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  1. Spontaneous pneumothorax due to bronchopleural fistula following reirradiation for locoregionally recurrent squamous cell lung cancer.

    Science.gov (United States)

    Ota, Takayo; Suzumura, Tomohiro; Sugiura, Takamune; Hasegawa, Yoshikazu; Yonesaka, Kimio; Makihara, Masaru; Tsukuda, Hiroshi; Tada, Takuhito; Fukuoka, Masahiro

    2016-05-01

    Spontaneous pneumothorax following radiotherapy for pulmonary malignancy is an unusual clinical condition. Here, we report a case of a 78-year-old male suffering from dyspnea during radiotherapy for squamous cell lung cancer of the right main bronchus. Imaging studies and fiberoptic bronchoscopy revealed that pneumothorax was due to a bronchopleural fistula. PMID:27190612

  2. Tolvaptan Treatment in Syndrome of Inappropriate ADH Secretion due to Small Cell Lung Cancer

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    Mucahit Gur

    2014-06-01

    Full Text Available Experience of ADH receptor antagonist (-vaptanes treatment in hyponatremia in malign patient is very limited. 68 years old male patient admitted to our department with a complain of nause, vomitting and epigastric pain. He has advanced stage of small cell lung cancer. He had treated with cisplatin and etoposide regimen 10 days ago as a first cure. We diagnosed inapropriate secretion of antidiuretic hormone syndrome (SIADH with low sodium level (118 meq/dl. Although the treatment with water restriction and 3% NaCl infusion, sodium level was not in normal. So we ordered 30 mg tolvaptan tablet. And then sodium levels were reached normal. After one month of discharge from hospital, he has hospitilized with same symptom and diagnosis. And again we ordered same treatment procedure and tolvaptane treatment. He had normal sodium (136 mEq/dl level during his follow up. This case demostrate that tolvaptane treatment is suitable aproaches in hyponatremia due to SIADH in oncologic patient.

  3. Caspase 8 and maspin are downregulated in breast cancer cells due to CpG site promoter methylation

    International Nuclear Information System (INIS)

    Epigenetic changes associated with promoter DNA methylation results in silencing of several tumor suppressor genes that lead to increased risk for tumor formation and for progression of the cancer. Methylation specific PCR (MSP) and bisulfite sequencing were used for determination of proapoptotic gene Caspase 8 (CASP8) and the tumor suppressor gene maspin promoter methylation in four breast cancer and two non-tumorigenic breast cell lines. Involvement of histone H3 methylation in those cell lines were examined by CHIP assay. The CpG sites in the promoter region of CASP8 and maspin were methylated in all four breast cancer cell lines but not in two non-tumorigenic breast cell lines. Demethylation agent 5-aza-2'-deoxycytidine (5-aza-dc) selectively inhibits DNA methyltransferases, DNMT3a and DNMT3b, and restored CASP8 and maspin gene expression in breast cancer cells. 5-aza-dc also reduced histone H3k9me2 occupancy on CASP8 promoter in SKBR3cells, but not in MCF-7 cells. Combination of histone deacetylase inhibitor Trichostatin A (TSA) and 5-aza-dc significant decrease in nuclear expression of Di-methyl histone H3-Lys27 and slight increase in acetyl histone H3-Lys9 in MCF-7 cells. CASP8 mRNA and protein level in MCF-7 cells were increased by the 5-aza-dc in combination with TSA. Data from our study also demonstrated that treatment with 5-FU caused a significant increase in unmethylated CASP8 and in CASP8 mRNA in all 3 cancer lines. CASP8 and maspin expression were reduced in breast cancer cells due to promoter methylation. Selective application of demethylating agents could offer novel therapeutic opportunities in breast cancer

  4. Interleukin-6 expression under gravitational stress due to vibration and hypergravity in follicular thyroid cancer cells.

    Directory of Open Access Journals (Sweden)

    Xiao Ma

    Full Text Available It is known that exposing cell lines in vitro to parabolic flights changes their gene expression and protein production patterns. Parabolic flights and spaceflight in general are accompanied by transient hypergravity and vibration, which may impact the cells and therefore, have to be considered too. To estimate the possible impact of transient hypergravity and vibration, we investigated the effects of these forces separately using dedicated ground-based facilities. We placed follicular thyroid ML-1 and CGTH W-1 cancer cells in a specific centrifuge (MuSIC Multi Sample Incubator Centrifuge; SAHC Short Arm Human Centrifuge simulating the hypergravity phases that occur during one (P1 and 31 parabolas (P31 of parabolic flights, respectively. On the Vibraplex device, the same cell lines were treated with vibration waves corresponding to those that occur during a whole parabolic flight lasting for two hours. After the various treatments, cells were harvested and analyzed by quantitative real-time PCR, focusing on the genes involved in forming (ACTB, MYO9, TUBB, VIM, TLN1, and ITGB1 and modulating (EZR, RDX, and MSN the cytoskeleton, as well as those encoding growth factors (EGF, CTGF, IL6, and IL8 or protein kinases (PRKAA1 and PRKCA. The analysis revealed alterations in several genes in both cell lines; however, fewer genes were affected in ML-1 than CGTH W-1 cells. Interestingly, IL6 was the only gene whose expression was changed in both cell lines by each treatment, while PKCA transcription remained unaffected in all experiments. We conclude that a PKCa-independent mechanism of IL6 gene activation is very sensitive to physical forces in thyroid cells cultured in vitro as monolayers.

  5. Facial skin metastasis due to small-cell lung cancer: a case report

    Directory of Open Access Journals (Sweden)

    Barbetakis Nikolaos

    2009-01-01

    Full Text Available Abstract Introduction Cutaneous metastases in the facial region occur in less than 0.5% of patients with metastatic cancer. They are an important finding and are not often the first sign leading to diagnosis. Case presentation We describe the case of a 64-year-old male patient who presented with dyspnea, pleuritic pain, loss of weight and a nodule on his left cheek. A chest X-ray revealed a left upper lobe mass with mediastinal lymphadenopathy. Excision biopsy of the facial nodule revealed small-cell lung carcinoma. Palliative chemo-radiotherapy was administered and the patient survived for 12 months. Conclusion A high index of suspicion is necessary for the early detection of facial cutaneous metastases. Appropriate treatment may prolong patient survival.

  6. Interleukin-6 Expression under Gravitational Stress Due to Vibration and Hypergravity in Follicular Thyroid Cancer Cells

    OpenAIRE

    Xiao Ma; Markus Wehland; Ganna Aleshcheva; Jens Hauslage; Kai Waßer; Ruth Hemmersbach; Manfred Infanger; Johann Bauer; Daniela Grimm

    2013-01-01

    It is known that exposing cell lines in vitro to parabolic flights changes their gene expression and protein production patterns. Parabolic flights and spaceflight in general are accompanied by transient hypergravity and vibration, which may impact the cells and therefore, have to be considered too. To estimate the possible impact of transient hypergravity and vibration, we investigated the effects of these forces separately using dedicated ground-based facilities. We placed follicular thyroi...

  7. Hypotension due to Chemotherapy in a Patient with Small Cell Lung Cancer and Lambert-Eaton Myasthenic Syndrome Undergoing Hemodialysis: A First Case Report

    Directory of Open Access Journals (Sweden)

    Taiji Kuwata

    2012-01-01

    Full Text Available We present the first case of small cell lung cancer with Lambert-Eaton myasthenic syndrome during hemodialysis (HD. A 72-year-old male patient receiving HD experienced progressive muscle weakness. He was diagnosed with small cell lung cancer with Lambert-Eaton myasthenic syndrome due to an increased serum level of anti-voltage-gated calcium channel antibody and aspiration cytology on endobronchial ultrasonography for the swelling of a subcarinal lymph node. He received chemotherapy consisting of carboplatin (300 mg/m2 and etoposide (50 mg/m2, to which he had a partial response. However, the second therapy course could not be administered because of the unexpected development of severe hematological adverse events, which also prevented him from undergoing further HD. This case indicates that caution should be taken when using chemotherapy for such patients because of hypotension due to chemotherapy, with which it is impossible to undergo HD.

  8. Influence of low doses of radiation due to 222Rn on proliferation of fibroblasts and MCF-7 human breast cancer cells in vitro

    International Nuclear Information System (INIS)

    The aim of the present study is to analyze the effects of low doses of radiation due to radon (within the range present in the environment) in the proliferation of normal (fibroblasts) and tumoral (MCF-7 human breast cancer cells) mammalian cells. Both fibroblast and MCF-7 cells were incubated in culture media with different levels of radon (doses of 10-15,000 μGy), or non-radon (control). After incubation the number of cells per plate was measured with a hemocytometer. The dissolution of radon in the culture media decreased the proliferation of MCF-7 cells (not the fibroblasts). Within the range of doses used in this experiment, the lowest as well as the highest doses of radiation had the lowest antiproliferative effects. Intermediate doses strongly decreased the number of final cells with respect to those in the control population

  9. Stem Cell Therapy and Breast Cancer Treatment: Review of Stem Cell Research and Potential Therapeutic Impact Against Cardiotoxicities Due to Breast Cancer Treatment

    OpenAIRE

    Sharp, Thomas E.; George, Jon C.

    2014-01-01

    A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually ...

  10. Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Arenz, Andrea; Ziemann, Frank; Wittig, Andrea; Preising, Stefanie; Engenhart-Cabillic, Rita [Philipps-University, Department of Radiotherapy and Radiooncology, BMFZ - Biomedical Research Center, Marburg (Germany); Mayer, Christina; Wagner, Steffen; Klussmann, Jens-Peter; Wittekindt, Claus [Justus Liebig University, Department of Otorhinolaryngology and Head and Neck Surgery, Giessen (Germany); Dreffke, Kirstin [Philipps-University, Institute for Radiobiology and Molecular Radiooncology, Marburg (Germany)

    2014-09-15

    Human Papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) respond favourably to radiotherapy as compared to HPV-unrelated HNSCC. We investigated DNA damage response in HPV-positive and HPV-negative HNSCC cell lines aiming to identify mechanisms, which illustrate reasons for the increased sensitivity of HPV-positive cancers of the oropharynx. Radiation response including clonogenic survival, apoptosis, DNA double-strand break (DSB) repair, and cell cycle redistribution in four HPV-positive (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) and four HPV-negative (UD-SCC-1, UM-SCC-6, UM-SCC-11b, UT-SCC-33) cell lines was evaluated. HPV-positive cells were more radiosensitive (mean SF2: 0.198 range: 0.22-0.18) than HPV-negative cells (mean SF2: 0.34, range: 0.45-0.27; p = 0.010). Irradiated HPV-positive cell lines progressed faster through S-phase showing a more distinct accumulation in G2/M. The abnormal cell cycle checkpoint activation was accompanied by a more pronounced increase of cell death after x-irradiation and a higher number of residual and unreleased DSBs. The enhanced responsiveness of HPV-related HNSCC to radiotherapy might be caused by a higher cellular radiosensitivity due to cell cycle dysregulation and impaired DNA DSB repair. (orig.) [German] Fuer Patienten mit HPV-assoziierten Kopf-Hals-Tumoren (HNSCC) ist im Vergleich zu Patienten mit nicht-HPV-assoziierten Tumoren ein besseres Ueberleben nach Radiotherapie gesichert. Ziel der Untersuchung war die Identifizierung von Unterschieden in der zellulaeren DNA-Schadensantwort von HPV-positiven und HPV-negativen Zelllinien, wodurch die bereits in Erprobung stehende Deeskalation einer Radiotherapie bei Patienten mit HPV-assoziierten HNSCC durch experimentelle Daten abgesichert werden koennte. Klonogenes Ueberleben, Induktion von Apoptose, DNA-Doppelstrang-Reparatur und Zellzyklusverhalten wurden in vier HPV-positiven (UM-SCC-47, UM-SCC-104, 93-VU-147T, UPCI:SCC152) und vier HPV

  11. 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 ...

  12. 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 ...

  13. 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...

  14. 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 ...

  15. 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)

  16. Radiation resistance due to high expression of miR-21 and G2/M checkpoint arrest in breast cancer cells

    International Nuclear Information System (INIS)

    There is evidence that the extent of the G2/M arrest following irradiation is correlated with tumour cell survival and hence therapeutic success. We studied the regulation of cellular response to radiation treatment by miR-21-mediated modulation of cell cycle progression in breast cancer cells and analysed miR-21 expression in breast cancer tissue samples with long-term follow up. The miR-21 expression levels were quantified (qRT-PCR) in a panel of 86 cases of invasive breast carcinomas in relation to metastasis free survival. The cellular radiosensitivity of human breast cancer cells after irradiation was determined comparing two cell lines (T47D and MDA-MB-361) by cell proliferation and colony forming assays. The influence of miR-21 overexpression or downregulation on cell cycle progression and G2/M checkpoint arrest after irradiation was assessed by flow cytometric analysis. The expression of miR-21 was transiently increased 8 hours after irradiation in the radioresistant T47D cells and significantly changed with lower extent in radiosensitive MDA-MB-361 cells. Anti-miR-21 treated breast cancer cells failed to exhibit the DNA damage-G2 checkpoint increase after irradiation. Apoptotic activity was significantly enhanced from 7% to 27% in T47D cells and from 18% to 30% in MDA-MB-361 cells 24 hours after 5 Gy irradiation. Additionally, we characterized expression of miR-21 in invasive breast carcinomas. In comparison to non-cancerous adjacent breast tissue, tumours samples had increased miR-21 expression that inversely correlated with the distant metastases-free survival of patients (p = 0.029). Our data indicate that miR-21 expression in breast cancer cells contributes to radiation resistance by compromising cell cycle progression. These data point to the potential of combining radiotherapy with an anti-miR-21 as a potent G2/M check point inhibitor in overcoming radiation resistance of tumours

  17. Radiation resistance due to high expression of miR-21 and G2/M checkpoint arrest in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Anastasov Nataša

    2012-12-01

    Full Text Available Abstract Background There is evidence that the extent of the G2/M arrest following irradiation is correlated with tumour cell survival and hence therapeutic success. We studied the regulation of cellular response to radiation treatment by miR-21-mediated modulation of cell cycle progression in breast cancer cells and analysed miR-21 expression in breast cancer tissue samples with long-term follow up. Methods The miR-21 expression levels were quantified (qRT-PCR in a panel of 86 cases of invasive breast carcinomas in relation to metastasis free survival. The cellular radiosensitivity of human breast cancer cells after irradiation was determined comparing two cell lines (T47D and MDA-MB-361 by cell proliferation and colony forming assays. The influence of miR-21 overexpression or downregulation on cell cycle progression and G2/M checkpoint arrest after irradiation was assessed by flow cytometric analysis. Results The expression of miR-21 was transiently increased 8 hours after irradiation in the radioresistant T47D cells and significantly changed with lower extent in radiosensitive MDA-MB-361 cells. Anti-miR-21 treated breast cancer cells failed to exhibit the DNA damage-G2 checkpoint increase after irradiation. Apoptotic activity was significantly enhanced from 7% to 27% in T47D cells and from 18% to 30% in MDA-MB-361 cells 24 hours after 5 Gy irradiation. Additionally, we characterized expression of miR-21 in invasive breast carcinomas. In comparison to non-cancerous adjacent breast tissue, tumours samples had increased miR-21 expression that inversely correlated with the distant metastases-free survival of patients (p = 0.029. Conclusions Our data indicate that miR-21 expression in breast cancer cells contributes to radiation resistance by compromising cell cycle progression. These data point to the potential of combining radiotherapy with an anti-miR-21 as a potent G2/M check point inhibitor in overcoming radiation resistance of tumours.

  18. Attempts to predict the long-term decrease in lung function due to radiotherapy of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: To obtain a model which can predict long-term decrease in lung function due to radiation damage from dose-volume data for patients with non-small cell lung cancer. Patients and methods: 27 patients were included, all long-term survivors after radical radiation therapy. For each patient a regression analysis was performed on a post-RT succession of measurements of FEV1 in order to estimate the decrease after 2 years and a standard error (SE) on this regression estimate. The modelling was based on dose-volume histograms (DVH) exported from the treatment planning system, and involved fits of threshold models, a mean lung dose model as well as more complex models based on the relative damaged volume (rdV). Results: Decreases after 2 years of up to 28% in FEV1 was measured (median 10%), with significant day-to-day variation in FEV1 for the individual patient. The threshold models predicted the long-term decrease in FEV1 well when the SE was interpreted as the uncertainty of the measured decrease. The best threshold value, marginally, was 30 Gy with an R2 of 0.46. The mean lung dose model did not perform so well. A complex model based on rdV performed better than any of the other models (R2 =0.52). Conclusion: The long-term decrease in FEV1 could be predicted from a simple dose-volume model when the SE was interpreted as the uncertainty of the measured decrease

  19. 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.

  20. 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 ...

  1. MiR-27b is epigenetically downregulated in tamoxifen resistant breast cancer cells due to promoter methylation and regulates tamoxifen sensitivity by targeting HMGB3.

    Science.gov (United States)

    Li, Xiunan; Wu, Yumei; Liu, Aihui; Tang, Xin

    2016-09-01

    MiR-27b downregulation is significantly associated with tamoxifen resistance in breast cancer cells. However, how it is downregulated in tamoxifen resistant (TamR) breast cancer cells and its downstream regulation were not clear. By performing MSP assay and QRT-PCR analysis with the use of 5-AZA-dC, a DNA methyltransferase inhibitor, we observed that TamR MCF-7 cells had significantly higher levels of methylation in the miR-27b promoter region than tamoxifen sensitive MCF-7 (TamS) cells and demethylation restored miR-27b expression. Re-expression of miR-27b sensitized TamR MCF-7 cells to tamoxifen, inhibited invasion and reversed epithelial-mesenchymal transition (EMT)-like properties. By using bioinformatics analysis and following dual luciferase and western blot analysis, this study confirmed a direct regulation of miR-27b on HMGB3 expression by binding to the 3'UTR. In addition, this study also found that silencing of HMGB3 indeed partially phenocopied the effects of miR-27b in reducing tamoxifen resistance and cell invasion and in reversing EMT-like properties. Therefore, we infer that HMGB3 is a functional target of miR-27b in modulation of tamoxifen resistance and EMT. PMID:27363334

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. Association between micronuclei frequency in pollen mother cells of Tradescantia and mortality due to cancer and cardiovascular diseases: A preliminary study in Sao Jose dos Campos, Brazil

    International Nuclear Information System (INIS)

    The present study was designed to explore the correlation between the frequency of micronuclei in Trad-MN, measured across 28 biomonitoring stations during the period comprised between 11 of May and 2 of October, 2006, and adjusted mortality rates due to cardiovascular, respiratory diseases and cancer in Sao Jose dos Campos, Brazil, an area with different sources of air pollution. For controlling purposes, mortality rate due to gastrointestinal diseases (an event less prone to be affected by air pollution) was also considered in the analysis. Spatial distribution of micronuclei frequency was determined using average interpolation. The association between health estimators and micronuclei frequency was determined by measures of Pearson's correlation. Higher frequencies of micronuclei were detected in areas with high traffic and close to a petrochemical pole. Significant associations were detected between micronuclei frequency and adjusted mortality rate due to cardiovascular diseases (r = 0.841, p = 0.036) and cancer (r = 0.890, p = 0.018). The association between mortality due to chronic obstructive pulmonary diseases was positive but did not reach statistical significance (r = 0.640, p = 0.172), probably because of the small number of events. Gastrointestinal mortality did not exhibit significant association with micronuclei frequency. Because the small number of observations and the nature of an ecological study, the present findings must be considered with caution and considered as preliminary. Further studies, performed in different conditions of contamination and climate should be done before considering Trad-MN in the evaluation of human health risk imposed by air pollutants. - Bioassay used to explore the correlation between air pollution exposition and mortality rates.

  7. Association between micronuclei frequency in pollen mother cells of Tradescantia and mortality due to cancer and cardiovascular diseases: A preliminary study in Sao Jose dos Campos, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Mariani, Rauda Lucia [Department of Geochemistry, Fluminense Federal University (UFF), Niteroi, RJ (Brazil); Martins Jorge, Maria Paulete; Pereira, Sergio Silva; Melione, Luiz Paulo [National Institute for Space Research, Sao Jose dos Campos, SP (Brazil); Carvalho-Oliveira, Regiani [Experimental Air Pollution Laboratory, Department of Pathology, Sao Paulo University Medical School, Sao Paulo (Brazil); Ma, Te Hsiu [Department of Biological Sciences, Western Illinois University, Macomb, IL 61455 (United States); Nascimento Saldiva, Paulo Hilario, E-mail: pepino@usp.b [Experimental Air Pollution Laboratory, Department of Pathology, Sao Paulo University Medical School, Sao Paulo (Brazil)

    2009-06-15

    The present study was designed to explore the correlation between the frequency of micronuclei in Trad-MN, measured across 28 biomonitoring stations during the period comprised between 11 of May and 2 of October, 2006, and adjusted mortality rates due to cardiovascular, respiratory diseases and cancer in Sao Jose dos Campos, Brazil, an area with different sources of air pollution. For controlling purposes, mortality rate due to gastrointestinal diseases (an event less prone to be affected by air pollution) was also considered in the analysis. Spatial distribution of micronuclei frequency was determined using average interpolation. The association between health estimators and micronuclei frequency was determined by measures of Pearson's correlation. Higher frequencies of micronuclei were detected in areas with high traffic and close to a petrochemical pole. Significant associations were detected between micronuclei frequency and adjusted mortality rate due to cardiovascular diseases (r = 0.841, p = 0.036) and cancer (r = 0.890, p = 0.018). The association between mortality due to chronic obstructive pulmonary diseases was positive but did not reach statistical significance (r = 0.640, p = 0.172), probably because of the small number of events. Gastrointestinal mortality did not exhibit significant association with micronuclei frequency. Because the small number of observations and the nature of an ecological study, the present findings must be considered with caution and considered as preliminary. Further studies, performed in different conditions of contamination and climate should be done before considering Trad-MN in the evaluation of human health risk imposed by air pollutants. - Bioassay used to explore the correlation between air pollution exposition and mortality rates.

  8. 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 ...

  9. 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...

  10. 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...

  11. 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...

  12. Calculated lung cancer mortality due to radon

    International Nuclear Information System (INIS)

    From studies of miners, it is clear that an exposure to high concentrations of radon daughters leads to an increased incidence of lung cancer. In this Chapter the authors discuss how the experience for miners is used to estimate the incidence of radon-induced lung cancer among the general population. Such estimates cannot be very precise, in part because the miners studies do not lead to a well-determined relationship between the rate of cancer induction and the exposure levels. In particular, there are disparities in the results of studies for different groups of miners. These disparities may arise from the difficulties in obtaining accurate crucial data, such as the year-by-year exposure history over the working lifetime of the individual miners. Other differences may arise from differences in the smoking patterns in different groups and in details of the handling of the data. In any event, there remain substantial uncertainties in the conclusions for the miners themselves, both as to the ''average'' rate of cancer induction per WLM and as to the variation of this rate with the magnitude of the total exposure. Further, there are problems in using results obtained for miners at relatively high radon exposure levels for the prediction of the effects of radon at the much lower levels encountered in the normal indoor environment. Here one faces the problem of extrapolating from large dose levels to small dose levels. The generally adopted solution is to assume linearity

  13. A new approach to cancer therapy due to appropriate uptake and retention kinetics of meta-tetrahydroxy-phenylchlorin in a human fibroblast cell line.

    Science.gov (United States)

    Wierrani, F; Fiedler, D; Schnitzhofer, G; Stewart, J C; Gharehbaghi, K; Henry, M; Grin, W; Grünberger, W; Krammer, B

    1996-04-01

    Studies have shown that meta-tetrahydroxy-phenylchlorin is an efficient tumor targeting agent for laser photodynamic therapy. The effectiveness of this approach for cancer treatment depends on drug concentration, incubation time and extracellular protein. We studied uptake and retention kinetics of mTHPC in a human fibroblast cell line. Our results clearly demonstrate a difference in the amount of extracellular mTHPC at an incubation temperature of 37 degrees C compared to 20 degrees C and 4 degrees C. pH-values were always constant and not responsible for the increase. Furthermore, both absorption and fluorescence of mTHPC increase when incubated at normal human body temperature. Incubation of human fibroblast cells with mTHPC (10 micg/mL) showed that intracellular mTHPC increases in a linear manner reaching saturation after 24 hours and declining until 48 hours with concommitant increase of supernatant mTHPC. Therefore, we believe that tumor cells can be treated optimally with PDT following a delay > 24 hours after drug administration with a minimum of damage to surrounding normal tissues. PMID:8937740

  14. Esophageo pleural fistula due to esophageal cancer

    Directory of Open Access Journals (Sweden)

    Ruchi Sachdeva

    2015-01-01

    Full Text Available A 61-year-old male admitted in chest clinic with complaints of left-sided chest pain, sudden onset breathlessness, and cough since last 15 days. Patient was anex-smoker with no past history of tuberculosis. He was diagnosed with esophageal cancer and received radiotherapy 1 year back. On chest X-ray, left-sided hydropneumothorax was found and intercostal drainage insertion was done. A week later patient complained of extrusion of food particles into intercostal drainage bag. On evaluation, esophageopleural (EP fistula was confirmed.

  15. Esophageo pleural fistula due to esophageal cancer

    OpenAIRE

    Ruchi Sachdeva; Sandeep Sachdeva

    2015-01-01

    A 61-year-old male admitted in chest clinic with complaints of left-sided chest pain, sudden onset breathlessness, and cough since last 15 days. Patient was anex-smoker with no past history of tuberculosis. He was diagnosed with esophageal cancer and received radiotherapy 1 year back. On chest X-ray, left-sided hydropneumothorax was found and intercostal drainage insertion was done. A week later patient complained of extrusion of food particles into intercostal drainage bag. On evaluation, es...

  16. Cancer cells become susceptible to natural killer cell killing after exposure to histone deacetylase inhibitors due to glycogen synthase kinase-3-dependent expression of MHC class I-related chain A and B

    DEFF Research Database (Denmark)

    Skov, Søren; Pedersen, Marianne Terndrup; Andresen, Lars; Straten, Per Thor; Woetmann, Anders; Odum, Niels

    2005-01-01

    We show that histone deacetylase (HDAC) inhibitors lead to functional expression of MHC class I-related chain A and B (MICA/B) on cancer cells, making them potent targets for natural killer (NK) cell-mediated killing through a NK group 2, member D (NKG2D) restricted mechanism. Blocking either...

  17. 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...

  18. 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 ...

  19. 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.

  20. 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...

  1. Risk of thyroid cancer due to I-131

    International Nuclear Information System (INIS)

    The process of increasing thyroid cancer in children after Chernobyl accident is explained. The current situation of thyroid exposure and ultrasonography of thyroid after Fukushima nuclear accident are compared with the experiment of Chernobyl. It is consisted of 1) thyroid and iodine, medical treatment for radioactive iodine, 2) adult thyroid cancer due to Chernobyl nuclear accident, 3) increase of adult thyroid cancer after Chernobyl nuclear accident, 4) Fukushima nuclear accident and thyroid cancer and 5) principle of future research of thyroid. Nuclear tests in the world and change of I-131 in thyroid of sheep in Tokyo (1955 to 1987), ultrasonography of thyroid for atomic bomb survivor, some examples of many adult patients of thyroid cancer at EU mission, annual incidence of adult thyroid cancer after Chernobyl accident (1986 to 1995), distribution of thyroid I-131 from March 26 to 30, 2011, and results of thyroid test in Fukushima prefecture are illustrated. (S.Y.)

  2. 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

  3. Quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer

    International Nuclear Information System (INIS)

    The optimal timing of chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC) hasn’t been established, although evidence from studies supported that patients can benefit from early radiation therapy. The purpose of this study was to quantify tumor shrinkage in response to induction chemotherapy (IC), evaluate the impact of tumor shrinkage on radiation dosimetric parameters and determine its implication for the timing of radiation therapy for patients with LS-SCLC. Twenty patients with LS-SCLC who were treated with IC followed by concomitant radiation therapy were investigated retrospectively. Ten patients received 1 cycle of IC, and 10 patients received 2 cycles of IC. Pre-IC CT imaging was coregistered with a simulation CT, and virtual radiation plans were created for pre- and post-IC thoracic disease in each case. The changes in the gross target volume (GTV), planning target volume (PTV) and dosimetric factors associated with the lungs, esophagus and heart were analyzed. The mean GTV and PTV for all of the patients decreased by 60.9% and 40.2%, respectively, which resulted in a significant reduction in the radiation exposure to the lungs, esophagus and heart. Changes in the PTV and radiation exposure of normal tissue were not significantly affected by the number of chemotherapy cycles delivered, although patients who received 2 cycles of IC had a greater decrease in GTV than those who received only 1 cycle of IC (69.6% vs. 52.1%, p = 0.273). Our data showed that targeting the tumor post-IC may reduce the radiation dose to normal tissue in patients with LS-SCLC. However, the benefit to the normal tissue was not increased by an additional cycle of IC. These findings suggest that the first cycle of chemotherapy is very important for tumor shrinkage and that initiating thoracic radiation therapy at the second cycle of chemotherapy may be a reasonable strategy for timing of radiation therapy in LS-SCLC treatment

  4. 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...

  5. 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

  6. 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

  7. 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,...

  8. 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...

  9. 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 ...

  10. 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...

  11. 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...

  12. 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.

  13. 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

  14. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

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

  15. 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...

  16. 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.

  17. Breast cancer stem cells and radiation

    Science.gov (United States)

    Phillips, Tiffany Marie

    2007-12-01

    The present studies explore the response of breast cancer stem cells (BCSC's) to radiation and the implications for clinical cancer treatment. Current cancer therapy eliminates bulky tumor mass but may fail to eradicate a critical tumor initiating cell population termed "cancer stem cells". These cells are potentially responsible for tumor formation, metastasis, and recurrence. Recently cancer stem cells have been prospectively identified in various malignancies, including breast cancer. The breast cancer stem cell has been identified by the surface markers CD44+/CD24 -(low). In vitro mammosphere cultures allow for the enrichment of the cancer stem cell population and were utilized in order to study differential characteristics of BCSC's. Initial studies found that BCSC's display increased radiation resistance as compared to other non-stem tumor cells. This resistance was accompanied by decreased H2AX phosphorylation, decreased reactive oxygen species formation, and increased phosphorylation of the checkpoint protein Chk1. These studies suggest differential DNA damage and repair within the BCSC population. Studies then examined the consequences of fractionated radiation on the BCSC population and found a two-fold increase in BCSC's following 5 x 3Gy. This observation begins to tie cancer stem cell self-renewal to the clinical stem cell phenomenon of accelerated repopulation. Accelerated repopulation is observed when treatment gaps increase between sequential fractions of radiotherapy and may be due to cancer stem cell symmetric self-renewal. The balance between asymmetric and symmetric stem cell division is vital for proper maintenance; deregulation is likely linked to cancer initiation and progression. The developmental Notch-1 pathway was found to regulate BCSC division. Over-expressing the constitutively active Notch-1-ICD in MCF7 cells produced an increase in the BCSC population. Additionally, radiation was observed to increase the expression of the Notch-1

  18. 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...

  19. Palliative surgery for intestinal obstruction due to recurrent ovarian cancer

    International Nuclear Information System (INIS)

    Intestinal Obstruction is a frequent complication after operation for Ovarian Cancer. This study was done to see the outcome of palliative surgery for Intestinal Obstruction due to recurrent ovarian Cancer. We retrospectively evaluated the records of all the patients who presented with intestinal obstruction after operations for Ovarian Cancer in all the three Surgical Units of Ayub Teaching Hospital Abbottabad from March 1998 to April, 2009. Demographic data, type of management, morbidity, mortality, hospital stay, surgical procedure, symptomatic relief, return of bowel function and outcome were analyzed. There were 56 patients with symptoms of partial or complete intestinal obstruction. Conservative treatment was successful in 22 (39%) patients. Laparotomy was done in 30 (53.5%) patients. The cause of intestinal obstruction was adhesions 8 (26.6%), local recurrence 10 (33.3%) and diffuse carcinomatosis in 12 (40%) patients. Palliative surgery was done in 20 (66.6%) patients while 8 (26.6%) had adhesionolysis only. 9 (30%) patients had resection and anastomosis, 7 (23.3%) had bypass surgery, 3 (10%) had colostomy and one (3%) had Hartmann procedure. Postoperative complications occurred in 26 (86.6%) patients. 12 (40 %) patients died after surgery. Mean hospital stay was 18 (9-42) days. Palliative surgery was successful in 8 (26.65%). Majority of patients with Intestinal obstruction after operation for Ovarian Cancer can be managed conservatively. Palliative surgery is associated with high mortality and morbidity but it should be done in patients not responding to conservative measures. (Author)

  20. 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)

  1. Ovarian failure due to cancer treatment and fertility preservation options

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2016-04-01

    Full Text Available Primary ovarian insufficiency (POI, commonly referred to premature ovarian failure, is defined as ovarian failure before the age of 40 years. It is the loss of ovarian function caused by a process directly affecting ovaries. Cancer therapy which includes surgery, radiotherapy, and chemotherapy influence ovarian function, leading to premature menopause and loss of fertility. POI is idiopathic in most cases (74-90%. The known causes, in addition to anticancer treatment, are other processes like chromosomal abnormalities, autoimmunity, and natural aging can result in secondary ovarian failure, which is detected by an increase in serum gonadotropin levels (FSH and LH. There are evident risks of POI in women treated for cancer. Those who receive anticancer treatments have an increased risk of developing POI. There by, anticancer drugs and radiation therapy are considered as the most common toxins of ovaries. Although cancer incidence rates in women less than 50 years old continue to increase during recent years, mortality rates are dramatically decreasing due to modern advances in treatment. Increasing numbers of survivors are now confronted with the long-term consequences of exposure to these treatments. The pool of primordial follicles in the ovary is fixed and any injury to the ovary can potentially reduce this ovarian reserve, effectively advancing the patient’s reproductive age, thus narrowing the window of reproductive opportunity. Ovarian failure occurs in a significant percentage of childhood cancer survivors and many of them will seek care for reproductive dysfunction. Nevertheless, Embryo cryopreservation, oocyte cryopreservation, ovary tissue cryopreservation, ovarian suppression and oophoro-pexy are some options to preserve fertility in these groups. As a result, having foreknowledge of potential treatment related ovarian failure will allow the physician to give a better counsel to patients and their family regarding the importance and

  2. 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...

  3. 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.

  4. 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...

  5. Effect of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality

    Science.gov (United States)

    Zhang, Sui-Liang; Chen, Ting-Song; Ma, Chen-Yun; Meng, Yong-Bin; Zhang, Yu-Fei; Chen, Yi-Wei; Zhou, Yu-Hao

    2016-01-01

    Abstract Background: Observational studies have suggested that vitamin B supplementation is associated with cancer risk, but this association remains controversial. A pooled data-based meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCTs) investigating the effects of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality. Methods: PubMed, EmBase, and the Cochrane Library databases were searched to identify trials to fit our analysis through August 2015. Relative risk (RR) was used to measure the effect of vitamin B supplementation on the risk of cancer incidence, death due to cancer, and total mortality using a random-effect model. Cumulative meta-analysis, sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. Results: Eighteen RCTs reporting the data on 74,498 individuals were included in the meta-analysis. Sixteen of these trials included 4103 cases of cancer; in 6 trials, 731 cancer-related deaths occurred; and in 15 trials, 7046 deaths occurred. Vitamin B supplementation had little or no effect on the incidence of cancer (RR: 1.04; 95% confidence interval [CI]: 0.98–1.10; P = 0.216), death due to cancer (RR, 1.05; 95% CI: 0.90–1.22; P = 0.521), and total mortality (RR, 1.00; 95% CI: 0.94–1.06; P = 0.952). Upon performing a cumulative meta-analysis for cancer incidence, death due to cancer, and total mortality, the nonsignificance of the effect of vitamin B persisted. With respect to specific types of cancer, vitamin B supplementation significantly reduced the risk of skin melanoma (RR, 0.47; 95% CI: 0.23–0.94; P = 0.032). Conclusion: Vitamin B supplementation does not have an effect on cancer incidence, death due to cancer, or total mortality. It is associated with a lower risk of skin melanoma, but has no effect on other cancers. PMID:27495015

  6. 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...

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. Thyroid cancer incidence due to technogenic exposure in childhood.

    Science.gov (United States)

    Koshurnikova, Nina Alexandrovna; Kaigorodova, Larissa Y; Rabinovich, Evgenya I; Martinenko, Irina I; Okatenko, Pavel A; Khokhryakov, Victor V; Mosharova, Elena P; Mokrov, Juri; Fomin, Evgeny; Alekseyev, Valery S; Panteleyev, Nikolay T; Sannikova, Lubov A; Ryzhykh, Tatyana V

    2012-07-01

    Thyroid cancer incidence was studied in the cohort of residents of Ozyorsk and Kyshtym, the nearest upwind cities to the Mayak Production Association (Mayak PA), Russia's first plutonium production facility, which has been in operation since 1948. Radioactive contamination of areas around the Mayak PA were from unmonitored releases of inert gases produced by industrial reactors and also from the release of uranium fission products from a radiochemical plant stack where irradiated uranium blocks were refined. Iodine-131 (131I) was the main contributor to the technogenic dose from atmospheric releases. Routine monitoring of gaseous releases began in the mid-1960s, when a gas purification system was perfected. Children were a critical group due to their higher radiosensitivity and specific diet (dairy products and vegetables). Both cities maintain Registries containing over 100,000 individuals born from 1934-2006. Among this group, more than 100 cases of thyroid cancer were registered during 1948-2009. The relative risk of thyroid cancer incidence is 1.5 times higher than in the Chelyabinsk. PMID:22647908

  11. Increase in head and neck cancer in younger patients due to human papillomavirus (HPV).

    Science.gov (United States)

    Young, David; Xiao, Christopher C; Murphy, Benjamin; Moore, Michael; Fakhry, Carole; Day, Terry A

    2015-08-01

    The face of head and neck cancer has changed dramatically over the past 30 years. There has been a steady decline in the number of tobacco and alcohol related squamous cell carcinomas over the past 30 years, but and increasing incidence of human papillomavirus (HPV) related cancers. Some estimates suggest that 70-90% of new oropharyngeal cancers have evidence of HPV. These patients have different demographic patterns, in that they are more likely to be younger, white adults in their 40s and 50s who are never smokers or have reduced tobacco exposure. Studies have shown that a higher number of lifetime oral sex partners (>5) and a higher number of lifetime vaginal sex partners (>25) have been associated with increased risk of HPV positive head and neck cancer. People can also reduce their risk of HPV linked head and neck cancer by receiving the HPV vaccine series prior to becoming sexually active. Recent evidence suggests HPV related head and neck cancers present with different symptoms than those caused by tobacco. The most popular test for HPV status is the p16 immunohistochemical stain because it is cheap, simple, and studies have shown it to have comparable sensitivity and specificity to the previous standards. It is widely recommended that all cancers of the oropharynx be tested for the presence of HPV, and some recommend it for all head and neck cancers. Overall 2-year and 5-year survival for HPV positive head and neck cancer is significantly greater than for HPV negative cancers, likely due to HPV positive cancers being more responsive to treatment. PMID:26066977

  12. 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 ...

  13. 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...

  14. 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

  15. 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...

  16. 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.

  17. Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment.

    Directory of Open Access Journals (Sweden)

    Bin Bao

    Full Text Available Hypoxia is known to play critical roles in cell survival, angiogenesis, tumor invasion, and metastasis. Hypoxia mediated over-expression of hypoxia-inducible factor (HIF has been shown to be associated with therapeutic resistance, and contributes to poor prognosis of cancer patients. Emerging evidence suggest that hypoxia and HIF pathways contributes to the acquisition of epithelial-to-mesenchymal transition (EMT, maintenance of cancer stem cell (CSC functions, and also maintains the vicious cycle of inflammation-all which lead to therapeutic resistance. However, the precise molecular mechanism(s by which hypoxia/HIF drives these events are not fully understood. Here, we show, for the first time, that hypoxia leads to increased expression of VEGF, IL-6, and CSC signature genes Nanog, Oct4 and EZH2 consistent with increased cell migration/invasion and angiogenesis, and the formation of pancreatospheres, concomitant with increased expression of miR-21 and miR-210 in human pancreatic cancer (PC cells. The treatment of PC cells with CDF, a novel synthetic compound inhibited the production of VEGF and IL-6, and down-regulated the expression of Nanog, Oct4, EZH2 mRNAs, as well as miR-21 and miR-210 under hypoxia. CDF also led to decreased cell migration/invasion, angiogenesis, and formation of pancreatospheres under hypoxia. Moreover, CDF decreased gene expression of miR-21, miR-210, IL-6, HIF-1α, VEGF, and CSC signatures in vivo in a mouse orthotopic model of human PC. Collectively, these results suggest that the anti-tumor activity of CDF is in part mediated through deregulation of tumor hypoxic pathways, and thus CDF could become a novel, and effective anti-tumor agent for PC therapy.

  18. 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.

  19. 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...

  20. 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...

  1. 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...

  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. Bioengineering Embryonic Stem Cell Microenvironments for the Study of Breast Cancer

    OpenAIRE

    Yubing Xie; Bridget M. Mooney; Nurazhani Abdul Raof

    2011-01-01

    Breast cancer is the most prevalent disease amongst women worldwide and metastasis is the main cause of death due to breast cancer. Metastatic breast cancer cells and embryonic stem (ES) cells display similar characteristics. However, unlike metastatic breast cancer cells, ES cells are nonmalignant. Furthermore, embryonic microenvironments have the potential to convert metastatic breast cancer cells into a less invasive phenotype. The creation of in vitro embryonic microenvironments will enab...

  4. 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...

  5. 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...

  6. Stem Cell Based Gene Therapy in Prostate Cancer

    OpenAIRE

    Jae Heon Kim; Hong Jun Lee; Yun Seob Song

    2014-01-01

    Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new ...

  7. 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....

  8. 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, ...

  9. 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...

  10. 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.

  11. 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.

  12. Stochastic model for computer simulation of the number of cancer cells and lymphocytes in homogeneous sections of cancer tumors

    CERN Document Server

    Castellanos-Moreno, Arnulfo; Corella-Madueño, Adalberto; Gutiérrez-López, Sergio; Rosas-Burgos, Rodrigo

    2014-01-01

    We deal with a small enough tumor section to consider it homogeneous, such that populations of lymphocytes and cancer cells are independent of spatial coordinates. A stochastic model based in one step processes is developed to take into account natural birth and death rates. Other rates are also introduced to consider medical treatment: natural birth rate of lymphocytes and cancer cells; induced death rate of cancer cells due to self-competition, and other ones caused by the activated lymphocytes acting on cancer cells. Additionally, a death rate of cancer cells due to induced apoptosis is considered. Weakness due to the advance of sickness is considered by introducing a lymphocytes death rate proportional to proliferation of cancer cells. Simulation is developed considering different combinations of the parameters and its values, so that several strategies are taken into account to study the effect of anti-angiogenic drugs as well the self-competition between cancer cells. Immune response, with the presence ...

  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. 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...

  15. 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...

  16. 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.

  17. 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 ...

  18. 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 ...

  19. [Mortality due to bronchopulmonary cancers in workers of 2 foundries].

    Science.gov (United States)

    Moulin, J J; Lafontaine, M; Mantout, B; Belanger, A; Michel, M; Wild, P; Clavel, T; Fournier, M; Fontana, J M

    1995-01-01

    A mortality study was carried out in two factories producing stainless steel in order to assess lung cancer risk among workers employed in coke oven, blast and open hearth furnaces, foundry, electric furnace, hot and cold rolling mills and pickling areas. Occupational exposures of interest were chromium compounds, nickel compounds, polycyclic aromatic hydrocarbons (PAH), silica and asbestos. All male workers having at least one year of employment between 01.01.1960 and 31.12.1990 were followed up for mortality. The vital status was assessed from birth place registries. Complete job histories since date of first employment were abstracted from the company files. The smoking habits of 50% of the cohort members were known from medical records. The observed number of deaths (obs) were compared with the expected ones based on regional rates with adjustment for age, sex and calendar time (Standardized Mortality Ratio, SMR). The cohorts included 6324 (factory 1) and 5270 (factory 2) workers. The overall mortality did not differ markedly from that expected in both factories: SMR = 0.95 (obs = 1540, p = 0.05) in factory 1 and SMR = 1.06 (obs = 916, non-significant) in factory 2. SMRs for lung cancer did not differ from unity, respectively 0.99 (obs = 105) and 1.00 (obs = 54), in whole cohorts. Non-significant lung cancer excesses were observed among workers of some workshops where exposures of interest might have occurred: coke oven (SMR = 2.04), blast furnace (SMR = 1.36), open hearth furnace (SMR = 1.75), hot rolling mills (SMR = 1.29). These processes, however, are no longer involved in the study factories. Furthermore, no lung cancer excess was observed among workers employed in current workshops: electric furnaces and cold rolling mills. PMID:7732197

  20. 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...

  1. Predictors of re-operation due to post-surgical bleeding in breast cancer patients

    DEFF Research Database (Denmark)

    Winther Lietzen, L; Cronin-Fenton, Deirdre; Garne, Jens Peter;

    2012-01-01

    To assess the risk of re-operation due to post-surgical bleeding after initial breast cancer surgery and to identify predictors of re-operation.......To assess the risk of re-operation due to post-surgical bleeding after initial breast cancer surgery and to identify predictors of re-operation....

  2. 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...

  3. 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 ...

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. [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

  10. 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...

  11. 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.

  12. 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

  13. 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...

  14. 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...

  15. Reliable in vitro studies require appropriate ovarian cancer cell lines.

    Science.gov (United States)

    Jacob, Francis; Nixdorf, Sheri; Hacker, Neville F; Heinzelmann-Schwarz, Viola A

    2014-01-01

    Ovarian cancer is the fifth most common cause of cancer death in women and the leading cause of death from gynaecological malignancies. Of the 75% women diagnosed with locally advanced or disseminated disease, only 30% will survive five years following treatment. This poor prognosis is due to the following reasons: limited understanding of the tumor origin, unclear initiating events and early developmental stages of ovarian cancer, lack of reliable ovarian cancer-specific biomarkers, and drug resistance in advanced cases. In the past, in vitro studies using cell line models have been an invaluable tool for basic, discovery-driven cancer research. However, numerous issues including misidentification and cross-contamination of cell lines have hindered research efforts. In this study we examined all ovarian cancer cell lines available from cell banks. Hereby, we identified inconsistencies in the reporting, difficulties in the identification of cell origin or clinical data of the donor patients, restricted ethnic and histological type representation, and a lack of tubal and peritoneal cancer cell lines. We recommend that all cell lines should be distributed via official cell banks only with strict guidelines regarding the minimal available information required to improve the quality of ovarian cancer research in future. PMID:24936210

  16. 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

  17. From embryonic stem cells to testicular germ cell cancer-- should we be concerned?

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Sonne, Si Brask; Hoei-Hansen, Christina E;

    2006-01-01

    initial hypothesis but also indicating that CIS cells have a striking phenotypic similarity to embryonic stem cells (ESC). Many cancers have been proposed to originate from tissue-specific stem cells [so-called 'cancer stem cells' (CSC)] and we argue that CIS may be a very good example of a CSC, but with...... exceptional features due to the retention of embryonic pluripotency. In addition, considering the fact that pre-invasive CIS cells are transformed from early fetal cells, possibly due to environmentally induced alterations of the niche, we discuss potential risks linked to the uncontrolled therapeutic use of...

  18. DNA Methylation and Apoptosis Resistance in Cancer Cells

    OpenAIRE

    Pierre-François Cartron; François Marie Vallette; Eric Hervouet; Mathilde Cheray

    2013-01-01

    Apoptosis is a cell death programme primordial to cellular homeostasis efficiency. This normal cell suicide program is the result of the activation of a cascade of events in response to death stimuli. Apoptosis occurs in normal cells to maintain a balance between cell proliferation and cell death. A deregulation of this balance due to modifications in the apoptosic pathway leads to different human diseases including cancers. Apoptosis resistance is one of the most important hallmarks of cance...

  19. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    International Nuclear Information System (INIS)

    Highlights: • As2O3 inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As2O3 than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As2O3 than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As2O3 is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As2O3) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As2O3 induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As2O3 on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As2O3 than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As2O3 than HPV 16-positive CaSki and SiHa cells. After As2O3 treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As2O3 is a potential anticancer drug for cervical 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. 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-...

  2. 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...

  3. 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

  4. 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

  5. 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....

  6. 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...

  7. 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 ...

  8. 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...

  9. 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...

  10. 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.

  11. Influence of Obesity on Anastomotic Leakage After Anterior Rectal Resectionperformed Due to Cancer

    Directory of Open Access Journals (Sweden)

    Piecuch Jerzy

    2015-03-01

    Full Text Available Anterior resection for rectal cancer carries the risk of serious complications, especially fistulas at the site of anastomosis. Numerous factors have been shown to impact anastomotic leakage. The results of studies on the influence of obesity on the frequency of anastomotic leakage after rectal resection performed due to cancer have been contradictory.

  12. 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

  13. Nerve Growth Factor in Cancer Cell Death and Survival

    International Nuclear Information System (INIS)

    One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer

  14. 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.

  15. 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...

  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. Cytotoxic activities of amentoflavone against human breast and cervical cancers are mediated by increasing of PTEN expression levels due to peroxisomes proliferate-activated receptor {gamma} activation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunjung; Shin, Soyoung; Lee, Jeeyoung; Lee, So Jung; Kim, Jinkyoung; Yoon, Doyoung; Kim, Yangmee [Konkuk Univ., Seoul (Korea, Republic of); Woo, Eunrhan [Chosun Univ., Gwangju (Korea, Republic of)

    2012-07-15

    Human peroxisomes proliferate-activated receptor gamma (hPPAR{gamma}) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. Previously, we verified that amentoflavone is an activator of hPPAR{gamma} and probed the molecular basis of its action. In this study, we investigated the mechanism of action of amentoflavone in cancer cells and demonstrated that amentoflavone showed strong cytotoxicity against MCF-7 and HeLa cancer cell lines. We showed that hPPAR{gamma} expression in MCF-7 and HeLa cells is specifically stimulated by amentoflavone, and suggested that amentoflavone-induced cytotoxic activities are mediated by activation of hPPAR{gamma} in these two cancer cell lines. Moreover, amentoflavone increased PTEN levels in these two cancer cell lines, indicating that the cytotoxic activities of amentoflavone are mediated by increasing of PTEN expression levels due to hPPAR{gamma} activation.

  18. Cytotoxic activities of amentoflavone against human breast and cervical cancers are mediated by increasing of PTEN expression levels due to peroxisomes proliferate-activated receptor γ activation

    International Nuclear Information System (INIS)

    Human peroxisomes proliferate-activated receptor gamma (hPPARγ) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. Previously, we verified that amentoflavone is an activator of hPPARγ and probed the molecular basis of its action. In this study, we investigated the mechanism of action of amentoflavone in cancer cells and demonstrated that amentoflavone showed strong cytotoxicity against MCF-7 and HeLa cancer cell lines. We showed that hPPARγ expression in MCF-7 and HeLa cells is specifically stimulated by amentoflavone, and suggested that amentoflavone-induced cytotoxic activities are mediated by activation of hPPARγ in these two cancer cell lines. Moreover, amentoflavone increased PTEN levels in these two cancer cell lines, indicating that the cytotoxic activities of amentoflavone are mediated by increasing of PTEN expression levels due to hPPARγ activation

  19. 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...

  20. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue due to cancer recurrence

    DEFF Research Database (Denmark)

    Ernst, EH; Offersen, Birgitte Vrou; Andersen, Claus Yding;

    2013-01-01

    To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer.......To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer....

  1. 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.

  2. 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...

  3. 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...

  4. Fermented red ginseng extract inhibits cancer cell proliferation and viability.

    Science.gov (United States)

    Oh, Jisun; Jeon, Seong Bin; Lee, Yuri; Lee, Hyeji; Kim, Ju; Kwon, Bo Ra; Yu, Kang-Yeol; Cha, Jeong-Dan; Hwang, Seung-Mi; Choi, Kyung-Min; Jeong, Yong-Seob

    2015-04-01

    Red ginseng (Panax ginseng C.A. Meyer) is the most widely recognized medicinal herb due to its remedial effects in various disorders, such as cancers, diabetes, and heart problems. In this study, we investigated the anticancer effect of fermented red ginseng extract (f-RGE; provided by Jeonju Biomaterials Institute, Jeonju, South Korea) in a parallel comparison with the effect of nonfermented red ginseng extract (nf-RGE; control) on several cancer cell lines--MCF-7 breast cancer cells, HepG2 hepatocellular carcinoma cells, and reprogrammed MCF-7 cells (mimicking cancer stem cells). Cells were cultured at various concentrations of RGE (from 0.5 up to 5 mg/mL) and their viabilities and proliferative properties were examined. Our data demonstrate the following: (1) nf-RGE inhibited cell viability at ≥1 mg/mL for MCF-7 cells and ≥2 mg/mL for HepG2 cells, (2) in the presence of a carcinogenic agent, 12-O-tetradecanoylphorbol-13-acetate (TPA), nf-RGE treatment in combination with paclitaxel synergistically decreased MCF-7 as well as HepG2 cell viability, (3) f-RGE (which contained a greater level of Rg3 content) more effectively decreased the viability of MCF-7 and HepG2 cells compared to nf-RGE, and (4) f-RGE appeared more potent for inhibiting cancerous differentiation of reprogrammed MCF-7 cells in a synergistic fashion with paclitaxel, especially in the presence of TPA, compared to nf-RGE. These findings suggest that f-RGE treatment may be more effective for decreasing cancer cell survival by inducing apoptotic cell death and also presumably for preventing cancer stem cell differentiation compared to nf-RGE. PMID:25658580

  5. 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

  6. 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...

  7. 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...

  8. 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...

  9. 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.

  10. 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...

  11. 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...

  12. 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 ...

  13. 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.

  14. 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.

  15. 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.

  16. Discovery of the cancer stem cell related determinants of radioresistance

    International Nuclear Information System (INIS)

    Tumors are known to be heterogeneous containing a dynamic mixture of phenotypically and functionally different tumor cells. The two concepts attempting to explain the origin of intratumor heterogeneity are the cancer stem cell hypothesis and the clonal evolution model. The stochastic model argues that tumors are biologically homogenous and all cancer cells within the tumor have equal ability to propagate the tumor growth depending on continuing mutations and selective pressure. By contrast, the stem cells model suggests that cancer heterogeneity is due to the hierarchy that originates from a small population of cancer stem cells (CSCs) which are biologically distinct from the bulk tumor and possesses self-renewal, tumorigenic and multilineage potential. Although these two hypotheses have been discussed for a long time as mutually exclusive explanations of tumor heterogeneity, they are easily reconciled serving as a driving force of cancer evolution and diversity. Recent discovery of the cancer cell plasticity and heterogeneity makes the CSC population a moving target that could be hard to track and eradicate. Understanding the signaling mechanisms regulating CSCs during the course of cancer treatment can be indispensable for the optimization of current treatment strategies

  17. 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

  18. 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.

  19. 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.

  20. 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...

  1. Investigation of Solar Cells Power Degradation Due to Electrostatic Discharge

    Directory of Open Access Journals (Sweden)

    Hossein Fayazi

    2014-07-01

    Full Text Available Satellites are surrounded with protons, electrons and heavy charged particles. Space radiation impact on satellite sub-systems cause several anomalies which are important problem for satellite designers. Until recently, the majority of spacecraft primary power systems used solar arrays and rechargeable batteries to supply 28 V. For low-inclination spacecraft, 28 V systems have not been observed to arc. As the power requirements for spacecraft increased, however, high-voltage solar arrays were baselined to minimize total mass and increase power production efficiency. With the advent of 100 V systems in the late 1980s, arcing began to be observed on a number of spacecraft. The mechanism proposed in this paper, described electrical and physical degradation of solar cells due to electrostatic discharge anomalies on satellites. The cell was characterized again after arcing to determine the change in efficiency. This paper details the process for designing the circuit to create the arcing, and the different setups used to degrade the cells electrically and physically. It also describes the final setups to be used in space laboratory. This model is designed using Matlab and SPENVIS. Identification and simulation this mechanism is an important step in solar array design for space application

  2. Properties of resistant cells generated from lung cancer cell lines treated with EGFR inhibitors

    International Nuclear Information System (INIS)

    Epidermal growth factor receptor (EGFR) signaling plays an important role in non-small cell lung cancer (NSCLC) and therapeutics targeted against EGFR have been effective in treating a subset of patients bearing somatic EFGR mutations. However, the cancer eventually progresses during treatment with EGFR inhibitors, even in the patients who respond to these drugs initially. Recent studies have identified that the acquisition of resistance in approximately 50% of cases is due to generation of a secondary mutation (T790M) in the EGFR kinase domain. In about 20% of the cases, resistance is associated with the amplification of MET kinase. In the remaining 30-40% of the cases, the mechanism underpinning the therapeutic resistance is unknown. An erlotinib resistant subline (H1650-ER1) was generated upon continuous exposure of NSCLC cell line NCI-H1650 to erlotinib. Cancer stem cell like traits including expression of stem cell markers, enhanced ability to self-renew and differentiate, and increased tumorigenicity in vitro were assessed in erlotinib resistant H1650-ER1 cells. The erlotinib resistant subline contained a population of cells with properties similar to cancer stem cells. These cells were found to be less sensitive towards erlotinib treatment as measured by cell proliferation and generation of tumor spheres in the presence of erlotinib. Our findings suggest that in cases of NSCLC accompanied by mutant EGFR, treatment targeting inhibition of EGFR kinase activity in differentiated cancer cells may generate a population of cancer cells with stem cell properties

  3. 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.

  4. 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...

  5. 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.

  6. 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, ...

  7. 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

  8. 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

  9. 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.

  10. 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...

  11. 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 ...

  12. 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...

  13. 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...

  14. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells | Office of Cancer Genomics

    Science.gov (United States)

    The discovery of cancer dependencies has the potential to inform therapeutic strategies and to identify putative drug targets. Integrating data from comprehensive genomic profiling of cancer cell lines and from functional characterization of cancer cell dependencies, we discovered that loss of the enzyme methylthioadenosine phosphorylase (MTAP) confers a selective dependence on protein arginine methyltransferase 5 (PRMT5) and its binding partner WDR77. MTAP is frequently lost due to its proximity to the commonly deleted tumor suppressor gene, CDKN2A.

  15. 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.

  16. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain

    OpenAIRE

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi Reddy; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M.

    2014-01-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain-metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustai...

  17. 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

  18. 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...

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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 ...

  4. Enhanced Microwave Hyperthermia of Cancer Cells with Fullerene.

    Science.gov (United States)

    Sun, Mingrui; Kiourti, Asimina; Wang, Hai; Zhao, Shuting; Zhao, Gang; Lu, Xiongbin; Volakis, John L; He, Xiaoming

    2016-07-01

    Hyperthermia generated with various energy sources including microwave has been widely studied for cancer treatment. However, the potential damage due to nontargeted heating of normal tissue is a major hurdle to its widespread application. Fullerene is a potential agent for improving cancer therapy with microwave hyperthermia but is limited by its poor solubility in water for biomedical applications. Here we report a combination therapy for enhanced cancer cell destruction by combining microwave heating with C60-PCNPs consisting of fullerene (C60) encapsulated in Pluronic F127-chitosan nanoparticles (PCNPs) with high water solubility. A cell culture dish integrated with an antenna was fabricated to generate microwave (2.7 GHz) for heating PC-3 human prostate cancer cells either with or without the C60-PCNPs. The cell viability data show that the C60-PCNPs alone have minimal cytotoxicity. The combination of microwave heating and C60-PCNPs is significantly more effective than the microwave heating alone in killing the cancer cells (7.5 versus 42.2% cell survival). Moreover, the combination of microwave heating and C60-PCNPs is significantly more destructive to the cancer cells than the combination of simple water-bath heating (with a similar thermal history to microwave heating) and C60-PCNPs (7.5 versus 32.5% survival) because the C60 in the many nanoparticles taken up by the cells can absorb the microwave energy and convert it into heat to enhance heating inside the cells under microwave irradiation. These data suggest the great potential of targeted heating via fullerene for enhanced cancer treatment by microwave hyperthermia. PMID:27195904

  5. 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

  6. A genome-wide systematic analysis reveals different and predictive proliferation expression signatures of cancerous vs. non-cancerous cells.

    Directory of Open Access Journals (Sweden)

    Yedael Y Waldman

    Full Text Available Understanding cell proliferation mechanisms has been a long-lasting goal of the scientific community and specifically of cancer researchers. Previous genome-scale studies of cancer proliferation determinants have mainly relied on knockdown screens aimed to gauge their effects on cancer growth. This powerful approach has several limitations such as off-target effects, partial knockdown, and masking effects due to functional backups. Here we employ a complementary approach and assign each gene a cancer Proliferation Index (cPI that quantifies the association between its expression levels and growth rate measurements across 60 cancer cell lines. Reassuringly, genes found essential in cancer gene knockdown screens exhibit significant positive cPI values, while tumor suppressors exhibit significant negative cPI values. Cell cycle, DNA replication, splicing and protein production related processes are positively associated with cancer proliferation, while cellular migration is negatively associated with it - in accordance with the well known "go or grow" dichotomy. A parallel analysis of genes' non-cancerous proliferation indices (nPI across 224 lymphoblastoid cell lines reveals surprisingly marked differences between cancerous and non-cancerous proliferation. These differences highlight genes in the translation and spliceosome machineries as selective cancer proliferation-associated proteins. A cross species comparison reveals that cancer proliferation resembles that of microorganisms while non-cancerous proliferation does not. Furthermore, combining cancerous and non-cancerous proliferation signatures leads to enhanced prediction of patient outcome and gene essentiality in cancer. Overall, these results point to an inherent difference between cancerous and non-cancerous proliferation determinants, whose understanding may contribute to the future development of novel cancer-specific anti-proliferative drugs.

  7. The stem cell patent landscape as relevant to cancer vaccines.

    Science.gov (United States)

    Wang, Shyh-Jen

    2011-10-01

    Cancer vaccine targeting cancer stem cells is proposed to serve as a potent immunotherapy. Thus, it would be useful to examine the main trends in stem cell patenting activity as a guide for those seeking to develop such cancer vaccines. We found that a substantial number of stem cell patents were granted up to the end of 2010, including ~2000 issued in the US. Many of these have been filed since 2001, including 7,551 applications in the US. Stem cell development, as evidenced by the numbers of PubMed articles, has matured steadily in recent years. However, the other metrics, such as the number of patent applications, the technology-science linkage and the number of patent assignees, have been stagnant. Moreover, the ownership of stem cell patents is still quiet fragmented across multiple organizations, and the number of stem cell patent assignees from the business sector has not increased significantly. Academic and nonprofit institutions not only account for a large share of stem cell patents but also apply for patents continually. Based on this analysis, the strength of stem cell resources seems to remain stagnant in recent years due to the ban on government funding of embryonic stem cell research. Furthermore, the patent prosecution or technical barriers in the field of stem cells would be another main reason that the number of US-issued stem cell patents for each application have been in gradual decline since 2000. Therefore, we consider stem cell technology to still be under development. PMID:21957493

  8. 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.

  9. 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

  10. 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 ...

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongtao [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China); Gao, Peng [Department of Internal Medicine, University of Iowa, Iowa City, IA 52242 (United States); Zheng, Jie, E-mail: jiezheng54@126.com [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China)

    2014-09-05

    Highlights: • As{sub 2}O{sub 3} inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As{sub 2}O{sub 3} is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As{sub 2}O{sub 3}) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As{sub 2}O{sub 3} induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As{sub 2}O{sub 3} on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As{sub 2}O{sub 3} than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As{sub 2}O{sub 3} than HPV 16-positive CaSki and SiHa cells. After As{sub 2}O{sub 3} treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As{sub 2}O{sub 3} is a potential anticancer drug for cervical cancer.

  17. Therapies targeting cancer stem cells: Current trends and future challenges

    Institute of Scientific and Technical Information of China (English)

    Denisa; L; Dragu; Laura; G; Necula; Coralia; Bleotu; Carmen; C; Diaconu; Mihaela; Chivu-Economescu

    2015-01-01

    Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers.

  18. 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

  19. 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.

  20. Molecular markers for tumor cell dissemination in female cancers

    International Nuclear Information System (INIS)

    In the fight against cancer many advances have been made in early detection and treatment of the disease during the last few decades. Nevertheless, many patients still die of cancer due to metastatic spreading of the disease. Tumor cell dissemination may occur very early and usually is not discovered at the time of initial diagnosis. In these cases, the mere excision of the primary tumor is an insufficient treatment. Microscopic tumor residues will remain in the blood, lymph nodes, or the bone marrow and will cause disease recurrence. To improve the patient's prognosis, a sensitive tool for the detection of single tumor cells supplementing conventional diagnostic procedures is required. As the blood is more easily accessible than the bone marrow or tissue biopsies, we intended to identify gene markers for the detection of circulating tumor cells in the blood of cancer patients. We focused on patients with breast, ovarian, endometrial or cervical cancer. Starting from a genome-wide gene expression analysis of tumor cells and blood cells, we found six genes higher expression levels in cancer patients compared to healthy women. These findings suggest that an increased expression of these genes in the blood indicates the presence of circulating tumor cells inducing future metastases and thus the need for adjuvant therapy assisting the primary treatment. Measuring the expression levels of these six genes in the blood may supplement conventional diagnostic tests and improve the patient's prognosis. (author)

  1. 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- ...

  2. 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- ...

  3. 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- ...

  4. 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- ...

  5. A Research Agenda for Appearance Changes Due to Breast Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Mia K. Markey

    2008-01-01

    Full Text Available Breast cancer is one of the most prevalent forms of cancer in the US. It is estimated that more than 180,000 American women will be diagnosed with invasive breast cancer in 2008. Fortunately, the survival rate is relatively high and continually increasing due to improved detection techniques and treatment methods. However, maintaining quality of life is a factor often under emphasized for breast cancer survivors. Breast cancer treatments are invasive and can lead to deformation of the breast. Breast reconstruction is important for restoring the survivor’s appearance. However, more work is needed to develop technologies for quantifying surgical outcomes and understanding women’s perceptions of changes in their appearance. A method for objectively measuring breast anatomy is needed in order to help both the breast cancer survivors and their surgeons take expected changes to the survivor’s appearance into account when considering various treatment options. In the future, augmented reality tools could help surgeons reconstruct a survivor’s breasts to match her preferences as much as possible.

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

    Science.gov (United States)

    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 effects and mechanisms of metformin. Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P metformin. Also over-expression of miR-26a can inhibited cell proliferation by down-regulating Bcl-2, cyclin D1 and up-regulating PTEN expression. Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene. PMID:25419360

  7. 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.

  8. Gene sensitizes cancer cells to chemotherapy drugs

    Science.gov (United States)

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

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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, ...

  14. 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.

  15. Inhibition of glucose turnover by 3-bromopyruvate counteracts pancreatic cancer stem cell features and sensitizes cells to gemcitabine

    OpenAIRE

    Isayev, Orkhan; Rausch, Vanessa; BAUER, NATHALIE; Liu, Li; Fan, Pei; Zhang, Yiyao; Gladkich, Jury; Nwaeburu, Clifford C.; Mattern, Jürgen; Mollenhauer, Martin; Rückert, Felix; Zach, Sebastian; Haberkorn, Uwe; Gross, Wolfgang; Schönsiegel, Frank

    2014-01-01

    According to the cancer stem cell (CSC) hypothesis, the aggressive growth and early metastasis of pancreatic ductal adenocarcinoma (PDA) is due to the activity of CSCs, which are not targeted by current therapies. Otto Warburg suggested that the growth of cancer cells is driven by a high glucose metabolism. Here, we investigated whether glycolysis inhibition targets CSCs and thus may enhance therapeutic efficacy. Four established and 3 primary PDA cell lines, non-malignant cells, and 3 patien...

  16. 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

  17. 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, ...

  18. 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)

  19. 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.

  20. Drug delivery system and breast cancer cells

    Science.gov (United States)

    Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita

    2016-06-01

    Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications. At the request of all authors of the paper an updated version was published on 12 July 2016. The manuscript was prepared and submitted without Dr. Francesca Cavalieri's contribution and her name was added without her consent. Her name has been removed in the updated and re-published article.

  1. Recurrence after surgery due to cervical cancer - An evaluation of the follow-up program

    DEFF Research Database (Denmark)

    Fuglsang, Katrine; Petersen, Lone Kjeld; Blaakær, Jan

    , Aarhus University Hospital we identified 567 patients from 1996 to 2011 matching the diagnosis cervical cancer combined with a surgical procedure. From the Danish Pathology Data Bank the following information is collected: - Stage of disease - Histology - Surgical procedure - Number of follow-up visit......Objective During the last 20 years the follow-up program after surgical treatment for cervical cancer has remained unchanged. Surprisingly, little is communicated in relation to the follow-up program even though it has a huge impact on the life of the women and their relatives for five years...... consequences, but there is a need for a foundation prior to an adjustment of the follow-up program. Methods Design: retrospective study of a cohort of women attending follow-up program after surgery due to cervical cancer. Material: From the patient register at the Department of Gynaecology and Obstetrics...

  2. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatlı

    2013-01-01

    Full Text Available Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

  3. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Science.gov (United States)

    Tatlı, Ali Murat; Göksu, Sema Sezgin; Arslan, Deniz; Başsorgun, Cumhur İbrahim; Coşkun, Hasan Şenol

    2013-01-01

    Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient's history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage. PMID:23956898

  4. Overcome Cancer Cell Drug Resistance Using Natural Products

    Directory of Open Access Journals (Sweden)

    Pu Wang

    2015-01-01

    Full Text Available Chemotherapy is one of the major treatment methods for cancer. However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance. Management of drug resistance is important towards successful chemotherapy. There are many reports in the Chinese literature that natural products can overcome cancer cell drug resistance, which deserve sharing with scientific and industrial communities. We summarized the reports into four categories: (1 in vitro studies using cell line models; (2 serum pharmacology; (3 in vivo studies using animal models; and (4 clinical studies. Fourteen single compounds were reported to have antidrug resistance activity for the first time. In vitro, compounds were able to overcome drug resistance at nontoxic or subtoxic concentrations, in a dose-dependent manner, by inhibiting drug transporters, cell detoxification capacity, or cell apoptosis sensitivity. Studies in vivo showed that single compounds, herbal extract, and formulas had potent antidrug resistance activities. Importantly, many single compounds, herbal extracts, and formulas have been used clinically to treat various diseases including cancer. The review provides comprehensive data on use of natural compounds to overcome cancer cell drug resistance in China, which may facilitate the therapeutic development of natural products for clinical management of cancer drug resistance.

  5. [Genetic-metabolic model of cancer cell behavior].

    Science.gov (United States)

    Dil'man, V M; Blagosklonnyĭ, M V

    1980-01-01

    It is suggested that the transforming protein (type pp60) induce "insulinization" of the cell membrane. It is mostly due to this effect that the cell sensitivity to insulin and insulin-like factors of the body internal medium is enhanced, which in turn results in the increased glucosa transport into cell. The transforming protein is also supposed to increase the activity of the glycolysis key enzymes by phosphorylating them. The presence of these two effects seems to be sufficient enough to explain "the biochemical behaviour" of the cancerous cell. PMID:7385728

  6. 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...

  7. Repression of mammosphere formation in breast cancer cells by soy isoflavone genistein and blueberry polyphenols

    Science.gov (United States)

    Epidemiological evidence implicates diets rich in fruits and vegetables in breast cancer prevention due to their phytochemical components, yet mechanisms for their anti-tumor activities are not well-understood. A small population of mammary epithelial cells, termed cancer stem cells (CSC), may be re...

  8. Greater Omental Pancake Tumour due to Metastasis of Ovarian Cancer – A Cadaveric Study

    Science.gov (United States)

    Bhusari, Prashant A.; Khairnar, Karan B.

    2014-01-01

    Cancer of ovary is the one of the common of all gynecological tumors and is the leading cause of death among women. A unique attempt is made to trace masses & its causes found in an abdomen of female cadaver during routine anatomy dissection. The mass was thick, hard and somewhat nodular in the region of greater omentum, After dissecting the pelvic cavity, it was found that both the ovaries were bulky, nodular & hard. Whole abdominal cavity was dissected & found that liver also involved by metastasis. Case suggests that there is the development of metastatic omental mass from grade IV ovarian cancer. Primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells. Adipokines like interleukin-8 (IL-8) mediate these activities. PMID:24596747

  9. Greater Omental Pancake Tumour due to Metastasis of Ovarian Cancer - A Cadaveric Study.

    Science.gov (United States)

    Bhusari, Prashant A; Khairnar, Karan B

    2014-01-01

    Cancer of ovary is the one of the common of all gynecological tumors and is the leading cause of death among women. A unique attempt is made to trace masses & its causes found in an abdomen of female cadaver during routine anatomy dissection. The mass was thick, hard and somewhat nodular in the region of greater omentum, After dissecting the pelvic cavity, it was found that both the ovaries were bulky, nodular & hard. Whole abdominal cavity was dissected & found that liver also involved by metastasis. Case suggests that there is the development of metastatic omental mass from grade IV ovarian cancer. Primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells. Adipokines like interleukin-8 (IL-8) mediate these activities. PMID:24596747

  10. Diabetes Insipidus and Anterior Pituitary Insufficiency Due to Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Ayşe Arduç

    2016-03-01

    Full Text Available Metastases from breast cancer to the pituitary gland are uncommon. We present a 35-year-old woman with diabetes insipidus and anterior pituitary insufficiency resulting from breast cancer metastases to the pituitary gland. The patient presented with reduced consciousness, fatigue, polyuria, and polydipsia. Hypernatremia (sodium: 154 mmol/L, hypostenuria (urine density: 1001, and hypopituitarism were present on laboratory evaluation. Magnetic resonance imaging (MRI revealed heterogeneous pituitary gland, thickened pituitary stalk (8mm, and loss of normal hyperintense signal of the posterior pituitary. Based on the clinical, laboratory, and MRI findings, the patient was diagnosed with diabetes insipidus and anterior pituitary insufficiency due to pituitary metastases from breast cancer. She received desmopressin, L-thyroxine, and prednisolone, which resulted in improvement of her symptoms and laboratory results. The patient, who also received Gamma Knife radiosurgery and chemotherapy, died six months later due to disseminated metastases. Although pituitary metastasis is rare, it should be kept in mind in patients with breast cancer since early detection and treatment can improve symptoms of patients.

  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. A novel transferrin receptor-targeted hybrid peptide disintegrates cancer cell membrane to induce rapid killing of cancer cells

    International Nuclear Information System (INIS)

    Transferrin receptor (TfR) is a cell membrane-associated glycoprotein involved in the cellular uptake of iron and the regulation of cell growth. Recent studies have shown the elevated expression levels of TfR on cancer cells compared with normal cells. The elevated expression levels of this receptor in malignancies, which is the accessible extracellular protein, can be a fascinating target for the treatment of cancer. We have recently designed novel type of immunotoxin, termed 'hybrid peptide', which is chemically synthesized and is composed of target-binding peptide and lytic peptide containing cationic-rich amino acids components that disintegrates the cell membrane for the cancer cell killing. The lytic peptide is newly designed to induce rapid killing of cancer cells due to conformational change. In this study, we designed TfR binding peptide connected with this novel lytic peptide and assessed the cytotoxic activity in vitro and in vivo. In vitro: We assessed the cytotoxicity of TfR-lytic hybrid peptide for 12 cancer and 2 normal cell lines. The specificity for TfR is demonstrated by competitive assay using TfR antibody and siRNA. In addition, we performed analysis of confocal fluorescence microscopy and apoptosis assay by Annexin-V binding, caspase activity, and JC-1 staining to assess the change in mitochondria membrane potential. In vivo: TfR-lytic was administered intravenously in an athymic mice model with MDA-MB-231 cells. After three weeks tumor sections were histologically analyzed. The TfR-lytic hybrid peptide showed cytotoxic activity in 12 cancer cell lines, with IC50 values as low as 4.0-9.3 μM. Normal cells were less sensitive to this molecule, with IC50 values > 50 μM. Competition assay using TfR antibody and knockdown of this receptor by siRNA confirmed the specificity of the TfR-lytic hybrid peptide. In addition, it was revealed that this molecule can disintegrate the cell membrane of T47D cancer cells just in 10 min, to effectively

  13. Sensitivity of cancer cells to truncated diphtheria toxin.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    Full Text Available BACKGROUND: Diphtheria toxin (DT has been utilized as a prospective anti-cancer agent for the targeted delivery of cytotoxic therapy to otherwise untreatable neoplasia. DT is an extremely potent toxin for which the entry of a single molecule into a cell can be lethal. DT has been targeted to cancer cells by deleting the cell receptor-binding domain and combining the remaining catalytic portion with targeting proteins that selectively bind to the surface of cancer cells. It has been assumed that "receptorless" DT cannot bind to and kill cells. In the present study, we report that "receptorless" recombinant DT385 is in fact cytotoxic to a variety of cancer cell lines. METHODS: In vitro cytotoxicity of DT385 was measured by cell proliferation, cell staining and apoptosis assays. For in vivo studies, the chick chorioallantoic membrane (CAM system was used to evaluate the effect of DT385 on angiogenesis. The CAM and mouse model system was used to evaluate the effect of DT385 on HEp3 and Lewis lung carcinoma (LLC tumor growth, respectively. RESULTS: Of 18 human cancer cell lines tested, 15 were affected by DT385 with IC(50 ranging from 0.12-2.8 microM. Furthermore, high concentrations of DT385 failed to affect growth arrested cells. The cellular toxicity of DT385 was due to the inhibition of protein synthesis and induction of apoptosis. In vivo, DT385 diminished angiogenesis and decreased tumor growth in the CAM system, and inhibited the subcutaneous growth of LLC tumors in mice. CONCLUSION: DT385 possesses anti-angiogenic and anti-tumor activity and may have potential as a therapeutic agent.

  14. A Genome-Wide Systematic Analysis Reveals Different and Predictive Proliferation Expression Signatures of Cancerous vs. Non-Cancerous Cells

    OpenAIRE

    Waldman, Yedael Y.; Geiger, Tamar; Ruppin, Eytan

    2013-01-01

    Understanding cell proliferation mechanisms has been a long-lasting goal of the scientific community and specifically of cancer researchers. Previous genome-scale studies of cancer proliferation determinants have mainly relied on knockdown screens aimed to gauge their effects on cancer growth. This powerful approach has several limitations such as off-target effects, partial knockdown, and masking effects due to functional backups. Here we employ a complementary approach and assign each gene ...

  15. 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.

  16. 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.

  17. Experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer

    OpenAIRE

    Gláucia Sousa Oliveira; Marina Bavaresco; Cibelle Barcelos Fillipini; Sara Rodrigues Rosado; Eliza Maria Rezende Dázio; Silvana Maria Coelho Leite Fava

    2014-01-01

    This is a study with the objective to know the experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer. A qualitative research, grounded on the humanization referential, made in 2013, through serialized semi-structured interviews and inductive analysis. It was approved by the Ethics and Research Committee under legal opinion no. 237,771. Seven family caregivers participated in this study in a county of southern Minas Gerais state, Brazil. Three categori...

  18. Beau´s lines due to cytostatic drugs in a patient with breast cancer

    Directory of Open Access Journals (Sweden)

    Patricia Chang

    2014-04-01

    Full Text Available Female patient, 47 years old who was hospitalized due to urinary tract infection, during her hospitalization bullous lesions appeared on her left limb and interconsultation to the Dermatology Department was made. The patient has been treated by breast cancer with docetaxel, doxorubicin and cyclophosphamide; she had received 5 cycles of chemotherapy Clinical examination showed vesicles on an erythematous base of the left arm following a linear pattern and the diagnosis of herpes zoster was done.

  19. 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...

  20. 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)

  1. 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...

  2. 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...

  3. 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

  4. 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.

  5. 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.

  6. Genomic and phenotypic profiles of two Brazilian breast cancer cell lines derived from primary human tumors

    DEFF Research Database (Denmark)

    Corrêa, Natássia C R; Kuasne, Hellen; Faria, Jerusa A Q A;

    2013-01-01

    Breast cancer is the most common type of cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors may provide valuable additional knowledge regarding this type of cancer. Therefore, the aim of this study was to investigate the phenotypic profiles of MACL-1...... and MGSO-3, the only Brazilian breast cancer cell lines available for comparative studies. We evaluated the presence of hormone receptors, proliferation, differentiation and stem cell markers, using immunohistochemical staining of the primary tumor, cultured cells and xenografts implanted....... This shift in expression may be due to the selection of an 'establishment' phenotype in vitro. Whole-genome DNA evaluation showed a large amount of copy number alterations (CNAs) in the two cell lines. These findings render MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines...

  7. 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

  8. 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

  9. Enhanced endocytosis of nano-curcumin in nasopharyngeal cancer cells: An atomic force microscopy study

    Science.gov (United States)

    Prasanth, R.; Nair, Greshma; Girish, C. M.

    2011-10-01

    Recent studies in drug development have shown that curcumin can be a good competent due to its improved anticancer, antioxidant, anti-proliferative, and anti-inflammatory activities. A detailed real time characterization of drug (curcumin)-cell interaction is carried out in human nasopharyngeal cancer cells using atomic force microscopy. Nanocurcumin shows an enhanced uptake over micron sized drugs attributed to the receptor mediated route. Cell membrane stiffness plays a critical role in the drug endocytosis in nasopharyngeal cancer cells.

  10. 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

  11. 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.

  12. Comparison of monocyte-derived dendritic cells from colorectal cancer patients, non-small-cell-lung-cancer patients and healthy donors

    DEFF Research Database (Denmark)

    Kvistborg, P; Bechmann, C M; Pedersen, A W;

    2009-01-01

    Dendritic cells (DCs) are bone marrow-derived professional antigen presenting cells. Due to their role as potent inducers of immune responses, these cells are widely used as adjuvant in experimental clinical settings for cancer immune therapy. We have developed a DC-based vaccine using autologous...... blood monocytes loaded with allogeneic tumor cell lysate rich in cancer/testis antigens. This vaccine has at present been tested for activity in three phase II clinical trials including two cohorts of patients with advanced colorectal cancer (CRC) and one cohort of patients with advanced non-small-cell-lung-cancer...... (NSCLC). In the present paper we retrospectively compare the maturation profile based on surface marker expression on DCs generated from the three patient cohorts and between cancer patient cohorts and a cohort of healthy donors. Vaccines were generated under cGMP conditions and phenotypic profiles of DC...

  13. 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.

  14. 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...

  15. 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

  16. Single-molecule genomic data delineate patient-specific tumor profiles and cancer stem cell organization

    OpenAIRE

    Sottoriva, Andrea; Spiteri, Inmaculada; Shibata, Darryl; Curtis, Christina; Tavaré, Simon

    2012-01-01

    Substantial evidence supports the concept that cancers are organized in a cellular hierarchy with cancer stem cells (CSCs) at the apex. To date, the primary evidence for CSCs derives from transplantation assays, which have known limitations. In particular, they are unable to report on the fate of cells within the original human tumor. Due to the difficulty in measuring tumor characteristics in patients, cellular organization and other aspects of cancer dynamics have not been quantified direct...

  17. Lineage tracing of metastasis in a mouse model for Non-small cell lung cancer (NSCLC)

    OpenAIRE

    Thakur, Chitra

    2012-01-01

    Non-small cell lung cancer (NSCLC) is the deadliest form of lung cancer and has a poor prognosis due to its high rate of metastasis. Notably, metastasis is one of the leading causes of death among cancer patients. Despite the clinical importance, the cellular and molecular mechanisms that govern the initiation, establishment and progression of metastasis remain unclear. Moreover, knowledge gained on metastatic process was largely based on cultured or in vitro manipulated cells that were reint...

  18. 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

  19. 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...

  20. 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.

  1. Determination of telomerase activity in stem cells and non-stem cells of breast cancer

    Institute of Scientific and Technical Information of China (English)

    LI Zhi; HE Yanli; ZHANG Jiahua; ZHANG Jinghui; HUANG Tao

    2007-01-01

    Although all normal tissue cells,including stem cells,are genetically homologous,variation in gene expression patterns has already determined the distinct roles for individual cells in the physiological process due to the occurrence of epigenetic modification.This is of special importance for the existenee of tissue stem cells because they are exclusively immortal within the body,capable of selfreplicating and differentiating by which tissues renew and repair itself and the total tissue cell population maintains a steady-state.Impairment of tissue stem cells is usually accompanied by a reduction in cell number,slows down the repair process and causes hypofunction.For instance,chemotherapy usually leads to depression of bone marrow and hair loss.Cellular aging is closely associated with the continuous erosion of the telomere while activation of telomerase repairs and maintains telomeres,thus slowing the aging process and prolonging cell life.In normal adults,telomerase activation mainly presents in tissue stem cells and progenitor cells giving them unlimited growth potential.Despite the extensive demonstration of telomerase activation in malignancy(>80%),scientists found that heterogeneity also exists among the tumor cells and only minorities of cells,designated as cancer stem cells,andergo processes analogous to the self-renewal and differentiation of normal stem ceils while the rest have limited lifespans.In this study,telomerase activity was measured and compared in breast cancer stem cells and non-stem cells that were phenotypically sorted by examining surface marker expression.The results indicated that cancer stem cells show a higher level of enzyme activity than non-stem cells.In addition,associated with the repair of cancer tissue(or relapse)after chemotherapy,telomerase activity in stem cells was markedly increased.

  2. CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel.

    Science.gov (United States)

    Muntimadugu, Eameema; Kumar, Rajendra; Saladi, Shantikumar; Rafeeqi, Towseef Amin; Khan, Wahid

    2016-07-01

    This combinational therapy is mainly aimed for complete eradication of tumor by killing both cancer cells and cancer stem cells. Salinomycin (SLM) was targeted towards cancer stem cells whereas paclitaxel (PTX) was used to kill cancer cells. Drug loaded poly (lactic-co-glycolic acid) nanoparticles were prepared by emulsion solvent diffusion method using cationic stabilizer. Size of the nanoparticles (below 150nm) was determined by dynamic light scattering technique and transmission electron microscopy. In vitro release study confirmed the sustained release pattern of SLM and PTX from nanoparticles more than a month. Cytotoxicity studies on MCF-7 cells revealed the toxicity potential of nanoparticles over drug solutions. Hyaluronic acid (HA) was coated onto the surface of SLM nanoparticles for targeting CD44 receptors over expressed on cancer stem cells and they showed the highest cytotoxicity with minimum IC50 on breast cancer cells. Synergistic cytotoxic effect was also observed with combination of nanoparticles. Cell uptake studies were carried out using FITC loaded nanoparticles. These particles showed improved cellular uptake over FITC solution and HA coating further enhanced the effect by 1.5 folds. CD44 binding efficiency of nanoparticles was studied by staining MDA-MB-231 cells with anti CD44 human antibody and CD44(+) cells were enumerated using flow cytometry. CD44(+) cell count was drastically decreased when treated with HA coated SLM nanoparticles indicating their efficiency towards cancer stem cells. Combination of HA coated SLM nanoparticles and PTX nanoparticles showed the highest cytotoxicity against CD44(+) cells. Hence combinational therapy using conventional chemotherapeutic drug and cancer stem cell inhibitor could be a promising approach in overcoming cancer recurrence due to resistant cell population. PMID:27045981

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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...

  8. 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

  9. CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Chien-Chih [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Liu, Ren-Shyan [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, National PET/Cyclotron Center, Taipei (China); National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei (China); Yang, An-Hang [Taipei Veterans General Hospital, Department of Pathology and Laboratory Medicine, Taipei (China); National Yang-Ming University, Department of Pathology, School of Medicine, Taipei (China); Liu, Ching-Sheng [National Yang-Ming University Medical School, Department of Nuclear Medicine, School of Medicine, Taipei (China); Chi, Chin-Wen [National Yang-Ming University, Institute of Pharmacology, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China); Tseng, Ling-Ming [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Tsai, Yi-Fan [Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Ho, Jennifer H. [Taipei Medical University, Graduate Institute of Clinical Medicine, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Department of Ophthalmology, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Center for Stem Cell Research, Taipei (China); Lee, Chen-Hsen [NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Lee, Oscar K. [Taipei Veterans General Hospital, Department of Orthopedics, Taipei (China); National Yang-Ming University, Stem Cell Research Center, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China)

    2013-01-15

    {sup 131}I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133{sup +} cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133{sup +} cells and higher radioresistance. After {gamma}-irradiation of the cells, the CD133{sup +} population was enriched due to the higher apoptotic rate of CD133{sup -} cells. In vivo {sup 131}I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133{sup +} cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133{sup +} cells. (orig.)

  10. CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy

    International Nuclear Information System (INIS)

    131I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133+ cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133+ cells and higher radioresistance. After γ-irradiation of the cells, the CD133+ population was enriched due to the higher apoptotic rate of CD133- cells. In vivo 131I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133+ cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133+ cells. (orig.)

  11. 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

  12. 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...

  13. 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...

  14. 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.

  15. 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...

  16. Biomedical Applications of Low Temperature Atmospheric Pressure Plasmas to Cancerous Cell Treatment and Tooth Bleaching

    Science.gov (United States)

    Lee, Jae Koo; Kim, Myoung Soo; Byun, June Ho; Kim, Kyong Tai; Kim, Gyoo Cheon; Park, Gan Young

    2011-08-01

    Low temperature atmospheric pressure plasmas have attracted great interests and they have been widely applied to biomedical applications to interact with living tissues, cells, and bacteria due to their non-thermal property. This paper reviews the biomedical applications of low temperature atmospheric pressure plasmas to cancerous cell treatment and tooth bleaching. Gold nanoparticles conjugated with cancer-specific antibodies have been introduced to cancerous cells to enhance selective killing of cells, and the mechanism of cell apoptosis induced by plasma has been investigated. Tooth exposed to helium plasma jet with hydrogen peroxide has become brighter and the productions of hydroxyl radicals from hydrogen peroxide have been enhanced by plasma exposure.

  17. A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy

    International Nuclear Information System (INIS)

    Highlights: ► A CDK4 inhibitor may be used for breast cancer stem cell-targeted therapy. ► The CDK4 inhibitor differentiated the cancer stem cell population (CD24−/CD44+) of MDA-MB-231. ► The differentiation of the cancer stem cells by the CDK4 inhibitor radiosensitized MDA-MB-231. -- Abstract: Cancer stem cells (CSCs) are one of the main reasons behind cancer recurrence due to their resistance to conventional anti-cancer therapies. Thus, many efforts are being devoted to developing CSC-targeted therapies to overcome the resistance of CSCs to conventional anti-cancer therapies and decrease cancer recurrence. Differentiation therapy is one potential approach to achieve CSC-targeted therapies. This method involves inducing immature cancer cells with stem cell characteristics into more mature or differentiated cancer cells. In this study, we found that a CDK4 inhibitor sensitized MDA-MB-231 cells but not MCF7 cells to irradiation. This difference appeared to be associated with the relative percentage of CSC-population between the two breast cancer cells. The CDK4 inhibitor induced differentiation and reduced the cancer stem cell activity of MDA-MB-231 cells, which are shown by multiple marker or phenotypes of CSCs. Thus, these results suggest that radiosensitization effects may be caused by reducing the CSC-population of MDA-MB-231 through the use of the CDK4 inhibitor. Thus, further investigations into the possible application of the CDK4 inhibitor for CSC-targeted therapy should be performed to enhance the efficacy of radiotherapy for breast cancer

  18. A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yu Kyeong; Lee, Jae Ho; Park, Ga-Young; Chun, Sung Hak; Han, Jeong Yun; Kim, Sung Dae [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953 (Korea, Republic of); Lee, Janet [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746 (Korea, Republic of); Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746 (Korea, Republic of); Lee, Chang-Woo [Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746 (Korea, Republic of); Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746 (Korea, Republic of); Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Suwon, Gyeonggi 440-746 (Korea, Republic of); Yang, Kwangmo [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953 (Korea, Republic of); Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953 (Korea, Republic of); Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-709 (Korea, Republic of); Lee, Chang Geun, E-mail: cglee@dirams.re.kr [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953 (Korea, Republic of)

    2013-01-25

    Highlights: ► A CDK4 inhibitor may be used for breast cancer stem cell-targeted therapy. ► The CDK4 inhibitor differentiated the cancer stem cell population (CD24{sup −}/CD44{sup +}) of MDA-MB-231. ► The differentiation of the cancer stem cells by the CDK4 inhibitor radiosensitized MDA-MB-231. -- Abstract: Cancer stem cells (CSCs) are one of the main reasons behind cancer recurrence due to their resistance to conventional anti-cancer therapies. Thus, many efforts are being devoted to developing CSC-targeted therapies to overcome the resistance of CSCs to conventional anti-cancer therapies and decrease cancer recurrence. Differentiation therapy is one potential approach to achieve CSC-targeted therapies. This method involves inducing immature cancer cells with stem cell characteristics into more mature or differentiated cancer cells. In this study, we found that a CDK4 inhibitor sensitized MDA-MB-231 cells but not MCF7 cells to irradiation. This difference appeared to be associated with the relative percentage of CSC-population between the two breast cancer cells. The CDK4 inhibitor induced differentiation and reduced the cancer stem cell activity of MDA-MB-231 cells, which are shown by multiple marker or phenotypes of CSCs. Thus, these results suggest that radiosensitization effects may be caused by reducing the CSC-population of MDA-MB-231 through the use of the CDK4 inhibitor. Thus, further investigations into the possible application of the CDK4 inhibitor for CSC-targeted therapy should be performed to enhance the efficacy of radiotherapy for breast cancer.

  19. 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...

  20. KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Laurila, Eeva; Vuorinen, Elisa [Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere (Finland); Fimlab Laboratories, Biokatu 4, 33520 Tampere (Finland); Savinainen, Kimmo; Rauhala, Hanna [Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere (Finland); Kallioniemi, Anne, E-mail: anne.kallioniemi@uta.fi [Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere (Finland); Fimlab Laboratories, Biokatu 4, 33520 Tampere (Finland)

    2014-03-10

    Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: • KPNA7 expression is elevated in several pancreatic cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy.

  1. KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

    International Nuclear Information System (INIS)

    Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: • KPNA7 expression is elevated in several pancreatic cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy

  2. Paediatric cyclical Cushing's disease due to corticotroph cell hyperplasia.

    LENUS (Irish Health Repository)

    Noctor, E

    2015-06-01

    Cushing\\'s disease is very rare in the paediatric population. Although uncommon, corticotroph hyperplasia causing Cushing\\'s syndrome has been described in the adult population, but appears to be extremely rare in children. Likewise, cyclical cortisol hypersecretion, while accounting for 15 % of adult cases of Cushing\\'s disease, has only rarely been described in the paediatric population. Here, we describe a very rare case of a 13-year old boy with cyclical cortisol hypersecretion secondary to corticotroph cell hyperplasia.

  3. Obstructive jaundice due to ampullary metastasis of renal cell carcinoma

    OpenAIRE

    Karakatsanis, Andreas; Vezakis, Antonios; Fragulidis, Georgios; Staikou, Chryssa; Carvounis, Eleni E; Polydorou, Andreas

    2013-01-01

    Renal cell carcinoma is often characterized by the presence of metachronous metastases in unusual sites. The presence of isolated metastases is treated with surgical excision with good anticipated results. On the other hand, systemic chemotherapy is administered in the context of metastatic spread, usually sunitib or sorafenib. In such cases, however, the presence of symptomatic foci calls for minimal intervention. We present a case of a 77-year-old patient who presented with obstructive jaun...

  4. 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.

  5. 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)

  6. 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

  7. Clear cell ovarian cancer and endometriosis: is there a relationship?

    Science.gov (United States)

    Suzin, Jacek; Obirek, Katarzyna; Sochacka, Amanda; Łoszakiewicz, Marta

    2016-01-01

    Introduction Ovarian clear cell carcinoma is a rare type of ovarian cancer. In recent years, issues of the common genetic origin of endometriosis and ovarian clear cell carcinoma have been raised. Aim of this study Aim of this study was to evaluate the prevalence of this type of cancer, risk factors, prognosis and its potential aetiological association with endometriosis. Material and methods In a retrospective study, we analysed histopathological data of patients operated in the First Department of Gynaecology and Obstetrics (MU, Lodz) due to ovarian cancer in 2004-2014. Among the 394 patients operated on for ovarian cancer, clear cell carcinoma was found in 0.02% (9/394). Menstrual history, parity, comorbidities, data from physical examination, operational protocols and histopathological diagnoses were analysed. Follow-up was obtained from 77.8% of patients. Statistical analysis was performed using Microsoft Excel 2013. Results The mean age of patients at diagnosis was 57.6 years; the BMI in the study group was 27.2; the majority of patients were multiparous (77.8%). Clear cell carcinoma was detected mostly at stage Ia (n = 4). The concentration of Ca125 in the study group had an average of 142.75 U/ml and a median of 69.3 U/ml. The coexistence of endometriosis could not be clinically or histologically confirmed amongst our patients. The most common comorbidity in the study group was hypertension. Conclusions In our clinical material, ovarian clear cell carcinoma is a rare histopathological specimen with a prognostic value comparable to that of serous ovarian cancer. Due to the rarity of this histopathological subtype, proving a cause-and-effect relationship between it and endometriosis can only be elucidated through statistical studies of the entire population.

  8. 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

  9. 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...

  10. Tcf3 and cell cycle factors contribute to butyrate resistance in colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chiaro, Christopher, E-mail: cchiaro@tcmedc.org [Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509 (United States); Lazarova, Darina L., E-mail: dlazarova@tcmedc.org [Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509 (United States); Bordonaro, Michael, E-mail: mbordonaro@tcmedc.org [Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509 (United States)

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer We investigate mechanisms responsible for butyrate resistance in colon cancer cells. Black-Right-Pointing-Pointer Tcf3 modulates butyrate's effects on Wnt activity and cell growth in resistant cells. Black-Right-Pointing-Pointer Tcf3 modulation of butyrate's effects differ by cell context. Black-Right-Pointing-Pointer Cell cycle factors are overexpressed in the resistant cells. Black-Right-Pointing-Pointer Reversal of altered gene expression can enhance the anti-cancer effects of butyrate. -- Abstract: Butyrate, a fermentation product of dietary fiber, inhibits clonal growth in colorectal cancer (CRC) cells dependent upon the fold induction of Wnt activity. We have developed a CRC cell line (HCT-R) that, unlike its parental cell line, HCT-116, does not respond to butyrate exposure with hyperactivation of Wnt signaling and suppressed clonal growth. PCR array analyses revealed Wnt pathway-related genes, the expression of which differs between butyrate-sensitive HCT-116 CRC cells and their butyrate-resistant HCT-R cell counterparts. We identified overexpression of Tcf3 as being partially responsible for the butyrate-resistant phenotype, as this DNA-binding protein suppresses the hyperinduction of Wnt activity by butyrate. Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells; thus, in HCT-116 cells Tcf3 suppresses proliferation without rendering the cells resistant to butyrate. In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G{sub 1} to S transition. Knowledge of the molecular mechanisms determining the variable sensitivity of CRC cells to butyrate may assist in developing approaches that

  11. Tcf3 and cell cycle factors contribute to butyrate resistance in colorectal cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► We investigate mechanisms responsible for butyrate resistance in colon cancer cells. ► Tcf3 modulates butyrate’s effects on Wnt activity and cell growth in resistant cells. ► Tcf3 modulation of butyrate’s effects differ by cell context. ► Cell cycle factors are overexpressed in the resistant cells. ► Reversal of altered gene expression can enhance the anti-cancer effects of butyrate. -- Abstract: Butyrate, a fermentation product of dietary fiber, inhibits clonal growth in colorectal cancer (CRC) cells dependent upon the fold induction of Wnt activity. We have developed a CRC cell line (HCT-R) that, unlike its parental cell line, HCT-116, does not respond to butyrate exposure with hyperactivation of Wnt signaling and suppressed clonal growth. PCR array analyses revealed Wnt pathway-related genes, the expression of which differs between butyrate-sensitive HCT-116 CRC cells and their butyrate-resistant HCT-R cell counterparts. We identified overexpression of Tcf3 as being partially responsible for the butyrate-resistant phenotype, as this DNA-binding protein suppresses the hyperinduction of Wnt activity by butyrate. Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells; thus, in HCT-116 cells Tcf3 suppresses proliferation without rendering the cells resistant to butyrate. In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G1 to S transition. Knowledge of the molecular mechanisms determining the variable sensitivity of CRC cells to butyrate may assist in developing approaches that prevent or reverse butyrate resistance.

  12. Technical Evaluation of the NASA Model for Cancer Risk to Astronauts Due to Space Radiation

    Science.gov (United States)

    2012-01-01

    At the request of NASA, the National Research Council's (NRC's) Committee for Evaluation of Space Radiation Cancer Risk Model reviewed a number of changes that NASA proposes to make to its model for estimating the risk of radiation-induced cancer in astronauts. The NASA model in current use was last updated in 2005, and the proposed model would incorporate recent research directed at improving the quantification and understanding of the health risks posed by the space radiation environment. NASA's proposed model is defined by the 2011 NASA report Space Radiation Cancer Risk Projections and Uncertainties 2010 (Cucinotta et al., 2011). The committee's evaluation is based primarily on this source, which is referred to hereafter as the 2011 NASA report, with mention of specific sections or tables cited more formally as Cucinotta et al. (2011). The overall process for estimating cancer risks due to low linear energy transfer (LET) radiation exposure has been fully described in reports by a number of organizations. They include, more recently: (1) The "BEIR VII Phase 2" report from the NRC's Committee on Biological Effects of Ionizing Radiation (BEIR) (NRC, 2006); (2) Studies of Radiation and Cancer from the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR, 2006), (3) The 2007 Recommendations of the International Commission on Radiological Protection (ICRP), ICRP Publication 103 (ICRP, 2007); and (4) The Environmental Protection Agency s (EPA s) report EPA Radiogenic Cancer Risk Models and Projections for the U.S. Population (EPA, 2011). The approaches described in the reports from all of these expert groups are quite similar. NASA's proposed space radiation cancer risk assessment model calculates, as its main output, age- and gender-specific risk of exposure-induced death (REID) for use in the estimation of mission and astronaut-specific cancer risk. The model also calculates the associated uncertainties in REID. The general approach for

  13. 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.

  14. 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

  15. Naxos disease: Cardiocutaneous syndrome due to cell adhesion defect

    Directory of Open Access Journals (Sweden)

    Protonotarios Nikos

    2006-03-01

    Full Text Available Abstract Naxos disease is a recessively inherited condition with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C and a cutaneous phenotype, characterised by peculiar woolly hair and palmoplantar keratoderma. The disease was first described in families originating from the Greek island of Naxos. Moreover, affected families have been identified in other Aegean islands, Turkey, Israel and Saudi Arabia. A syndrome with the same cutaneous phenotype and predominantly left ventricular involvement has been described in families from India and Ecuador (Carvajal syndrome. Woolly hair appears from birth, palmoplantar keratoderma develop during the first year of life and cardiomyopathy is clinically manifested by adolescence with 100% penetrance. Patients present with syncope, sustained ventricular tachycardia or sudden death. Symptoms of right heart failure appear during the end stages of the disease. In the Carvajal variant the cardiomyopathy is clinically manifested during childhood leading more frequently to heart failure. Mutations in the genes encoding the desmosomal proteins plakoglobin and desmoplakin have been identified as the cause of Naxos disease. Defects in the linking sites of these proteins can interrupt the contiguous chain of cell adhesion, particularly under conditions of increased mechanical stress or stretch, leading to cell death, progressive loss of myocardium and fibro-fatty replacement. Implantation of an automatic cardioverter defibrillator is indicated for prevention of sudden cardiac death. Antiarrhythmic drugs are used for preventing recurrences of episodes of sustained ventricular tachycardia and classical pharmacological treatment for congestive heart failure, while heart transplantation is considered at the end stages.

  16. 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...

  17. 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...

  18. 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...

  19. Advances of Immunotherapy in Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jingjing LIU

    2014-06-01

    Full Text Available Small cell lung cancer (SCLC is complex heterogeneous due to unclear biological characteristics in terms of cell origin, pathogenesis and driver genes etc. Diagnosis and treatment of SCLC has been slowly improved and few breakthroughs have been discovered up to now. Therefore new strategies are urgently needed to improve the efficacy of SCLC treatment. Tumor immunotherapy has potential to restore and trigger the immune system to recognize and eliminate tumor cells, notably it has only minimal adverse impact on normal tissue. Cancer vaccine, adoptive immunotherapy, cytokines and checkpoint inhibitors have now been launched for clinical treatment of SCLC. Ipilimumab is the most promising medicine of immunotherapy. Immunotherapy is expected to bring new vision to the treatment of SCLC. And further researches are needed on such problems affecting efficacy of immunotherapy as the heterogeneity of SCLC, the uncertainty of target for immunotherapy, the immune tolerance, etc.

  20. 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.

  1. Effectiveness of liposomal paclitaxel against MCF-7 breast cancer cells.

    Science.gov (United States)

    Heney, Melanie; Alipour, Misagh; Vergidis, Dimitrios; Omri, Abdelwahab; Mugabe, Clement; Th'ng, John; Suntres, Zacharias

    2010-12-01

    Paclitaxel is an effective chemotherapeutic agent that is widely used for the treatment of several cancers, including breast, ovarian, and non-small-cell lung cancer. Due to its high lipophilicity, paclitaxel is difficult to administer and requires solubilization with Cremophor EL (polyethoxylated castor oil) and ethanol, which often lead to adverse side effects, including life-threatening anaphylaxis. Incorporation of paclitaxel in dimyristoylphosphatidylcholine:dimyristoylphosphatidylglycerol (DPPC:DMPG) liposomes can facilitate its delivery to cancer cells and eliminate the adverse reactions associated with the Cremophor EL vehicle. Accordingly, the effectiveness of liposomal paclitaxel on MCF-7 breast cancer cells was examined. The results from this study showed that (i) the lipid components of the liposomal formulation were nontoxic, (ii) the cytotoxic effects of liposomal paclitaxel were improved when compared with those seen with conventional paclitaxel, and (iii) the intracellular paclitaxel levels were higher in MCF-7 cells treated with the liposomal paclitaxel formulation. The results of these studies showed that delivery of paclitaxel as a liposomal formulation could be a promising strategy for enhancing its chemotherapeutic effects. PMID:21164564

  2. 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

  3. 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...

  4. 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

  5. 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.

  6. Lung cancer risk due to exposure to indoor radon in Western Germany

    International Nuclear Information System (INIS)

    In a case-control study in West-Germany the lung cancer risk due to exposure to indoor radon was investigated. From 1990 to 1996 incident lung cancer patients as well as a random sample recruited from the population were interviewed according to their residential history, smoking, occupational exposure and other risk factors. 2 charcoal canisters and 2 alpha track detectors were placed for 1 year in the present and former dwellings of participants. The evaluation included 1449 cases and 2297 controls recruited from the entire study area, and 365 cases and 595 controls recruited from radon-prone matching areas within the entire study area. Odds ratios were estimated according to a logistic regression model simultaneously adjusted to smoking and to exposure to asbestos. Furthermore the linear trend was calculated. In the entire study area no elevated odds ratio is seen. However, in the radon-prone matching areas a clear influence of exposure to radon on the lung cancer risk is observed. The adjusted odds ratio [95% CI] is 1.59 [1.08, 2.27], 1.93 [1.19, 3.13] and 1.93 [0.99, 3.77] for 50-80, 80-140 and over 140 Bq/m3 compared to 0-50 Bq/m3. The odds ratio for the linear trends is 1.13 [0.88, 1.46] for an increase in exposure of 100 Bq/m3. (orig./MG)

  7. 32-Phosphorus for bone pain palliation due to bone metastases, its safety and efficacy in patients with advanced cancer

    International Nuclear Information System (INIS)

    Bone pain due to bony metastases can seriously affect a patient's quality of life. External irradiation, narcotic drugs and polyphosphates may cause important side effects or are expensive, therefore in many patients radionuclide treatment using a single dose of beta emitting bone seeking radiopharmaceuticals has become widely accepted. Except 32-Phosphorus (32-P) all of them are expensive and difficult to obtain in certain countries. The aim of the study was to evaluate safety and efficacy of 32-P for palliation of bone pain due to bony metastases by comparing it to 89-Strontium (89-Sr), the most commonly used radiopharmaceutical for bone pain palliation in the framework of a prospective IAEA co-ordinated multicenter study. A very strict protocol for unified patient inclusion and follow up was used. 93 cancer patients with osteoblastic bony metastases were included into the study, 48 were treated by 89-Sr (150 MBq) and 45 by 32-P (450 MBq). Pain score, analgesic consumption, quality of life, and indices of bone marrow depression were monitored 2 weeks pre- and up to 4 months post treatment. Favourable response to treatment was recorded in 75% of the patients treated with 89-Sr and in 60% of those treated with 32-P (p=0,122). There was no significant difference between the duration of favourable effect for both radiopharmaceuticals. Moderate decrease of white blood cell (WBC) and platelet counts, and haemoglobin (Hb) levels was detected more often in the 32-P treated group. Although 32-P appears to be more toxic, no toxic effects requiring specific treatment were seen in either group. Due to its comparable efficacy and safety, general availability and low cost its more widespread use should be encouraged to increase quality of life and reduce cost of medical care of patients with intractable bone pain due to cancer metastases. (author)

  8. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines

    International Nuclear Information System (INIS)

    Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for μ, δ, and κ opioid agonists and for nicotine and α-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas μ, δ, and κ opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides (β-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer

  9. 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.

  10. REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells.

    Science.gov (United States)

    Wang, Wenjie; Sheng, Wenjiong; Yu, Chenxiao; Cao, Jianping; Zhou, Jundong; Wu, Jinchang; Zhang, Huojun; Zhang, Shuyu

    2015-09-01

    Lung cancer remains the leading cause of cancer-related mortality worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all cases of lung cancer. Cisplatin plays a significant role in the management of human lung cancer. Translesion DNA synthesis (TLS) is involved in DNA damage repair. DNA polymerase ζ (Pol ζ) is able to mediate the DNA replication bypass of DNA damage, which is suggested to be involved in chemoresistance. REV3L is the catalytic subunit of Pol ζ. Due to its critical role in translesion DNA synthesis, whether REV3L modulates cisplatin response in NSCLC cells remains unknown. In this study, REV3L overexpression and silencing H1299 cell lines were established. The reports showed that cisplatin induced the expression of REV3L by recruiting Sp1 to its promoter. Similar results were obtained when the ability of the cells to express luciferase from a platinated plasmid was measured. Co-transfection of the reporter with the REV3L overexpression vector or REV3L plus REV7L significantly enhanced the reporter activity. Nuclear condensation and fragmentation of shRNA-REV3L H1299 cells were more pronounced than shRNA-NC H1299 cells after cisplatin exposure, indicating that REV3L overexpression abolished cisplatin-induced DNA damage. Moreover, a forced expression of REV3L conferred the resistance of H1299 cells to cisplatin, whereas the knockdown of REV3L sensitized cisplatin efficacy in H1299 cells. Taken together, we demonstrated that inhibition of REV3L sensitized lung cancer H1299 cells to cisplatin treatment. Thus, REV3L may be a novel target for the chemotherapy of NSCLC. PMID:26165320

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. Identification of Distinct Breast Cancer Stem Cell Populations Based on Single-Cell Analyses of Functionally Enriched Stem and Progenitor Pools

    OpenAIRE

    Nina Akrap; Daniel Andersson; Eva Bom; Pernilla Gregersson; Anders Ståhlberg; Göran Landberg

    2016-01-01

    Summary The identification of breast cancer cell subpopulations featuring truly malignant stem cell qualities is a challenge due to the complexity of the disease and lack of general markers. By combining extensive single-cell gene expression profiling with three functional strategies for cancer stem cell enrichment including anchorage-independent culture, hypoxia, and analyses of low-proliferative, label-retaining cells derived from mammospheres, we identified distinct stem cell clusters in b...

  16. MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells

    International Nuclear Information System (INIS)

    Prostate cancer is one of the most common malignant cancers in men. Recent studies have shown that microRNA-21 (miR-21) is overexpressed in various types of cancers including prostate cancer. Studies on glioma, colon cancer cells, hepatocellular cancer cells and breast cancer cells have indicated that miR-21 is involved in tumor growth, invasion and metastasis. However, the roles of miR-21 in prostate cancer are poorly understood. In this study, the effects of miR-21 on prostate cancer cell proliferation, apoptosis, and invasion were examined. In addition, the targets of miR-21 were identified by a reported RISC-coimmunoprecipitation-based biochemical method. Inactivation of miR-21 by antisense oligonucleotides in androgen-independent prostate cancer cell lines DU145 and PC-3 resulted in sensitivity to apoptosis and inhibition of cell motility and invasion, whereas cell proliferation were not affected. We identified myristoylated alanine-rich protein kinase c substrate (MARCKS), which plays key roles in cell motility, as a new target in prostate cancer cells. Our data suggested that miR-21 could promote apoptosis resistance, motility, and invasion in prostate cancer cells and these effects of miR-21 may be partly due to its regulation of PDCD4, TPM1, and MARCKS. Gene therapy using miR-21 inhibition strategy may therefore be useful as a prostate cancer therapy.

  17. Retinal Targets ALDH Positive Cancer Stem Cell and Alters the Phenotype of Highly Metastatic Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Xiaodong Mu

    2015-01-01

    Full Text Available Aldehyde dehydrogenase (ALDH is a cancer stem cell marker. Retinoic acid has antitumor properties, including the induction of apoptosis and inhibition of proliferation. Retinal, the precursor of retinoic acid, can be oxidized to retinoic acid by dehydrogenases, including ALDH. We hypothesized that retinal could potentially be transformed to retinoic acid with higher efficiency by cancer stem cells, due to the higher ALDH activity. We previously observed that ALDH activity is greater in highly metastatic K7M2 osteosarcoma (OS cells than in nonmetastatic K12 OS cells. We also demonstrated that ALDH activity correlates with clinical metastases in bone sarcoma patients, suggesting that ALDH may be a therapeutic target specific to cells with high metastatic potential. Our current results demonstrated that retinal preferentially affected the phenotypes of ALDH-high K7M2 cells in contrast to ALDH-low K12 cells, which could be mediated by the more efficient transformation of retinal to retinoic acid by ALDH in K7M2 cells. Retinal treatment of highly metastatic K7M2 cells decreased their proliferation, invasion capacity, and resistance to oxidative stress. Retinal altered the expression of metastasis-related genes. These observations indicate that retinal may be used to specifically target metastatic cancer stem cells in OS.

  18. [Incidence and mortality due to cancer in Navarre, 1998-2002. Trends in the last 30 years].

    Science.gov (United States)

    Ardanaz, E; Moreno-Iribas, C; Pérez de Rada, M E; Ezponda, C; Floristán, Y; Navaridas, N; Martínez-Peñuela, J M; Puras, A; Santamaría, M; Ezpeleta, I; Valerdi, J J; Pardo, F J; Monzón, F J; Lizarraga, J; Ortigosa, C; Resano, J; Barricarte, A

    2007-01-01

    Between 1998-2002, 16,952 new cases of cancer were registered in Navarre. In men, the most frequently diagnosed cancers were in the following order: prostate, lung, colon and rectum, bladder and stomach, which accounted for 63.2%. In women, the sites were breast, colon and rectum, corpus uteri, stomach and ovary, which accounted for 57.6% of the cases. In the same period, 1998-2002, 4,127 men and 2,470 women died from cancer. Sixty percent of all deaths due to malign tumours in men were due to cancer of the lung, prostate, colon and rectum, stomach and bladder. In women this was due to cancers of colon and rectum, breast, stomach, pancreas and lung, which accounted for 49% of the cases. In men in Navarre there has been an increase in the incidence rates of cancer of the prostate, kidney and non-Hodgkin lymphoma. Avoidable cancers such as those related to smoking (lung, oral cavity and pharynx or pancreas) continue to rise, and represent a greater global risk of dying from cancer in the latest period studied than in the decades of the 1970s and 1980s. From 1995 up to the present, mortality due to cancer has moved from occupying the second place to become the first cause of death among men in Navarre. The global risk of death due to cancer in men is now equal to the first period studied, 1975-1977. Amongst women the global risk of death due to cancer fell by 25% between 1975 and 2002, basically at the cost of breast and stomach cancer. Tumours related to smoking increased both in mortality and in incidence and appear as a significant health problem amongst women in Navarre. Breast cancer has increased in incidence, with lower mortality figures than those of the first period 1975-1977. Invasive cancer of the cervix remains at very low rates in comparison with many European countries, including Spain. In both sexes colorectal and skin cancer has increased, while the incidence and mortality of stomach cancer continues to fall. PMID:17898820

  19. Ileal Intussusception Due to Metastasis from Squamous Cell Carcinoma of the Lung Resected 12 Years Previously.

    Science.gov (United States)

    Nakamura, Tomoki; Chino, Osamu; Tajima, Takayuki; Tanaka, Yoichi; Yokoyama, Daiki; Hanashi, Tomoko; Sadahiro, Sotaro; Makuuchi, Hiroyasu

    2015-12-01

    An 88-year-old woman, with a history of resection of stage IIA lung cancer in 1998, was referred to our hospital in August 2010 complaining of upper abdominal pain, vomiting, and dark brown stools. After endoscopic examination, she was admitted with a diagnosis of Mallory-Weiss syndrome. Vomiting occurred when food intake was resumed after fasting. Intestinal obstruction was suspected on abdominal radiography, and complete small bowel obstruction was confirmed by contrast-enhanced imaging after placement of an ileus tube. A small intestinal tumor with intussusception was detected by computed tomography. At laparotomy, there was no ascites. Intussusception was found due to an ileal tumor located approximately 50 cm from the ileocecal valve, and we performed partial small bowel resection. The resected small intestine contained a submucosal tumor approximately 40 mm in diameter that had penetrated the bowel wall to reach the serosa. Pathological examination revealed a submucosal tumor that showed poor continuity with the surrounding mucosa, while the histology was squamous cell carcinoma. Immunohistochemistry showed that the tumor was CK7 positive, CK20 negative, TTF-1 negative, and CK10 positive. Based on these findings, we made a diagnosis of small intestinal metastasis at 12 years after radical resection of squamous cell carcinoma of the lung. PMID:26662663

  20. Emerging role of microRNAs in cancer stem cells:Implications in cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Minal; Garg

    2015-01-01

    A small subset of cancer cells that act as tumor initiating cells or cancer stem cells(CSCs) maintain self-renewal and growth promoting capabilities of cancer and are responsible for drug/treatment resistance,tumor recurrence and metastasis. Due to their potential clinical importance,many researchers have put their efforts over decades to unravel the molecular mechanisms that regulate CSCs functions. Micro RNAs(mi RNAs) which are 21-23 nucleotide long,endogenous noncoding RNAs,regulate gene expression through gene silencing at post-transcriptional level by binding to the 3’-untranslated regions or the open reading frames of target genes,thereby result in target mR NA degradation or its translational repression and serve important role in several cellular,physiological and developmental processes. Aberrant mi RNAs expression and their implication in CSCs regulation by controlling asymmetric cell division,drug/treatment resistance and metastasis make mi RNAs a tool of great therapeutic potential against cancer. Recent advancements on the biological complexities of CSCs,modulation in CSCs properties by mi RNA network and development of mi RNA based treatment strategies specifically targeting the CSCs as an attractive therapeutic targets for clinical application are being critically analysed.

  1. 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.

  2. 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

  3. 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.

  4. Cancer cell imaging by stable wet near-field scanning optical microscope with resonance tracking method

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kyoung-Duck [Sungkyunkwan University, Suwon (Korea, Republic of); Inha University, Incheon (Korea, Republic of); Park, Doo-Jae; Jeong, Mun-Seok [Sungkyunkwan University, Suwon (Korea, Republic of); Choi, Geun-Chang [Seoul National University, Seoul (Korea, Republic of); Lee, Seung-Gol [Inha University, Incheon (Korea, Republic of); Byeon, Clare-Chisu [Kyungpook National University, Daegu (Korea, Republic of); Choi, Soo-Bong [Incheon National University, Incheon (Korea, Republic of)

    2014-05-15

    We report on a successful topographical and optical imaging of various cancer cells in liquid and in air by using a stable wet near-field scanning optical microscope that utilizes a resonance tracking method. We observed a clear dehydration which gives rise to a decrease in the cell volume down to 51%. In addition, a micro-ball lens effect due to the round-shaped young cancer cells was observed from near-field imaging, where the refractive index of young cancer cells was deduced.

  5. Cancer cell imaging by stable wet near-field scanning optical microscope with resonance tracking method

    International Nuclear Information System (INIS)

    We report on a successful topographical and optical imaging of various cancer cells in liquid and in air by using a stable wet near-field scanning optical microscope that utilizes a resonance tracking method. We observed a clear dehydration which gives rise to a decrease in the cell volume down to 51%. In addition, a micro-ball lens effect due to the round-shaped young cancer cells was observed from near-field imaging, where the refractive index of young cancer cells was deduced.

  6. 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.

  7. 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...

  8. 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

  9. 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

  10. Targeting DNA Damage Response in the Radio(Chemo)therapy of Non-Small Cell Lung Cancer

    OpenAIRE

    Ling Li; Tao Zhu; Yuan-Feng Gao; Wei Zheng; Chen-Jing Wang; Ling Xiao; Ma-Sha Huang; Ji-Ye Yin; Hong-Hao Zhou; Zhao-Qian Liu

    2016-01-01

    Lung cancer is the leading cause of cancer death worldwide due to its high incidence and mortality. As the most common lung cancer, non-small cell lung cancer (NSCLC) is a terrible threat to human health. Despite improvements in diagnosis and combined treatments including surgical resection, radiotherapy and chemotherapy, the overall survival for NSCLC patients still remains poor. DNA damage is considered to be the primary cause of lung cancer development and is normally recognized and repair...

  11. SU-E-J-95: Predicting Treatment Outcomes for Prostate Cancer: Irradiation Responses of Prostate Cancer Stem Cells

    International Nuclear Information System (INIS)

    Purpose: Most prostate cancers are slow-growing diseases but normally require much higher doses (80Gy) with conventional fractionation radiotherapy, comparing to other more aggressive cancers. This study is to disclose the radiobiological basis of this discrepancy by proposing the concept of prostate cancer stem cells (CSCs) and examining their specific irradiation responses. Methods: There are overwhelming evidences that CSC may keep their stemness, e.g. the competency of cell differentiation, in hypoxic microenvironments and hence become radiation resistive, though the probability is tiny for aggressiveness cancers. Tumor hypoxia used to be considered as an independent reason for poor treatment outcomes, and recent evidences showed that even prostate cancers were also hypoxic though they are very slow-growing. In addition, to achieve comparable outcomes to other much more aggressive cancers, much higher doses (rather than lower doses) are always needed for prostate cancers, regardless of its non-aggressiveness. All these abnormal facts can only be possibly interpreted by the irradiation responses characteristics of prostate CSCs. Results: Both normal cancer cells (NCCs) and CSCs exiting in tumors, in which NCCs are mainly for symptoms whereas killing all CSCs achieves disease-free. Since prostate cancers are slow-growing, the hypoxia in prostate cancers cannot possibly from NCCs, thus it is caused by hypoxic CSCs. However, single hypoxic cell cannot be imaged due to limitation of imaging techniques, unless a large group of hypoxic cells exist together, thus most of CSCs in prostate cancers are virtually hypoxic, i.e. not in working mode because CSCs in proliferating mode have to be normoxic, and this explains why prostate cancers are unaggressive. Conclusion: The fractional dose in conventional radiotherapy (∼2Gy) could only kill NCCs and CSCs in proliferating modes, whereas most CSCs survived fractional treatments since they were hypoxic, thus to eliminate all

  12. SU-E-J-95: Predicting Treatment Outcomes for Prostate Cancer: Irradiation Responses of Prostate Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, K [University of Miami, Miami, FL (United States)

    2014-06-01

    Purpose: Most prostate cancers are slow-growing diseases but normally require much higher doses (80Gy) with conventional fractionation radiotherapy, comparing to other more aggressive cancers. This study is to disclose the radiobiological basis of this discrepancy by proposing the concept of prostate cancer stem cells (CSCs) and examining their specific irradiation responses. Methods: There are overwhelming evidences that CSC may keep their stemness, e.g. the competency of cell differentiation, in hypoxic microenvironments and hence become radiation resistive, though the probability is tiny for aggressiveness cancers. Tumor hypoxia used to be considered as an independent reason for poor treatment outcomes, and recent evidences showed that even prostate cancers were also hypoxic though they are very slow-growing. In addition, to achieve comparable outcomes to other much more aggressive cancers, much higher doses (rather than lower doses) are always needed for prostate cancers, regardless of its non-aggressiveness. All these abnormal facts can only be possibly interpreted by the irradiation responses characteristics of prostate CSCs. Results: Both normal cancer cells (NCCs) and CSCs exiting in tumors, in which NCCs are mainly for symptoms whereas killing all CSCs achieves disease-free. Since prostate cancers are slow-growing, the hypoxia in prostate cancers cannot possibly from NCCs, thus it is caused by hypoxic CSCs. However, single hypoxic cell cannot be imaged due to limitation of imaging techniques, unless a large group of hypoxic cells exist together, thus most of CSCs in prostate cancers are virtually hypoxic, i.e. not in working mode because CSCs in proliferating mode have to be normoxic, and this explains why prostate cancers are unaggressive. Conclusion: The fractional dose in conventional radiotherapy (∼2Gy) could only kill NCCs and CSCs in proliferating modes, whereas most CSCs survived fractional treatments since they were hypoxic, thus to eliminate all

  13. Testicular germ cell cancer incidence in an immigration perspective, Denmark, 1978 to 2003

    DEFF Research Database (Denmark)

    Schmiedel, Sven; Schüz, Joachim; Skakkebaek, Niels E; Johansen, Christoffer

    2010-01-01

    The incidence rate of testicular germ cell cancer in Denmark increased up to the 1990s to become among the highest in the world. Since recently rate stabilization was suggested, we determined whether it is due to an increasing number of immigrants at lower risk for this cancer....

  14. 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.

  15. 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...

  16. Cancer stem cells generated by alcohol, diabetes, and HCV

    OpenAIRE

    Machida, Keigo; Chen, Chia-Lin; Liu, Jian-Chang; Kashiwabara, Claudine; Feldman, Douglas; French, Samuel W.; Sher, Linda; Hyeongnam, Jeong Joseph; Tsukamoto, Hidekazu

    2012-01-01

    Cancer stem cells (Tumor-initiating stem-like cells: TISCs) are resistant to chemotherapy and are associated with metastatic hepatocellular carcinoma (HCC), which is commonly observed in hepatitis C virus (HCV)-infected patients with obesity or alcohol abuse. However, it is unknown whether the TLR4-NANOG pathway serves as a universal oncogenic signaling in the genesis of TISCs and HCC. We aimed to determine whether Tlr4 is a putative proto-oncogene for TISCs in liver oncogenesis due to differ...

  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. The role of estrogen receptor alpha in mediating chemoresistance in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Jiang Zhinong

    2012-05-01

    Full Text Available Abstract Introduction Previous studies suggested that estrogen receptor alpha (ERα plays an important role in the chemoresistance of breast cancers. However, large random trials failed to demonstrate any benefit of the concurrent estrogen antagonist tamoxifen on the chemotherapy efficacy. Thus, in the present study, the importance of the role of ERα in the chemoresistance of breast cancer cells was investigated. Methods The ERα-transfected Bcap37 cells and natural ERα-positive T47D breast cancer cells were treated using chemotherapeutic agents with or without 17-beta estradiol (E2 pretreatment. Their viabilities were assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays. The dead cell rates were determined using propidium iodide dye exclusion tests, and the expression levels of Bcl-2 and Bax were detected through Western blot analysis. The effects of E2 on the growth of breast cancer cells were also determined via cell growth curve and cell cycle analysis. Results ERα activation by E2 increased the sensitivity of natural ERα-positive T47D breast cancer cells to chemotherapeutic agents. However, the increase in ERα expression in ERα-negative Bcap37 breast cancer cells also significantly increased their resistance. These phenomena cannot be explained by asserting that ERα mediated the chemoresistance of breast cancer cells by regulating the expression of Bcl-2 and Bax. Our findings show that ERα activation upregulated the expression of Bcl-2 in natural ERα-positive T47D breast cancer cells, whereas ERα activation by E2 downregulated and upregulated the Bcl-2 and Bax expression levels, respectively, in ERα-transfected Bcap37 cells. This phenomenon was due to the influence of ERα on the growth of breast cancer cells. Specifically, ERα activation enhanced the growth of natural ERα-positive breast cancer cells and thus increased their sensitivity to chemotherapeutic agents. However, ERα activation also

  19. Study of epidemiological risk of lung cancer in Mexico due indoor radon exposure

    Science.gov (United States)

    Ángeles, A.; Espinosa, G.

    2014-07-01

    In this work the lifetime relative risks (LRR) of lung cancer due to exposure to indoor 222Rn on the Mexican population is calculated. Cigarette smoking is the number one risk factor for lung cancer (LC), because that, to calculate the number of cases of LC due to exposure to 222Rn is necessary considers the number of cases of LC for smoking cigarette. The lung cancer mortality rates published by the "Secretaría de Salud" (SSA), the mexican population data published by the "Consejo Nacional de Población" (CONAPO), smoking data in the mexican population, published by the "Comisión Nacional Contra las Adicciones" (CONADIC), the "Organización Panamericana de la Salud" (OPS) and indoor 222Rn concentrations in Mexico published in several recent studies are used. To calculate the lifetime relative risks (LRR) for different segments of the Mexican population, firstly the Excess Relative Risk (ERR) is calculated using the method developed by the BEIR VI committee and subsequently modified by the USEPA and published in the report "EPA Assessment of Risks from Radon in Homes". The excess relative risks were then used to calculate the corresponding lifetime relative risks, again using the method developed by the BEIR VI committee. The lifetime relative risks for Mexican male and female eversmokers and Mexican male and female never-smokers were calculated for radon concentrations spanning the range found in recent studies of indoor radon concentrations in Mexico. The lifetime relative risks of lung cancer induced by lifetime exposure to the mexican average indoor radon concentration were estimated to be 1.44 and 1.40 for never-smokers mexican females and males respectively, and 1.19 and 1.17 for ever-smokers Mexican females and males respectively. The Mexican population LRR values obtained in relation to the USA and Canada LRR published values in ever-smokers for both gender are similar with differences less than 4%, in case of never-smokers in relation with Canada

  20. 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.

  1. Fluorescent Cy5 silica nanoparticles for cancer cell imaging

    Science.gov (United States)

    O'Connell, Claire; Nooney, Robert I.; Glynn, MacDara; Ducree, Jens; McDonagh, Colette

    2015-08-01

    Cancer is a leading cause of death worldwide, with metastasis responsible for the majority of cancer-related deaths. Circulating tumour cells (CTCs) play a central role in metastasis. Fluorescent silica particles (NPs), of diameter ~50 nm which contain a large concentration of Cy5 dye molecules and are extremely bright, have been developed to detect these rare CTCs. Due to this brightness, the particles have superior performance compared to single Cy5 dye molecule labels, for detecting cancer cells. Fluorescence measurements show that the NPs are almost 100 times brighter than the free dye. They do not photo bleach as readily and, due to the biocompatible silica surface, they can be chemically modified, layer-by-layer, in order to bind to cells. The choice of these chemical layers, in particular the NP to antibody linker, along with the incubation period and type of media used in the incubation, has a strong influence on the specific binding abilities of the NPs. In this work, NPs have been shown to selectively bind to the MCF-7 cell line by targeting epithelial cellular adhesion molecule (EpCAM) present on the MCF-7 cell membrane by conjugating anti-EpCAM antibody to the NP surface. Results have shown a high signal to noise ratio for this cell line in comparison to a HeLa control line. NP attachment to cells was verified qualitatively with the use of fluorescence microscopy and quantitatively using image analysis methods. Once the system has been optimised, other dyes will be doped into the silica NPs and their use in multiplexing will be investigated.

  2. 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...

  3. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors.

    Science.gov (United States)

    Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois

    2016-04-01

    Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate. PMID:26976217

  4. Stem cells, senescence, neosis and self-renewal in cancer

    Directory of Open Access Journals (Sweden)

    Rajaraman Murali M

    2006-11-01

    Full Text Available Abstract We describe the basic tenets of the current concepts of cancer biology, and review the recent advances on the suppressor role of senescence in tumor growth and the breakdown of this barrier during the origin of tumor growth. Senescence phenotype can be induced by (1 telomere attrition-induced senescence at the end of the cellular mitotic life span (MLS* and (2 also by replication history-independent, accelerated senescence due to inadvertent activation of oncogenes or by exposure of cells to genotoxins. Tumor suppressor genes p53/pRB/p16INK4A and related senescence checkpoints are involved in effecting the onset of senescence. However, senescence as a tumor suppressor mechanism is a leaky process and senescent cells with mutations or epimutations in these genes escape mitotic catastrophe-induced cell death by becoming polyploid cells. These polyploid giant cells, before they die, give rise to several cells with viable genomes via nuclear budding and asymmetric cytokinesis. This mode of cell division has been termed neosis and the immediate neotic offspring the Raju cells. The latter inherit genomic instability and transiently display stem cell properties in that they differentiate into tumor cells and display extended, but, limited MLS, at the end of which they enter senescent phase and can undergo secondary/tertiary neosis to produce the next generation of Raju cells. Neosis is repeated several times during tumor growth in a non-synchronized fashion, is the mode of origin of resistant tumor growth and contributes to tumor cell heterogeneity and continuity. The main event during neosis appears to be the production of mitotically viable daughter genome after epigenetic modulation from the non-viable polyploid genome of neosis mother cell (NMC. This leads to the growth of resistant tumor cells. Since during neosis, spindle checkpoint is not activated, this may give rise to aneuploidy. Thus, tumor cells also are destined to die due to

  5. 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...

  6. 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.

  7. 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)

  8. 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...

  9. Relationships between stem cells and cancer stem cells

    OpenAIRE

    Crowe, D.L.; Parsa, B.; Sinha, U.K.

    2004-01-01

    Stem cells have been shown to exist in a variety of tissues. Recent studies have characterized stem cell gene expression patterns, phenotypes, and potential therapeutic uses. One of the most important properties of stem cells is that of self renewal. This raises the possibility that some of the clinical properties of human tumors may be due to transformed stem cells. Similar signaling pathways may regulate self renewal in normal and transformed stem cells. Thes...

  10. 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. ...

  11. Dendritic Cells in the Cancer Microenvironment

    Directory of Open Access Journals (Sweden)

    Yang Ma, Galina V. Shurin, Zhu Peiyuan, Michael R. Shurin

    2013-01-01

    Full Text Available The complexity of the tumor immunoenvironment is underscored by the emergence and discovery of different subsets of immune effectors and regulatory cells. Tumor-induced polarization of immune cell differentiation and function makes this unique environment even more intricate and variable. Dendritic cells (DCs represent a special group of cells that display different phenotype and activity at the tumor site and exhibit differential pro-tumorigenic and anti-tumorigenic functions. DCs play a key role in inducing and maintaining the antitumor immunity, but in the tumor environment their antigen-presenting function may be lost or inefficient. DCs might be also polarized into immunosuppressive/tolerogenic regulatory DCs, which limit activity of effector T cells and support tumor growth and progression. Although various factors and signaling pathways have been described to be responsible for abnormal functioning of DCs in cancer, there are still no feasible therapeutic modalities available for preventing or reversing DC malfunction in tumor-bearing hosts. Thus, better understanding of DC immunobiology in cancer is pivotal for designing novel or improved therapeutic approaches that will allow proper functioning of DCs in patients with cancer.

  12. 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

  13. Osthole inhibits proliferation of human breast cancer cells by inducing cell cycle arrest and apoptosis

    Institute of Scientific and Technical Information of China (English)

    Lintao Wang; Yanyan Peng; Kaikai Shi; Haixiao Wang; Jianlei Lu; Yanli Li; Changyan Ma

    2015-01-01

    Recent studies have revealed that osthole,an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson,a traditional Chinese medicine,possesses anticancer activity.However,its effect on breast cancer cells so far has not been elucidated clearly.In the present study,we evaluated the effects of osthole on the proliferation,cell cycle and apoptosis of human breast cancer cells MDA-MB 435.We demonstrated that osthole is effective in inhibiting the proliferation of MDA-MB 435 cells,The mitochondrion-mediated apoptotic pathway was involved in apoptosis induced by osthole,as indicated by activation of caspase-9 and caspase-3 followed by PARP degradation.The mechanism underlying its effect on the induction of G1 phase arrest was due to the up-regulation of p53 and p21 and down-regulation of Cdk2 and cyclin D1 expression.Were observed taken together,these findings suggest that the anticancer efficacy of osthole is mediated via induction of cell cycle arrest and apoptosis in human breast cancer cells and osthole may be a potential chemotherapeutic agent against human breast cancer.

  14. 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

  15. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

    OpenAIRE

    Aaraby Yoheswaran Nielsen; Morten Frier Gjerstorff

    2016-01-01

    Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the ...

  16. Genetic Variation in Cell Cycle Regulatory Gene AURKA and Association With Intrinsic Breast Cancer Subtype

    OpenAIRE

    Taylor, Nicholas J.; Bensen, Jeannette T.; Poole, Charles; Troester, Melissa A.; Gammon, Marilie D.; Luo, Jingchun; Millikan, Robert C.; Olshan, Andrew F.

    2014-01-01

    AURKA is a putative low-penetrance tumor susceptibility gene due to its prominent role in cell cycle regulation and centrosomal function. Germline variation in AURKA was evaluated for association with breast cancer and intrinsic breast cancer subtypes in the Carolina Breast Cancer Study (CBCS), a population-based case-control study of African Americans (AA) and Caucasians (Cau). Tag and candidate single nucleotide polymorphisms (SNPs) on AURKA were genotyped in 1946 cases and 1747 controls. I...

  17. 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

  18. Three cases of lumbo-sacral neuropathy due to radiation for uterine cancer

    International Nuclear Information System (INIS)

    Case 1: The 61-year-old woman developed uterine cancer at age 50. Radiation therapy was initiated to the pelvic lumen from both anterior and posterior sides with a total dose of 21,000 rads. Radiation ulcerative neterocolitis and dermatitis revealed at the end of the therapy. At age 52 (2 years after radiation), she noticed muscle weakness and dysesthesia of the lower legs. These symptoms progressed and amyotrophy of the legs appeared. At age 54 (4 years after radiation), she became unable to walk. Case 2: The 51-year-old woman developed uterine cancer at age 40. Postoperative radiation was initiated by the same dose and the same way as in Case 1 and she suffered from radiation dermatitis. At age 49 (9 years after radiation), she noticed dysesthesia of the right toe, which gradually spread to another side. Ten years after radiation, she began to note weakness in dorsiflexion of feet. Case 3: The 69-year-old woman developed uterine cancer at age 67. Radiation (Linac 4,000 rads, Ralstron 2,000 rads) was performed for 3 months into the pelvic lumen. Two years later, she noted dysesthesia and weakness of her legs. These symptoms progressed gradually. In these 3 cases, EMG showed neurogenic changes, suggesting peripheral nerve lesions. Nerve conduction velocities were decreased. Nerve and muscle biopsies revealed neurogenic changes. No abnormal findings were detected by spinal X-rays and myelography. The neurological findings of these patients were compatible with the lumbo-sacrol plexus injuries apparently due to late radiation effect. (J.P.N.)

  19. Three cases of lumbo-sacral neuropathy due to radiation for uterine cancer

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Yoshikazu; Hokezu, Yoichi; Kanehisa, Yoshihide; Nagamatsu, Keiji; Onishi, Akio

    1985-01-01

    Case 1: The 61-year-old woman developed uterine cancer at age 50. Radiation therapy was initiated to the pelvic lumen from both anterior and posterior sides with a total dose of 21,000 rads. Radiation ulcerative enterocolitis and dermatitis revealed at the end of the therapy. At age 52 (2 years after radiation), she noticed muscle weakness and dysesthesia of the lower legs. These symptoms progressed and amyotrophy of the legs appeared. At age 54 (4 years after radiation), she became unable to walk. Case 2: The 51-year-old woman developed uterine cancer at age 40. Postoperative radiation was initiated by the same dose and the same way as in Case 1 and she suffered from radiation dermatitis. At age 49 (9 years after radiation), she noticed dysesthesia of the right toe, which gradually spread to another side. Ten years after radiation, she began to note weakness in dorsiflexion of feet. Case 3: The 69-year-old woman developed uterine cancer at age 67. Radiation (Linac 4,000 rads, Ralstron 2,000 rads) was performed for 3 months into the pelvic lumen. Two years later, she noted dysesthesia and weakness of her legs. These symptoms progressed gradually. In these 3 cases, EMG showed neurogenic changes, suggesting peripheral nerve lesions. Nerve conduction velocities were decreased. Nerve and muscle biopsies revealed neurogenic changes. No abnormal findings were detected by spinal X-rays and myelography. The neurological findings of these patients were compatible with the lumbo-sacrol plexus injuries apparently due to late radiation effect. (J.P.N.).

  20. 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.

  1. 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

  2. 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...

  3. 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

  4. 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

  5. ANALYSIS OF COMPLICATIONS DUE TO INTRATISSUE RADIOTHERAPY USING CONSTANT SOURCES IN PATIENTS WITH PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Petrovsky

    2014-07-01

    Full Text Available Brachytherapy is a standard treatment for localized advanced prostate cancer (PC. Complications due to interstitial radiotherapy using permanent sources were analyzed in 149 patients. The incidence of early grade 3 radiation urethritis was 7.4 % and that of rectitis was 3.4%. Late radiation urethritis and rectitis were recorded in 3.4 and 0.7 %, respectively. Sexual function 12 months later was preserved in 86.6 % of the patients. Studies established no statistically significant factors that influenced the frequency of complications. The patients with a prostate volume of > 50 cm3, a preoperative international prostate symptom score of > 15, a urine flow rate of < 15 ml/min, and urethral andrectal radiation doses of > 210 and > 180 Gy, respectively, tended to have more common radiation reactions. Thus, brachytherapy is a reasonably safe treatment for PC.

  6. Experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer

    Directory of Open Access Journals (Sweden)

    Gláucia Sousa Oliveira

    2014-04-01

    Full Text Available This is a study with the objective to know the experiences of the family caregiver of a person with intestinal ostomy due to colorectal cancer. A qualitative research, grounded on the humanization referential, made in 2013, through serialized semi-structured interviews and inductive analysis. It was approved by the Ethics and Research Committee under legal opinion no. 237,771. Seven family caregivers participated in this study in a county of southern Minas Gerais state, Brazil. Three categories emerged from the data: Relation with the disease and its treatments; Impact facing treatment and rehabilitation and Nets of support. The representation of the disease associated to finitude is reaffirmed. In order to lessen anguish and suffering, the family caregivers search support, mainly in spirituality. The impact resulting from the illness and the rehabilitation process imposes a new order to the caregivers, with personal and social renouncing, which provides a closer and more dedicated relation with the patient.

  7. Quantitative analysis of pulmonary functional damage due to heavy ion particle irradiation therapy for lung cancer

    International Nuclear Information System (INIS)

    Seventeen patients with clinical stage I lung cancer were given irradiation therapy with heavy ion radioactive rays at 73.1±11.2 GyE. Lung injury due to irradiation was evaluated by measuring routine parameters of pulmonary function. No statistically significant changes in these parameters were observed after irradiation, even in patients followed up for a period of 1 year. Chest X-ray examinations, including CT scan images, disclosed the development of nonsegmental consolidations in the irradiated areas, changing into minor fibrosis 1 year later. We concluded that heavy ion particle irradiation has minimal impact on pulmonary function, and is of therapeutic valve to elderly patients and patients with complications. (author)

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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+...

  13. The Effects of Zeolite X and Y on Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Noor Azhana Ghazi

    2012-07-01

    Full Text Available Zeolites are hydrated silicates of aluminium that have been very useful in many industry because of its microporous property, absorbance ability and ion exchange capacity. It is currently viewed as a potential adjuvant in cancer therapy due to its ability to inhibit the proliferation of cancer cells. Research on natural zeolite clinoptilolite application as anticancer agent has been proven by others. However, the effect of other types of zeolite on cancer cells is still uncertain. This study is performed to determine the effects of zeolite X and Y on cancer cell lines proliferation in vitro. Cancer cell lines HeLa, AsPC-1 and 911 cells were cultured in designated medium treated with zeolite X and zeolite Y at the concentration of 5 mg/ml and 50 mg/ml. Fetal Bovine Serum (FBS concentrations were modified to 5%, 10%, 15% and 20%. After 72 hours incubation, the efficacy of zeolite to treat cancer cell lines were measured by means of cell viability test via MTT assay. Overall results showed that cancer cell lines cultivated in the medium treated with 50 mg/ml of zeolite X and 5% FBS exhibited the highest inhibition of cell proliferation and decrease in cell viability. This finding provides preliminary information in the study of determining the potential use of zeolite as anticancer agent for alternative or complementary therapy.

  14. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    OpenAIRE

    Taylor David J; Parsons Christine E; Han Haiyong; Jayaraman Arul; Rege Kaushal

    2011-01-01

    Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, ...

  15. 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, ...

  16. 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 ...

  17. 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

  18. Increasing incidence of base of tongue cancers from 2000 to 2010 due to HPV

    DEFF Research Database (Denmark)

    Garnaes, E; Kiss, K; Andersen, L;

    2015-01-01

    BACKGROUND: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence. METHODS: We performed HPV DNA PCR and p16 immunohistochemistry analysis...... for all (n=210) BSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and the Danish Pathology Data Bank, and genotyped all HPV-positive specimens with amplicon-based next-generation sequencing. RESULTS: The overall crude incidence of BSCCs increased significantly significant increase...... in the number of HPV-positive BSCCs (8.1% per year), whereas the number of HPV-negative BSCCs did not increase significantly. The overall HPV prevalence was 51%, with HPV16 as the predominant HPV type.(5.4% per year) during the study period. This was explained by a CONCLUSIONS: The increased number of HPV...

  19. 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...

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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...

  6. Thyroid metastases in renal cell cancer: two case reports

    International Nuclear Information System (INIS)

    Non-thyroid cancers rarely metastasize to the thyroid gland. Metastases can be divided into those with clinical expression and those identified at necropsy. Symptom producing thyroid metastases are usually due to a primary renal cell cancer. We report two cases of thyroid metastasis of a clear cell renal carcinoma. In the first case, an 82-year-old woman presented with an enlarged thyroid metastasis and identification of recurrent renal cell carcinoma which had been treated by radiotherapy 24 years earlier. After radiotherapy for a concomitant pulmonary metastasis, the patient is in good general health with no signs of recurrence. In the second case, increased thyroid volume led to signs of compression in a 71-year-old-man. The pathology report after left lobular thyroidectomy suggested trabecular adenoma or metastasis of a clear-cell primary tumour. Abdominal CT-scan revealed a 3.5 cm tumour found to be a clear-cell renal carcinoma at nephrectomy. Another osteolytic metastasis to the femur was also observed three months after surgery. The patient is in good health 15 months after the initial diagnosis. The significance of thyroid metastasis of renal cell carcinoma would vary according to the different cases reported in the literature with survival ranging from 32 months to 3-7 years after surgical exeresis. Prognosis would thus not appear to be as poor as for thyroid metastasis from other primary tumours. (authors). 24 refs

  7. 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

  8. 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...

  9. 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.

  10. Overcoming cancer cell resistance to VSV oncolysis with JAK1/2 inhibitors

    OpenAIRE

    Escobar-Zarate, D; Liu, Y-P; Suksanpaisan, L; Russell, SJ; Peng, K-W

    2013-01-01

    Oncolytic vesicular stomatitis virus (VSV) has potent antitumor activity but some cancer cells are resistant to VSV killing, either constitutively or due to type I interferon (IFN) inducing an antiviral state in the cells. Here, we evaluated VSV oncolysis of a panel of human head and neck cancer cells and showed that VSV resistance in SCC25 and SCC15 cells could be reversed with Janus kinase (JAK) 1/2 inhibitors (JAK inhibitor I and ruxolitinib). Pre-treatment of cells with JAK1/2 inhibitors ...

  11. 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

  12. 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

  13. (-)-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...

  14. 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

  15. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, H

    2014-06-01

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

  16. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    International Nuclear Information System (INIS)

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging

  17. 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.

  18. 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.

  19. A New Biological Feature of Natural Killer Cells: The Recognition of Solid Tumor-Derived Cancer Stem Cells

    Science.gov (United States)

    Tallerico, Rossana; Garofalo, Cinzia; Carbone, Ennio

    2016-01-01

    Natural killer (NK) cells are classified as a member of the innate lymphoid cells (ILCs) group 1. ILCs have been recently identified and grouped on the basis of their phenotypical and functional characteristics. They are effectors of innate immunity and are involved in secondary lymphoid organ generation and tissue remodeling. NK cells are powerful cytotoxic lymphocytes able to recognize and eliminate tumor- and virus-infected cells by limiting their spread and tissue damage. The recognition of tumor cells is mediated by both activating and inhibitory receptors. While in hematological malignancies the role played by NK cells is widely known, their role in recognizing solid tumors remains unclear. Recently, tumor cell populations have been divided into two compartments: cancer-initiating cells (CICs) or cancer stem cells (CSCs) and senescent tumor cells. Here, CSC will be used. CSCs are a small subset of malignant cells with stem-like properties that are involved in tumor maintenance and recurrence due to their ability to survive to traditional therapies; they are, moreover, poorly recognized by T lymphocytes. Recent data showed that NK cells recognize in vitro cancer-initiating cells derived from colon cancer, glioblastoma, and melanoma. However, more in vivo studies are urgently required to fully understand whether these new antitumor NK cells with cytotoxic capability may be considered in the design of new immunotherapeutic interventions. PMID:27242786

  20. 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.

  1. 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.

  2. 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...

  3. 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...

  4. 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...

  5. 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)

  6. 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

  7. 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.

  8. CD133-positive cells are resistant to TRAIL due to up-regulation of FLIP

    Czech Academy of Sciences Publication Activity Database

    Zobalová, Renata; McDermott, L.; Stantic, M.; Prokopová, Kateřina; Dong, L.-F.; Neužil, Jiří

    2008-01-01

    Roč. 373, č. 4 (2008), s. 567-571. ISSN 0006-291X R&D Projects: GA AV ČR(CZ) IAA500520702 Institutional research plan: CEZ:AV0Z50520701 Keywords : Cancer stem cells * apoptosis * resistance to apoptosis induction Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.648, year: 2008

  9. 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...

  10. 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.

  11. 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...

  12. 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.

  13. Pancreatic cancer stem cell markers and exosomes - the incentive push.

    Science.gov (United States)

    Heiler, Sarah; Wang, Zhe; Zöller, Margot

    2016-07-14

    Pancreatic cancer (PaCa) has the highest death rate and incidence is increasing. Poor prognosis is due to late diagnosis and early metastatic spread, which is ascribed to a minor population of so called cancer stem cells (CSC) within the mass of the primary tumor. CSC are defined by biological features, which they share with adult stem cells like longevity, rare cell division, the capacity for self renewal, differentiation, drug resistance and the requirement for a niche. CSC can also be identified by sets of markers, which for pancreatic CSC (Pa-CSC) include CD44v6, c-Met, Tspan8, alpha6beta4, CXCR4, CD133, EpCAM and claudin7. The functional relevance of CSC markers is still disputed. We hypothesize that Pa-CSC markers play a decisive role in tumor progression. This is fostered by the location in glycolipid-enriched membrane domains, which function as signaling platform and support connectivity of the individual Pa-CSC markers. Outside-in signaling supports apoptosis resistance, stem cell gene expression and tumor suppressor gene repression as well as miRNA transcription and silencing. Pa-CSC markers also contribute to motility and invasiveness. By ligand binding host cells are triggered towards creating a milieu supporting Pa-CSC maintenance. Furthermore, CSC markers contribute to the generation, loading and delivery of exosomes, whereby CSC gain the capacity for a cell-cell contact independent crosstalk with the host and neighboring non-CSC. This allows Pa-CSC exosomes (TEX) to reprogram neighboring non-CSC towards epithelial mesenchymal transition and to stimulate host cells towards preparing a niche for metastasizing tumor cells. Finally, TEX communicate with the matrix to support tumor cell motility, invasion and homing. We will discuss the possibility that CSC markers are the initial trigger for these processes and what is the special contribution of CSC-TEX. PMID:27468191

  14. Pancreatic cancer stem cell markers and exosomes - the incentive push

    Science.gov (United States)

    Heiler, Sarah; Wang, Zhe; Zöller, Margot

    2016-01-01

    Pancreatic cancer (PaCa) has the highest death rate and incidence is increasing. Poor prognosis is due to late diagnosis and early metastatic spread, which is ascribed to a minor population of so called cancer stem cells (CSC) within the mass of the primary tumor. CSC are defined by biological features, which they share with adult stem cells like longevity, rare cell division, the capacity for self renewal, differentiation, drug resistance and the requirement for a niche. CSC can also be identified by sets of markers, which for pancreatic CSC (Pa-CSC) include CD44v6, c-Met, Tspan8, alpha6beta4, CXCR4, CD133, EpCAM and claudin7. The functional relevance of CSC markers is still disputed. We hypothesize that Pa-CSC markers play a decisive role in tumor progression. This is fostered by the location in glycolipid-enriched membrane domains, which function as signaling platform and support connectivity of the individual Pa-CSC markers. Outside-in signaling supports apoptosis resistance, stem cell gene expression and tumor suppressor gene repression as well as miRNA transcription and silencing. Pa-CSC markers also contribute to motility and invasiveness. By ligand binding host cells are triggered towards creating a milieu supporting Pa-CSC maintenance. Furthermore, CSC markers contribute to the generation, loading and delivery of exosomes, whereby CSC gain the capacity for a cell-cell contact independent crosstalk with the host and neighboring non-CSC. This allows Pa-CSC exosomes (TEX) to reprogram neighboring non-CSC towards epithelial mesenchymal transition and to stimulate host cells towards preparing a niche for metastasizing tumor cells. Finally, TEX communicate with the matrix to support tumor cell motility, invasion and homing. We will discuss the possibility that CSC markers are the initial trigger for these processes and what is the special contribution of CSC-TEX. PMID:27468191

  15. Gene mutation discovery research of non-smoking lung cancer patients due to indoor radon exposure

    OpenAIRE

    Choi, Jung Ran; Park, Seong Yong; Noh, O Kyu; Koh, Young Wha; Kang, Dae Ryong

    2016-01-01

    Although the incidence and mortality for most cancers such as lung and colon are decreasing in several countries, they are increasing in several developed countries because of an unhealthy western lifestyles including smoking, physical inactivity and consumption of calorie-dense food. The incidences for lung and colon cancers in a few of these countries have already exceeded those in the United States and other western countries. Among them, lung cancer is the main cause of cancer death in wo...

  16. Sudden hearing loss due to internal auditory canal metastasis of Her2-positive gastric cancer: A case report

    OpenAIRE

    Kim, Chang-Hee; Shin, Jung Eun; Roh, Hong Gee; LEE, JONG SIK; Yoon, So Young

    2014-01-01

    Internal auditory canal (IAC) metastasis due to leptomeningeal carcinomatosis (LMC) from gastric cancer (GC) has rarely been reported. Early manifestation of symptoms, such as hearing loss, vertigo and facial paralysis, in cases of IAC metastasis due to LMC may facilitate the early detection of brain metastasis. To the best of our knowledge, the present study is the first to report IAC metastasis due to LMC in human epidermal growth factor receptor 2 (Her2)-positive GC. This study reports a c...

  17. Diabetes, cancer, and metformin: connections of metabolism and cell proliferation.

    Science.gov (United States)

    Gallagher, Emily Jane; LeRoith, Derek

    2011-12-01

    Diabetes is associated with an increased risk of developing and dying from cancer. This increased risk may be due to hyperglycemia, hyperinsulinemia, and insulin resistance or other factors. Metformin has recently gained much attention as it appears to reduce cancer incidence and improve prognosis of patients with diabetes. In vitro data and animal studies support these findings from human epidemiological studies. Metformin has multiple potential mechanisms by which it inhibits cancer development and growth. For example, metaformin inhibits hepatic gluconeogenesis, thus decreasing circulating glucose levels, and it increases insulin sensitivity, thus reducing circulating insulin levels. Intracellularly, metformin activates AMPK, which decreases protein synthesis and cell proliferation. Metaformin also reduces aromatase activity in the stromal cells of the mammary gland. Finally, metformin may diminish the recurrence and aggressiveness of tumors by reducing the stem cell population and inhibiting epithelial to mesenchymal transition. Here, we discuss the metabolic abnormalities that occur in tumor development and some of the mechanisms through which metformin may alter these pathways and reduce tumor growth. PMID:22211893

  18. 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.

  19. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ulf Geisen

    2015-07-01

    Full Text Available Pancreatic cancer is one of the most aggressive cancer entities, with an extremely poor 5-year survival rate. Therefore, novel therapeutic agents with specific modes of action are urgently needed. Marine organisms represent a promising source to identify new pharmacologically active substances. Secondary metabolites derived from marine algae are of particular interest. The present work describes cellular and molecular mechanisms induced by an HPLC-fractionated, hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus (Fv1. Treatment with Fv1 resulted in a strong inhibition of viability in various pancreatic cancer cell lines. This extract inhibited the cell cycle of proliferating cells due to the up-regulation of cell cycle inhibitors, shown on the mRNA (microarray data and protein level. As a result, cells were dying in a caspase-independent manner. Experiments with non-dividing cells showed that proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1 showed low cytotoxic activity against non-malignant resting T cells and terminally differentiated cells like erythrocytes. Interestingly, accelerated killing effects were observed in combination with inhibitors of autophagy. Our in vitro data suggest that Fv1 may represent a promising new agent that deserves further development towards clinical application.

  20. 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...

  1. 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...

  2. 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

  3. 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

  4. Silencing of HMGA2 promotes apoptosis and inhibits migration and invasion of prostate cancer cells

    Indian Academy of Sciences (India)

    Zhan Shi; Ding Wu; Run Tang; Xiang Li; Renfu Chen; Song Xue; Chengjing Zhang; Xiaoqing Sun

    2016-06-01

    The high mobility group protein A2 (HMGA2) has been demonstrated as an architectural transcription factor that is associated with pathogenesis of many malignant cancers, however, its role in prostate cancer cells remains largely unknown. To explore whether HMGA2 participates in the development and progression of prostate cancer, small interfering RNA (siRNA) targeted on human HMGA2 was transfected to suppress the HMGA2 expression in prostate cancer PC3 and DU145 cells, and then we examined the cellular biology changes after decreased the expression of HMGA2. Our results showed that knockdown of HMGA2 markedly inhibited cell proliferation, this reduced cell proliferation was due to the promotion of cell apoptosis as the Bcl-xl was decreased, whereas Bax was up-regulated. In addition, we found that HMGA2 knockdown resulted in reduction of cell migration and invasion, as well as repressed the expression of matrix metalloproteinases (MMPs) and affected the occurrence of epithelial-mesenchymal transition (EMT) in both cell types. We further found that decreased HMGA2 expression inhibited the transforming growth factor-β (TGF-β)/Smad signaling pathway in cancer cells. In conclusion, our data indicated that HMGA2 was associated with apoptosis, migration and invasion of prostate cancer, which might be a promising therapeutic target for prostate cancer.

  5. 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.

  6. Mesenchymal stromal cells from female donors enhance breast cancer cell proliferation in vitro.

    Science.gov (United States)

    Pasanen, Ilkka; Pietilä, Mika; Lehtonen, Siri; Lehtilahti, Elisa; Hakkarainen, Tanja; Blanco Sequeiros, Roberto; Lehenkari, Petri; Kuvaja, Paula

    2015-01-01

    The interplay between tumor stroma and breast cancer cells (BCCs) is thought to play a significant role in breast cancer. The current knowledge of human mesenchymal stromal cell (MSC) and BCC interaction is contradictory, and the donor sex issue is not addressed at all. We hypothesized that donor sex could have an effect on proliferation of MSCs or BCCs in co-culture in vitro. Three estrogen receptor-negative BCC lines, 19 primary human MSCs and breast tissue-derived fibroblasts from 4 donors were used. MSCs from female donors enhanced BCC proliferation (p = 0.005). The change in BCC proliferation was only partly due to soluble factors excreted by MSCs. The highly aggressive BCC line MDA-MB- 231 induced the proliferation of MSCs (p < 0.001) and fibroblasts (p = 0.037) in co-culture experiments. The magnitude in proliferation change was cell line dependent and partly sex dependent. PMID:25502907

  7. 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

  8. Gas generation mechanism due to electrolyte decomposition in commercial lithium-ion cell

    Science.gov (United States)

    Kumai, Kazuma; Miyashiro, Hajime; Kobayashi, Yo; Takei, Katsuhito; Ishikawa, Rikio

    To elucidate the gas generation mechanism due to electrolyte decomposition in commercial lithium-ion cells after long cycling, we developed a device which can accurately determine the volume of generated gas in the cell. Experiments on Li xC 6/Li 1- xCoO 2 cells using electrolytes such as 1 M LiPF 6 in propylene carbonate (PC), dimethyl carbonate (DMC), ethyl methyl carbonate (EMC), and diethyl carbonate (DEC) are presented and discussed. In the nominal voltage range (4.2-2.5 V), compositional change due mainly to ester exchange reaction occurs, and gaseous products in the cell are little. Generated gas volume and compositional change in the electrolyte are detected largely in overcharged cells, and we discussed that gas generation due to electrolyte decomposition involves different decomposition reactions in overcharged and overdischarged cells.

  9. 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

  10. 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...

  11. 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...

  12. 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...

  13. 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.

  14. 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...

  15. 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.

  16. 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

  17. 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...

  18. 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.

  19. Natural and induced T regulatory cells in cancer.

    Science.gov (United States)

    Adeegbe, Dennis O; Nishikawa, Hiroyoshi

    2013-01-01

    CD4+Foxp3+ T regulatory (Treg) cells control many facets of immune responses ranging from autoimmune diseases, to inflammatory conditions, and cancer in an attempt to maintain immune homeostasis. Natural Treg (nTreg) cells develop in the thymus and constitute a critical arm of active mechanisms of peripheral tolerance particularly to self antigens. A growing body of knowledge now supports the existence of induced Treg (iTreg) cells which may derive from a population of conventional CD4+ T cells. The fork-head transcription factor (Foxp3) typically is expressed by natural CD4+ Treg cells, and thus serves as a marker to definitively identify these cells. On the contrary, there is less consensus on what constitutes iTreg cells as their precise definition has been somewhat elusive. This is in part due to their distinct phenotypes which are shaped by exposure to certain inflammatory or "assault" signals stemming from the underlying immune disorder. The "policing" activity of Treg cells tends to be uni-directional in several pathological conditions. On one end of the spectrum, Treg cell suppressive activity is beneficial by curtailing T cell response against self-antigens and allergens thus preventing autoimmune diseases and allergies. On the other end however, their inhibitory roles in limiting immune response against pseudo-self antigens as in tumors often culminates into negative outcomes. In this review, we focus on this latter aspect of Treg cell immunobiology by highlighting the involvement of nTreg cells in various animal models and human tumors. We further discuss iTreg cells, relationship with their natural counterpart, and potential co-operation between the two in modulating immune response against tumors. Lastly, we discuss studies focusing on these cells as targets for improving anti-tumor immunity. PMID:23874336

  20. 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

  1. Involvement of epigenetic modifiers in the pathogenesis of testicular dysgenesis and germ cell cancer

    DEFF Research Database (Denmark)

    Lawaetz, Andreas C.; Almstrup, Kristian

    2015-01-01

    cell is a fetal germ cell that has been arrested during development due to testicular dysgenesis. CIS cells retain a fetal and open chromatin structure, and recently several epigenetic modifiers have been suggested to be involved in testicular dysgenesis in mice. We here review the possible involvement...... of epigenetic modifiers with a focus on jumonji C enzymes in the development of testicular dysgenesis and germ cell cancer in men....

  2. Monitoring of changes in lipid profiles during PLK1 knockdown in cancer cells using DESI MS.

    Science.gov (United States)

    Jayashree, Balasubramanyam; Srimany, Amitava; Jayaraman, Srinidhi; Bhutra, Anjali; Janakiraman, Narayanan; Chitipothu, Srujana; Krishnakumar, Subramanian; Baddireddi, Lakshmi Subhadra; Elchuri, Sailaja; Pradeep, Thalappil

    2016-08-01

    The importance of the polo-like kinase 1 (PLK1) gene is increasing substantially both as a biomarker and as a target for highly specific cancer therapy. This is due to its involvement in multiple points of cell progression and carcinogenesis. PLK1 inhibitors' efficacy in treating human cancers has been limited due to the lack of a specific targeting strategy. Here, we describe a method of targeted downregulation of PLK1 in cancer cells and the concomitant rapid detection of surface lipidomic perturbations using desorption electrospray ionization mass spectrometry (DESI MS). The efficient delivery of siRNA targeting PLK1 gene selectively to the cancer cells is achieved by targeting overexpressed cell surface epithelial cell adhesion molecule (EpCAM) by the EpDT3 aptamer. The chimeric aptamer (EpDT3-siPLK1) showed the knockdown of PLK1 gene expression and PLK1 protein levels by quantitative PCR and western blotting, respectively. The abundant surface lipids, phosphatidylcholines (PCs), such as PC(32:1) (m/z 754.6), PC(34:1) (m/z 782.6), and PC(36:2) (m/z 808.6), were highly expressed in MCF-7 and WERI-RB1 cancer cells compared to normal MIO-M1 cells and they were observed using DESI MS. These overexpressed cell surface lipids in the cancer cells were downregulated upon the treatment of EpDT3-siPLK1 chimera indicating a novel role of PLK1 to regulate surface lipid expression in addition to the efficient selective cancer targeting ability. Our results indicate that DESI MS has a potential ability to rapidly monitor aptamer-mediated cancer therapy and accelerate the drug discovery process. Graphical abstract Binding of aptamer chimera to the cells and changes in lipid profile. PMID:27277815

  3. Clinical experience of Sheriproct suppository to rectitis due to radiotherapy of cancer of the uterine cervix

    International Nuclear Information System (INIS)

    The subject was 30 cases of cancer of the uterine cervix, which were composed of 13 cases of acute rectitis and 17 cases of delayed rectitis due to radiotherapy. Out of them, 25 cases were treated with radiation, alone and 5 cases were treated with postoperative irradiation. The acute cases were administered Sheriproct alone twice a day (in the morning and in the evening) until symptoms disappeared. The delayed cases were administered two or three suppositories per a day together with antihemorrhagics for one to three weeks, decreasing the administration dose according to severity of symptoms. In the delayed cases, this suppository showed effectiveness in prolapsed hemorrhoids with a recovery rate of 88.9%, and it showed effectiveness in a pain with that of 71.4%. However, this depository showed ineffectiveness in hemorrhage, inhibition of mucous stool, and inhibition of secrete, and these symptoms were generally resistant to this suppository. On the other hand, in the acute cases, this suppository showed ineffectiveness only in prolapsed hemorrhoids with a recovery rate of 63.3%, and it showed marked effectiveness in hemorrhage with that of 100%. It also showed effectiveness in a pain, inhibition of mucose stool, and inhibition of secrete. These symptoms responded well to this suppository. Consequently, use of this drug seemed to be significant in making it possible to perform radiotherapy. (Kanao, N.)

  4. Difference of cell cycle arrests induced by lidamycin in human breast cancer cells.

    Science.gov (United States)

    Liu, Xia; He, Hongwei; Feng, Yun; Zhang, Min; Ren, Kaihuan; Shao, Rongguang

    2006-02-01

    Lidamycin (LDM) is a member of the enediyne antibiotic family. It is undergoing phase I clinical trials in China as a potential chemotherapeutic agent. In the present study, we investigated the mechanism by which LDM induced cell cycle arrest in human breast cancer cells. The results showed that LDM induced G1 arrest in p53 wild-type MCF-7 cells at low concentrations, and caused both G1 and G2/M arrests at higher concentrations. In contrast, LDM induced only G2/M arrest in p53-mutant MCF-7/DOX cells. Western blotting analysis indicated that LDM-induced G1 and G2/M arrests in MCF-7 cells were associated with an increase of p53 and p21, and a decrease of phosphorylated retinoblastoma tumor suppressor protein, cyclin-dependent kinase (Cdk), Cdc2 and cyclin B1 protein levels. However, LDM-induced G2/M arrest in MCF-7/DOX cells was correlated with the reduction of cyclin B1 expression. Further study indicated that the downregulation of cyclin B1 by LDM in MCF-7 cells was associated with decreasing cyclin B1 mRNA levels and promoting protein degradation, whereas it was only due to inducing cyclin B1 protein degradation in MCF-7/DOX cells. In addition, activation of checkpoint kinases Chk1 or Chk2 maybe contributed to LDM-induced cell cycle arrest. Taken together, we provide the first evidence that LDM induces different cell cycle arrests in human breast cancer cells, which are dependent on drug concentration and p53 status. These findings are helpful in understanding the molecular anti-cancer mechanisms of LDM and support its clinical trials. PMID:16428935

  5. 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...

  6. CCL21 Facilitates Chemoresistance and Cancer Stem Cell-Like Properties of Colorectal Cancer Cells through AKT/GSK-3β/Snail Signals

    Directory of Open Access Journals (Sweden)

    Lin-Lin Lu

    2016-01-01

    Full Text Available Some evidence indicated that chemoresistance associates with the acquisition of cancer stem-like properties. Recent studies suggested that chemokines can promote the chemoresistance and stem cell properties in various cancer cells, while the underling mechanism is still not completely illustrated. In our study, we found that CCL21 can upregulate the expression of P-glycoprotein (P-gp and stem cell property markers such as Bmi-1, Nanog, and OCT-4 in colorectal cancer (CRC HCT116 cells and then improve the cell survival rate and mammosphere formation. Our results suggested that Snail was crucial for CCL21-mediated chemoresistance and cancer stem cell property in CRC cells. Further, we observed that CCL21 treatment increased the protein but not mRNA levels of Snail, which suggested that CCL21 upregulates Snail via posttranscriptional ways. The downstream signals AKT/GSK-3β mediated CCL21 induced the upregulation of Snail due to the fact that CCL21 treatment can obviously phosphorylate both AKT and GSK-3β. The inhibitor of PI3K/Akt, LY294002 significantly abolished CCL21 induced chemoresistance and mammosphere formation of HCT116 cells. Collectively, our results in the present study revealed that CCL21 can facilitate chemoresistance and stem cell property of CRC cells via the upregulation of P-gp, Bmi-1, Nanog, and OCT-4 through AKT/GSK-3β/Snail signals, which suggested a potential therapeutic approach to CRC patients.

  7. CCL21 Facilitates Chemoresistance and Cancer Stem Cell-Like Properties of Colorectal Cancer Cells through AKT/GSK-3β/Snail Signals.

    Science.gov (United States)

    Lu, Lin-Lin; Chen, Xiao-Hui; Zhang, Ge; Liu, Zong-Cai; Wu, Nong; Wang, Hao; Qi, Yi-Fei; Wang, Hong-Sheng; Cai, Shao Hui; Du, Jun

    2016-01-01

    Some evidence indicated that chemoresistance associates with the acquisition of cancer stem-like properties. Recent studies suggested that chemokines can promote the chemoresistance and stem cell properties in various cancer cells, while the underling mechanism is still not completely illustrated. In our study, we found that CCL21 can upregulate the expression of P-glycoprotein (P-gp) and stem cell property markers such as Bmi-1, Nanog, and OCT-4 in colorectal cancer (CRC) HCT116 cells and then improve the cell survival rate and mammosphere formation. Our results suggested that Snail was crucial for CCL21-mediated chemoresistance and cancer stem cell property in CRC cells. Further, we observed that CCL21 treatment increased the protein but not mRNA levels of Snail, which suggested that CCL21 upregulates Snail via posttranscriptional ways. The downstream signals AKT/GSK-3β mediated CCL21 induced the upregulation of Snail due to the fact that CCL21 treatment can obviously phosphorylate both AKT and GSK-3β. The inhibitor of PI3K/Akt, LY294002 significantly abolished CCL21 induced chemoresistance and mammosphere formation of HCT116 cells. Collectively, our results in the present study revealed that CCL21 can facilitate chemoresistance and stem cell property of CRC cells via the upregulation of P-gp, Bmi-1, Nanog, and OCT-4 through AKT/GSK-3β/Snail signals, which suggested a potential therapeutic approach to CRC patients. PMID:27057280

  8. G9a is essential for EMT-mediated metastasis and maintenance of cancer stem cell-like characters in head and neck squamous cell carcinoma

    OpenAIRE

    Shuli LIU; Ye, Dongxia; Guo, Wenzheng; Yu, Wenwen; He, Yue; Hu, Jingzhou; Wang, Yanan; Zhang, Ling; Liao, Yueling; Song, Hongyong; Zhong, Shuangshuang; Xu, Dongliang; Yin, Huijing; Sun, Beibei; Wang, Xiaofei

    2015-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates wi...

  9. 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.

  10. 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

  11. SSX2-4 expression in early-stage non-small cell lung cancer

    DEFF Research Database (Denmark)

    Greve, K B V; Pøhl, M; Olsen, K E; Nielsen, O; Ditzel, H J; Gjerstorff, M F

    2014-01-01

    The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies......-4 expression was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC....

  12. Identification of Distinct Breast Cancer Stem Cell Populations Based on Single-Cell Analyses of Functionally Enriched Stem and Progenitor Pools

    Directory of Open Access Journals (Sweden)

    Nina Akrap

    2016-01-01

    Full Text Available The identification of breast cancer cell subpopulations featuring truly malignant stem cell qualities is a challenge due to the complexity of the disease and lack of general markers. By combining extensive single-cell gene expression profiling with three functional strategies for cancer stem cell enrichment including anchorage-independent culture, hypoxia, and analyses of low-proliferative, label-retaining cells derived from mammospheres, we identified distinct stem cell clusters in breast cancer. Estrogen receptor (ERα+ tumors featured a clear hierarchical organization with switch-like and gradual transitions between different clusters, illustrating how breast cancer cells transfer between discrete differentiation states in a sequential manner. ERα− breast cancer showed less prominent clustering but shared a quiescent cancer stem cell pool with ERα+ cancer. The cellular organization model was supported by single-cell data from primary tumors. The findings allow us to understand the organization of breast cancers at the single-cell level, thereby permitting better identification and targeting of cancer stem cells.

  13. 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.

  14. 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...

  15. 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...

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Convective cell formation and anomalous diffusion due to electromagnetic drift wave turbulence

    International Nuclear Information System (INIS)

    Convective cell formation and spectral cascade processes due to gravitational drift Alfven waves are studied using a new type of model equation. Conservation relations are derived and explosive instability is found for systems near marginal finite β stability. This instability also remains when the effects of poor as well as favorable curvature regions are included, i.e., for ballooning modes. The anomalous diffusion due to convective cells and quasi-linear effects are compared

  1. Determination of Invisible Environmental Pollution Due to Cell Phones EMF Radiation and projections for 2030

    OpenAIRE

    K Parandham Gowd; Gupta, R P; Sangeeta Jauhari

    2013-01-01

    In the last decades cell phones usage have altered the land scape of modern human beings in countless ways, in office, at home and on mobility. However, created the environmental electronic pollution due to electromagnetic fields. In spite of the recent studies indicating possible harmful impact of EMF pollution on several species, there is no long term data available on the environmental impacts of EMF pollution and how much power density is radiated in the environment due to cell phones. T...

  2. 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...

  3. 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...

  4. Screen-detected vs symptomatic breast cancer: is improved survival due to stage migration alone?

    OpenAIRE

    Wishart, G. C.; Greenberg, D. C.; Britton, P D; Chou, P; Brown, C.H.; Purushotham, A. D.; Duffy, S W

    2008-01-01

    This paper examines whether screen-detected breast cancer confers additional prognostic benefit to the patient, over and above that expected by any shift in stage at presentation. In all, 5604 women (aged 50–70 years) diagnosed with invasive breast cancer between 1998 and 2003 were identified by the Eastern Cancer Registration and Information Centre (ECRIC) and mammographic screening status was determined. Using proportional hazards regression, we estimated the effect of screen detection comp...

  5. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    OpenAIRE

    Ali Murat Tatlı; Seyda Gunduz; Sema Sezgin Göksu; Deniz Arslan; Mukremin Uysal; Cumhur İbrahim Başsorgun; Hasan Şenol Coşkun

    2013-01-01

    Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we ...

  6. 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

  7. Ovarian Cancer Cell Adhesion/Migration Dynamics on Micro-Structured Laminin Gradients Fabricated by Multiphoton Excited Photochemistry

    OpenAIRE

    Ruei-Yu He; Visar Ajeti; Shean-Jen Chen; Brewer, Molly A; Campagnola, Paul J.

    2015-01-01

    Haptotaxis, i.e., cell migration in response to adhesive gradients, has been previously implicated in cancer metastasis. A better understanding of cell migration dynamics and their regulation could ultimately lead to new drug targets, especially for cancers with poor prognoses, such as ovarian cancer. Haptotaxis has not been well-studied due to the lack of biomimetic, biocompatible models, where, for example, microcontact printing and microfluidics approaches are primarily limited to 2D surfa...

  8. Lineage relationship of prostate cancer cell types based on gene expression

    Directory of Open Access Journals (Sweden)

    Ware Carol B

    2011-05-01

    Full Text Available Abstract Background Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells. Methods Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology and pattern 4 (aglandular sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype and LuCaP 49 (neuroendocrine/small cell carcinoma grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts. Results Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness. Conclusions Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

  9. 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...

  10. 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...

  11. Myc Is a Metastasis Gene for Non-Small-Cell Lung Cancer

    OpenAIRE

    Rapp, U R; Korn, C.; Ceteci, F.; Karreman, C; Luetkenhaus, K.; Serafin, V; Zanucco, E.; Castro, I.; Potapenko, T.

    2009-01-01

    Background Metastasis is a process by which cancer cells learn to form satellite tumors in distant organs and represents the principle cause of death of patients with solid tumors. NSCLC is the most lethal human cancer due to its high rate of metastasis. Methodology/Principal Findings Lack of a suitable animal model has so far hampered analysis of metastatic progression. We have examined c-MYC for its ability to induce metastasis in a C-RAF-driven mouse model for non-small-cell lung cancer. c...

  12. 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

  13. Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining

    International Nuclear Information System (INIS)

    non-transformed prostate epithelial cells using fluorescent glucose or lipid uptake kinetics. However, metastatic prostate cancer cells in plasma could be clearly distinguished from blood nucleated cells due to the presence of intracellular lipid bodies. Fluorescent labeling of lipid bodies permitted a simple and sensitive means for high throughput detection of metastatic prostate cancer cells in human plasma

  14. 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

  15. 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.

  16. 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.

  17. 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 ...

  18. 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...

  19. 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...

  20. 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...

  1. 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.

  2. Augmented delivery of gemcitabine in lung cancer cells exploring mannose anchored solid lipid nanoparticles.

    Science.gov (United States)

    Soni, Namrata; Soni, Neetu; Pandey, Himanshu; Maheshwari, Rahul; Kesharwani, Prashant; Tekade, Rakesh Kumar

    2016-11-01

    Gemcitabine (GmcH) is an effective anti-cancer agent used in the chemotherapy of lung cancer. However, the clinical applications of GmcH has been impeded primarily due to its low blood residence time, unfavorable pharmacokinetic and pharmacodynamic (PK/PD) profile, and poor penetration in the complex environment of lung cancer cells. Thus, the present study aims to formulate GmcH loaded mannosylated solid lipid nanoparticles (GmcH-SLNs) for improving its drug uptake into the lung cancer cells. GmcH-SLNs were prepared by emulsification and solvent evaporation process, and surface modification was done with mannose using ring opening technique. The cellular toxicity and cell uptake studies were performed in A549 lung adenocarcinoma cell line. The developed nanoformulation appears to be proficient in targeted delivery of GmcH with improved therapeutic effectiveness and enhanced safety. PMID:27459173

  3. Atypical presentation of primary renal squamous cell cancer: a case report

    Directory of Open Access Journals (Sweden)

    Mrinal Pahwa

    2014-02-01

    Full Text Available Renal squamous cell cancer is one of the rare primary urothelial tumors with only a handful of cases reported in literature. Because of high grade, advanced and late presentation, they herald a grave prognosis. They are frequently associated with calculus disease, smoking, phenacetin consumption and foci of squamous metaplasia due to chronic irritation. Nephroureterectomy is the treatment of choice for such tumors. We hereby present a case of 59 year old female who presented with squamous cell cancer of renal pelvis. The case presented here is different from what has already been reported in literature, as the patient had no antecedent risk factors for renal squamous cell carcinoma.-------------------------------------------------Cite this article as: Pahwa M, Pahwa AR, Girotra M, Chawla A. Atypical presentation of primary renal squamous cell cancer: a case report. Int J Cancer Ther Oncol 2014; 2(1:02015.DOI: http://dx.doi.org/10.14319/ijcto.0201.5

  4. Medical treatment of advanced non-small cell lung cancer: progress in 2014

    Directory of Open Access Journals (Sweden)

    Yong SONG

    2015-04-01

    Full Text Available Non-small cell lung cancer is the most common pathological type of lung cancer. Along with the rising incidence in recent years, lung cancer has been the leading cause of death due to malignancies both in our country and worldwide. Due to simplistic therapeutic approach for lung cancer decades ago, those patients suffering from advanced lung cancer had short lifetime, and it was difficult to ensure their life quality. In recent years, many molecular targeted drugs, such as Gefitinib, Erlotinib and Crizotinib etc., have been successively applied in clinical use, and they bring about a substantial prolongation of survival life and improvement in life quality of those patients with advanced lung cancer. In 2014, there was a number of important reports concerning the diagnosis and treatment of non-small cell lung cancer in the annual meetings of either American Society of Clinical Oncology or European Society for Medical Oncology. On the basis of the relevant reports delivered in the conferences, it is our attempt to summarize the recent advances in regard to chemotherapy, molecular targeted therapy, measures to treat TKI therapy resistant cases, and immune therapy, followed by a comment regarding recent advances in the treatment of non-small cell lung cancer in 2014. DOI: 10.11855/j.issn.0577-7402.2015.01.03

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. A Case of Congenital Hypothyroidism Due to Organification Defect Associated wth Huerthle Cell Adenoma

    International Nuclear Information System (INIS)

    Congenital hypothyroidism due to organification defect was first reported by Haddad and Sidbury in 1959. The organification defect is easily proved by perchlorate discharge test. We experienced a patient who had large goiter, growth and mental retardation, and revealed positive response to perchlorate discharges test, and the surgical biopsied specimen showed Huerthle cell adenoma, which was probably due to chronic stimulation of thyroid stimulating hormone, or coexisted incidentally. Described here a case of congenital hypothyroidism due to organification defect associated with Huerthle cell adenoma, with review of some literatures.

  11. Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation.

    Science.gov (United States)

    Sellers, Katherine; Fox, Matthew P; Bousamra, Michael; Slone, Stephen P; Higashi, Richard M; Miller, Donald M; Wang, Yali; Yan, Jun; Yuneva, Mariia O; Deshpande, Rahul; Lane, Andrew N; Fan, Teresa W-M

    2015-02-01

    Anabolic biosynthesis requires precursors supplied by the Krebs cycle, which in turn requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the activity of pyruvate carboxylase (PC) and glutaminase 1 (GLS1), respectively. Due to their rapid proliferation, cancer cells have increased anabolic and energy demands; however, different cancer cell types exhibit differential requirements for PC- and GLS-mediated pathways for anaplerosis and cell proliferation. Here, we infused patients with early-stage non-small-cell lung cancer (NSCLC) with uniformly 13C-labeled glucose before tissue resection and determined that the cancerous tissues in these patients had enhanced PC activity. Freshly resected paired lung tissue slices cultured in 13C6-glucose or 13C5,15N2-glutamine tracers confirmed selective activation of PC over GLS in NSCLC. Compared with noncancerous tissues, PC expression was greatly enhanced in cancerous tissues, whereas GLS1 expression showed no trend. Moreover, immunohistochemical analysis of paired lung tissues showed PC overexpression in cancer cells rather than in stromal cells of tumor tissues. PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model. Growth inhibition was accompanied by perturbed Krebs cycle activity, inhibition of lipid and nucleotide biosynthesis, and altered glutathione homeostasis. These findings indicate that PC-mediated anaplerosis in early-stage NSCLC is required for tumor survival and proliferation. PMID:25607840

  12. Aminomethylphosphonic Acid and Methoxyacetic Acid Induce Apoptosis in Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Keshab R. Parajuli

    2015-05-01

    Full Text Available Aminomethylphosphonic acid (AMPA and its parent compound herbicide glyphosate are analogs to glycine, which have been reported to inhibit proliferation and promote apoptosis of cancer cells, but not normal cells. Methoxyacetic acid (MAA is the active metabolite of ester phthalates widely used in industry as gelling, viscosity and stabilizer; its exposure is associated with developmental and reproductive toxicities in both rodents and humans. MAA has been reported to suppress prostate cancer cell growth by inducing growth arrest and apoptosis. However, it is unknown whether AMPA and MAA can inhibit cancer cell growth. In this study, we found that AMPA and MAA inhibited cell growth in prostate cancer cell lines (LNCaP, C4-2B, PC-3 and DU-145 through induction of apoptosis and cell cycle arrest at the G1 phase. Importantly, the AMPA-induced apoptosis was potentiated with the addition of MAA, which was due to downregulation of the anti-apoptotic gene baculoviral inhibitor of apoptosis protein repeat containing 2 (BIRC2, leading to activation of caspases 7 and 3. These results demonstrate that the combination of AMPA and MAA can promote the apoptosis of prostate cancer cells, suggesting that they can be used as potential therapeutic drugs in the treatment of prostate cancer.

  13. Degradation of solar cell electric performance due to arcing in LEO plasma environment

    OpenAIRE

    Okumura, Teppei; Hosoda, Satoshi; Kagawa, Hideshi; 奥村 哲平; 細田 聡史; Kim, Jeongho; Cho, Mengu; 香河 英史

    2005-01-01

    When we operate solar array at high voltage (greater than 100 V) in LEO environment, arcing occurs on the solar array surface. The solar cell can suffer degradation of electric performance due to only one arc with some probability. We performed degradation test of solar array coupons against arcing under simulated LEO environment in order to identify the threshold of arc energy to cause the solar cell degradation. The solar array coupons are made of silicon solar cells. The LCR circuit was at...

  14. Isolation and characterization of circulating tumor cells in prostate cancer

    Directory of Open Access Journals (Sweden)

    Elan Shlomo Diamond

    2012-10-01

    Full Text Available Circulating tumor cells (CTCs are tumor cells found in the peripheral blood that originate from established sites of malignancy and likely have metastatic potential. Analysis of circulating tumor cells CTCs has shown great promise as a prognostic marker as well as a potential source of novel therapeutics. Isolation and characterization these cells for study, however, remain challenging due to their rarity in comparison with other cellular components of peripheral blood. Several techniques that exploit the unique biochemical properties of CTCs have been developed to facilitate isolation of these cells. Positive selection of CTCs is achieved using microfluidic surfaces coated with antibodies against epithelial cell markers or tumor specific antigens such as EpCAM or prostate specific membrane antigen (PSMA. Following isolation, characterization of CTCs may help guide clinical decision-making. For instance, molecular and genetic characterization may shed light on the development of chemotherapy resistance and mechanisms of metastasis without the need for tissue biopsy. This paper will review novel isolation techniques to capture CTCs from patients with advanced cancers, as well as efforts to characterize the CTCs. We will also review ways in which these analyses can assist in clinical decision-making,Conclusion: The study of CTCs provides insight into the molecular biology of their tumors of origin that will eventually guide the development tailored therapeutics. These advances are predicated on high yield and accurate isolation techniques that exploit the unique biochemical features of these cells.

  15. The Role of Cancer Stem Cells in the Organ Tropism of Breast Cancer Metastasis: A Mechanistic Balance between the Seed and the Soil?

    International Nuclear Information System (INIS)

    Breast cancer is a prevalent disease worldwide, and the majority of deaths occur due to metastatic disease. Clinical studies have identified a specific pattern for the metastatic spread of breast cancer, termed organ tropism; where preferential secondary sites include lymph node, bone, brain, lung, and liver. A rare subpopulation of tumor cells, the cancer stem cells (CSCs), has been hypothesized to be responsible for metastatic disease and therapy resistance. Current treatments are highly ineffective against metastatic breast cancer, likely due to the innate therapy resistance of CSCs and the complex interactions that occur between cancer cells and their metastatic micro environments. A better understanding of these interactions is essential for the development of novel therapeutic targets for metastatic disease. This paper summarizes the characteristics of breast CSCs and their potential metastatic micro environments. Furthermore, it raises the question of the existence of a CSC niche and highlights areas for future investigation.

  16. 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

  17. HPV genotype distribution in older Danish women undergoing surgery due to cervical cancer

    DEFF Research Database (Denmark)

    Hammer, Anne; Mejlgaard, Else; Gravitt, Patti;

    2015-01-01

    INTRODUCTION: The prevalence of human papillomavirus (HPV)16/18 in cervical cancer may decrease with age. This study aimed to describe the HPV genotype distribution in Danish women aged 55 years or older with cervical cancer. MATERIAL AND METHODS: In this cross-sectional study we identified 153...... cases of cervical cancer diagnosed at Aarhus University Hospital, Denmark (1990-2012) and Copenhagen University Hospital Herlev, Denmark (2007-2012). All women had surgery to treat the disease. HPV genotyping was performed on cervical cancer tissue using the INNO LiPA HPV genotyping extra (Fujirebio......, Belgium) at the Department of Pathology, Aarhus University Hospital, Denmark. The main outcome was to estimate the age-specific prevalence of high-risk HPV genotypes included in the bivalent, the quadrivalent, and the nonavalent vaccine. RESULTS: Of 121 cases of cervical cancer included in this study, 113...

  18. 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...

  19. 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...

  20. 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...