer cells using electrospun etchable MnO2 nanofibers integrated in microchannels

    Science.gov (United States)

    Liu, Hui-qin; Yu, Xiao-lei; Cai, Bo; You, Su-jian; He, Zhao-bo; Huang, Qin-qin; Rao, Lang; Li, Sha-sha; Liu, Chang; Sun, Wei-wei; Liu, Wei; Guo, Shi-shang; Zhao, Xing-zhong

    2015-03-01

    This paper introduces a cancer cell capture/release microchip based on the self-sacrificed MnO2 nanofibers. Through electrospinning, lift-off and soft-lithography procedures, MnO2 nanofibers are tactfully fabricated in microchannels to implement enrichment and release of cancer cells in liquid samples. The MnO2 nanofiber net which mimics the extra cellular matrix can lead to high capture ability with the help of a cancer cell-specific antibody bio-conjugation. Subsequently, an effective and friendly release method is carried out by using low concentration of oxalic acid to dissolve the MnO2 nanofiber substrate while keeping high viability of those released cancer cells at the same time. It is conceivable that our microchip may have potentials in realizing biomedical analysis of circulating tumor cells for biological and clinical researches in oncology.

  20. Oxidative Stress Mediates the Antiproliferative Effects of Nelfinavir in Breast Cancer Cells

    Science.gov (United States)

    Rusciano, Maria Rosaria; Maione, Angela Serena; Limite, Gennaro; Forestieri, Pietro; D’Angelo, Dario; D’Alessio, Matteo; Campiglia, Pietro; Formisano, Pietro; Iaccarino, Guido; Bianco, Roberto

    2016-01-01

    The discovery of the anti-proliferative activity of nelfinavir in HIV-free models has encouraged its investigation as anticancer drug. Although the molecular mechanism by which nelfinavir exerts antitumor activity is still unknown, its effects have been related to Akt inhibition. Here we tested the effects of nelfinavir on cell proliferation, viability and death in two human breast cancer cell lines and in human normal primary breast cells. To identify the mechanism of action of nelfinavir in breast cancer, we evaluated the involvement of the Akt pathway as well as the effects of nelfinavir on reactive oxygen species (ROS) production and ROS-related enzymes activities. Nelfinavir reduced breast cancer cell viability by inducing apoptosis and necrosis, without affecting primary normal breast cells. The antitumor activity of nelfinavir was related to alterations of the cell redox state, coupled with an increase of intracellular ROS production limited to cancer cells. Nelfinavir treated tumor cells also displayed a downregulation of the Akt pathway due to disruption of the Akt-HSP90 complex, and subsequent degradation of Akt. These effects resulted to be ROS dependent, suggesting that ROS production is the primary step of nelfinavir anticancer activity. The analysis of ROS-producers and ROS-detoxifying enzymes revealed that nelfinavir-mediated ROS production was strictly linked to flavoenzymes activation. We demonstrated that ROS enhancement represents the main molecular mechanism required to induce cell death by nelfinavir in breast cancer cells, thus supporting the development of new and more potent oxidizing molecules for breast cancer therapy. PMID:27280849

  1. Silencing NOTCH signaling causes growth arrest in both breast cancer stem cells and breast cancer cells

    Science.gov (United States)

    Suman, S; Das, T P; Damodaran, C

    2013-01-01

    Background: Breast cancer stem cells (BCSCs) are characterized by high aldehyde dehydrogenase (ALDH) enzyme activity and are refractory to current treatment modalities, show a higher risk for metastasis, and influence the epithelial to mesenchymal transition (EMT), leading to a shorter time to recurrence and death. In this study, we focused on examination of the mechanism of action of a small herbal molecule, psoralidin (Pso) that has been shown to effectively suppress the growth of BSCSs and breast cancer cells (BCCs), in breast cancer (BC) models. Methods: ALDH− and ALDH+ BCCs were isolated from MDA-MB-231 cells, and the anticancer effects of Pso were measured using cell viability, apoptosis, colony formation, invasion, migration, mammosphere formation, immunofluorescence, and western blot analysis. Results: Psoralidin significantly downregulated NOTCH1 signaling, and this downregulation resulted in growth inhibition and induction of apoptosis in both ALDH− and ALDH+ cells. Molecularly, Pso inhibited NOTCH1 signaling, which facilitated inhibition of EMT markers (β-catenin and vimentin) and upregulated E-cadherin expression, resulting in reduced migration and invasion of both ALDH− and ALDH+ cells. Conclusion: Together, our results suggest that inhibition of NOTCH1 by Pso resulted in growth arrest and inhibition of EMT in BCSCs and BCCs. Psoralidin appears to be a novel agent that targets both BCSCs and BCCs. PMID:24129237

  2. Dominant B-cell epitopes from cancer/stem cell antigen SOX2 recognized by serum samples from cancer patients

    OpenAIRE

    Shih, Julia; Rahman, Munira; Luong, Quang T; Lomeli, Shirley H.; Riss, Joseph; Prins, Robert M.; Gure, Ali O.; Zeng, Gang

    2014-01-01

    Human sex determining region Y-box 2 (SOX2) is an important transcriptional factor involved in the pluripotency and stemness of human embryonic stem cells. SOX2 plays important roles in maintaining cancer stem cell activities of melanoma and cancers of the brain, prostate, breast, and lung. SOX2 is also a lineage survival oncogene for squamous cell carcinoma of the lung and esophagus. Spontaneous cellular and humoral immune responses against SOX2 present in cancer patients classify it as a tu...

  3. Ganoderma lucidum (Reishi) Inhibits Cancer Cell Growth and Expression of Key Molecules in Inflammatory Breast Cancer

    OpenAIRE

    Martínez-Montemayor, Michelle M; Acevedo, Raysa Rosario; Otero-Franqui, Elisa; Cubano, Luis A.; Suranganie F. Dharmawardhane

    2011-01-01

    Inflammatory breast cancer (IBC) is the most lethal and least understood form of advanced breast cancer. Its lethality originates from its nature of invading the lymphatic system and absence of a palpable tumor mass. Different from other metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that retain E-cadherin-based cell–cell adhesions. Herein we describe the potential of the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for anti-IBC therapy...

  4. Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer

    OpenAIRE

    Weifeng Huang; Chunpeng Wan; Qicong Luo; Zhengjie Huang; Qi Luo

    2014-01-01

    Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 µM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere f...

  5. Targeting cancer stem cells: a new therapy to cure cancer patients

    OpenAIRE

    Hu, Yapeng; Fu, Liwu

    2012-01-01

    Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. They have been identified in blood, breast, brain, colon, melanoma, pancreatic, prostate, ovarian, lung cancers and so on. It is often considered to be associated with chemo-resistance and radio-resistance that lead to the failure of traditional therapies. Most therapies are directed at the fast growing tumor ...

  6. Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice.

    Directory of Open Access Journals (Sweden)

    Karsten Buschard

    Full Text Available BACKGROUND: Ethanol ('alcohol' is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. METHODS: The study included cellular in vitro tests using α-galactosylceramide (αGalCer, and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. RESULTS: Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05. CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05, whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. CONCLUSION: Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.

  7. Stem cells in radiation and oral cancer research

    International Nuclear Information System (INIS)

    Cancer stem cells (CSCs) are defined as a small sub population of cancer cells that constitute a pool of self sustaining cells with the exclusive ability to cause the heterogeneous lineages of cancer cells that comprise the tumour. There are three main characteristics of CSCs. Initially the cell must show potent tumour initiation in that it can regenerate the tumour which it was derived from a limited number of cells. In addition, the cells should demonstrate self renewal in vivo, which is practically observed via regrowth of phenotypically indistinguishable and heterogeneous tumours following serial transplantation of re-isolated CSCs in secondary and tertiary recipients. Finally, the cells must show a differentiation capacity, allowing them to give rise to a heterogeneous progeny, which represents a phenocopy of the original tumour. This article highlights the radiation therapy resulting in radiation resistance in cancer stem cells. (author)

  8. Investigation of the selenium metabolism in cancer cell lines

    DEFF Research Database (Denmark)

    Lunøe, Kristoffer; Gabel-Jensen, Charlotte; Stürup, Stefan; Andresen, Lars; Skov, Søren; Gammelgaard, Bente

    2011-01-01

    The aim of this work was to compare different selenium species for their ability to induce cell death in different cancer cell lines, while investigating the underlying chemistry by speciation analysis. A prostate cancer cell line (PC-3), a colon cancer cell line (HT-29) and a leukaemia cell line...... incubated with cells for 24 h and the induction of cell death was measured using flow cytometry. The amounts of total selenium in cell medium, cell lysate and the insoluble fractions was determined by ICP-MS. Speciation analysis of cellular fractions was performed by reversed phase, anion exchange and size...... exclusion chromatography and ICP-MS detection. The selenium compounds exhibited large differences in their ability to induce cell death in the three cell lines and the susceptibilities of the cell lines were different. Full recovery of selenium in the cellular fractions was observed for all Se compounds...

  9. Optimization of an Enrichment process for Circulating tumor cells from the blood of Head and Neck Cancer patients through depletion of normal cells

    OpenAIRE

    Yang, Liying; Lang, James C.; Balasubramanian, Priya; Jatana, Kris R.; Schuller, David; Agrawal, Amit; Zborowski, Maciej; Chalmers, Jeffrey J.

    2009-01-01

    The optimization of a purely negative depletion, enrichment process for circulating tumor cells, CTC's, in the peripheral blood of Head and Neck cancer patients is presented. The enrichment process uses a red cell lysis step followed by immunomagnetic labeling, and subsequent depletion, of CD45 positive cells. A number of relevant variables are quantified, or attempted to be quantified, which control the performance of the enrichment process. Six different immunomagnetic labeling combinations...

  10. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

    Science.gov (United States)

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate tha...

  11. Characterization of normal and cancer stem cells: One experimental paradigm for two kinds of stem cells

    OpenAIRE

    Mayol, Jean-François; Loeuillet, Corinne; Hérodin, Francis; Wion, Didier

    2009-01-01

    The characterization of normal stem cells and cancer stem cells uses the same paradigm. These cells are isolated by a Fluorescent-Activated Cell Sorting step and their stemness is assayed following implantation into animals. However, differences exist between these two kinds of stem cells. Therefore, the translation of the experimental procedures used for normal stem cell isolation into the cancer stem cell research field is a potential source of artefacts. In addition, normal stem cell thera...

  12. Experimental studies on ultralow frequency pulsed gradient magnetic field inducing apoptosis of cancer cell and inhibiting growth of cancer cell

    Institute of Scientific and Technical Information of China (English)

    曾繁清; 郑从义; 张新晨; 李宗山; 李朝阳; 王川婴; 张新松; 黄晓玲; 张沪生

    2002-01-01

    The morphology characteristics of cell apoptosis of the malignant tumour cells in magnetic field-treated mouse was observed for the first time. The apoptotic cancer cell contracted, became rounder and divorced from adjacent cells; the heterochromatin condensed and coagulated together along the inner side of the nuclear membrane; the endoplasmic reticulums(ER) expanded and fused with the cellular membrane; many apoptotic bodies which were packed by the cellular membrane appeared and were devoured by some lymphocytes and plasma. Apoptosis of cancer cells was detected by terminal deoxynucleotidyl transferase mediated in situ nick end labeling(TUNEL). It was found that the number of apoptosis cancer cells of the sample treated by the magnetic field is more than that of the control sample. The growth of malignant tumour in mice was inhibited and the ability of immune cell to dissolve cancer cells was improved by ultralow frequency(ULF) pulsed gradient magnetic field; the nuclei DNA contents decreased, indicating that magnetic field can block DNA replication and inhibit mitosis of cancer cells. It was suggested that magnetic field could inhibit the metabolism of cancer cell, lower its malignancy, and restrain its rapid and heteromorphic growth. Since ULF pulsed gradient magnetic field can induce apoptosis of cancer cells and inhibit the growth of malignant tumour, it could be used as a new method to treat cancer.

  13. Cancer Stem Cells in Small Cell Lung Cancer Cell Line H446: Higher Dependency on Oxidative Phosphorylation and Mitochondrial Substrate-Level Phosphorylation than Non-Stem Cancer Cells

    OpenAIRE

    Gao, Cuicui; Shen, Yao; Jin, Fang; Miao, Yajing; Qiu, Xiaofei

    2016-01-01

    Recently, targeting cancer stem cells (CSCs) metabolism is becoming a promising therapeutic approach to improve cancer treatment outcomes. However, knowledge of the metabolic state of CSCs in small cell lung cancer is still lacking. In this study, we found that CSCs had significantly lower oxygen consumption rate and extracellular acidification rate than non-stem cancer cells. Meanwhile, this subpopulation of cells consumed less glucose, produced less lactate and maintained lower ATP levels. ...

  14. The role of bisphosphonates in breast cancer: Direct effects of bisphosphonates on breast cancer cells

    International Nuclear Information System (INIS)

    In addition to inhibiting bone resorption, bisphosphonates have also been shown to exhibit antitumour effects. In vitro, bisphosphonates inhibit proliferation and induce apoptosis in cultured human breast cancer cells. In addition, bisphosphonate treatment interferes with breast cancer cell adhesion to bone matrix, and inhibits cell migration and invasion. The combination of bisphosphonates with other anticancer drugs such as the taxoids markedly enhances these effects. These newly recognized direct actions of bisphosphonates on breast cancer cells indicate that these agents may have a greater role to play in treatment of patients suffering from cancers with a propensity to metastasize to bone

  15. Pancreatic involvement in small cell lung cancer

    International Nuclear Information System (INIS)

    Few data are available concerning incidence, clinical picture, and prognosis for pancreatic metastases of small cell lung carcinoma. In this paper we review the related literature available in English language. Although pancreatic metastases are generally asymptomatic, they can rarely produce clinical symptoms or functional abnormalities. The widespread use of multi-detector computerised tomography (CT) in contemporary medical practice has led to an increased detection of pancreatic metastases in oncology patients. Tissue diagnosis is imperative because radiological techniques alone are incapable of differentiating them from primary pancreatic tumours. Pancreatic metastases occur in the relative end stage of small cell lung cancer. The main complications of these lesions, although rare, are acute pancreatitis and obstructive jaundice. Early chemotherapy can provide a survival benefit even in patients with mild acute pancreatitis or extrahepatic biliary obstruction

  16. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  17. Liver Label Retaining Cancer Cells Are Relatively Resistant to the Reported Anti-Cancer Stem Cell Drug Metformin

    OpenAIRE

    Xin, Hong-Wu; Ambe, Chenwi M.; Miller, Tyler C.; Chen, Jin-Qiu; Wiegand, Gordon W.; Anderson, Andrew J.; Ray, Satyajit; Mullinax, John E.; Hari, Danielle M; Koizumi, Tomotake; Godbout, Jessica D.; Goldsmith, Paul K.; Stojadinovic, Alexander; Rudloff, Udo; Thorgeirsson, Snorri S.

    2016-01-01

    Background & Aims: Recently, we reported that liver Label Retaining Cancer Cells (LRCC) can initiate tumors with only 10 cells and are relatively resistant to the targeted drug Sorafenib, a standard of practice in advanced hepatocellular carcinoma (HCC). LRCC are the only cancer stem cells (CSC) isolated alive according to a stem cell fundamental function, asymmetric cell division. Metformin has been reported to preferentially target many other types of CSC of different organs, including live...

  18. Stem cells and cancer: Evidence for bone marrow stem cells in epithelial cancers

    Institute of Scientific and Technical Information of China (English)

    Han-Chen Li; Calin Stoicov; Arlin B Rogers; JeanMarie Houghton

    2006-01-01

    Cancer commonly arises at the sites of chronic inflammation and infection. Although this association has long been recognized, the reason has remained unclear. Within the gastrointestinal tract, there are many examples of inflammatory conditions associated with cancer, and these include reflux disease and Barrett's adenocarcinoma of the esophagus, Helicobacter infection and gastric cancer, inflammatory bowel disease and colorectal cancer and viral hepatitis leading to hepatocellular carcinoma.There are several mechanisms by which chronic inflammation has been postulated to lead to cancer which includes enhanced proliferation in an endless attempt to heal damage, the presence of a persistent inflammatory environment creating a pro-carcinogenic environment and more recently a role for engraftment of circulating marrow-derived stem cells which may contribute to the stromal components of the tumor as well as the tumor mass itself. Here we review the recent advances in our understanding of the contributions of circulating bone marrow-derived stem cells to the formation of tumors in animal models as well as in human beings.

  19. Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells

    Science.gov (United States)

    Xu, Wenwei; Mezencev, Roman; Kim, Byungkyu; Wang, Lijuan; McDonald, John; Sulchek, Todd; Sulchek Team; McDonald Team

    2013-03-01

    The metastatic potential of cells is an important parameter in the design of optimal strategies for the personalized treatment of cancer. Using atomic force microscopy (AFM), we show that ovarian cancer cells are generally softer and display lower intrinsic variability in cell stiffness than non-malignant ovarian epithelial cells. A detailed study of highly invasive ovarian cancer cells (HEY A8) and their less invasive parental cells (HEY), demonstrates that deformability can serve as an accurate biomarker of metastatic potential. Comparative gene expression profiling indicate that the reduced stiffness of highly metastatic HEY A8 cells is associated with actin cytoskeleton remodeling, microscopic examination of actin fiber structure in these cell lines is consistent with this prediction. Our results indicate that cell stiffness not only distinguishes ovarian cancer cells from non-malignant cells, but may also be a useful biomarker to evaluate the relative metastatic potential of ovarian and perhaps other types of cancer cells.

  20. Oxidative stress in NSC-741909-induced apoptosis of cancer cells

    Directory of Open Access Journals (Sweden)

    Huang Peng

    2010-04-01

    Full Text Available Abstract Background NSC-741909 is a novel anticancer agent that can effectively suppress the growth of several cell lines derived from lung, colon, breast, ovarian, and kidney cancers. We recently showed that NSC-741909-induced antitumor activity is associated with sustained Jun N-terminal kinase (JNK activation, resulting from suppression of JNK dephosphorylation associated with decreased protein levels of MAPK phosphatase-1. However, the mechanisms of NSC-741909-induced antitumor activity remain unclear. Because JNK is frequently activated by oxidative stress in cells, we hypothesized that reactive oxygen species (ROS may be involved in the suppression of JNK dephosphorylation and the cytotoxicity of NSC-741909. Methods The generation of ROS was measured by using the cell-permeable nonfluorescent compound H2DCF-DA and flow cytometry analysis. Cell viability was determined by sulforhodamine B assay. Western blot analysis, immunofluorescent staining and flow cytometry assays were used to determine apoptosis and molecular changes induced by NSC-741909. Results Treatment with NSC-741909 induced robust ROS generation and marked MAPK phosphatase-1 and -7 clustering in NSC-741909-sensitive, but not resistant cell lines, in a dose- and time-dependent manner. The generation of ROS was detectable as early as 30 min and ROS levels were as high as 6- to 8-fold above basal levels after treatment. Moreover, the NSC-741909-induced ROS generation could be blocked by pretreatment with antioxidants, such as nordihydroguaiaretic acid, aesculetin, baicalein, and caffeic acid, which in turn, inhibited the NSC-741909-induced JNK activation and apoptosis. Conclusion Our results demonstrate that the increased ROS production was associated with NSC-741909-induced antitumor activity and that ROS generation and subsequent JNK activation is one of the primary mechanisms of NSC-741909-mediated antitumor cell activity.