Sample records for cancer cells due

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

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    Mucahit Gur


    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.

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

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    Koeffler Phillip


    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions 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.

  3. Heterogeneity between triple negative breast cancer cells due to differential activation of Wnt and PI3K/AKT pathways. (United States)

    Martínez-Revollar, Gabriela; Garay, Erika; Martin-Tapia, Dolores; Nava, Porfirio; Huerta, Miriam; Lopez-Bayghen, Esther; Meraz-Cruz, Noemí; Segovia, José; González-Mariscal, Lorenza


    The lack of a successful treatment for triple-negative breast cancer demands the study of the heterogeneity of cells that constitute these tumors. With this aim, two clones from triple negative breast MDA-MB-231 cancer cells were isolated: One with fibroblast-like appearance (F) and another with semi-epithelial (SE) morphology. Cells of the F clone have a higher migration and tumorigenesis capacity than SE cells, suggesting that these cells are in a more advanced stage of epithelial to mesenchymal transformation. In agreement, F cells have a diminished expression of the tight junction proteins claudins 1 and 4, and an increased content of β-catenin. The latter is due to an augmented activity of the canonical Wnt route and of the EGFR/PI3K/mTORC2/AKT pathway favoring the cytoplasmic accumulation of β-catenin and its transcriptional activity. In addition, F cells display increased phosphorylation of β-catenin at Tyr654 by Src. These changes favor in F cells, the over-expression of Snail that promotes EMT. Finally, we observe that both F and SE cells display markers of cancer stem cells, which are more abundant in the F clone.

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

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    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. Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2. (United States)

    Biernacka, K M; Uzoh, C C; Zeng, L; Persad, R A; Bahl, A; Gillatt, D; Perks, C M; Holly, J M P


    Clinically relevant prostate cancer (PCa) is more frequent in Westernised societies and increasingly men have co-morbidities associated with a Western lifestyle, primarily diabetes, characterised by hyperinsulinaemia and hyperglycaemia. IGFs and their binding proteins (IGFBPs) are important mediators of the effects of nutrition on growth and play a key role in the development of PCa. We used DU145, PC3 and LNCaP PCa cell lines to examine how hyperglycaemia altered their response to docetaxel. Trypan Blue dye-exclusion assay was used to determine the percentage of cell death. Protein abundance was determined using western immunoblotting. Levels of IGFBP2 were measured using an ELISA. IGFBP2 gene silencing was achieved using siRNA technology. DNA methylation was assessed using combined bisulphide restriction analysis. Acetylation status of histones H3 and H4 associated with IGFBP2 gene was assessed using chromatin immunoprecipitation assay. Hyperglycaemia reduced docetaxel-induced apoptosis by 40% for DU145 cells and by 88% for LNCaP cells. This reduced cell death was mediated by a glucose-induced up-regulation of IGFBP2, as silencing IGFBP2 negated the survival effect of high glucose. Glucose increased IGFBP2 via increasing the acetylation of histones associated with the IGFBP2 gene promoter. This finding could have important implications in relation to therapeutic strategies as epigenetic modulation could be reversible.

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

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    Barbetakis Nikolaos


    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.

  7. An autopsy case of subacute cor pulmonale due to pulmonary tumor cell emboli in a patient with gastric cancer. (United States)

    Iwakami, Shin-ichiro; Sato, Teruhiko; Takagi, Haruhi; Fujii, Mitsuhiro; Iwakami, Naoko; Yoshimi, Kaku; Koyama, Ryo; Ichikawa, Masako; Yoshioka, Masakata; Takahashi, Kazuhisa


    A 53-year-old woman was admitted to our hospital due to a severe respiratory condition and malnutrition. Radiological and electrophysiological findings suggested the existence of inexplicable cor pulmonale. Although we commenced to determine the causes of her severe condition, she suddenly died 3 days after admission. Postmortem autopsy revealed tumor cell microemboli in the small pulmonary arteries due to gastric cancer. Such a case of cor pulmonale as the first clinical manifestation is exceptionally rare. Occult malignancy should be considered as a differential diagnosis when one encounters a patient with subacutely aggravated respiratory condition and inexplicable cor pulmonale.

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


    Barbetakis Nikolaos; Samanidis Georgios; Paliouras Dimitrios; Samanidou Elpida; Tzimorota Zoi; Asteriou Christos; Xirou Persefoni; Tsilikas Christodoulos


    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 sm...

  9. Acute myocardial infarction mimicking squamous cell lung cancer with bone metastases due to hypercalcemia: a case report

    Institute of Scientific and Technical Information of China (English)

    FANG Chong-feng; XU Geng; CHEN Yang-xin


    @@ Acute myocardial infarction (AMI), the most severe coronary artery disease, is one of the most frequent cardiac emergencies, and early diagnosis and treatment are very important to decrease the subsequent cardiac adverse events such as malignant arrhythmia and sudden cardiac death. But in fact, lots of diseases are similar to AMI in clinical practice, of which the most common are myocarditis, pulmonary embolism in department of cardiology. Here we report a case of AMI-like squamous cell lung cancer with bone metastases.

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

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    Taiji Kuwata


    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.

  11. Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer. (United States)

    Balko, Justin M; Schwarz, Luis J; Bhola, Neil E; Kurupi, Richard; Owens, Phillip; Miller, Todd W; Gómez, Henry; Cook, Rebecca S; Arteaga, Carlos L


    Basal-like breast cancer (BLBC) is an aggressive disease that lacks a clinically approved targeted therapy. Traditional chemotherapy is effective in BLBC, but it spares the cancer stem cell (CSC)-like population, which is likely to contribute to cancer recurrence after the initial treatment. Dual specificity phosphatase-4 (DUSP4) is a negative regulator of the mitogen-activated protein kinase (MAPK) pathway that is deficient in highly aggressive BLBCs treated with chemotherapy, leading to aberrant MAPK activation and resistance to taxane-induced apoptosis. Herein, we investigated how DUSP4 regulates the MAP-ERK kinase (MEK) and c-jun-NH2-kinase (JNK) pathways in modifying CSC-like behavior. DUSP4 loss increased mammosphere formation and the expression of the CSC-promoting cytokines interleukin (IL)-6 and IL-8. These effects were caused in part by loss of control of the MEK and JNK pathways and involved downstream activation of the ETS-1 and c-JUN transcription factors. Enforced expression of DUSP4 reduced the CD44(+)/CD24(-) population in multiple BLBC cell lines in a MEK-dependent manner, limiting tumor formation of claudin-low SUM159PT cells in mice. Our findings support the evaluation of MEK and JNK pathway inhibitors as therapeutic agents in BLBC to eliminate the CSC population.

  12. Mortality due to lung cancer in Mexico. (United States)

    Ruíz-Godoy, L; Rizo Rios, P; Sánchez Cervantes, F; Osornio-Vargas, A; García-Cuellar, C; Meneses García, A


    The highest mortality due to cancer worldwide for both genders corresponds to lung cancer (1,179,000 deaths). In Mexico, the crude mortality rate due to lung cancer was of 5.01 per 10(5) inhabitants in 1979. The most important risk factor is smoking. The present study was aimed at analyzing the mortality due to lung cancer in Mexico, assessing data from each of the states constituting the Mexican Republic during the 1998-2004 period. Data were obtained from the National Institute of Statistics, Geography and Informatics (INEGI, for its initials in Spanish) corresponding to deaths due to lung cancer (1998-2004). We estimated the mean annual mortality rate (MAMR) for each of the 32 states of Mexico. We used the "World Population Standard". The MAMR was standardized according to age (ARS) direct method, and the standard error was determined by Poisson's approximation at a 95% confidence interval. To know the excess risk due to mortality, we calculated the standardized mortality ratios (SMRs) of ARS for each federal state, using the national rate as reference. In this period, 397,400 deaths due to malignant neoplasms were recorded, corresponding 45,578 (11.5%) to lung cancer; for men, 31,025 (68.1%) with MAMR of 8.9 and the respective ARS of 13.2 both x10(5) inhabitants. For women, results were 4553 (31.9%) deaths with MAMR of 4.1 and ARS of 5.4 both x10(5) inhabitants. The highest mortality rates due to lung cancer in both genders were observed in the north of Mexico, whereas for women this was observed in the central states. Although smoking is the main risk for lung cancer, there are other factors such as environmental pollution or exposure to toxicants that could be associated to this cancer. The years potentially lost due to lung cancer were 258,550 for men and 133,315 for women, with a total of 391,865 according to histopathology registry neoplasm malignant RHNM (1985-1995). Studies focused on the characterization and measurement of polluting agents would be a

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

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    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)


    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

  14. Lung cancer - small cell (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 ...

  15. Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-alpha dependent up-regulation of matrix metalloproteases. (United States)

    Hagemann, Thorsten; Robinson, Stephen C; Schulz, Matthias; Trümper, Lorenz; Balkwill, Frances R; Binder, Claudia


    Apart from the neoplastic cells, malignant tumours consist of the extracellular matrix (ECM) and normal cells, in particular tumour-associated macrophages (TAM). To understand the mechanisms by which TAM can influence tumour cell invasion we co-cultured the human breast cancer cell lines MCF-7, SK-BR-3 and the benign mammary epithelial cell line hTERT-HME1 with macrophages. Co-incubation enhanced invasiveness of the tumour cells, while hTERT-HME1 remained non-invasive. Addition of the broad-spectrum matrix metalloprotease (MMP)-inhibitor FN 439, neutralizing MMP-9 or tumour necrosis factor-alpha (TNF-alpha) antibodies reduced invasiveness to basal levels. As shown by zymography, all cell lines produced low amounts of MMP-2, -3, -7 and -9 under control conditions. Basal MMP production by macrophages was significantly higher. Upon co-incubation, supernatant levels of MMPs -2, -3, -7 and -9 increased significantly, paralleled by an increase of MMP-2 activation. MMP-2 and -9 induction could be blocked by TNF-alpha antibodies. Co-culture of macrophages and hTERT-HME1 did not lead to MMP induction. In the co-cultures, mRNAs for MMPs and TNF-alpha were significantly up-regulated in macrophages, while the mRNA concentrations in the tumour cells remained unchanged. In summary, we have found that co-cultivation of tumour cells with macrophages leads to enhanced invasiveness of the malignant cells due to TNF-alpha dependent MMP induction in the macrophages.

  16. Squamous cell skin cancer (United States)

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

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

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    Anastasov Nataša


    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. An autopsy case of acute cor pulmonale and paradoxical systemic embolism due to tumour cell microemboli in a patient with breast cancer. (United States)

    Uga, Sayuri; Ikeda, Shuntaro; Matsukage, Sho-ichi; Hamada, Mareomi


    A 62-year-old woman was admitted to our hospital because of severe respiratory distress. Diagnostic imaging studies suggested the existence of inexplicable cor pulmonale. Although we immediately sought the aetiology of her severe condition, she died suddenly on the fourth day after admission. Postmortem autopsy revealed tumour cell microemboli in the small pulmonary arteries. In addition, tumour cell embolisation identical to that in primary breast cancer cells was also observed in microvessels in systemic multiple organs, such as the liver, brain, kidneys, spleen, uterus, bone marrow and adrenal glands-with simultaneous findings of peripheral infarction. Systemic tumour cell embolism mediated through the patent foramen ovale superimposed on pulmonary tumour cell emboli (PTCE) is considered to be the mechanism underlying inexplicable cor pulmonale. The rapid aggravation of her condition terminated in death.

  19. Cell phones and cancer (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 ...

  20. Lung Cancer Stem Cells

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    Sharon R. Pine


    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.

  1. Stages of Renal Cell Cancer (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 ...

  2. 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


    by small interfering RNA or by different inhibitors showed that GSK-3 activity is essential for the induced MICA/B expression. We thus present evidence that cancer cells which survive the direct induction of cell death by HDAC inhibitors become targets for NKG2D-expressing cells like NK cells, gammadelta T......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...... apoptosis or oxidative stress caused by HDAC inhibitor treatment did not affect MICA/B expression, suggesting involvement of a separate signal pathway not directly coupled to induction of cell death. HDAC inhibitor treatment induced glycogen synthase kinase-3 (GSK-3) activity and down-regulation of GSK-3...

  3. Road for understanding cancer stem cells

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    Serakinci, Nedime; Erzik, Can


    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...... 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...

  4. Burden of disease due to cancer in Spain

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    Pérez-Gómez Beatriz


    Full Text Available Abstract Background Burden of disease is a joint measure of mortality and morbidity which makes it easier to compare health problems in which these two components enjoy different degrees of relative importance. The objective of this study is ascertaining the burden of disease due to cancer in Spain via the calculation of disability-adjusted life years (DALYs. Methods DALYs are the sum of years of life lost due to premature mortality and years lost due to disability. World Health Organization methodology and the following sources of data were used: the Mortality Register and Princeton Model Life Table for Years of life lost due to premature mortality and population, incidence estimates (Spanish tumour registries and fitting of generalized linear mixed models, duration (from data of survival in Spain from the EUROCARE-3 study and fitting of Weibull distribution function and disability (weights published in the literature for Years lost due to disability. Results There were 828,997 DALYs due to cancer (20.5 DALYs/1,000 population, 61% in men. Of the total, 51% corresponded to lung, colorectal, breast, stomach and prostate cancers. Mortality (84% of DALYs predominated over disability. Subjects aged under 20 years accounted for 1.6% and those aged over 70 years accounted for 30.1% of DALYs. Conclusion Lung, colorectal and breast cancers are responsible for the highest number of DALYs in Spain. Even if the burden of disease due to cancer is predominantly caused by mortality, some cancers have a significant weight of disability. Information on 2000 burden of disease due to cancer can be useful to assess how it has evolved over time and the impact of medical advances on it in terms of mortality and disability.

  5. Oxidative phosphorylation in cancer cells. (United States)

    Solaini, Giancarlo; Sgarbi, Gianluca; Baracca, Alessandra


    Evidence suggests that mitochondrial metabolism may play a key role in controlling cancer cells life and proliferation. Recent evidence also indicates how the altered contribution of these organelles to metabolism and the resistance of cancer mitochondria against apoptosis-associated permeabilization are closely related. The hallmarks of cancer growth, increased glycolysis and lactate production in tumours, have raised attention due to recent observations suggesting a wide spectrum of oxidative phosphorylation deficit and decreased availability of ATP associated with malignancies and tumour cell expansion. More specifically, alteration in signal transduction pathways directly affects mitochondrial proteins playing critical roles in controlling the membrane potential as UCP2 and components of both MPTP and oxphos complexes, or in controlling cells life and death as the Bcl-2 proteins family. Moreover, since mitochondrial bioenergetics and dynamics, are also involved in processes of cells life and death, proper regulation of these mitochondrial functions is crucial for tumours to grow. Therefore a better understanding of the key pathophysiological differences between mitochondria in cancer cells and in their non-cancer surrounding tissue is crucial to the finding of tools interfering with these peculiar tumour mitochondrial functions and will disclose novel approaches for the prevention and treatment of malignant diseases. Here, we review the peculiarity of tumour mitochondrial bioenergetics and the mode it is linked to the cell metabolism, providing a short overview of the evidence accumulated so far, but highlighting the more recent advances.

  6. Inflammation and cancer stem cells. (United States)

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


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

  7. Cancer stem cells, cancer cell plasticity and radiation therapy. (United States)

    Vlashi, Erina; Pajonk, Frank


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

  8. 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: [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)


    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.

  9. Invasive cancer cells and metastasis (United States)

    Mierke, Claudia Tanja


    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

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

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam


    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

  11. Breast cancer stem cells and radiation (United States)

    Phillips, Tiffany Marie


    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

  12. Cancer stem cells and personalized cancer nanomedicine. (United States)

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


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

  13. Laryngeal cancer stem cells

    Directory of Open Access Journals (Sweden)

    Antonio Greco


    Full Text Available Laryngeal squamous cell carcinoma (LSCC is one of the most commonly diagnosed malignancies in the head and neck region with an increased incidence rate worldwide. Cancer stem cells (CSCs are a group of cells with eternal life or infinite self-renewal ability, which have high migrating, infiltrative, and metastatic abilities. Though CSCs only account for a small proportion in tumors, the high resistance to traditional therapy exempts them from therapy killing and thus they can reconstruct tumors. Our current knowledge, about CSCs in the LSCC, largely depends on head and neck studies with a lack of systematic data about the evidences of CSCs in tumorigenesis of LSCC. Certainly, the combination of therapies aimed at debulking the tumour (e.g. surgery, conventional chemotherapy, radiotherapy together with targeted therapies aimed at the elimination of the CSCs might have a positive impact on the long-term outcome of patients with laryngeal cancer (LC in the future and may cast a new light on the cancer treatment.

  14. Redox Regulation in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Shijie Ding


    Full Text Available 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 cancer stem cells (CSCs has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortunately, how CSCs control ROS production and scavenging and how ROS-dependent signaling pathways contribute to CSCs function remain poorly understood. This review focuses on the role of redox balance, especially in ROS-dependent cellular processes in cancer stem cells (CSCs. We updated recent advances in our understanding of ROS generation and elimination in CSCs and their effects on CSC self-renewal and differentiation through modulating signaling pathways and transcriptional activities. The review concludes that targeting CSCs by manipulating ROS metabolism/dependent pathways may be an effective approach for improving cancer treatment.

  15. Stem Cells and Cancer; Celulas madre y cancer

    Energy Technology Data Exchange (ETDEWEB)

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


    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. 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


    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.

  17. Treatment Options for Renal Cell Cancer (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 ...

  18. General Information about Renal Cell Cancer (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 ...

  19. Treatment Option Overview (Renal Cell Cancer) (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 ...

  20. Lung cancer - non-small cell (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

  1. Cell Polarity Proteins in Breast Cancer Progression. (United States)

    Rejon, Carlis; Al-Masri, Maia; McCaffrey, Luke


    Breast cancer, one of the leading causes of cancer related death in women worldwide, is a heterogeneous disease with diverse subtypes that have different properties and prognoses. The developing mammary gland is a highly proliferative and invasive tissue, and some of the developmental programs may be aberrantly activated to promote breast cancer progression. In the breast, luminal epithelial cells exhibit apical-basal polarity, and the failure to maintain this organizational structure, due to disruption of polarity complexes, is implicated in promoting hyperplasia and tumors. Therefore, understanding the mechanisms underlying loss of polarity will contribute to our knowledge of the early stages leading to the pathogenesis of the disease. In this review, we will discuss recent findings that support the idea that loss of apical-basal cell polarity is a crucial step in the acquisition of the malignant phenotype. Oncogene induced loss of tissue organization shares a conserved cellular mechanism with developmental process, we will further describe the role of the individual polarity complexes, the Par, Crumbs, and Scribble, to couple cell division orientation and cell growth. We will examine symmetric or asymmetric cell divisions in mammary stem cell and their contribution to the development of breast cancer subtypes and cancer stem cells. Finally, we will highlight some of the recent advances in our understanding of the molecular mechanisms by which changes in epithelial polarity programs promote invasion and metastasis through single cell and collective cell modes. J. Cell. Biochem. 117: 2215-2223, 2016. © 2016 Wiley Periodicals, Inc.

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

    DEFF Research Database (Denmark)

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


    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...

  3. 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.

  4. Cancer stem cells in human gastrointestinal cancer. (United States)

    Taniguchi, Hiroaki; Moriya, Chiharu; Igarashi, Hisayoshi; Saitoh, Anri; Yamamoto, Hiroyuki; Adachi, Yasushi; Imai, Kohzoh


    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer-related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer-related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non-CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side-population fraction, show high aldehyde dehydrogenase-1 activity, form tumorspheres when cultured in non-adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.

  5. Cancer cells with irons in the fire. (United States)

    Bystrom, Laura M; Rivella, Stefano


    Iron is essential for the growth and proliferation of cells, as well as for many biological processes that are important for the maintenance and survival of the human body. However, excess iron is associated with the development of cancer and other pathological conditions, due in part to the pro-oxidative nature of iron and its damaging effects on DNA. Current studies suggest that iron depletion may be beneficial for patients that have diseases associated with iron overload or other iron metabolism disorders that may increase the risk for cancer. On the other hand, studies suggest that cancer cells are more vulnerable to the effects of iron depletion and oxidative stress in comparison to normal cells. Therefore, cancer patients might benefit from treatments that alter both iron metabolism and oxidative stress. This review highlights the pro-oxidant effects of iron, the relationship between iron and cancer development, the vulnerabilities of the iron-dependent cancer phenotype, and how these characteristics may be exploited to prevent or treat cancer.

  6. Embryonic stem cell factors and pancreatic cancer. (United States)

    Herreros-Villanueva, Marta; Bujanda, Luis; Billadeau, Daniel D; Zhang, Jin-San


    Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic tumor, is a highly aggressive human cancer with the lowest five-year survival rate of any human maligancy primarily due to its early- metastasis and lack of response to chemotherapy and radiation. Recent research suggests that PDAC cells comprise a hierarchy of tumor cells that develop around a population of cancer stem cells (CSCs), a small and distinct population of cancer cells that mediates tumoregenesis, metastasis and resistance to standard treatments. Thus, CSCs could be a target for more effective treatment options. Interestingly, pancreatic CSCs are subject to regulation by some of key embryonic stem cell (ESC) transctiption factors abberently expressed in PDAC, such as SOX2, OCT4 and NANOG. ESC transcription factors are important DNA-binding proteins present in both embryonic and adult somatic cells. The critical role of these factors in reprogramming processes makes them essential not only for embryonic development but also tumorigenesis. Here we provide an overview of stem cell transcription factors, particularly SOX2, OCT4, and NANOG, on their expression and function in pancreatic cancer. In contrast to embryonic stem cells, in which OCT4 and SOX2 are tightly regulated and physically interact to regulate a wide spectrum of target genes, de novo SOX2 expression alone in pancreatic cancer cells is sufficient to promote self-renewal, de-differentiation and imparting stemness characteristics via impacting specific cell cycle regulatory genes and epithelial-mesnechymal transtion driver genes. Thus, targeting ESC factors, particularly SOX2, could be a worthy strategy for pancreatic cancer therapy.

  7. NSAIDs and Cell Proliferation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Raj Ettarh


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

  8. General Information about Small Cell Lung Cancer (United States)

    ... lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The ... diagnosed, tests are done to find out if cancer cells have spread within the chest or to other ...

  9. Treatment Option Overview (Small Cell Lung Cancer) (United States)

    ... lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The ... diagnosed, tests are done to find out if cancer cells have spread within the chest or to other ...

  10. Stages of Small Cell Lung Cancer (United States)

    ... lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The ... diagnosed, tests are done to find out if cancer cells have spread within the chest or to other ...

  11. Therapeutic implications of colon cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Eros; Fabrizi; Simona; di; Martino; Federica; Pelacchi; Lucia; Ricci-Vitiani


    Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert no...

  12. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R


    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  13. Cell Phones and Cancer Risk (United States)

    ... have the potential of accumulating more years of cell phone exposure than adults do. Thus far, the data from studies in children with cancer do not support this theory. The first published analysis came from a large ...

  14. IL-33 facilitates endocrine resistance of breast cancer by inducing cancer stem cell properties. (United States)

    Hu, Haiyan; Sun, Jiaxing; Wang, Chunhong; Bu, Xiangmao; Liu, Xiangping; Mao, Yan; Wang, Haibo


    Breast cancers with estrogen receptor (ER) expressions account for the majority of all clinical cases. Due to hormone therapy with tamoxifen, prognoses of patients with ER-positive breast cancer are significantly improved. However, endocrine resistance to tamoxifen is common and inevitable, leading to compromised efficacy of hormone therapy. Herein, we identify a crucial role of IL-33 in inducing endocrine resistance of breast cancer. IL-33 overexpression in breast cancer cells results in resistance to tamoxifen-induced tumor growth inhibition, while IL-33 knockdown corrects this problem. Mechanistically, IL-33 induces breast cancer stem cell properties evidenced by mammosphere formation and xenograft tumorigenesis, as well as expression of cancer stem cell genes including ALDH1A3, OCT4, NANOG and SOX2. In breast cancer patients, higher serum IL-33 levels portend advanced clinical stages, poorly differentiated cancer cells and tumor recurrence. IL-33 expression levels in patients' freshly isolated breast cancer cells predicts tamoxifen resistance and cancer stem cell features in individual patient. Collectively, IL-33 induces endocrine resistance of breast cancer by promoting cancer stem cell properties. These findings provide novel mechanisms connecting IL-33 with cancer pathogenesis and pinpoint IL-33 as a promising target for optimizing hormone therapy in clinical practice.

  15. Cancer Stem Cells in Osteosarcoma


    Heymann, D; Brown, H K; Tellez-Gabriel, M.


    Osteosarcoma is the most common primary bone tumour in children and adolescents and advanced osteosarcoma patients with evidence of metastasis share a poor prognosis. Osteosarcoma frequently gains resistance to standard therapies highlighting the need for improved treatment regimens and identification of novel therapeutic targets. Cancer stem cells (CSC) represent a sub-type of tumour cells attributed to critical steps in cancer including tumour propagation, therapy resistance, recurrence and...

  16. Isolation of rare cancer cells from blood cells using dielectrophoresis. (United States)

    Salmanzadeh, Alireza; Sano, Michael B; Shafiee, Hadi; Stremler, Mark A; Davalos, Rafael V


    In this study, we investigate the application of contactless dielectrophoresis (cDEP) for isolating cancer cells from blood cells. Devices with throughput of 0.2 mL/hr (equivalent to sorting 3×10(6) cells per minute) were used to trap breast cancer cells while allowing blood cells through. We have shown that this technique is able to isolate cancer cells in concentration as low as 1 cancer cell per 10(6) hematologic cells (equivalent to 1000 cancer cells in 1 mL of blood). We achieved 96% trapping of the cancer cells at 600 kHz and 300 V(RMS).

  17. 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


    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 ...

  18. Demyelinating Peripheral Neuropathy Due to Renal Cell Carcinoma (United States)

    Nishioka, Kenya; Fujimaki, Motoki; Kanai, Kazuaki; Ishiguro, Yuta; Nakazato, Tomoko; Tanaka, Ryota; Yokoyama, Kazumasa; Hattori, Nobutaka


    Renal cell carcinoma (RCC) patients who develop a paraneoplastic syndrome may present with neuromuscular disorders. We herein report the case of a 50-year-old man who suffered from progressive gait disturbance and muscle weakness. The results of a nerve conduction study fulfilled the criteria of chronic inflammatory demyelinating polyneuropathy. An abdominal CT scan detected RCC, the pathological diagnosis of which was clear cell type. After tumor resection and a single course of intravenous immunoglobulin therapy, the patient's symptoms drastically improved over the course of one year. The patient's neurological symptoms preceded the detection of cancer. A proper diagnosis and the initiation of suitable therapies resulted in a favorable outcome. PMID:28049985

  19. Role of microRNAs in maintaining cancer stem cells. (United States)

    Garofalo, Michela; Croce, Carlo M


    Increasing evidence sustains that the establishment and maintenance of many, if not all, human cancers are due to cancer stem cells (CSCs), tumor cells with stem cell properties, such as the capacity to self-renew or generate progenitor and differentiated cells. CSCs seem to play a major role in tumor metastasis and drug resistance, but albeit the potential clinical importance, their regulation at the molecular level is not clear. Recent studies have highlighted several miRNAs to be differentially expressed in normal and cancer stem cells and established their role in targeting genes and pathways supporting cancer stemness properties. This review focuses on the last advances on the role of microRNAs in the regulation of stem cell properties and cancer stem cells in different tumors.

  20. Combination therapy targeting both cancer stem-like cells and bulk tumor cells for improved efficacy of breast cancer treatment. (United States)

    Wang, Tao; Narayanaswamy, Radhika; Ren, Huilan; Torchilin, Vladimir P


    Many types of tumors are organized in a hierarchy of heterogeneous cell populations. The cancer stem-like cells (CSCs) hypothesis suggests that tumor development and metastasis are driven by a minority population of cells, which are responsible for tumor initiation, growth and recurrences. The inability to efficiently eliminate CSCs during chemotherapy, together with CSCs being highly tumorigenic and invasive, may result in treatment failure due to cancer relapse and metastases. CSCs are emerging as a promising target for the development of translational cancer therapies. Ideal panacea for cancer would kill all malignant cells, including CSCs and bulk tumor cells. Since both chemotherapy and CSCs-specific therapy are insufficient to cure cancer, we propose combination therapy with CSCs-targeted agents and chemotherapeutics for improved breast cancer treatment. We generated in vitro mammosphere of 2 breast cancer cell lines, and demonstrated ability of mammospheres to grow and enrich cancer cells with stem-like properties, including self-renewal, multilineage differentiation and enrichment of cells expressing breast cancer stem-like cell biomarkers CD44(+)/CD24(-/low). The formation of mammospheres was significantly inhibited by salinomycin, validating its pharmacological role against the cancer stem-like cells. In contrast, paclitaxel showed a minimal effect on the proliferation and growth of breast cancer stem-like cells. While combination therapies of salinomycin with conventional chemotherapy (paclitaxel or lipodox) showed a potential to improve tumor cell killing, different subtypes of breast cancer cells showed different patterns in response to the combination therapies. While optimization of combination therapy is warranted, the design of combination therapy should consider phenotypic attributes of breast cancer types.

  1. Innate Lymphoid Cells in Cancer. (United States)

    Vallentin, Blandine; Barlogis, Vincent; Piperoglou, Christelle; Cypowyj, Sophie; Zucchini, Nicolas; Chéné, Matthieu; Navarro, Florent; Farnarier, Catherine; Vivier, Eric; Vély, Frédéric


    The world of lymphocytes has recently expanded. A group of cells, innate lymphoid cells (ILC), has been defined. It includes lymphoid cells that have been known for decades, such as natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells. NK cells recognize a vast array of tumor cells, which they help to eliminate through cytotoxicity and the production of cytokines, such as IFNγ. Advances in our understanding of NK-cell biology have led to a growing interest in the clinical manipulation of these cells in cancer. The other ILCs are found mostly in the mucosae and mucosal-associated lymphoid tissues, where they rapidly initiate immune responses to pathogens without the need for specific sensitization. Here, we outline the basic features of ILCs and review the role of ILCs other than NK cells in cancer. Much of the role of these ILCs in cancer remains unknown, but several findings should lead to further efforts to dissect the contribution of different ILC subsets to the promotion, maintenance, or elimination of tumors at various anatomic sites. This will require the development of standardized reagents and protocols for monitoring the presence and function of ILCs in human blood and tissue samples.

  2. Recurrent Syncope due to Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    A. Casini


    Full Text Available Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus by metastases of a carcinoma of the esophagus, successfully treated by radiotherapy. In such cases, surgery, chemotherapy or radiotherapy can be performed. Because syncope may be an early sign of neck or cervical cancer, the diagnostic approach of syncope in patients with a past history of cancer should include the possibility of neck tumor recurrence or metastasis and an oncologic workout should be considered.

  3. Municipal mortality due to thyroid cancer in Spain

    Directory of Open Access Journals (Sweden)

    Gómez-Barroso Diana


    Full Text Available Abstract Background Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. Methods It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardized mortality ratios, smoothed relative risk (RR estimates, and the posterior probability that RR > 1. Results From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna and western areas of Asturias and Orense. Conclusion The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor.

  4. Tumor metabolism: cancer cells give and take lactate. (United States)

    Semenza, Gregg L


    Tumors contain well-oxygenated (aerobic) and poorly oxygenated (hypoxic) regions, which were thought to utilize glucose for oxidative and glycolytic metabolism, respectively. In this issue of the JCI, Sonveaux et al. show that human cancer cells cultured under hypoxic conditions convert glucose to lactate and extrude it, whereas aerobic cancer cells take up lactate via monocarboxylate transporter 1 (MCT1) and utilize it for oxidative phosphorylation (see the related article beginning on page 3930). When MCT1 is inhibited, aerobic cancer cells take up glucose rather than lactate, and hypoxic cancer cells die due to glucose deprivation. Treatment of tumor-bearing mice with an inhibitor of MCT1 retarded tumor growth. MCT1 expression was detected exclusively in nonhypoxic regions of human cancer biopsy samples, and in combination, these data suggest that MCT1 inhibition holds potential as a novel cancer therapy.

  5. Metabolic profiling of breast cancer: Differences in central metabolism between subtypes of breast cancer cell lines. (United States)

    Willmann, Lucas; Schlimpert, Manuel; Halbach, Sebastian; Erbes, Thalia; Stickeler, Elmar; Kammerer, Bernd


    Although the concept of aerobic glycolysis in cancer was already reported in the 1930s by Otto Warburg, the understanding of metabolic pathways remains challenging especially due to the heterogeneity of cancer. In consideration of four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling of metabolites was performed on cell extracts and supernatants of breast cancer cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct methanolic extraction, cell scraping and cell disruption was executed to obtain central metabolites. Major differences in biochemical pathways have been observed in the breast cancer cell lines compared to the breast epithelial cell line, as well as between the breast cancer cell lines themselves. Characteristics of breast cancer subtypes could be correlated to their individual metabolic profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF-10A based on elevated amino acid levels. The observed metabolic signatures have great potential as biomarker for breast cancer as well as an improved understanding of subtype specific phenomenons of breast cancer.

  6. Do Cell Phones Cause Cancer?

    CERN Document Server

    Leikind, Bernard


    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...

  7. 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


    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......, we show that SSX2 is involved in regulation of cancer cell growth. We found that ectopic expression of SSX2 in melanoma and colon cancer cells strongly reduced cell growth and induced apoptosis in vitro. Importantly, in a xenograft mouse model, the growth of tumors derived from SSX2 overexpressing...... an 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...

  8. Cancer stem cells and metastasis. (United States)

    Sampieri, Katia; Fodde, Riccardo


    Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in haematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.

  9. Cancer stem cells: therapeutic implications and perspectives in cancer therapy

    Directory of Open Access Journals (Sweden)

    Lu Han


    Full Text Available The cancer stem cell (CSC theory is gaining increasing attention from researchers and has become an important focus of cancer research. According to the theory, a minority population of cancer cells is capable of self-renewal and generation of differentiated progeny, termed cancer stem cells (CSCs. Understanding the properties and characteristics of CSCs is key to future study on cancer research, such as the isolation and identification of CSCs, the cancer diagnosis, and the cancer therapy. Standard oncology treatments, such as chemotherapy, radiotherapy and surgical resection, can only shrink the bulk tumor and the tumor tends to relapse. Thus, therapeutic strategies that focus on targeting CSCs and their microenvironmental niche address the ineffectiveness of traditional cancer therapies to eradicate the CSCs that otherwise result in therapy resistance. The combined use of traditional therapies with targeted CSC-specific agents may target the whole cancer and offer a promising strategy for lasting treatment and even cure.

  10. Notch signaling in cancer stem cells. (United States)

    Wang, Jialiang; Sullenger, Bruce A; Rich, Jeremy N


    Subpopulations of cancer cells with stem cell-like characteristics, termed cancer stem cells, have been identified in a wide range of human cancers. Cancer stem cells are defined by their ability to self-renew as well as recapitulate the original heterogeneity of cancer cells in culture and in serial xenotransplants. Not only are cancer stem cells highly tumorigenic, but these cells are implicated in tumor resistance to conventional chemotherapy and radiotherapy, thus highlighting their significance as therapeutic targets. Considerable similarities have been found between cancer stem cells and normal stem cells on their dependence on certain signaling pathways. More specifically, the core stem cell signaling pathways, such as the Wnt, Notch and Hedgehog pathways, also critically regulate the self-renewal and survival of cancer stem cells. While the oncogenic functions of Notch pathway have been well documented, its role in cancer stem cells is just emerging. In this chapter, we will discuss recent advances in cancer stem cell research and highlight the therapeutic potential of targeting Notch in cancer stem cells.

  11. The role of dendritic cells in cancer

    DEFF Research Database (Denmark)

    Hansen, Morten; Andersen, Mads Hald


    Though present in low numbers, dendritic cells (DCs) are recognized as major players in the control of cancer by adaptive immunity. The roles of cytotoxic CD8+ T-cells and Th1 helper CD4+ T-cells are well-documented in murine models of cancer and associated with a profound prognostic impact when...... treatment regimens against cancer....

  12. Exometabolom analysis of breast cancer cell lines: Metabolic signature. (United States)

    Willmann, Lucas; Erbes, Thalia; Halbach, Sebastian; Brummer, Tilman; Jäger, Markus; Hirschfeld, Marc; Fehm, Tanja; Neubauer, Hans; Stickeler, Elmar; Kammerer, Bernd


    Cancer cells show characteristic effects on cellular turnover and DNA/RNA modifications leading to elevated levels of excreted modified nucleosides. We investigated the molecular signature of different subtypes of breast cancer cell lines and the breast epithelial cell line MCF-10A. Prepurification of cell culture supernatants was performed by cis-diol specific affinity chromatography using boronate-derivatized polyacrylamide gel. Samples were analyzed by application of reversed phase chromatography coupled to a triple quadrupole mass spectrometer. Collectively, we determined 23 compounds from RNA metabolism, two from purine metabolism, five from polyamine/methionine cycle, one from histidine metabolism and two from nicotinate and nicotinamide metabolism. We observed major differences of metabolite excretion pattern between the breast cancer cell lines and MCF-10A, just as well as between the different breast cancer cell lines themselves. Differences in metabolite excretion resulting from cancerous metabolism can be integrated into altered processes on the cellular level. Modified nucleosides have great potential as biomarkers in due consideration of the heterogeneity of breast cancer that is reflected by the different molecular subtypes of breast cancer. Our data suggests that the metabolic signature of breast cancer cell lines might be a more subtype-specific tool to predict breast cancer, rather than a universal approach.

  13. The relationship of cancer stem cells in urological cancers

    Directory of Open Access Journals (Sweden)

    Marta Pokrywczyńska


    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.

  14. Current advances in T-cell-based cancer immunotherapy. (United States)

    Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu


    Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

  15. Adrenal Failure due to Adrenal Metastasis of Lung Cancer: A Case Report (United States)

    Faulhaber, Gustavo Adolpho Moreira; Borges, Flavia Kessler; Ascoli, Aline Maria; Seligman, Renato; Furlanetto, Tania Weber


    We report a case of a patient with adrenal failure due to bilateral adrenal metastasis of lung cancer. This is a rare presentation of lung cancer. We review the differential diagnosis of weight loss and how to make diagnosis of adrenal insufficiency. PMID:22606443

  16. Adrenal Failure due to Adrenal Metastasis of Lung Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Gustavo Adolpho Moreira Faulhaber


    Full Text Available We report a case of a patient with adrenal failure due to bilateral adrenal metastasis of lung cancer. This is a rare presentation of lung cancer. We review the differential diagnosis of weight loss and how to make diagnosis of adrenal insufficiency.

  17. Colorectal Cancer Stem Cells and Cell Death

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  18. Glutathione in Cancer Cell Death

    Directory of Open Access Journals (Sweden)

    Jose M. Estrela


    Full Text Available 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.

  19. 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: [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain)


    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.

  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;


    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. Prostate Cancer Stem Cells: Research Advances. (United States)

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina


    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.

  2. Prostate Cancer Stem Cells: Research Advances

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska


    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.

  3. Measuring the societal burden of cancer: the cost of lost productivity due to premature cancer-related mortality in Europe. (United States)

    Hanly, Paul; Soerjomataram, Isabelle; Sharp, Linda


    Every cancer-related death in someone of working age represents an economic loss to society. To inform priorities for cancer control, we estimated costs of lost productivity due to premature cancer-related mortality across Europe, for all cancers and by site, gender, region and country. Cancer deaths in 2008 were obtained from GLOBOCAN for 30 European countries across four regions. Costs were valued using the human capital approach. Years of productive life lost (YPLL) were computed by multiplying deaths between 15 and 64 years by working-life expectancy, then by country-, age- and gender-specific annual wages, corrected for workforce participation and unemployment. Lost productivity costs due to premature cancer-related mortality in Europe in 2008 were €75 billion. Male costs (€49 billion) were almost twice female costs (€26 billion). The most costly sites were lung (€17 billion; 23% of total costs), breast (€7 billion; 9%) and colorectum (€6 billion; 8%). Stomach cancer (in Southern and Central-Eastern Europe) and pancreatic cancer (in Northern and Western Europe) were also among the most costly sites. The average lost productivity cost per cancer death was €219,241. Melanoma had the highest cost per death (€312,798), followed by Hodgkin disease (€306,628) and brain and CNS cancer (€288,850). Premature mortality costs were 0.58% of 2008 European gross domestic product, highest in Central-Eastern Europe (0.81%) and lowest in Northern Europe (0.51%). Premature cancer-related mortality costs in Europe are significant. These results provide a novel perspective on the societal cancer burden and may be used to inform priority setting for cancer control.

  4. 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)


    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.

  5. Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. (United States)

    Gupte, Anshul; Mumper, Russell J


    As we gain a better understanding of the factors affecting cancer etiology, we can design improved treatment strategies. Over the past three to four decades, there have been numerous successful efforts in recognizing important cellular proteins essential in cancer growth and therefore these proteins have been targeted for cancer treatment. However, studies have shown that targeting one or two proteins in the complex cancer cascade may not be sufficient in controlling and/or inhibiting cancer growth. Therefore, there is a need to examine features which are potentially involved in multiple facets of cancer development. In this review we discuss the targeting of the elevated copper (both in serum and tumor) and oxidative stress levels in cancer with the aid of a copper chelator d-penicillamine (d-pen) for potential cancer treatment. Numerous studies in the literature have reported that both the serum and tumor copper levels are elevated in a variety of malignancies, including both solid tumor and blood cancer. Further, the elevated copper levels have been shown to be directly correlated to cancer progression. Enhanced levels of intrinsic oxidative stress has been shown in variety of tumors, possibly due to the combination of factors such as elevated active metabolism, mitochondrial mutation, cytokines, and inflammation. The cancer cells under sustained ROS stress tend to heavily utilize adaptation mechanisms and may exhaust cellular ROS-buffering capacity. Therefore, the elevated copper levels and increased oxidative stress in cancer cells provide for a prospect of selective cancer treatment.

  6. All-trans retinoic acid stealth liposomes prevent the relapse of breast cancer arising from the cancer stem cells. (United States)

    Li, Ruo-Jing; Ying, Xue; Zhang, Yan; Ju, Rui-Jun; Wang, Xiao-Xing; Yao, Hong-Juan; Men, Ying; Tian, Wei; Yu, Yang; Zhang, Liang; Huang, Ren-Jie; Lu, Wan-Liang


    The relapse of cancer is mostly due to the proliferation of cancer stem cells which could not be eliminated by a standard chemotherapy. A new kind of all-trans retinoic acid stealth liposomes was developed for preventing the relapse of breast cancer and for treating the cancer in combination with a cytotoxic agent, vinorelbine stealth liposomes. In vitro studies were performed on the human breast cancer MCF-7 and MDA-MB-231 cells. In vivo evaluations were performed on the newly established relapse model with breast cancer stem cells. Results showed that the particle size of all-trans retinoic acid stealth liposomes was approximately 80nm, and the encapsulation efficiency was >90%. Breast cancer stem cells were identified with the CD44(+)/CD24(-) phenotype and characterized with properties: resistant to cytotoxic agent, stronger capability of proliferation, and stronger capability of differentiation. Inhibitory effect of all-trans retinoic acid stealth liposomes was more potent in cancer stem cells than in cancer cells. The mechanisms were defined to be two aspects: arresting breast cancer stem cells at the G(0)/G(1) phase in mitosis, and inducing the differentiation of breast cancer stem cells. The cancer relapse model was successfully established by xenografting breast cancer stem cells into NOD/SCID mice, and the formation and growth of the xenografted tumors were significantly inhibited by all-trans retinoic acid stealth liposomes. The combination therapy of all-trans retinoic acid stealth liposomes with vinorelbine stealth liposomes produced the strongest inhibitory effect to the relapse tumor model. It could be concluded that all-trans retinoic acid stealth liposomes could be used for preventing the relapse of breast cancer by differentiating cancer stem cells and arresting the cell-cycle, and for treating breast cancer as a co-therapy, thus providing a novel strategy for treating breast cancer and preventing relapse derived from breast cancer stem cells.

  7. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. (United States)

    Tomasetti, Cristian; Li, Lu; Vogelstein, Bert


    Cancers are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replication errors (R). We studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries throughout the world. The data revealed a strong correlation (median = 0.80) between cancer incidence and normal stem cell divisions in all countries, regardless of their environment. The major role of R mutations in cancer etiology was supported by an independent approach, based solely on cancer genome sequencing and epidemiological data, which suggested that R mutations are responsible for two-thirds of the mutations in human cancers. All of these results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment. Moreover, they accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable R mutations.

  8. Nanomaterials in Targeting Cancer Stem Cells for Cancer Therapy (United States)

    Qin, Weiwei; Huang, Guan; Chen, Zuanguang; Zhang, Yuanqing


    Cancer stem cells (CSCs) have been identified in almost all cancers and give rise to metastases and can also act as a reservoir of cancer cells that may cause a relapse after surgery, radiation, or chemotherapy. Thus they are obvious targets in therapeutic approaches and also a great challenge in cancer treatment. The threat presented by CSCs lies in their unlimited proliferative ability and multidrug resistance. These findings have necessitated an effective novel strategy to target CSCs for cancer treatment. Nanomaterials are on the route to providing novel methods in cancer therapies. Although, there have been a large number of excellent work in the field of targeted cancer therapy, it remains an open question how nanomaterials can meet future demands for targeting and eradicating of CSCs. In this review, we summarized recent and highlighted future prospects for targeting CSCs for cancer therapies by using a variety of nanomaterials.

  9. Drugs Approved for Kidney (Renal Cell) Cancer (United States)

    ... 2015 2014 2013 2012 Media Resources Media Contacts Multicultural Media ... This page lists cancer drugs approved by the Food and Drug Administration (FDA) for kidney (renal cell) cancer. The list ...

  10. 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


    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.

  11. Colon Cancer Cell Separation by Dielectrophoresis (United States)

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


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

  12. Significance of Cancer Stem Cells in Anti-Cancer Therapies (United States)

    Botelho, Mónica; Alves, Helena


    Stem cells are the focus of cutting edge research interest because of their competence both to self-renew and proliferate, and to differentiate into a variety of tissues, offering enticing prospects of growing replacement organs in vitro, among other possible therapeutic implications. It is conceivable that cancer stem cells share a number of biological hallmarks that are different from their normal-tissue counterparts and that these might be taken advantage of for therapeutic benefits. In this review we discuss the significance of cancer stem cells in diagnosis and prognosis of cancer as well as in the development of new strategies for anti-cancer drug design.

  13. Targetless T cells in cancer immunotherapy

    DEFF Research Database (Denmark)

    thor Straten, Eivind Per; Garrido, Federico


    Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell...... infiltrate tumor tissues and destroy HLA class I positive tumor cells expressing the specific antigen. In fact, current progress in the field of cancer immune therapy is based on the capacity of T cells to kill cancer cells that present tumor antigen in the context on an HLA class I molecule. However......, it is also well established that cancer cells are often characterized by loss or down regulation of HLA class I molecules, documented in a variety of human tumors. Consequently, immune therapy building on CD8 T cells will be futile in patients harboring HLA class-I negative or deficient cancer cells...

  14. Pancreatic cancer stem cells: fact or fiction? (United States)

    Bhagwandin, Vikash J; Shay, Jerry W


    The terms cancer-initiating or cancer stem cells have been the subject of great interest in recent years. In this review we will use pancreatic cancer as an overall theme to draw parallels with historical findings to compare to recent reports of stem-like characteristics in pancreatic cancer. We will cover such topics as label-retaining cells (side-population), ABC transporter pumps, telomerase, quiescence, cell surface stem cell markers, and epithelial-mesenchymal transitions. Finally we will integrate the available findings into a pancreatic stem cell model that also includes metastatic disease.

  15. Apoptotic effect of noscapine in breast cancer cell lines. (United States)

    Quisbert-Valenzuela, Edwin O; Calaf, Gloria M


    Cancer is a public health problem in the world and breast cancer is the most frequently cancer in women. Approximately 15% of the breast cancers are triple-negative. Apoptosis regulates normal growth, homeostasis, development, embryogenesis and appropriate strategy to treat cancer. Bax is a protein pro-apoptotic enhancer of apoptosis in contrast to Bcl-2 with antiapoptotic properties. Initiator caspase-9 and caspase-8 are features of intrinsic and extrinsic apoptosis pathway, respectively. NF-κB is a transcription factor known to be involved in the initiation and progression of breast cancer. Noscapine, an alkaloid derived from opium is used as antitussive and showed antitumor properties that induced apoptosis in cancer cell lines. The aim of the present study was to determine the apoptotic effect of noscapine in breast cancer cell lines compared to breast normal cell line. Three cell lines were used: i) a control breast cell line MCF-10F; ii) a luminal-like adenocarcinoma triple-positive breast cell line MCF-7; iii) breast cancer triple-negative cell line MDA-MB-231. Our results showed that noscapine had lower toxicity in normal cells and was an effective anticancer agent that induced apoptosis in breast cancer cells because it increases Bax gene and protein expression in three cell lines, while decreases Bcl-xL gene expression, and Bcl-2 protein expression decreased in breast cancer cell lines. Therefore, Bax/Bcl-2 ratio increased in the three cell lines. This drug increased caspase-9 gene expression in breast cancer cell lines and caspase-8 gene expression increased in MCF-10F and MDA-MB-231. Furthermore, it increased cleavage of caspase-8, suggesting that noscapine-induced apoptosis is probably due to the involvement of extrinsic and intrinsic apoptosis pathways. Antiapoptotic gene and protein expression diminished and proapoptotic gene and protein expression increased noscapine-induced expression, probably due to decrease in NF-κB gene and protein expression

  16. Fermented red ginseng extract inhibits cancer cell proliferation and viability. (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


    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.

  17. Stem Cell Based Gene Therapy in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jae Heon Kim


    Full Text Available 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 upgraded cellular vehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using stem cells in prostate cancer include the cytosine deaminase/5-fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review the stem cell therapy in prostate cancer including its proven mechanisms and also limitations.

  18. 3D printing of biomimetic microstructures for cancer cell migration (United States)

    Huang, Tina Qing; Qu, Xin; Liu, Justin; Chen, Shaochen


    To understand the physical behavior and migration of cancer cells, a 3D in vitro micro-chip in hydrogel was created using 3D projection printing. The micro-chip has a honeycomb branched structure, aiming to mimic 3D vascular morphology to test, monitor, and analyze differences in the behavior of cancer cells (i.e. HeLa) vs. non-cancerous cell lines (i.e. 10T1/2). The 3D Projection Printing system can fabricate complex structures in seconds from user-created designs. The fabricated microstructures have three different channel widths of 25, 45, and 120 microns wide to reflect a range of blood vessel diameters. HeLa and 10T1/2 cells seeded within the micro-chip were then analyzed for morphology and cell migration speed. 10T1/2 cells exhibited greater changes in morphology due to channel size width than HeLa cells; however, channel width had a limited effect on 10T1/2 cell migration while HeLa cancer cell migration increased as channel width decreased. This physiologically relevant 3D cancer tissue model has the potential to be a powerful tool for future drug discoveries and cancer migration studies PMID:24150602

  19. Pulmonary Lymphangitic Carcinomatosis due to Renal Cell Carcinoma. (United States)

    Guddati, Achuta K; Marak, Creticus P


    Renal cell carcinoma is an aggressive disease with a high rate of mortality. It is known to metastasize to the lung, liver, bone and brain. However, manifestation through lymphatic spread to the lungs is rare. Lymphangitic carcinomatosis is commonly observed in malignancies of the breast, lung, pancreas, colon and cervix. It is unusual to observe lymphangitic carcinomatosis of the lungs due to renal cell carcinoma. Lymphangitic carcinomatosis of the lungs may result in severe respiratory distress and may be the direct cause of death. Currently, there are no known modalities of preventing or slowing lymphangitic carcinomatosis besides treating the primary tumor. However, early detection may change the course of the disease and may prolong survival. This is compounded by the difficulty involved in diagnosing lymphangitic carcinomatosis of the lung which frequently involves lung biopsy. Immunohistochemical studies are often used in conjunction with regular histochemistry in ascertaining the primary tumor and in differentiating it from pulmonary metastasis. In this case report, we describe the presentation and clinical course of renal cell carcinoma in a patient which manifested as lymphangitis carcinomatosa of the lungs. The patient underwent surgical resection of the primary tumor with lymph node resection but presented with a fulminant lymphangitic carcinomatosis of the lungs within two weeks. Immunohistochemistry of the tissue obtained by the biopsy confirmed the diagnosis which was subsequently corroborated during his autopsy. This case illustrates the necessity of an urgent follow-up of chemotherapy and immunotherapy in such patients.

  20. Pulmonary Lymphangitic Carcinomatosis due to Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Achuta K. Guddati


    Full Text Available Renal cell carcinoma is an aggressive disease with a high rate of mortality. It is known to metastasize to the lung, liver, bone and brain. However, manifestation through lymphatic spread to the lungs is rare. Lymphangitic carcinomatosis is commonly observed in malignancies of the breast, lung, pancreas, colon and cervix. It is unusual to observe lymphangitic carcinomatosis of the lungs due to renal cell carcinoma. Lymphangitic carcinomatosis of the lungs may result in severe respiratory distress and may be the direct cause of death. Currently, there are no known modalities of preventing or slowing lymphangitic carcinomatosis besides treating the primary tumor. However, early detection may change the course of the disease and may prolong survival. This is compounded by the difficulty involved in diagnosing lymphangitic carcinomatosis of the lung which frequently involves lung biopsy. Immunohistochemical studies are often used in conjunction with regular histochemistry in ascertaining the primary tumor and in differentiating it from pulmonary metastasis. In this case report, we describe the presentation and clinical course of renal cell carcinoma in a patient which manifested as lymphangitis carcinomatosa of the lungs. The patient underwent surgical resection of the primary tumor with lymph node resection but presented with a fulminant lymphangitic carcinomatosis of the lungs within two weeks. Immunohistochemistry of the tissue obtained by the biopsy confirmed the diagnosis which was subsequently corroborated during his autopsy. This case illustrates the necessity of an urgent follow-up of chemotherapy and immunotherapy in such patients.

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

    Directory of Open Access Journals (Sweden)

    Hossein Fayazi


    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. The biology of cancer stem cells. (United States)

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


    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.

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


    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


    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...

  4. The Implications of Cancer Stem Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wenjing Jiang


    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.

  5. Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. (United States)

    Yamazaki, Ken; Takamura, Masaaki; Masugi, Yohei; Mori, Taisuke; Du, Wenlin; Hibi, Taizo; Hiraoka, Nobuyoshi; Ohta, Tsutomu; Ohki, Misao; Hirohashi, Setsuo; Sakamoto, Michiie


    Pancreatic cancer has the worst prognosis among cancers due to the difficulty of early diagnosis and its aggressive behavior. To characterize the aggressiveness of pancreatic cancers on gene expression, pancreatic cancer xenografts transplanted into severe combined immunodeficient mice served as a panel for gene-expression profiling. As a result of profiling, the adenylate cyclase-associated protein 1 (CAP1) gene was shown to be overexpressed in all of the xenografts. The expression of CAP1 protein in all 73 cases of pancreatic cancer was recognized by immunohistochemical analyses. The ratio of CAP1-positive tumor cells in clinical specimens was correlated with the presence of lymph node metastasis and neural invasion, and also with the poor prognosis of patients. Immunocytochemical analyses in pancreatic cancer cells demonstrated that CAP1 colocalized to the leading edge of lamellipodia with actin. Knockdown of CAP1 by RNA interference resulted in the reduction of lamellipodium formation, motility, and invasion of pancreatic cancer cells. This is the first report demonstrating the overexpression of CAP1 in pancreatic cancers and suggesting the involvement of CAP1 in the aggressive behavior of pancreatic cancer cells.

  6. 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


    @@ 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.

  7. 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


    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.

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


    Zhi-xiang Yuan; Jingxin Mo; Guixian Zhao; Gang Shu; Hua-lin Fu; Wei Zhao


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

  9. 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


    that 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......Since the discovery of testicular carcinoma in situ (CIS) -- the precursor cell for the vast majority of germ cell tumours -- it has been proposed that CIS cells could be derived from transformed primordial germ cells or gonocytes. Here, we review recent discoveries not only substantiating...

  10. Breathless cancer cells get fat on glutamine

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Anastasiou; Lewis C Cantley


    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.

  11. Radiofrequency treatment alters cancer cell phenotype (United States)

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


    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.

  12. Microfluidic channel for characterizing normal and breast cancer cells (United States)

    TruongVo, T. N.; Kennedy, R. M.; Chen, H.; Chen, A.; Berndt, A.; Agarwal, M.; Zhu, L.; Nakshatri, H.; Wallace, J.; Na, S.; Yokota, H.; Ryu, J. E.


    A microfluidic channel was designed and fabricated for the investigation of behaviors of normal and cancer cells in a narrow channel. A specific question addressed in this study was whether it is possible to distinguish normal versus cancer cells by detecting their stationary and passing behaviors through a narrow channel. We hypothesized that due to higher deformability, softer cancer cells will pass through the channel further and quicker than normal cells. Two cell lines, employed herein, were non-tumor breast epithelial cells (MCF-10A; 11.2  ±  2.4 µm in diameter) and triple negative breast cancer cells (MDA-MB-231; 12.4  ±  2.1 µm in diameter). The microfluidic channel was 300 µm long and linearly tapered with a width of 30 µm at an inlet to 5 µm at an outlet. The result revealed that MDA-MB-231 cells entered and stuck further toward the outlet than MCF-10A cells in response to a slow flow (2 µl min‑1). Further, in response to a fast flow (5 µl min‑1), the passage time (mean  ±  s.d.) was 26.6  ±  43.9 s for normal cells (N  =  158), and 1.9  ±  1.4 s for cancer cells (N  =  128). The measurement of stiffness by atomic force microscopy as well as model-based predictions pointed out that MDA-MB-231 cells are significantly softer than MCF-10A cells. Collectively, the result in this study suggests that analysis of an individual cell’s behavior through a narrow channel can characterize deformable cancer cells from normal ones, supporting the possibility of enriching circulating tumor cells using novel microfluidics-based analysis.

  13. Abnormalities in human pluripotent cells due to reprogramming mechanisms. (United States)

    Ma, Hong; Morey, Robert; O'Neil, Ryan C; He, Yupeng; Daughtry, Brittany; Schultz, Matthew D; Hariharan, Manoj; Nery, Joseph R; Castanon, Rosa; Sabatini, Karen; Thiagarajan, Rathi D; Tachibana, Masahito; Kang, Eunju; Tippner-Hedges, Rebecca; Ahmed, Riffat; Gutierrez, Nuria Marti; Van Dyken, Crystal; Polat, Alim; Sugawara, Atsushi; Sparman, Michelle; Gokhale, Sumita; Amato, Paula; Wolf, Don P; Ecker, Joseph R; Laurent, Louise C; Mitalipov, Shoukhrat


    Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the 'gold standard', they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.

  14. 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


    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.

  15. Stem cell characteristics in prostate cancer cell lines.

    NARCIS (Netherlands)

    Pfeiffer, M.J.; Schalken, J.A.


    BACKGROUND: Recent studies indicate the presence of a small, stem-like cell population in several human cancers that is crucial for the tumour (re)population. OBJECTIVE: Six established prostate cancer (PCa) cell lines-DU145, DuCaP, LAPC-4, 22Rv1, LNCaP, and PC-3-were examined for their stem cell pr

  16. Interfacial geometry dictates cancer cell tumorigenicity (United States)

    Lee, Junmin; Abdeen, Amr A.; Wycislo, Kathryn L.; Fan, Timothy M.; Kilian, Kristopher A.


    Within the heterogeneous architecture of tumour tissue there exists an elusive population of stem-like cells that are implicated in both recurrence and metastasis. Here, by using engineered extracellular matrices, we show that geometric features at the perimeter of tumour tissue will prime a population of cells with a stem-cell-like phenotype. These cells show characteristics of cancer stem cells in vitro, as well as enhanced tumorigenicity in murine models of primary tumour growth and pulmonary metastases. We also show that interfacial geometry modulates cell shape, adhesion through integrin α5β1, MAPK and STAT activity, and initiation of pluripotency signalling. Our results for several human cancer cell lines suggest that interfacial geometry triggers a general mechanism for the regulation of cancer-cell state. Similar to how a growing tumour can co-opt normal soluble signalling pathways, our findings demonstrate how cancer can also exploit geometry to orchestrate oncogenesis.

  17. Targeting the osteosarcoma cancer stem cell

    Directory of Open Access Journals (Sweden)

    Qin Ling


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

  18. Characteristics of breast cancer patients who experience menopausal transition due to treatment

    NARCIS (Netherlands)

    S.F.A. Duijts; A.C. Stolk-Vos; H.S.A. Oldenburg; M. van Beurden; N.K. Aaronson


    Objective To identify patient-related and treatment-related factors associated significantly with climacteric symptoms in young patients who experience menopausal transition due to adjuvant treatment for breast cancer. Methods This cross-sectional study used questionnaire data collected to screen br

  19. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  20. Extracellular Molecules Involved in Cancer Cell Invasion

    Directory of Open Access Journals (Sweden)

    Theodora Stivarou


    Full Text Available 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.

  1. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

    Directory of Open Access Journals (Sweden)

    John Koren

    Full Text Available MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB. Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

  2. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance. (United States)

    Koren, John; Miyata, Yoshinari; Kiray, Janine; O'Leary, John C; Nguyen, Lana; Guo, Jianping; Blair, Laura J; Li, Xiaokai; Li, Xiokai; Jinwal, Umesh K; Cheng, Jin Q; Gestwicki, Jason E; Dickey, Chad A


    MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB). Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

  3. Natural Killer cells as helper cells in Dendritic cell cancer vaccines

    Directory of Open Access Journals (Sweden)

    María Betina Pampena


    Full Text Available Vaccine-based cancer immunotherapy has generated highly variable clinical results due to differing methods of vaccine preparation and variation in patient populations, among other lesser factors. Moreover, these clinical responses do not necessarily correspond with the induction of tumor-specific cytotoxic lymphocytes. Here we review the participation of natural killer (NK cells as alternative immune components that could cooperate in successful vaccination treatment. NK cells have been described as helper cells in dendritic cell-based cancer vaccines, but the role in other kinds of vaccination strategies (whole cells, peptide or DNA- based vaccines is poorly understood. In this article we address the following issues regarding the role of NK cells in cancer vaccines: NK cell anti-tumor action sites, and the loci of NK cell interaction with other immune cells; descriptions of new data on the memory characteristics of NK cells described in infectious diseases; and finally phenotypical and functional changes after vaccination measured by immunomonitoring in preclinical and clinical settings.

  4. Single-cell analysis in cancer genomics (United States)

    Saadatpour, Assieh; Lai, Shujing; Guo, Guoji; Yuan, Guo-Cheng


    Genetic changes and environmental differences result in cellular heterogeneity among cancer cells within the same tumor, thereby complicating treatment outcomes. Recent advances in single-cell technologies have opened new avenues to characterize the intra-tumor cellular heterogeneity, identify rare cell types, measure mutation rates, and, ultimately, guide diagnosis and treatment. In this paper, we review the recent single-cell technological and computational advances at the genomic, transcriptomic, and proteomic levels, and discuss their applications in cancer research. PMID:26450340

  5. Loss of cadherin-based cell adhesion and the progression of Invasive Lobular Breast Cancer

    NARCIS (Netherlands)

    Vlug, E.J.


    Lobular breast cancer is a type of breast cancer that is histologically characterized by a noncohesive growth pattern of small regular cells, where single cells infiltrate as one-layered strands of cells. This noncohesive growth pattern is due to inactivation of the E-cadherin complex and a subseque

  6. An immunosurveillance mechanism controls cancer cell ploidy. (United States)

    Senovilla, Laura; Vitale, Ilio; Martins, Isabelle; Tailler, Maximilien; Pailleret, Claire; Michaud, Mickaël; Galluzzi, Lorenzo; Adjemian, Sandy; Kepp, Oliver; Niso-Santano, Mireia; Shen, Shensi; Mariño, Guillermo; Criollo, Alfredo; Boilève, Alice; Job, Bastien; Ladoire, Sylvain; Ghiringhelli, François; Sistigu, Antonella; Yamazaki, Takahiro; Rello-Varona, Santiago; Locher, Clara; Poirier-Colame, Vichnou; Talbot, Monique; Valent, Alexander; Berardinelli, Francesco; Antoccia, Antonio; Ciccosanti, Fabiola; Fimia, Gian Maria; Piacentini, Mauro; Fueyo, Antonio; Messina, Nicole L; Li, Ming; Chan, Christopher J; Sigl, Verena; Pourcher, Guillaume; Ruckenstuhl, Christoph; Carmona-Gutierrez, Didac; Lazar, Vladimir; Penninger, Josef M; Madeo, Frank; López-Otín, Carlos; Smyth, Mark J; Zitvogel, Laurence; Castedo, Maria; Kroemer, Guido


    Cancer cells accommodate multiple genetic and epigenetic alterations that initially activate intrinsic (cell-autonomous) and extrinsic (immune-mediated) oncosuppressive mechanisms. Only once these barriers to oncogenesis have been overcome can malignant growth proceed unrestrained. Tetraploidization can contribute to oncogenesis because hyperploid cells are genomically unstable. We report that hyperploid cancer cells become immunogenic because of a constitutive endoplasmic reticulum stress response resulting in the aberrant cell surface exposure of calreticulin. Hyperploid, calreticulin-exposing cancer cells readily proliferated in immunodeficient mice and conserved their increased DNA content. In contrast, hyperploid cells injected into immunocompetent mice generated tumors only after a delay, and such tumors exhibited reduced DNA content, endoplasmic reticulum stress, and calreticulin exposure. Our results unveil an immunosurveillance system that imposes immunoselection against hyperploidy in carcinogen- and oncogene-induced cancers.

  7. Clinical experience of Pseudo-Meigs' Syndrome due to colon cancer

    Institute of Scientific and Technical Information of China (English)

    HiromichiMaeda; TakehrioOkabayashi; KazuhiroHanazaki; MichiyaKobayashi


    We report a rare case of Pseudo-Meigs' Syndrome caused by ovarian metastasis from sigmoid colon cancer, which was accompanied by peritoneal dissemination. A 58-year-old female patient presented with massive right pleural effusion, ascites and a huge pelvic mass. Under the diagnosis of an advanced ovarian tumor, bilateral oophorectomy was performed and sigmoidectomy was also carried out after intraoperative diagnosis of peritoneal dissemination involving the sigmoid colon. How- ever, immunohistochemical staining revealed that the ovarian lesions were metastasis from the primary advanced colon cancer. Postoperatively, ascites and pleural effusion subsided, and the diagnosis of Pseudo-Meigs' Syndrome due to a metastatic ovarian tumor from colon cancer was determined. The patient is now undergoing a regimen of chemotherapy for colon cancer without recurrence of ascites or hydrothorax 10 mo after the surgery. Pseudo-Meigs' Syndrome due to a metastaticovarian tumor from colon cancer is rare but clinically important because long-term alleviation of symptoms can be achieved by surgical resection. This case report suggests that selected patients, even with peritoneal dissemination, may obtain palliation from surgical resection of metastatic ovarian tumors.

  8. Dies1/VISTA expression loss is a recurrent event in gastric cancer due to epigenetic regulation. (United States)

    Oliveira, Patrícia; Carvalho, Joana; Rocha, Sara; Azevedo, Mafalda; Reis, Inês; Camilo, Vânia; Sousa, Bárbara; Valente, Sofia; Paredes, Joana; Almeida, Raquel; Huntsman, David; Oliveira, Carla


    Dies1/VISTA induces embryonic stem-cell differentiation, via BMP-pathway, but also acts as inflammation regulator and immune-response modulator. Dies1 inhibition in a melanoma-mouse model led to increased tumour-infiltrating T-cells and decreased tumour growth, emphasizing Dies1 relevance in tumour-microenvironment. Dies1 is involved in cell de/differentiation, inflammation and cancer processes, which mimic those associated with Epithelial-to-Mesenchymal-Transition (EMT). Despite this axis linking Dies1 with EMT and cancer, its expression, modulation and relevance in these contexts is unknown. To address this, we analysed Dies1 expression, its regulation by promoter-methylation and miR-125a-5p overexpression, and its association with BMP-pathway downstream-effectors, in a TGFβ1-induced EMT-model, cancer cell-lines and primary samples. We detected promoter-methylation as a mechanism controlling Dies1 expression in our EMT-model and in several cancer cell-lines. We showed that the relationship between Dies1 expression and BMP-pathway effectors observed in the EMT-model, was not present in all cell-lines, suggesting that Dies1 has other cell-specific effectors, beyond the BMP-pathway. We further demonstrated that: Dies1 expression loss is a recurrent event in GC, caused by promoter methylation and/or miR-125a-5p overexpression and; GC-microenvironment myofibroblasts overexpress Dies1. Our findings highlight Dies1 as a novel player in GC, with distinct roles within tumour cells and in the tumour-microenvironment.

  9. Ionizing radiation induces stemness in cancer cells.

    Directory of Open Access Journals (Sweden)

    Laura Ghisolfi

    Full Text Available The cancer stem cell (CSC model posits the presence of a small number of CSCs in the heterogeneous cancer cell population that are ultimately responsible for tumor initiation, as well as cancer recurrence and metastasis. CSCs have been isolated from a variety of human cancers and are able to generate a hierarchical and heterogeneous cancer cell population. CSCs are also resistant to conventional chemo- and radio-therapies. Here we report that ionizing radiation can induce stem cell-like properties in heterogeneous cancer cells. Exposure of non-stem cancer cells to ionizing radiation enhanced spherogenesis, and this was accompanied by upregulation of the pluripotency genes Sox2 and Oct3/4. Knockdown of Sox2 or Oct3/4 inhibited radiation-induced spherogenesis and increased cellular sensitivity to radiation. These data demonstrate that ionizing radiation can activate stemness pathways in heterogeneous cancer cells, resulting in the enrichment of a CSC subpopulation with higher resistance to radiotherapy.

  10. Mast cells and cancer: enemies or allies? (United States)

    Dyduch, Grzegorz; Kaczmarczyk, Karolina; Okoń, Krzysztof


    Mast cells are a component of cancer microenvironment the role of which is complex and poorly understood. Mast cells promote cancer growth by stimulation of neoangiogenesis, tissue remodeling and by modulation of the host immune response. The mediators of cancer promotion include protease-activated receptors, mitogen activated protein kinases, prostaglandins and histamine. Histamine may induce tumor proliferation and immunosuppression through H1 and H2 receptors, respectively. The mast cell-derived modulators of immune response include also interleukin 10 (IL-10), tumor necrosis factor α (TNF-α) and CD30L. Possibly stimulation of angiogenesis is the most important. Mast cells release potent proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor β (TGF-β), TNF- α and IL-8, and mast cells' enzymes, like metaloproteinases (MMPs), tryptase and chymase participate in vessels' formation. The anti-cancer actions of mast cells include direct growth inhibition, immunologic stimulation, inhibition of apoptosis and decreased cell mobility; the mediators of these processes include chymase, tryptase, TNF-α, IL-1 and IL-6. The very same mediators may exert both pro- or anti-cancer effects depending on concentration, presence of cofactors or location of secreting cells. In fact, peri- and intra-tumoral mast cells may have dissimilar effects. Understanding of the role of mast cells in cancer could lead to improved prognostication and development of therapeutic methods targeting the mast cells.

  11. Dendritic cell-based cancer immunotherapy for colorectal cancer. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Mia K. Markey


    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.

  13. Depletion of Aurora-A in zebrafish causes growth retardation due to mitotic delay and p53-dependent cell death. (United States)

    Jeon, Hee-Yeon; Lee, Hyunsook


    Aurora-A is a serine/threonine mitotic kinase that is required for centrosome maturation. Many cancer cells over-express Aurora-A, and several reports have suggested that Aurora-A has prognostic value in the clinical treatment of cancer. Therefore, inhibitors for Aurora-A kinase have been developed. However, studies on Aurora-A are largely performed in cancer cell lines and are sometimes controversial. For effective evaluation of Aurora-A inhibitors in cancer treatment, it is essential to understand its function at the organism level. Here, we report the crucial functions of Aurora-A in homeostasis of spindle organization in mitosis using zebrafish embryogenesis as a model system. Using morpholino technology, we show that depletion of Aurora-A in zebrafish embryogenesis results in short bent trunks, accompanied by growth retardation and eventual cell death. Live-imaging and immunofluorescence analyses of the embryos revealed that the developmental defects are due to problems in mitosis, manifested through monopolar and disorganized spindle formation. Aurora-A-depleted cells exhibited mitotic arrest with congression failure, leading to activation of the spindle assembly checkpoint. Cell death in the absence of Aurora-A was partially rescued by co-injection of the p53 morpholino, suggesting that apoptosis after Aurora-A depletion is p53-dependent. The clinical implications of these results relate to the indication that Aurora-A inhibitors may be effective towards cancers with intact p53.

  14. Wnt Signaling in Cancer Stem Cell Biology. (United States)

    de Sousa E Melo, Felipe; Vermeulen, Louis


    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.

  15. Relevance of mortalin to cancer cell stemness and cancer therapy. (United States)

    Yun, Chae-Ok; Bhargava, Priyanshu; Na, Youjin; Lee, Jung-Sun; Ryu, Jihoon; Kaul, Sunil C; Wadhwa, Renu


    Mortalin/mtHsp70 is a member of Hsp70 family of proteins. Enriched in a large variety of cancers, it has been shown to contribute to the process of carcinogenesis by multiple ways including inactivation of tumor suppressor p53 protein, deregulation of apoptosis and activation of EMT signaling. In this study, we report that upregulation of mortalin contributes to cancer cell stemness. Several cancer cell stemness markers, such as ABCG2, OCT-4, CD133, ALDH1, CD9, MRP1 and connexin were upregulated in mortalin-overexpressing cells that showed higher ability to form spheroids. These cells also showed higher migration, and were less responsive to a variety of cancer chemotherapeutic drugs. Of note, knockdown of mortalin by specific shRNA sensitized these cells to all the drugs used in this study. We report that low doses of anti-mortalin molecules, MKT-077 and CAPE, also caused similar sensitization of cancer cells to chemotherapeutic drugs and hence are potential candidates for effective cancer chemotherapy.

  16. Relevance of mortalin to cancer cell stemness and cancer therapy (United States)

    Yun, Chae-Ok; Bhargava, Priyanshu; Na, Youjin; Lee, Jung-Sun; Ryu, Jihoon; Kaul, Sunil C.; Wadhwa, Renu


    Mortalin/mtHsp70 is a member of Hsp70 family of proteins. Enriched in a large variety of cancers, it has been shown to contribute to the process of carcinogenesis by multiple ways including inactivation of tumor suppressor p53 protein, deregulation of apoptosis and activation of EMT signaling. In this study, we report that upregulation of mortalin contributes to cancer cell stemness. Several cancer cell stemness markers, such as ABCG2, OCT-4, CD133, ALDH1, CD9, MRP1 and connexin were upregulated in mortalin-overexpressing cells that showed higher ability to form spheroids. These cells also showed higher migration, and were less responsive to a variety of cancer chemotherapeutic drugs. Of note, knockdown of mortalin by specific shRNA sensitized these cells to all the drugs used in this study. We report that low doses of anti-mortalin molecules, MKT-077 and CAPE, also caused similar sensitization of cancer cells to chemotherapeutic drugs and hence are potential candidates for effective cancer chemotherapy. PMID:28165047

  17. The direct effect of estrogen on cell viability and apoptosis in human gastric cancer cells. (United States)

    Qin, Jian; Liu, Min; Ding, Qianshan; Ji, Xiang; Hao, Yarong; Wu, Xiaomin; Xiong, Jie


    Epidemiology researches indicated that gastric cancer is a male-predominant disease; both expression level of estrogen and expression pattern of estrogen receptors (ERs) influence its carcinogenesis. But the direct effect of estrogen on gastric cancer cells is still unclear. This study aimed to explore the direct effect of β-estradiol (E2) on gastric cancer cells. SGC7901 and BGC823 were treated with a serial of concentrations of E2. The survival rates of both the cell lines were significantly reduced, and the reduction of viability was due to apoptosis triggered by E2 treatment. Caspase 3 was activated in response to the increasing E2 concentration in both SGC7901 and BGC823. Cleaved Caspase 3 fragments were detected, and the expression levels of Bcl-2 and Bcl-xL were reduced. Apoptosis was further confirmed by flow cytometry. The expression level of PEG10, an androgen receptor target gene, was reduced during E2 treatment. Both ERα and ERβ were expressed in these cell lines, and the result of bioinformatics analysis of gastric cancer from GEO datasets indicated that the expression levels of both ERα and ERβ were significantly higher in noncancerous gastric tissues than in gastric cancer tissues. Our research indicated that estrogen can reduce cell viability and promote apoptosis in gastric cancer cells directly; ERs expression level is associated with gastric cancer. Our research will help to understand the mechanism of gender disparity in gastric cancer.

  18. Repression of cancer cell senescence by PKCι. (United States)

    Paget, J A; Restall, I J; Daneshmand, M; Mersereau, J A; Simard, M A; Parolin, D A E; Lavictoire, S J; Amin, M S; Islam, S; Lorimer, I A J


    Senescence is an irreversible growth arrest phenotype adopted by cells that has a key role in protecting organisms from cancer. There is now considerable interest in therapeutic strategies that reactivate this process to control the growth of cancer cells. Protein kinase-Cι (PKCι) is a member of the atypical PKC family and an important downstream mediator in the phosphoinositide-3-kinase (PI-3-kinase) pathway. PKCι expression was found to be upregulated in a subset of breast cancers and breast cancer cell lines. Activation of the PI-3-kinase pathway by introduction of mutant, oncogenic PIK3CA into breast mammary epithelial cells increased both the expression and activation of PKCι. In breast cancer cells lines overexpressing PKCι, depletion of PKCι increased the number of senescent cells, as assessed by senescence-associated β-galactosidase, morphology and bromodeoxyuridine incorporation. This phenomenon was not restricted to breast cancer cells, as it was also seen in glioblastoma cells in which PKCι is activated by loss of PTEN. Senescence occurred in the absence of a detectable DNA-damage response, was dependent on p21 and was enhanced by the aurora kinase inhibitor VX-680, suggesting that senescence is triggered by defects in mitosis. Depletion of PKCι had no effect on senescence in normal mammary epithelial cell lines. We conclude that PKCι is overexpressed in a subset of cancers where it functions to suppress premature senescence. This function appears to be restricted to cancer cells and inhibition of PKCι may therefore be an effective way to selectively activate premature senescence in cancer cells.

  19. Tumor acidosis enhances cytotoxic effects and autophagy inhibition by salinomycin on cancer cell lines and cancer stem cells (United States)

    Pellegrini, Paola; Dyczynski, Matheus; Sbrana, Francesca Vittoria; Karlgren, Maria; Buoncervello, Maria; Hägg-Olofsson, Maria; Ma, Ran; Hartman, Johan; Bajalica-Lagercrantz, Svetlana; Grander, Dan; Kharaziha, Pedram; De Milito, Angelo


    Sustained autophagy contributes to the metabolic adaptation of cancer cells to hypoxic and acidic microenvironments. Since cells in such environments are resistant to conventional cytotoxic drugs, inhibition of autophagy represents a promising therapeutic strategy in clinical oncology. We previously reported that the efficacy of hydroxychloroquine (HCQ), an autophagy inhibitor under clinical investigation is strongly impaired in acidic tumor environments, due to poor uptake of the drug, a phenomenon widely associated with drug resistance towards many weak bases. In this study we identified salinomycin (SAL) as a potent inhibitor of autophagy and cytotoxic agent effective on several cancer cell lines under conditions of transient and chronic acidosis. Since SAL has been reported to specifically target cancer-stem cells (CSC), we used an established model of breast CSC and CSC derived from breast cancer patients to examine whether this specificity may be associated with autophagy inhibition. We indeed found that CSC-like cells are more sensitive to autophagy inhibition compared to cells not expressing CSC markers. We also report that the ability of SAL to inhibit mammosphere formation from CSC-like cells was dramatically enhanced in acidic conditions. We propose that the development and use of clinically suitable SAL derivatives may result in improved autophagy inhibition in cancer cells and CSC in the acidic tumor microenvironment and lead to clinical benefits. PMID:27248168

  20. Nucleolar function and size in cancer cells.


    Derenzini, M; Trerè, D; Pession, A; Montanaro, L; Sirri, V.; Ochs, R. L.


    We have have studied the relationship between nucleolar function and size and cell doubling time in cancer cells. Seven human cancer cell lines characterized by different proliferation rates were used. Nucleolar functional activity was evaluated by measuring RNA polymerase I activity and expression of RNA polymerase I upstream binding factor (UBF), DNA topoisomerase I, and fibrillarin, three proteins involved in synthesis and processing of rRNA. Transcriptional activity of RNA polymerase I wa...

  1. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng


    Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

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

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


    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

  3. 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


    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.

  4. Triiodothyronine regulates cell growth and survival in renal cell cancer. (United States)

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


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

  5. Simvastatin suppresses breast cancer cell proliferation induced by senescent cells

    NARCIS (Netherlands)

    Liu, Su; Uppal, Harpreet; Demaria, Marco; Desprez, Pierre-Yves; Campisi, Judith; Kapahi, Pankaj


    Cellular senescence suppresses cancer by preventing the proliferation of damaged cells, but senescent cells can also promote cancer though the pro-inflammatory senescence-associated secretory phenotype (SASP). Simvastatin, an HMG-coA reductase inhibitor, is known to attenuate inflammation and preven

  6. Tyrosine kinase inhibitors target cancer stem cells in renal cell cancer. (United States)

    Czarnecka, Anna M; Solarek, Wojciech; Kornakiewicz, Anna; Szczylik, Cezary


    This study was designed to analyze the impact of multi-targeted tyrosine kinase inhibitors on the cancer stem cell subpopulation in renal cell cancer. The second objective was to evaluate the effect of tumor growth inhibition related to a tumor niche factor - oxygen deprivation - as hypoxia develops along with the anti-angiogenic activity of tyrosine kinase inhibitors in renal tumors. Cells were treated with tyrosine kinase inhibitors, sunitinib, sorafenib and axitinib, in 2D and 3D culture conditions. Cell proliferation along with drug toxicity were evaluated. It was shown that the proliferation rate of cancer stem cells was decreased by the tyrosine kinase inhibitors. The efficacy of the growth inhibition was limited by hypoxic conditions and 3D intratumoral cell-cell interactions. We conclude that understanding the complex molecular interaction feedback loops between differentiated cancer cells, cancer stem cells and the tumor microenvironment in 3D culture should aid the identification of novel treatment targets and to evalute the efficacy of renal cancer therapies. Cell-cell interaction may represent a critical microenvironmental factor regulating cancer stem cell self-renewal potential, enhancing the stem cell phenotype and limiting drug toxicity. At the same time the role of hypoxia in renal cancer stem cell biology is also significant.

  7. Regulation of cancer cell migration and invasion by sphingosine-1-phosphate

    Institute of Scientific and Technical Information of China (English)

    James; R; Van; Brocklyn


    Sphingosine-1-phosphate (S1P) is a bioactive sphingo-lipid that has been implicated in regulation of a number of cancer cell malignant behaviors, including cell proliferation, survival, chemotherapeutic resistance and angiogenesis. However, the effects of S1P on cancer cell migration, invasion and metastasis, are perhaps its most complex, due to the fact that, depending upon the S1P receptors that mediate its responses and the crosstalk with other signaling pathways, S1P can either positively or negatively regulate invasion. This review summarizes the effects of S1P on cancer cell invasion and the mechanisms by which it affects this important aspect of cancer cell behavior.

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

    Directory of Open Access Journals (Sweden)

    Ayşe Arduç


    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.

  9. 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

    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....... The focus for this study is to evaluate the follow-up program in fulfilling the purpose for early diagnosis of recurrence while reminding and concerning women, who we consider healthy after surgery, 10 times during five years. Already politicians are focusing on the subject due to the socioeconomic...... 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...

  10. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    Patricia Chang


    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.

  12. Urethral Fistula and Scrotal Abscess Associated with Colovesical Fistula Due to the Sigmoid Colon Cancer



    We report here a rare case of urethral fistula and scrotal abscess associated with colovesical fistula due to sigmoid colon cancer. An 84-year-old male was referred to our hospital complaining of macrohematuria, fecaluria, pneumaturia and micturitional pain. Computed tomography (CT) showed colovesical fistula. Other examinations, including colonoscopy and cystoscopy, did not reveal a clear cause for the colovesical fistula. Only an elevated serum level of the tumor marker CA19-9 suggested the...

  13. Stem cell concepts renew cancer research. (United States)

    Dick, John E


    Although uncontrolled proliferation is a distinguishing property of a tumor as a whole, the individual cells that make up the tumor exhibit considerable variation in many properties, including morphology, proliferation kinetics, and the ability to initiate tumor growth in transplant assays. Understanding the molecular and cellular basis of this heterogeneity has important implications in the design of therapeutic strategies. The mechanistic basis of tumor heterogeneity has been uncertain; however, there is now strong evidence that cancer is a cellular hierarchy with cancer stem cells at the apex. This review provides a historical overview of the influence of hematology on the development of stem cell concepts and their linkage to cancer.

  14. Updates in colorectal cancer stem cell research

    Directory of Open Access Journals (Sweden)

    Chun-Jie Li


    Full Text Available Colorectal cancer (CRC is one of the world most common malignant tumors, also is the main disease, which cause tumor-associated death. Surgery and chemotherapy are the most used treatment of CRC. Recent research reported that, cancer stem cells (CSCs are considered as the origin of tumor genesis, development, metastasis and recurrence in theory. At present, it has been proved that, CSCs existed in many tumors including CRC. In this review, we summary the identification of CSCs according to the cell surface markers, and the development of drugs that target colorectal cancer stem cells.

  15. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin


    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.

  16. A rare case of repeated anastomotic recurrence due to tumor implantation after curative surgery for sigmoid colon cancer

    Directory of Open Access Journals (Sweden)

    Shiokawa Hiroyuki


    Full Text Available Abstract Background Anastomotic recurrence is often experienced at colocolic or colorectal anastomoses. Tumor cell implantation has been reported as the mechanism of anastomotic recurrence. However, anastomotic recurrence occurring repeatedly after curative surgery is rare. We herein report a rare case of repeated anastomotic recurrence after curative surgery for sigmoid colon cancer. Case presentation A 51-year-old man underwent radical surgery for sigmoid colon cancer. However, anastomotic recurrence developed three times during three years and six months after the initial operation in spite of irrigation with 5% povidone-iodine before anastomosis. The serum carcinoembryonic antigen (CEA level had been within normal limits after sigmoidectomy. Finally, the patient underwent abdominoperineal resection. The clinico-pathological findings revealed that possible tumor cell implantation caused these anastomotic recurrences. The patients survived without recurrence during the follow-up period of seven years and nine months. Conclusion We experienced a rare case of repeated anastomotic recurrence due to possible tumor implantation after curative surgery for sigmoid colon cancer; however the prognosis was ultimately very good. CEA monitoring was insensitive for detection of anastomotic recurrence in this case.

  17. 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: [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China)


    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.

  18. Metformin induces apoptosis of pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)


    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.

  19. Treatment Options by Stage (Small Cell Lung Cancer) (United States)

    ... lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The ... diagnosed, tests are done to find out if cancer cells have spread within the chest or to other ...

  20. Induction of cancer cell stemness by chemotherapy. (United States)

    Hu, Xingwang; Ghisolfi, Laura; Keates, Andrew C; Zhang, Jian; Xiang, Shuanglin; Lee, Dong-ki; Li, Chiang J


    Recent studies indicate that cancer stem cells (CSCs) exist in most hematological and solid tumors. CSCs are characterized by their ability to self-renew and their capacity to differentiate into the multitude of cells that comprise the tumor mass. Moreover, these cells have been shown to be intrinsically resistant to conventional anticancer therapies. Despite their fundamental role in cancer pathogenesis, the cellular origin of CSCs remains highly controversial. The aim of this study was to examine whether heterogeneous cancer cells can acquire stem cell-like properties in response to chemotherapy. We demonstrate that carboplatin can induce the self-renewal (spherogenesis) and pluripotency (Sox2 and Oct3/4 expression) of hepatocellular carcinoma (HCC) cells grown under stem cell culture conditions. Moreover, we show that non-CSC cells, obtained by side population flow cytometric sorting using Hoechst 33342, can acquire stem-like properties after exposure to carboplatin. Finally, we show that knockdown of Sox2 and Oct3/4 gene expression in HCC cells can reduce carboplatin-mediated increases in sphere formation and increase cellular sensitivity to chemotherapy. Taken together, our data indicate that bulk cancer cells may be an important source of CSCs during tumor development, and that targeting Sox2 and/or Oct3/4 may be a promising approach for targeting CSCs in clinical cancer treatment.

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


    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


    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...

  2. Targetless T cells in cancer immunotherapy

    DEFF Research Database (Denmark)

    Thor Straten, Per; Garrido, Federico


    Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulating T-cell cytotoxicity has achieved impressive clinical responses, as has adoptive cell ...

  3. Gene sensitizes cancer cells to chemotherapy drugs (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

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

    Directory of Open Access Journals (Sweden)

    Bhushan Murkey


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

  5. Low white blood cell count and cancer (United States)

    ... this page: // Low white blood cell count and cancer To use ... high blood pressure, or seizures Continue Reading How Low is too Low? When your blood is tested, ...

  6. Drug delivery system and breast cancer cells (United States)

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


    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.

  7. Orbital Infarction due to Sickle Cell Disease without Orbital Pain

    Directory of Open Access Journals (Sweden)

    Cameron L. McBride


    Full Text Available Sickle cell disease is a hemoglobinopathy that results in paroxysmal arteriolar occlusion and tissue infarction that can manifest in a plurality of tissues. Rarely, these infarcted crises manifest in the bony orbit. Orbital infarction usually presents with acute onset of periorbital tenderness, swelling, erythema, and pain. Soft tissue swelling can result in proptosis and attenuation of extraocular movements. Expedient diagnosis of sickle cell orbital infarction is crucial because this is a potentially sight-threatening entity. Diagnosis can be delayed since the presentation has physical and radiographic findings mimicking various infectious and traumatic processes. We describe a patient who presented with sickle cell orbital crisis without pain. This case highlights the importance of maintaining a high index of suspicion in patients with known sickle cell disease or of African descent born outside the United States in a region where screening for hemoglobinopathy is not routine, even when the presentation is not classic.

  8. 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


    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.

  9. Cancer Stem Cells in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Xiao-Jing Wang


    Full Text Available Head and neck cancer (HNC is the sixth most common malignancy world-wide, however the survival rate has not improved for the past 20 years. In recent years, the cancer stem cell (CSC hypothesis has gained ground in several malignancies and there is mounting evidence suggesting CSCs mediate tumor resistance to chemotherapy and radiation therapy. However, the CSC theory is also challenged at least in certain types of cancer. Here we review the progress of CSC studies in HNC, which suggest that HNC conforms to the CSC model. The identified CSC markers and their tumor initiation properties provide a framework for the development of novel therapeutic strategies for HNC.

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

  11. PTEN, Stem Cells, and Cancer Stem Cells*S⃞


    Hill, Reginald; Wu, Hong


    Like normal stem cells, “cancer stem cells” have the capacity for indefinite proliferation and generation of new cancerous tissues through self-renewal and differentiation. Among the major intracellular signaling pathways, WNT, SHH, and NOTCH are known to be important in regulating normal stem cell activities, and their alterations are associated with tumorigenesis. It has become clear recently that PTEN (phosphatase and tensin homologue) is also critical for stem cell...

  12. Targeting Prostate Cancer Stem Cells with Alpha-Particle Therapy (United States)

    Ceder, Jens; Elgqvist, Jörgen


    Modern molecular and radiopharmaceutical development has brought the promise of tumor-selective delivery of antibody–drug conjugates to tumor cells for the diagnosis and treatment of primary and disseminated tumor disease. The classical mode of discourse regarding targeted therapy has been that the antigen targeted must be highly and homogenously expressed in the tumor cell population, and at the same time exhibit low expression in healthy tissue. However, there is increasing evidence that the reason cancer patients are not cured by current protocols is that there exist subpopulations of cancer cells that are resistant to conventional therapy including radioresistance and that these cells express other target antigens than the bulk of the tumor cells. These types of cells are often referred to as cancer stem cells (CSCs). The CSCs are tumorigenic and have the ability to give rise to all types of cells found in a cancerous disease through the processes of self-renewal and differentiation. If the CSCs are not eradicated, the cancer is likely to recur after therapy. Due to some of the characteristics of alpha particles, such as short path length and high density of energy depositions per distance traveled in tissue, they are especially well suited for use in targeted therapies against microscopic cancerous disease. The characteristics of alpha particles further make it possible to minimize the irradiation of non-targeted surrounding healthy tissue, but most importantly, make it possible to deliver high-absorbed doses locally and therefore eradicating small tumor cell clusters on the submillimeter level, or even single tumor cells. When alpha particles pass through a cell, they cause severe damage to the cell membrane, cytoplasm, and nucleus, including double-strand breaks of DNA that are very difficult to repair for the cell. This means that very few hits to a cell by alpha particles are needed in order to cause cell death, enabling killing of cells, such as CSCs

  13. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors. (United States)

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


    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.

  14. Cancer Vaccine by Fusions of Dendritic and Cancer Cells


    Shigeo Koido; Eiichi Hara; Sadamu Homma; Yoshihisa Namiki; Toshifumi Ohkusa; Jianlin Gong; Hisao Tajiri


    Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived...

  15. Reducing bone cancer cell functions using selenium nanocomposites. (United States)

    Stolzoff, Michelle; Webster, Thomas J


    Cancer recurrence at the site of tumor resection remains a major threat to patient survival despite modern cancer therapeutic advances. Osteosarcoma, in particular, is a very aggressive primary bone cancer that commonly recurs after surgical resection, radiation, and chemotherapeutic treatment. The objective of the present in vitro study was to develop a material that could decrease bone cancer cell recurrence while promoting healthy bone cell functions. Selenium is a natural part of our diet which has shown promise for reducing cancer cell functions, inhibiting bacteria, and promoting healthy cells functions, yet, it has not been widely explored for osteosarcoma applications. For this purpose, due to their increased surface area, selenium nanoparticles (SeNP) were precipitated on a very common orthopedic tissue engineering material, poly-l-lactic acid (or PLLA). Selenium-coated PLLA materials were shown to selectively decrease long-term osteosarcoma cell density while promoting healthy, noncancerous, osteoblast functions (for example, up to two times more alkaline phosphatase activity on selenium coated compared to osteoblasts grown on typical tissue culture plates), suggesting they should be further studied for replacing tumorous bone tissue with healthy bone tissue. Importantly, results of this study were achieved without the use of chemotherapeutics or pharmaceutical agents, which have negative side effects.

  16. Advances and perspectives of colorectal cancer stem cell vaccine. (United States)

    Guo, Mei; Dou, Jun


    Colorectal cancer is essentially an environmental and genetic disease featured by uncontrolled cell growth and the capability to invade other parts of the body by forming metastases, which inconvertibly cause great damage to tissues and organs. It has become one of the leading causes of cancer-related mortality in the developed countries such as United States, and approximately 1.2 million new cases are yearly diagnosed worldwide, with the death rate of more than 600,000 annually and incidence rates are increasing in most developing countries. Apart from the generally accepted theory that pathogenesis of colorectal cancer consists of genetic mutation of a certain target cell and diversifications in tumor microenvironment, the colorectal cancer stem cells (CCSCs) theory makes a different explanation, stating that among millions of colon cancer cells there is a specific and scanty cellular population which possess the capability of self-renewal, differentiation and strong oncogenicity, and is tightly responsible for drug resistance and tumor metastasis. Based on these characteristics, CCSCs are becoming a novel target cells both in the clinical and the basic studies, especially the study of CCSCs vaccines due to induced efficient immune response against CCSCs. This review provides an overview of CCSCs and preparation technics and targeting factors related to CCSCs vaccines in detail.

  17. Multiple myeloma cancer stem cells (United States)

    Gao, Minjie; Kong, Yuanyuan; Yang, Guang; Gao, Lu; Shi, Jumei


    Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contributes to disease relapse, but the mechanisms of drug resistance have not been fully understood. The major signaling pathways involved in the regulation of self-renewal and differentiation of MMSCs include Hedgehog (Hh), Wingless (Wnt), Notch and PI3K/Akt/mTOR. However, the precise role of these signaling pathways needs to be clarified. It has been reported that the microRNA profile of MMSCs is remarkably different than that of non-MMSCs. Therefore, the search for targeting MMSCs has also been focused on microRNAs. Complex and mutual interactions between the MMSC and the surrounding bone marrow (BM) microenvironment sustain self-renewal and survival of MMSC. However, the required molecules for the interaction of the MMSC and the surrounding BM microenvironment need to be further identified. In this review, we summarize the current state of knowledge of MMSCs regarding their phenotype, mechanisms of drug resistance, signaling pathways that regulate MMSCs self-renewal and differentiation, abnormal microRNAs expression, and their interactions with the BM microenvironment. PMID:27007154

  18. Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas (United States)


    progenitor cells (NPCs) by expressing an activated form of Notch1 (N1ICD) or oncogenic PIK3CA (PIK3CA*) in the developing mouse cerebellum, using cell...resistance, pediatric cancer, brain tumor, Notch1, PIK3CA, cell of origin, molecular subtypes, neural stem cells, neural progenitor cells, tumor initiation...neural progenitor cells, tumor initiation. 3. ACCOMPLISHMENTS: Major goals of the project: The stated goals of this project are to: 1) test the

  19. Exercise regulates breast cancer cell viability

    DEFF Research Database (Denmark)

    Dethlefsen, Christine; Lillelund, Christian; Midtgaard, Julie


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

  20. Cancer and deregulation of stem cells pathways

    Directory of Open Access Journals (Sweden)

    Filipe Correia Martins


    Full Text Available Stem cells may have an important etiological role in cancer. Their classic regulatory pathways are deregulated in tumors, strengthening the stem cell theory of cancer. In this manuscript, we review Wnt, Notch and Hedhehog pathways, describing which of their factors may be responsible for the neoplastic development. Furthermore, we classify these elements as oncogenes or tumor suppressor genes, demonstrating their mutation implications in cancer. The activation of these pathways is associated with the expression of certain genes which maintain proliferation and apoptosis inhibition. Further work should be carried out in the future in order to control tumor development by controlling these signaling cascades.

  1. Ultrasonic Detection of Microscopic Breast Cancer in Cell Cultures (United States)

    Goodrich, Jeffrey B.; Patel, Hemang; Doyle, Timothy E.; Kwon, Soonjo


    A current problem in breast cancer treatment is the detection of microscopic cancer in surgical margins to ensure all of the cancer has been removed. Current methods rely on extensive pathology work that may take several days to complete. Positive findings for cancer in margins require follow-up surgery for up to 50% of lumpectomy patients to remove more tissue. A microscopic detection method for use during surgery would be preferable to reduce the risks, costs, and patient suffering of follow-up operations. Ultrasound is a promising in vivo detection method due to its low cost, portability, and ability to detect malignant tissue changes. Recent experiments have demonstrated the ultrasonic detection of microscopic cancer in cell cultures. Ultrasonic waveforms from pulse echo measurements showed significant differences between normal and malignant cell monolayers. The ultrasound also detected normal and malignant monolayer growth that displayed good correlations with cell counts. These results support the use of ultrasound as a viable method for in vivo detection. Testing of surgical samples at the Huntsman Cancer Institute is now in progress.

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

    Directory of Open Access Journals (Sweden)

    Kawamoto Megumi


    Full Text Available Abstract Background 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. Methods 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. Results 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 T47

  3. Recurrent Syncope due to Esophageal Squamous Cell Carcinoma



    Syncope is caused by a wide variety of disorders. Recurrent syncope as a complication of malignancy is uncommon and may be difficult to diagnose and to treat. Primary neck carcinoma or metastases spreading in parapharyngeal and carotid spaces can involve the internal carotid artery and cause neurally mediated syncope with a clinical presentation like carotid sinus syndrome. We report the case of a 76-year-old man who suffered from recurrent syncope due to invasion of the right carotid sinus b...

  4. MiR-197 induces Taxol resistance in human ovarian cancer cells by regulating NLK. (United States)

    Zou, Dongling; Wang, Dong; Li, Rong; Tang, Ying; Yuan, Li; Long, Xingtao; Zhou, Qi


    Chemotherapy is the preferred therapeutic approach for the therapy of advanced ovarian cancer, but 5-year survival rate remains low due to the development of drug resistance. Increasing evidence has documented that microRNAs (miRNAs) act important roles in drug resistance in a variety types of cancer. However, the roles of miRNA in regulating Taxol resistance in ovarian cancer and the detailed mechanism are less reported. We used Taqman probe stem loop real-time PCR to accurately measure the levels of miR-197 in normal ovarian cells, ovarian cancer cells, and Taxol-resistant ovarian cancer cells and found that miR-197 was significantly increased in Taxol-resistant ovarian cancer cells. Enforced expression of miR-197 can promote Taxol resistance, cell proliferation, and invasion of ovarian cancer cells. Meanwhile, repression of miR-197 in ovarian cancer cells can sensitize its response to Taxol and also induced attenuated cell proliferation and invasion ability. Furthermore, investigation of the detailed mechanism showed that the promotion of miR-197 on drug resistance in ovarian cancer cells was partially mediated by downregulating NLK, a negative regulator of WNT signaling pathway. Taken together, our work first demonstrated that miR-197 can confer drug resistance to Taxol, by regulating tumor suppressor, NLK expression in ovarian cancer cells.

  5. 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


    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...

  6. The effects of cyclooxygenase-2 inhibitors on urological cancer cells. (United States)

    Yoshimura, Rikio; Matsuyama, Masahide; Kawahito, Yutaka; Takemoto, Yoshiaki; Tsuchida, Kenji; Kuratsukuri, Katsuyuki; Segawa, Yoshihiro; Shinnka, Toshiaki; Sano, Hajime; Nakatani, Tatsuya


    Cyclooxygenase (COX)-2 plays an important role in the development of various cancers due to its angiogenic function. We have demonstrated that the expression of COX-2 was up-regulated in human renal cell carcinoma (RCC), bladder tumor (BT) and prostate cancer (PC). In this study, we examined the effects of COX-2 inhibitors on cell proliferation in RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. COX-2 inhibitors did not induce a reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, showed no inhibition of cell proliferation using COX-2 inhibitors. COX-2 inhibitors could not stop the growth of RCC, BT and PC cells. Typical characteristics of apoptosis, i.e. chromatin condensation, cellular shrinkage, small membrane-bound bodies (apoptotic bodies) and cytoplasmic condensation, did not occur. Although the expression of COX-2 was up-regulated in human RCC, BT and PC tissues, COX-2 inhibitors have only slight anti-proliferative effects against RCC, BT and PC cells through differentiation. Thus, using only down-regulation of arachidonic acid (AA) metabolizing enzyme, COX may be an unsuccessful approach in providing new anti-cancer therapies.

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

    Directory of Open Access Journals (Sweden)

    Evelyn Lamy

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

  8. Overcoming Multidrug Resistance in Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Karobi Moitra


    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.

  9. Neurotrophin signaling in cancer stem cells. (United States)

    Chopin, Valérie; Lagadec, Chann; Toillon, Robert-Alain; Le Bourhis, Xuefen


    Cancer stem cells (CSCs), are thought to be at the origin of tumor development and resistance to therapies. Thus, a better understanding of the molecular mechanisms involved in the control of CSC stemness is essential to the design of more effective therapies for cancer patients. Cancer cell stemness and the subsequent expansion of CSCs are regulated by micro-environmental signals including neurotrophins. Over the years, the roles of neurotrophins in tumor development have been well established and regularly reviewed. Especially, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are reported to stimulate tumor cell proliferation, survival, migration and/or invasion, and favors tumor angiogenesis. More recently, neurotrophins have been reported to regulate CSCs. This review briefly presents neurotrophins and their receptors, summarizes their roles in different cancers, and discusses the emerging evidence of neurotrophins-induced enrichment of CSCs as well as the involved signaling pathways.

  10. Knockdown of Immature Colon Carcinoma Transcript 1 Inhibits Proliferation and Promotes Apoptosis of Non-Small Cell Lung Cancer Cells. (United States)

    Wang, Yiling; He, Jiantao; Zhang, Shenghui; Yang, Qingbo; Wang, Bo; Liu, Zhiyu; Wu, Xintian


    Non-small cell lung cancer, as the most frequent type lung cancer, has lower survival rate of 5 years, despite improvements in surgery and chemotherapy. Previous studies showed immature colon carcinoma transcript 1 is closely related to tumorigenesis of human cancer cells. In the present study, we found immature colon carcinoma transcript 1 was overexpressed in lung cancer tissues using Oncomine database mining, and the biological effect of immature colon carcinoma transcript 1 was investigated in non-small cell lung cancer cell lines 95D and A549. Lentivirus-mediated RNA interference was used to knock down immature colon carcinoma transcript 1 expression in 95D and A549 cells in vitro, and the knockdown efficiency was determined using quantitative real-time polymerase chain reaction and Western blot assay. Knockdown of immature colon carcinoma transcript 1 significantly suppressed non-small cell lung cancer cell proliferation and colony formation ability confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Flow cytometry was applied to measure cell cycle arrest, and the result showed the cell cycle arrested in G2/M phase in 95D cells and arrested in G0/G1 phase in A549 cells. Furthermore, we measured the levels of cell cycle-associated proteins by Western blot analysis and found immature colon carcinoma transcript 1-mediated cell proliferation inhibition appeared due to downregulation of cell cycle activator cyclin D1 and upregulation of cell cycle inhibitor p21. In addition, immature colon carcinoma transcript 1 silencing significantly induced non-small cell lung cancer cell apoptosis by annexin V/7-amino-actinomycin D double-staining assay. All our data suggest that immature colon carcinoma transcript 1 may play an important role for non-small cell lung cancer cell proliferation and could be a potential molecular target for diagnosing and treating human non-small cell lung cancer.

  11. Isolation of Cancer Stem Cells From Human Prostate Cancer Samples (United States)

    Vidal, Samuel J.; Quinn, S. Aidan; de la Iglesia-Vicente, Janis; Bonal, Dennis M.; Rodriguez-Bravo, Veronica; Firpo-Betancourt, Adolfo; Cordon-Cardo, Carlos; Domingo-Domenech, Josep


    The cancer stem cell (CSC) model has been considerably revisited over the last two decades. During this time CSCs have been identified and directly isolated from human tissues and serially propagated in immunodeficient mice, typically through antibody labeling of subpopulations of cells and fractionation by flow cytometry. However, the unique clinical features of prostate cancer have considerably limited the study of prostate CSCs from fresh human tumor samples. We recently reported the isolation of prostate CSCs directly from human tissues by virtue of their HLA class I (HLAI)-negative phenotype. Prostate cancer cells are harvested from surgical specimens and mechanically dissociated. A cell suspension is generated and labeled with fluorescently conjugated HLAI and stromal antibodies. Subpopulations of HLAI-negative cells are finally isolated using a flow cytometer. The principal limitation of this protocol is the frequently microscopic and multifocal nature of primary cancer in prostatectomy specimens. Nonetheless, isolated live prostate CSCs are suitable for molecular characterization and functional validation by transplantation in immunodeficient mice. PMID:24686446

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

    LENUS (Irish Health Repository)

    Noctor, E


    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.

  13. Gonadal vein tumor thrombosis due to renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hamidreza Haghighatkhah


    Full Text Available Renal cell carcinoma (RCC had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC

  14. Gonadal vein tumor thrombosis due to renal cell carcinoma. (United States)

    Haghighatkhah, Hamidreza; Karimi, Mohammad Ali; Taheri, Morteza Sanei


    Renal cell carcinoma (RCC) had a tendency to extend into the renal vein and inferior vena cava, while extension into the gonadal vein has been rarely reported. Gonadal vein tumor thrombosis appears as an enhancing filling defect within the dilated gonadal vein anterior to the psoas muscle and shows an enhancement pattern identical to that of the original tumor. The possibility of gonadal vein thrombosis should be kept in mind when looking at an imaging study of patients with RCC.

  15. Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor (United States)

    Guo, W; Liu, R; Bhardwaj, G; Yang, J C; Changou, C; Ma, A-H; Mazloom, A; Chintapalli, S; Xiao, K; Xiao, W; Kumaresan, P; Sanchez, E; Yeh, C-T; Evans, C P; Patterson, R; Lam, K S; Kung, H-J


    Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a ‘wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model. PMID:25188519

  16. Technical Evaluation of the NASA Model for Cancer Risk to Astronauts Due to Space Radiation (United States)


    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

  17. 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.

  18. Cancer Cells Hijack Gluconeogenic Enzymes to Fuel Cell Growth. (United States)

    Balsa-Martinez, Eduardo; Puigserver, Pere


    In this issue and the October 15th issue of Molecular Cell, studies by Montal et al. (2015) and Vincent et al. (2015) report that certain types of cancer cells utilize the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxykinase 2 (PCK2) to reprogram anabolic metabolism and support cell growth.

  19. Cell polarity signaling in the plasticity of cancer cell invasiveness. (United States)

    Gandalovičová, Aneta; Vomastek, Tomáš; Rosel, Daniel; Brábek, Jan


    Apico-basal polarity is typical of cells present in differentiated epithelium while front-rear polarity develops in motile cells. In cancer development, the transition from epithelial to migratory polarity may be seen as the hallmark of cancer progression to an invasive and metastatic disease. Despite the morphological and functional dissimilarity, both epithelial and migratory polarity are controlled by a common set of polarity complexes Par, Scribble and Crumbs, phosphoinositides, and small Rho GTPases Rac, Rho and Cdc42. In epithelial tissues, their mutual interplay ensures apico-basal and planar cell polarity. Accordingly, altered functions of these polarity determinants lead to disrupted cell-cell adhesions, cytoskeleton rearrangements and overall loss of epithelial homeostasis. Polarity proteins are further engaged in diverse interactions that promote the establishment of front-rear polarity, and they help cancer cells to adopt different invasion modes. Invading cancer cells can employ either the collective, mesenchymal or amoeboid invasion modes or actively switch between them and gain intermediate phenotypes. Elucidation of the role of polarity proteins during these invasion modes and the associated transitions is a necessary step towards understanding the complex problem of metastasis. In this review we summarize the current knowledge of the role of cell polarity signaling in the plasticity of cancer cell invasiveness.

  20. Induction of Cancer Stem Cell Properties in Colon Cancer Cells by Defined Factors


    Oshima, Nobu


    Oshima N, Yamada Y, Nagayama S, Kawada K, Hasegawa S, et al. (2014) Induction of Cancer Stem Cell Properties in Colon Cancer Cells by Defined Factors. PLoS ONE 9(7): e101735. doi:10.1371/journal.pone.0101735

  1. Phenotype heterogeneity in cancer cell populations (United States)

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


    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

  2. Squamous cell cancer of the rectum

    Institute of Scientific and Technical Information of China (English)

    Tara Dyson; Peter V Draganov


    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.

  3. Alpha-fetoprotein, stem cells and cancer: how study of the production of alpha-fetoprotein during chemical hepatocarcinogenesis led to reaffirmation of the stem cell theory of cancer. (United States)

    Sell, Stewart


    Identification of the cells in the liver that produce alpha-fetoprotein during development, in response to liver injury and during the early stages of chemical hepatocarcinogenesis led to the conclusion that maturation arrest of liver-determined tissue stem cells was the cellular process that gives rise to hepatocellular carcinomas. When the cellular changes in these processes were compared to that of the formation of teratocarcinomas, the hypothesis arose that all cancers arise from maturation arrest of tissue-determined stem cells. This was essentially a reinterpretation of the embryonal rest theory of cancer whereby tissue stem cells take the role of embryonal rests. A corollary of the stem cell theory of the origin of cancer is that cancers contain the same functional cell populations as normal tissues: stem cells, transit-amplifying cells and mature cells. Cancer stem cells retain the essential feature of normal stem cells: the ability to self-renew. Growth of cancers is due to continued proliferation of cancer transit-amplifying cells that do not differentiate to mature cells (maturation arrest). On the other hand, cancer stem cells generally divide very rarely and contribute little to tumor growth. However, the presence of cancer stem cells in tumors is believed to be responsible for the properties of immortalization, transplantability and resistance to therapy characteristic of cancers. Current therapies for cancer (chemotherapy, radiotherapy, antiangiogenesis and differentiation therapy) are directed against the cancer transit-amplifying cells. When these therapies are discontinued, the cancer reforms from the cancer stem cells. Therapy directed toward interruption of the cell signaling pathways that maintain cancer stem cells could lead to new modalities to the prevention of regrowth of the cancer.

  4. Germ cell cancer and disorders of spermatogenesis

    DEFF Research Database (Denmark)

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


    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...... is a neoplastic caricature of embryonic growth. We consider the possibility that CIS cells may loose their stem cell potential with ageing. Along these lines, a seminoma is regarded a gonocytoma where the single gonocytes have little or no stem cell potential. The Sertoli and Leydig cells, which are activated......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...

  5. Cell-of-Origin of Cancer versus Cancer Stem Cells: Assays and Interpretations. (United States)

    Rycaj, Kiera; Tang, Dean G


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

  6. Stem Cell Transplants in Cancer Treatment (United States)

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

  7. Enteric Bacteria and Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Jun Sun


    Full Text Available Intestinal bacteria can contribute to cell proliferation and cancer development, particularly in chronic infectious diseases in which bacteria and/or bacterial components might interfere with cell function. The number of microbial cells within the gut lumen is estimated to be 100 trillion, which is about 10-times larger than the number of eukaryotic cells in the human body. Because of the complexity of the gut flora, identifying the specific microbial agents related to human diseases remains challenging. Recent studies have demonstrated that the stemness of colon cancer cells is, in part, orchestrated by the microenvironment and is defined by high Wnt activity. In this review article, we will discuss recent progress with respect to intestinal stem cells, cancer stem cells, and the molecular mechanisms of enteric bacteria in the activation of the Wnt pathway. We will also discuss the roles of other pathways, including JAK-STAT, JNK, and Notch, in regulating stem cell niches during bacterial infections using Drosophila models. Insights gained from understanding how host-bacterial interaction during inflammation and cancer may serve as a paradigm for understanding the nature of self-renewal signals.

  8. Human recombinant erythropoietin does not promote cancer growth in presence of functional receptors expressed in cancer cells. (United States)

    Belda-Iniesta, Cristóbal; Perona, Rosario; Carpeño, Javier de Castro; Cejas, Paloma; Casado, Enrique; Manguan-García, Cristina; Ibanez de Caceres, Inmaculada; Sanchez-Perez, Isabel; Andreu, Francisco Bernabeu; Ferreira, Javier Alves; Aguilera, Alfredo; de la Peña, Javier; Perez-Sánchez, Elia; Madero, Rosario; Feliu, Jaime; Sereno, María; González-Barón, Manuel


    Human recombinant erythropoietin (hrEPO) therapy might be associated with tumor progression and death. This effect has been suggested to be secondary to rhEPO binding to its receptor (EPOR) expressed on cancer cells. However, there are several concerns about EPOR functionality when expressed on cancer cells. In this paper we have provided evidence that EPOR expressed in cancer cells could be implicated in proliferation events because a transfection of EPOR siRNA to EPOR-expressing bladder cancer cells resulted in a marked reduction in cell growth. However, these cell lines do not grow in the presence of hrEPO. Furthermore, bladder cancer patients that expressed EPOR in tumor samples had a reduced survival in absence of rhEPO treatment. Therefore, EPOR is implicated in bladder cancer growth but this effect appears to be independent from rhEPO supplementation. Reports which suggest that rhEPO promotes cancer growth due to the expression of EPOR in cancer cells must be observed with caution since in the presence of functional EPOR rhEPO does not promote growth.

  9. [Present aspects and problems regarding occupational bladder cancer due to exposure to aromatic amines]. (United States)

    Yamamura, J


    About a century has passed since the first case of bladder cancer due to occupational exposure to carcinogenic aromatic amines was reported. In the major developed countries of the world, it is forbidden to manufacture and/or to use such aromatic amines. In Japan in the 1950's, many workers were exposed to carcinogenic aromatic amines, but in 1972, the Labor Safety and Health Act came into force and manufacturing and/or using of four kinds of aromatic amines were forbidden. Recently it has been reported that the risk of bladder cancer in workers exposed to aromatic amines before the ban of these chemicals is approximately from several times to a hundred times compared with the general population, and some reports say that dose-response relationship was observed. The important issues now are the carcinogenicity of other kinds of aromatic amines besides benzidine and 2-naphthylamine, carcinogenicity of metabolites of several substances like synthetic dyes, and carcinogenic aromatic amines as impurities in substances imported from developing countries. The type of exposure to these carcinogens changes low level and long period exposures. In addition to the chemical or dye industries, an increased risk of bladder cancer was observed among workers handling leather and rubber and those engaged in printing, textile industries, hairdressing, truck driving and so on. In the future, it will be necessary to cooperate with the departments of epidemiology, toxicology and clinical medicine for the purpose of estimating the risk of these occupations and the health care administration of the exposed workers.

  10. [Urethral Fistula and Scrotal Abscess Associated with Colovesical Fistula Due to the Sigmoid Colon Cancer]. (United States)

    Nakazawa, Shigeaki; Uemura, Motohide; Miyagawa, Yasushi; Tsujimura, Akira; Nonomura, Norio


    We report here a rare case of urethral fistula and scrotal abscess associated with colovesical fistula due to sigmoid colon cancer. An 84-year-old male was referred to our hospital complaining of macrohematuria, fecaluria, pneumaturia and micturitional pain. Computed tomography (CT) showed colovesical fistula. Other examinations, including colonoscopy and cystoscopy, did not reveal a clear cause for the colovesical fistula. Only an elevated serum level of the tumor marker CA19-9 suggested the possibility of sigmoid colon cancer. Eleven days after hospitalization, bilateral scrotal contents had swollen rapidly to the size of a goose egg. CT suggested urethral fistula with scrotal abscess formation. Drainage of scrotal abscess and colostomy were performed. Intraoperatively, the fistula of the bulbar urethra was revealed. Because increased serum CA19-9 suggested a diagnosis of sigmoid colon cancer, cystectomy and sigmoid colectomy with right nephrectomy were performed. Pathological examination revealed adenocarcinoma of sigmoid colon with bladder invasion. His condition was improved with rehabilitation 6 months after operation.

  11. Estimating the loss in expectation of life due to cancer using flexible parametric survival models. (United States)

    Andersson, Therese M-L; Dickman, Paul W; Eloranta, Sandra; Lambe, Mats; Lambert, Paul C


    A useful summary measure for survival data is the expectation of life, which is calculated by obtaining the area under a survival curve. The loss in expectation of life due to a certain type of cancer is the difference between the expectation of life in the general population and the expectation of life among the cancer patients. This measure is used little in practice as its estimation generally requires extrapolation of both the expected and observed survival. A parametric distribution can be used for extrapolation of the observed survival, but it is difficult to find a distribution that captures the underlying shape of the survival function after the end of follow-up. In this paper, we base our extrapolation on relative survival, because it is more stable and reliable. Relative survival is defined as the observed survival divided by the expected survival, and the mortality analogue is excess mortality. Approaches have been suggested for extrapolation of relative survival within life-table data, by assuming that the excess mortality has reached zero (statistical cure) or has stabilized to a constant. We propose the use of flexible parametric survival models for relative survival, which enables estimating the loss in expectation of life on individual level data by making these assumptions or by extrapolating the estimated linear trend at the end of follow-up. We have evaluated the extrapolation from this model using data on four types of cancer, and the results agree well with observed data.

  12. Assessment of damage from reduction of expected lifespan due to cancer

    Directory of Open Access Journals (Sweden)

    Boris Alengordovich Korobitsyn


    Full Text Available This paper presents the theoretical and methodological approaches to the assessment of damage from premature mortality and reduction of life expectancy due to various reasons. The concepts measuring the price of a human life are analyzed: the evaluation from the standpoint of the theory of human capital; indirect estimation taking into account non-monetary social costs; evaluation of individuals’ willingness to pay for the elimination of the risk of death; estimation based on the determination of insurance premiums and compensations under court decision; evaluation of the social investments, aimed to reduce the risk of premature mortality of the individual. The following indexes were calculated for all subordinate entities of the Russian Federation: reduction of life expectancy, lost years of potential life in the working age, and gross regional product lost due to the reduction of years of potential life in the working-age population as a result of cancer

  13. [A case of meningeal carcinomatosis due to gastric cancer treated with intrathecal chemotherapy]. (United States)

    Kobayashi, Yuka; Sugitani, Soichi; Oseki, Koshi; Iiri, Takao


    A 71-year-old man was admitted to our hospital in September 2009 because of severe headache due to meningeal carcinomatosis. In July 2007, subtotal gastrectomy was carried out for gastric cancer. Because intraabdominal cytodiagnosis was positive, he received systemic chemotherapy for 2 years. Recurrent signs were not found on chest or abdominal CT just before hospitalization. He was given NSAIDs and corticosteroid, but his symptom did not improve. Subsequent intrathecal chemotherapy with MTX and Ara-C improved clinical symptoms dramatically. He received care at home for 3 months before he passed away due to pleural and peritoneal recurrence. Recently, since the frequency of meningeal carcinomatosis is increasing, combination treatment of intrathecal chemotherapy and systemic chemotherapy should be considered not only for improvement of clinical manifestations, but also for prognostic improvement.

  14. CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel. (United States)

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


    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.

  15. Primary instabilities in convective cells due to nonuniform heating (United States)

    Mancho, A. M.; Herrero, H.; Burguete, J.


    We study a convection problem in a container with a surface open to the air and heated by a long wire placed at the bottom. Coupled buoyancy and thermocapillarity effects are taken into account. A basic convective state appears as soon as a temperature gradient with horizontal component different from zero is applied. It consists of two big rolls that fill the convective cell and are parallel to the heater. A numerical solution allows us to determine this basic state. A linear stability analysis on this solution is carried out. For different values of the applied temperature gradient the basic rolls undergo a stationary bifurcation. The thresholds depend on the fluid properties, on the geometry of the heater, and on the heat exchange on the free surface. This confirms the results obtained in recent experiments.

  16. 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


    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.

  17. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells. (United States)

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


    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rationale for therapies targeting this aggressive cell population. Precise identification of renal CSC populations and the complete cell hierarchy will accurately inform characterization of disease subtypes. This will ultimately contribute to more personalized and targeted therapies. Here, we summarize potential targeting strategies for renal cancer cells and renal CSCs, including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors (mTOR), interleukins, CSC marker inhibitors, bone morphogenetic protein-2, antibody drug conjugates, and nanomedicine. In conclusion, targeting therapies for RCC represent new directions for exploration and clinical investigation and they plant a seed of hope for advanced clinical care.

  18. ERBB2 increases metastatic potentials specifically in androgen-insensitive prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Jessica Tome-Garcia

    Full Text Available Despite all the blood-based biomarkers used to monitor prostate cancer patients, prostate cancer remains as the second common cause of cancer mortality in men in the United States. This is largely due to a lack of understanding of the molecular pathways that are responsible for the aggressive forms of prostate cancers, the castrate-resistant prostate cancer and the metastatic prostate cancer. Cell signaling pathways activated by the ERBB2 oncogene or the RAS oncogene are frequently found to be altered in metastatic prostate cancers. To evaluate and define the role of the ERBB2/RAS pathway in prostate cancer metastasis, we have evaluated the impact of ERBB2- or RAS-overexpression on the metastatic potentials for four prostate cancer cell lines derived from tumors with different androgen sensitivities. To do so, we transfected the human DU145, LnCaP, and PC3 prostate cancer cells and the murine Myc-CaP prostate cancer cells with the activated form of ERBB2 or H-RAS and assessed their metastatic potentials by three complementary assays, a wound healing assay, a transwell motility assay, and a transwell invasion assay. We showed that while overexpression of ERBB2 increased the metastatic potential of the androgen-insensitive prostate cancer cells (i.e. PC3 and DU145, it did not affect metastatic potentials of the androgen-sensitive prostate cancer cells (i.e. LnCaP and Myc-CaP. In contrast, overexpression of H-RAS only increased the cell motility of Myc-CaP cells, which overexpress the human c-MYC oncogene. Our data suggest that ERBB2 collaborates with androgen signaling to promote prostate cancer metastasis, and that although RAS is one of the critical downstream effectors of ERBB2, it does not phenocopy ERBB2 for its impact on the metastatic potentials of prostate cancer cell lines.

  19. Cupressus lusitanica (Cupressaceae) leaf extract induces apoptosis in cancer cells. (United States)

    Lopéz, L; Villavicencio, M A; Albores, A; Martínez, M; de la Garza, J; Meléndez-Zajgla, J; Maldonado, V


    A crude ethanolic extract of Cupressus lusitanica Mill. leaves demonstrate cytotoxicity in a panel of cancer cell lines. Cell death was due to apoptosis, as assessed by morphologic features (chromatin condensation and apoptotic bodies formation) and specific DNA fragmentation detected by in situ end-labeling of DNA breaks (TUNEL). The apoptotic cell death was induced timely in a dose-dependent manner. Despite the absence of changes in the expression levels of antiapoptotic protein Bcl-2, proapoptotic Bax protein variants omega and delta were increased. These results warrant further research of possible antitumor compounds in this plant.

  20. Current Status on Stem Cells and Cancers of the Gastric Epithelium

    Directory of Open Access Journals (Sweden)

    Werner Hoffmann


    Full Text Available Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells.

  1. Response to microtubule-interacting agents in primary epithelial ovarian cancer cells (United States)


    Background Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. Standard first line adjuvant chemotherapy treatments include Paclitaxel (Taxol) and platinum-based agents. Taxol, epothilone B (EpoB) and discodermolide belong to a family of anti-neoplastic agents that specifically interferes with microtubules and arrests cells in the G2/M phase of the cell cycle. Despite initial success with chemotherapy treatment, many patients relapse due to chemotherapy resistance. In vitro establishment of primary ovarian cancer cells provides a powerful tool for better understanding the mechanisms of ovarian cancer resistance. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer. Methods Chemosensitivity of these cell lines to Taxol, EpoB and discodermolide was tested, and cell cycle analysis was compared to that of immortalized ovarian cancer cell lines SKOV3 and Hey. The relationship between drug resistance and αβ-tubulin and p53 status was also investigated. Results All newly generated primary cancer cells were highly sensitive to the drugs. αβ-tubulin mutation was not found in any primary cell lines tested. However, one cell line that harbors p53 mutation at residue 72 (Arg to Pro) exhibits altered cell cycle profile in response to all drug treatments. Immortalized ovarian cancer cells respond differently to EpoB treatment when compared to primary ovarian cancer cells, and p53 polymorphism suggests clinical significance in the anti-tumor response in patients. Conclusions The isolation and characterization of primary ovarian cancer cells from ovarian cancer patients’ specimens contribute to further understanding the nature of drug resistance to microtubule interacting agents (MIAs) currently used in clinical settings. PMID:23574945

  2. [Extended salvage pelvic and retroperitoneal lymph node dissection due to prostate cancer relapse]. (United States)

    Osmonov, D K; Aksenov, A V; Jünemann, K-P


    Treatment of a biochemical prostate cancer relapse represents a difficult clinical dilemma, which has remained without a definitive solution so far. Based on clinical studies, we combine radical prostatectomy with extended pelvic lymph node dissection in intermediate and high risk patients as a routine procedure at our clinic. In this paper, we report on a case of extended salvage lymphadenectomy performed due to biochemical prostate cancer recurrence. The 56-year-old patient came to our clinic in April 2012 with a finding of lymph node metastasis according to PET-CT imaging. Laparoscopic radical retropubic prostatectomy with lymphadenectomy had been performed in 2008 [pT3a, N0 (0/4), M0, R0, GS 5+4=9, iPSA 26.67 ng/mL], and followed by radiotherapy as of September 2009. The extended salvage lymphadenectomy was performed in April 2012 due to a PSA-level rise up to 24 ng/mL and the aforementioned PET-CT findings. A total of 22 lymph nodes were removed, among them 3 lymph nodes with metastases. In the fossa obturatoria on the right we identified a walnut-size lymph node relapse with tumour necrosis, which fully corresponded to the PET-CT scan. The PSA level subsequently dropped to 0.4 ng/mL postoperatively, and further to the current value of 0.02 ng/mL (August 2012).

  3. Cancer Stem Cells: A Moving Target. (United States)

    Francipane, Maria Giovanna; Chandler, Julie; Lagasse, Eric


    Even though the number of anti-cancer drugs entering clinical trials and approved by the FDA has increased in recent years, many cancer patients still experience poor survival outcome. The main explanation for such a dismal prognosis is that current therapies might leave behind a population of cancer cells with the capacity for long-term self-renewal, so-called cancer stem cells (CSCs), from which most tumors are believed to be derived and fueled. CSCs might favor local and distant recurrence even many years after initial treatment, thus representing a potential target for therapies aimed at improving clinical outcome. In this review, we will address the CSC hypothesis with a particular emphasis on its current paradigms and debates, and discuss several mechanisms of CSC resistance to conventional therapies.

  4. Altered calcium signaling in cancer cells. (United States)

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


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

  5. 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: [Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere (Finland); Fimlab Laboratories, Biokatu 4, 33520 Tampere (Finland)


    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.

  6. Getting to the heart of the matter in cancer: Novel approaches to targeting cancer stem cells. (United States)

    Colvin, Hugh; Mori, Masaki


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

  7. Microfluidics and cancer analysis: cell separation, cell/tissue culture, cell mechanics, and integrated analysis systems. (United States)

    Pappas, Dimitri


    Among the growing number of tools available for cancer studies, microfluidic systems have emerged as a promising analytical tool to elucidate cancer cell and tumor function. Microfluidic methods to culture cells have created approaches to provide a range of environments from single-cell analysis to complex three-dimensional devices. In this review we discuss recent advances in tumor cell culture, cancer cell analysis, and advanced studies enabled by microfluidic systems.

  8. Targeting regulatory T cells in cancer.

    LENUS (Irish Health Repository)

    Byrne, William L


    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.

  9. From cell signaling to cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Jin DING; Yun FENG; Hong-yang WANG


    Cancer has been seriously threatening the health and life of humans for a long period. Despite the intensive effort put into revealing the underlying mechanisms of cancer, the detailled machinery of carcinogenesis is still far from fully understood.Numerous studies have illustrated that cell signaling is extensively involved in tumor initiation, promotion and progression. Therefore, targeting the key mol-ecules in the oncogenic signaling pathway might be one of the most promising ways to conquer cancer. Some targeted drugs, such as imatinib mesylate (Gleevec),herceptin, gefitinib (Iressa), sorafenib (Nexavar) and sunitinib (Sutent), which evolve from monotarget drug into multitarget ones, have been developed with encouraging effects.

  10. The telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Maria Szubert


    Full Text Available 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 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.

  12. Utility of multidetector row computed tomography and virtual bronchoscopy in evaluation of hemoptysis due to lung cancer

    Directory of Open Access Journals (Sweden)

    Sherif A.A. Mohamed


    Conclusion: MDCT angiography is a useful and non invasive method that allows a rapid and detailed identification of abnormal vasculature responsible for hemoptysis in patients with lung cancer. MDCT-generated virtual bronchoscopy is an accurate, and non invasive method for evaluating obstructions, endoluminal masses, and external compressions in patients with hemoptysis due to lung cancer.

  13. The cancer stem cell theory: is it correct? (United States)

    Yoo, Min-Hyuk; Hatfield, Dolph L


    The cancer stem cell hypothesis posits that tumor growth is driven by a rare subpopulation of cells, designated cancer stem cells (CSC). Studies supporting this theory are based in large part on xenotransplantation experiments wherein human cancer cells are grown in immunocompromised mice and only CSC, often constituting less than 1% of the malignancy, generate tumors. Herein, we show that all colonies derived from randomly chosen single cells in mouse lung and breast cancer cell lines form tumors following allografting histocompatible mice. Our study suggests that the majority of malignant cells rather than CSC can sustain tumors and that the cancer stem cell theory must be reevaluated.

  14. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats

    Directory of Open Access Journals (Sweden)

    Priyank Ashok Shenoy


    Full Text Available The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.

  15. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats. (United States)

    Shenoy, Priyank A; Kuo, Andy; Vetter, Irina; Smith, Maree T


    The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.

  16. Cell Membrane Softening in Cancer Cells (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.

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

    Directory of Open Access Journals (Sweden)

    Kid Törnquist


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

  18. The metabolic landscape of cancer stem cells. (United States)

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


    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.

  19. Study of epidemiological risk of lung cancer in Mexico due indoor radon exposure (United States)

    Ángeles, A.; Espinosa, G.


    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. GLUL Promotes Cell Proliferation in Breast Cancer. (United States)

    Wang, Yanyan; Fan, Shaohua; Lu, Jun; Zhang, Zifeng; Wu, Dongmei; Wu, Zhiyong; Zheng, Yuanlin


    Glutamate-ammonia ligase (GLUL) belongs to the glutamine synthetase family. It catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. Here, we found higher expression of GLUL in the breast cancer patients was associated with larger tumor size and higher level of HER2 expression. In addition, GLUL was heterogeneously expressed in various breast cancer cells. The mRNA and protein expression levels of GLUL in SK-BR-3 cells were obviously higher than that in the other types of breast cancer cells. Results showed GLUL knockdown in SK-BR-3 cells could significantly decrease the proliferation ability. Furthermore, GLUL knockdown markedly inhibited the p38 MAPK and ERK1/ERK2 signaling pathways in SK-BR-3 cells. Thus, GLUL may represent a novel target for selectively inhibiting p38 MAPK and ERK1/ERK2 signaling pathways and the proliferation potential of breast cancer cells. This article is protected by copyright. All rights reserved.

  1. Immunology of Stem Cells and Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Yang


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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

  3. Induction of premature senescence by hsp90 inhibition in small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Ian J Restall

    Full Text Available BACKGROUND: The molecular chaperone Hsp90 is a promising new target in cancer therapy and selective Hsp90 inhibitors are currently in clinical trials. Previously these inhibitors have been reported to induce either cell cycle arrest or cell death in cancer cells. Whether the cell cycle arrest is reversible or irreversible has not generally been assessed. Here we have examined in detail the cell cycle arrest and cell death responses of human small cell lung cancer cell lines to Hsp90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: In MTT assays, small cell lung cancer cells showed a biphasic response to the Hsp90 inhibitors geldanamycin and radicicol, with low concentrations causing proliferation arrest and high concentrations causing cell death. Assessment of Hsp90 intracellular activity using loss of client protein expression showed that geldanamycin concentrations that inhibited Hsp90 correlated closely with those causing proliferation arrest but not cell death. The proliferation arrest induced by low concentrations of geldanamycin was not reversed for a period of over thirty days following drug removal and showed features of senescence. Rare populations of variant small cell lung cancer cells could be isolated that had additional genetic alterations and no longer underwent irreversible proliferation arrest in response to Hsp90 inhibitors. CONCLUSIONS/SIGNIFICANCE: We conclude that: (1 Hsp90 inhibition primarily induces premature senescence, rather than cell death, in small cell lung cancer cells; (2 small cell lung cancer cells can bypass this senescence through further genetic alterations; (3 Hsp90 inhibitor-induced cell death in small cell lung cancer cells is due to inhibition of a target other than cytosolic Hsp90. These results have implications with regard to how these inhibitors will behave in clinical trials and for the design of future inhibitors in this class.

  4. An update on the biology of cancer stem cells in breast cancer. (United States)

    García Bueno, José María; Ocaña, Alberto; Castro-García, Paola; Gil Gas, Carmen; Sánchez-Sánchez, Francisco; Poblet, Enrique; Serrano, Rosario; Calero, Raúl; Ramírez-Castillejo, Carmen


    Breast cancer stem cells are defined as cancer cells with self-renewal capacity. These cells represent a small subpopulation endowed with the ability to form new tumours when injected in nude mice. Markers of differentiation have been used to identify these cancer cells. In the case of breast cancer, CD44+/CD24- select a population with stem cell properties. The fact that these cells have self-renewal ability has suggested that this population could be responsible for new tumour formation and cancer relapse. These cells have been shown to be more resistant to chemotherapy and radiotherapy than normal cancer cells. The identification of the molecular druggable alterations responsible for the initiation and maintenance of cancer stem cells is an important goal. In this article we will review all these points with special emphasis on the possible role of new drugs designed to interact with molecular pathways of cancer stem cells.

  5. Cancer stem cells and field cancerization of oral squamous cell carcinoma. (United States)

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


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

  6. What Is Kidney Cancer (Renal Cell Carcinoma)? (United States)

    ... Treatment? Kidney Cancer About Kidney Cancer What Is Kidney Cancer? Kidney cancer is a cancer that starts ... and spread, see What Is Cancer? About the kidneys To understand more about kidney cancer, it helps ...

  7. Advances of Immunotherapy in Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jingjing LIU


    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.

  8. EF5 and Motexafin Lutetium in Detecting Tumor Cells in Patients With Abdominal or Non-Small Cell Lung Cancer (United States)


    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

  9. Cancer Vaccine by Fusions of Dendritic and Cancer Cells

    Directory of Open Access Journals (Sweden)

    Shigeo Koido


    Full Text Available Dendritic cells (DCs are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived costimulatory molecules. DCs/tumor fusion vaccine stimulates potent antitumor immunity in the animal tumor models. In the human studies, T cells stimulated by DC/tumor fusion cells are effective in lysis of tumor cells that are used as the fusion partner. In the clinical trials, clinical and immunological responses were observed in patients with advanced stage of malignant tumors after being vaccinated with DC/tumor fusion cells, although the antitumor effect is not as vigorous as in the animal tumor models. This review summarizes recent advances in concepts and techniques that are providing new impulses to DCs/tumor fusions-based cancer vaccination.

  10. Cancer Stem Cells and Pediatric Solid Tumors

    Directory of Open Access Journals (Sweden)

    Gregory K. Friedman


    Full Text Available 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.

  11. 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


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  13. Translational potential of cancer stem cells: A review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment. (United States)

    Islam, Farhadul; Gopalan, Vinod; Smith, Robert A; Lam, Alfred K-Y


    Cancer stem cells (CSCs) are a subpopulation of cancer cells with many clinical implications in most cancer types. One important clinical implication of CSCs is their role in cancer metastases, as reflected by their ability to initiate and drive micro and macro-metastases. The other important contributing factor for CSCs in cancer management is their function in causing treatment resistance and recurrence in cancer via their activation of different signalling pathways such as Notch, Wnt/β-catenin, TGF-β, Hedgehog, PI3K/Akt/mTOR and JAK/STAT pathways. Thus, many different therapeutic approaches are being tested for prevention and treatment of cancer recurrence. These may include treatment strategies targeting altered genetic signalling pathways by blocking specific cell surface molecules, altering the cancer microenvironments that nurture cancer stem cells, inducing differentiation of CSCs, immunotherapy based on CSCs associated antigens, exploiting metabolites to kill CSCs, and designing small interfering RNA/DNA molecules that especially target CSCs. Because of the huge potential of these approaches to improve cancer management, it is important to identify and isolate cancer stem cells for precise study and application of prior the research on their role in cancer. Commonly used methodologies for detection and isolation of CSCs include functional, image-based, molecular, cytological sorting and filtration approaches, the use of different surface markers and xenotransplantation. Overall, given their significance in cancer biology, refining the isolation and targeting of CSCs will play an important role in future management of cancer.

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


    Nogueira, Veronique; Hay, Nissim


    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...

  15. Toward a stem cell gene therapy for breast cancer. (United States)

    Li, ZongYi; Liu, Ying; Tuve, Sebastian; Xun, Ye; Fan, Xiaolong; Min, Liang; Feng, Qinghua; Kiviat, Nancy; Kiem, Hans-Peter; Disis, Mary Leonora; Lieber, André


    Current approaches for treatment of late-stage breast cancer rarely result in a long-term cure. In part this is due to tumor stroma that prevents access of systemically or intratumorally applied therapeutics. We propose a stem cell gene therapy approach for controlled tumor stroma degradation that uses the pathophysiologic process of recruitment of inflammatory cells into the tumor. This approach involves genetic modification of hematopoietic stem cells (HSCs) and their subsequent transplantation into tumor-bearing mice. We show that inducible, intratumoral expression of relaxin (Rlx) either by transplanting tumor cells that contained the Rlx gene or by transplantation of mouse HSCs transduced with an Rlx-expressing lentivirus vector delays tumor growth in a mouse model of breast cancer. The antitumor effect of Rlx was mediated through degradation of tumor stroma, which provided increased access of infiltrating antitumor immune cells to their target tumor cells. Furthermore, we have shown in a human/mouse chimeric model that genetically modified HSCs expressing a transgene can access the tumor site. Our findings are relevant for cancer gene therapy and immunotherapy.

  16. Cancer Cell Colonisation in the Bone Microenvironment

    Directory of Open Access Journals (Sweden)

    Casina Kan


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

  17. Understanding cancer stem cell heterogeneity and plasticity

    Institute of Scientific and Technical Information of China (English)

    Dean G Tang


    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.

  18. Cancer Cell Colonisation in the Bone Microenvironment (United States)

    Kan, Casina; Vargas, Geoffrey; Le Pape, François; Clézardin, Philippe


    Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts. Cross-talk with the bone may alter tumour cell properties and, conversely, tumour cells may also acquire characteristics of the surrounding microenvironment, in a process known as osteomimicry. Alternatively, these cells may also express osteomimetic genes that allow cell survival or favour seeding to the bone marrow. The seeding of tumour cells in the bone disrupts bone-forming and bone-resorbing activities, which can lead to macrometastasis in bone. At present, bone macrometastases are incurable with only palliative treatment available. A better understanding of how these processes influence the early onset of bone metastasis may give insight into potential therapies. This review will focus on the early steps of bone colonisation, once disseminated tumour cells enter the bone marrow. PMID:27782035

  19. REV3L modulates cisplatin sensitivity of non-small cell lung cancer H1299 cells. (United States)

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


    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.

  20. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR


    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

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

    Directory of Open Access Journals (Sweden)

    Naugler Christopher T


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


    Directory of Open Access Journals (Sweden)

    A. V. Petrovsky


    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.

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

    Directory of Open Access Journals (Sweden)

    Gláucia Sousa Oliveira


    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.

  4. Cell membrane softening in human breast and cervical cancer cells (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.


    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.

  5. Drug treatment of cancer cell lines: a way to select for cancer stem cells? (United States)

    Chiodi, Ilaria; Belgiovine, Cristina; Donà, Francesca; Scovassi, A Ivana; Mondello, Chiara


    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.

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

    Directory of Open Access Journals (Sweden)

    Ilaria Chiodi


    Full Text Available 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.

  7. 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: [Institute of Molecular Genetics, CNR, via Abbiategrasso 207, 27100 Pavia (Italy)


    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.

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

    Institute of Scientific and Technical Information of China (English)

    Minal; Garg


    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.

  9. Fusarin C acts like an estrogenic agonist and stimulates breast cancer cells in vitro

    DEFF Research Database (Denmark)

    Søndergaard, Teis; Hansen, Frederik Teilfeldt; Purup, Stig;


    Fusarin C is a mycotoxin produced by several Fusarium species and has been associated with esophageal cancer due to its carcinogenic effects. Here, we report that fusarin C stimulates growth of the breast cancer cell line MCF-7. This suggests that fusarin C can act as an estrogenic agonist...

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

    DEFF Research Database (Denmark)

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


    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....

  11. 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)


    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. The cancer burden in the United Kingdom in 2007 due to radiotherapy. (United States)

    Maddams, Jacob; Parkin, D Maxwell; Darby, Sarah C


    The number of long-term cancer survivors in the general population of the UK is substantial and increasing rapidly. Many cancer survivors have been treated with radiotherapy but the likely number of radiotherapy-related second cancers has not previously been estimated. We used estimates of the numbers of cancer survivors in the UK at the beginning of 2007, in conjunction with estimates of the relative risk of a second primary cancer associated with previous radiotherapy from the United States Surveillance Epidemiology and End Results (SEER) programme, to estimate the numbers of incident cancers in the UK in 2007 that were associated with radiotherapy for a previous cancer and that may have been caused by it. We estimated that 1,346 cases of cancer, or about 0.45% of the 298,000 new cancers registered in the UK in 2007, were associated with radiotherapy for a previous cancer. The largest numbers of radiotherapy-related second cancers were lung cancer (23.7% of the total), oesophageal cancer (13.3%), and female breast cancer (10.6%); 54% of radiotherapy-related second cancers were in individuals aged 75 or over. The highest percentages of second cancers related to radiotherapy were among survivors of Hodgkin's disease and cancers of the oral cavity and pharynx and cervix uteri; over 15% of second cancers among these survivors were associated with radiotherapy for the first cancer. These calculations, which involve a number of assumptions and approximations, provide a reasonable, if conservative, estimate of the fraction of incident cancers in the UK that are attributable to past radiation therapy.

  13. Vasculogenic mimicry in small cell lung cancer. (United States)

    Williamson, Stuart C; Metcalf, Robert L; Trapani, Francesca; Mohan, Sumitra; Antonello, Jenny; Abbott, Benjamin; Leong, Hui Sun; Chester, Christopher P E; Simms, Nicole; Polanski, Radoslaw; Nonaka, Daisuke; Priest, Lynsey; Fusi, Alberto; Carlsson, Fredrika; Carlsson, Anders; Hendrix, Mary J C; Seftor, Richard E B; Seftor, Elisabeth A; Rothwell, Dominic G; Hughes, Andrew; Hicks, James; Miller, Crispin; Kuhn, Peter; Brady, Ged; Simpson, Kathryn L; Blackhall, Fiona H; Dive, Caroline


    Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form 'endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (Pcisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention.

  14. Expression of Cyclooxygenase-2 in Ovarian Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)


    To investigate the expression of cyclooxygenase-2 (COX-2) in ovarian cancer cell lines,RT-PCR and immunocytochemistry were used to detect the expression of COX-2 in 5 ovarian cancer cell lines. The expression of COX-2 mRNA and protein was detected in all 5 cell lines. It is suggested that COX-2 is expressed in ovarian cancer cell lines, which provides a basis for the chemoprevention of ovarian cancer.

  15. 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: [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)


    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.

  16. Circulating Tumor Cells in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Brian Hu


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  18. Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism. (United States)

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


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

  19. Human Colon Cancer Cells Cultivated in Space (United States)


    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.

  20. Diet, Stem Cells, and Breast Cancer Prevention (United States)


    comprised of fibroblasts, endothelial cells and adipocytes, which collectively form the mammary fat pad . Breast cancer originates from subversions of...luminal epithelial cells embedded in a complex stromal matrix (‘mammary fat pad ’) comprised predominantly of fibroblasts, adipocytes and macrophages (Fig., we showed that limited exposure (i.e., in utero and lactational only) of female rat offspring to a maternal diet containing soy protein isolate

  1. Current therapy of small cell lung cancer

    DEFF Research Database (Denmark)

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


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

  2. Forcing Cancer Cells to Commit Suicide

    NARCIS (Netherlands)

    Vangestel, Christel; Van de Wiele, Christophe; Mees, Gilles; Peeters, Marc


    Apoptosis plays a crucial role in the normal development, homeostasis of multicellular organisms, carcinogenic process, and response of cancer cells to anticancer drugs. It is a genetically strictly regulated process, controlled by the balance between pro-and antiapoptotic proteins. Resistance to st

  3. Mortalin sensitizes human cancer cells to MKT-077-induced senescence. (United States)

    Deocaris, Custer C; Widodo, Nashi; Shrestha, Bhupal G; Kaur, Kamaljit; Ohtaka, Manami; Yamasaki, Kazuhiko; Kaul, Sunil C; Wadhwa, Renu


    Mortalin is a chaperone protein that functions in many cellular processes such as mitochondrial biogenesis, intracellular trafficking, cell proliferation and signaling. Its upregulation in many human cancers makes it a candidate target for therapeutic intervention by small molecule drugs. In continuation to our earlier studies showing mortalin as a cellular target of MKT-077, a mitochondrion-seeking delocalized cationic dye that causes selective death of cancer cells, in this work, we report that MKT-077 binds to the nucleotide-binding domain of mortalin, causes tertiary structural changes in the protein, inactivates its chaperone function, and induces senescence in human tumor cell lines. Interestingly, in tumor cells with elevated level of mortalin expression, fairly low drug doses were sufficient to induce senescence. Guided by molecular screening for mortalin in tumor cells, our results led to the idea that working at low doses of the drug could be an alternative senescence-inducing cancer therapeutic strategy that could, in theory, avoid renal toxicities responsible for the abortion of MKT-077 clinical trials. Our work may likely translate to a re-appraisal of the therapeutic benefits of low doses of several classes of anti-tumor drugs, even of those that had been discontinued due to adverse effects.

  4. Evodiamine selectively targets cancer stem-like cells through the p53-p21-Rb pathway. (United States)

    Han, Seula; Woo, Jong Kyu; Jung, Yuchae; Jeong, Dawoon; Kang, Minsook; Yoo, Young-Ji; Lee, Hani; Oh, Seung Hyun; Ryu, Jae-Ha; Kim, Woo-Young


    In spite of the recent improvements, the resistance to chemotherapy/radiotherapy followed by relapse is the main hurdle for the successful treatment of breast cancer, a leading cause of death in women. A small population of breast cancer cells that have stem-like characteristics (cancer stem-like cells; CSLC) may contribute to this resistance and relapse. Here, we report on a component of a traditional Chinese medicine, evodiamine, which selectively targets CSLC of breast cancer cell lines MCF7 and MDAMB 231 at a concentration that does show a little or no cytotoxic effect on bulk cancer cells. While evodiamine caused the accumulation of bulk cancer cells at the G2/M phase, it did not hold CSLC in a specific cell cycle phase but instead, selectively killed CSLC. This was not due to the culture of CSLC in suspension or without FBS. A proteomic analysis and western blotting revealed that evodiamine changed the expression of cell cycle regulating molecules more efficiently in CSLC cells than in bulk cancer cells. Surprisingly, evodiamine selectively activated p53 and p21 and decreased inactive Rb, the master molecules in G1/S checkpoint. These data collectively suggest a novel mechanism involving CSLC-specific targeting by evodiamine and its possible use to the therapy of breast cancer.

  5. Differentially expressed miRNAs in cancer-stem-like cells: markers for tumor cell aggressiveness of pancreatic cancer. (United States)

    Bao, Bin; Ali, Shadan; Ahmad, Aamir; Li, Yiwei; Banerjee, Sanjeev; Kong, Dejuan; Aboukameel, Amro; Mohammad, Ramzi; Van Buren, Eric; Azmi, Asfar S; Sarkar, Fazlul H


    Pancreatic cancer (PC) is one of the most deadly cancers. The higher mortality is in part due to treatment resistance and early onset of metastasis. The existence of cancer-stem-like cells (CSLCs) has been widely accepted to be responsible for tumor aggressiveness in PC. Emerging evidence suggests that CSLCs have the capacity for increased cell growth, cell migration/invasion, metastasis, and treatment resistance, which leads to poor clinical outcome. However, the molecular role of CSLCs in tumor development and progression is poorly understood. Therefore, mechanistic understanding, and targeted killing of CSLCs may provide a newer therapeutic strategy for the treatment of PC. It has been well accepted that microRNAs (miRNAs) play critical roles during tumor development and progression through deregulation of multiple genes. Moreover, deregulated expression of miRNAs may also play a key role in the regulation of CSLC characteristics and functions. Here we show that isolated CD44(+)/CD133(+)/EpCAM(+) cells (triple-marker-positive cells) from human PC cell lines, MiaPaCa-2 and L3.6pl cells, display aggressive characteristics, such as increased cell growth, clonogenicity, cell migration, and self-renewal capacity, which is consistent with overexpression of CSLC signatures/markers. We also found deregulated expression of over 400 miRNAs, including let-7, miR-30, miR-125b, and miR-335, in CSLCs. As a proof-of-concept, knockdown of miR-125b resulted in the inhibition of tumor cell aggressiveness of CSLCs (triple-marker-positive cells), consistent with the downregulation of CD44, EpCAM, EZH2, and snail. These results clearly suggest the importance of miRNAs in the regulation of CSLC characteristics, and may serve as novel targets for therapy.

  6. Cerebellar Hemorrhage due to a Direct Carotid–Cavernous Fistula after Surgery for Maxillary Cancer (United States)

    Kamio, Yoshinobu; Hiramatsu, Hisaya; Kamiya, Mika; Yamashita, Shuhei; Namba, Hiroki


    Infratentorial cerebral hemorrhage due to a direct carotid–cavernous fistula (CCF) is very rare. To our knowledge, only four such cases have been reported. Cerebellar hemorrhage due to a direct CCF has not been reported. We describe a 63-year-old female who presented with reduced consciousness 3 days after undergoing a maxillectomy for maxillary cancer. Computed tomography showed a cerebellar hemorrhage. Magnetic resonance angiography showed a left-sided direct CCF draining into the left petrosal and cerebellar veins through the left superior petrosal sinus (SPS). Her previous surgery had sacrificed the pterygoid plexus and facial vein. Increased blood flow and reduced drainage could have led to increased venous pressure in infratentorial veins, including the petrosal and cerebellar veins. The cavernous sinus has several drainage routes, but the SPS is one of the most important routes for infratentorial venous drainage. Stenosis or absence of the posterior segment of the SPS can also result in increased pressure in the cerebellar and pontine veins. We emphasize that a direct CCF with cortical venous reflux should be precisely evaluated to determine the hemodynamic status and venous drainage from the cavernous sinus. PMID:28061497

  7. Targeting cancer stem cells with p53 modulators (United States)

    Hayashi, Ryo; Appella, Ettore; Kopelovich, Levy; DeLeo, Albert B.


    Cancer stem cells (CSC) typically over-express aldehyde dehydrogenase (ALDH). Thus, ALDHbright tumor cells represent targets for developing novel cancer prevention/treatment interventions. Loss of p53 function is a common genetic event during cancer development wherein small molecular weight compounds (SMWC) that restore p53 function and reverse tumor growth have been identified. Here, we focused on two widely studied p53 SMWC, CP-31398 and PRIMA-1, to target ALDHbright CSC in human breast, endometrial and pancreas carcinoma cell lines expressing mutant or wild type (WT) p53. CP-31398 and PRIMA-1 significantly reduced CSC content and sphere formation by these cell lines in vitro. In addition, these agents were more effective in vitro against CSC compared to cisplatin and gemcitabine, two often-used chemotherapeutic agents. We also tested a combinatorial treatment in methylcholantrene (MCA)-treated mice consisting of p53 SMWC and p53-based vaccines. Yet using survival end-point analysis, no increased efficacy in the presence of either p53 SMWC alone or with vaccine compared to vaccine alone was observed. These results may be due, in part, to the presence of immune cells, such as activated lymphocytes expressing WT p53 at levels comparable to some tumor cells, wherein further increase of p53 expression by p53 SMWC may alter survival of these immune cells and negatively impact an effective immune response. Continuous exposure of mice to MCA may have also interfered with the action of these p53 SMWC, including potential direct interaction with MCA. Nonetheless, the effect of p53 SMWC on CSC and cancer treatment remains of great interest. PMID:27074569

  8. Fluorescent Cy5 silica nanoparticles for cancer cell imaging (United States)

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


    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.

  9. Stemness is derived from thyroid cancer cells

    Directory of Open Access Journals (Sweden)

    Risheng eMa


    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.

  10. Spontaneous cancer-stromal cell fusion as a mechanism of prostate cancer androgen-independent progression.

    Directory of Open Access Journals (Sweden)

    Ruoxiang Wang

    Full Text Available We have previously shown that human prostate cancer cells are capable of acquiring malignant attributes through interaction with stromal cells in the tumor microenvironment, while the interacting stromal cells can also become affected with both phenotypic and genotypic alterations. This study used a co-culture model to investigate the mechanism underlying the co-evolution of cancer and stromal cells. Red fluorescent androgen-dependent LNCaP prostate cancer cells were cultured with a matched pair of normal and cancer-associated prostate myofibroblast cells to simulate cancer-stromal interaction, and cellular changes in the co-culture were documented by tracking the red fluorescence. We found frequent spontaneous fusions between cancer and stromal cells throughout the co-culture. In colony formation assays assessing the fate of the hybrid cells, most of the cancer-stromal fusion hybrids remained growth-arrested and eventually perished. However, some of the hybrids survived to form colonies from the co-culture with cancer-associated stromal cells. These derivative clones showed genomic alterations together with androgen-independent phenotype. The results from this study reveal that prostate cancer cells are fusogenic, and cancer-stromal interaction can lead to spontaneous fusion between the two cell types. While a cancer-stromal fusion strategy may allow the stromal compartment to annihilate invading cancer cells, certain cancer-stromal hybrids with increased survival capability may escape annihilation to form a derivative cancer cell population with an altered genotype and increased malignancy. Cancer-stromal fusion thus lays a foundation for an incessant co-evolution between cancer and the cancer-associated stromal cells in the tumor microenvironment.

  11. New insights into pancreatic cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Chinthalapally V Rao; Altaf Mohammed


    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.

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

    Directory of Open Access Journals (Sweden)

    Wenke YUE


    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.

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



    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 in...

  14. Cancer immunotherapy: nanodelivery approaches for immune cell targeting and tracking (United States)

    Conniot, João; Silva, Joana; Fernandes, Joana; Silva, Liana; Gaspar, Rogério; Brocchini, Steve; Florindo, Helena; Barata, Teresa


    Cancer is one of the most common diseases afflicting people globally. New therapeutic approaches are needed due to the complexity of cancer as a disease. Many current treatments are very toxic and have modest efficacy at best. Increased understanding of tumor biology and immunology has allowed the development of specific immunotherapies with minimal toxicity. It is important to highlight the performance of monoclonal antibodies, immune adjuvants, vaccines and cell-based treatments. Although these approaches have shown varying degrees of clinical efficacy, they illustrate the potential to develop new strategies. Targeted immunotherapy is being explored to overcome the heterogeneity of malignant cells and the immune suppression induced by both the tumor and its microenvironment. Nanodelivery strategies seek to minimize systemic exposure to target therapy to malignant tissue and cells. Intracellular penetration has been examined through the use of functionalized particulates. These nano-particulate associated medicines are being developed for use in imaging, diagnostics and cancer targeting. Although nano-particulates are inherently complex medicines, the ability to confer, at least in principle, different types of functionality allows for the plausible consideration these nanodelivery strategies can be exploited for use as combination medicines. The development of targeted nanodelivery systems in which therapeutic and imaging agents are merged into a single platform is an attractive strategy. Currently, several nanoplatform-based formulations, such as polymeric nanoparticles, micelles, liposomes and dendrimers are in preclinical and clinical stages of development. Herein, nanodelivery strategies presently investigated for cancer immunotherapy, cancer targeting mechanisms and nanocarrier functionalization methods will be described. We also intend to discuss the emerging nano-based approaches suitable to be used as imaging techniques and as cancer treatment options.

  15. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Yun-Jung Choi


    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  16. 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


    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.

  17. Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer (United States)


    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

  18. Dendritic Cells in the Cancer Microenvironment

    Directory of Open Access Journals (Sweden)

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


    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.

  19. Implications of cancer stem cell theory for cancer chemoprevention by natural dietary compounds. (United States)

    Li, Yanyan; Wicha, Max S; Schwartz, Steven J; Sun, Duxin


    The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anticancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anticancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine and vitamin D(3), are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor-initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival.

  20. Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer (United States)

    Somasagara, Ranganatha R.; Tripathi, Kaushlendra; Spencer, Sebastian M.; Clark, David W.; Barnett, Reagan; Bachaboina, Lavanya; Scalici, Jennifer; Rocconi, Rodney P.; Piazza, Gary A.; Palle, Komaraiah


    Ovarian cancer is the fifth most deadly cancer in women in the United States and despite advances in surgical and chemotherapeutic treatments survival rates have not significantly improved in decades. The poor prognosis for ovarian cancer patients is largely due to the extremely high (80%) recurrence rate of ovarian cancer and because the recurrent tumors are often resistant to the widely utilized platinum-based chemotherapeutic drugs. In this study, expression of Rad6, an E2 ubiquitin-conjugating enzyme, was found to strongly correlate with ovarian cancer progression. Furthermore, in ovarian cancer cells Rad6 was found to stabilize β-catenin promoting stem cell-related characteristics, including expression of stem cell markers and anchorage-independent growth. Cancer stem cells can promote chemoresistance, tumor recurrence and metastasis, all of which are limiting factors in treating ovarian cancer. Thus it is significant that Rad6 overexpression led to increased resistance to the chemotherapeutic drug carboplatin and correlated with tumor cell invasion. These findings show the importance of Rad6 in ovarian cancer and emphasize the need for further studies of Rad6 as a potential target for the treatment of ovarian cancer. PMID:26679603

  1. Linoleic acid suppresses colorectal cancer cell growth by inducing oxidant stress and mitochondrial dysfunction

    Directory of Open Access Journals (Sweden)

    Shen Shengrong


    Full Text Available Abstract Some polyunsaturated fatty acids (PUFAs, if not all, have been shown to have tumoricidal action, but their exact mechanism(s of action is not clear. In the present study, we observed that n-6 PUFA linoleic acid (LA inhibited tumor cell growth at high concentrations (above 300 μM; while low concentrations (100-200 μM promoted proliferation. Analysis of cell mitochondrial membrane potential, reactive oxygen species (ROS formation, malondialdehyde (MDA accumulation and superoxide dismutase (SOD activity suggested that anti-cancer action of LA is due to enhanced ROS generation and decreased cell anti-oxidant capacity that resulted in mitochondrial damage. Of the three cell lines tested, semi-differentiated colorectal cancer cells RKO were most sensitive to the cytotoxic action of LA, followed by undifferentiated colorectal cancer cell line (LOVO while the normal human umbilical vein endothelial cells (HUVEC were the most resistant (the degree of sensitivity to LA is as follows: RKO > LOVO > HUVEC. LA induced cell death was primed by mitochondrial apoptotic pathway. Pre-incubation of cancer cells with 100 μM LA for 24 hr enhanced sensitivity of differentiated and semi-differentiated cells to the subsequent exposure to LA. The relative resistance of LOVO cells to the cytotoxic action of LA is due to a reduction in the activation of caspase-3. Thus, LA induced cancer cell apoptosis by enhancing cellular oxidant status and inducing mitochondrial dysfunction.

  2. Verrucous Squamous Cell Cancer in the Esophagus

    DEFF Research Database (Denmark)

    Egeland, Charlotte; Achiam, Michael P; Federspiel, Birgitte


    Verrucous carcinoma is a rare, slow-growing type of squamous cell cancer. Fewer than 50 patients with verrucous carcinoma in the esophagus have been described worldwide. In 2014, two male patients were diagnosed with verrucous carcinoma in the distal part of the esophagus. The endoscopic...... examinations showed a similar wart-like, white, irregular mucosa in both cases. The diagnosis was difficult to make since all biopsies taken from the affected area showed no malignancy. This cancer type has a relatively good prognosis when the diagnosis is finally obtained. Both our patients presented...

  3. 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


    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

  4. Constitutional mosaic genome-wide uniparental disomy due to diploidisation: an unusual cancer-predisposing mechanism. (United States)

    Romanelli, Valeria; Nevado, Julián; Fraga, Mario; Trujillo, Alex Martín; Mori, Maria Ángeles; Fernández, Luis; Pérez de Nanclares, Guiomar; Martínez-Glez, Víctor; Pita, Guillermo; Meneses, Heloisa; Gracia, Ricardo; García-Miñaur, Sixto; García de Miguel, Purificación; Lecumberri, Beatriz; Rodríguez, José Ignacio; González Neira, Anna; Monk, David; Lapunzina, Pablo


    Molecular studies in a patient with Beckwith-Wiedemann syndrome phenotype who developed two different tumours revealed an unexpected observation of almost complete loss of heterozygosity of all chromosomes. It is shown, by means of numerous molecular methods, that the absence of maternal contribution in somatic cells is due to high-degree (∼ 85%) genome-wide paternal uniparental disomy (UPD). The observations indicate that the genome-wide UPD results from diploidisation, and have important implications for genetic counselling and tumour surveillance for the growing number of UPD associated imprinting disorders.

  5. [Mechanism research on the lupeol treatment on MCF-7 breast cancer cells based on cell metabonomics]. (United States)

    Shi, Dongdong; Kuang, Yuanyuan; Wang, Guiming; Peng, Zhangxiao; Wang, Yan; Yan, Chao


    The objective of this research is to investigate the suppressive effects of lupeol on MCF-7 breast cancer cells, and explore its mechanism on inhibiting the proliferation of MCF-7 cells based on cell metabonomics and cell cycle. Gas chromatography-mass spectrometry (GC-MS) was used in the cell metabonomics assay to identify metabolites of MCF-7 cells and MCF-7 cells treated with lupeol. Then, orthogonal partial least squares discriminant analysis (OPLS-DA) was used to process the metabolic data and model parameters of OPLS-DA were as follows: R2Ycum = 0.988, Q2Ycum = 0.964, which indicated that these two groups could be distinguished clearly. The metabolites (VIP (variable importance in the projection) > 1) were analyzed by t-test, and finally, metabolites (t < 0.05) were identified to be biomarkers. Eleven metabolites such as butanedioic acid, phosphoric acid, L-leucine and isoleucine which had a significant contribution to classification were selected and preliminarily identified due to the accurate mass. Cell cycle assay was analyzed by FACSCalibur. Since the cells in the phase of G1 were increased significantly after the treatment of lupeol, we speculated that lupeol has a blocking effect on the generation of succinyl-CoA and the reaction of substrate phosphorylation of tricarboxylic acid cycle of MCF-7 cells. This study provided a novel approach to the mechanism research on the lupeol treatment on MCF-7 breast cancer cells based on cell metabonomics.

  6. Essential Oil from Myrica rubra Leaves Potentiated Antiproliferative and Prooxidative Effect of Doxorubicin and its Accumulation in Intestinal Cancer Cells. (United States)

    Ambrož, Martin; Hanušová, Veronika; Skarka, Adam; Boušová, Iva; Králová, Věra; Langhasová, Lenka; Skálová, Lenka


    Essential oil from the leaves of Myrica rubra, a subtropical Asian fruit tree traditionally used in folk medicines, has a significant antiproliferative effect in several intestinal cancer cell lines. Doxorubicin belongs to the most important cytostatics used in cancer therapy. The present study was designed to evaluate the effects of defined essential oil from M. rubra leaves on efficacy, prooxidative effect, and accumulation of doxorubicin in cancer cell lines and in non-cancerous cells. For this purpose, intestinal adenocarcinoma CaCo2 cells were used. Human fibroblasts (periodontal ligament) and a primary culture of rat hepatocytes served as models of non-cancerous cells. The results showed that the sole essential oil from M. rubra has a strong prooxidative effect in cancer cells while it acts as a mild antioxidant in hepatocytes. Combined with doxorubicin, the essential oil enhanced the antiproliferative and prooxidative effects of doxorubicin in cancer cells. At higher concentrations, synergism of doxorubicin and essential oil from M. rubra was proved. In non-cancerous cells, the essential oil did not affect the toxicity of doxorubicin and the doxorubicin-mediated reactive oxygen species formation. The essential oil increased the intracellular concentration of doxorubicin and enhanced selectively the doxorubicin accumulation in nuclei of cancer cells. Taken together, essential oil from M. rubra leaves could be able to improve the doxorubicin efficacy in cancer cells due to an increased reactive oxygen species production, and the doxorubicin accumulation in nuclei of cancer cells.

  7. [Experimental models in oncology: contribution of cell culture on understanding the biology of cancer]. (United States)

    Cruz, Mariana; Enes, Margarida; Pereira, Marta; Dourado, Marília; Sarmento Ribeiro, Ana Bela


    In the beginning of the 20th century, tissue culture was started with the aim of studying the behaviour of animal cells in normal and stress conditions. The cell study at molecular level depends on their capacity of growing and how they can be manipulated in laboratory. In vitro cell culture allows us the possibility of studying biological key processes, such as growth, differentiation and cell death, and also to do genetic manipulations essential to the knowledge of structure and genes function. Human stem cells culture provides strategies to circumvent other models' deficiencies. It seems that cancer stem cells remain quiescent until activation by appropriated micro-environmental stimulation. Several studies reveal that different cancer types could be due to stem cell malignant transformations. Removal of these cells is essential to the development of more effective cancer therapies for advanced disease. On the other hand, dendritic cells modified in culture may be used as a therapeutic vaccine in order to induce tumour withdraw.

  8. 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


    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.

  9. Are breast cancer stem cells the key to resolving clinical issues in breast cancer therapy? (United States)

    Shima, Hidetaka; Ishikawa, Takashi; Endo, Itaru


    Despite the dramatic advances in breast cancer treatment over the past two decades, it is still the most common malignancies in women. One of the reasons patients succumb to breast cancer is treatment resistance leading to metastasis and recurrence. Recently, cancer stem cells (CSCs) have been suggested as a cause of metastasis and recurrence in several cancers because of their unique characteristics, including self-renewal, pluripotency, and high proliferative ability. Increasing evidence has implicated breast cancer stem cells (BCSCs) as essential for tumor development, progression, recurrence, and treatment resistance. BCSCs exhibit resistance to treatment owing to several inter-related factors, including overexpression of ATP-binding cassette (ABC) transporters and increased aldehyde dehydrogenase (ALDH) activity, DNA repair, and reactive oxygen species (ROS) scavenging. In addition, the Notch, Hedgehog, and Wnt signaling pathways have been suggested as the major pathways involved in the self-renewal and differentiation of BCSCs. Despite growing evidence suggesting the importance of BCSCs in progression and metastasis, clear criteria for the identification of BCSCs in clinical practice have yet to be established. Several potential markers have been suggested, including CD44+/CD24−/low, ALDH1, EpCAM/ESA, and nestin; however, there is no standard method to detect BCSCs. Triple-negative breast cancer, which shows initial chemosensitivity, demonstrates worsened prognosis due to therapy resistance, which might be related to the presence of BCSCs. Several clinical trials aimed at the identification of BCSCs or the development of BCSC-targeted therapy are in progress. Determining the clinical relevance of BCSCs may provide clues for overcoming therapy resistance in breast cancer. PMID:28210556

  10. Review: Biological relevance of disseminated tumor cells in cancer patients. (United States)

    Riethdorf, Sabine; Wikman, Harriet; Pantel, Klaus


    The prognosis of cancer patients is largely determined by the occurrence of distant metastases. In patients with primary tumors, this relapse is mainly due to clinically occult micrometastasis present in secondary organs at primary diagnosis but not detectable even with high resolution imaging procedures. Sensitive and specific immunocytochemical and molecular assays enable the detection and characterization of disseminated tumor cells (DTC) at the single cell level in bone marrow (BM) as the common homing site of DTC and circulating tumor cells (CTC) in peripheral blood. Because of the high variability of results in DTC and CTC detection, there is an urgent need for standardized methods. In this review, we will focus on BM and present currently available methods for the detection and characterization of DTC. Furthermore, we will discuss data on the biology of DTC and the clinical relevance of DTC detection. While the prognostic impact of DTC in BM has clearly been shown for primary breast cancer patients, less is known about the clinical relevance of DTC in patients with other carcinomas. Current findings suggest that DTC are capable to survive chemotherapy and persist in a dormant nonproliferating state over years. To what extent these DTC have stem cell properties is subject of ongoing investigations. Further characterization is required to understand the biology of DTC and to identify new targets for improved risk prevention and tailoring of therapy. Our review will focus on breast, colon, lung, and prostate cancer as the main tumor entities in Europe and the United States.

  11. Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Yun-feng Lou

    Full Text Available Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor synergized with gefitinib (an EGFR inhibitor to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1 which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon

  12. Light induced drug delivery into cancer cells. (United States)

    Shamay, Yosi; Adar, Lily; Ashkenasy, Gonen; David, Ayelet


    Cell-penetrating peptides (CPPs) can be used for intracellular delivery of a broad variety of cargoes, including various nanoparticulate pharmaceutical carriers. However, the cationic nature of all CPP sequences, and thus lack of cell specificity, limits their in vivo use for drug delivery applications. Here, we have devised and tested a strategy for site-specific delivery of dyes and drugs into cancer cells by using polymers bearing a light activated caged CPP (cCPP). The positive charge of Lys residues on the minimum sequence of the CPP penetratin ((52)RRMKWKK(58)) was masked with photo-cleavable groups to minimize non-specific adsorption and cellular uptake. Once illuminated by UV light, these protecting groups were cleaved, the positively charged CPP regained its activity and facilitated rapid intracellular delivery of the polymer-dye or polymer-drug conjugates into cancer cells. We have found that a 10-min light illumination time was sufficient to enhance the penetration of the polymer-CPP conjugates bearing the proapoptotic peptide, (D)(KLAKLAK)(2), into 80% of the target cells, and to promote a 'switch' like cytotoxic activity resulting a shift from 100% to 10% in cell viability after 2 h. This report provides an example for tumor targeting by means of light activation of cell-penetrating peptides for intracellular drug delivery.

  13. Cancer-secreted AGR2 induces programmed cell death in normal cells (United States)

    Vitello, Elizabeth A.; Quek, Sue-Ing; Kincaid, Heather; Fuchs, Thomas; Crichton, Daniel J.; Troisch, Pamela; Liu, Alvin Y.


    Anterior Gradient 2 (AGR2) is a protein expressed in many solid tumor types including prostate, pancreatic, breast and lung. AGR2 functions as a protein disulfide isomerase in the endoplasmic reticulum. However, AGR2 is secreted by cancer cells that overexpress this molecule. Secretion of AGR2 was also found in salamander limb regeneration. Due to its ubiquity, tumor secretion of AGR2 must serve an important role in cancer, yet its molecular function is largely unknown. This study examined the effect of cancer-secreted AGR2 on normal cells. Prostate stromal cells were cultured, and tissue digestion media containing AGR2 prepared from prostate primary cancer 10-076 CP and adenocarcinoma LuCaP 70CR xenograft were added. The control were tissue digestion media containing no AGR2 prepared from benign prostate 10-076 NP and small cell carcinoma LuCaP 145.1 xenograft. In the presence of tumor-secreted AGR2, the stromal cells were found to undergo programmed cell death (PCD) characterized by formation of cellular blebs, cell shrinkage, and DNA fragmentation as seen when the stromal cells were UV irradiated or treated by a pro-apoptotic drug. PCD could be prevented with the addition of the monoclonal AGR2-neutralizing antibody P3A5. DNA microarray analysis of LuCaP 70CR media-treated vs. LuCaP 145.1 media-treated cells showed downregulation of the gene SAT1 as a major change in cells exposed to AGR2. RT-PCR analysis confirmed the array result. SAT1 encodes spermidine/spermine N1-acetyltransferase, which maintains intracellular polyamine levels. Abnormal polyamine metabolism as a result of altered SAT1 activity has an adverse effect on cells through the induction of PCD. PMID:27283903

  14. A Stochastic Model for Cancer Stem Cell Origin in Metastatic Colon Cancer (United States)

    Odoux, Christine; Fohrer, Helene; Hoppo, Toshitaka; Guzik, Lynda; Stolz, Donna Beer; Lewis, Dale W.; Gollin, Susanne M.; Gamblin, T. Clark; Geller, David A.; Lagasse, Eric


    Human cancers have been found to include transformed stem cells that may drive cancer progression to metastasis. Here we report that metastatic colon cancer contains clonally derived tumor cells with all of the critical properties expected of stem cells, including self-renewal and to the ability to differentiate into mature colon cells. Additionally, when injected into mice, these cells initiated tumors that closely resemble human cancer. Karyotype analyses of parental and clonally-derived tumor cells expressed many consistent (clonal), along with unique chromosomal aberrations, suggesting the presence of chromosomal instability in the cancer stem cells. Thus, this new model for cancer origin and metastatic progression includes features of both the hierarchical model for cancerous stem cells and the stochastic model, driven by the observation of chromosomal instability. PMID:18757407

  15. Stiffness of cancer cells measured with an AFM indentation method. (United States)

    Hayashi, Kozaburo; Iwata, Mayumi


    The stiffness of cancer cells and its changes during metastasis are very important for understanding the pathophysiology of cancer cells and the mechanisms of metastasis of cancer. As the first step of the studies on the mechanics of cancer cells during metastasis, we determined the elasticity and stiffness of cancer cells with an indentation method using an atomic force microscope (AFM), and compared with those of normal cells. In most of the past AFM studies, Young׳s elastic moduli of cells have been calculated from force-indentation data using Hertzian model. As this model is based on several important assumptions including infinitesimal strain and Hooke׳s linear stress-strain law, in the exact sense it cannot be applied to cells that deform very largely and nonlinearly. To overcome this problem, we previously proposed an equation F=a[exp(bδ)-1] to describe relations between force (F) and indentation (δ), where a and b are parameters relating with cellular stiffness. In the present study, we applied this method to cancer cells instead of Young׳s elastic modulus. The conclusions obtained are: 1) AFM indentation test data of cancer cells can be very well described by the above equation, 2) cancer cells are softer than normal cells, and 3) there are no significant locational differences in the stiffness of cancer cells between the central and the peripheral regions. These methods and results are useful for studying the mechanics of cancer cells and the mechanisms of metastasis.

  16. Primary cultures of human colon cancer as a model to study cancer stem cells. (United States)

    Koshkin, Sergey; Danilova, Anna; Raskin, Grigory; Petrov, Nikolai; Bajenova, Olga; O'Brien, Stephen J; Tomilin, Alexey; Tolkunova, Elena


    The principal cause of death in cancer involves tumor progression and metastasis. Since only a small proportion of the primary tumor cells, cancer stem cells (CSCs), which are the most aggressive, have the capacity to metastasize and display properties of stem cells, it is imperative to characterize the gene expression of diagnostic markers and to evaluate the drug sensitivity in the CSCs themselves. Here, we have examined the key genes that are involved in the progression of colorectal cancer and are expressed in cancer stem cells. Primary cultures of colorectal cancer cells from a patient's tumors were studied using the flow cytometry and cytological methods. We have evaluated the clinical and stem cell marker expression in these cells, their resistance to 5-fluorouracil and irinotecan, and the ability of cells to form tumors in mice. The data shows the role of stem cell marker Oct4 in the resistance of primary colorectal cancer tumor cells to 5-fluorouracil.

  17. Stem cells in normal mammary gland and breast cancer. (United States)

    Luo, Jie; Yin, Xin; Ma, Tao; Lu, Jun


    The mammary gland is a structurally dynamic organ that undergoes dramatic alterations with age, menstrual cycle, and reproductive status. Mammary gland stem cells, the minor cell population within the mature organ, are thought to have multiple functions in regulating mammary gland development, tissue maintenance, major growth, and structural remodeling. In addition, accumulative evidence suggests that breast cancers are initiated and maintained by a subpopulation of tumor cells with stem cell features (called cancer stem cells). A variety of methods have been developed to identify and characterize mammary stem cells, and several signal transduction pathways have been identified to be essential for the self-renewal and differentiation of mammary gland stem cells. Understanding the origin of breast cancer stem cells, their relationship to breast cancer development, and the differences between normal and cancer stem cells may lead to novel approaches to breast cancer diagnosis, prevention, and treatment.

  18. Guidelines on renal cell cancer

    NARCIS (Netherlands)

    Mickisch, G; Carballido, J; Hellsten, S; Schuize, H; Mensink, H


    Objectives., On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and. Follow Up of Renal. Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost-effectiveness and clinical feasibility. Method: A sy

  19. Microchimeric Cells, Sex Chromosome Aneuploidies and Cancer. (United States)

    Korkmaz, Deniz Taştemir; Demirhan, Osman; Abat, Deniz; Demirberk, Bülent; Tunç, Erdal; Kuleci, Sedat


    The phenomenon of feta-maternal microchimerisms inspires numerous questions. Many questions remain to be answered regarding this new avenue of genetics. The X and Y chromosomes have been associated with malignancy in different types of human tumors. We aimed to investigate the numerical aberrations of chromosomes X and Y in lung cancer (LC) and bladder cancer (BC) and review recent evidence for possible roles of microchimeric cells (McCs) in these cancers. We carried out cytogenetic analysis of the tumor and blood sampling in 52 cases of people with BC and LC, and also with 30 healthy people. A total of 48 (92.3 %) of the patients revealed sex chromosome aneuploidies (SCAs). A total SCAs was found in 9.8 % of 2282 cells that were analyzed as one or more cells in each case. The 68 and 95 SCAs were found in the 1952 (8.4 %) cells in peripheral blood, and 41 and 19 SCAs in the 330 (18.2 %) cells in the tumoral tissues respectively. There was a significant difference in the frequencies of SCAs between the patients and the control groups determined by the Fischer's Exact Test (p chromosome monosomies. Largely a Y chromosome loss was present in 77.8 % of the men, and the 47, XXY karyotype was found in 33.3 % of them. The second most common SCA was monosomy X, and was found in 71.4 % of the women. McCs were observed in 26.9 % of the 52 patients, and the frequencies of McCs were higher in the blood than in the tissues (p aneuploidies of X and Y chromosomes play a role in the pathogenesis of cancers.

  20. Aldehyde dehydrogenase-expressing colon stem cells contribute to tumorigenesis in the transition from colitis to cancer. (United States)

    Carpentino, Joseph E; Hynes, Mark J; Appelman, Henry D; Zheng, Tong; Steindler, Dennis A; Scott, Edward W; Huang, Emina H


    Patients with chronic ulcerative colitis are at increased risk of developing colorectal cancer. Although current hypotheses suggest that sporadic colorectal cancer is due to inability to control cancer stem cells, the cancer stem cell hypothesis has not yet been validated in colitis-associated cancer. Furthermore, the identification of the colitis to cancer transition is challenging. We recently showed that epithelial cells with the increased expression of aldehyde dehydrogenase in sporadic colon cancer correlate closely with tumor-initiating ability. We sought to determine whether ALDH can be used as a marker to isolate tumor-initiating populations from patients with chronic ulcerative colitis. We used fluorescence-activated cell sorting to identify precursor colon cancer stem cells from colitis patients and report both their transition to cancerous stem cells in xenografting studies as well as their ability to generate spheres in vitro. Similar to sporadic colon cancer, these colitis-derived tumors were capable of propagation as sphere cultures. However, unlike the origins of sporadic colon cancer, the primary colitic tissues did not express any histologic evidence of dysplasia. To elucidate a potential mechanism for our findings, we compared the stroma of these different environments and determined that at least one paracrine factor is up-regulated in the inflammatory and malignant stroma compared with resting, normal stroma. These data link colitis and cancer identifying potential tumor-initiating cells from colitic patients, suggesting that sphere and/or xenograft formation will be useful to survey colitic patients at risk of developing cancer.

  1. Tumoral stem cell reprogramming as a driver of cancer: Theory, biological models, implications in cancer therapy. (United States)

    Vicente-Dueñas, Carolina; Hauer, Julia; Ruiz-Roca, Lucía; Ingenhag, Deborah; Rodríguez-Meira, Alba; Auer, Franziska; Borkhardt, Arndt; Sánchez-García, Isidro


    Cancer is a clonal malignant disease originated in a single cell and characterized by the accumulation of partially differentiated cells that are phenotypically reminiscent of normal stages of differentiation. According to current models, therapeutic strategies that block oncogene activity are likely to selectively target tumor cells. However, recent evidences have revealed that cancer stem cells could arise through a tumor stem cell reprogramming mechanism, suggesting that genetic lesions that initiate the cancer process might be dispensable for tumor progression and maintenance. This review addresses the impact of these results toward a better understanding of cancer development and proposes new approaches to treat cancer in the future.

  2. Sulindac sulfide inhibits colon cancer cell growth and downregulates specificity protein transcription factors


    Li, Xi; Pathi, Satya S.; Safe, Stephen


    Background Specificity protein (Sp) transcription factors play pivotal roles in maintaining the phenotypes of many cancers. We hypothesized that the antineoplastic effects of sulindac and its metabolites were due, in part, to targeting downregulation of Sp transcription factors. Methods The functional effects of sulindac, sulindac sulfone and sulindac sulfide on colon cancer cell proliferation were determined by cell counting. Effects of these compounds on expression of Sp1, Sp3, Sp4 and pro-...

  3. A functional role for tumor cell heterogeneity in a mouse model of small cell lung cancer. (United States)

    Calbo, Joaquim; van Montfort, Erwin; Proost, Natalie; van Drunen, Ellen; Beverloo, H Berna; Meuwissen, Ralph; Berns, Anton


    Small cell lung cancer (SCLC) is the lung neoplasia with the poorest prognosis, due to its high metastatic potential and chemoresistance upon relapse. Using the previously described mouse model for SCLC, we found that the tumors are often composed of phenotypically different cells with either a neuroendocrine or a mesenchymal marker profile. These cells had a common origin because they shared specific genomic aberrations. The transition from neuroendocrine to mesenchymal phenotype could be achieved by the ectopic expression of oncogenic Ras(V12). Crosstalk between mesenchymal and neuroendocrine cells strongly influenced their behavior. When engrafted as a mixed population, the mesenchymal cells endowed the neuroendocrine cells with metastatic capacity, illustrating the potential relevance of tumor cell heterogeneity in dictating tumor properties.

  4. Therapeutic strategies for targeting cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Yu Jeong Kim; Elizabeth L Siegler; Natnaree Siriwon; Pin Wang


    The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy; these shortcomings are largely attributed to the ability of cancer cells to repopulate and metastasize after initial therapies. Compelling evidence suggests that cancer stem cells (CSCs) have a crucial impact in current shortcomings of cancer therapy because they are largely responsible for tumor initiation, relapse, metastasis, and chemo-resistance. Thus, a better understanding of the properties and mechanisms underlying CSC resistance to treatments is necessary to improve patient outcomes and survival rates. In this review, the authors characterize and compare different CSC-speciifc biomarkers that are present in various types of tumors. We further discuss multiple targeting approaches currently in preclinical or clinical testing that show great potential for targeting CSCs. This review discusses numerous strategies to eliminate CSCs by targeting surface biomarkers, regulating CSC-associated oncogenes and signaling pathways, inhibiting drug-eflfux pumps involved in drug resistance, modulating the tumor microenvironment and immune system, and applying drug combination therapy using nanomedicine.

  5. Heat induces gene amplification in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Bin, E-mail: [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)


    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, H


    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.

  7. Circulating tumor cells: exploring intratumor heterogeneity of colorectal cancer. (United States)

    Raimondi, Cristina; Nicolazzo, Chiara; Gradilone, Angela; Giannini, Giuseppe; De Falco, Elena; Chimenti, Isotta; Varriale, Elisa; Hauch, Siegfried; Plappert, Linda; Cortesi, Enrico; Gazzaniga, Paola


    The hypothesis of the "liquid biopsy" using circulating tumor cells (CTCs) emerged as a minimally invasive alternative to traditional tissue biopsy to determine cancer therapy. Discordance for biomarkers expression between primary tumor tissue and circulating tumor cells (CTCs) has been widely reported, thus rendering the biological characterization of CTCs an attractive tool for biomarkers assessment and treatment selection. Studies performed in metastatic colorectal cancer (mCRC) patients using CellSearch, the only FDA-cleared test for CTCs assessment, demonstrated a much lower yield of CTCs in this tumor type compared with breast and prostate cancer, both at baseline and during the course of treatment. Thus, although attractive, the possibility to use CTCs as therapy-related biomarker for colorectal cancer patients is still limited by a number of technical issues mainly due to the low sensitivity of the CellSearch method. In the present study we found a significant discordance between CellSearch and AdnaTest in the detection of CTCs from mCRC patients. We then investigated KRAS pathway activating mutations in CTCs and determined the degree of heterogeneity for KRAS oncogenic mutations between CTCs and tumor tissues. Whether KRAS gene amplification may represent an alternative pathway responsible for KRAS activation was further explored. KRAS gene amplification emerged as a functionally equivalent and mutually exclusive mechanism of KRAS pathway activation in CTCs, possibly related to transcriptional activation. The serial assessment of CTCs may represent an early biomarker of treatment response, able to overcome the intrinsic limit of current molecular biomarkers represented by intratumor heterogeneity.

  8. In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer. (United States)

    Hamilton, Amanda M; Foster, Paula J


    Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

  9. Luteolin inhibits lung metastasis, cell migration, and viability of triple-negative breast cancer cells (United States)

    Cook, Matthew T; Liang, Yayun; Besch-Williford, Cynthia; Hyder, Salman M


    Most breast cancer-related deaths from triple-negative breast cancer (TNBC) occur following metastasis of cancer cells and development of tumors at secondary sites. Because TNBCs lack the three receptors targeted by current chemotherapeutic regimens, they are typically treated with extremely aggressive and highly toxic non-targeted treatment strategies. Women with TNBC frequently develop metastatic lesions originating from drug-resistant residual cells and have poor prognosis. For this reason, novel therapeutic strategies that are safer and more effective are sought. Luteolin (LU) is a naturally occurring, non-toxic plant compound that has proven effective against several types of cancer. With this in mind, we conducted in vivo and in vitro studies to determine whether LU might suppress metastasis of TNBC. In an in vivo mouse metastasis model, LU suppressed metastasis of human MDA-MB-435 and MDA-MB-231 (4175) LM2 TNBC cells to the lungs. In in vitro assays, LU inhibited cell migration and viability of MDA-MB-435 and MDA-MB-231 (4175) LM2 cells. Further, LU induced apoptosis in MDA-MB-231 (4175) LM2 cells. Relatively low levels (10 µM) of LU significantly inhibited vascular endothelial growth factor (VEGF) secretion in MDA-MB-231 (4175) LM2 cells, suggesting that it has the ability to suppress a potent angiogenic and cell survival factor. In addition, migration of MDA-MB-231 (4175) LM2 cells was inhibited upon exposure to an antibody against the VEGF receptor, KDR, but not by exposure to a VEGF165 antibody. Collectively, these data suggest that the anti-metastatic properties of LU may, in part, be due to its ability to block VEGF production and KDR-mediated activity, thereby inhibiting tumor cell migration. These studies suggest that LU deserves further investigation as a potential treatment option for women with TNBC. PMID:28096694

  10. Determination of the optimum conditions for lung cancer cells treatment using cold atmospheric plasma (United States)

    Akhlaghi, Morteza; Rajaei, Hajar; Mashayekh, Amir Shahriar; Shafiae, Mojtaba; Mahdikia, Hamed; Khani, Mohammadreza; Hassan, Zuhair Mohammad; Shokri, Babak


    Cold atmospheric plasmas (CAPs) can affect live cells and organisms due to the production of different reactive species. In this paper, the effects of various parameters of the CAP such as the treatment time, gas mixture, gas flow rate, applied voltage, and distance from the nozzle on the LL/2 lung cancer cell line have been studied. The probable effect of UV radiation has also been investigated using an MgF2 filter. Besides the cancerous cells, the 3T3 fibroblast cell line as a normal cell has been treated with the CAP. The Methylthiazol Tetrazolium assay showed that all parameters except the gas flow rate could impress effectively on the cancer cell viability. The cell proliferation seemed to be stopped after plasma treatment. The flow cytometry assay revealed that apoptosis and necrosis were appreciable. It was also found that treating time up to 2 min will not exert any effect on the normal cells.

  11. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy (United States)

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


    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.

  12. LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer. (United States)

    Amsterdam, Abraham; Raanan, Calanit; Schreiber, Letizia; Polin, Nava; Givol, David


    Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer.

  13. Raman spectra of single cell from gastrointestinal cancer patients

    Institute of Scientific and Technical Information of China (English)

    Xun-Ling Yan; Rui-Xin Dong; Lei Zhang; Xue-Jun Zhang; Zong-Wang Zhang


    AIM: To explore the difference between cancer cells and normal cells, we investigated the Raman spectra of singlecells from gastrointestinal cancer patients. METHODS: All samples were obtained from 30 diagnosed as gastrointestinal cancer patients. The flesh tumor specimen is located in the center of tumor tissue, while the normal ones were 5 cm away from the outside tumor section. The imprint was put under the microscope and a single cell was chosen for Raman measurement. All spectra were collected at confocal Raman micro-spectroscopy (British Renishaw) with NIR 780 nm laser.RESULTS: We measured the Raman spectra of several cells from gastrointestinal cancer patients. The result shows that there exists the strong line at 1 002/cm with less half-width assigned to the phenylalanine in several cells. The Raman lines of white cell were lower and less, while those of red cell were not only higher in intensity and more abundant, but also had a parti cular C-N breathing stretching band of pyrrole ring at 1 620-1 540/cm. The line at 1 084/cm assigned to phosphate backbone of DNA became obviously weaker in cancer cell. The Raman spectra of stomach cancer cells were similar to those of normal cells, but the Raman intensity of cancer cells was much lower than that of normal cells, and even some lines disappear. The lines of enteric cancer cells became weaker than spectra above and many lines disappeared, and the cancer cells in different position had different fluorescence intensity.CONCLUSION: The Raman spectra of several cells from cancer patients show that the structural changes of cancer cells happen and many bonds rupture so that the biological function of cells are lost. The results indicate that Raman spectra can offer the experiment basis for the cancer diagnosis and treatment.

  14. Induction of iPS cells and of cancer stem cells: the stem cell or reprogramming hypothesis of cancer? (United States)

    Trosko, James E


    This article as designed to examine whether the "stoichiometric" or "elite models" of the origin of the "induced pluripotent stem" (iPS) cells fits some experiment facts from the developmental biology of adult stem cells and from the field of cancer research. In brief, since the evidence presented to support the stoichiometric model failed to recognize the factual existence of adult organ specific stem cells, the model has not been rigorously tested. In addition, the demonstration of a subset of cells (MUSE cells) in normal primary in vitro cultures of human fibroblasts (the usual source of iPS cells) seems to be the origin of the iPS cells. Moreover, from the field of carcinogenesis, the "stem cell" versus "de-differentiation" or "reprogramming" hypotheses were examined. Again, using the role of glycolysis, known to be associated with the Warburg effect in cancer cells, a list of experiments showing that (a) normal stem cells, which have few mitochondria, metabolize via glycolysis; (b) the stem cells are targets for "initiation" or "immortalization" or the blockage of differentiation and apoptosis of the stem cells by "immortalizing viruses"; (c) Lactate dehydrogenase A (LDHA), when expressed, is associated with glycolysis and therefore, must be expressed in normal adult stem cells, as well as in cancer cells; and (d) p53, depleted or rendered dysfunctional by SV40 Large T antigen, is associated with the reduction of mitochondrial function and mass and is associated with the Warburg effect. Together, these observations from the iPS and "cancer stem cell" fields support the idea that both iPS cells and cancer stem cell are derived from adult organ-specific stem cells that do not restore or switch their metabolism of glucose from oxidative metabolism to glycolysis but, rather, in both cases, the adult stem cell, which metabolizes by glycolysis, is prevented from differentiation or from metabolizing by oxidative phosphorylation.

  15. Deciphering the role of microRNA 21 in cancer stem cells (CSCs

    Directory of Open Access Journals (Sweden)

    Durairaj Sekar


    Full Text Available Irrespective of positive developments of cancer treatment, the mortality due to various cancers remains high and the mechanisms of cancer initiation and the development also remains mysterious. As we know that microRNAs are considered to be a short noncoding RNA molecules consisting of 21–25 nucleotides (nt in length and they silence their target genes by inhibiting mRNA translation or degrading the mRNA molecules by binding to their 3′-untranslated (UTR region and play a very important role in cancer biology. Recent evidences indicate that miR-21 is over expressed in cancer stem cells and plays a vital role in cell proliferation, apoptosis, and invasion. Even though an increased expression level of miR-21 has been observed in cancer stem cells, studies related to the role of miR-21 in cancer stem cells are limited. The main aim of this mini review is to explain the potency of miR-21 in various cancer stem cells (CSCs and as a new target for therapeutic interventions of cancer progression.

  16. PNIPAAm-MAA nanoparticles as delivery vehicles for curcumin against MCF-7 breast cancer cells. (United States)

    Zeighamian, Vahideh; Darabi, Masoud; Akbarzadeh, Abolfazl; Rahmati-Yamchi, Mohammad; Zarghami, Nosratollah; Badrzadeh, Fariba; Salehi, Roya; Mirakabad, Fatemeh Sadat Tabatabaei; Taheri-Anganeh, Mortaza


    Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm-MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

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



    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...

  18. 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.

  19. Advances in Lung Stem Cells and Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Huijing YIN


    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.

  20. [Advances in Lung Stem Cells and Lung Cancer Stem Cells]. (United States)

    Yin, Huijing; Deng, Jiong


    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. Exercise-Dependent Regulation of NK Cells in Cancer Protection

    DEFF Research Database (Denmark)

    Idorn, Manja; Hojman, Pernille


    Natural killer (NK) cells are the most responsive immune cells to exercise, displaying an acute mobilization to the circulation during physical exertion. Recently, exercise-dependent mobilization of NK cells was found to play a central role in exercise-mediated protection against cancer. Here, we...... a mechanistic explanation for the protective effect of exercise on cancer, and we propose that exercise represents a potential strategy as adjuvant therapy in cancer, by improving NK cell recruitment and infiltration in solid tumors....

  2. Glioblastoma cancer stem cells: Biomarker and therapeutic advances. (United States)

    Pointer, Kelli B; Clark, Paul A; Zorniak, Michael; Alrfaei, Bahauddeen M; Kuo, John S


    Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans. It accounts for fifty-two percent of primary brain malignancies in the United States and twenty percent of all primary intracranial tumors. Despite the current standard therapies of maximal safe surgical resection followed by temozolomide and radiotherapy, the median patient survival is still less than 2 years due to inevitable tumor recurrence. Glioblastoma cancer stem cells (GSCs) are a subgroup of tumor cells that are radiation and chemotherapy resistant and likely contribute to rapid tumor recurrence. In order to gain a better understanding of the many GBM-associated mutations, analysis of the GBM cancer genome is on-going; however, innovative strategies to target GSCs and overcome tumor resistance are needed to improve patient survival. Cancer stem cell biology studies reveal basic understandings of GSC resistance patterns and therapeutic responses. Membrane proteomics using phage and yeast display libraries provides a method to identify novel antibodies and surface antigens to better recognize, isolate, and target GSCs. Altogether, basic GBM and GSC genetics and proteomics studies combined with strategies to discover GSC-targeting agents could lead to novel treatments that significantly improve patient survival and quality of life.

  3. Synergistic enhancement of breast cancer cell death using ultrasound-microbubbles in combination with cisplatin (United States)

    Jetha, Sheliza; Karshafian, Raffi


    Cisplatin (CDDP), an anti-cancer agent, can effectively treat several cancerous tumourstumors such as testicular, bladder, and ovarian cancers. CDDP binds to specific DNA bases causing 1,2-intrastrand cross-links, single strand and double strand breaks inducing apoptosis. However, the effectiveness of CDDP is limited in tumourtumors such as breast cancer due to drug resistance. In this study, the application of ultrasound-microbubble (USMB) in improving the therapeutic effect of CDDP in breast cancer cell line is investigated. Human breast cancer (MDA-MB-231) cells in suspension (2×106 cells/mL concentration and 0.6 mL volume) were treated with CDDP (3 µM, 30 µM and 300 µM) and USMB at 0.5 MHz pulse centered frequency, 60 s insonation time, 16 µs pulse duration, 1 kHz pulse repetition frequency, and 1.7% v/v (volume concentration) of Definity microbubble agent. Following USMB treatment, cells were plated in 96-well plates for 24 and 48-hour incubation, after which cell viability was measured using MTT assay (VMTT). Cell viability decreased significantly with the combined treatment of CDDP and USMB compared to CDDP alone (pcancer cells. However, this enhanced effectiveness, in breast cancer cells (MDA-MB-231), is dependent on incubation time and cisplatin (CDDP) concentration.

  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


    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. Can a Cancer Cell Turn into a Normal Cell?

    Directory of Open Access Journals (Sweden)

    Ranan Gülhan Aktas


    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.

  6. DNA-templated antibody conjugation for targeted drug delivery to cancer cells

    DEFF Research Database (Denmark)

    Liu, Tianqiang


    -templated organic synthesis due to the wide existence of the 3-histidine cluster in most wild-type proteins. In this thesis, three projects that relate to targeted drug delivery to cancer cells based on the DTPC method is described. The first project was a delivery system which uses transferrin as the targeting...... ligand and saporin (ribosome inactivating protein) as the warhead to achieve enhanced cellular uptake and cytotoxicity of saporin to transferrin receptor overexpressed cancer cell line. The transferrin-saporin conjugate complex are formed by linking the site-selective DNA-transferrin conjugates with mono...... to cancer cells. The DNA duplex in the conjugates could be used for doxorubicin intercalation since it contains CGA repeats. Confocal microscopy and flow cytometry results showed a receptor-mediated targeting manner to EGFR+ cancer cell lines (KB and MDA-MB-231), and resulted in enhanced cell killing...

  7. Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance

    DEFF Research Database (Denmark)

    D’Andrea, Filippo P.; Safwat, Akmal; Kassem, Moustapha;


    BackgroundCancer stem cells are thought to be a radioresistant population and may be the seeds for recurrence after radiotherapy. Using tumorigenic clones of retroviral immortalized human mesenchymal stem cell with small differences in their phenotype, we investigated possible genetic expression...... that could explain cancer stem cell radiation resistance. MethodsTumorigenic mesenchymal cancer stem cell clones BB3 and CE8 were irradiated at varying doses and assayed for clonogenic surviving fraction. Altered gene expression before and after 2Gy was assessed by Affymetric exon chip analysis and further...... found the genes involved in cancer, proliferation, DNA repair and cell death. ConclusionsThe higher radiation resistance in clone CE8 is likely due to NNMT overexpression. The higher levels of NNMT could affect the cellular damage resistance through depletion of the accessible amounts of nicotinamide...

  8. 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


    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.

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


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


    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.

  10. Breast Cancer Cells May Change When They Spread to Brain (United States)

    ... page: Breast Cancer Cells May Change When They Spread to Brain: ... 2016 WEDNESDAY, Dec. 7, 2016 (HealthDay News) -- When breast cancer spreads to the brain, important molecular changes may ...

  11. Treatment Options by Stage (Non-Small Cell Lung Cancer) (United States)

    ... Cancer Screening Research Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Non-Small ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  12. TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells. (United States)

    Moniri, M R; Sun, X-Y; Rayat, J; Dai, D; Ao, Z; He, Z; Verchere, C B; Dai, L-J; Warnock, G L


    Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy owing to their tumor-oriented homing capacity and the feasibility of autologous transplantation. Currently, pancreatic cancer patients face a very poor prognosis, primarily due to the lack of therapeutic strategies with an effective degree of specificity. Anticancer gene-engineered MSCs specifically target tumor sites and can produce anticancer agents locally and constantly. This study was performed to characterize pancreas-derived MSCs and investigate the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on pancreatic cancer cells under different culture conditions. Pancreas-derived MSCs exhibited positive expression on CD44, CD73, CD95, CD105, negative on CD34 and differentiated into adipogenic and osteogenic cells. TRAIL expression was assessed by both enzyme-linked immunosorbent assay and western blot analysis. Different patterns of TRAIL receptor expression were observed on the pancreatic cancer cell lines, including PANC1, HP62, ASPC1, TRM6 and BXPC3. Cell viability was assessed using a real-time monitoring system. Pancreatic cancer cell death was proportionally related to conditioned media from MSC(nsTRAIL) and MSC(stTRAIL). The results suggest that MSCs exhibit intrinsic inhibition of pancreatic cancer cells and that this effect can be potentiated by TRAIL-transfection on death receptor-bearing cell types.

  13. SC1, an immunoglobulin-superfamily cell adhesion molecule, is involved in the brain metastatic activity of lung cancer cells (United States)



    SC1 is a cell adhesion molecule that belongs to the immunoglobulin superfamily; this molecule was initially purified from the chick embryonic nervous system and was reported to exhibit homophilic adhesion activity. SC1 is transiently expressed in various organs during development and has been identified in numerous neoplastic tissues, including lung cancer and colorectal carcinomas. The present study focused on the encephalic metastasis of lung cancer cells with respect to the potential function of SC1, as this molecule is known to be consistently expressed in the central nervous system as well as lung cancers. SC1 complementary DNA was introduced into A549 cells, a human lung cancer-derived cell line. The stable overexpression of the SC1 protein in A549 cells was demonstrated to enhance the self-aggregation of the cells. In addition, the SC1 transfectants enhanced the metastatic and invasive potential to the encephalic parenchyma following implantation into nude mice. In conclusion, the results of the present study demonstrated that cell adhesion due interactions between SC1 on brain tissue and SC1 on lung cancer cells was involved in the malignant aspects of lung cancer, including invasion and metastasis to the brain. PMID:26622821

  14. 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


    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.

  15. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells. (United States)

    Geisen, Ulf; Zenthoefer, Marion; Peipp, Matthias; Kerber, Jannik; Plenge, Johannes; Managò, Antonella; Fuhrmann, Markus; Geyer, Roland; Hennig, Steffen; Adam, Dieter; Piker, Levent; Rimbach, Gerald; Kalthoff, Holger


    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.

  16. Nonequilibrium population dynamics of phenotype conversion of cancer cells.

    Directory of Open Access Journals (Sweden)

    Joseph Xu Zhou

    Full Text Available Tumorigenesis is a dynamic biological process that involves distinct cancer cell subpopulations proliferating at different rates and interconverting between them. In this paper we proposed a mathematical framework of population dynamics that considers both distinctive growth rates and intercellular transitions between cancer cell populations. Our mathematical framework showed that both growth and transition influence the ratio of cancer cell subpopulations but the latter is more significant. We derived the condition that different cancer cell types can maintain distinctive subpopulations and we also explain why there always exists a stable fixed ratio after cell sorting based on putative surface markers. The cell fraction ratio can be shifted by changing either the growth rates of the subpopulations (Darwinism selection or by environment-instructed transitions (Lamarckism induction. This insight can help us to understand the dynamics of the heterogeneity of cancer cells and lead us to new strategies to overcome cancer drug resistance.

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

    DEFF Research Database (Denmark)

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


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


    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

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

    DEFF Research Database (Denmark)

    Greve, K B V; Pøhl, M; Olsen, K E


    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...... 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....

  20. 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


    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.

  1. Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines (United States)

    Kloudová, Kamila; Hromádková, Hana; Partlová, Simona; Brtnický, Tomáš; Rob, Lukáš; Bartůňková, Jiřina; Hensler, Michal; Halaška, Michael J.; Špíšek, Radek; Fialová, Anna


    In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue. More than 90% of tumor samples expressed very high levels of CA125, FOLR1, EPCAM and MUC-1 and elevated levels of Her-2/neu, similarly to OVCAR-3 cell line. The combination of OV-90 and OVCAR-3 cell lines showed the highest overlap with patients' samples in the TAA expression profile. PMID:27323861

  2. 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)


    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.

  3. Would cancer stem cells affect the future investment in stem cell therapy. (United States)

    Rameshwar, Pranela


    The common goal within the overwhelming interests in stem cell research is to safely translate the science to patients. Although there are various methods by which this goal can be reached, this editorial emphasizes the safety of mesenchymal stem cell (MSC) transplant and possible confounds by the growing information on cancer stem cells (CSCs). There are several ongoing clinical trials with MSCs and their interactions with CSCs need to be examined. The rapid knowledge on MSCs and CSCs has now collided with regards to the safe treatment of MSCs. The information discussed on MSCs can be extrapolated to other stem cells with similar phenotype and functions such as placenta stem cells. MSCs are attractive for cell therapy, mainly due to reduced ethical concerns, ease in expansion and reduced ability to be transformed. Also, MSCs can exert both immune suppressor and tissue regeneration simultaneously. It is expected that any clinical trial with MSCs will take precaution to ensure that the cells are not transformed. However, going forward, the different centers should be aware that MSCs might undergo oncogenic events, especially as undifferentiated cells or early differentiated cells. Another major concern for MSC therapy is their ability to promote tumor growth and perhaps, to protect CSCs by altered immune responses. These issues are discussed in light of a large number of undiagnosed cancers.

  4. Mitochondrial Oxidative Stress due to Complex I Dysfunction Promotes Fibroblast Activation and Melanoma Cell Invasiveness

    Directory of Open Access Journals (Sweden)

    Maria Letizia Taddei


    Full Text Available Increased ROS (cellular reactive oxygen species are characteristic of both fibrosis and tumour development. ROS induce the trans-differentiation to myofibroblasts, the activated form of fibroblasts able to promote cancer progression. Here, we report the role of ROS produced in response to dysfunctions of mitochondrial complex I, in fibroblast activation and in tumour progression. We studied human fibroblasts with mitochondrial dysfunctions of complex I, leading to hyperproduction of ROS. We demonstrated that ROS level produced by the mutated fibroblasts correlates with their activation. The increase of ROS in these cells provides a greater ability to remodel the extracellular matrix leading to an increased motility and invasiveness. Furthermore, we evidentiated that in hypoxic conditions these fibroblasts cause HIF-1α stabilization and promote a proinvasive phenotype of human melanoma cells through secretion of cytokines. These data suggest a possible role of deregulated mitochondrial ROS production in fibrosis evolution as well as in cancer progression and invasion.

  5. Study of gemcitabine-sensitive/resistant cancer cells by cell cloning and synchrotron FTIR microspectroscopy. (United States)

    Rutter, Abigail V; Siddique, Muhammad R; Filik, Jacob; Sandt, Christophe; Dumas, Paul; Cinque, Gianfelice; Sockalingum, Ganesh D; Yang, Ying; Sulé-Suso, Josep


    Over the last few years, significant scientific insight on the effects of chemotherapy drugs at cellular level using synchrotron-based FTIR (S-FTIR) microspectroscopy has been obtained. The work carried out so far has identified spectral differences in cancer cells before and after the addition of drugs. However, this had to account for the following issues. First, chemotherapy agents cause both chemical and morphological changes in cells, the latter being responsible for changes in the spectral profile not correlated with biochemical characteristics. Second, as the work has been carried out in mixed populations of cells (resistant and sensitive), it is important to distinguish the spectral differences which are due to sensitivity/resistance to those due to cell morphology and/or cell mixture. Here, we successfully cloned resistant and sensitive lung cancer cells to a chemotherapy drug. This allowed us to study a more uniform population and, more important, allowed us to study sensitive and resistant cells prior to the addition of the drug with S-FTIR microscopy. Principal component analysis (PCA) did not detect major differences in resistant cells prior to and after adding the drug. However, PCA separated sensitive cells prior to and after the addition of the drug. This would indicate that the spectral differences between cells prior to and after adding a drug might reside on those more or less sensitive cells that have been able to remain alive when they were collected to be studied with S-FTIR microspectroscopy. This is a proof of concept and a feasibility study showing a methodology that opens a new way to identify the effects of drugs on more homogeneous cell populations using vibrational spectroscopy.

  6. Neuropeptide Y Y1 receptors meditate targeted delivery of anticancer drug with encapsulated nanoparticles to breast cancer cells with high selectivity and its potential for breast cancer therapy. (United States)

    Li, Juan; Shen, Zheyu; Ma, Xuehua; Ren, Wenzhi; Xiang, Lingchao; Gong, An; Xia, Tian; Guo, Junming; Wu, Aiguo


    By enabling nanoparticle-based drug delivery system to actively target cancer cells with high selectivity, active targeted molecules have attracted great attention in the application of nanoparticles for anticancer drug delivery. However, the clinical application of most active targeted molecules in breast cancer therapy is limited, due to the low expression of their receptors in breast tumors or coexpression in the normal and tumor breast tissues. Here, a neuropeptide Y Y1 receptors ligand PNBL-NPY, as a novel targeted molecule, is conjugated with anticancer drug doxorubicin encapsulating albumin nanoparticles to investigate the effect of Y1 receptors on the delivery of drug-loaded nanoparticles to breast cancer cells and its potential for breast cancer therapy. The PNBL-NPY can actively recognize and bind to the Y1 receptors that are significantly overexpressed on the surface of the breast cancer cells, and the drug-loaded nanoparticles are delivered directly into the cancer cells through internalization. This system is highly selective and able to distinguish the breast cancer cells from the normal cells, due to normal breast cells that express Y2 receptors only. It is anticipated that this study may provide a guidance in the development of Y1 receptor-based nanoparticulate drug delivery system for a safer and more efficient breast cancer therapy.

  7. 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


    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.


    Directory of Open Access Journals (Sweden)

    Gregory Lee


    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.

  9. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer (United States)


    Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  10. NK Cells Preferentially Target Tumor Cells with a Cancer Stem Cell Phenotype. (United States)

    Ames, Erik; Canter, Robert J; Grossenbacher, Steven K; Mac, Stephanie; Chen, Mingyi; Smith, Rachel C; Hagino, Takeshi; Perez-Cunningham, Jessica; Sckisel, Gail D; Urayama, Shiro; Monjazeb, Arta M; Fragoso, Ruben C; Sayers, Thomas J; Murphy, William J


    Increasing evidence supports the hypothesis that cancer stem cells (CSCs) are resistant to antiproliferative therapies, able to repopulate tumor bulk, and seed metastasis. NK cells are able to target stem cells as shown by their ability to reject allogeneic hematopoietic stem cells but not solid tissue grafts. Using multiple preclinical models, including NK coculture (autologous and allogeneic) with multiple human cancer cell lines and dissociated primary cancer specimens and NK transfer in NSG mice harboring orthotopic pancreatic cancer xenografts, we assessed CSC viability, CSC frequency, expression of death receptor ligands, and tumor burden. We demonstrate that activated NK cells are capable of preferentially killing CSCs identified by multiple CSC markers (CD24(+)/CD44(+), CD133(+), and aldehyde dehydrogenase(bright)) from a wide variety of human cancer cell lines in vitro and dissociated primary cancer specimens ex vivo. We observed comparable effector function of allogeneic and autologous NK cells. We also observed preferential upregulation of NK activation ligands MICA/B, Fas, and DR5 on CSCs. Blocking studies further implicated an NKG2D-dependent mechanism for NK killing of CSCs. Treatment of orthotopic human pancreatic cancer tumor-bearing NSG mice with activated NK cells led to significant reductions in both intratumoral CSCs and tumor burden. Taken together, these data from multiple preclinical models, including a strong reliance on primary human cancer specimens, provide compelling preclinical evidence that activated NK cells preferentially target cancer cells with a CSC phenotype, highlighting the translational potential of NK immunotherapy as part of a combined modality approach for refractory solid malignancies.

  11. Cathepsin G, a Neutrophil Protease, Induces Compact Cell-Cell Adhesion in MCF-7 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Tomoya Kudo


    Full Text Available Cathepsin G is a serine protease secreted by activated neutrophils that play a role in the inflammatory response. Because neutrophils are known to be invading leukocytes in various tumors, their products may influence the characteristics of tumor cells such as the growth state, motility, and the adhesiveness between cells or the extracellular matrix. Here, we demonstrate that cathepsin G induces cell-cell adhesion of MCF-7 human breast cancer cells resulting from the contact inhibition of cell movement on fibronectin but not on type IV collagen. Cathepsin G subsequently induced cell condensation, a very compact cell colony, resulting due to the increased strength of E-cadherin-mediated cell-cell adhesion. Cathepsin G action is protease activity-dependent and was inhibited by the presence of serine protease inhibitors. Cathepsin G promotes E-cadherin/catenin complex formation and Rap1 activation in MCF-7 cells, which reportedly regulates E-cadherin-based cell-cell junctions. Cathepsin G also promotes E-cadherin/protein kinase D1 (PKD1 complex formation, and Go6976, the selective PKD1 inhibitor, suppressed the cathepsin G-induced cell condensation. Our findings provide the first evidence that cathepsin G regulates E-cadherin function, suggesting that cathepsin G has a novel modulatory role against tumor cell-cell adhesion.

  12. Cancer Stem Cell Biomarker Discovery Using Antibody Array Technology. (United States)

    Burgess, Rob; Huang, Ruo-Pan


    Cancer is a complex disease involving hundreds of pathways and numerous levels of disease progression. In addition, there is a growing body of evidence that the origins and growth rates of specific types of cancer may involve "cancer stem cells," which are defined as "cells within a tumor that possess the capacity to self-renew and to cause the development of heterogeneous lineages of cancer cells that comprise the tumor.(1)" Many types of cancer are now thought to harbor cancer stem cells. These cells themselves are thought to be unique in comparison to other cells types present within the tumor and to exhibit characteristics that allow for the promotion of tumorigenesis and in some cases metastasis. In addition, it is speculated that each type of cancer stem cell exhibits a unique set of molecular and biochemical markers. These markers, alone or in combination, may act as a signature for defining not only the type of cancer but also the progressive state. These biomarkers may also double as signaling entities which act autonomously or upon neighboring cancer stem cells or other cells within the local microenvironment to promote tumorigenesis. This review describes the heterogeneic properties of cancer stem cells and outlines the identification and application of biomarkers and signaling molecules defining these cells as they relate to different forms of cancer. Other examples of biomarkers and signaling molecules expressed by neighboring cells in the local tumor microenvironment are also discussed. In addition, biochemical signatures for cancer stem cell autocrine/paracrine signaling, local site recruitment, tumorigenic potential, and conversion to a stem-like phenotype are described.

  13. Effects of Thymus serpyllum extract on cell proliferation, apoptosis and epigenetic events in human breast cancer cells. (United States)

    Bozkurt, Emir; Atmaca, Harika; Kisim, Asli; Uzunoglu, Selim; Uslu, Ruchan; Karaca, Burcak


    Thymus (T.) serpyllum (wild thyme) is an aromatic medicinal plant due to its several biological properties, including anticancer activity. Breast cancer is one of the most common malignancies and increasing evidence supports that it is not only a genetic but also an epigenetic disease. Epigenetics investigates changes in gene expression caused by mechanisms that do not involve alterations in DNA sequence. DNA methylation and histone acetylation are the most widely studied epigenetic changes in cancer cells. This study evaluated the effects of T. serpyllum on apoptosis and epigenetic events in breast cancer cells. XTT cell viability assay was used to determine cytotoxicity. DNA fragmentation and caspase 3/7 activity assays were used in the assesment of apoptosis. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities were evaluated by ELISA and verified by qRT-PCR. T. serpyllum extract induced significant cytotoxicity in breast cancer cells (MCF-7 and MDA-MB-231) but not in normal cells. It also induced apoptosis and inhibited the DNMT and HDAC activities in MDA-MB-231 cells. In the present study, the first preliminary data on the effects of the methanolic extract of T. serpyllum in normal and breast cancer cells were obtained and suggest that T. serpyllum may be a promising candidate in the development of novel therapeutic drugs for breast cancer treatment.

  14. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. (United States)

    Oser, Matthew G; Niederst, Matthew J; Sequist, Lecia V; Engelman, Jeffrey A


    Lung cancer is the most common cause of cancer deaths worldwide. The two broad histological subtypes of lung cancer are small-cell lung cancer (SCLC), which is the cause of 15% of cases, and non-small-cell lung cancer (NSCLC), which accounts for 85% of cases and includes adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma. Although NSCLC and SCLC are commonly thought to be different diseases owing to their distinct biology and genomic abnormalities, the idea that these malignant disorders might share common cells of origin has been gaining support. This idea has been supported by the unexpected findings that a subset of NSCLCs with mutated EGFR return as SCLC when resistance to EGFR tyrosine kinase inhibitors develops. Additionally, other case reports have described the coexistence of NSCLC and SCLC, further challenging the commonly accepted view of their distinct lineages. Here, we summarise the published clinical observations and biology underlying tumours with combined SCLC and NSCLC histology and cancers that transform from adenocarcinoma to SCLC. We also discuss pre-clinical studies pointing to common potential cells of origin, and speculate how the distinct paths of differentiation are determined by the genomics of each disease.

  15. Targeting Notch to target cancer stem cells. (United States)

    Pannuti, Antonio; Foreman, Kimberly; Rizzo, Paola; Osipo, Clodia; Golde, Todd; Osborne, Barbara; Miele, Lucio


    The cellular heterogeneity of neoplasms has been at the center of considerable interest since the "cancer stem cell hypothesis", originally formulated for hematologic malignancies, was extended to solid tumors. The origins of cancer "stem" cells (CSC) or tumor-initiating cells (TIC; henceforth referred to as CSCs) and the methods to identify them are hotly debated topics. Nevertheless, the existence of subpopulations of tumor cells with stem-like characteristics has significant therapeutic implications. The stem-like phenotype includes indefinite self-replication, pluripotency, and, importantly, resistance to chemotherapeutics. Thus, it is plausible that CSCs, regardless of their origin, may escape standard therapies and cause disease recurrences and/or metastasis after apparently complete remissions. Consequently, the idea of selectively targeting CSCs with novel therapeutics is gaining considerable interest. The Notch pathway is one of the most intensively studied putative therapeutic targets in CSC, and several investigational Notch inhibitors are being developed. However, successful targeting of Notch signaling in CSC will require a thorough understanding of Notch regulation and the context-dependent interactions between Notch and other therapeutically relevant pathways. Understanding these interactions will increase our ability to design rational combination regimens that are more likely to prove safe and effective. Additionally, to determine which patients are most likely to benefit from treatment with Notch-targeting therapeutics, reliable biomarkers to measure pathway activity in CSC from specific tumors will have to be identified and validated. This article summarizes the most recent developments in the field of Notch-targeted cancer therapeutics, with emphasis on CSC.

  16. 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


    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.

  17. Advanced Merkel cell cancer and the elderly.

    LENUS (Irish Health Repository)

    Bird, B R


    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.

  18. Therapeutic Approaches to Target Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Arlhee, E-mail:; Leon, Kalet [Department of Systems Biology, Center of Molecular Immunology, 216 Street, PO Box 16040, Atabey, Havana 11600 (Cuba)


    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC.

  19. How Taxol/paclitaxel kills cancer cells. (United States)

    Weaver, Beth A


    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, recent evidence demonstrates that intratumoral concentrations of paclitaxel are too low to cause mitotic arrest and result in multipolar divisions instead. It is hoped that this insight can now be used to develop a biomarker to identify the ∼50% of patients that will benefit from paclitaxel therapy. Here I discuss the history of paclitaxel and our recently evolved understanding of its mechanism of action.

  20. NK cell phenotypic modulation in lung cancer environment.

    Directory of Open Access Journals (Sweden)

    Shi Jin

    Full Text Available Nature killer (NK cells play an important role in anti-tumor immunotherapy. But it indicated that tumor cells impacted possibly on NK cell normal functions through some molecules mechanisms in tumor microenvironment.Our study analyzed the change about NK cells surface markers (NK cells receptors through immunofluorescence, flow cytometry and real-time PCR, the killed function from mouse spleen NK cell and human high/low lung cancer cell line by co-culture. Furthermore we certificated the above result on the lung cancer model of SCID mouse.We showed that the infiltration of NK cells in tumor periphery was related with lung cancer patients' prognosis. And the number of NK cell infiltrating in lung cancer tissue is closely related to the pathological types, size of the primary cancer, smoking history and prognosis of the patients with lung cancer. The expression of NK cells inhibitor receptors increased remarkably in tumor micro-environment, in opposite, the expression of NK cells activated receptors decrease magnificently.The survival time of lung cancer patient was positively related to NK cell infiltration degree in lung cancer. Thus, the down-regulation of NKG2D, Ly49I and the up-regulation of NKG2A may indicate immune tolerance mechanism and facilitate metastasis in tumor environment. Our research will offer more theory for clinical strategy about tumor immunotherapy.

  1. Liver cancer stem cell markers: Progression and therapeutic implications (United States)

    Sun, Jing-Hui; Luo, Qing; Liu, Ling-Ling; Song, Guan-Bin


    Cancer stem cells (CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identification of CSC subpopulations inside a tumor presents a new understanding of cancer development because it implies that tumors can only be eradicated by targeting CSCs. Although advances in liver cancer detection and treatment have increased the possibility of curing the disease at early stages, unfortunately, most patients will relapse and succumb to their disease. Strategies aimed at efficiently targeting liver CSCs are becoming important for monitoring the progress of liver cancer therapy and for evaluating new therapeutic approaches. Herein, we provide a critical discussion of biological markers described in the literature regarding liver cancer stem cells and the potential of these markers to serve as therapeutic targets. PMID:27053846

  2. Effects of bile acids on proliferation and ultrastructural alteration of pancreatic cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Zheng Wu; Yi Lüi; Bo Wang; Chang Liu; Zuo-Ren Wang,


    AIM: Pancreatic cancer in the head is frequently accompanied by jaundice and high bile acid level in serum. This study focused on the direct effects of bile acids on proliferation and ultrastructural alteration of pancreatic cancer.METHODS: Pancreatic cancer cell lines PANC-1, MIA PaCa2 and PGHAM-1 were explored in this study. The cell lines were cultured in media supplemented with certain bile acids,CA, DCA, LCA, TCDC, TDCA and GCA. Their influence on cell growth was measured with MTT assay after 72 h of incubation. Cell cycles of PANC-1 cells in 40 μM of bile acids media were analyzed by flow cytometry. Ultrastructural alteration of PANC-1 cells induced by DCA was observed using scanning and transmission electron microscope (SEM and TEM).RESULTS: At various concentrations of bile acids and incubation time, no enhanced effects of bile acids on cell proliferation were observed. Significant inhibitory effects were obtained in almost all media with bile acids. DCA and CA increased the percentage of G0+G1 phase cells, while GCA and TDCA elevated the S phase cell number. After 48 h of incubation in DCA medium, PANC-1 cells showed some structural damages such as loss of their microvilli and vacuolization of organelles in cytoplasm.CONCLUSION: Bile acids can reduce proliferation of pancreatic cancer cells due to their direct cytotoxicity. This result implies that elevation of bile acids in jaundiced serum may inhibit pancreatic cancer progression.

  3. Multi-Walled Carbon Nanotubes Inhibit Breast Cancer Cell Migration. (United States)

    Graham, Elizabeth G; Wailes, Elizabeth M; Levi-Polyachenko, Nicole H


    According to the American Cancer Society, breast cancer is the second leading cause of cancer death in the US. Cancerous cells may have inadequate adhesions to the extracellular matrix and adjacent cells. Previous work has suggested that restoring these contacts may negate the cancer phenotype. This work aims to restore those contacts using multi-walled carbon nanotubes (MWNTs). Varying concentrations of carboxylated MWNTs in water, with or without type I collagen, were dried to create a thin film upon which one of three breast cell lines were seeded: cancerous and metastatic MDA- MB-231 cells, cancerous but non-metastatic MCF7 cells, or non-cancerous MCF10A cells. Proliferation, adhesion, scratch and autophagy assays, western blots, and immunochemical staining were used to assess adhesion and E-cadherin expression. Breast cancer cells grown on a MWNT-collagen coated surface displayed increased adhesion and decreased migration which correlated with an increase in E-cadherin. This work suggests an alternative approach to cancer treatment by physically mediating the cells' microenvironment.

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

    Directory of Open Access Journals (Sweden)

    Ware Carol B


    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.

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

    Directory of Open Access Journals (Sweden)

    Yong SONG


    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

  6. Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy (United States)


    AD_________________ (Leave blank) Award Number: W81XWH-14-1-0350 TITLE: Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After...30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTILE Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy 5a. CONTRACT NUMBER...Innovative reporter gene systems are designed to mark quiescent or proliferating lung cancer cells (Aim 1) and then used to track and trace the dynamics of

  7. Detecting the effect of targeted anti-cancer medicines on single cancer cells using a poly-silicon wire ion sensor integrated with a confined sensitive window. (United States)

    Wu, You-Lin; Hsu, Po-Yen; Hsu, Chung-Ping; Lin, Jing-Jenn


    A mold-cast polydimethylsiloxane (PDMS) confined window was integrated with a poly-silicon wire (PSW) ion sensor. The PSW sensor surface inside the confined window was coated with a 3-aminopropyltriethoxysilane (γ-APTES) sensitive layer which allowed a single living cell to be cultivated. The change in the microenvironment due to the extracellular acidification of the single cell could then be determined by measuring the current flowing through the PSW channel. Based on this, the PSW sensor integrated with a confined sensitive window was used to detect the apoptosis as well as the effect of anti-cancer medicines on the single living non-small-lung-cancer (NSLC) cells including lung adenocarcinoma cancer cells A549 and H1299, and lung squamous-cell carcinoma CH27 cultivated inside the confined window. Single human normal cells including lung fibroblast cells WI38, lung fibroblast cells MRC5, and bronchial epithelium cell Beas-2B were tested for comparison. Two targeted anti-NSCLC cancer medicines, Iressa and Staurosporine, were used in the present study. It was found that the PSW sensor can be used to accurately detect the apoptosis of single cancer cells after the anti-cancer medicines were added. It was also found that Staurosporine is more effective than Iressa in activating the apoptosis of cancer cells.

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

    Directory of Open Access Journals (Sweden)

    Mrinal Pahwa


    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:

  9. RhoC and ROCKs regulate cancer cell interactions with endothelial cells. (United States)

    Reymond, Nicolas; Im, Jae Hong; Garg, Ritu; Cox, Susan; Soyer, Magali; Riou, Philippe; Colomba, Audrey; Muschel, Ruth J; Ridley, Anne J


    RhoC is a member of the Rho GTPase family that is implicated in cancer progression by stimulating cancer cell invasiveness. Here we report that RhoC regulates the interaction of cancer cells with vascular endothelial cells (ECs), a crucial step in the metastatic process. RhoC depletion by RNAi reduces PC3 prostate cancer cell adhesion to ECs, intercalation between ECs as well as transendothelial migration in vitro. Depletion of the kinases ROCK1 and ROCK2, two known RhoC downstream effectors, similarly decreases cancer interaction with ECs. RhoC also regulates the extension of protrusions made by cancer cells on vascular ECs in vivo. Transient RhoC depletion is sufficient to reduce both early PC3 cell retention in the lungs and experimental metastasis formation in vivo. Our results indicate RhoC plays a central role in cancer cell interaction with vascular ECs, which is a critical event for cancer progression.

  10. Cell migration towards CXCL12 in leukemic cells compared to breast cancer cells. (United States)

    Mills, Shirley C; Goh, Poh Hui; Kudatsih, Jossie; Ncube, Sithembile; Gurung, Renu; Maxwell, Will; Mueller, Anja


    Chemotaxis or directed cell migration is mediated by signalling events initiated by binding of chemokines to their cognate receptors and the activation of a complex signalling cascade. The molecular signalling pathways involved in cell migration are important to understand cancer cell metastasis. Therefore, we investigated the molecular mechanisms of CXCL12 induced cell migration and the importance of different signalling cascades that become activated by CXCR4 in leukemic cells versus breast cancer cells. We identified Src kinase as being essential for cell migration in both cancer types, with strong involvement of the Raf/MEK/ERK1/2 pathway. We did not detect any involvement of Ras or JAK2/STAT3 in CXCL12 induced migration in Jurkat cells. Preventing PKC activation with inhibitors does not affect migration in Jurkat cells at all, unlike in the adherent breast cancer cell line MCF-7 cells. However, in both cell lines, knock down of PKCα prevents migration towards CXCL12, whereas the expression of PKCζ is less crucial for migration. PI3K activation is essential in both cell types, however LY294002 usage in MCF-7 cells does not block migration significantly. These results highlight the importance of verifying specific signalling pathways in different cell settings and with different approaches.

  11. 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


    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.


    Institute of Scientific and Technical Information of China (English)

    李济宇; 全志伟; 张强; 刘建文


    Objective To explore the effect of somatostatin on the cell cycle of human gallbladder cancer cell. Methods Growth curve of gallbladder cancer cell was measured after somatostatin treated on gradient concentration. Simultaneously, the change of gallbladder cancer cell cycle was detected using flow cytometry.Results Concentration-dependent cell growth inhibition caused by somatostatin was detected in gallbladder cancer cell(P<0.05). Cell growth was arrested in S phase since 12h after somatostatin treated, which reached its peak at 24h, then fell down. The changes in apoptosis index of gallbladder cancer cell caused by somatostatin correlated with that's in cell cycle. Conclusion Somatostatin could inhibit the cell growth of human gallbladder cancer cell in vitro on higher concentration. It might result from inducing growth arrest in S phase in early stage and inducing apoptosis in the late stage.

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

    Directory of Open Access Journals (Sweden)

    Keshab R. Parajuli


    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.

  14. Hazards Due to Overdischarge in Lithium-ion Cylindrical Cells in Multi-cell Configurations (United States)

    Jeevarajan, Judith; Strangways, Brad; Nelson, Tim


    Lithium-ion cells in the cylindrical Commercial-off-the-shelf 18650 design format were used to study the hazards associated with overdischarge. The cells in series or in parallel configurations were subjected to different conditions of overdischarge. The cells in parallel configurations were all overdischarged to 2.0 V for 75 cycles with one cell removed at 25 cycles to study the health of the cell. The cells in series were designed to be in an unbalanced configuration by discharging one cell in each series configuration before the start of test. The discharge consisted of removing a pre-determined capacity from the cell. This ranged from 50 to 150 mAh removal. The cells were discharged down to a predetermined end-of-discharge voltage cutoff which allowed the cell with lower capacity to go into an overdischarge mode. The cell modules that survived the 75 cycles were subjected to one overvoltage test to 4.4 V/cell.

  15. Biscoumarin derivatives: Synthesis, crystal structure, theoretical studies and induced apoptosis activity on bladder urothelial cancer cell (United States)

    Xin, Jia-jia; Li, Jing; Zhang, Zi-dan; Hu, Xing-bin; Li, Ming-kai


    In this study, five new biscoumarin derivatives (1-5) were synthesized and compound 4 inhibited the proliferation of the bladder urothelial cells (J82 cell line) obviously after 48 h treatment at different concentration (1, 5 and 10 μmol/L), and J82 cells were predominantly induced to apoptotic cell death after compound 4 treatment. Morphologic changes of bladder urothelial cancer cells were also observed under transmission electron microscopy (TEM) after compound 4 treatment. In addition, compound 4 had much less toxicity to human umbilical vein endothelial cells. To explore the possible anti-cancer mechanism of compound 4, two classical intramolecular Osbnd H⋯O hydrogen bonds (HBs) in their structures and the corresponding HB energies were performed with the density functional theory (DFT) [B3LYP/6-31G∗] method. Anti-bladder cancer activity of compound 4 is possible due to the intramolecular weakest HB energies.

  16. Study by Monte Carlo simulation of the absorbed dose in cells of breast cancer of the line MDA-MB231, due to sources of {sup 111}In, {sup 177}Lu and {sup 99m}Tc internalized in the nucleus. First results; Estudio por simulacion Monte Carlo de la dosis absorbida en celulas de cancer de seno de la linea MDA-MB231, debida a fuentes de {sup 11I}n, {sup 177}Lu y {sup 99m}Tc internalizadas en el nucleo. Primeros resultados

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E. L.; Perez A, M., E-mail: [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)


    The necessity to design innovative treatments and to diagnose the cancer early, has taken to investigate therapies at cellular and molecular level. The design of appropriate radio-molecules to these therapies makes necessary to characterize in way exhaustive radionuclides that they are of accessible production in our country and to study as distributing the dose at cellular level with bio-molecules glued them. In this context, was realized the present work. Using Monte Carlo simulation, the energy deposited in a geometric model of cells of breast cancer was obtained, MDA-MB231, due to different radionuclides. The energy deposited in the nucleus was evaluated, in the cytoplasm and in the membrane of the cell, using the simulation code Monte Carlo Penelope 2008. A punctual source was simulated in the center of the cell nucleus. In each case all the emissions of each radionuclide majors to 400 eV were simulated. The energies deposited by disintegration in the nucleus, cytoplasm, membrane of the cell and in a sphere of 2 cm surrounding the source (in eV) were: 4.30E3, 4.85E2, 1.07E2 and 3.29E4, correspondingly, for the {sup 111}In; 4.46E3, 3.76E3, 1.26E3 and 1.33E5 for the {sup 177}Lu and; 2.12E3, 2.58E2, 9.33E1 and 1.88E4 for the {sup 99m}Tc. We can conclude that if the union of these radionuclides happens to a compound that was internalized to the cell nucleus, the best for therapy at this level is the conjugate with the {sup 177}Lu, followed by that with {sup 111}In and in third place that with {sup 99m}Tc. (Author)

  17. Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer (United States)


    Extensive Stage Small Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  18. Is the inverse association between selenium and bladder cancer due to confounding by smoking? (United States)

    Beane Freeman, Laura E; Karagas, Margaret R; Baris, Dalsu; Schwenn, Molly; Johnson, Alison T; Colt, Joanne S; Jackson, Brian; Hosain, G M Monawar; Cantor, Kenneth P; Silverman, Debra T


    Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association.

  19. Top Notch cancer stem cells by paracrine NF-κB signaling in breast cancer. (United States)

    Zhang, Weizhou; Grivennikov, Sergei I


    Cancer stem cells are likely to play critical roles in metastasis, therapy resistance, and recurrence of hematological and solid malignancies. It is well known that the stem cell niche plays a key role for asymmetric division and homeostasis of normal stem cells, whereas cancer stem cells seem to use these niches. Among many pathways involved in self-renewal of cancer stem cells, nuclear factor-kappa B (NF-κB) signaling has been documented to promote their expansion in a cell-autonomous fashion. A recent study, however, suggests that paracrine NF-κB activation promotes the expansion of cancer stem cells through the activation of Notch in basal-type breast cancer cells.

  20. The anti-cancer effects of poi (Colocasia esculenta) on colonic adenocarcinoma cells In vitro. (United States)

    Brown, Amy C; Reitzenstein, Jonathan E; Liu, Jessie; Jadus, Martin R


    Hawaiians tend to have lower incidence rates of colorectal cancer and it was hypothesized that this may be due to ethnic differences in diet, specifically, their consumption of poi, a starchy paste made from the taro (Colocasia esulenta L.) plant corm. Soluble extracts of poi were incubated at 100 mg/mL in vitro for antiproliferative activity against the rat YYT colon cancer cell line. (3)H-thymidine incorporation studies were conducted to demonstrate that the poi inhibited the proliferation of these cancer cells in a dose-dependent manner. The greatest suppression of YYT colon cancer growth occurred when 25% concentration was used. When poi was incubated with the YYT cells after 2 days, the YYT cells underwent apoptotic changes as evidenced by a positive terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) stain. Poi enhanced the proliferation of normal mouse splenocyte control cells, suggesting that poi is not simply toxic to all cells but even has a positive immunostimulatory role. By flow cytometry, T cells (CD4+ and CD8+) were predominantly activated by the poi. Although numerous factors can contribute to the risk of colon cancer, perhaps poi consumption may contribute to the lower colon cancer rates among Hawaiians by two distinct mechanisms. First, by inducing apoptosis within colon cancer cells; second, by non-specifically activating lymphocytes, which in turn can lyse cancerous cells. Our results suggest for the first time that poi may have novel tumor specific anti-cancer activities and future research is suggested with animal studies and human clinical trials.

  1. Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in early-stage ovarian cancer

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Alvero, Ayesha B; Yang, Yingkui


    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+ ...

  2. Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care (United States)


    Adenocarcinoma of the Lung; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Squamous Cell Lung Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

  3. Human prostate cancer stem cells: new features unveiled

    Institute of Scientific and Technical Information of China (English)

    Yuting Sun; Wei-Qiang Gao


    @@ 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.


    Institute of Scientific and Technical Information of China (English)

    张建军; 丁尔迅; 王强; 陈学云; 付志仁


    To investigate the expression of Fas ligand in human colon carcinoma cell lines. Methods: A total of six human colon cancer cell lines were examined for the expression of Fas ligand mRNA and cell surface protein by using RT-PCR and flow cytometry respectively. Results: The results showed that Fas ligand mRNA was expressed in all of the six cancer cell lines and Fas ligand cell surface protein was expressed in part of them. Conclusion: These data suggest that Fas ligand was expressed, at least in part, in human colon cancer cell lines and might facilitate to escape from immune surveillance of the host.

  5. Diversity of cell-mediated adhesions in breast cancer spheroids. (United States)

    Ivascu, Andrea; Kubbies, Manfred


    Due to their three dimensional (3D) architecture, multicellular tumor spheroids mimic avascular tumor areas comprising the establishment of diffusion gradients, reduced proliferation rates and increased drug resistance. We have shown recently that the spontaneous formation of spheroids is restricted to a limited number of cell lines whereas the majority grow only as aggregates of cells with loose cell-cell contacts when cultured in 3D. However, by the addition of reconstituted basement membrane (rBM, Matrigel), aggregates can be transformed into spheroids with diffusion barriers and development of quiescent therapy-resistant cells. In this report, we investigated adhesion molecules responsible for rBM-driven versus spontaneous spheroid formation in a diverse population of eight breast tumor cell lines relevant for in vitro and in vivo antitumor drug testing. Inhibition of spheroid formation was monitored in the presence of adhesion molecule functional blocking antibodies and after siRNA-mediated down-regulation of E- and N-cadherin and integrin beta1 adhesion receptors. We identified that E-cadherin mediates the spontaneous formation of spheroids in MCF7, BT-474, T-47D and MDA-MB-361 cells, whereas N-cadherin is responsible for tight packing of MDA-MB-435S cells. In contrast, the matrix protein-induced transformation of 3D aggregates into spheroids in MDA-MB-231 and SK-BR-3 cells is mediated primarily by the collagen I/integrin beta1 interaction with no cadherin involvement. A combination of both, homophilic E-cadherin and integrin beta1/collagen I interaction establishes spheroids in MDA-MB-468 cells. These findings indicate that an evolutionary diverse and complex pattern of interacting cell surface proteins exists in breast cancer cells that determines the 3D growth characteristic in vitro, thereby influencing small molecule or antibody permeation in preclinical in vitro and in vivo tumor models.


    Directory of Open Access Journals (Sweden)

    Ya. A. Udalova


    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. X Inactivation and Progenitor Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruben Agrelo


    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.

  8. Cells of Origin of Epithelial Ovarian Cancers (United States)


    AWARD NUMBER: W81XWH-14-1-0280 TITLE: Cells of Origin of Epithelial Ovarian Cancers PRINCIPAL INVESTIGATOR: Zhe Li, PhD CONTRACTING...Xie, Zhe Li 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND...Lined Inclusion Cysts or Teratomas. PLoS ONE 8, e65067. Sherman-Baust, C.A., Kuhn, E., Valle, B.L., Shih Ie, M., Kurman, R.J., Wang , T.L., Amano, T

  9. Implication of expression of Nanog in prostate cancer cells and their stem cells. (United States)

    Gong, Chen; Liao, Hui; Guo, Fengjin; Qin, Liang; Qi, Jun


    Recent studies suggested that the prostate cancer may arise from prostate cancer stem cells that share some same characteristics with normal stem cells. The purpose of this study was to detect the differences of Nanog expression between PC3 prostate cancer cell line and its tumor stem cells, and the relationship was preliminarily examined between Nanog and prostate cancer and its tumor stem cells. By using magnetic active cell sorting (MACS), we isolated a population of CD44(+)/CD133(+) prostate cancer cells that display stem cell characteristics from PC3 cell line. Immunohistochemistry revealed positive expressions of CD44, CD133 and α(2)β(1)-integin in the isolated cells. CCK-8 analysis showed that isolated cells had a strong proliferative ability. The formation of the cell spheres in serum-free medium and holoclones in serum-supplied medium showed that the cells were capable of self-renewing, indicating that the isolated cells were a population of cancer stem-like cells derived from PC3 cell line. Western blotting exhibited that the isolated cells had higher experession of Nanog, an embryonic stem marker, as compared with PC3 cells. Our study showed that Nanog might be helpful in sustaining the self-renewal and the undifferentiation of prostate cancer stem cells, and may serve as a marker for prostate cancer stem cells for isolation and identification.

  10. Contact-independent cell death of human microglial cells due to pathogenic Naegleria fowleri trophozoites. (United States)

    Kim, Jong-Hyun; Kim, Daesik; Shin, Ho-Joon


    Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increase of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.

  11. Impaired germ cell development due to compromised cell cycle progression in Skp2-deficient mice

    Directory of Open Access Journals (Sweden)

    Nakayama Keiko


    Full Text Available Abstract Background The gonads are responsible for the production of germ cells through both mitosis and meiosis. Skp2 is the receptor subunit of an SCF-type ubiquitin ligase and is a major regulator of the progression of cells into S phase of the cell cycle, which it promotes by mediating the ubiquitin-dependent degradation of p27, an inhibitor of cell proliferation. However, the role of the Skp2-p27 pathway in germ cell development remains elusive. Results We now show that disruption of Skp2 in mice results in a marked impairment in the fertility of males, with the phenotypes resembling Sertoli cell-only syndrome in men. Testes of Skp2-/- mice manifested pronounced germ cell hypoplasia accompanied by massive apoptosis in spermatogenic cells. Flow cytometry revealed an increased prevalence of polyploidy in spermatozoa, suggesting that the aneuploidy of these cells is responsible for the induction of apoptosis. Disruption of the p27 gene of Skp2-/- mice restored germ cell development, indicating that the testicular hypoplasia of Skp2-/- animals is attributable to the antiproliferative effect of p27 accumulation. Conclusion Our results thus suggest that compromised cell cycle progression caused by the accumulation of p27 results in aneuploidy and the induction of apoptosis in gonadal cells of Skp2-/- mice. The consequent reduction in the number of mature gametes accounts for the decreased fertility of these animals. These findings reinforce the importance of the Skp2-p27 pathway in cell cycle regulation and in germ cell development.

  12. Ganoderma lucidum (Reishi) Inhibits Cancer Cell Growth and Expression of Key Molecules in Inflammatory Breast Cancer



    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...

  13. Cancer (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  14. Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Hougaard, S; Nørgaard, P; Abrahamsen, N;


    Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...... cancer (SCLC). The purpose of this study was to examine the cause of absent RII expression in SCLC cell lines. Northern blot analysis showed that RII RNA expression was very weak in 16 of 21 cell lines. To investigate if the absence of RII transcript was due to mutations, we screened the poly-A tract...... for mutations, but no mutations were detected. Additional screening for mutations of the RII gene revealed a GG to TT base substitution in one cell line, which did not express RII. This mutation generates a stop codon resulting in predicted synthesis of a truncated RII of 219 amino acids. The nature...

  15. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (United States)

    Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate tha...

  16. Regulation of apoptosis pathways in cancer stem cells. (United States)

    Fulda, Simone


    Cancer stem cell are considered to represent a population within the bulk tumor that share many similarities to normal stem cells as far as their capacities to self-renew, differentiate, proliferate and to reconstitute the entire tumor upon serial transplantation are concerned. Since cancer stem cells have been shown to be critical for maintaining tumor growth and have been implicated in treatment resistance and tumor progression, they constitute relevant targets for therapeutic intervention. Indeed, it has been postulated that eradication of cancer stem cells will be pivotal in order to achieve long-term relapse-free survival. However, one of the hallmarks of cancer stem cells is their high resistance to undergo cell death including apoptosis in response to environmental cues or cytotoxic stimuli. Since activation of apoptosis programs in tumor cells underlies the antitumor activity of most currently used cancer therapeutics, it will be critical to develop strategies to overcome the intrinsic resistance to apoptosis of cancer stem cells. Thus, a better understanding of the molecular mechanisms that are responsible for the ability of cancer stem cells to evade apoptosis will likely open new avenues to target this critical pool of cells within the tumor in order to develop more efficient treatment options for patients suffering from cancer.

  17. A multi-phenotypic cancer model with cell plasticity. (United States)

    Zhou, Da; Wang, Yue; Wu, Bin


    The conventional cancer stem cell (CSC) theory indicates a hierarchy of CSCs and non-stem cancer cells (NSCCs), that is, CSCs can differentiate into NSCCs but not vice versa. However, an alternative paradigm of CSC theory with reversible cell plasticity among cancer cells has received much attention very recently. Here we present a generalized multi-phenotypic cancer model by integrating cell plasticity with the conventional hierarchical structure of cancer cells. We prove that under very weak assumption, the nonlinear dynamics of multi-phenotypic proportions in our model has only one stable steady state and no stable limit cycle. This result theoretically explains the phenotypic equilibrium phenomena reported in various cancer cell lines. Furthermore, according to the transient analysis of our model, it is found that cancer cell plasticity plays an essential role in maintaining the phenotypic diversity in cancer especially during the transient dynamics. Two biological examples with experimental data show that the phenotypic conversions from NCSSs to CSCs greatly contribute to the transient growth of CSCs proportion shortly after the drastic reduction of it. In particular, an interesting overshooting phenomenon of CSCs proportion arises in three-phenotypic example. Our work may pave the way for modeling and analyzing the multi-phenotypic cell population dynamics with cell plasticity.

  18. Maintenance of mesenchymal stem cells culture due to the cells with reduced attachment rate

    Directory of Open Access Journals (Sweden)

    Shuvalova N. S.


    Full Text Available Aim. The classic detachment techniques lead to changes in cells properties. We offer a simple method of cultivating the population of cells that avoided an influence on the surface structures. Methods. Mesenchymal stem cells (MSC from human umbilical cord matrix were obtained and cultivated in standard conditions. While substituting the culture media by a fresh portion, the conditioned culture medium, where the cells were maintained for three days, was transferred to other culture flacks with addition of serum and growth factors. Results. In the flacks, one day after medium transfer, we observed attached cells with typical MSC morphology. The cultures originated from these cells had the same rate of surface markers expression and clonogenic potential as those replated by standard methods. Conclusions. MSC culture, derived by preserving the cells with reduced attachment ability, actually has the properties of «parent» passage. Using this method with accepted techniques of cells reseeding would allow maintaining the cells that avoided an impact on the cell surface proteins.

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

    Directory of Open Access Journals (Sweden)

    K Parandham Gowd


    Full Text Available 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. The aim of this research work is to experimentally measure the EMF radiated electronic pollution levels of cell phones in three different states such as on(sleep/idle mode, receive and transmit modes as an invisible environmental pollution. These measurements are carried out at the centre frequency of 1800 MHz and in the 300 MHz- 50 GHz frequency band. Another main aim is to carry out the projections of cell phones growth due to exponentially expanding mobile technology products, industrialization along with urbanization. Further to estimate the current (2013 EMF radiation pollution levels into environment and projections for 2030 due to cell phones.

  20. Cell migration or cytokinesis and proliferation? – Revisiting the “go or grow” hypothesis in cancer cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Garay, Tamás; Juhász, Éva; Molnár, Eszter [2nd Department of Pathology, Semmelweis University, Budapest (Hungary); Eisenbauer, Maria [Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Czirók, András [Department of Biological Physics, Eötvös University, Budapest (Hungary); Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS (United States); Dekan, Barbara; László, Viktória; Hoda, Mir Alireza [Department of Thoracic Surgery, Medical University of Vienna, Vienna (Austria); Döme, Balázs [Department of Thoracic Surgery, Medical University of Vienna, Vienna (Austria); National Korányi Institute of TB and Pulmonology, Budapest (Hungary); Tímár, József [2nd Department of Pathology, Semmelweis University, Budapest (Hungary); MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest (Hungary); Klepetko, Walter [Department of Thoracic Surgery, Medical University of Vienna, Vienna (Austria); Berger, Walter [Institute of Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Vienna (Austria); Hegedűs, Balázs, E-mail: [Department of Thoracic Surgery, Medical University of Vienna, Vienna (Austria); MTA-SE Tumor Progression Research Group, Hungarian Academy of Sciences, Budapest (Hungary)


    The mortality of patients with solid tumors is mostly due to metastasis that relies on the interplay between migration and proliferation. The “go or grow” hypothesis postulates that migration and proliferation spatiotemporally excludes each other. We evaluated this hypothesis on 35 cell lines (12 mesothelioma, 13 melanoma and 10 lung cancer) on both the individual cell and population levels. Following three-day-long videomicroscopy, migration, proliferation and cytokinesis-length were quantified. We found a significantly higher migration in mesothelioma cells compared to melanoma and lung cancer while tumor types did not differ in mean proliferation or duration of cytokinesis. Strikingly, we found in melanoma and lung cancer a significant positive correlation between mean proliferation and migration. Furthermore, non-dividing melanoma and lung cancer cells displayed slower migration. In contrast, in mesothelioma there were no such correlations. Interestingly, negative correlation was found between cytokinesis-length and migration in melanoma. FAK activation was higher in melanoma cells with high motility. We demonstrate that the cancer cells studied do not defer proliferation for migration. Of note, tumor cells from various organ systems may differently regulate migration and proliferation. Furthermore, our data is in line with the observation of pathologists that highly proliferative tumors are often highly invasive. - Highlights: • We investigated the “go or grow” hypothesis in human cancer cells in vitro. • Proliferation and migration positively correlate in melanoma and lung cancer cells. • Duration of cytokinesis and migration shows inverse correlation. • Increased FAK activation is present in highly motile melanoma cells.

  1. Experimental studies on ultralow frequency pulsed gradient magnetic field inducing apoptosis of cancer cell and inhibiting growth of cancer cell

    Institute of Scientific and Technical Information of China (English)

    曾繁清; 郑从义; 张新晨; 李宗山; 李朝阳; 王川婴; 张新松; 黄晓玲; 张沪生


    The morphology characteristics of cell apoptosis of the malignant tumour cells in magnetic field-treated mouse was observed for the first time. The apoptotic cancer cell contracted, became rounder and divorced from adjacent cells; the heterochromatin condensed and coagulated together along the inner side of the nuclear membrane; the endoplasmic reticulums(ER) expanded and fused with the cellular membrane; many apoptotic bodies which were packed by the cellular membrane appeared and were devoured by some lymphocytes and plasma. Apoptosis of cancer cells was detected by terminal deoxynucleotidyl transferase mediated in situ nick end labeling(TUNEL). It was found that the number of apoptosis cancer cells of the sample treated by the magnetic field is more than that of the control sample. The growth of malignant tumour in mice was inhibited and the ability of immune cell to dissolve cancer cells was improved by ultralow frequency(ULF) pulsed gradient magnetic field; the nuclei DNA contents decreased, indicating that magnetic field can block DNA replication and inhibit mitosis of cancer cells. It was suggested that magnetic field could inhibit the metabolism of cancer cell, lower its malignancy, and restrain its rapid and heteromorphic growth. Since ULF pulsed gradient magnetic field can induce apoptosis of cancer cells and inhibit the growth of malignant tumour, it could be used as a new method to treat cancer.

  2. Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. (United States)

    Sakamoto, Takako; Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio


    Phytoestrogens have attracted attention as being safer alternatives to hormone replacement therapy (HRT) and as chemopreventive reagents for breast cancer because dietary soy isoflavone intake has been correlated with reduction in risk. To identify safe and effective phytoestrogen candidates for HRT and breast cancer prevention, we investigated the effects of daidzein, genistein, coumestrol, resveratrol and glycitein on cell growth, cell cycle, cyclin D1 expression, apoptosis, Bcl-2/Bax expression ratio and p53-dependent or NF-kappaB-dependent transcriptional activity in MCF-7 breast cancer cells. Phytoestrogens, except for glycitein, significantly enhanced estrogen-response-element-dependent transcriptional activity up to a level similar to that of 17beta-estradiol (E(2)). E(2) increased cell growth significantly, coumestrol increased cell growth moderately, and resveratrol and glycitein reduced cell growth. Phytoestrogens, except for glycitein, stimulated the promotion of cells to G(1)/S transition in cell cycle analysis, similar to E(2). This stimulation was accompanied by transient up-regulation of cyclin D1. While genistein, resveratrol and glycitein all increased apoptosis and reduced the Bcl-2/Bax ratio, resveratrol reduced this ratio more than either genistein or glycitein. Moreover, resveratrol significantly enhanced p53-dependent transcriptional activity, but slightly reduced NF-kappaB-dependent transcriptional activity. On knockdown analysis, genistein, resveratrol and glycitein all reduced the Bcl-2/Bax ratio in the presence of apoptosis-inducing stimuli, and estrogen receptor (ER) alpha silencing had no effect on these reductions. In contrast, in the absence of apoptosis-inducing stimuli, only resveratrol reduced the ratio, and ERalpha silencing abolished this reduction. Thus, resveratrol might be the most promising candidate for HRT and chemoprevention of breast cancer due to its estrogenic activity and high antitumor activity.

  3. A comparative analysis of lncRNAs in prostate cancer exosomes and their parental cell lines

    Directory of Open Access Journals (Sweden)

    Alireza Ahadi


    Full Text Available Prostate cancer is the second leading cancer in men world-wide. Due to its heterogeneous nature, a considerable amount of research effort has been dedicated in identifying effective clinical biomarkers with a focus on proteins, messenger RNA and microRNAs [1]. However, there is limited data on the role and expression of long noncoding RNAs (lncRNAs in prostate cancer exosomes [2]. This array dataset which is linked to our publication describes the profiling of human lncRNAs in prostate cancer and their exosomes from five different cell lines [3]. From this dataset, we identified a list of statistically significant prostate cancer lncRNAs which are differentially expressed in the exosomes compared to their parent cell lines. This dataset has been deposited into Gene Expression Omnibus (GSE81034.

  4. Mortality due to lung, laryngeal and bladder cancer in towns lying in the vicinity of combustion installations

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Perez, Javier [Environmental and Cancer Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, C/Sinesio Delgado, 6, 28029 Madrid (Spain); CIBER en Epidemiologia y Salud Publica (CIBERESP) (Spain)], E-mail:; Pollan, Marina; Boldo, Elena; Perez-Gomez, Beatriz; Aragones, Nuria; Lope, Virginia; Ramis, Rebeca; Vidal, Enrique; Lopez-Abente, Gonzalo [Environmental and Cancer Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, C/Sinesio Delgado, 6, 28029 Madrid (Spain); CIBER en Epidemiologia y Salud Publica (CIBERESP) (Spain)


    Background: Installations that burn fossil fuels to generate power may represent a health problem due to the toxic substances which they release into the environment. Objectives: To investigate whether there might be excess mortality due to tumors of lung, larynx and bladder in the population residing near Spanish combustion installations included in the European Pollutant Emission Register. Methods: Ecologic study designed to model sex-specific standardized mortality ratios for the above three tumors in Spanish towns, over the period 1994-2003. Population exposure to pollution was estimated on the basis of distance from town of residence to pollution source. Using mixed Poisson regression models, we analyzed: risk of dying from cancer in a 5-kilometer zone around installations that commenced operations before 1990; effect of type of fuel used; and risk gradient within a 50-kilometer radius of such installations. Results: Excess mortality (relative risk, 95% confidence interval) was detected in the vicinity of pre-1990 installations for lung cancer (1.066, 1.041-1.091 in the overall population; 1.084, 1.057-1.111 in men), and laryngeal cancer among men (1.067, 0.992-1.148). Lung cancer displayed excess mortality for all types of fuel used, whereas in laryngeal and bladder cancer, the excess was associated with coal-fired industries. There was a risk gradient effect in the proximity of a number of installations. Conclusions: Our results could support the hypothesis of an association between risk of lung, laryngeal and bladder cancer mortality and proximity to Spanish combustion installations.

  5. Segmentation and Analysis of Cancer Cells in Blood Samples

    Directory of Open Access Journals (Sweden)

    Arjun Nelikanti


    Full Text Available Blood cancer is an umbrella term for cancers that affect the blood, bone marrow and lymphatic system. Acute Lymphoblastic Leukemia (ALL is one of the kinds of blood cancer which can be affected at any age in the humans. The analysis of peripheral blood samples is an important test in the procedures for the diagnosis of leukemia. In this paper the blood sample images are used and implementing a clustering algorithm for detection of the cancer cells. This paper also implements morphological operations and feature extraction techniques using MATLAB for the analysis of cancer cells in the images.

  6. Stem cells and cancer: Evidence for bone marrow stem cells in epithelial cancers

    Institute of Scientific and Technical Information of China (English)

    Han-Chen Li; Calin Stoicov; Arlin B Rogers; JeanMarie Houghton


    Cancer commonly arises at the sites of chronic inflammation and infection. Although this association has long been recognized, the reason has remained unclear. Within the gastrointestinal tract, there are many examples of inflammatory conditions associated with cancer, and these include reflux disease and Barrett's adenocarcinoma of the esophagus, Helicobacter infection and gastric cancer, inflammatory bowel disease and colorectal cancer and viral hepatitis leading to hepatocellular carcinoma.There are several mechanisms by which chronic inflammation has been postulated to lead to cancer which includes enhanced proliferation in an endless attempt to heal damage, the presence of a persistent inflammatory environment creating a pro-carcinogenic environment and more recently a role for engraftment of circulating marrow-derived stem cells which may contribute to the stromal components of the tumor as well as the tumor mass itself. Here we review the recent advances in our understanding of the contributions of circulating bone marrow-derived stem cells to the formation of tumors in animal models as well as in human beings.

  7. Human lung cancer cell line SPC-A1 contains cells with characteristics of cancer stem cells. (United States)

    Zhou, C H; Yang, S F; Li, P Q


    Cancer stem cells (CSCs) play important roles in occurrence, development, recurrence and metastasis of cancer. Isolation and identification of CSCs have been performed from some cancer tissues or cells. In this paper, human lung adenocarcinoma stem cells were induced and isolated from SPC-A1 cells and their characteristics were determined. SPC-A1 cells were cultured in serum-free medium and epidermal growth factor and basic fibroblast growth factor were added into the medium to induce the formation of multicellular tumor spheroids. The results showed that floating multicellular tumor spheroids (named pulmospheres) were formed 5-10 d after the induction of SPC-A1 cells. Real-time PCR analysis showed that in the pulmospheres, the marker of bronchioalveolar stem cells, Clara cell secretary protein and the marker of AT2 cells, alveolar surfactant protein C were highly expressed. Furthermore, such embryonic stem cell markers as octamer-binding transcription factor 4 (OCT-4), Bmi-1, and thyroid transcription factor -1 (TTF-1) were also highly expressed. Some miRNAs as hsa-miR-126, hsa-miR-145, hsa-let-7g, hsa-let-7d, hsa-let-7c, hsa-let-7e and hsa-miR-98, which were lowly expressed in SPC-A1 cells, were not expressed in the pulmospheres. Cell cycle analysis showed that 94.29 % of the pulmosphere cells were in G1 stages. Further study showed that these cells possessed higher proliferation and invasion activity than SPC-A1 cells. Tumorigenicity activity experiments on BALB/c nude mice showed that 1 × 103 of the pulmosphere cells could form tumors with similar pathological features with lung adenocarcinoma. In conclusion, lung adenocarcinoma stem cells were enriched in the pulmosphere cells and were with high tumorigenicity.

  8. The Interconnectedness of Cancer Cell Signaling

    Directory of Open Access Journals (Sweden)

    Alnawaz Rehemtulla


    Full Text Available The elegance of fundamental and applied research activities have begun to reveal a myriad of spatial and temporal alterations in downstream signaling networks affected by cell surface receptor stimulation including G protein– coupled receptors and receptor tyrosine kinases. Interconnected biochemical pathways serve to integrate and distribute the signaling information throughout the cell by orchestration of complex biochemical circuits consisting of protein interactions and covalent modification processes. It is clear that scientific literature summarizing results from both fundamental and applied scientific research activities has served to provide a broad foundational biologic data-base that has been instrumental in advancing our continued understanding of underlying cancer biology. This article reflects on historical advances and the role of innovation in the competitive world of grant-sponsored research.

  9. Aromatase expression increases the survival and malignancy of estrogen receptor positive breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Keya De Mukhopadhyay

    Full Text Available In postmenopausal women, local estrogen produced by adipose stromal cells in the breast is believed to support estrogen receptor alpha (ERα positive breast cancer cell survival and growth. This raises the question of how the ERα positive metastatic breast cancer cells survive after they enter blood and lymph circulation, where estrogen level is very low in postmenopausal women. In this study, we show that the aromatase expression increased when ERα positive breast cancer cells were cultured in suspension. Furthermore, treatment with the aromatase substrate, testosterone, inhibited suspension culture-induced apoptosis whereas an aromatase inhibitor attenuated the effect of testosterone suggesting that suspended circulating ERα positive breast cancer cells may up-regulate intracrine estrogen activity for survival. Consistent with this notion, a moderate level of ectopic aromatase expression rendered a non-tumorigenic ERα positive breast cancer cell line not only tumorigenic but also metastatic in female nude mice without exogenous estrogen supplementation. The increased malignant phenotype was confirmed to be due to aromatase expression as the growth of orthotopic tumors regressed with systemic administration of an aromatase inhibitor. Thus, our study provides experimental evidence that aromatase plays an important role in the survival of metastatic ERα breast cancer cells by suppressing anoikis.

  10. GLUT 5 is not over-expressed in breast cancer cells and patient breast cancer tissues.

    Directory of Open Access Journals (Sweden)

    Gayatri Gowrishankar

    Full Text Available F18 2-Fluoro 2-deoxyglucose (FDG has been the gold standard in positron emission tomography (PET oncologic imaging since its introduction into the clinics several years ago. Seeking to complement FDG in the diagnosis of breast cancer using radio labeled fructose based analogs, we investigated the expression of the chief fructose transporter-GLUT 5 in breast cancer cells and human tissues. Our results indicate that GLUT 5 is not over-expressed in breast cancer tissues as assessed by an extensive immunohistochemistry study. RT-PCR studies showed that the GLUT 5 mRNA was present at minimal amounts in breast cancer cell lines. Further knocking down the expression of GLUT 5 in breast cancer cells using RNA interference did not affect the fructose uptake in these cell lines. Taken together these results are consistent with GLUT 5 not being essential for fructose uptake in breast cancer cells and tissues.

  11. Photothermal effects of multi-walled carbon nanotubes on the viability of BT-474 cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chou, Hung-Tao [Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Wang, Tsung-Pao [Department of Medical Science, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Lee, Chi-Young [Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Tai, Nyan-Hwa, E-mail: [Department of Materials Science and Engineering, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China); Chang, Hwan-You, E-mail: [Department of Medical Science, National Tsing Hua University, No. 101, Sec. 2 Kuang-Fu Rd., Hsin-chu 30013, Taiwan (China)


    Functionalized multi-walled carbon nanotubes (f-MWCNTs) were conjugated to an antibody of BT-474 cancer cells (f-MWCNTs-ab), and the photothermal effect of the f-MWCNTs-ab for BT-474 cancer cell destruction was demonstrated. After near-infrared irradiation, the f-MWCNTs-ab were more capable of killing cancer cells and possessed higher cell specificity than f-MWCNTs. Quantitative results showed that the viability of the cancer cells was affected by the concentration of the f-MWCNTs-ab solution, irradiation time, and settling time after irradiation. The membrane impermeable fluorescence dye ethidium bromide was used to detect cell viability after near-infrared irradiation, and the results agreed with those obtained from the Alamar Blue cell viability assay. The EtBr fluorescence results suggest that the cell membrane, attached to f-MWCNTs-ab, was damaged after irradiation, which led to cell death and necrosis. Using confocal microscopy, a few f-MWCNTs-ab were detected in the cell, indicating the endocytosis effect. The results not only explain the improved efficiency of thermotherapy but also indicate that necrosis may result from protein denaturation attributing to the heated f-MWCNTs-ab in the cell. Highlights: Black-Right-Pointing-Pointer f-MWCNTs conjugated with anti-HER2 antibody by chemical method. Black-Right-Pointing-Pointer Kill breast cancer cells by using low dose f-MWCNTs-ab due to photothermal effect. Black-Right-Pointing-Pointer Use EtBr fluorescent to prove that the cell membrane was broken by heated f-MWCNTs. Black-Right-Pointing-Pointer Few f-MWCNTs-ab were detected in the cell indicating the endocytosis effect. Black-Right-Pointing-Pointer Necrosis may result from protein denaturation due to contact with the heated CNTs.

  12. Gene-modified bone marrow cell therapy for prostate cancer. (United States)

    Wang, H; Thompson, T C


    There is a critical need to develop new and effective cancer therapies that target bone, the primary metastatic site for prostate cancer and other malignancies. Among the various therapeutic approaches being considered for this application, gene-modified cell-based therapies may have specific advantages. Gene-modified cell therapy uses gene transfer and cell-based technologies in a complementary fashion to chaperone appropriate gene expression cassettes to active sites of tumor growth. In this paper, we briefly review potential cell vehicles for this approach and discuss relevant gene therapy strategies for prostate cancer. We further discuss selected studies that led to the conceptual development and preclinical testing of IL-12 gene-modified bone marrow cell therapy for prostate cancer. Finally, we discuss future directions in the development of gene-modified cell therapy for metastatic prostate cancer, including the need to identify and test novel therapeutic genes such as GLIPR1.

  13. Impact of Annexin A3 expression in gastric cancer cells. (United States)

    Yu, S Y; Li, Y; Fan, L Q; Zhao, Q; Tan, B B; Liu, Y


    Annexin A3 participates in various biological processes, including tumorigenesis, drug resistance, and metastasis. The aim of this study was to investigate the expression of Annexin A3 in gastric cancer and its relationship with cell differentiation, migration, and invasion of gastric cancer cells. Annexin A3 expression in gastric cancer tissues was detected by quantitative real-time PCR and Western blotting. The proliferation of gastric cancer cells was measured by the MTT assay. Cell migration and invasion were determined via wound healing and transwell assays, respectively. Knock down of endogenous Annexin A3 in gastric cancer BGC823 cells was performed using siRNA technology. The expression of Annexin A3 was significantly upregulated in gastric cancer tissues, and negatively correlated with the differentiation degree. Silencing of endogenous Annexin A3 suppressed the proliferation, migration, and invasion of BGC823 cells. Additionally, the expression of p21, p27, TIMP-1, and TIMP-2 was upregulated, and the expression of PCNA, cyclin D1, MMP-1, and MMP-2 decreased in cells treated with Annexin A3-siRNA. Annexin A3 was upregulated in gastric cancer cells. Deletion of endogenous Annexin A3 significantly inhibited gastric cancer cell proliferation, migration, and invasion.

  14. Apoptosis of human pancreatic cancer cells induced by Triptolide

    Institute of Scientific and Technical Information of China (English)

    Guo-Xiong Zhou; Xiao-Ling Ding; Jie-Fei Huang; Hong Zhang; Sheng-Bao Wu; Jian-Ping Cheng; Qun Wei


    AIM:To investigate apoptosis in human pancreatic cancer ceils induced by Triptolide (TL),and the relationship between this apoptosis and expression of caspase-3' bcl-2 and bax.METHODS:Human pancreatic cancer cell line SW1990 was cultured in DIEM media for this study.MTT assay was used to determine the cell growth inhibitory rate in vitro.Flow cytometry and TUNEL assay were used to detect the apoptosis of human pancreatic cancer cells before and after TL treatment.RT-PCR was used to detect the expression of apoptosis-associated gene caspase-3' bcl-2 and bax.RESULTS:TL inhibited the growth of human pancreatic cancer cells in a dose-and time-dependent manner.TL induced human pancreatic cancer cells to undergo apoptosis with typically apoptotic characteristics.TUNEL assay showed that after the treatment of human pancreatic cancer cells with 40 ng/mL TL for 12 h and 24 h,the apoptotic rates of human pancreatic cancer cells increased significantly.RT-PCR demonstrated that caspase-3 and bax were significantly up-regulated in SW1990 cells treated with TL while bcl-2 mRNA was not.CONCLUSION:TL is able to induce the apoptosis in human pancreatic cancer cells.This apoptosis may be mediated by up-regulating the expression of apoptosisassociated caspase-3 and bax gene.

  15. Catheter-Related Bacteremia Due to Kocuria kristinae in a Patient with Ovarian Cancer (United States)

    Basaglia, G.; Carretto, E.; Barbarini, D.; Moras, L.; Scalone, S.; Marone, P.; De Paoli, P.


    We report on the first case of a catheter-related recurrent bacteremia caused by Kocuria kristinae, a gram-positive microorganism belonging to the family Micrococcaceae, in a 51-year-old woman with ovarian cancer. This unusual pathogen may cause opportunistic infections in patients with severe underlying diseases. PMID:11773142

  16. An Automatic Framework for Assessing Breast Cancer Risk Due to Various Hormone Replacement Therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; brandt, sami; Nielsen, Mads

    It is well known that menopausal hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998), J.M. Boone...

  17. False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening.

    NARCIS (Netherlands)

    Rossum, L.G.M. van; Rijn, A.F. van; Oijen, M.G.H. van; Fockens, P.; Laheij, R.J.F.; Verbeek, A.L.M.; Jansen, J.B.M.J.; Dekker, E.


    Delayed return of immunochemical fecal occult blood test (iFOBT) samples to a laboratory might cause false negatives because of hemoglobin degradation. Quantitative iFOBT's became increasingly more accepted in colorectal cancer screening. Therefore, we studied the effects of delay between sampling a

  18. Definition of molecular determinants of prostate cancer cell bone extravasation. (United States)

    Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J


    Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

  19. ATM participates in the regulation of viability and cell cycle via ellipticine in bladder cancer (United States)

    Tao, Shuixiang; Meng, Shuai; Zheng, Xiangyi; Xie, Liping


    Ellipticine, an alkaloid isolated from Apocyanaceae plants, has been demonstrated to exhibit antitumor activity in several cancers. However, the effect and the mechanisms underlying its action have not been investigated in human bladder cancer cells. The aim of the present study was to investigate the effect and mechanism of ellipticine on the behavior of T-24 bladder cancer cells. T-24 cells were treated with varying concentrations and durations of ellipticine. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell motility was analyzed by Transwell migration assay. Flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blot analyses were performed to detect the cell cycle and signaling pathways involved. The results demonstrated that ellipticine suppressed proliferation and inhibited the migration ability of T-24 bladder cancer cells in a dose- and time-dependent manner, and resulted in G2/M cell cycle arrest. The mechanism of this action was demonstrated to be due to ellipticine-triggered activation of the ATM serine/threonine kinase pathway. These data therefore suggest that ellipticine may be effective towards treating human bladder cancer. PMID:28138703

  20. The role of regulatory T cells in cancer immunology


    Whiteside TL


    Theresa L Whiteside University of Pittsburgh Cancer Institute, Pittsburgh, PA, US Abstract: Regulatory T cells (Treg) are generally considered to be significant contributors to tumor escape from the host immune system. Emerging evidence suggests, however, that in some human cancers, Treg are necessary to control chronic inflammation, prevent tissue damage, and limit inflammation-associated cancer development. The dual role of Treg in cancer and underpinnings of Treg diversity are not well und...

  1. Dihydroartemisinin is an inhibitor of ovarian cancer cell growth

    Institute of Scientific and Technical Information of China (English)

    Yang JIAO; Chun-min GE; Qing-hui MENG; Jian-ping CAO; Jian TONG; Sai-jun FAN


    Aim: To investigate the anticancer activity of dihydroartemisinin (DHA), a deriva-tive of antimalaria drug artemisinin in a panel of human ovarian cancer cell lines. Methods: Cell growth was determined by the MTT viability assay. Apoptosis and cell cycle progression were evaluated by a DNA fragmentation gel electro-phoresis, flow cytometry assay, and TUNEL assay; protein and mRNA expression were analyzed by Western blotting and RT-PCR assay. Results: Artemisinin and its derivatives, including artesunate, arteether, artemether, arteannuin, and DHA, exhibit anticancer growth activities in human ovarian cancer cells. Among them, DHA is the most effective in inhibiting cell growth. Ovarian cancer cell lines are more sensitive (5-10-fold) to DHA treatment compared to normal ovarian cell lines. DHA at micromolar dose levels exhibits a dose- and time-dependent cyto-toxicity in ovarian cancer cell lines. Furthermore, DHA induced apoptosis and G2 cell cycle arrest, accompanied by a decrease of Bcl-xL and Bcl-2 and an increase of Bax and Bad. Conclusion: The promising results show for the first time that DHA inhibits the growth of human ovarian cancer cells. The selective inhibition of ovarian cancer cell growth, apoptosis induction, and G2 arrest provide in vitro evidence for further studies of DHA as a possible anticancer drug in the clinical treatment of ovarian cancer.

  2. Upregulated microRNA-224 promotes ovarian cancer cell proliferation by targeting KLLN. (United States)

    Hu, Ke; Liang, Meng


    Human epithelial ovarian cancer is a complex disease, with low 5-yr survival rate largely due to the terminal stage at diagnosis in most patients. MicroRNAs play critical roles during epithelial ovarian cancer progression in vivo and have also been shown to regulate characteristic of ovarian cancer cell line in vitro. Alterative microRNA-224 (microRNA-224) expression affects human epithelial ovarian cancer cell survival, apoptosis, and metastasis. However, people know little about the effects of microRNA-224 on epithelial ovarian cancer cell proliferation. In the current study, we found that the microRNA-224 expression level of human syngeneic epithelial ovarian cancer cells HO8910 (low metastatic ability) was lower than that of HO8910PM (high metastatic ability). Furthermore, microRNA-224 was confirmed to target KLLN in HO8910 and HO8910PM. The known KLLN downstream target cyclin A was regulated by microRNA-224 in HO8910 and HO8910PM. In addition, overexpression of microRNA-224 enhanced the proliferation abilities of HO8910 and knockdown of microRNA-224 suppressed the proliferation abilities of HO8910PM by KLLN-cyclin A pathway. Our results provide new data about microRNAs and their targets involved in proliferation of epithelial ovarian cancer cells by modulating the downstream signaling.

  3. Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. (United States)

    Lu, Jun; Chen, Jian; Xu, Nianjun; Wu, Jun; Kang, Yani; Shen, Tingting; Kong, Hualei; Ma, Chao; Cheng, Ming; Shao, Zhifeng; Xu, Ling; Zhao, Xiaodong


    Application of cisplatin (DDP) for treating lung cancer is restricted due to its toxicity and lung cancer's drug resistance. In this study, we examined the effect of Jinfukang (JFK), an effective herbal medicine against lung cancer, on DDP-induced cytotoxicity in lung cancer cells. Morphologically, we observed that JFK increases DDP-induced pro-apoptosis in A549 cells in a synergistic manner. Transcriptome profiling analysis indicated that the combination of JFK and DDP regulates genes involved in apoptosis-related signaling pathways. Moreover, we found that the combination of JFK and DDP produces synergistic pro-apoptosis effect in other lung cancer cell lines, such as NCI-H1975, NCI-H1650, and NCI-H2228. Particularly, we demonstrated that AIFM2 is activated by the combined treatment of JFK and DDP and partially mediates the synergistic pro-apoptosis effect. Collectively, this study not only offered the first evidence that JFK promotes DDP-induced cytotoxicity, and activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress, but also provided a novel insight for improving cytotoxicity by combining JFK with DDP to treat lung cancer cells.

  4. Ki-67 is required for maintenance of cancer stem cells but not cell proliferation (United States)

    Cidado, Justin; Wong, Hong Yuen; Rosen, D. Marc; Cimino-Mathews, Ashley; Garay, Joseph P.; Fessler, Abigail G.; Rasheed, Zeshaan A.; Hicks, Jessica; Cochran, Rory L.; Croessmann, Sarah; Zabransky, Daniel J.; Mohseni, Morassa; Beaver, Julia A.; Chu, David; Cravero, Karen; Christenson, Eric S.; Medford, Arielle; Mattox, Austin; De Marzo, Angelo M.; Argani, Pedram; Chawla, Ajay; Hurley, Paula J.; Lauring, Josh; Park, Ben Ho


    Ki-67 expression is correlated with cell proliferation and is a prognostic marker for various cancers; however, its function is unknown. Here we demonstrate that genetic disruption of Ki-67 in human epithelial breast and colon cancer cells depletes the cancer stem cell niche. Ki-67 null cells had a proliferative disadvantage compared to wildtype controls in colony formation assays and displayed increased sensitivity to various chemotherapies. Ki-67 null cancer cells showed decreased and delayed tumor formation in xenograft assays, which was associated with a reduction in cancer stem cell markers. Immunohistochemical analyses of human breast cancers revealed that Ki-67 expression is maintained at equivalent or greater levels in metastatic sites of disease compared to matched primary tumors, suggesting that maintenance of Ki-67 expression is associated with metastatic/clonogenic potential. These results elucidate Ki-67's role in maintaining the cancer stem cell niche, which has potential diagnostic and therapeutic implications for human malignancies. PMID:26823390

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

    Directory of Open Access Journals (Sweden)

    Soma Seal

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

  6. Protective mechanism against cancer found in progeria patient cells (United States)

    NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

  7. Mathematical models in cell biology and cancer chemotherapy

    CERN Document Server

    Eisen, Martin


    The purpose of this book is to show how mathematics can be applied to improve cancer chemotherapy. Unfortunately, most drugs used in treating cancer kill both normal and abnormal cells. However, more cancer cells than normal cells can be destroyed by the drug because tumor cells usually exhibit different growth kinetics than normal cells. To capitalize on this last fact, cell kinetics must be studied by formulating mathematical models of normal and abnormal cell growth. These models allow the therapeutic and harmful effects of cancer drugs to be simulated quantitatively. The combined cell and drug models can be used to study the effects of different methods of administering drugs. The least harmful method of drug administration, according to a given criterion, can be found by applying optimal control theory. The prerequisites for reading this book are an elementary knowledge of ordinary differential equations, probability, statistics, and linear algebra. In order to make this book self-contained, a chapter on...

  8. Reversal by EGTA of the enhanced secretory responsiveness of mast cells due to treatment with ouabain

    DEFF Research Database (Denmark)

    Johansen, Torben; Knudsen, T; Bertelsen, Niels Haldor


    The effect of EGTA on the enhancement by ouabain of compound 48/80-induced secretion from mast cells was compared with the effect on the Na(+)-K+ pump activity. The time-dependent secretory enhancement by ouabain was blocked by addition of EGTA to the cell suspension concomitantly with the addition...... of ouabain, and EGTA caused a large increase in the pump activity. Addition of 10 microM EGTA to ouabain-treated cells stopped but did not reverse the enhancement. The experiments show that the effect of ouabain was due to changes in a calcium pool utilized in compound 48/80-induced secretion following...

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

    DEFF Research Database (Denmark)

    Lawaetz, Andreas C.; Almstrup, Kristian


    Testicular germ cell cancer manifests mainly in young adults as a seminoma or non-seminoma. The solid tumors are preceded by the presence of a non-invasive precursor cell, the carcinoma in situ cell (CIS), which shows great similarity to fetal germ cells. It is therefore hypothesized that the CIS...... of epigenetic modifiers with a focus on jumonji C enzymes in the development of testicular dysgenesis and germ cell cancer in men....... 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...

  10. A mathematical model of cancer cells with phenotypic plasticity

    Directory of Open Access Journals (Sweden)

    Da Zhou


    Full Text Available Purpose: The phenotypic plasticity of cancer cells is recently becoming a cutting-edge research area in cancer, which challenges the cellular hierarchy proposed by the conventional cancer stem cell theory. In this study, we establish a mathematical model for describing the phenotypic plasticity of cancer cells, based on which we try to find some salient features that can characterize the dynamic behavior of the phenotypic plasticity especially in comparison to the hierarchical model of cancer cells. Methods: We model cancer as population dynamics composed of different phenotypes of cancer cells. In this model, not only can cancer cells divide (symmetrically and asymmetrically and die, but they can also convert into other cellular phenotypes. According to the Law of Mass Action, the cellular processes can be captured by a system of ordinary differential equations (ODEs. On one hand, we can analyze the long-term stability of the model by applying qualitative method of ODEs. On the other hand, we are also concerned about the short-term behavior of the model by studying its transient dynamics. Meanwhile, we validate our model to the cell-state dynamics in published experimental data.Results: Our results show that the phenotypic plasticity plays important roles in both stabilizing the distribution of different phenotypic mixture and maintaining the cancer stem cells proportion. In particular, the phenotypic plasticity model shows decided advantages over the hierarchical model in predicting the phenotypic equilibrium and cancer stem cells’ overshoot reported in previous biological experiments in cancer cell lines.Conclusion: Since the validity of the phenotypic plasticity paradigm and the conventional cancer stem cell theory is still debated in experimental biology, it is worthy of theoretically searching for good indicators to distinguish the two models through quantitative methods. According to our study, the phenotypic equilibrium and overshoot

  11. Chemoresistance of CD133+ cancer stem cells in laryngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    YANG Jing-pu; LIU Yan; ZHONG Wei; YU Dan; WEN Lian-ji; JIN Chun-shun


    Background Mounting evidence suggests that tumors are histologically heterogeneous and are maintained by a small population of tumor cells termed cancer stem cells. CD133 has been identified as a candidate marker of cancer stem cells in laryngeal carcinoma. This study aimed to analyze the chemoresistance of CD133+ cancer stem cells.Methods The response of Hep-2 cells to different chemotherapeutic agents was investigated and the expression of CD133 was studied. Fluorescence-activated cell sorting analysis was used to identify CD133,and the CD133+ subset of cells was separated and analyzed in colony formation assays,cell invasion assays,chemotherapy resistance studies,and analyzed for the expression of the drug resistance gene ABCG2.Results About 1%-2% of Hep-2 cells were CD133+ cells,and the CD133+ proportion was enriched by chemotherapy.CD133+ cancer stem cells exhibited higher potential for clonogenicity and invasion,and were more resistant to chemotherapy. This resistance was correlated with higher expression of ABCG2.Conclusions This study suggested that CD133+ cancer stem cells are more resistant to chemotherapy. The expression of ABCG2 could be partially responsible for this. Targeting this small population of CD133+ cancer stem cells could be a strategy to develop more effective treatments for laryngeal carcinoma.

  12. EGFR-targeted magnetic nanoparticle heaters kill cancer cells without a perceptible temperature rise. (United States)

    Creixell, Mar; Bohórquez, Ana C; Torres-Lugo, Madeline; Rinaldi, Carlos


    It is currently believed that magnetic nanoparticle heaters (MNHs) can kill cancer cells only when the temperature is raised above 43 °C due to energy dissipation in an alternating magnetic field. On the other hand, simple heat conduction arguments indicate that in small tumors or single cells the relative rates of energy dissipation and heat conduction result in a negligible temperature rise, thus limiting the potential of MNHs in treating small tumors and metastatic cancer. Here we demonstrate that internalized MNHs conjugated to epidermal growth factor (EGF) and which target the epidermal growth factor receptor (EGFR) do result in a significant (up to 99.9%) reduction in cell viability and clonogenic survival in a thermal heat dose dependent manner, without the need for a perceptible temperature rise. The effect appears to be cell type specific and indicates that magnetic nanoparticles in alternating magnetic fields may effectively kill cancer cells under conditions previously considered as not possible.

  13. Natural Killer Cells in Human Cancer: From Biological Functions to Clinical Applications

    Directory of Open Access Journals (Sweden)

    Estrella Mariel Levy


    Full Text Available Natural killer (NK cells are central components of the innate immunity. In murine models, it has been shown that NK cells can control both local tumor growth and metastasis due to their ability to exert direct cellular cytotoxicity without prior sensitization and to secrete immunostimulatory cytokines like IFN-γ. The latter participates in cancer elimination by inhibiting cellular proliferation and angiogenesis, promoting apoptosis, and stimulating the adaptive immune system, and it is instrumental for enhancing Ag processing and presentation. Nevertheless, NK cells display impaired functionality and capability to infiltrate tumors in cancer patients. Also, NK cells are feasible targets of stimulation to participate in immunotherapeutic approaches like antibody-based strategies and adoptive cell transfer. Thus, multiple attempts currently aim to manipulate NK for utilization in the immunotherapy of cancer.

  14. Pulmonary tumor thrombotic microangiopathy with cor pulmonale due to desmoplastic small round cell tumor. (United States)

    Sadimin, Evita T; Collier, Adrienne G; Gaffney, Joseph W; Fyfe, Billie


    A 12-year-old boy presented acutely after an episode of syncope with perioral cyanosis. He died 19 hours after admission due to cor pulmonale as a complication of metastatic desmoplastic small round cell tumor in the lungs with associated tumor thrombotic microangiopathy.

  15. When grief turns into love: understanding the experience of parents who have revived after losing a child due to cancer. (United States)

    Vega, Paula; Rivera, Maria Soledad; González, Rina


    A child's death caused by cancer generates a deep impact on his/her parents, who can be affected by serious health problems due to an impairment of their lifestyle. Notwithstanding their suffering, some parents manage to overcome it and discover a new meaning for their lives. The goal of this phenomenological study is to understand the lived experiences that help parents to revive after the death of their child due to cancer. The participants were fathers and mothers who believe that they have elaborated their mourning. Their lived experiences were collected in interviews they had previously agreed to give. The question that steered the interview was: "What is the experience you went through that helped you to revive after your child died due to cancer?" Data were analyzed using Streubert's method. Analyzing the interviews of the participants, 3 interweaved essences were detected: transition from surviving to reviving themselves; ascribing a sense and meaning to the life, agony, and death of a child; and helping other parents through one's own experience.

  16. Breast Cancer Vaccines Based on Dendritic Cells and the Chemokines (United States)


    In: Cancer: Principles and Practice of Oncology . DeVita Jr VT, Hellman S, Rosenberg SA (eds.), JB Lippincott Co., Philadelphia, p. 293, 1993. 2...Alteration of signal transduction in T cells from cancer patients. In: Important Advances in Oncology 1995. DeVita Jr VT, Hellman S, Rosenberg SA (eds.), JB...Rosenberg SA: Cell transfer therapy: Clinical applications. In: Biologic Therapy of Cancer. DeVita Jr VT, Hellman S, Rosenberg SA (eds.), JB Lippincott

  17. Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized Nanoparticles Carrying γ-secretase Inhibitors. (United States)

    Mamaeva, Veronika; Niemi, Rasmus; Beck, Michaela; Özliseli, Ezgi; Desai, Diti; Landor, Sebastian; Gronroos, Tove; Kronqvist, Pauliina; Pettersen, Ina K N; McCormack, Emmet; Rosenholm, Jessica M; Linden, Mika; Sahlgren, Cecilia


    Cancer stem cells (CSCs) are a challenge in cancer treatment due to their therapy resistance. We demonstrated that enhanced Notch signaling in breast cancer promotes self-renewal of CSCs that display high glycolytic activity and aggressive hormone-independent tumor growth in vivo. We took advantage of the glycolytic phenotype and the dependence on Notch activity of the CSCs and designed nanoparticles to target the CSCs. Mesoporous silica nanoparticles were functionalized with glucose moieties and loaded with a γ-secretase inhibitor, a potent interceptor of Notch signaling. Cancer cells and CSCs in vitro and in vivo efficiently internalized these particles, and particle uptake correlated with the glycolytic profile of the cells. Nanoparticle treatment of breast cancer transplants on chick embryo chorioallantoic membranes efficiently reduced the cancer stem cell population of the tumor. Our data reveal that specific CSC characteristics can be utilized in nanoparticle design to improve CSC-targeted drug delivery and therapy.

  18. Therapeutic potential of mTOR inhibitors for targeting cancer stem cells. (United States)

    Francipane, Maria Giovanna; Lagasse, Eric


    The mammalian target of rapamycin (mTOR) pathway is aberrantly activated in many cancer types. As the intricate network of regulatory mechanisms controlling mTOR activity is uncovered, more refined drugs are designed and tested in clinical trials. While first generation mTOR inhibitors have failed to show clinical efficacy due partly to the feedback relief of oncogenetic circuits, newly developed inhibitors show greater promise as anti-cancer agents. An effective drug must defeat the cancer stem cells (CSCs) while sparing the normal stem cells. Due to its opposing role on normal and malignant stem cells, mTOR lends itself very well as a therapeutic target. Indeed, a preferential inhibitory effect on CSCs has already been shown for some mTOR inhibitors. These results provide a compelling rationale for the clinical development of mTOR-targeted therapies.

  19. Comprehensive genomic characterization of squamous cell lung cancers

    NARCIS (Netherlands)

    Hammerman, Peter S.; Lawrence, Michael S.; Voet, Douglas; Jing, Rui; Cibulskis, Kristian; Sivachenko, Andrey; Stojanov, Petar; McKenna, Aaron; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Sougnez, Carrie; Imielinski, Marcin; Helman, Elena; Hernandez, Bryan; Pho, Nam H.; Meyerson, Matthew; Chu, Andy; Chun, Hye-Jung E.; Mungall, Andrew J.; Pleasance, Erin; Robertson, A. Gordon; Sipahimalani, Payal; Stoll, Dominik; Balasundaram, Miruna; Birol, Inanc; Butterfield, Yaron S. N.; Chuah, Eric; Coope, Robin J. N.; Corbett, Richard; Dhalla, Noreen; Guin, Ranabir; Hirst, Anhe Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; Mungall, Karen; Nip, Ka Ming; Olshen, Adam; Schein, Jacqueline E.; Slobodan, Jared R.; Tam, Angela; Thiessen, Nina; Varhol, Richard; Zeng, Thomas; Zhao, Yongjun; Jones, Steven J. M.; Marra, Marco A.; Saksena, Gordon; Cherniack, Andrew D.; Schumacher, Stephen E.; Tabak, Barbara; Carter, Scott L.; Pho, Nam H.; Nguyen, Huy; Onofrio, Robert C.; Crenshaw, Andrew; Ardlie, Kristin; Beroukhim, Rameen; Winckler, Wendy; Hammerman, Peter S.; Getz, Gad; Meyerson, Matthew; Protopopov, Alexei; Zhang, Jianhua; Hadjipanayis, Angela; Lee, Semin; Xi, Ruibin; Yang, Lixing; Ren, Xiaojia; Zhang, Hailei; Shukla, Sachet; Chen, Peng-Chieh; Haseley, Psalm; Lee, Eunjung; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Socci, Nicholas D.; Liang, Yupu; Schultz, Nikolaus; Borsu, Laetitia; Lash, Alex E.; Viale, Agnes; Sander, Chris; Ladanyi, Marc; Auman, J. Todd; Hoadley, Katherine A.; Wilkerson, Matthew D.; Shi, Yan; Liquori, Christina; Meng, Shaowu; Li, Ling; Turman, Yidi J.; Topal, Michael D.; Tan, Donghui; Waring, Scot; Buda, Elizabeth; Walsh, Jesse; Jones, Corbin D.; Mieczkowski, Piotr A.; Singh, Darshan; Wu, Junyuan; Gulabani, Anisha; Dolina, Peter; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; O'Connor, Brian D.; Prins, Jan F.; Liu, Jinze; Chiang, Derek Y.; Hayes, D. Neil; Perou, Charles M.; Cope, Leslie; Danilova, Ludmila; Weisenberger, Daniel J.; Maglinte, Dennis T.; Pan, Fei; Van den Berg, David J.; Triche, Timothy; Herman, James G.; Baylin, Stephen B.; Laird, Peter W.; Getz, Gad; Noble, Michael; Voet, Doug; Saksena, Gordon; Gehlenborg, Nils; DiCara, Daniel; Zhang, Jinhua; Zhang, Hailei; Wu, Chang-Jiun; Liu, Spring Yingchun; Lawrence, Michael S.; Zou, Lihua; Sivachenko, Andrey; Lin, Pei; Stojanov, Petar; Jing, Rui; Cho, Juok; Nazaire, Marc-Danie; Robinson, Jim; Thorvaldsdottir, Helga; Mesirov, Jill; Park, Peter J.; Chin, Lynda; Schultz, Nikolaus; Sinha, Rileen; Ciriello, Giovanni; Cerami, Ethan; Gross, Benjamin; Jacobsen, Anders; Gao, Jianjiong; Aksoy, B. Arman; Weinhold, Nils; Ramirez, Ricardo; Taylor, Barry S.; Antipin, Yevgeniy; Reva, Boris; Shen, Ronglai; Mo, Qianxing; Seshan, Venkatraman; Paik, Paul K.; Ladanyi, Marc; Sander, Chris; Akbani, Rehan; Zhang, Nianxiang; Broom, Bradley M.; Casasent, Tod; Unruh, Anna; Wakefield, Chris; Cason, R. Craig; Baggerly, Keith A.; Weinstein, John N.; Haussler, David; Benz, Christopher C.; Stuart, Joshua M.; Zhu, Jingchun; Szeto, Christopher; Scott, Gary K.; Yau, Christina; Ng, Sam; Goldstein, Ted; Waltman, Peter; Sokolov, Artem; Ellrott, Kyle; Collisson, Eric A.; Zerbino, Daniel; Wilks, Christopher; Ma, Singer; Craft, Brian; Wilkerson, Matthew D.; Auman, J. Todd; Hoadley, Katherine A.; Du, Ying; Cabanski, Christopher; Walter, Vonn; Singh, Darshan; Wu, Junyuan; Gulabani, Anisha; Bodenheimer, Tom; Hoyle, Alan P.; Simons, Janae V.; Soloway, Matthew G.; Mose, Lisle E.; Jefferys, Stuart R.; Balu, Saianand; Marron, J. S.; Liu, Yufeng; Wang, Kai; Liu, Jinze; Prins, Jan F.; Hayes, D. Neil; Perou, Charles M.; Creighton, Chad J.; Zhang, Yiqun; Travis, William D.; Rekhtman, Natasha; Yi, Joanne; Aubry, Marie C.; Cheney, Richard; Dacic, Sanja; Flieder, Douglas; Funkhouser, William; Illei, Peter; Myers, Jerome; Tsao, Ming-Sound; Penny, Robert; Mallery, David; Shelton, Troy; Hatfield, Martha; Morris, Scott; Yena, Peggy; Shelton, Candace; Sherman, Mark; Paulauskis, Joseph; Meyerson, Matthew; Baylin, Stephen B.; Govindan, Ramaswamy; Akbani, Rehan; Azodo, Ijeoma; Beer, David; Bose, Ron; Byers, Lauren A.; Carbone, David; Chang, Li-Wei; Chiang, Derek; Chu, Andy; Chun, Elizabeth; Collisson, Eric; Cope, Leslie; Creighton, Chad J.; Danilova, Ludmila; Ding, Li; Getz, Gad; Hammerman, Peter S.; Hayes, D. Neil; Hernandez, Bryan; Herman, James G.; Heymach, John; Ida, Cristiane; Imielinski, Marcin; Johnson, Bruce; Jurisica, Igor; Kaufman, Jacob; Kosari, Farhad; Kucherlapati, Raju; Kwiatkowski, David; Ladanyi, Marc; Lawrence, Michael S.; Maher, Christopher A.; Mungall, Andy; Ng, Sam; Pao, William; Peifer, Martin; Penny, Robert; Robertson, Gordon; Rusch, Valerie; Sander, Chris; Schultz, Nikolaus; Shen, Ronglai; Siegfried, Jill; Sinha, Rileen; Sivachenko, Andrey; Sougnez, Carrie; Stoll, Dominik; Stuart, Joshua; Thomas, Roman K.; Tomaszek, Sandra; Tsao, Ming-Sound; Travis, William D.; Vaske, Charles; Weinstein, John N.; Weisenberger, Daniel; Wheeler, David; Wigle, Dennis A.; Wilkerson, Matthew D.; Wilks, Christopher; Yang, Ping; Zhang, Jianjua John; Jensen, Mark A.; Sfeir, Robert; Kahn, Ari B.; Chu, Anna L.; Kothiyal, Prachi; Wang, Zhining; Snyder, Eric E.; Pontius, Joan; Pihl, Todd D.; Ayala, Brenda; Backus, Mark; Walton, Jessica; Baboud, Julien; Berton, Dominique L.; Nicholls, Matthew C.; Srinivasan, Deepak; Raman, Rohini; Girshik, Stanley; Kigonya, Peter A.; Alonso, Shelley; Sanbhadti, Rashmi N.; Barletta, Sean P.; Greene, John M.; Pot, David A.; Tsao, Ming-Sound; Bandarchi-Chamkhaleh, Bizhan; Boyd, Jeff; Weaver, JoEllen; Wigle, Dennis A.; Azodo, Ijeoma A.; Tomaszek, Sandra C.; Aubry, Marie Christine; Ida, Christiane M.; Yang, Ping; Kosari, Farhad; Brock, Malcolm V.; Rogers, Kristen; Rutledge, Marian; Brown, Travis; Lee, Beverly; Shin, James; Trusty, Dante; Dhir, Rajiv; Siegfried, Jill M.; Potapova, Olga; Fedosenko, Konstantin V.; Nemirovich-Danchenko, Elena; Rusch, Valerie; Zakowski, Maureen; Iacocca, Mary V.; Brown, Jennifer; Rabeno, Brenda; Czerwinski, Christine; Petrelli, Nicholas; Fan, Zhen; Todaro, Nicole; Eckman, John; Myers, Jerome; Rathmell, W. Kimryn; Thorne, Leigh B.; Huang, Mei; Boice, Lori; Hill, Ashley; Penny, Robert; Mallery, David; Curley, Erin; Shelton, Candace; Yena, Peggy; Morrison, Carl; Gaudioso, Carmelo; Bartlett, Johnm. S.; Kodeeswaran, Sugy; Zanke, Brent; Sekhon, Harman; David, Kerstin; Juhl, Hartmut; Van Le, Xuan; Kohl, Bernard; Thorp, Richard; Tien, Nguyen Viet; Van Bang, Nguyen; Sussman, Howard; Phu, Bui Duc; Hajek, Richard; PhiHung, Nguyen; Khan, Khurram Z.; Muley, Thomas; Shaw, Kenna R. Mills; Sheth, Margi; Yang, Liming; Buetow, Ken; Davidsen, Tanja; Demchok, John A.; Eley, Greg; Ferguson, Martin; Dillon, Laura A. L.; Schaefer, Carl; Guyer, Mark S.; Ozenberger, Bradley A.; Palchik, Jacqueline D.; Peterson, Jane; Sofia, Heidi J.; Thomson, Elizabeth; Meyerson, Matthew


    Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment.

  20. Chestnut extract induces apoptosis in AGS human gastric cancer cells. (United States)

    Lee, Hyun Sook; Kim, Eun Ji; Kim, Sun Hyo


    In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with 200 µg/mL CPE for 24 hr. CPE at various concentrations (0-200 µg/mL) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPE exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer.

  1. Pitavastatin suppressed liver cancer cells in vitro and in vivo (United States)

    You, He-Yi; Zhang, Wei-Jian; Xie, Xue-Meng; Zheng, Zhi-Hai; Zhu, Heng-Liang; Jiang, Fei-Zhao


    Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy. PMID:27621652

  2. Sudden hearing loss due to oxaliplatin use in a patient with colon cancer. (United States)

    Güvenç, M Güven; Dizdar, Denizhan; Dizdar, Senem Kurt; Okutur, Sadi Kerem; Demir, Gökhan


    Oxaliplatin is used to treat advanced colorectal cancer. Platinum-containing chemotherapeutic agents are known to be ototoxic. However, ototoxicity is rare with newer generation platinum-derived agents, such as oxaliplatin. This case report presents a rare case of sudden unilateral sensorineural hearing loss following intravenous (IV) infusion of oxaliplatin in a 64-year-old woman with advanced colon cancer. The hearing loss was severe and did not respond to treatment. To the best of our knowledge, this is the fifth reported case of oxaliplatin ototoxicity. Although oxaliplatin ototoxicity is rare, physicians must be aware of this important adverse effect, and an audiometric evaluation must be performed when necessary. Patients treated with oxaliplatin should be followed closely for early signs and symptoms of hearing loss, and if hearing loss is detected, treatment should be stopped immediately.

  3. An Automatic Framework for Assessing Breast Cancer Risk Due to Various Hormone Replacement Therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Brandt, Sami; Nielsen, Mads

    measurements of breast density changes related to HRT. 2) To investigate whether transdermal low dose estradiol treatment induces changes in mammographic density compared to raloxifene and if these findings indicate elevation of breast cancer risk by treatment. Material and Methods: Digitised mammographies......Background: It is well known that Menopausal Hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998), J...... of 2x135 completers of a two year, randomised, trial formed the base of the present analysis. Active treatments were transdermal estradiol releasing 0.014mg E2/week and orally administered raloxifene hydrochloride, 60mg/day respectively. Influence of the therapies on breast density was assessed...

  4. Risk estimates of liver cancer due to aflatoxin exposure from peanuts and peanut products

    Energy Technology Data Exchange (ETDEWEB)

    Dichter, C.R.


    An assessment was undertaken of the risk of liver cancer in the USA associated with aflatoxin ingestion from peanuts. Both laboratory-animal data and epidemiological data collected from the scientific literature and several prominent mathematical extrapolation techniques were used. Risk estimates differed by a factor of greater than 1000 when the extrapolated results of three selected animal studies were analysed. Dose-response data for the male Fischer rat, the most sensitive mammalian species studied, produced an estimate of 158 cases of liver cancer per year in the USA at current levels of aflatoxin exposure. An estimate of 58 annual cases was predicted on the basis of epidemiological data of populations in Africa and Thailand.

  5. Total triterpenoids from Ganoderma Lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis. (United States)

    Wang, Tao; Xie, Zi-ping; Huang, Zhan-sen; Li, Hao; Wei, An-yang; Di, Jin-ming; Xiao, Heng-jun; Zhang, Zhi-gang; Cai, Liu-hong; Tao, Xin; Qi, Tao; Chen, Di-ling; Chen, Jun


    In this study, one immortalized human normal prostatic epithelial cell line (BPH) and four human prostate cancer cell lines (LNCaP, 22Rv1, PC-3, and DU-145) were treated with Ganoderma Lucidum triterpenoids (GLT) at different doses and for different time periods. Cell viability, apoptosis, and cell cycle were analyzed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR and Western blotting. It was found that GLT dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. GLT-induced apoptosis was due to activation of Caspases-9 and -3 and turning on the downstream apoptotic events. GLT-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and E2F1 expression at the late time. These findings demonstrate that GLT suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which might suggest that GLT or Ganoderma Lucidum could be used as a potential therapeutic drug for prostate cancer.

  6. Unlocking Pandora's box: personalising cancer cell death in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Fennell Dean A


    Full Text Available Abstract Evasion of apoptosis is a hallmark of tumorigenesis and a recognised cause of multidrug resistance. Over the last decade, insights into how apoptosis might be exploited in non-small cell lung cancer (NSCLC and how cancer therapeutics might be used to engage apoptotic signalling in a personalised manner have changed markedly. We are now in the wake of a paradigm shift in stratified therapeutic approaches related to NSCLC. At the heart of this shift in thinking is the emerging knowledge that even the most drug-resistant cancers exhibit a functional death pathway and, critically, that this pathway can be efficiently engaged, leading to clinical benefit. This review will summarise current knowledge of mitochondrial apoptotic pathway dysfunction in NSCLC and how the next generation of targeted therapeutics might be used to exploit deficiencies in apoptotic signalling in a personalised manner to improve clinical outcome and predict therapeutic benefit.


    Energy Technology Data Exchange (ETDEWEB)

    JIANG, YI [Los Alamos National Laboratory


    Cancer remains to be one of the leading causes of death due to diseases. We use a systems approach that combines mathematical modeling, numerical simulation, in vivo and in vitro experiments, to develop a predictive model that medical researchers can use to study and treat cancerous tumors. The multiscale, cell-based model includes intracellular regulations, cellular level dynamics and intercellular interactions, and extracellular level chemical dynamics. The intracellular level protein regulations and signaling pathways are described by Boolean networks. The cellular level growth and division dynamics, cellular adhesion and interaction with the extracellular matrix is described by a lattice Monte Carlo model (the Cellular Potts Model). The extracellular dynamics of the signaling molecules and metabolites are described by a system of reaction-diffusion equations. All three levels of the model are integrated through a hybrid parallel scheme into a high-performance simulation tool. The simulation results reproduce experimental data in both avasular tumors and tumor angiogenesis. By combining the model with experimental data to construct biologically accurate simulations of tumors and their vascular systems, this model will enable medical researchers to gain a deeper understanding of the cellular and molecular interactions associated with cancer progression and treatment.

  8. Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hye Kyung; Kim, Mi Sook; Jeong, Jae Hoon [Korea Institute of Radiologicaland Medical Sciences, Seoul (Korea, Republic of)


    To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

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

    Directory of Open Access Journals (Sweden)

    Aaraby Yoheswaran Nielsen


    Full Text Available 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 similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies.

  10. a Simple Evolutionary Model for Cancer Cell Population and its Implications on Cancer Therapy (United States)

    Yao, Peng; Wen, Shutang; Li, Baoshun; Li, Yuxiao

    We established a simple evolutionary model based on the cancer stem cell hypothesis. By taking cellular interactions into consideration, we introduced the evolutionary games theory into the quasispecies model. The fitness values are determined by both genotypes and cellular interactions. In the evolutionary model, a cancer cell population can evolve in different patterns. For single peak intrinsic fitness landscape, the evolution pattern can transit with increasing differentiation probability from malignant cells to benign cells in four different modes. For a large enough value of differentiation probability, the evolution is always the case that the malignant cells extinct ultimately, which might give some implications on cancer therapy.

  11. Cell volume regulation in epithelial physiology and cancer

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Hoffmann, Else Kay; Novak, Ivana


    The physiological function of epithelia is transport of ions, nutrients, and fluid either in secretory or absorptive direction. All of these processes are closely related to cell volume changes, which are thus an integrated part of epithelial function. Transepithelial transport and cell volume...... expression of ion transporters and channels is now recognized as one of the hallmarks of cancer, it is timely to consider this especially for epithelia. Epithelial cells are highly proliferative and epithelial cancers, carcinomas, account for about 90% of all cancers. In this review we will focus on ion...... transporters and channels with key physiological functions in epithelia and known roles in the development of cancer in these tissues. Their roles in cell survival, cell cycle progression, and development of drug resistance in epithelial cancers will be discussed....

  12. Canine Mammary Cance