Science.gov

Sample records for cancer cells part

  1. Micro RNA 100 sensitizes luminal A breast cancer cells to paclitaxel treatment in part by targeting mTOR

    PubMed Central

    He, Yuan; Fu, Xing; Fu, Liya; Zhu, Zhengmao; Fu, Li; Dong, Jin-Tang

    2016-01-01

    Luminal A breast cancer usually responds to hormonal therapies but does not benefit from chemotherapies, including microtubule-targeted paclitaxel. MicroRNAs could play a role in mediating this differential response. In this study, we examined the role of micro RNA 100 (miR-100) in the sensitivity of breast cancer to paclitaxel treatment. We found that while miR-100 was downregulated in both human breast cancer primary tumors and cell lines, the degree of downregulation was greater in the luminal A subtype than in other subtypes. The IC50 of paclitaxel was much higher in luminal A than in basal-like breast cancer cell lines. Ectopic miR-100 expression in the MCF-7 luminal A cell line enhanced the effect of paclitaxel on cell cycle arrest, multinucleation, and apoptosis, while knockdown of miR-100 in the MDA-MB-231 basal-like line compromised these effects. Similarly, overexpression of miR-100 enhanced the effects of paclitaxel on tumorigenesis in MCF-7 cells. Rapamycin-mediated inhibition of the mammalian target of rapamycin (mTOR), a target of miR-100, also sensitized MCF-7 cells to paclitaxel. Gene set enrichment analysis showed that genes that are part of the known paclitaxel-sensitive signature had a significant expression correlation with miR-100 in breast cancer samples. In addition, patients with lower levels of miR-100 expression had worse overall survival. These results suggest that miR-100 plays a causal role in determining the sensitivity of breast cancers to paclitaxel treatment. PMID:26744318

  2. Lung cancer - small cell

    MedlinePlus

    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 ...

  3. Update in Cancer Chemotherapy: Genitourinary Tract Cancer, Part 1

    PubMed Central

    Wright, Jane C.

    1987-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series. Included in the review are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 1 focuses on the kidney. In this heterogeneous group of tumors, the major triumphs of cancer chemotherapy are in the control of the less common of these tumors, namely, gestational trophoblastic neoplasms in women, in combination with surgery in the control of the embryonal cell cancer of the testis in men, and in combination with surgery and radiation therapy in the control of the Wilms' tumor in children. Important progress is being made in the control of the other tumors of the genitourinary tract with the use of cancer chemotherapy. PMID:3323538

  4. Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB‑231 partly through suppression of the Akt pathway.

    PubMed

    Jin, Hana; Lee, Won Sup; Eun, So Young; Jung, Ji Hyun; Park, Hyeon-Soo; Kim, Gonsup; Choi, Yung Hyun; Ryu, Chung Ho; Jung, Jin Myung; Hong, Soon Chan; Shin, Sung Chul; Kim, Hye Jung

    2014-10-01

    Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB‑231 breast cancer cells from low doses (50 µM) without cytotoxicity. In addition, morin changed MDA-MB‑231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB‑231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB‑231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB‑231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB‑231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.

  5. Comparative Phytochemical Analysis of Essential Oils from Different Biological Parts of Artemisia herba alba and Their Cytotoxic Effect on Cancer Cells

    PubMed Central

    Tilaoui, Mounir; Ait Mouse, Hassan; Jaafari, Abdeslam; Zyad, Abdelmajid

    2015-01-01

    Purpose Carrying out the chemical composition and antiproliferative effects against cancer cells from different biological parts of Artemisia herba alba. Methods Essential oils were studied by gas chromatography coupled to mass spectrometry (GC–MS) and their antitumoral activity was tested against P815 mastocytoma and BSR kidney carcinoma cell lines; also, in order to evaluate the effect on normal human cells, oils were tested against peripheral blood mononuclear cells PBMCs. Results Essential oils from leaves and aerial parts (mixture of capitulum and leaves) were mainly composed by oxygenated sesquiterpenes 39.89% and 46.15% respectively; capitulum oil contained essentially monoterpenes (22.86%) and monocyclic monoterpenes (21.48%); esters constituted the major fraction (62.8%) of stem oil. Essential oils of different biological parts studied demonstrated a differential antiproliferative activity against P815 and BSR cancer cells; P815 cells are the most sensitive to the cytotoxic effect. Leaves and capitulum essential oils are more active than aerial parts. Interestingly, no cytotoxic effect of these essential oils was observed on peripheral blood mononuclear cells. Conclusion Our results showed that the chemical composition variability of essential oils depends on the nature of botanical parts of Artemisia herba alba. Furthermore, we have demonstrated that the differential cytotoxic effect depends not only on the essential oils concentration, but also on the target cells and the botanical parts of essential oils used. PMID:26196123

  6. EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer

    PubMed Central

    Han, Ting; Jiao, Feng; Hu, Hai; Yuan, Cuncun; Wang, Lei; Jin, Zi-Liang; Song, Wei-feng; Wang, Li-Wei

    2016-01-01

    Enhancer of zeste homolog 2 (EZH2) is an essential component of the polycomb repressive complex 2 (PRC2), which is required for epigenetic silencing of target genes, including those affecting cancer progression. Its role in pancreatic cancer remains to be clarified; therefore, we investigated the effects of aberrantly expressed EZH2 on pancreatic cancer. We found that EZH2 expression is up-regulated in pancreatic cancer tissues and positively correlated with lymph node metastasis and advanced clinical stage in pancreatic cancer patients. EZH2 knockdown in pancreatic cancer cell lines inhibited cell migration and invasion, but did not alter cell proliferation. Silencing of EZH2 also increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with EZH2 expression in pancreatic cancer tissue samples. Patients with high EZH2 and low E-cadherin expression had the worst prognosis. RIP and ChIP assays suggest that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E-cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer. PMID:26848980

  7. EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer.

    PubMed

    Han, Ting; Jiao, Feng; Hu, Hai; Yuan, Cuncun; Wang, Lei; Jin, Zi-Liang; Song, Wei-Feng; Wang, Li-Wei

    2016-03-01

    Enhancer of zeste homolog 2 (EZH2) is an essential component of the polycomb repressive complex 2 (PRC2), which is required for epigenetic silencing of target genes, including those affecting cancer progression. Its role in pancreatic cancer remains to be clarified; therefore, we investigated the effects of aberrantly expressed EZH2 on pancreatic cancer. We found that EZH2 expression is up-regulated in pancreatic cancer tissues and positively correlated with lymph node metastasis and advanced clinical stage in pancreatic cancer patients. EZH2 knockdown in pancreatic cancer cell lines inhibited cell migration and invasion, but did not alter cell proliferation. Silencing of EZH2 also increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with EZH2 expression in pancreatic cancer tissue samples. Patients with high EZH2 and low E-cadherin expression had the worst prognosis. RIP and ChIP assays suggest that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E-cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer.

  8. Ovarian cancer, Part II: Treatment.

    PubMed

    Ozols, R F

    1992-01-01

    The death rate from epithelial ovarian cancer has only slightly decreased in the past decade. In contrast, there have been dramatic improvements in the treatment of germ cell tumors of the ovary and the majority of patients even with advanced disease is now cured because of the development of effective platinum-based combination chemotherapy. Unfortunately, most patients with ovarian cancer have the epithelial histologic type, and only one third of these patients can be cured with standard approaches. It has recently been shown that a subset of patients with early stage ovarian cancer has a greater than 90% cure rate without chemotherapy. Consequently, a major focus of current research is to develop effective screening modalities in order to diagnose epithelial tumors when they are still confined to the ovaries and pelvis. Currently, three fourths of patients are diagnosed at the time the disease has spread throughout the peritoneal cavity, and the standard approach has been cytoreductive surgery followed by combination chemotherapy. The two-drug combination of carboplatin plus cyclophosphamide has now become the treatment of choice, although it is equally effective as and less toxic than a regimen of cisplatin plus cyclophosphamide. In addition, Taxol has been identified as an extremely active agent against this disease, and new Taxol-containing combinations are under clinical investigation. Clinical trials are also in progress with hexamethylmelamine and ifosfamide combinations as well as with more dose-intense regimens based on considerable retrospective evidence that survival is correlated with the dose intensity of platinum compounds. New agents such as WR2721, IL-3, and IL-1 alpha are undergoing clinical evaluation to determine whether the toxicities of platinum compounds can be decreased and lead to further exploitation of the dose response relationship. After induction chemotherapy, approximately 50% of patients will be in a clinical complete remission

  9. Cell phones and cancer

    MedlinePlus

    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 ...

  10. Update in Cancer Chemotherapy: Genitourinary Tract Cancer, Part 4: Testicular Cancer

    PubMed Central

    Wright, Jane C.

    1988-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series: included are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 4 is a review of treatments for cancer of the testicles. Testicular cancer is highly curable and responds well to both surgery and chemotherapy. Patients with stage I and stage II nonseminomatous germ-cell tumors may be cured by surgery alone or in combination with chemotherapy. In patients with pathologic stage II disease, the use of adjuvant chemotherapy with two courses of platinum-based combination drugs has been successful in preventing relapse. Further refinements in management and research could banish the problem of testicular cancer. PMID:3290501

  11. Microbead analysis of cell binding to immobilized lectin. Part II: Quantitative kinetic profile assay for possible identification of anti-infectivity and anti-cancer reagents.

    PubMed

    Ghazarian, Anasheh; Oppenheimer, Steven B

    2014-10-01

    There has been a re-emergence of the use of lectins in a variety of therapeutic venues. In addition lectins are often responsible for the binding of pathogens to cells and for cancer cell clumping that increases their escape from body defenses. It is important to define precisely the activity of inhibitors of lectin-binding that may be used in anti-infection and anti-cancer therapeutics. Here we describe a kinetic assay that measures the activity of saccharide inhibitors of lectin binding using a model system of yeast (Saccharomyces cerevisiae) and lectin (Concanavalin A, Con A) derivatized agarose microbeads that mimics pathogen-cell binding. We show that old methods (part I of this study) used to identify inhibitor activity using only one sugar concentration at one time point can easily provide wrong information about inhibitor activity. We assess the activity of 4 concentrations of 10 saccharides at 4 different times in 400 trials and statistically evaluate the results. We show that d-melezitose is the best inhibitor of yeast binding to the lectin microbeads. These results, along with physical chemistry studies, provide a solid foundation for the development of drugs that may be useful in anti-infectivity and anti-cancer therapeutics.

  12. [Stem cells and cancer].

    PubMed

    Arvelo, Francisco; Cotte, Carlos; Sojo, Felipe

    2014-12-01

    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. Cancer stem cells are a subpopulation of the cells that form the tumor. The discovery of these human cancer cells opens a perspective for understanding tumor recurrence, drug resistance and metastasis; and opens up new research directions on how cancer cells are capable of switching from dormancy to malignancy. Therapeutic alternatives emerge from a better understanding of the biology and the environment of tumor stem cells. The present paper aims to summarize the characteristics and properties of cancer stem cells, the ongoing research, as well as the best strategies for prevention and control of the mechanisms of tumor recurrence.

  13. Interference with endogenous EZH2 reverses the chemotherapy drug resistance in cervical cancer cells partly by up-regulating Dicer expression.

    PubMed

    Cai, Liqiong; Wang, Zehua; Liu, Denghua

    2016-05-01

    Cervical cancer is one of the most common female malignancies in the world, and chemotherapeutic drug resistance is a major obstacle to cancer therapy. Enhancer of zeste homolog 2 (EZH2) is an enzymatic subunit of polycomb repressive complex 2 (PRC2) and catalyzes the repressive histone H3 lysine 27 trimethylation (H3K27me3). However, the role of EZH2 on the chemotherapy drug resistance in cervical cancers remains unclear. In the present study, the cervical carcinoma specimens and paired normal tissue specimens were obtained and the expression of EZH2 was detected by western blotting. The results showed that high levels of EZH2 were detected in cervical carcinoma tissues, compared with paired control tissues (**p < 0.01). Next, three pairs of shRNA specific to EZH2 were designed and used to interfere with endogenous EZH2 expression. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays following treatment with various concentrations of cisplatin in HeLa and HeLa/DDP cells. The MTT assay results showed that knockdown of EZH2 in HeLa/DDP cells caused a 2.29- or 1.83-fold decrease in the cisplatin IC50 values (for shRNA1-EZH2, 34.88 vs. 15.21 μg/mL; p < 0.01; for shRNA3-EZH2, 34.88 vs. 19.09 μg/mL; p < 0.01). The EZH2 activity was also suppressed by 3-deazaneplanocin A (DZNep), EZH2 inhibitor, and the results demonstrated that, meanwhile, DZNep potently inhibited cell viability of HeLa/DDP cells, partly by suppression the levels of EZH2 and H3K27me3, but not H3K27me2, which was detected by western blotting analysis. Moreover, cell migration assay results showed that knockdown of EZH2 decreased cell metastasis of cervical cancer cells. Furthermore, cell cycle was detected by fluorescence-activated cell sorting (FACS) assay and the results demonstrated that interference with EZH2 expression increased the percentage of cells at G0/G1 phase and the HeLa/DDP cells were blocked at G0/G1 phase. Interestingly

  14. Pancreatic cancer stem cells

    PubMed Central

    Zhu, Ya-Yun; Yuan, Zhou

    2015-01-01

    Studies are emerging in support of the cancer stem cells (CSCs) theory which considers that a tiny subset of cancer cells is exclusively responsible for the initiation and malignant behavior of a cancer. This cell population, also termed CSCs, possesses the capacity both to self-renew, producing progeny that have the identical tumorigenic potential, and to differentiate into the bulk of cancer cells, helping serve the formation of the tumor entities, which, altogether, build the hierarchically organized structure of a cancer. In this review, we try to articulate the complicated signaling pathways regulating the retention of the characteristics of pancreatic CSCs, and in the wake of which, we seek to offer insights into the CSCs-relevant targeted therapeutics which are, in the meantime, confronted with bigger challenges than ever. PMID:26045976

  15. Ovarian cancer stem cells enrichment.

    PubMed

    Yang, Lijuan; Lai, Dongmei

    2013-01-01

    The concept of cancer stem cells (CSCs) provides a new paradigm for understanding cancer biology. Cancer stem cells are defined as a minority of cancer cells with stem cell properties responsible for maintenance and growth of tumors. The targeting of CSCs is a potential therapeutic strategy to combat ovarian cancer. Ovarian epithelial cancer cells cultured in serum-free medium can form sphere cells. These sphere cells may be enriched for cancer stem cells (CSCs). The isolation of sphere cells from solid tumors is an important technique in studying cancer cell biology. Here we describe the isolation of sphere cells from primary ovarian cancer tissue, ascites fluid, and the cancer cell line SKOV3 with stem cell selection medium. PMID:23913228

  16. Fragmentation of cancer cells

    NASA Astrophysics Data System (ADS)

    Vanapalli, Siva; Kamyabi, Nabiollah

    Tumor cells have to travel through blood capillaries to be able to metastasize and colonize in distant organs. Among the numerous cells that are shed by the primary tumor, very few survive in circulation. In vivo studies have shown that tumor cells can undergo breakup at microcapillary junctions affecting their survival. It is currently unclear what hydrodynamic and biomechanical factors contribute to fragmentation and moreover how different are the breakup dynamics of highly and weakly metastatic cells. In this study, we use microfluidics to investigate flow-induced breakup of prostate and breast cancer cells. We observe several different modes of breakup of cancer cells, which have striking similarities with breakup of viscous drops. We quantify the breakup time and find that highly metastatic cancer cells take longer to breakup than lowly metastatic cells suggesting that tumor cells may dynamically modify their deformability to avoid fragmentation. We also identify the role that cytoskeleton and membrane plays in the breakup process. Our study highlights the important role that tumor cell fragmentation plays in cancer metastasis. Cancer Prevention and Research Institute of Texas.

  17. Basal cell cancer (image)

    MedlinePlus

    ... is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and location of the cancer. Early treatment by a dermatologist may result in a cure rate of more than 95%, but regular examination ...

  18. Chemotherapy targeting cancer stem cells.

    PubMed

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future.

  19. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  20. Mitochondria, cholesterol and cancer cell metabolism.

    PubMed

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

    2016-12-01

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

  1. Therapeutic targeting of autophagy in cancer. Part II: pharmacological modulation of treatment-induced autophagy.

    PubMed

    Nagelkerke, Anika; Bussink, Johan; Geurts-Moespot, Anneke; Sweep, Fred C G J; Span, Paul N

    2015-04-01

    Autophagy, the catabolic pathway in which cells recycle organelles and other parts of their own cytoplasm, is increasingly recognised as an important cytoprotective mechanism in cancer cells. Several cancer treatments stimulate the autophagic process and when autophagy is inhibited, cancer cells show an enhanced response to multiple treatments. These findings have nourished the theory that autophagy provides cancer cells with a survival advantage during stressful conditions, including exposure to therapeutics. Therefore, interference with the autophagic response can potentially enhance the efficacy of cancer therapy. In this review we examine two approaches to modulate autophagy as complementary cancer treatment: inhibition and induction. Inhibition of autophagy during cancer treatment eliminates its cytoprotective effects. Conversely, induction of autophagy combined with conventional cancer therapy exerts severe cytoplasmic degradation that can ultimately lead to cell death. We will discuss how autophagy can be therapeutically manipulated in cancer cells and how interactions between the conventional cancer therapies and autophagy modulation influence treatment outcome.

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

    PubMed

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

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

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

    PubMed Central

    Vlashi, Erina; Pajonk, Frank

    2014-01-01

    Summary 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. PMID:25025713

  4. Low white blood cell count and cancer

    MedlinePlus

    Neutropenia and cancer; Absolute neutrophil count and cancer; ANC and cancer ... A person with cancer can get a low white blood cell count from the cancer or from treatment for the cancer. Cancer may ...

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

    SciTech Connect

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-05-04

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

  6. Extragonadal Germ Cell Cancer (EGC)

    MedlinePlus

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

  7. Gene sensitizes cancer cells to chemotherapy drugs

    Cancer.gov

    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

  8. Membrane in cancer cells

    SciTech Connect

    Galeotti, T.; Cittadini, A.; Neri, G.; Scarpa, A.

    1988-01-01

    This book contains papers presented at a conference on membranes in cancer cells. Topics covered include Oncogenies, hormones, and free-radical processes in malignant transformation in vitro and Superoxide onion may trigger DNA strand breaks in human granulorytes by acting as a membrane target.

  9. Pancreatic small cell cancer.

    PubMed

    El Rassy, Elie; Tabchi, Samer; Kourie, Hampig Raphael; Assi, Tarek; Chebib, Ralph; Farhat, Fadi; Kattan, Joseph

    2016-06-01

    Small cell carcinoma (SCC) is most commonly associated with lung cancer. Extra-pulmonary SCC can originate in virtually any organ system, with the gastrointestinal tract being the most common site of involvement. We review the clinical presentation, pathogenesis, histology, imaging modalities and optimal therapeutic management of PSCC in light of available evidence. PMID:26566245

  10. Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and γ-radiation sensitivity

    SciTech Connect

    Kim, In Gyu; Kim, Seo Yoen; Kim, Hyun A; Kim, Jeong Yul; Lee, Jae Ha; Choi, Soo Im; Han, Jeong Ran; Kim, Kug Chan; Cho, Eun Wie

    2014-01-03

    Highlights: •DKK1 was expressed differently among non-small-cell lung cancer cell lines. •DKK1 negatively regulated ROMO1 gene expression. •Disturbance of DKK1 level induced the imbalance of cellular ROS. •DKK1/ROMO1-induced ROS imbalance is involved in cell survival in NSCLC. -- Abstract: Dickkopf1 (DKK1), a secreted protein involved in embryonic development, is a potent inhibitor of the Wnt signaling pathway and has been postulated to be a tumor suppressor or tumor promoter depending on the tumor type. In this study, we showed that DKK1 was expressed differently among non-small-cell lung cancer cell lines. The DKK1 expression level was much higher in A549 cells than in H460 cells. We revealed that blockage of DKK1 expression by silencing RNA in A549 cells caused up-regulation of intracellular reactive oxygen species (ROS) modulator (ROMO1) protein, followed by partial cell death, cell growth inhibition, and loss of epithelial–mesenchymal transition property caused by ROS, and it also increased γ-radiation sensitivity. DKK1 overexpression in H460 significantly inhibited cell survival with the decrease of ROMO1 level, which induced the decrease of cellular ROS. Thereafter, exogenous N-acetylcysteine, an antioxidant, or hydrogen peroxide, a pro-oxidant, partially rescued cells from death and growth inhibition. In each cell line, both overexpression and blockage of DKK1 not only elevated p-RB activation, which led to cell growth arrest, but also inactivated AKT/NF-kB, which increased radiation sensitivity and inhibited cell growth. This study is the first to demonstrate that strict modulation of DKK1 expression in different cell types partially maintains cell survival via tight regulation of the ROS-producing ROMO1 and radiation resistance.

  11. P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression

    PubMed Central

    Zhang, E-b; Yin, D-d; Sun, M; Kong, R; Liu, X-h; You, L-h; Han, L; Xia, R; Wang, K-m; Yang, J-s; De, W; Shu, Y-q; Wang, Z-x

    2014-01-01

    Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. Here we report that taurine-upregulated gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC) tissues. In a cohort of 192 NSCLC patients, the lower expression of TUG1 was associated with a higher TNM stage and tumor size, as well as poorer overall survival (P<0.001). Univariate and multivariate analyses revealed that TUG1 expression serves as an independent predictor for overall survival (P<0.001). Further experiments revealed that TUG1 expression was induced by p53, and luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1 was a direct transcriptional target of p53. TUG1 knockdown significantly promoted the proliferation in vitro and in vivo. Moreover, the lncRNA-mediated regulation of the expression of HOX genes in tumorigenesis and development has been recently receiving increased attention. Interestingly, inhibition of TUG1 could upregulate homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of PRC2, and was H3K27 trimethylated. This TUG1-mediated growth regulation is in part due to specific modulation of HOXB7, thus participating in AKT and MAPK pathways. Together, these results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7. The p53/TUG1/PRC2/HOXB7 interaction might serve as targets for NSCLC diagnosis and therapy. PMID:24853421

  12. Breast Cancer Stem Cells

    PubMed Central

    Velasco-Velázquez, Marco A.; Homsi, Nora; De La Fuente, Marisol; Pestell, Richard G.

    2012-01-01

    Breast cancer stem cells (BCSCs) constitute a subpopulation of tumor cells that express stem cell-associated markers and have a high capacity for tumor generation in vivo. Identification of BCSCs from tumor samples or breast cancer cell lines has been based mainly on CD44+/CD24−/low or ALDH+ phenotypes. BCSCs isolation has allowed the analysis of the molecular mechanisms involved in their origin, self-renewal, differentiation into tumor cells, resistance to radiation therapy and chemotherapy, and invasiveness and metastatic ability. Molecular genetic analysis using knockout animals and inducible transgenics have identified NF-κB, c-Jun, p21CIP1, and Forkhead-like-protein Dach1 in BCSC expansion and fate. Clinical analyses of BCSCs in breast tumors have found a correlation between the proportion of BCSCs and poor prognosis. Therefore, new therapies that specifically target BCSCs are an urgent need. We summarize recent evidence that partially explain the biological characteristics of BCSCs. PMID:22249027

  13. Overexpression of Lin28 Decreases the Chemosensitivity of Gastric Cancer Cells to Oxaliplatin, Paclitaxel, Doxorubicin, and Fluorouracil in Part via microRNA-107

    PubMed Central

    Teng, Rongyue; Hu, Yan; Zhou, Jichun; Seifer, Benjamin; Chen, Yongxia

    2015-01-01

    Higher Lin28 expression is associated with worse pathologic tumor responses in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. However, the characteristics of Lin28 and its mechanism of action in chemotherapy resistance is still unclear. In this study, we found that transfection of Lin28 into gastric cancer cells (MKN45 and MKN28) increased their resistance to the chemo-drugs oxaliplatin (OXA), paclitaxel (PTX), doxorubicin (ADM), and fluorouracil (5-Fu) compared with gastric cancer cells transfected with a control vector. When knockdown Lin28 expression by Lin28 small interfering RNA (siRNA) was evaluated in vitro, we found that the resistance to chemo-drugs was reduced. Furthermore, we found that Lin28 up-regulates C-myc and P-gp and down-regulates Cylin D1. Finally, we found that miR-107 is a target microRNA of Lin28 and that it participates in the mechanism of chemotherapy resistance. Our results suggest that the Lin28/miR-107 pathway could be one of many signaling pathways regulated by Lin28 and associated with gastric cancer chemo-resistance. PMID:26636340

  14. Cancer stem cells in small cell lung cancer.

    PubMed

    Codony-Servat, Jordi; Verlicchi, Alberto; Rosell, Rafael

    2016-02-01

    Small cell lung cancer (SCLC) is one of the most aggressive lung tumors, with poor survival rates. Although patients may initially respond to treatment, this is followed by rapid development of drug resistance and disease progression. SCLC patients often present with metastasis at time of diagnosis, ruling out surgery as a treatment option. Currently, treatment options for this disease remain limited and platinum-based chemotherapy is the treatment of choice. A better understanding of the biology of SCLC could allow us to identify new therapeutic targets. Cancer stem cell (CSC) theory is currently crucial in cancer research and could provide a viable explanation for the heterogeneity, drug resistance, recurrence and metastasis of several types of tumors. Some characteristics of SCLC, such as aggressiveness, suggest that this kind of tumor could be enriched in CSCs, and drug resistance in SCLC could be attributable to the existence of a CSC subpopulation in SCLC. Herein we summarize current understanding of CSC in SCLC, including the evidence for CSC markers and signaling pathways involved in stemness. We also discuss potential ongoing strategies and areas of active research in SCLC, such as immunotherapy, that focus on inhibition of signaling pathways and targeting molecules driving stemness. Understanding of signaling pathways and the discovery of new therapeutic markers specific to CSCs will lead to new advances in therapy and improvements in prognosis of SCLC patients. Therefore, evaluation of these CSC-specific molecules and pathways may become a routine part of SCLC diagnosis and therapy.

  15. Cancer stem cells in small cell lung cancer

    PubMed Central

    Verlicchi, Alberto; Rosell, Rafael

    2016-01-01

    Small cell lung cancer (SCLC) is one of the most aggressive lung tumors, with poor survival rates. Although patients may initially respond to treatment, this is followed by rapid development of drug resistance and disease progression. SCLC patients often present with metastasis at time of diagnosis, ruling out surgery as a treatment option. Currently, treatment options for this disease remain limited and platinum-based chemotherapy is the treatment of choice. A better understanding of the biology of SCLC could allow us to identify new therapeutic targets. Cancer stem cell (CSC) theory is currently crucial in cancer research and could provide a viable explanation for the heterogeneity, drug resistance, recurrence and metastasis of several types of tumors. Some characteristics of SCLC, such as aggressiveness, suggest that this kind of tumor could be enriched in CSCs, and drug resistance in SCLC could be attributable to the existence of a CSC subpopulation in SCLC. Herein we summarize current understanding of CSC in SCLC, including the evidence for CSC markers and signaling pathways involved in stemness. We also discuss potential ongoing strategies and areas of active research in SCLC, such as immunotherapy, that focus on inhibition of signaling pathways and targeting molecules driving stemness. Understanding of signaling pathways and the discovery of new therapeutic markers specific to CSCs will lead to new advances in therapy and improvements in prognosis of SCLC patients. Therefore, evaluation of these CSC-specific molecules and pathways may become a routine part of SCLC diagnosis and therapy. PMID:26958490

  16. Nonthermal Plasma-Mediated Cancer Cell Death; Targeted Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Choi, Byul-Bora; Choi, Yeon-Sik; Lee, Hae-Jun; Lee, Jae-Koo; Kim, Uk-Kyu; Kim, Gyoo-Cheon

    Non-thermal air plasma can kill cancer cells. However, there is no selectivity between normal and cancer cells. Therefore, cancer specific antibody conjugated gold nanoparticle (GNP) was pretreated before plasma irradiation. Stimulation of antibody conjugated GNP by plasma treatment resulted in a significant decrease in viability of cancer cells. This technology shows the feasibility of using plasma therapy for killing cancer cells selectively.

  17. Bioassay-guided isolation and identification of bioactive compound from aerial parts of Luffa acutangula against lung cancer cell line NCI-H460.

    PubMed

    Vanajothi, Ramar; Srinivasan, Pappu

    2015-01-01

    Luffa acutangula (Cucurbitaceae) is widely used as a traditional medicine in India and was reported to possess various pharmacological activities including its anti-proliferative effects. In this study, the bioactive compound of ethanolic extract of L. acutangula (LA) was isolated using bioassay-guided approach. Five major fractions were collected and evaluated for their anti-proliferative activity against non-small cell lung cancer cells (NCI-H460). Among the test fractions, the fraction LA/FII effectively decreased the growth of cancer cells with IC50 values of 10 µg/ml concentration. Furthermore, it significantly increased intracellular reactive oxygen species and decreased the mitochondrial membrane potential. The apoptogenic activity of fraction LA/FII was confirmed by cell shrinkage, membrane blebbing and formation of apoptotic bodies. A single bioactive compound was isolated from the active faction, LA/FII and subsequently identified as 1,8 dihydroxy-4-methylanthracene 9,10-dione (compound 1) by comparing its spectral data [Ultraviolet (UV), Infrared (IR), Nuclear magnetic resonance (NMR) and Electrospray Ionization-Mass Spectroscopy (ESI-MS)] with literature values. This is the first report on the isolation of compound 1 from this plant.

  18. Treatment Option Overview (Small Cell Lung Cancer)

    MedlinePlus

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

  19. Stages of Small Cell Lung Cancer

    MedlinePlus

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

  20. Ascites-induced shift along epithelial-mesenchymal spectrum in ovarian cancer cells: enhancement of their invasive behavior partly dependant on αv integrins.

    PubMed

    Carduner, L; Leroy-Dudal, J; Picot, C R; Gallet, O; Carreiras, F; Kellouche, S

    2014-08-01

    At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence. The presence of ascites, which acts as a dynamic reservoir of active molecules and cellular components, correlates with the OC peritoneal metastasis and is associated with poor prognosis. Since epithelial-mesenchymal transition (EMT) is involved in different phases of OC progression, we have investigated the effect of the unique ascitic tumor microenvironment on the EMT status and the behavior of OC cells. The exposure of three OC cell lines to ascites leads to changes in cellular morphologies. Within ascites, OC cells harboring an initial intermediate epithelial phenotype are characterized by marked dislocation of epithelial markers (E-cadherin, ZO-1 staining) while OC cells initially harboring an intermediate mesenchymal phenotype strengthen their mesenchymal markers (N-cadherin, vimentin). Ascites differentially triggers a dissemination phenotype related to the initial cell features by either allowing the proliferation and the formation of spheroids and the extension of colonies for cells that present an initial epithelial intermediate phenotype, or favoring the migration of cells with a mesenchymal intermediate phenotype. In an ascitic microenvironment, a redeployment of αv integrins into cells was observed and the ascites-induced accentuation of the two different invasive phenotypes (i.e. spheroids formation or migration) was shown to involve αv integrins. Thus, ascites induces a shift toward an unstable intermediate state of the epithelial-mesenchymal spectrum and confers a more aggressive cell behavior that takes on a different pathway based on the initial epithelial-mesenchymal cell features. PMID:24946950

  1. Stem cells, colorectal cancer and cancer stem cell markers correlations.

    PubMed

    Cherciu, Irina; Bărbălan, A; Pirici, D; Mărgăritescu, C; Săftoiu, A

    2014-01-01

    : The idea of stem cells as being progenitors of cancer was initially controversial, but later supported by research in the field of leukemia and solid tumors. Afterwards, it was established that genetic abnormalities can affect the stem and progenitor cells, leading to uncontrolled replication and deregulated differentiation. These alterations will cause the changeover to cancerous stem cells (CSC) having two main characteristics: tumor initiation and maintenance. This review will focus on the colorectal cancer stem cell (CR-CSCs) theory which provides a better understanding of different tumor processes: initiation, aggressive growth, recurrence, treatment resistance and metastasis. A search in PubMed/Medline was performed using the following keywords: colorectal cancer stem cells (CR-CSCs), colorectal neoplasms stem cells, colorectal cancer stem cell (CR-CSCs) markers, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Isolation of CR-CSCs can be achieved by targeting and selecting subpopulation of tumor cells based on expression of one or multiple cell surface markers associated with cancer self-renewal, markers as: CD133, CD166, CD44, CD24, beta1 integrin-CD29, Lgr5, EpCAM (ESA), ALDH-1, Msi-1, DCAMLK1 or EphB receptors. The identification and localization of CR-CSCs through different markers will hopefully lead to a better stratification of prognosis and treatment response, as well as the development of new effective strategies for cancer management.

  2. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  3. Contemporary Renal Cell Cancer Epidemiology

    PubMed Central

    Chow, Wong-Ho; Devesa, Susan S.

    2010-01-01

    We analyzed renal cell cancer incidence patterns in the United States and reviewed recent epidemiologic evidence with regard to environmental and host genetic determinants of renal cell cancer risk. Renal cell cancer incidence rates continued to rise among all racial/ethnic groups in the United States, across all age groups, and for all tumor sizes, with the most rapid increases for localized stage disease and small tumors. Recent cohort studies confirmed the association of smoking, excess body weight, and hypertension with an elevated risk of renal cell cancer, and suggested that these factors can be modified to reduce the risk. There is increasing evidence for an inverse association between renal cell cancer risk and physical activity and moderate intake of alcohol. Occupational exposure to TCE has been positively associated with renal cell cancer risk in several recent studies, but its link with somatic mutations of the VHL gene has not been confirmed. Studies of genetic polymorphisms in relation to renal cell cancer risk have produced mixed results, but genome-wide association studies with larger sample size and a more comprehensive approach are underway. Few epidemiologic studies have evaluated risk factors by subtypes of renal cell cancer defined by somatic mutations and other tumor markers. PMID:18836333

  4. Energy Restriction-mimetic Agents Induce Apoptosis in Prostate Cancer Cells in Part through Epigenetic Activation of KLF6 Tumor Suppressor Gene Expression*

    PubMed Central

    Chen, Chun-Han; Huang, Po-Hsien; Chu, Po-Chen; Chen, Mei-Chuan; Chou, Chih-Chien; Wang, Dasheng; Kulp, Samuel K.; Teng, Che-Ming; Wang, Qianben; Chen, Ching-Shih

    2011-01-01

    Although energy restriction has been recognized as an important target for cancer prevention, the mechanism by which energy restriction-mimetic agents (ERMAs) mediate apoptosis remains unclear. By using a novel thiazolidinedione-derived ERMA, CG-12 (Wei, S., Kulp, S. K., and Chen, C. S. (2010) J. Biol. Chem. 285, 9780–9791), vis-à-vis 2-deoxyglucose and glucose deprivation, we obtain evidence that epigenetic activation of the tumor suppressor gene Kruppel-like factor 6 (KLF6) plays a role in ERMA-induced apoptosis in LNCaP prostate cancer cells. KLF6 regulates the expression of many proapoptotic genes, and shRNA-mediated KLF6 knockdown abrogated the ability of ERMAs to induce apoptosis. Chromatin immunoprecipitation analysis indicates that this KLF6 transcriptional activation was associated with increased histone H3 acetylation and histone H3 lysine 4 trimethylation occupancy at the promoter region. Several lines of evidence demonstrate that the enhancing effect of ERMAs on these active histone marks was mediated through transcriptional repression of histone deacetylases and H3 lysine 4 demethylases by down-regulating Sp1 expression. First, putative Sp1-binding elements are present in the promoters of the affected histone-modifying enzymes, and luciferase reporter assays indicate that site-directed mutagenesis of these Sp1 binding sites significantly diminished the promoter activities. Second, shRNA-mediated knockdown of Sp1 mimicked the repressive effect of energy restriction on these histone-modifying enzymes. Third, ectopic Sp1 expression protected cells from the repressive effect of CG-12 on these histone-modifying enzymes, thereby abolishing the activation of KLF6 expression. Together, these findings underscore the intricate relationship between energy restriction and epigenetic regulation of tumor suppressor gene expression, which has therapeutic relevance to foster novel strategies for prostate cancer therapy. PMID:21282102

  5. Small Cell Lung Cancer.

    PubMed

    Bernhardt, Erica B; Jalal, Shadia I

    2016-01-01

    Small cell lung cancer (SCLC) is an aggressive cancer of neuroendocrine origin, which is strongly associated with cigarette smoking. Patients typically present with a short duration of symptoms and frequently (60-65 %) with metastatic disease. SCLC is a heterogeneous disease including extremely chemosensitive and chemoresistant clones. For this reason, a high percentage of patients respond to first-line chemotherapy but rapidly succumb to the disease. SCLC is generally divided into two stages, limited and extensive. Standard treatment of limited stage disease includes combination chemotherapy with cisplatin and etoposide for four cycles, thoracic radiation initiated early with the first cycle of chemotherapy, and consideration of prophylactic cranial irradiation (PCI) in the subset of patients with good response. Surgery may play a role in TNM stages I and II. In extensive disease, platinum agents and etoposide, used in combination, are again the first-line standard of care in the USA. However, thoracic radiation therapy is used predominately in patients where local control is important and PCI is of uncertain benefit. Despite these treatments, prognosis remains poor and novel therapies are needed to improve survival in this disease. PMID:27535400

  6. Update in Cancer Chemotherapy: Genitourinary Tract Cancer, Part 2: Wilms' Tumor and Bladder Cancer

    PubMed Central

    Wright, Jane C.

    1988-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of genitourinary tract cancer is described in this multi-part series. Included in the review are cancers of the kidney, bladder, prostate, testicle, ovary, uterus, vulva, and gestational trophoblastic neoplasms. Part 2 focuses on Wilms' tumor and bladder cancer. Major advances have been made in the control of Wilms' tumor in children. The combination of surgery, chemotherapy, and radiotherapy have significantly improved survival rates. Likewise, the early diagnosis and control of bladder cancer has also improved survival. Surgery predominates among the treatment modalities for carcinoma of the bladder. Important progress is being made in the control of these conditions, as well as with other tumors of the genitourinary tract, with the use of cancer chemotherapy. PMID:2853770

  7. Intraoperative photodynamic therapy in laryngeal part of pharynx cancers

    NASA Astrophysics Data System (ADS)

    Loukatch, Erwin V.; Trojan, Vasily; Loukatch, Vjacheslav

    1996-12-01

    In clinic intraoperative photodynamic therapy (IPT) was done in patients with primal squamous cells cancer of the laryngeal part of the pharynx. The He-Ne laser and methylene blue as a photosensibilizator were used. Cobalt therapy in the postoperative period was done in dose 45 Gr. Patients of control groups (1-th group) with only laser and (2-th group) only methylene blue were controlled during three years with the main group. The statistics show certain differences of recidives in the main group compared to the control groups. These facts are allowing us to recommend the use of IPT as an additional method in ENT-oncology diseases treatment.

  8. Stress Modulus of Cancer Cells

    NASA Astrophysics Data System (ADS)

    Bonin, Keith; Guthold, Martin; Guo, Xinyi; Sigley, Justin

    2012-02-01

    Our main goal is to study the different physical and mechanical properties of cells as they advance through different stages of neoplastic transformation from normal to the metastatic state. Since recent reports indicate there is significant ambiguity about how these properties change for different cancer cells, we plan to measure these properties for a single line of cells, and to determine whether the changes vary for different cellular components: i.e. whether the change in physical properties is due to a change in the cytoskeleton, the cell membrane, the cytoplasm, or a combination of these elements. Here we expect to present data on the stress modulus of cancer cells at different stages: normal, mortal cancerous, immortal cancerous, and tumorigenic. The cells are Weinberg cell line Human Mammary Epithelial (HME) cells. Atomic force microscope (AFM) probes with different diameters are used to push on the cell membrane to measure the local, regional and global cell stress modulus. Preliminary results on normal HME cells suggests a stress modulus of 1.5 ± 0.8 kPa when pushing with 7 μm spherical probes. We anticipate reporting an improved value for the modulus as well as results for some of the Weinberg cancer cells.

  9. Altered calcium signaling in cancer cells.

    PubMed

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

    2015-10-01

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

  10. Cancer Cells with Irons in the Fire

    PubMed Central

    Bystrom, Laura M.; Rivella, Stefano

    2014-01-01

    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 iron-dependent cancer phenotype, and how these characteristics may be exploited to prevent or treat cancer. PMID:24835768

  11. CANCER STEM CELLS AND RADIORESISTANCE

    PubMed Central

    K, Rycaj; D.G, Tang

    2015-01-01

    Purpose Radiation therapy has made significant contributions to cancer therapy. However, despite continuous improvements, tumor recurrence and therapy resistance still occur in a high proportion of patients. One underlying reason for this radioresistance might be attributable to the presence of cancer stem cells (CSCs). Conclusions This review discusses CSC-specific mechanisms that confer radiation resistance with a focus on breast cancer and glioblastoma multiforme (GBM), thereby emphasizing the addition of these potential therapeutic targets in order to potentiate radiotherapy efficacy. PMID:24527669

  12. Drugs Approved for Kidney (Renal Cell) Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs ... that are not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) ...

  13. Invasive cancer cells and metastasis

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia Tanja

    2013-12-01

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

  14. Phenotype heterogeneity in cancer cell populations

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  15. Cancer stem cells: impact, heterogeneity, and uncertainty

    PubMed Central

    Magee, Jeffrey A.; Piskounova, Elena; Morrison, Sean J.

    2015-01-01

    The differentiation of tumorigenic cancer stem cells into non-tumorigenic cancer cells confers heterogeneity to some cancers beyond that explained by clonal evolution or environmental differences. In such cancers, functional differences between tumorigenic and non-tumorigenic cells influence response to therapy and prognosis. However, it remains uncertain whether the model applies to many, or few, cancers due to questions about the robustness of cancer stem cell markers and the extent to which existing assays underestimate the frequency of tumorigenic cells. In cancers with rapid genetic change, reversible changes in cell states, or biological variability among patients the stem cell model may not be readily testable. PMID:22439924

  16. Probiotics, dendritic cells and bladder cancer.

    PubMed

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette-Guérin).

  17. Probiotics, dendritic cells and bladder cancer.

    PubMed

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  18. Oxidative phosphorylation in cancer cells.

    PubMed

    Solaini, Giancarlo; Sgarbi, Gianluca; Baracca, Alessandra

    2011-06-01

    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.

  19. Squamous cell skin cancer

    MedlinePlus

    ... occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. The earliest form of ... skin cancer is to reduce your exposure to sunlight . Always use sunscreen: Apply sunscreen with sun protection ...

  20. Basal cell skin cancer

    MedlinePlus

    ... occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. This type of skin ... skin cancer is to reduce your exposure to sunlight . Always use sunscreen: Apply sunscreen with sun protection ...

  1. Schwann cells induce cancer cell dispersion and invasion

    PubMed Central

    Deborde, Sylvie; Lyubchik, Anna; Zhou, Yi; He, Shizhi; McNamara, William F.; Chernichenko, Natalya; Lee, Sei-Young; Barajas, Fernando; Chen, Chun-Hao; Bakst, Richard L.; Vakiani, Efsevia; He, Shuangba; Hall, Alan; Wong, Richard J.

    2016-01-01

    Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis. Furthermore, the innervation of some cancers promotes growth and metastases. It remains unclear, however, how nerves mechanistically contribute to cancer progression. Here, we demonstrated that Schwann cells promote cancer invasion through direct cancer cell contact. Histological evaluation of murine and human cancer specimens with perineural invasion uncovered a subpopulation of Schwann cells that associates with cancer cells. Coculture of cancer cells with dorsal root ganglion extracts revealed that Schwann cells direct cancer cells to migrate toward nerves and promote invasion in a contact-dependent manner. Upon contact, Schwann cells induced the formation of cancer cell protrusions in their direction and intercalated between the cancer cells, leading to cancer cell dispersion. The formation of these processes was dependent on Schwann cell expression of neural cell adhesion molecule 1 (NCAM1) and ultimately promoted perineural invasion. Moreover, NCAM1-deficient mice showed decreased neural invasion and less paralysis. Such Schwann cell behavior reflects normal Schwann cell programs that are typically activated in nerve repair but are instead exploited by cancer cells to promote perineural invasion and cancer progression. PMID:26999607

  2. Schwann cells induce cancer cell dispersion and invasion.

    PubMed

    Deborde, Sylvie; Omelchenko, Tatiana; Lyubchik, Anna; Zhou, Yi; He, Shizhi; McNamara, William F; Chernichenko, Natalya; Lee, Sei-Young; Barajas, Fernando; Chen, Chun-Hao; Bakst, Richard L; Vakiani, Efsevia; He, Shuangba; Hall, Alan; Wong, Richard J

    2016-04-01

    Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis. Furthermore, the innervation of some cancers promotes growth and metastases. It remains unclear, however, how nerves mechanistically contribute to cancer progression. Here, we demonstrated that Schwann cells promote cancer invasion through direct cancer cell contact. Histological evaluation of murine and human cancer specimens with perineural invasion uncovered a subpopulation of Schwann cells that associates with cancer cells. Coculture of cancer cells with dorsal root ganglion extracts revealed that Schwann cells direct cancer cells to migrate toward nerves and promote invasion in a contact-dependent manner. Upon contact, Schwann cells induced the formation of cancer cell protrusions in their direction and intercalated between the cancer cells, leading to cancer cell dispersion. The formation of these processes was dependent on Schwann cell expression of neural cell adhesion molecule 1 (NCAM1) and ultimately promoted perineural invasion. Moreover, NCAM1-deficient mice showed decreased neural invasion and less paralysis. Such Schwann cell behavior reflects normal Schwann cell programs that are typically activated in nerve repair but are instead exploited by cancer cells to promote perineural invasion and cancer progression.

  3. Innate Lymphoid Cells in Cancer.

    PubMed

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

    2015-10-01

    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.

  4. Innate Lymphoid Cells in Cancer.

    PubMed

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

    2015-10-01

    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. PMID:26438443

  5. Cancer stem cell signaling pathways.

    PubMed

    Matsui, William H

    2016-09-01

    Tissue development and homeostasis are governed by the actions of stem cells. Multipotent cells are capable of self-renewal during the course of one's lifetime. The accurate and appropriate regulation of stem cell functions is absolutely critical for normal biological activity. Several key developmental or signaling pathways have been shown to play essential roles in this regulatory capacity. Specifically, the Janus-activated kinase/signal transducer and activator of transcription, Hedgehog, Wnt, Notch, phosphatidylinositol 3-kinase/phosphatase and tensin homolog, and nuclear factor-κB signaling pathways have all been shown experimentally to mediate various stem cell properties, such as self-renewal, cell fate decisions, survival, proliferation, and differentiation. Unsurprisingly, many of these crucial signaling pathways are dysregulated in cancer. Growing evidence suggests that overactive or abnormal signaling within and among these pathways may contribute to the survival of cancer stem cells (CSCs). CSCs are a relatively rare population of cancer cells capable of self-renewal, differentiation, and generation of serially transplantable heterogeneous tumors of several types of cancer. PMID:27611937

  6. Cancer Chemotherapy: Past, Present, and Future—Part I

    PubMed Central

    Wright, Jane C.

    1984-01-01

    Cancer is of major concern today because of its high mortality. It is estimated that 66 million people in this country will eventually develop cancer; 1983 estimates were 855,000 new cases and 440,000 deaths from cancer. Because of limitations of surgery and radiation therapy in effecting a cure for cancer, chemotherapy has become increasingly important. The developments in the chemical control of cancer in man are encouraging. This two-part paper covers the historical milestones in the development of the chemical and hormonal control of cancer, present successes with the use of polychemotherapy, and the hopeful trends in research. Part II will be published in a future issue of this journal. PMID:6381742

  7. Guanylate-Binding Protein-1 protects ovarian cancer cell lines but not breast cancer cell lines from killing by paclitaxel.

    PubMed

    Tipton, Aaron R; Nyabuto, Geoffrey O; Trendel, Jill A; Mazur, Travis M; Wilson, John P; Wadi, Suzan; Justinger, Jacob S; Moore, Garret L; Nguyen, Peter T; Vestal, Deborah J

    2016-09-30

    Forced expression of the cytokine-induced large GTPase, human Guanylate-Binding Protein-1 (hGBP-1), in ovarian cancer cell lines increases resistance to paclitaxel. Elevated hGBP-1 RNA in ovarian tumors correlates with shorter recurrence-free survival. In contract, hGBP-1 is part of a gene signature predicting improved prognosis in all subtypes of breast cancers. hGBP-1 does not confer paclitaxel resistance on MCF-7 and TMX2-28 breast cancer cells. Expression of the isotype of the hGBP-1-interacting protein, PIM1, which may contribute to paclitaxel resistance when associated with hGBP-1, is different in breast and ovarian cancer cell lines. Breast cancer cell lines express the 44 kDa isoform of PIM-1, and ovarian cancer cell lines express the 33 kDa isoform. PMID:27590579

  8. Nanomechanical analysis of cells from cancer patients

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

  9. Mouth Cancer for Clinicians. Part 11: Cancer Treatment (Radiotherapy).

    PubMed

    Kalavrezos, Nicholas; Scully, Crispian

    2016-06-01

    A MEDLINE search early in 2015 revealed more than 250,000 papers on head and neck cancer; over 100,000 on oral cancer; and over 60,000 on mouth cancer. Not all publications contain robust evidence. We endeavour to encapsulate the most important of the latest information and advances now employed in practice, in a form comprehensible to healthcare workers, patients and their carers. This series offers the primary care dental team in particular, an overview of the aetiopathogenesis, prevention, diagnosis and multidisciplinary care of mouth cancer, the functional and psychosocial implications, and minimization of the impact on the quality of life of patient and family. Clinical Relevance: This article offers the dental team an overview of the use of radiotherapy, and its effects on the mouth and other tissues. PMID:27529915

  10. Cancer stem cells and metastasis.

    PubMed

    Sampieri, Katia; Fodde, Riccardo

    2012-06-01

    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.

  11. General Information about Small Cell Lung Cancer

    MedlinePlus

    ... Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  12. General Information about Renal Cell Cancer

    MedlinePlus

    ... Renal Cell Cancer Treatment (PDQ®)–Patient Version General Information About Renal Cell Cancer Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  13. Invasive cancer cells and metastasis

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia Tanja

    2013-12-01

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

  14. Alternative Fuels for Cancer Cells

    PubMed Central

    Keenan, Melissa; Chi, Jen-Tsan

    2015-01-01

    Tumor metabolism is significantly altered to support the various metabolic needs of tumor cells. The most prominent change is the increased tumor glycolysis that leads to increased glucose uptake and utilization. However, it has become obvious that many non-glucose nutrients, such as amino acids, lactate, acetate and macromolecules, can serve as alternative fuels for cancer cells. This knowledge reveals an unexpected flexibility and evolutionarily-conserved model in which cancer cells uptake nutrients from their external environment to fulfill their necessary energetic needs. It is possible that tumor cells have evolved the ability to utilize different carbon sources due to the limited supply of nutrient that can be driven by oncogenic mutations and tumor microenvironmental stresses. In certain cases, these factors permanently alter the tumor cells’ metabolism, causing certain nutrients to become indispensable and thus creating opportunities for therapeutic intervention to eradicate tumors by their metabolic vulnerabilities. PMID:25815843

  15. Prostate cancer stem cell biology

    PubMed Central

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

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of signaling pathways in prostate CSCs (4) involvement of prostate CSCs in metastasis of PCa and (5) microRNA-mediated regulation of prostate CSCs. Although definitive evidence for the identification and characterization of prostate CSCs still remains unclear, future directions pursuing therapeutic targets of CSCs may provide novel insights for the treatment of PCa. PMID:22402315

  16. Promise of cancer stem cell vaccine

    PubMed Central

    Zhou, Li; Lu, Lin; Wicha, Max S; Chang, Alfred E; Xia, Jian-chuan; Ren, Xiubao; Li, Qiao

    2015-01-01

    Dendritic cell (DC)-based vaccines designed to target cancer stem cells (CSC) can induce significant antitumor responses via conferring host anti-CSC immunity. Our recent studies have demonstrated that CSC-DC vaccine could inhibit metastasis of primary tumors and induce humoral immune responses against cancer stem cells. This approach highlights the promise of cancer stem cell vaccine in cancer immunotherapy. PMID:26337078

  17. NK Cells Preferentially Target Tumor Cells with a Cancer Stem Cell Phenotype

    PubMed Central

    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.

    2016-01-01

    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 dehydrogenasebright) 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. PMID:26363055

  18. NK Cells Preferentially Target Tumor Cells with a Cancer Stem Cell Phenotype.

    PubMed

    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

    2015-10-15

    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.

  19. Targeting the Checkpoint to Kill Cancer Cells.

    PubMed

    Benada, Jan; Macurek, Libor

    2015-01-01

    Cancer treatments such as radiotherapy and most of the chemotherapies act by damaging DNA of cancer cells. Upon DNA damage, cells stop proliferation at cell cycle checkpoints, which provides them time for DNA repair. Inhibiting the checkpoint allows entry to mitosis despite the presence of DNA damage and can lead to cell death. Importantly, as cancer cells exhibit increased levels of endogenous DNA damage due to an excessive replication stress, inhibiting the checkpoint kinases alone could act as a directed anti-cancer therapy. Here, we review the current status of inhibitors targeted towards the checkpoint effectors and discuss mechanisms of their actions in killing of cancer cells. PMID:26295265

  20. Targeting the Checkpoint to Kill Cancer Cells

    PubMed Central

    Benada, Jan; Macurek, Libor

    2015-01-01

    Cancer treatments such as radiotherapy and most of the chemotherapies act by damaging DNA of cancer cells. Upon DNA damage, cells stop proliferation at cell cycle checkpoints, which provides them time for DNA repair. Inhibiting the checkpoint allows entry to mitosis despite the presence of DNA damage and can lead to cell death. Importantly, as cancer cells exhibit increased levels of endogenous DNA damage due to an excessive replication stress, inhibiting the checkpoint kinases alone could act as a directed anti-cancer therapy. Here, we review the current status of inhibitors targeted towards the checkpoint effectors and discuss mechanisms of their actions in killing of cancer cells. PMID:26295265

  1. Why have ovarian cancer mortality rates declined? Part I. Incidence.

    PubMed

    Sopik, Victoria; Iqbal, Javaid; Rosen, Barry; Narod, Steven A

    2015-09-01

    The age-adjusted mortality rate from ovarian cancer in the United States has declined over the past several decades. The decline in mortality might be the consequence of a reduced number of cases (incidence) or a reduction in the proportion of patients who die from their cancer (case-fatality). In part I of this three-part series, we examine rates of ovarian cancer incidence and mortality from the Surveillance Epidemiology and End Results (SEER) registry database and we explore to what extent the observed decline in mortality can be explained by a downward shift in the stage distribution of ovarian cancer (i.e. due to early detection) or by fewer cases of ovarian cancer (i.e. due to a change in risk factors). The proportion of localized ovarian cancers did not increase, suggesting that a stage-shift did not contribute to the decline in mortality. The observed decline in mortality paralleled a decline in incidence. The trends in ovarian cancer incidence coincided with temporal changes in the exposure of women from different birth cohorts to various reproductive risk factors, in particular, to changes in the use of the oral contraceptive pill and to declining parity. Based on recent changes in risk factor propensity, we predict that the trend of the declining age-adjusted incidence rate of ovarian cancer in the United States will reverse and rates will increase in coming years. PMID:26080287

  2. Targeting Breast Cancer Stem Cells

    PubMed Central

    McDermott, Sean P.; Wicha, Max S.

    2010-01-01

    The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. Although, the CSC hypothesis does not directly address the cell of origin of cancer, it is postulated that tissue-resident stem or progenitors are the most common targets of transformation. Clinically, CSCs are predicted to mediate tumor recurrence after chemo- and radiation-therapy due to the relative inability of these modalities to effectively target CSCs. If this is the case, then CSC must be efficiently targeted to achieve a true cure. Similarities between normal and malignant stem cells, at the levels of cell-surface proteins, molecular pathways, cell cycle quiescence, and microRNA signaling present challenges in developing CSC-specific therapeutics. Approaches to targeting CSCs include the development of agents targeting known stem cell regulatory pathways as well as unbiased high-throughput siRNA or small-molecule screening. Based on studies of pathways present in normal stem cells, recent work has identified potential “Achilles heals” of CSC, whereas unbiased screening provides opportunities to identify new pathways utilized by CSC as well as develop potential therapeutic agents. Here, we review both approaches and their potential to effectively target breast CSC. PMID:20599450

  3. Glutathione in Cancer Cell Death

    PubMed Central

    Ortega, Angel L.; Mena, Salvador; Estrela, Jose M.

    2011-01-01

    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. PMID:24212662

  4. [Dendritic cells in cancer immunotherapy].

    PubMed

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

    2015-01-01

    Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are still first line treatments. Even so, there is a quantity of experimental evidence demonstrating that cancer cells are immunogenic. However, the effective activation of anti-cancer T cell responses closely depends on an efficient antigen presentation carried out by professional antigen presenting cells such as DC. Although there are a number of strategies to strengthen antigen presentation by DC, anti-cancer immunotherapy is not as effective as we would expect according to preclinical data accumulated in recent decades. We do not aim to make an exhaustive review of DC immunotherapy here, which is an extensive research subject already dealt with in many specialised reviews. Instead, we present the experimental approaches undertaken by our group over the last decade, by modifying DC to improve their anti-tumour capacities. PMID:26486534

  5. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  6. Prostate Cancer Stem Cells: Research Advances.

    PubMed

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

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

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

    ClinicalTrials.gov

    2013-08-14

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

  8. The effect of cancer procoagulant on expression of metastatic and angiogenic markers in breast cancer and embryonic stem cell lines.

    PubMed

    Kee, Nalise Low Ah; Naudé, Ryno J; Blatch, Gregory L; Frost, Carminita L

    2012-03-01

    Cancer procoagulant is present only in malignant tumours and the undifferentiated tissues of human placenta. Its possible role in angiogenesis and metastasis was investigated. Cancer procoagulant increased the steady-state mRNA level of L1 cell adhesion molecule (L1CAM) in MCF-7 breast cancer cells and E14 mouse embryonic stem cells (MESCs), while an increase in angiogenin mRNA was observed in MDA-MB-231 breast cancer cells. Furthermore, production of vascular endothelial growth factor (VEGF) protein in MCF-7 breast cancer cells and E14 MESCs, but decreased in MDA-MB-231 breast cancer cells. We conclude that cancer procoagulant could potentially play a part in angiogenesis in cancer and vascular development during embryonic development. PMID:22718627

  9. The effect of cancer procoagulant on expression of metastatic and angiogenic markers in breast cancer and embryonic stem cell lines.

    PubMed

    Kee, Nalise Low Ah; Naudé, Ryno J; Blatch, Gregory L; Frost, Carminita L

    2012-03-01

    Cancer procoagulant is present only in malignant tumours and the undifferentiated tissues of human placenta. Its possible role in angiogenesis and metastasis was investigated. Cancer procoagulant increased the steady-state mRNA level of L1 cell adhesion molecule (L1CAM) in MCF-7 breast cancer cells and E14 mouse embryonic stem cells (MESCs), while an increase in angiogenin mRNA was observed in MDA-MB-231 breast cancer cells. Furthermore, production of vascular endothelial growth factor (VEGF) protein in MCF-7 breast cancer cells and E14 MESCs, but decreased in MDA-MB-231 breast cancer cells. We conclude that cancer procoagulant could potentially play a part in angiogenesis in cancer and vascular development during embryonic development.

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

    PubMed Central

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

    2014-01-01

    Nowadays, the cancer stem cells are considered to be significantly responsible for growth, metastasis, invasion and recurrence of all cancer. Cancer stem cells are typically characterized by continuous proliferation and self-renewal as well as by differentiation potential, while stem cells are considered to differentiate into tissue- specific phenotype of mature cells under the influence of micro-environment. Cancer stem cells should be traced to the stem cells under the influence of a micro-environment, which induces malignant tumors. In this review, we propose this micro-environment as a ‘cancerous niche’ and discuss its importance on the formation and maintenance of cancer stem cells with the recent experimental results to establish cancer stem cell models from induced pluripotent stem cells. These models of cancer stem cell will provide the great advantages in cancer research and its therapeutic applications in the future. PMID:25075155

  11. Update in Cancer Chemotherapy: Gastrointestinal Cancer—Colorectal Cancer, Part 2

    PubMed Central

    Wright, Jane C.

    1986-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of gastrointestinal tract cancer is described in a multi-part series. Part 1 surveyed colorectal cancer and the use of single-agent chemotherapy in the April issue of the Journal. Part 2 of colorectal cancer will describe combination chemotherapy, preoperative and postoperative radiation, and combinations of chemotherapy and radiation, and adjuvant chemotherapy. In advanced gastrointestinal tract cancer, chemotherapy is only of palliative value with response rates generally under 50 percent and survival rates of several months to one year or more. Combination chemotherapy often produces higher response rates, yet there is no acceptable evidence that survival is improved. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers may be due to lack of data. PMID:3519988

  12. Multiple Myeloma Cancer Stem Cells

    PubMed Central

    Huff, Carol Ann; Matsui, William

    2008-01-01

    Multiple myeloma is characterized by the clonal expansion of neoplastic plasma cells within the bone marrow, elevated serum immunoglobulin, and osteolytic bone disease. The disease is highly responsive to a wide variety of anticancer treatments including conventional cytotoxic chemotherapy, corticosteroids, radiation therapy, and a growing number of agents with novel mechanisms of action. However, few if any patients are cured with these modalities and relapse remains a critical issue. A better understanding of clonogenic multiple myleoma cells is essential to ultimately improving long-term outcomes, but the nature of the cells responsible for myeloma regrowth and disease relapse is unclear. We review evidence that functional heterogeneity exists in multiple myeloma and discuss potential strategies and clinical implications of the stem-cell model of cancer in this disease. PMID:18539970

  13. How cell death shapes cancer

    PubMed Central

    Labi, V; Erlacher, M

    2015-01-01

    Apoptosis has been established as a mechanism of anti-cancer defense. Members of the BCL-2 family are critical mediators of apoptotic cell death in health and disease, often found to be deregulated in cancer and believed to lead to the survival of malignant clones. However, over the years, a number of studies pointed out that a model in which cell death resistance unambiguously acts as a barrier against malignant disease might be too simple. This is based on paradoxical observations made in tumor patients as well as mouse models indicating that apoptosis can indeed drive tumor formation, at least under certain circumstances. One possible explanation for this phenomenon is that apoptosis can promote proliferation critically needed to compensate for cell loss, for example, upon therapy, and to restore tissue homeostasis. However, this, at the same time, can promote tumor development by allowing expansion of selected clones. Usually, tissue resident stem/progenitor cells are a major source for repopulation, some of them potentially carrying (age-, injury- or therapy-induced) genetic aberrations deleterious for the host. Thereby, apoptosis might drive genomic instability by facilitating the emergence of pathologic clones during phases of proliferation and subsequent replication stress-associated DNA damage. Tumorigenesis initiated by repeated cell attrition and repopulation, as confirmed in different genetic models, has parallels in human cancers, exemplified in therapy-induced secondary malignancies and myelodysplastic syndromes in patients with congenital bone marrow failure syndromes. Here, we aim to review evidence in support of the oncogenic role of stress-induced apoptosis. PMID:25741600

  14. Extinction models for cancer stem cell therapy

    PubMed Central

    Sehl, Mary; Zhou, Hua; Sinsheimer, Janet S.; Lange, Kenneth L.

    2012-01-01

    Cells with stem cell-like properties are now viewed as initiating and sustaining many cancers. This suggests that cancer can be cured by driving these cancer stem cells to extinction. The problem with this strategy is that ordinary stem cells are apt to be killed in the process. This paper sets bounds on the killing differential (difference between death rates of cancer stem cells and normal stem cells) that must exist for the survival of an adequate number of normal stem cells. Our main tools are birth–death Markov chains in continuous time. In this framework, we investigate the extinction times of cancer stem cells and normal stem cells. Application of extreme value theory from mathematical statistics yields an accurate asymptotic distribution and corresponding moments for both extinction times. We compare these distributions for the two cell populations as a function of the killing rates. Perhaps a more telling comparison involves the number of normal stem cells NH at the extinction time of the cancer stem cells. Conditioning on the asymptotic time to extinction of the cancer stem cells allows us to calculate the asymptotic mean and variance of NH. The full distribution of NH can be retrieved by the finite Fourier transform and, in some parameter regimes, by an eigenfunction expansion. Finally, we discuss the impact of quiescence (the resting state) on stem cell dynamics. Quiescence can act as a sanctuary for cancer stem cells and imperils the proposed therapy. We approach the complication of quiescence via multitype branching process models and stochastic simulation. Improvements to the τ-leaping method of stochastic simulation make it a versatile tool in this context. We conclude that the proposed therapy must target quiescent cancer stem cells as well as actively dividing cancer stem cells. The current cancer models demonstrate the virtue of attacking the same quantitative questions from a variety of modeling, mathematical, and computational perspectives

  15. Anatomical relationship between traditional acupuncture point ST 36 and Omura's ST 36 (True ST 36) with their therapeutic effects: 1) inhibition of cancer cell division by markedly lowering cancer cell telomere while increasing normal cell telomere, 2) improving circulatory disturbances, with reduction of abnormal increase in high triglyceride, L-homocystein, CRP, or cardiac troponin I & T in blood by the stimulation of Omura's ST 36--Part 1.

    PubMed

    Omura, Yoshiaki; Chen, Yemeng; Lu, Dominic P; Shimotsura, Yasuhiro; Ohki, Motomu; Duvvi, Harsha

    2007-01-01

    Using Bi-Digital O-Ring Test Resonance Phenomena between 2 identical substances, Omura, Y. succeeded in making the image of the outline of internal organs without use of standard imaging devices since 1982. When he imaged the outline of the stomach on the abdominal wall, a number of the lines came out from upper and lower parts of stomach wall. When the lines were followed, they were very close to the well-known stomach meridians. Subsequently, he found a method of localizing meridians and their corresponding acupuncture points as well as shapes and diameters accurately. At the anatomical location of ST 36 described in traditional textbooks, Omura, Y. found there is no acupuncture point. However, in the close vicinity, there is an acupuncture point which he named as true ST 36 in the mid 1980s, but it is generally known as Omura's ST 36. When the effects of the acupuncture on these 2 locations were compared, Omura's ST 36 (true ST 36) produced very significant well-known acupuncture beneficial effects including improved circulation and blood chemistry, while in the traditional ST 36, the effects were small. In this article, the anatomical relationship between these two acupuncture points, with a short distance of 0.6 approximately 1.5 cm between the centers of these locations, was described. In early 2000, Omura, Y. found Press Needle Stimulation of Omura's ST 36, using "Press-Release" procedure repeated 200 times, 4 times a day to cancer patients reduced high cancer cell telomere of 600-1500ng and high Oncogen C-fos Ab2 and Integrin alpha5beta1 of 100-700ng BDORT units to close to lyg (= 10(-24) g) BDORT units. In addition there was a significant reduction of Asbestos and Hg from cancer cells, while markedly reduced normal cell telomere of lyg was increased to optimally high amounts of 500-530ng BDORTunits. Thus, cancer cells can no longer divide and cancer activity is inhibited. The authors have successfully applied this method for a variety of cancers as well as

  16. Cancer Cell Fusion: Mechanisms Slowly Unravel

    PubMed Central

    Noubissi, Felicite K.; Ogle, Brenda M.

    2016-01-01

    Although molecular mechanisms and signaling pathways driving invasion and metastasis have been studied for many years, the origin of the population of metastatic cells within the primary tumor is still not well understood. About a century ago, Aichel proposed that cancer cell fusion was a mechanism of cancer metastasis. This hypothesis gained some support over the years, and recently became the focus of many studies that revealed increasing evidence pointing to the possibility that cancer cell fusion probably gives rise to the metastatic phenotype by generating widespread genetic and epigenetic diversity, leading to the emergence of critical populations needed to evolve resistance to the treatment and development of metastasis. In this review, we will discuss the clinical relevance of cancer cell fusion, describe emerging mechanisms of cancer cell fusion, address why inhibiting cancer cell fusion could represent a critical line of attack to limit drug resistance and to prevent metastasis, and suggest one new modality for doing so. PMID:27657058

  17. Mast cells, angiogenesis and cancer.

    PubMed

    Ribatti, Domenico; Crivellato, Enrico

    2011-01-01

    Mast cells (MCs) were first described by Paul Ehrlich 1 in his doctoral thesis. MCs have long been implicated in the pathogenesis of allergic reactions and certain protective responses to parasites. As most tumors contain inflammatory cell infiltrates, which often include plentiful MCs, the question as to the possible contribution of MCs to tumor development has progressively been emerging. In this chapter, the specific involvement of MCs in tumor biology and tumor fate will be considered, with particular emphasis on the capacity of these cells to stimulate tumor growth by promoting angiogenesis and lymphangiogenesis. Data from experimental carcinogenesis and from different tumor settings in human pathology will be summarized. Information to be presented will suggest that MCs may serve as a novel therapeutic target for cancer treatment. PMID:21713661

  18. The biology of cancer stem cells.

    PubMed

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

    2007-01-01

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

  19. Restoration of normal phenotype in cancer cells

    DOEpatents

    Bissell, M.J.; Weaver, V.M.

    1998-12-08

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying {beta}{sub 1} integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive. 14 figs.

  20. Restoration of normal phenotype in cancer cells

    DOEpatents

    Bissell, Mina J.; Weaver, Valerie M.

    1998-01-01

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  1. Skin cancer in solid organ transplant recipients: advances in therapy and management: part I. Epidemiology of skin cancer in solid organ transplant recipients.

    PubMed

    Zwald, Fiona O'Reilly; Brown, Marc

    2011-08-01

    Skin cancer is the most frequent malignancy in organ transplant recipients, 95% of which are nonmelanoma skin cancer, especially squamous cell and basal cell carcinomas. This paper also discusses the incidence of other tumors (eg, melanoma, Merkel cell carcinoma, and Kaposi sarcoma) that are also increased in organ transplant patients compared to the general population. Part I of this two-part series describes the latest data concerning the epidemiologic and pathogenic aspects of nonmelanoma skin cancer development in solid organ transplant recipients. This review also highlights the concept of "field cancerization," represented by extensive areas of actinic damage and epidermal dysplasia, which accounts for increased risk of aggressive skin cancer development in susceptible patients. PMID:21763561

  2. Deregulation of Cell Signaling in Cancer

    PubMed Central

    Giancotti, Filippo G.

    2014-01-01

    Summary Oncogenic mutations disrupt the regulatory circuits that govern cell function, enabling tumor cells to undergo de-regulated mitogenesis, to resist to proapoptotic insults, and to invade through tissue boundaries. Cancer cell biology has played a crucial role in elucidating the signaling mechanisms by which oncogenic mutations sustain these malignant behaviors and thereby in identifying rational targets for cancer drugs. The efficacy of such targeted therapies illustrate the power of a reductionist approach to the study of cancer. PMID:24561200

  3. Cancer stem cells niche: a target for novel cancer therapeutics.

    PubMed

    Yi, Shan-Yong; Hao, Yi-Bin; Nan, Ke-Jun; Fan, Tian-Li

    2013-05-01

    Nowadays, cancer has been a frequent disease, and the first or second most common cause of death worldwide. Despite a better understanding of the biology of cancer cells, the therapy of most cancers has not significantly changed for the past four decades. It is because conventional chemotherapies and/or radiation therapies are usually designed to eradicate highly proliferative cells. Mounting evidence has implicated that cancer is a disease of stem cells. Cancer stem cells (CSC) are often relatively quiescent, and therefore may not be affected by therapies targeting rapidly dividing cells. Like normal stem cells (NSC) residing in a "stem cell niche" that maintains them in a stem-like state, CSC also require a special microenvironment to control their self-renewal and undifferentiated state. The "CSC niche" is likely to be the most crucial target in the treatment of cancer. In this article, we summarize the current knowledge regarding CSC and their niche microenvironments. Understanding of CSC's origin, molecular profile, and interaction with their microenvironments, this could be a paradigm shift in the treatment of cancer, away from targeting the blast cells and towards the targeting of the CSC, thus improving therapeutic outcome.

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

    MedlinePlus

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

  5. Pharmacogenomics: from cell to clinic (Part 1).

    PubMed

    Siest, Gérard; Medeiros, Rui; Melichar, Bohuslav; Stathopoulou, Maria; Van Schaik, Ron H N; Cacabelos, Ramon; Abt, Peter Meier; Monteiro, Carolino; Gurwitz, David; Queiroz, Jao; Mota-Filipe, Helder; Ndiaye, Ndieye Coumba; Visvikis-Siest, Sophie

    2014-04-01

    The second international European Society of Pharmacogenomics and Theranostics (ESPT) conference was organized in Lisbon, Portugal, and attracted 250 participants from 37 different countries. The participants could listen to 50 oral presentations, participate in five lunch symposia and were able to view 83 posters and an exhibition. The first part of this Conference Scene will focus on the pharmacogenomics and biomarkers used in medical oncology, and in particular solid tumors. In addition, this article covers the two keynote conference introductory lectures by Ann K Daly and Magnus Ingelman-Sundberg. The second part of this article will discuss the clinical implementation of pharmacogenomic tests; the role of transports and pharmacogenomics; how stem cells and other new tools are helping the development of pharmacogenomics and drug discovery; and an update on the clinical translation of pharmacogenomics to personalized medicine. Part two of this Conference Scene will be featured in the next issue of Pharmacogenomics.

  6. Pharmacogenomics: from cell to clinic (Part 1).

    PubMed

    Siest, Gérard; Medeiros, Rui; Melichar, Bohuslav; Stathopoulou, Maria; Van Schaik, Ron H N; Cacabelos, Ramon; Abt, Peter Meier; Monteiro, Carolino; Gurwitz, David; Queiroz, Jao; Mota-Filipe, Helder; Ndiaye, Ndieye Coumba; Visvikis-Siest, Sophie

    2014-04-01

    The second international European Society of Pharmacogenomics and Theranostics (ESPT) conference was organized in Lisbon, Portugal, and attracted 250 participants from 37 different countries. The participants could listen to 50 oral presentations, participate in five lunch symposia and were able to view 83 posters and an exhibition. The first part of this Conference Scene will focus on the pharmacogenomics and biomarkers used in medical oncology, and in particular solid tumors. In addition, this article covers the two keynote conference introductory lectures by Ann K Daly and Magnus Ingelman-Sundberg. The second part of this article will discuss the clinical implementation of pharmacogenomic tests; the role of transports and pharmacogenomics; how stem cells and other new tools are helping the development of pharmacogenomics and drug discovery; and an update on the clinical translation of pharmacogenomics to personalized medicine. Part two of this Conference Scene will be featured in the next issue of Pharmacogenomics. PMID:24798716

  7. Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway

    SciTech Connect

    Ahn, Hee-Jin; Kim, Gwangil; Park, Kyung-Soon

    2013-08-09

    Highlights: •Ell3 enhances proliferation and drug resistance of breast cancer cell lines. •Ell3 is related to the cancer stem cell characteristics of breast cancer cell lines. •Ell3 enhances oncogenicity of breast cancer through the ERK1/2 signaling pathway. -- Abstract: Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven−nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF-7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK−extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. These results suggest that Ell3 may play a critical role in promoting oncogenesis in breast cancer by regulating cell proliferation and cancer stem cell properties via the ERK1/2 signaling pathway.

  8. miRNAs expressed differently in cancer stem cells and cancer cells of human gastric cancer cell line MKN-45.

    PubMed

    Golestaneh, Azadeh Fahim; Atashi, Amir; Langroudi, Lida; Shafiee, Abbas; Ghaemi, Nasser; Soleimani, Masoud

    2012-07-01

    Recent studies show that cancers may originate from special cells named cancer stem cells (CSCs). As miRNAs have a prominent role in regulating cell activities, a question arise, that is, if there is any difference in miRNA expression level between CSC and other cancer cells of human gastric cancer cell line MKN-45. In this study, CSCs were isolated by fluorescence-activated cell sorter based on the expression level of cell surface marker CD44. CSC characteristics were checked using spheroid formation assay and soft agar assay. Using reverse transcriptase polymerase chain reaction (RT-PCR), the expression level of some stemness genes was studied. Real-time q-PCR was used for analysis of the expression level of miRNAs. CSCs were able to make spheroids and colonies, whereas other cancer cells failed to show aforementioned features. In addition, RT-PCR resulted in a difference in the expression levels of Nanog, Sox2, Lin28 and Oct-4 between these two kinds of cells. Real-time RT-PCR analysis demonstrated an increase in mir-21 and mir-302 expression level in CSCs, relative to cancer cells, whereas let-7a expression level was decreased in CSC in comparison with cancer cells, which may be due to their different differentiation level. On the other hand, mir-372, mir-373 and mir-520c-5p were markedly increased in cancer cells in comparison with CSCs. This study shows that there is a difference in miRNA expression level between CSCs and other cancer cells, which reflects dissimilar molecular pathways in these cells. These miRNAs may be promising objects for targeting CSCs specifically and efficiently.

  9. Radiofrequency treatment alters cancer cell phenotype

    PubMed Central

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

    2015-01-01

    The importance of evaluating physical cues in cancer research is gradually being realized. Assessment of cancer cell physical appearance, or phenotype, may provide information on changes in cellular behavior, including migratory or communicative changes. These characteristics are intrinsically different between malignant and non-malignant cells and change in response to therapy or in the progression of the disease. Here, we report that pancreatic cancer cell phenotype was altered in response to a physical method for cancer therapy, a non-invasive radiofrequency (RF) treatment, which is currently being developed for human trials. We provide a battery of tests to explore these phenotype characteristics. Our data show that cell topography, morphology, motility, adhesion and division change as a result of the treatment. These may have consequences for tissue architecture, for diffusion of anti-cancer therapeutics and cancer cell susceptibility within the tumor. Clear phenotypical differences were observed between cancerous and normal cells in both their untreated states and in their response to RF therapy. We also report, for the first time, a transfer of microsized particles through tunneling nanotubes, which were produced by cancer cells in response to RF therapy. Additionally, we provide evidence that various sub-populations of cancer cells heterogeneously respond to RF treatment. PMID:26165830

  10. Radiofrequency treatment alters cancer cell phenotype

    NASA Astrophysics Data System (ADS)

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

    2015-07-01

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

  11. Inside the 2016 American Society of Clinical Oncology Genitourinary Cancers Symposium: part 1 - kidney cancer.

    PubMed

    Buti, Sebastiano; Ciccarese, Chiara; Iacovelli, Roberto; Bersanelli, Melissa; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo; Tortora, Giampaolo; Massari, Francesco

    2016-09-01

    The American Society of Clinical Oncology Genitourinary Cancers Symposium, Moscone West Building, San Francisco, CA, USA, 7-9 January 2016 The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held in San Francisco (CA, USA), from 7 to 9 January 2016, focused on 'patient-centric care: translating research to results'. Every year, this meeting is a must for anyone studying genitourinary tumors to keep abreast of the most recent innovations in this field, exchange views on behaviors customarily adopted in daily clinical practice, and discuss future topics of scientific research. This two-part report highlights the key themes presented at the 2016 ASCO Genitourinary Cancers Symposium, with part 1 reporting the main novelties of kidney cancer and part 2 discussing the most relevant issues which have emerged for bladder and prostate tumors.

  12. Future Prospects in Breast Cancer Research – Cancer Stem Cells

    PubMed Central

    Franke, Henk R.; Klaase, Joost M.; Brinkhuis, Mariël; van den Berg, Albert; Vermes, István

    2012-01-01

    Breast cancer is one of the leading causes of cancer deaths among women. Although significant advances in the prevention, diagnosis and management are made, still every year half a million women die of breast cancer. Personalised treatment has the potential to increase treatment efficacy, and hence decrease mortality rates. Moreover, understanding cancer biology and translating this knowledge to the clinic, will improve the breast cancer therapy regime tremendously. Recently, it has been proposed that cancer stem cells (CSC) play an important role in tumour biology. CSC have the ability for self-renewal and are pivotal in setting the heterogeneous character of a tumour. Additionally, CSC possess several characteristics that make them resistant and more aggressive to the conventional chemo- and radiotherapy. Nowadays, breast cancer therapy is focused on killing the differentiated tumour cells, leaving the CSC unharmed, potentially causing recurrence of the disease and metastasis. Specific targeting of the CSC will improve the disease-free survival of breast cancer patients. In this article, two methods are described, aiming at specifically attacking the differentiated tumour cells (‘Apoptosis chip’) and the cancer stem cell. For this, microfluidics is used.

  13. Cancer stem cell targeted therapy: progress amid controversies

    PubMed Central

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

    2015-01-01

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

  14. Cancer stem cells in glioblastoma

    PubMed Central

    Lathia, Justin D.; Mack, Stephen C.; Mulkearns-Hubert, Erin E.; Valentim, Claudia L.L.; Rich, Jeremy N.

    2015-01-01

    Tissues with defined cellular hierarchies in development and homeostasis give rise to tumors with cellular hierarchies, suggesting that tumors recapitulate specific tissues and mimic their origins. Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor and contains self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumor initiation and therapeutic resistance. As normal stem and progenitor cells participate in tissue development and repair, these developmental programs re-emerge in CSCs to support the development and progressive growth of tumors. Elucidation of the molecular mechanisms that govern CSCs has informed the development of novel targeted therapeutics for GBM and other brain cancers. CSCs are not self-autonomous units; rather, they function within an ecological system, both actively remodeling the microenvironment and receiving critical maintenance cues from their niches. To fulfill the future goal of developing novel therapies to collapse CSC dynamics, drawing parallels to other normal and pathological states that are highly interactive with their microenvironments and that use developmental signaling pathways will be beneficial. PMID:26109046

  15. Cancer stem cells of the digestive system.

    PubMed

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

    2014-12-01

    Stem cells of the digestive system are ideal in many ways for research, given they are abundant, highly proliferative and have a uniform structural arrangement. This in turn has enormously aided the research of cancer stem cells of the digestive system, which is now shaping our understanding of cancer stem cells. In this review, the recent advances in the understanding of cancer stem cells of the digestive system have been summarized, including aspects such as their identification, origin, cell-cycle dormancy, relationship with epithelial-mesenchymal transition, cellular metabolism and the underlying molecular mechanisms. Newly acquired knowledge concerning cancer stem cells have led to the development of novel cancer therapeutics with provisional yet encouraging results.

  16. Allograft Cancer Cell Transplantation in Zebrafish.

    PubMed

    Moore, John C; Langenau, David M

    2016-01-01

    Allogeneic cell transplantation is the transfer of cells from one individual into another of the same species and has become an indispensable technique for studying development, immunology, regeneration and cancer biology. In experimental settings, tumor cell engraftment into immunologically competent recipients has greatly increased our understanding of the mechanisms that drive self-renewal, progression and metastasis in vivo. Zebrafish have quickly emerged as a powerful genetic model of cancer that has benefited greatly from allogeneic transplantation. Efficient engraftment can be achieved by transplanting cells into either early larval stage zebrafish that have not yet developed a functional acquired immune system or adult zebrafish following radiation or chemical ablation of the immune system. Alternatively, transplantation can be completed in adult fish using either clonal syngeneic strains or newly-generated immune compromised zebrafish models that have mutations in genes required for proper immune cell function. Here, we discuss the current state of cell transplantation as it pertains to zebrafish cancer and the available models used for dissecting important processes underlying cancer. We will also use the zebrafish model to highlight the power of cell transplantation, including its capacity to dynamically assess functional heterogeneity within individual cancer cells, visualize cancer progression and evolution, assess tumor-propagating potential and self-renewal, image cancer cell invasion and dissemination and identify novel therapies for treating cancer. PMID:27165358

  17. CASPASE CONTROL: PROTAGONISTS OF CANCER CELL APOPTOSIS

    PubMed Central

    Fiandalo, M.V.; Kyprianou, N.

    2013-01-01

    Emergence of castration-resistant metastatic prostate cancer is due to activation of survival pathways, including apoptosis suppression and anoikis resistance, and increased neovascularization. Thus targeting of apoptotic players is of critical significance in prostate cancer therapy since loss of apoptosis and resistance to anoikis are critical in aberrant malignant growth, metastasis and conferring therapeutic failure. The majority of therapeutic agents act through intrinsic mitochondrial, extrinsic death receptor pathways or endoplasmic reticulum stress pathways to induce apoptosis. Current therapeutic strategies target restoring regulatory molecules that govern the pro-survival pathways such as PTEN which regulates AKT activity. Other strategies focus on reactivating the apoptotic pathways either by down-regulating anti-apoptotic players such as BCL-2 or by up-regulating pro-apoptotic protein families, most notably, the caspases. Caspases are a family of cystine proteases which serve critical roles in apoptotic and inflammatory signaling pathways. During tumorigenesis, significant loss or inactivation of lead members in the caspase family leads to impairing apoptosis induction, causing a dramatic imbalance in the growth dynamics, ultimately resulting in aberrant growth of human cancers. Recent exploitation of apoptosis pathways towards re-instating apoptosis induction via caspase re-activation has provided new molecular platforms for the development of therapeutic strategies effective against advanced prostate cancer as well as other solid tumors. This review will discuss the current cellular landscape featuring the caspase family in tumor cells and their activation via pharmacologic intervention towards optimized anti-cancer therapeutic modalities. This article is part of a Special Issue entitled “Apoptosis: Four Decades Later”. PMID:23070001

  18. Interfacial geometry dictates cancer cell tumorigenicity

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  19. Single-Cell Analysis in Cancer Genomics.

    PubMed

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

    2015-10-01

    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

  20. Review of MicroRNA Deregulation in Oral Cancer. Part I

    PubMed Central

    Miloro, Michael; Zhou, Xiaofeng

    2011-01-01

    ABSTRACT Objectives Oral cancer is the sixth most common malignancy worldwide. Cancer development and progression requires inactivation of tumour suppressor genes and activation of proto-oncogenes. Expression of these genes is in part dependant on RNA and microRNA based mechanisms. MicroRNAs are essential regulators of diverse cellular processes including proliferation, differentiation, apoptosis, survival, motility, invasion and morphogenesis. Several microRNAs have been found to be aberrantly expressed in various cancers including oral cancer. The purpose of this article was to review the literature related to microRNA deregulation in the head and neck/oral cavity cancers. Material and Methods A comprehensive review of the available literature from 2000 to 2011 relevant to microRNA deregulation in oral cancer was undertaken using PubMed, Medline, Scholar Google and Scopus. Keywords for the search were: microRNA and oral cancer, microRNA and squamous cell carcinoma, microRNA deregulation. Only full length articles in the English language were included. Strengths and limitations of each study are presented in this review. Results Several studies were identified that investigated microRNA alternations in the head and neck/oral cavity cancers. Significant progress has been made in identification of microRNA deregulation in these cancers. It has been evident that several microRNAs were found to be deregulated specifically in oral cavity cancers. Among these, several microRNAs have been functionally validated and their potential target genes have been identified. Conclusions These findings on microRNA deregulation in cancer further enhance our understanding of the disease progression, response to treatment and may assist with future development of targeted therapy. PMID:24421988

  1. Lost expression of DCC gene in ovarian cancer and its inhibition in ovarian cancer cells.

    PubMed

    Meimei, Liu; Peiling, Li; Baoxin, Li; Changmin, Li; Rujin, Zhuang; Chunjie, Hu

    2011-03-01

    Ovarian cancer is a leading cause of cancer-related women mortality in China. In recent years, the molecular mechanisms involved in ovarian carcinoma development and/or progression have been intensely studied, and several genes have been identified. Deleted in Colorectal Carcinoma (DCC), is an important tumor suppressor gene, which is inactivated in many kinds of tumors, and its function(s) is not clarified. Even though the lost expression of DCC occurred in later stages of multistep colorectal carcinogenesis, its contribution to the onset or progression of ovarian cancer is not fully understood. To investigate DCC expression in ovarian cancer, we studied 254 clinical samples by RT-PCR. Our results revealed that 52% malignant ovarian cancer did not express DCC gene. By contrast, DCC expression was observed in all normal ovary tissues and 80% benign ovarian tumors. Obviously, there was a significant correlation between DCC expression and ovarian cancer, especially in the epithelial ovarian cancer. The present study also suggested that the loss expression of DCC occurred more frequently in the cases of later clinical stage, higher pathological grade, and poorer prognosis. In the other part of this study, we further explored DCC expression after transfection in two kinds of ovarian cancer cell lines, namely SKOV3 cell and HO-8910 cell, using RT-PCR and immunocytochemistry. The results indicated that DCC expressed in SKOV3-DCC and HO-8910-DCC cells, and ultrastructural analysis showed the appearance of apoptotic features in them. Furthermore, cell growth was markedly down-regulated in above groups of cells, indicating that transfection with the DCC constructs can suppress the growth of tumor cells. In conclusion, our results suggest an association of lost expression of DCC with the ovarian cancer, and DCC gene may inhibit the growth of ovarian carcinoma cells. However, this result needs further trials with a larger sample. PMID:20054719

  2. Learning about Cancer by Studying Stem Cells

    MedlinePlus

    ... About Cancer by Studying Stem Cells Inside Life Science View All Articles | Inside Life Science Home Page Learning About Cancer by Studying Stem ... Once Upon a Stem Cell This Inside Life Science article also appears on LiveScience . Learn about related ...

  3. Cancer modelling in the NGS era - Part I: Emerging technology and initial modelling.

    PubMed

    Rovigatti, Ugo

    2015-11-01

    It is today indisputable that great progresses have been made in our molecular understanding of cancer cells, but an effective implementation of such knowledge into dramatic cancer-cures is still belated and yet desperately needed. This review gives a snapshot at where we stand today in this search for cancer understanding and definitive treatments, how far we have progressed and what are the major obstacles we will have to overcome both technologically and for disease modelling. In the first part, promising 3rd/4th Generation Sequencing Technologies will be summarized (particularly IonTorrent and OxfordNanopore technologies). Cancer modelling will be then reviewed from its origin in XIX Century Germany to today's NGS applications for cancer understanding and therapeutic interventions. Developments after Molecular Biology revolution (1953) are discussed as successions of three phases. The first, PH1, labelled "Clonal Outgrowth" (from 1960s to mid 1980s) was characterized by discoveries in cytogenetics (Nowell, Rowley) and viral oncology (Dulbecco, Bishop, Varmus), which demonstrated clonality. Treatments were consequently dominated by a "cytotoxic eradication" strategy with chemotherapeutic agents. In PH2, (from the mid 1980s to our days) the description of cancer as "Gene Networks" led to targeted-gene-therapies (TGTs). TGTs are the focus of Section 3: in view of their apparent failing (Ephemeral Therapies), alternative strategies will be discussed in review part II (particularly cancer immunotherapy, CIT). Additional Pitfalls impinge on the concepts of tumour heterogeneity (inter/intra; ITH). The described pitfalls set the basis for a new phase, PH3, which is called "NGS Era" and will be also discussed with ten emerging cancer models in the Review 2nd part.

  4. Cancer modelling in the NGS era - Part I: Emerging technology and initial modelling.

    PubMed

    Rovigatti, Ugo

    2015-11-01

    It is today indisputable that great progresses have been made in our molecular understanding of cancer cells, but an effective implementation of such knowledge into dramatic cancer-cures is still belated and yet desperately needed. This review gives a snapshot at where we stand today in this search for cancer understanding and definitive treatments, how far we have progressed and what are the major obstacles we will have to overcome both technologically and for disease modelling. In the first part, promising 3rd/4th Generation Sequencing Technologies will be summarized (particularly IonTorrent and OxfordNanopore technologies). Cancer modelling will be then reviewed from its origin in XIX Century Germany to today's NGS applications for cancer understanding and therapeutic interventions. Developments after Molecular Biology revolution (1953) are discussed as successions of three phases. The first, PH1, labelled "Clonal Outgrowth" (from 1960s to mid 1980s) was characterized by discoveries in cytogenetics (Nowell, Rowley) and viral oncology (Dulbecco, Bishop, Varmus), which demonstrated clonality. Treatments were consequently dominated by a "cytotoxic eradication" strategy with chemotherapeutic agents. In PH2, (from the mid 1980s to our days) the description of cancer as "Gene Networks" led to targeted-gene-therapies (TGTs). TGTs are the focus of Section 3: in view of their apparent failing (Ephemeral Therapies), alternative strategies will be discussed in review part II (particularly cancer immunotherapy, CIT). Additional Pitfalls impinge on the concepts of tumour heterogeneity (inter/intra; ITH). The described pitfalls set the basis for a new phase, PH3, which is called "NGS Era" and will be also discussed with ten emerging cancer models in the Review 2nd part. PMID:26427785

  5. Do cancer cells undergo phenotypic switching? The case for imperfect cancer stem cell markers

    PubMed Central

    Zapperi, Stefano; La Porta, Caterina A. M.

    2012-01-01

    The identification of cancer stem cells in vivo and in vitro relies on specific surface markers that should allow to sort cancer cells in phenotypically distinct subpopulations. Experiments report that sorted cancer cell populations after some time tend to express again all the original markers, leading to the hypothesis of phenotypic switching, according to which cancer cells can transform stochastically into cancer stem cells. Here we explore an alternative explanation based on the hypothesis that markers are not perfect and are thus unable to identify all cancer stem cells. Our analysis is based on a mathematical model for cancer cell proliferation that takes into account phenotypic switching, imperfect markers and error in the sorting process. Our conclusion is that the observation of reversible expression of surface markers after sorting does not provide sufficient evidence in support of phenotypic switching. PMID:22679555

  6. Pericellular hydrogel/nanonets inhibit cancer cells.

    PubMed

    Kuang, Yi; Shi, Junfeng; Li, Jie; Yuan, Dan; Alberti, Kyle A; Xu, Qiaobing; Xu, Bing

    2014-07-28

    Fibrils formed by proteins are vital components for cells. However, selective formation of xenogenous nanofibrils of small molecules on mammalian cells has yet to be observed. Here we report an unexpected observation of hydrogel/nanonets of a small D-peptide derivative in pericellular space. Surface and secretory phosphatases dephosphorylate a precursor of a hydrogelator to trigger the self-assembly of the hydrogelator and to result in pericellular hydrogel/nanonets selectively around the cancer cells that overexpress phosphatases. Cell-based assays confirm that the pericellular hydrogel/nanonets block cellular mass exchange to induce apoptosis of cancer cells, including multidrug-resistance (MDR) cancer cells, MES-SA/Dx5. Pericellular hydrogel/nanonets of small molecules to exhibit distinct functions illustrates a fundamentally new way to engineer molecular assemblies spatiotemporally in cellular microenvironment for inhibiting cancer cell growth and even metastasis.

  7. Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells

    SciTech Connect

    Uchino, Keita; Hirano, Gen; Hirahashi, Minako; Isobe, Taichi; Shirakawa, Tsuyoshi; Kusaba, Hitoshi; Baba, Eishi; Tsuneyoshi, Masazumi; Akashi, Koichi

    2012-09-10

    There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 protein to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation. -- Highlights: Black-Right-Pointing-Pointer Nanog maintains pluripotency by regulating embryonic stem cells differentiation. Black-Right-Pointing-Pointer Nanog is expressed in cancer stem cells of human gastrointestinal cancer cells. Black-Right-Pointing-Pointer Nucleotide sequencing revealed that Nanog pseudogene8 but not Nanog was expressed. Black-Right-Pointing-Pointer Nanog pseudogene8 promotes cancer stem cells proliferation. Black-Right-Pointing-Pointer Nanog pseudogene8 is involved in gastrointestinal cancer development.

  8. In search of liver cancer stem cells.

    PubMed

    Ma, Stephanie; Chan, Kwok Wah; Guan, Xin-Yuan

    2008-09-01

    Recent research efforts in stem cell and cancer biology have put forth a "stem cell model of carcinogenesis" which stipulates that the capability to maintain tumor formation and growth specifically resides in a small population of cells called cancer stem cells. The stem cell-like characteristics of these cells, including their ability to self-renew and differentiate; and their limited number within the bulk of the tumor mass, are believed to account for their capability to escape conventional therapies. In the past few years, the hypothesis of stem cell-driven tumorigenesis in liver cancer has received substantial support from the recent ability to identify and isolate a subpopulation of liver cancer cells that is not only able to initiate tumor growth, but also serially establish themselves as tumor xenografts with high efficiency and consistency. In this review, stem cell biology that contributes to explain tumor development in the particular context of liver cancer will be discussed. We will begin by briefly considering the knowledge available on normal liver stem cells and their role in tissue renewal and regeneration. We will then summarize the current scientific knowledge of liver cancer stem cells, discuss their relevance to the diagnosis and treatment of the disease and consider the outstanding challenges and potential opportunities that lie ahead of us.

  9. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    PubMed

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

    2016-05-01

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

  10. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    PubMed

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

    2016-05-01

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

  11. Dendritic cell-based cancer immunotherapy for colorectal cancer

    PubMed Central

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

    2016-01-01

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

  12. Targeting prostate cancer stem cells for cancer therapy

    PubMed Central

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

    2012-01-01

    Prostate cancer (PCa) is the most common malignant neoplasm in men and the second most frequent cause of cancer death for males in the United States. Recently, emerging evidence suggests that prostate cancer stem cells (CSCs) may play a critical role in the development and progression of PCa. Therefore, targeting prostate CSCs for the prevention of tumor progression and treatment of PCa could become a novel strategy for better treatment of patients diagnosed with PCa. In this review article, we will summarize the most recent advances in the prostate CSCs field, with particular emphasis on targeting prostate CSCs to treat prostate cancer. PMID:22369972

  13. Wnt Signaling in Cancer Stem Cell Biology.

    PubMed

    de Sousa E Melo, Felipe; Vermeulen, Louis

    2016-06-27

    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.

  14. [Cancer stem cell research toward therapeutics].

    PubMed

    Ito, Keisuke

    2015-05-01

    The capacity of cancer stem cells, or cancer-initiating cells, to both provide mature tumor cells and perpetuate themselves through self-renewal is crucial to initiate and maintain tumorigenesis, and has become the focus of intense research interest as a promising source of new therapeutic strategies. However, many scientific challenges and technical barriers remain to be solved before recent findings can be translated into effective therapeutics. Here we highlight the latest advances in our knowledge of cancer stem cells, and provide a critical perspective on the clinical benefits promised by this developing area of research.

  15. Wnt Signaling in Cancer Stem Cell Biology

    PubMed Central

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

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

  16. Breast cancer stem cells and radiation

    NASA Astrophysics Data System (ADS)

    Phillips, Tiffany Marie

    2007-12-01

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

  17. Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation.

    PubMed

    Szalayova, Gabriela; Ogrodnik, Aleksandra; Spencer, Brianna; Wade, Jacqueline; Bunn, Janice; Ambaye, Abiy; James, Ted; Rincon, Mercedes

    2016-06-01

    Chronic inflammation is known to facilitate cancer progression and metastasis. Less is known about the effect of acute inflammation within the tumor microenvironment, resulting from standard invasive procedures. Recent studies in mouse models have shown that the acute inflammatory response triggered by a biopsy in mammary cancer increases the frequency of distal metastases. Although tumor biopsies are part of the standard clinical practice in breast cancer diagnosis, no studies have reported their effect on inflammatory response. The objective of this study is to (1) determine whether core needle biopsies in breast cancer patients trigger an inflammatory response, (2) characterize the type of inflammatory response present, and (3) evaluate the potential effect of any acute inflammatory response on residual tumor cells. The biopsy wound site was identified in the primary tumor resection tissue samples from breast cancer patients. The inflammatory response in areas adjacent (i.e., immediately around previous biopsy site) and distant to the wound biopsy was investigated by histology and immunohistochemistry analysis. Proliferation of tumor cells was also assayed. We demonstrate that diagnostic core needle biopsies trigger a selective recruitment of inflammatory cells at the site of the biopsy, and they persist for extended periods of time. While macrophages were part of the inflammatory response, an unexpected accumulation of eosinophils at the edge of the biopsy wound was also identified. Importantly, we show that biopsy causes an increase in the proliferation rate of tumor cells located in the area adjacent to the biopsy wound. Diagnostic core needle biopsies in breast cancer patients do induce a unique acute inflammatory response within the tumor microenvironment and have an effect on the surrounding tumor cells. Therefore, biopsy-induced inflammation could have an impact on residual tumor cell progression and/or metastasis in human breast cancer. These findings

  18. Visualizing how cancer chromosome abnormalities form in living cells

    Cancer.gov

    For the first time, scientists have directly observed events that lead to the formation of a chromosome abnormality that is often found in cancer cells. The abnormality, called a translocation, occurs when part of a chromosome breaks off and becomes attac

  19. Myeloid Derived Suppressor Cells in Breast Cancer

    PubMed Central

    Markowitz, Joseph; Wesolowski, Robert; Papenfuss, Tracey; Brooks, Taylor R.

    2013-01-01

    Myeloid Derived Suppressor Cells (MDSCs) are a population of immature myeloid cells defined by their suppressive actions on immune cells such as T cells, dendritic cells, and natural killer cells. MDSCs typically are positive for the markers CD33 and CD11b but express low levels of HLADR in humans. In mice, MDSCs are typically positive for both CD11b and Gr1. These cells exert their suppressive activity on the immune system via the production of reactive oxygen species, arginase, and cytokines. These factors subsequently inhibit the activity of multiple protein targets such as the T cell receptor, STAT1, and indoleamine-pyrrole 2,3-dioxygenase. The numbers of MDSCs tend to increase with cancer burden while inhibiting MDSCs improves disease outcome in murine models. MDSCs also inhibit immune cancer therapeutics. In light of the poor prognosis of metastatic breast cancer in women and the correlation of increasing levels of MDSCs with increasing disease burden, the purposes of this review are to 1) discuss why MDSCs may be important in breast cancer, 2) describe model systems used to study MDSCs in vitro and in vivo, 3) discuss mechanisms involved in MDSC induction/function in breast cancer, and 4) present pre-clinical and clinical studies that explore modulation of the MDSC-immune system interaction in breast cancer. MDSCs inhibit the host immune response in breast cancer patients and diminishing MDSC actions may improve therapeutic outcomes. PMID:23828498

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

    PubMed

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

    2015-12-14

    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 prevent certain cancers. Here, we show that simvastatin decreases the SASP of senescent human fibroblasts by inhibiting protein prenylation, without affecting the senescent growth arrest. The Rho family GTPases Rac1 and Cdc42 were activated in senescent cells, and simvastatin reduced both activities. Further, geranylgeranyl transferase, Rac1 or Cdc42 depletion reduced IL-6 secretion by senescent cells. We also show that simvastatin mitigates the effects of senescent conditioned media on breast cancer cell proliferation and endocrine resistance. Our findings identify a novel activity of simvastatin and mechanism of SASP regulation. They also suggest that senescent cells, which accumulate after radio/chemo therapy, promote endocrine resistance in breast cancer and that simvastatin might suppress this resistance.

  1. Cisplatin Induces Differentiation of Breast Cancer Cells

    PubMed Central

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

    2013-01-01

    Breast tumors are heterogeneous including cells with stem cell properties and more differentiated cells. This heterogeneity is reflected into the molecular breast cancer subtypes. Breast cancer stem cells are resistant to chemotherapy, thus recent efforts are focusing on identifying treatments that shift them toward a more differentiated phenotype, making them more susceptible to chemotherapy. We examined whether the drug cisplatin induces differentiation in breast cancer cell lines that represent different breast cancer subtypes. We used three cell lines representing triple-negative breast cancers, BT-549 and MDA-MB-231 (claudin-low), and MDA-MB-468 (basal-like), along with estrogen and progesterone receptor positive MCF-7 cells (luminal). Cisplatin was applied at 2.5, 5, 10, and 20 μM, and cell viability and proliferation were measured using MTS and BrdU assays, respectively. The effect of cisplatin on the cellular hierarchy was examined by flow cytometry, immunofluorescence and qRT-PCR. Cisplatin treatment of 10 and 20 μM reduced cell viability by 36–51% and proliferation capacity by 36–67%. Treatment with cisplatin resulted in 12–67% down-regulation of stem cell markers (CD49f, SSEA4) and 10–130% up-regulation of differentiation markers (CK18, SMA, β-tubulin). At the mRNA level, CD49f was down-regulated whilst β-tubulin was up-regulated in the claudin-low cell lines. SSEA4 protein expression decreased upon cisplatin treatment, but SSEA4 mRNA expression increased indicating a differential regulation of cisplatin at the post-transcriptional level. It is concluded that cisplatin reduces breast cancer cell survival and induces differentiation of stem/progenitor cell subpopulations within breast cancer cell lines. These effects indicate the potential of this drug to target specific chemotherapy-resistant cells within a tumor. PMID:23761858

  2. Redox Regulation in Cancer Stem Cells

    PubMed Central

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

    2015-01-01

    Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of 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. PMID:26273424

  3. Cancer Stem Cells in the Thyroid

    PubMed Central

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

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

  4. Cancer Stem Cells in the Thyroid.

    PubMed

    Nagayama, Yuji; Shimamura, Mika; Mitsutake, Norisato

    2016-01-01

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

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

    PubMed

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

    2016-10-01

    Triiodothyronine plays an important role in the regulation of kidney cell growth, differentiation and metabolism. Patients with renal cell cancer who develop hypothyreosis during tyrosine kinase inhibitor (TKI) treatment have statistically longer survival. In this study, we developed cell based model of triiodothyronine (T3) analysis in RCC and we show the different effects of T3 on renal cell cancer (RCC) cell growth response and expression of the thyroid hormone receptor in human renal cell cancer cell lines from primary and metastatic tumors along with human kidney cancer stem cells. Wild-type thyroid hormone receptor is ubiquitously expressed in human renal cancer cell lines, but normalized against healthy renal proximal tube cell expression its level is upregulated in Caki-2, RCC6, SKRC-42, SKRC-45 cell lines. On the contrary the mRNA level in the 769-P, ACHN, HKCSC, and HEK293 cells is significantly decreased. The TRβ protein was abundant in the cytoplasm of the 786-O, Caki-2, RCC6, and SKRC-45 cells and in the nucleus of SKRC-42, ACHN, 769-P and cancer stem cells. T3 has promoting effect on the cell proliferation of HKCSC, Caki-2, ASE, ACHN, SK-RC-42, SMKT-R2, Caki-1, 786-0, and SK-RC-45 cells. Tyrosine kinase inhibitor, sunitinib, directly inhibits proliferation of RCC cells, while thyroid hormone receptor antagonist 1-850 (CAS 251310‑57-3) has less significant inhibitory impact. T3 stimulation does not abrogate inhibitory effect of sunitinib. Renal cancer tumor cells hypostimulated with T3 may be more responsive to tyrosine kinase inhibition. Moreover, some tumors may be considered as T3-independent and present aggressive phenotype with thyroid hormone receptor activated independently from the ligand. On the contrary proliferation induced by deregulated VHL and or c-Met pathways may transgress normal T3 mediated regulation of the cell cycle. PMID:27632932

  6. Survivorship Care Planning in Patients With Colorectal or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-12-16

    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

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

    PubMed Central

    Hombach-Klonisch, Sabine; Natarajan, Suchitra; Thanasupawat, Thatchawan; Medapati, Manoj; Pathak, Alok; Ghavami, Saeid; Klonisch, Thomas

    2014-01-01

    The two main reasons for death of cancer patients, tumor recurrence and metastasis, are multi-stage cellular processes that involve increased cell plasticity and coincide with elevated resistance to anti-cancer treatments. Epithelial-to-mesenchymal transition (EMT) is a key contributor to metastasis in many cancer types, including thyroid cancer and is known to confer stem cell-like properties onto cancer cells. This review provides an overview of molecular mechanisms and factors known to contribute to cancer cell plasticity and capable of enhancing cancer cell resistance to radio- and chemotherapy. We elucidate the role of DNA repair mechanisms in contributing to therapeutic resistance, with a special emphasis on thyroid cancer. Next, we explore the emerging roles of autophagy and damage-associated molecular pattern responses in EMT and chemoresistance in tumor cells. Finally, we demonstrate how cancer cells, including thyroid cancer cells, can highjack the oncofetal nucleoprotein high-mobility group A2 to gain increased transformative cell plasticity, prevent apoptosis, and enhance metastasis of chemoresistant tumor cells. PMID:24723911

  8. Hallmarks of cancer stem cell metabolism

    PubMed Central

    Sancho, Patricia; Barneda, David; Heeschen, Christopher

    2016-01-01

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

  9. Hallmarks of cancer stem cell metabolism.

    PubMed

    Sancho, Patricia; Barneda, David; Heeschen, Christopher

    2016-06-14

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

  10. Tyrosine kinase inhibitors target cancer stem cells in renal cell cancer.

    PubMed

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

    2016-03-01

    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.

  11. Host epithelial geometry regulates breast cancer cell invasiveness

    PubMed Central

    Boghaert, Eline; Gleghorn, Jason P.; Lee, KangAe; Gjorevski, Nikolce; Radisky, Derek C.; Nelson, Celeste M.

    2012-01-01

    Breast tumor development is regulated in part by cues from the local microenvironment, including interactions with neighboring nontumor cells as well as the ECM. Studies using homogeneous populations of breast cancer cell lines cultured in 3D ECM have shown that increased ECM stiffness stimulates tumor cell invasion. However, at early stages of breast cancer development, malignant cells are surrounded by normal epithelial cells, which have been shown to exert a tumor-suppressive effect on cocultured cancer cells. Here we explored how the biophysical characteristics of the host microenvironment affect the proliferative and invasive tumor phenotype of the earliest stages of tumor development, by using a 3D microfabrication-based approach to engineer ducts composed of normal mammary epithelial cells that contained a single tumor cell. We found that the phenotype of the tumor cell was dictated by its position in the duct: proliferation and invasion were enhanced at the ends and blocked when the tumor cell was located elsewhere within the tissue. Regions of invasion correlated with high endogenous mechanical stress, as shown by finite element modeling and bead displacement experiments, and modulating the contractility of the host epithelium controlled the subsequent invasion of tumor cells. Combining microcomputed tomographic analysis with finite element modeling suggested that predicted regions of high mechanical stress correspond to regions of tumor formation in vivo. This work suggests that the mechanical tone of nontumorigenic host epithelium directs the phenotype of tumor cells and provides additional insight into the instructive role of the mechanical tumor microenvironment. PMID:23150585

  12. Fabrication and evaluation of novel zeolite membranes to control the neoplastic activity and anti-tumoral drug treatments in human breast cancer cells. Part 1: Synthesis and characterization of Pure Zeolite Membranes and Mixed Matrix Membranes for adhesion and growth of cancer cells.

    PubMed

    Tavolaro, Palmira; Martino, Guglielmo; Andò, Sebastiano; Tavolaro, Adalgisa

    2016-12-01

    Novel pure and hybrid zeolite membranes were prepared with appropriate different physicochemical characteristics such as frameworks, hydrophilicity, crystal size, chemical composition, acid-base properties (Point of Zero Charge, PZC) and surface morphology and used in inorganic cell/scaffold constructs. Because the control of cell interactions, as the adhesion, proliferation, remodelling and mobility, is important for differentiation and progression of tumors, this work focused on response of cancer cells adhered and grown on synthesized zeolite surfaces in order to study the influence of these scaffolds in controlled conditions. We have selected the MCF-7 and MDA-MB-231 human breast cancer cell line as model tumor cell lines. This study showed that all the zeolite membranes synthesized are excellent scaffolds because they are very selective materials to support the adhesion and growth of neoplastic cells. All zeolite scaffolds were characterized by FESEM, FTIR ATR, XRD, AFM, PZC and contact angle analyses. Cell adhesion, viability and morphology were measured by count, MTT assay and FESEM microphotography analysis, at various incubation times. PMID:27612784

  13. Fabrication and evaluation of novel zeolite membranes to control the neoplastic activity and anti-tumoral drug treatments in human breast cancer cells. Part 1: Synthesis and characterization of Pure Zeolite Membranes and Mixed Matrix Membranes for adhesion and growth of cancer cells.

    PubMed

    Tavolaro, Palmira; Martino, Guglielmo; Andò, Sebastiano; Tavolaro, Adalgisa

    2016-12-01

    Novel pure and hybrid zeolite membranes were prepared with appropriate different physicochemical characteristics such as frameworks, hydrophilicity, crystal size, chemical composition, acid-base properties (Point of Zero Charge, PZC) and surface morphology and used in inorganic cell/scaffold constructs. Because the control of cell interactions, as the adhesion, proliferation, remodelling and mobility, is important for differentiation and progression of tumors, this work focused on response of cancer cells adhered and grown on synthesized zeolite surfaces in order to study the influence of these scaffolds in controlled conditions. We have selected the MCF-7 and MDA-MB-231 human breast cancer cell line as model tumor cell lines. This study showed that all the zeolite membranes synthesized are excellent scaffolds because they are very selective materials to support the adhesion and growth of neoplastic cells. All zeolite scaffolds were characterized by FESEM, FTIR ATR, XRD, AFM, PZC and contact angle analyses. Cell adhesion, viability and morphology were measured by count, MTT assay and FESEM microphotography analysis, at various incubation times.

  14. Cancer stem cells in head and neck cancer.

    PubMed

    Allegra, Eugenia; Trapasso, Serena

    2012-01-01

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

  15. Cell Senescence: Aging and Cancer

    ScienceCinema

    Campisi, Judith

    2016-07-12

    Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

  16. Cell Senescence: Aging and Cancer

    SciTech Connect

    Campisi, Judith

    2008-01-01

    Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals.

  17. Cell Polarity As A Regulator of Cancer Cell Behavior Plasticity

    PubMed Central

    Muthuswamy, Senthil K; Xue, Bin

    2013-01-01

    Cell polarization is an evolutionarily conserved process that facilitates asymmetric distribution of organelles and proteins, is an evolutionarily conserved property that is modified dynamically during physiological processes such as cell division, migration, and morphogenesis. The plasticity with which cells change their behavior and phenotype in response to cell intrinsic and extrinsic cues is an essential feature of normal physiology. In disease states such as cancer, cells lose their ability to behave normally in response to physiological cues. A molecular understanding of mechanisms that alter the behavior of cancer cells is limited. Cell polarity proteins are an recognized class of molecules that can receive and interpret both intrinsic and extrinsic signals to modulate cell behavior. In this review, we discuss how cell polarity proteins regulate a diverse array of biological processes and how they can contribute to alterations in the behavior of cancer cells. PMID:22881459

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  19. Co-Eradication of Breast Cancer Cells and Cancer Stem Cells by Cross-Linked Multilamellar Liposomes Enhances Tumor Treatment.

    PubMed

    Kim, Yu Jeong; Liu, Yarong; Li, Si; Rohrs, Jennifer; Zhang, Rachel; Zhang, Xiaoyang; Wang, Pin

    2015-08-01

    The therapeutic limitations of conventional chemotherapeutic drugs have emerged as a challenge for breast cancer therapy; these shortcomings are likely due, at least in part, to the presence of the cancer stem cells (CSCs). Salinomycin, a polyether antibiotic isolated from Streptomyces albus, has been shown to selectively inhibit cancer stem cells; however, its clinical application has been hindered by the drug's hydrophobility, which limits the available administration routes. In this paper, a novel drug delivery system, cross-linked multilamellar liposomal vesicles (cMLVs), was optimized to allow for the codelivery of salinomycin (Sal) and doxorubicin (Dox), targeting both CSCs and breast cancer cells. The results show that the cMLV particles encapsulating different drugs have similar sizes with high encapsulation efficiencies (>80%) for both Dox and Sal. Dox and Sal were released from the particles in a sustained manner, indicating the stability of the cMLVs. Moreover, the inhibition of cMLV(Dox+Sal) against breast cancer cells was stronger than either single-drug treatment. The efficient targeting of cMLV(Dox+Sal) to CSCs was validated through in vitro experiments using breast cancer stem cell markers. In accordance with the in vitro combination treatment, in vivo breast tumor suppression by cMLV(Dox+Sal) was 2-fold more effective than single-drug cMLV treatment or treatment with the combination of cMLV(Dox) and cMLV(Sal). Thus, this study demonstrates that cMLVs represent a novel drug delivery system that can serve as a potential platform for combination therapy, allowing codelivery of an anticancer agent and a CSC inhibitor for the elimination of both breast cancer cells and cancer stem cells.

  20. Growth-stimulatory effect of resveratrol in human cancer cells.

    PubMed

    Fukui, Masayuki; Yamabe, Noriko; Kang, Ki Sung; Zhu, Bao Ting

    2010-08-01

    Earlier studies have shown that resveratrol could induce death in several human cancer cell lines in culture. Here we report our observation that resveratrol can also promote the growth of certain human cancer cells when they are grown either in culture or in athymic nude mice as xenografts. At relatively low concentrations (cancer cells, but this effect was not observed in several other human cell lines tested. Analysis of cell signaling molecules showed that resveratrol induced the activation of JNK, p38, Akt, and NF-kappaB signaling pathways in these cells. Further analysis using pharmacological inhibitors showed that only the NF-kappaB inhibitor (BAY11-7082) abrogated the growth-stimulatory effect of resveratrol in cultured cells. In athymic nude mice, resveratrol at 16.5 mg/kg body weight enhanced the growth of MDA-MB-435s xenografts compared to the control group, while resveratrol at the 33 mg/kg body weight dose did not have a similar effect. Additional analyses confirmed that resveratrol stimulated cancer cell growth in vivo through activation of the NF-kappaB signaling pathway. Taken together, these observations suggest that resveratrol at low concentrations could stimulate the growth of certain types of human cancer cells in vivo. This cell type-specific mitogenic effect of resveratrol may also partly contribute to the procarcinogenic effect of alcohol consumption (rich in resveratrol) in the development of certain human cancers.

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

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia T.

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

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

    NASA Astrophysics Data System (ADS)

    Mierke, Claudia T.

    2015-10-01

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

  3. Downregulation of gap junctions in cancer cells.

    PubMed

    Leithe, Edward; Sirnes, Solveig; Omori, Yasufumi; Rivedal, Edgar

    2006-12-01

    Gap junctions are intercellular plasma membrane domains enriched in channels that allow direct exchange of ions and small molecules between adjacent cells. Gap junction channels are composed of a family of transmembrane proteins called connexin. Connexins play important roles in the regulation of cell growth and differentiation. Cancer cells usually have downregulated levels of gap junctions, and several lines of evidence suggest that loss of gap junctional intercellular communication is an important step in carcinogenesis. In support of this hypothesis are studies showing that reexpression of connexins in cancer cells causes normalization of cell growth control and reduced tumor growth. To gain a more detailed understanding of the role of connexins as tumor suppressors, a clearer picture of the mechanisms involved in loss of gap junctions in cancer cells is needed. Furthermore, defining the mechanisms involved in downregulation of connexins in carcinogenesis will be an important step toward utilizing the potential of connexins as targets in cancer prevention and therapy. Various mechanisms are involved in the loss of gap junctions in cancer cells, ranging from loss of connexin gene transcription to aberrant trafficking of connexin proteins. This review will discuss our current knowledge on the molecular mechanisms involved in the downregulation of gap junctions in cancer cells. PMID:17425504

  4. Cancer stem cells: progress and challenges in lung cancer.

    PubMed

    Templeton, Amanda K; Miyamoto, Shinya; Babu, Anish; Munshi, Anupama; Ramesh, Rajagopal

    2014-01-01

    The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called "cancer stem cells" (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs. PMID:27358855

  5. Signaling in colon cancer stem cells.

    PubMed

    Roy, Sanchita; Majumdar, Adhip Pn

    2012-01-01

    : Colorectal cancer is the fourth most common form of cancer worldwide and ranks third among the cancer-related deaths in the US and other Western countries. It occurs with equal frequency in men and women, constituting 10% of new cancer cases in men and 11% in women. Despite recent advancement in therapeutics, the survival rates from metastatic are less than 5%. Growing evidence supports the contention that epithelial cancers including colorectal cancer, the incidence of which increases with aging, are diseases driven by the pluripotent, self-renewing cancer stem cells (CSCs). Dysregulation of Wnt, Notch, Hedgehog and/or TGF-β signaling pathways that are involved in proliferation and maintenance of CSCs leads to the development of CRC. This review focuses on the signaling pathways relevant for CRC to understand the mechanisms leading to tumor progression and therapy resistance, which may help in the development of therapeutic strategies for CRC. PMID:22866952

  6. Cell Polarity Proteins in Breast Cancer Progression.

    PubMed

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

    2016-10-01

    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.

  7. Cell Polarity Proteins in Breast Cancer Progression.

    PubMed

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

    2016-10-01

    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. PMID:27362918

  8. Advanced Cell Culture Techniques for Cancer Drug Discovery

    PubMed Central

    Lovitt, Carrie J.; Shelper, Todd B.; Avery, Vicky M.

    2014-01-01

    Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor. PMID:24887773

  9. Cancer stem cells targeting agents--a review.

    PubMed

    Shi, A-M; Tao, Z-Q; Li, H; Wang, Y-Q; Zhao, J

    2015-11-01

    Major current cancer strategies like surgery, radiotherapy, and chemotherapy are compromised due to major problem of recurrence, which usually lead to mortality. The widely accepted reason for this is resistance offered by cancer cells towards cancer drugs or inability of a therapeutic procedure to target real culprits viz. cancer-initiating cells (cancer stem cells). So, there is a current need of development of new agents targeting these cancer stem cells in order to overcome resistance to therapeutic procedures. The present review article is focused on new cancer cell targeting agents like salinomycin, apopotin etc and their mechanisms to target cancer stems cells will be discussed.

  10. Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia

    PubMed Central

    Schäfer, Michaela; Oeing, Christian U.; Rohm, Maria; Baysal-Temel, Ezgi; Lehmann, Lorenz H.; Bauer, Ralf; Volz, H. Christian; Boutros, Michael; Sohn, Daniela; Sticht, Carsten; Gretz, Norbert; Eichelbaum, Katrin; Werner, Tessa; Hirt, Marc N.; Eschenhagen, Thomas; Müller-Decker, Karin; Strobel, Oliver; Hackert, Thilo; Krijgsveld, Jeroen; Katus, Hugo A.; Berriel Diaz, Mauricio; Backs, Johannes; Herzig, Stephan

    2015-01-01

    Objectives Cancer cachexia affects the majority of tumor patients and significantly contributes to high mortality rates in these subjects. Despite its clinical importance, the identity of tumor-borne signals and their impact on specific peripheral organ systems, particularly the heart, remain mostly unknown. Methods and results By combining differential colon cancer cell secretome profiling with large-scale cardiomyocyte phenotyping, we identified a signature panel of seven “cachexokines”, including Bridging integrator 1, Syntaxin 7, Multiple inositol-polyphosphate phosphatase 1, Glucosidase alpha acid, Chemokine ligand 2, Adamts like 4, and Ataxin-10, which were both sufficient and necessary to trigger cardiac atrophy and aberrant fatty acid metabolism in cardiomyocytes. As a prototypical example, engineered secretion of Ataxin-10 from non-cachexia-inducing cells was sufficient to induce cachexia phenotypes in cardiomyocytes, correlating with elevated Ataxin-10 serum levels in murine and human cancer cachexia models. Conclusions As Ataxin-10 serum levels were also found to be elevated in human cachectic cancer patients, the identification of Ataxin-10 as part of a cachexokine cocktail now provides a rational approach towards personalized predictive, diagnostic and therapeutic measures in cancer cachexia. PMID:26909315

  11. Targeting natural killer cells in cancer immunotherapy.

    PubMed

    Guillerey, Camille; Huntington, Nicholas D; Smyth, Mark J

    2016-08-19

    Alteration in the expression of cell-surface proteins is a common consequence of malignant transformation. Natural killer (NK) cells use an array of germline-encoded activating and inhibitory receptors that scan for altered protein-expression patterns, but tumor evasion of detection by the immune system is now recognized as one of the hallmarks of cancer. NK cells display rapid and potent immunity to metastasis or hematological cancers, and major efforts are now being undertaken to fully exploit NK cell anti-tumor properties in the clinic. Diverse approaches encompass the development of large-scale NK cell-expansion protocols for adoptive transfer, the establishment of a microenvironment favorable to NK cell activity, the redirection of NK cell activity against tumor cells and the release of inhibitory signals that limit NK cell function. In this Review we detail recent advances in NK cell-based immunotherapies and discuss the advantages and limitations of these strategies. PMID:27540992

  12. Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment.

    PubMed

    Menko, Fred H; Maher, Eamonn R; Schmidt, Laura S; Middelton, Lindsay A; Aittomäki, Kristiina; Tomlinson, Ian; Richard, Stéphane; Linehan, W Marston

    2014-12-01

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition in which susceptible individuals are at risk for the development of cutaneous leiomyomas, early onset multiple uterine leiomyomas and an aggressive form of type 2 papillary renal cell cancer. HLRCC is caused by germline mutations in the fumarate hydratase (FH) gene which inactivate the enzyme and alters the function of the tricarboxylic acid (Krebs) cycle. Issues surrounding surveillance and treatment for HLRCC-associated renal cell cancer were considered as part of a recent international symposium on HLRCC. The management protocol proposed in this article is based on a literature review and a consensus meeting. The lifetime renal cancer risk for FH mutation carriers is estimated to be 15 %. In view of the potential for early onset of RCC in HLRCC, periodic renal imaging and, when available, predictive testing for a FH mutation is recommended from 8 to 10 years of age. However, the small risk of renal cell cancer in the 10-20 years age range and the potential drawbacks of screening should be carefully discussed on an individual basis. Surveillance preferably consists of annual abdominal MRI. Treatment of renal tumours should be prompt and generally consist of wide-margin surgical excision and consideration of retroperitoneal lymph node dissection. The choice for systemic treatment in metastatic disease should, if possible, be part of a clinical trial. Screening procedures in HLRCC families should preferably be evaluated in large cohorts of families.

  13. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2016-06-17

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  14. Measuring the metastatic potential of cancer cells

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  15. Cancer stem cells: progress and challenges in lung cancer

    PubMed Central

    Templeton, Amanda K.; Miyamoto, Shinya; Babu, Anish; Munshi, Anupama

    2014-01-01

    The identification of a subpopulation of tumor cells with stem cell-like characteristics first in hematological malignancies and later in solid tumors has emerged into a novel field of cancer research. It has been proposed that this aberrant population of cells now called “cancer stem cells” (CSCs) drives tumor initiation, progression, metastasis, recurrence, and drug resistance. CSCs have been shown to have the capacity of self-renewal and multipotency. Adopting strategies from the field of stem cell research has aided in identification, localization, and targeting of CSCs in many tumors. Despite the huge progress in other solid tumors such as brain, breast, and colon cancers no substantial advancements have been made in lung cancer. This is most likely due to the current rudimentary understanding of lung stem cell hierarchy and heterogeneous nature of lung disease. In this review, we will discuss the most recent findings related to identification of normal lung stem cells and CSCs, pathways involved in regulating the development of CSCs, and the importance of the stem cell niche in development and maintenance of CSCs. Additionally, we will examine the development and feasibility of novel CSC-targeted therapeutic strategies aimed at eradicating lung CSCs. PMID:27358855

  16. Curcumin: a promising agent targeting cancer stem cells.

    PubMed

    Zang, Shufei; Liu, Tao; Shi, Junping; Qiao, Liang

    2014-01-01

    Cancer stem cells are a subset of cells that are responsible for cancer initiation and relapse. They are generally resistant to the current anticancer agents. Successful anticancer therapy must consist of approaches that can target not only the differentiated cancer cells, but also cancer stem cells. Emerging evidence suggested that the dietary agent curcumin exerted its anti-cancer activities via targeting cancer stem cells of various origins such as those of colorectal cancer, pancreatic cancer, breast cancer, brain cancer, and head and neck cancer. In order to enhance the therapeutic potential of curcumin, this agent has been modified or used in combination with other agents in the experimental therapy for many cancers. In this mini-review, we discussed the effect of curcumin and its derivatives in eliminating cancer stem cells and the possible underlying mechanisms.

  17. Printing Cancer Cells into Intact Microvascular Networks: A Model for Investigating Cancer Cell Dynamics during Angiogenesis

    PubMed Central

    Phamduy, Theresa B.; Sweat, Richard S.; Azimi, Mohammad S.; Burow, Matthew E.; Murfee, Walter L.; Chrisey, Douglas B.

    2016-01-01

    While cancer cell invasion and metastasis is dependent on cancer cell-stroma, cancer cell-blood vessel, and cancer cell-lymphatic vessel interactions, our understanding of these interactions remain largely unknown. A need exists for physiologically-relevant models that more closely mimic the complexity of cancer cell dynamics in a real tissue environment. The objective of this study was to combine laser-based cell printing and tissue culture methods to create a novel ex vivo model in which cancer cell dynamics can be tracked during angiogenesis in an intact microvascular network. Laser direct-write (LDW) was utilized to reproducibly deposit breast cancer cells (MDA-MB-231 and MCF-7) and fibroblasts into spatially-defined patterns on cultured rat mesenteric tissues. In addition, heterogeneous patterns containing co-printed MDA-MB-231/fibroblasts or MDA-MB-231/MCF-7 cells were generated for fibroblast-directed and collective cell invasion models. Printed cells remained viable and the cells retained the ability to proliferate in serum-rich media conditions. Over a culture period of five days, time-lapse imaging confirmed fibroblast and MDA-MB-231 cell migration within the microvascular networks. Confocal microscopy indicated that printed MDA-MB-231 cells infiltrated the tissue thickness and were capable of interacting with endothelial cells. Angiogenic network growth in tissue areas containing printed cancer cells was characterized by significantly increased capillary sprouting compared to control tissue areas containing no printed cells. Our results establish an innovative ex vivo experimental platform that enables time-lapse evaluation of cancer cell dynamics during angiogenesis within a real microvascular network scenario. PMID:26190039

  18. Cancer Stem Cell Hierarchy in Glioblastoma Multiforme

    PubMed Central

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

    2016-01-01

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

  19. Multiple myeloma cancer stem cells

    PubMed Central

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

    2016-01-01

    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

  20. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-05-05

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  1. Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: part II. Autologous Transplantation-novel agents and immunomodulatory strategies.

    PubMed

    Avigan, David; Hari, Parameswaran; Battiwalla, Minoo; Bishop, Michael R; Giralt, Sergio A; Hardy, Nancy M; Kröger, Nicolaus; Wayne, Alan S; Hsu, Katharine C

    2013-12-01

    In the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on Autologous Transplantation addressed the role of novel agents and immunomodulatory strategies in management of relapse after autologous hematopoietic stem cell transplantation (AHSCT). Concepts were illustrated through in-depth discussion of multiple myeloma, with broader discussion of areas relevant for relapse of other malignancies as well as in the setting of allogeneic transplantation. Dr. Hari provided an overview of the epidemiology of relapse after AHSCT in multiple myeloma, addressing clinical patterns, management implications, and treatment options at relapse, highlighting the implications of novel therapeutic agents in initial, maintenance, and relapse treatment. Dr. Avigan discussed current concepts in tumor vaccine design, including whole cell and antigen-specific strategies, use of an AHSCT platform to reverse tumor-associated immunosuppression and tolerance, and combining vaccines with immunomodulatory agents to promote establishment of durable antitumor immunity. Dr. Hsu reviewed the immunogenetics of natural killer (NK) cells and general NK biology, the clinical importance of autologous NK activity (eg, lymphoma and neuroblastoma), the impact of existing therapies on promotion of NK cell activity (eg, immunomodulatory drugs, monoclonal antibodies), and strategies for enhancing autologous and allogeneic NK cell effects through NK cell gene profiling.

  2. Reducing bone cancer cell functions using selenium nanocomposites.

    PubMed

    Stolzoff, Michelle; Webster, Thomas J

    2016-02-01

    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. PMID:26454004

  3. Advances and perspectives of colorectal cancer stem cell vaccine.

    PubMed

    Guo, Mei; Dou, Jun

    2015-12-01

    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.

  4. Reducing bone cancer cell functions using selenium nanocomposites.

    PubMed

    Stolzoff, Michelle; Webster, Thomas J

    2016-02-01

    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.

  5. Embryonic stem cell-specific signature in cervical cancer.

    PubMed

    Organista-Nava, Jorge; Gómez-Gómez, Yazmín; Gariglio, Patricio

    2014-03-01

    The wide range of invasive and noninvasive lesion phenotypes associated with high-risk human papillomavirus (HR-HPV) infection in cervical cancer (CC) indicates that not only the virus but also specific cervical epithelial cells in the transformation zone (TZ), such as stem cells (SCs), play an important part in the development of cervical neoplasia. In this review, we focused in an expression signature that is specific to embryonic SCs and to poorly differentiated cervical malignant tumors and we hypothesize that this expression signature may play an important role to promote cell growth, survival, colony formation, lack of adhesion, as well as cell invasion and migration in CC.

  6. Glycosaminoglycans: key players in cancer cell biology and treatment.

    PubMed

    Afratis, Nikos; Gialeli, Chrisostomi; Nikitovic, Dragana; Tsegenidis, Theodore; Karousou, Evgenia; Theocharis, Achilleas D; Pavão, Mauro S; Tzanakakis, George N; Karamanos, Nikos K

    2012-04-01

    Glycosaminoglycans are natural heteropolysaccharides that are present in every mammalian tissue. They are composed of repeating disaccharide units that consist of either sulfated or non-sulfated monosaccharides. Their molecular size and the sulfation type vary depending on the tissue, and their state either as part of proteoglycan or as free chains. In this regard, glycosaminoglycans play important roles in physiological and pathological conditions. During recent years, cell biology studies have revealed that glycosaminoglycans are among the key macromolecules that affect cell properties and functions, acting directly on cell receptors or via interactions with growth factors. The accumulated knowledge regarding the altered structure of glycosaminoglycans in several diseases indicates their importance as biomarkers for disease diagnosis and progression, as well as pharmacological targets. This review summarizes how the fine structural characteristics of glycosaminoglycans, and enzymes involved in their biosynthesis and degradation, are involved in cell signaling, cell function and cancer progression. Prospects for glycosaminoglycan-based therapeutic targeting in cancer are also discussed.

  7. Genomic instability, driver genes and cell selection: Projections from cancer to stem cells.

    PubMed

    Ben-David, Uri

    2015-04-01

    Cancer cells and stem cells share many traits, including a tendency towards genomic instability. Human cancers exhibit tumor-specific genomic aberrations, which often affect their malignancy and drug response. During their culture propagation, human pluripotent stem cells (hPSCs) also acquire characteristic genomic aberrations, which may have significant impact on their molecular and cellular phenotypes. These aberrations vary in size from single nucleotide alterations to copy number alterations to whole chromosome gains. A prominent challenge in both cancer and stem cell research is to identify "driver aberrations" that confer a selection advantage, and "driver genes" that underlie the recurrence of these aberrations. Following principles that are already well-established in cancer research, candidate driver genes have also been suggested in hPSCs. Experimental validation of the functional role of such candidates can uncover whether these are bona fide driver genes. The identification of driver genes may bring us closer to a mechanistic understanding of the genomic instability of stem cells. Guided by terminologies and methodologies commonly applied in cancer research, such understanding may have important ramifications for both stem cell and cancer biology. This article is part of a Special Issue entitled: Stress as a fundamental theme in cell plasticity.

  8. Metastatic cancer stem cells: new molecular targets for cancer therapy.

    PubMed

    Leirós, G J; Balañá, M E

    2011-11-01

    The cancer stem cell (CSC) hypothesis, predicts that a small subpopulation of cancer cells that possess "stem-like" characteristics, are responsible for initiating and maintaining cancer growth. According to the CSC model the many cell populations found in a tumour might represent diverse stages of differentiation. From the cellular point of view metastasis is considered a highly inefficient process and only a subset of tumour cells is capable of successfully traversing the entire metastatic cascade and eventually re-initiates tumour growth at distant sites. Some similar features of both normal and malignant stem cells suggest that CSCs are not only responsible for tumorigenesis, but also for metastases. The CSC theory proposes that the ability of a tumour to metastasize is an inherent property of a subset of CSCs. The similar biological characteristics shared by normal stem cells (NSCs) and CSCs mainly implicate self-renewal and differentiation potential, survival ability, niche-specific microenvironment requirements and specific homing to metastatic sites and may have important implications in terms of new approaches to cancer therapy in the metastatic setting. There are several agents targeting many of these CSC features that have shown to be effective both in vitro and in vivo. Although clinical trials results are still preliminary and continue under investigation, these new therapies are very promising. The identification of new therapeutic targets and drugs based on CSC model constitutes a great challenge. PMID:21470128

  9. Metastatic cancer stem cells: new molecular targets for cancer therapy.

    PubMed

    Leirós, G J; Balañá, M E

    2011-11-01

    The cancer stem cell (CSC) hypothesis, predicts that a small subpopulation of cancer cells that possess "stem-like" characteristics, are responsible for initiating and maintaining cancer growth. According to the CSC model the many cell populations found in a tumour might represent diverse stages of differentiation. From the cellular point of view metastasis is considered a highly inefficient process and only a subset of tumour cells is capable of successfully traversing the entire metastatic cascade and eventually re-initiates tumour growth at distant sites. Some similar features of both normal and malignant stem cells suggest that CSCs are not only responsible for tumorigenesis, but also for metastases. The CSC theory proposes that the ability of a tumour to metastasize is an inherent property of a subset of CSCs. The similar biological characteristics shared by normal stem cells (NSCs) and CSCs mainly implicate self-renewal and differentiation potential, survival ability, niche-specific microenvironment requirements and specific homing to metastatic sites and may have important implications in terms of new approaches to cancer therapy in the metastatic setting. There are several agents targeting many of these CSC features that have shown to be effective both in vitro and in vivo. Although clinical trials results are still preliminary and continue under investigation, these new therapies are very promising. The identification of new therapeutic targets and drugs based on CSC model constitutes a great challenge.

  10. Natural flavonoids targeting deregulated cell cycle progression in cancer cells.

    PubMed

    Singh, Rana Pratap; Agarwal, Rajesh

    2006-03-01

    The prolonged duration requiring alteration of multi-genetic and epigenetic molecular events for cancer development provides a strong rationale for cancer prevention, which is developing as a potential strategy to arrest or reverse carcinogenic changes before the appearance of the malignant disease. Cell cycle progression is an important biological event having controlled regulation in normal cells, which almost universally becomes aberrant or deregulated in transformed and neoplastic cells. In this regard, targeting deregulated cell cycle progression and its modulation by various natural and synthetic agents are gaining widespread attention in recent years to control the unchecked growth and proliferation in cancer cells. In fact, a vast number of experimental studies convincingly show that many phytochemicals halt uncontrolled cell cycle progression in cancer cells. Among these phytochemicals, natural flavonoids have been identified as a one of the major classes of natural anticancer agents exerting antineoplastic activity via cell cycle arrest as a major mechanism in various types of cancer cells. This review is focused at the modulatory effects of natural flavonoids on cell cycle regulators including cyclin-dependent kinases and their inhibitors, cyclins, p53, retinoblastoma family of proteins, E2Fs, check-point kinases, ATM/ATR and survivin controlling G1/S and G2/M check-point transitions in cell cycle progression, and discusses how these molecular changes could contribute to the antineoplastic effects of natural flavonoids.

  11. Regulation of breast cancer stem cell features

    PubMed Central

    Kaminska, Bozena

    2015-01-01

    Cancer stem cells (CSCs) are rare, tumour-initiating cells that exhibit stem cell properties: capacity of self-renewal, pluripotency, highly tumorigenic potential, and resistance to therapy. Cancer stem cells have been characterised and isolated from many cancers, including breast cancer. Developmental pathways, such as the Wnt/β-catenin, Notch/γ-secretase/Jagged, Shh (sonic hedgehog), and BMP signalling pathways, which direct proliferation and differentiation of normal stem cells, have emerged as major signalling pathways that contribute to the self-renewal of stem and/or progenitor cells in a variety of organs and cancers. Deregulation of these signalling pathways is frequently linked to an epithelial-mesenchymal transition (EMT), and breast CSCs often possess properties of cells that have undergone the EMT process. Signalling networks mediated by microRNAs and EMT-inducing transcription factors tie the EMT process to regulatory networks that maintain “stemness”. Recent studies have elucidated epigenetic mechanisms that control pluripotency and stemness, which allows an assessment on how embryonic and normal tissue stem cells are deregulated during cancerogenesis to give rise to CSCs. Epigenetic-based mechanisms are reversible, and the possibility of “resetting” the abnormal cancer epigenome by applying pharmacological compounds targeting epigenetic enzymes is a promising new therapeutic strategy. Chemoresistance of CSCs is frequently driven by various mechanisms, including aberrant expression/activity of ABC transporters, aldehyde dehydrogenase and anti-oncogenic proteins (i.e. BCL2, B-cell lymphoma-2), enhanced DNA damage response, activation of pro-survival signalling pathways, and epigenetic deregulations. Despite controversy surrounding the CSC hypothesis, there is substantial evidence for their role in cancer, and a number of drugs intended to specifically target CSCs have entered clinical trials. PMID:25691826

  12. Regulation of breast cancer stem cell features.

    PubMed

    Czerwinska, Patrycja; Kaminska, Bozena

    2015-01-01

    Cancer stem cells (CSCs) are rare, tumour-initiating cells that exhibit stem cell properties: capacity of self-renewal, pluripotency, highly tumorigenic potential, and resistance to therapy. Cancer stem cells have been characterised and isolated from many cancers, including breast cancer. Developmental pathways, such as the Wnt/β-catenin, Notch/γ-secretase/Jagged, Shh (sonic hedgehog), and BMP signalling pathways, which direct proliferation and differentiation of normal stem cells, have emerged as major signalling pathways that contribute to the self-renewal of stem and/or progenitor cells in a variety of organs and cancers. Deregulation of these signalling pathways is frequently linked to an epithelial-mesenchymal transition (EMT), and breast CSCs often possess properties of cells that have undergone the EMT process. Signalling networks mediated by microRNAs and EMT-inducing transcription factors tie the EMT process to regulatory networks that maintain "stemness". Recent studies have elucidated epigenetic mechanisms that control pluripotency and stemness, which allows an assessment on how embryonic and normal tissue stem cells are deregulated during cancerogenesis to give rise to CSCs. Epigenetic-based mechanisms are reversible, and the possibility of "resetting" the abnormal cancer epigenome by applying pharmacological compounds targeting epigenetic enzymes is a promising new therapeutic strategy. Chemoresistance of CSCs is frequently driven by various mechanisms, including aberrant expression/activity of ABC transporters, aldehyde dehydrogenase and anti-oncogenic proteins (i.e. BCL2, B-cell lymphoma-2), enhanced DNA damage response, activation of pro-survival signalling pathways, and epigenetic deregulations. Despite controversy surrounding the CSC hypothesis, there is substantial evidence for their role in cancer, and a number of drugs intended to specifically target CSCs have entered clinical trials. PMID:25691826

  13. TWIST modulates prostate cancer cell-mediated bone cell activity and is upregulated by osteogenic induction.

    PubMed

    Yuen, Hiu-Fung; Kwok, Wai-Kei; Chan, Ka-Kui; Chua, Chee-Wai; Chan, Yuen-Piu; Chu, Ying-Ying; Wong, Yong-Chuan; Wang, Xianghong; Chan, Kwok-Wah

    2008-08-01

    TWIST, a helix-loop-helix transcription factor, is highly expressed in many types of human cancer. We have previously found that TWIST confers prostate cancer cells with an enhanced metastatic potential through promoting epithelial-mesenchymal transition (EMT) and a high TWIST expression in human prostate cancer is associated with an increased metastatic potential. The predilection of prostate cancer cells to metastasize to bone may be due to two interplaying mechanisms (i) by increasing the rate of bone remodeling and (ii) by undergoing osteomimicry. We further studied the role of TWIST in promoting prostate cancer to bone metastasis. TWIST expression in PC3, a metastatic prostate cancer cell line, was silenced by small interfering RNA and we found that conditioned medium from PC3 with lower TWIST expression had a lower activity on stimulating osteoclast differentiation and higher activity on stimulating osteoblast mineralization. In addition, we found that these effects were, at least partly, associated with TWIST-induced expression of dickkopf homolog 1 (DKK-1), a factor that promotes osteolytic metastasis. We also examined TWIST and RUNX2 expressions during osteogenic induction of an organ-confined prostate cancer cell, 22Rv1. We observed increased TWIST and RUNX2 expressions upon osteogenic induction and downregulation of TWIST through short hairpin RNA reduced the induction level of RUNX2. In summary, our results suggest that, in addition to EMT, TWIST may also promote prostate cancer to bone metastasis by modulating prostate cancer cell-mediated bone remodeling via regulating the expression of a secretory factor, DKK-1, and enhancing osteomimicry of prostate cancer cells, probably, via RUNX2.

  14. Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse After Hematopoietic Stem Cell Transplantation: part III. Prevention and treatment of relapse after allogeneic transplantation.

    PubMed

    de Lima, Marcos; Porter, David L; Battiwalla, Minoo; Bishop, Michael R; Giralt, Sergio A; Hardy, Nancy M; Kröger, Nicolaus; Wayne, Alan S; Schmid, Christoph

    2014-01-01

    In the Second Annual National Cancer Institute's Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Prevention and Treatment of Relapse after Allogeneic Transplantation highlighted progress in developing new therapeutic approaches since the first relapse workshop. Recent insights that might provide a basis for the development of novel, practical clinical trials were emphasized, including utilization of newer agents, optimization of donor lymphocyte infusion (DLI), and investigation of novel cellular therapies. Dr. de Lima discussed pre-emptive and maintenance strategies to prevent relapse after transplantation, for example, recent promising results suggestive of enhanced graft-versus-tumor activity with hypomethylating agents. Dr. Schmid provided an overview of adjunctive strategies to improve cell therapy for relapse, including cytoreduction before DLI, combination of targeted agents with DLI, and considerations in use of second transplantations. Dr. Porter addressed strategies to enhance T cell function, including ex vivo activated T cells and T cell engineering, and immunomodulatory approaches to enhance T cell function in vivo, including exogenous cytokines and modulation of costimulatory pathways.

  15. Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-06-04

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  16. Pharmacogenomic agreement between two cancer cell line data sets.

    PubMed

    2015-12-01

    Large cancer cell line collections broadly capture the genomic diversity of human cancers and provide valuable insight into anti-cancer drug response. Here we show substantial agreement and biological consilience between drug sensitivity measurements and their associated genomic predictors from two publicly available large-scale pharmacogenomics resources: The Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer databases.

  17. Stem cell plasticity in development and cancer: epigenetic origin of cancer stem cells.

    PubMed

    Shah, Mansi; Allegrucci, Cinzia

    2013-01-01

    Stem cells are unique cells that can self-renew and differentiate into many cell types. Plasticity is a fundamental characteristic of stem cells and it is regulated by reversible epigenetic modifications. Although gene-restriction programs are established during embryonic development when cell lineages are formed, stem cells retain a degree of flexibility that is essential for tissue regeneration. For instance, quiescent adult stem cells can be induced to proliferate and trans-differentiate in response to injury. The same degree of plasticity is observed in cancer, where cancer cells with stem cell characteristics (or cancer stem cells) are formed by transformation of normal stem cells or de-differentiation of somatic cells. Reprogramming experiments with normal somatic cells and cancer cells show that epigenetic landscapes are more plastic than originally thought and that their manipulation can induce changes in cell fate. Our knowledge of stem cell function is still limited and only by understanding the mechanisms regulating developmental potential together with the definition of epigenetic maps of normal and diseased tissues we can reveal the true extent of their plasticity. In return, the control of plastic epigenetic programs in stem cells will allow us to develop effective treatments for degenerative diseases and cancer. PMID:23150267

  18. Cancer - penis

    MedlinePlus

    ... an organ that makes up part of the male reproductive system. Causes The exact cause is unknown. Smegma, a ... Squamous cell cancer - penis Images Male reproductive anatomy Male reproductive system References National Comprehensive Cancer Network. National Comprehensive Cancer ...

  19. Overcoming Multidrug Resistance in Cancer Stem Cells

    PubMed Central

    Moitra, Karobi

    2015-01-01

    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. PMID:26649310

  20. Iron, inflammation and invasion of cancer cells

    PubMed Central

    FISCHER-FODOR, EVA; MIKLASOVA, NATALIA; BERINDAN-NEAGOE, IOANA; SAHA, BHASKAR

    2015-01-01

    Chronic inflammation is associated with the metastasis of tumor cells evolving from a benign tumor to disseminating cancer. Such a metastatic progression is fostered by the angiogenesis propelled by various mediators interacting at the site of tumor growth. Angiogenesis causes two major changes that are assisted by altered glycosylation and neo-antigen presentation by the cancer cells. The angiogenesis-promoted pathological changes include enhanced inflammation and degradation of tissue matrices releasing tumor cells from the site of its origin. The degraded tumor cells release the neo-antigens resulting from altered glycosylation. Presentation of neo-antigens to T cells escalates metastasis and inflammation. Inflammasome activation and inflammation in several infections are regulated by iron. Based on the discrete reports, we propose a link between iron, inflammation, angiogenesis and tumor growth. Knowing the link better may help us formulate a novel strategy for cancer immunotherapy. PMID:26609256

  1. Infection, Stem Cells and Cancer Signals

    PubMed Central

    Sell, S.

    2013-01-01

    The association of cancer with preceding parasitic infections has been observed for over 200 years. Some such cancers arise from infection of tissue stem cells by viruses with insertion of viral oncogenes into the host DNA (mouse polyoma virus, mouse mammary tumor virus). In other cases the virus does not insert its DNA into the host cells, but rather commandeers the metabolism of the infected cells, so that the cells continue to proliferate and do not differentiate (human papilloma virus and cervical cancer). Cytoplasmic Epstein Barr virus infection is associated with a specific gene translocation (Ig/c-myc) that activates proliferation of affected cells (Burkitt lymphoma). In chronic osteomyelitis an inflammatory reaction to the infection appears to act through production of inflammatory cytokines and oxygen radical formation to induce epithelial cancers. Infection with Helicobacter pylori leads to epigenetic changes in methylation and infection by a parasite. Clonorchis sinensis also acts as a promoter of cancer of the bile ducts of the liver (cholaniocarcinoma). The common thread among these diverse pathways is that the infections act to alter tissue stem cell signaling with continued proliferation of tumor transit amplifying cells. PMID:21044009

  2. Neurotrophin signaling in cancer stem cells.

    PubMed

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

    2016-05-01

    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.

  3. Biomechanical investigation of colorectal cancer cells

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  4. How to search for specific markers of cancer stem cells.

    PubMed

    Liu, Hai Guang; Zhang, Xiao Hua

    2009-01-01

    According to the cancer stem cell hypothesis, cancer stem cells with unlimited self-renewal and multi-differentiation properties such as adult stem cells are the root cause of cancer initiation and progression, and targeted therapy to cancer stem cells is to become the most efficient therapy of cancer. However, specific markers should be discovered to define cancer stem cells accurately before targeted therapy. Therefore, we propose a model of specific markers of cancer stem cells and how to search for such markers.

  5. Cancer stem cells: a metastasizing menace!

    PubMed

    Bandhavkar, Saurabh

    2016-04-01

    Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy. PMID:26773710

  6. Focus Issue: Cell biology meets cancer therapy.

    PubMed

    Gough, Nancy R

    2016-02-16

    Cells are the targets of anticancer therapy, whether the therapy is directed at the tumor cells themselves or the cells of the immune system. Articles in this issue and in the 2015 Science Signaling archives provide insights into what makes a cell responsive to therapy and how understanding the cellular processes affected by the drugs (including endosomal trafficking and response to proteotoxic stress) can lead to personalized cancer therapies, thereby minimizing side effects and ineffective treatment strategies.

  7. Isolation of Cancer Stem Cells From Human Prostate Cancer Samples

    PubMed Central

    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

    2014-01-01

    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

  8. Embryonic stem cell factors and pancreatic cancer

    PubMed Central

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

    2014-01-01

    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. PMID:24605024

  9. Embryonic stem cell factors and pancreatic cancer.

    PubMed

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

    2014-03-01

    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.

  10. Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1.

    PubMed

    Haustein, Maria; Ramer, Robert; Linnebacher, Michael; Manda, Katrin; Hinz, Burkhard

    2014-11-15

    Cannabinoids have been shown to promote the expression of the intercellular adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive and antimetastatic action. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study addressed the impact of cannabinoid-induced ICAM-1 on cancer cell adhesion to lymphokine-activated killer (LAK) cells and LAK cell-mediated cytotoxicity. Cannabidiol (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer cells to adhere to and subsequently be lysed by LAK cells, with both effects being reversed by a neutralizing ICAM-1 antibody. Increased cancer cell lysis by CBD was likewise abrogated when CBD-induced ICAM-1 expression was blocked by specific siRNA or by antagonists to cannabinoid receptors (CB1, CB2) and to transient receptor potential vanilloid 1. In addition, enhanced killing of CBD-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen-1 (LFA-1) suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ(9)-tetrahydrocannabinol (THC) and R(+)-methanandamide (MA), a hydrolysis-stable endocannabinoid analogue. Finally, each cannabinoid elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less pronounced (CBD, THC) or absent (MA) ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible for increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of cannabinoids.

  11. Cell polarity signaling in the plasticity of cancer cell invasiveness.

    PubMed

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

    2016-05-01

    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.

  12. Cell polarity signaling in the plasticity of cancer cell invasiveness

    PubMed Central

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

    2016-01-01

    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. PMID:26872368

  13. Biomechanics and biophysics of cancer cells

    PubMed Central

    Suresh, Subra

    2010-01-01

    The past decade has seen substantial growth in research into how changes in the biomechanical and biophysical properties of cells and subcellular structures influence, and are influenced by, the onset and progression of human diseases. This paper presents an overview of the rapidly expanding, nascent field of research that deals with the biomechanics and biophysics of cancer cells. The review begins with some key observations on the biology of cancer cells and on the role of actin microfilaments, intermediate filaments and microtubule biopolymer cytoskeletal components in influencing cell mechanics, locomotion, differentiation and neoplastic transformation. In order to set the scene for mechanistic discussions of the connections among alterations to subcellular structures, attendant changes in cell deformability, cytoadherence, migration, invasion and tumor metastasis, a survey is presented of the various quantitative mechanical and physical assays to extract the elastic and viscoelastic deformability of cancer cells. Results available in the literature on cell mechanics for different types of cancer are then reviewed. Representative case studies are presented next to illustrate how chemically induced cytoskeletal changes, biomechanical responses and signals from the intracellular regions act in concert with the chemomechanical environment of the extracellular matrix and the molecular tumorigenic signaling pathways to effect malignant transformations. Results are presented to illustrate how changes to cytoskeletal architecture induced by cancer drugs and chemotherapy regimens can significantly influence cell mechanics and disease state. It is reasoned through experimental evidence that greater understanding of the mechanics of cancer cell deformability and its interactions with the extracellular physical, chemical and biological environments offers enormous potential for significant new developments in disease diagnostics, prophylactics, therapeutics and drug

  14. Cytosine methylation profiling of cancer cell lines

    PubMed Central

    Ehrich, Mathias; Turner, Julia; Gibbs, Peter; Lipton, Lara; Giovanneti, Mara; Cantor, Charles; van den Boom, Dirk

    2008-01-01

    DNA-methylation changes in human cancer are complex and vary between the different types of cancer. Capturing this epigenetic variability in an atlas of DNA-methylation changes will be beneficial for basic research as well as translational medicine. Hypothesis-free approaches that interrogate methylation patterns genome-wide have already generated promising results. However, these methods are still limited by their quantitative accuracy and the number of CpG sites that can be assessed individually. Here, we use a unique approach to measure quantitative methylation patterns in a set of >400 candidate genes. In this high-resolution study, we employed a cell-line model consisting of 59 cancer cell lines provided by the National Cancer Institute and six healthy control tissues for discovery of methylation differences in cancer-related genes. To assess the effect of cell culturing, we validated the results from colon cancer cell lines by using clinical colon cancer specimens. Our results show that a large proportion of genes (78 of 400 genes) are epigenetically altered in cancer. Although most genes show methylation changes in only one tumor type (35 genes), we also found a set of genes that changed in many different forms of cancer (seven genes). This dataset can easily be expanded to develop a more comprehensive and ultimately complete map of quantitative methylation changes. Our methylation data also provide an ideal starting point for further translational research where the results can be combined with existing large-scale datasets to develop an approach that integrates epigenetic, transcriptional, and mutational findings. PMID:18353987

  15. Cancer stem cells and cell size: A causal link?

    PubMed

    Li, Qiuhui; Rycaj, Kiera; Chen, Xin; Tang, Dean G

    2015-12-01

    The majority of normal animal cells are 10-20 μm in diameter. Many signaling mechanisms, notably PI3K/Akt/mTOR, Myc, and Hippo pathways, tightly control and coordinate cell growth, cell size, cell division, and cell number during homeostasis. These regulatory mechanisms are frequently deregulated during tumorigenesis resulting in wide variations in cell sizes and increased proliferation in cancer cells. Here, we first review the evidence that primitive stem cells in adult tissues are quiescent and generally smaller than their differentiated progeny, suggesting a correlation between small cell sizes with the stemness. Conversely, increased cell size positively correlates with differentiation phenotypes. We then discuss cancer stem cells (CSCs) and present some evidence that correlates cell sizes with CSC activity. Overall, a causal link between CSCs and cell size is relatively weak and remains to be rigorously assessed. In the future, optimizing methods for isolating cells based on size should help elucidate the connection between cancer cell size and CSC characteristics.

  16. Cancer stem cell plasticity and tumor hierarchy

    PubMed Central

    Cabrera, Marina Carla; Hollingsworth, Robert E; Hurt, Elaine M

    2015-01-01

    The origins of the complex process of intratumoral heterogeneity have been highly debated and different cellular mechanisms have been hypothesized to account for the diversity within a tumor. The clonal evolution and cancer stem cell (CSC) models have been proposed as drivers of this heterogeneity. However, the concept of cancer stem cell plasticity and bidirectional conversion between stem and non-stem cells has added additional complexity to these highly studied paradigms and may help explain the tumor heterogeneity observed in solid tumors. The process of cancer stem cell plasticity in which cancer cells harbor the dynamic ability of shifting from a non-CSC state to a CSC state and vice versa may be modulated by specific microenvironmental signals and cellular interactions arising in the tumor niche. In addition to promoting CSC plasticity, these interactions may contribute to the cellular transformation of tumor cells and affect response to chemotherapeutic and radiation treatments by providing CSCs protection from these agents. Herein, we review the literature in support of this dynamic CSC state, discuss the effectors of plasticity, and examine their role in the development and treatment of cancer. PMID:25621103

  17. Cancer stem cell plasticity and tumor hierarchy.

    PubMed

    Cabrera, Marina Carla; Hollingsworth, Robert E; Hurt, Elaine M

    2015-01-26

    The origins of the complex process of intratumoral heterogeneity have been highly debated and different cellular mechanisms have been hypothesized to account for the diversity within a tumor. The clonal evolution and cancer stem cell (CSC) models have been proposed as drivers of this heterogeneity. However, the concept of cancer stem cell plasticity and bidirectional conversion between stem and non-stem cells has added additional complexity to these highly studied paradigms and may help explain the tumor heterogeneity observed in solid tumors. The process of cancer stem cell plasticity in which cancer cells harbor the dynamic ability of shifting from a non-CSC state to a CSC state and vice versa may be modulated by specific microenvironmental signals and cellular interactions arising in the tumor niche. In addition to promoting CSC plasticity, these interactions may contribute to the cellular transformation of tumor cells and affect response to chemotherapeutic and radiation treatments by providing CSCs protection from these agents. Herein, we review the literature in support of this dynamic CSC state, discuss the effectors of plasticity, and examine their role in the development and treatment of cancer.

  18. Hypoxic Tumor Microenvironment and Cancer Cell Differentiation

    PubMed Central

    Kim, Yuri; Lin, Qun; Glazer, Peter M.; Yun, Zhong

    2010-01-01

    Hypoxia or oxygen deficiency is a salient feature of solid tumors. Hypoxic tumors are often resistant to conventional cancer therapies, and tumor hypoxia correlates with advanced stages of malignancy. Hypoxic tumors appear to be poorly differentiated. Increasing evidence suggests that hypoxia has the potential to inhibit tumor cell differentiation and thus plays a direct role in the maintenance of cancer stem cells. Studies have also shown that hypoxia blocks differentiation of mesenchymal stem/progenitor cells, a potential source of tumor-associated stromal cells. It is therefore likely that hypoxia may have a profound impact on the evolution of the tumor stromal microenvironment. These observations have led to the emergence of a novel paradigm for a role of hypoxia in facilitating tumor progression. Hypoxia may help create a microenvironment enriched in poorly differentiated tumor cells and undifferentiated stromal cells. Such an undifferentiated hypoxic microenvironment may provide essential cellular interactions and environmental signals for the preferential maintenance of cancer stem cells. This hypothesis suggests that effectively targeting hypoxic cancer stem cells is a key to successful tumor control. PMID:19519400

  19. Dendritic cells and immunity against cancer

    PubMed Central

    Palucka, Karolina; Ueno, Hideki; Fay, Joseph; Banchereau, Jacques

    2010-01-01

    SUMMARY T cells can reject established tumors when adoptively transferred into patients, thereby demonstrating the power of the immune system for cancer therapy. However, it has proven difficult to maintain adoptively transferred T cells in the long term. Vaccines have the potential to induce tumor-specific effector and memory T cells. However, clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumor microenvironment. This can be achieved by exploiting the fast increasing knowledge about the dendritic cell (DC) system, including the existence of distinct DC subsets which respond differentially to distinct activation signals, (functional plasticity), both contributing to the generation of unique adaptive immune responses. We foresee that these novel cancer vaccines will be used as monotherapy in patients with resected disease, and in combination with drugs targeting regulatory/suppressor pathways in patients with metastatic disease. PMID:21158979

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

    PubMed Central

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

    2016-01-01

    Cancer cell lines are essential platforms for performing cancer research on human cells. We here demonstrate that, across tumor entities, human cancer cell lines harbor minority populations of putative stem-like cells, molecularly defined by dye extrusion resulting in the side population phenotype. These findings establish a heterogeneous nature of human cancer cell lines and argue for their stem cell origin. This should be considered when interpreting research involving these model systems. PMID:27226981

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

    PubMed Central

    Wang, Ying-Hua; Scadden, David T

    2015-01-01

    Elimination of malignant cells is an unmet challenge for most human cancer types even with therapies targeting specific driver mutations. Therefore, a multi-pronged strategy to alter cancer cell biology on multiple levels is increasingly recognized as essential for cancer cure. One such aspect of cancer cell biology is the relative apoptosis resistance of tumor-initiating cells. Here, we provide an overview of the mechanisms affecting the apoptotic process in tumor cells emphasizing the differences in the tumor-initiating or stem-like cells of cancer. Further, we summarize efforts to exploit these differences to design therapies targeting that important cancer cell population. PMID:26253117

  2. [Cancer stemness and circulating tumor cells].

    PubMed

    Saito, Tomoko; Mimori, Koshi

    2015-05-01

    The principle concept of cancer stem cells (CSCs) giving rise to the carcinogenesis, relapse or metastasis of malignancy is broadly recognized. On the other hand, circulating tumor cells (CTCs) also plays important roles in relapse or metastasis of malignancy, and there has been much focused on the association between CSCs and CTCs in cancer cases. The technical innovations for detection of CTCs enabled us to unveil the nature of CTCs. We now realize that CTCs isolated by cell surface antibodies, such as DCLK1, LGR5 indicated CSC properties, and CTCs with epitherial-mesenchymal transition(EMT) phenotype showed characteristics of CSCs. PMID:25985635

  3. Immune cell interplay in colorectal cancer prognosis

    PubMed Central

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

    2015-01-01

    The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, particularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship between cancer 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. PMID:26483876

  4. Cell Phones and Cancer Risk

    MedlinePlus

    ... Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at NCI (Intramural) ... is heating. The ability of microwave ovens to heat food is one example of this effect of ...

  5. Lipid metabolic reprogramming in cancer cells

    PubMed Central

    Beloribi-Djefaflia, S; Vasseur, S; Guillaumond, F

    2016-01-01

    Many human diseases, including metabolic, immune and central nervous system disorders, as well as cancer, are the consequence of an alteration in lipid metabolic enzymes and their pathways. This illustrates the fundamental role played by lipids in maintaining membrane homeostasis and normal function in healthy cells. We reviewed the major lipid dysfunctions occurring during tumor development, as determined using systems biology approaches. In it, we provide detailed insight into the essential roles exerted by specific lipids in mediating intracellular oncogenic signaling, endoplasmic reticulum stress and bidirectional crosstalk between cells of the tumor microenvironment and cancer cells. Finally, we summarize the advances in ongoing research aimed at exploiting the dependency of cancer cells on lipids to abolish tumor progression. PMID:26807644

  6. Open questions: The disrupted circuitry of the cancer cell

    SciTech Connect

    Wiley, H. Steven

    2014-10-18

    Every new decade of biology brings with it a change in outlook driven by new technologies and fresh perspectives. Such is the case for cancer and how we consider the disease. The advent of molecular biology led to the identification of altered signaling molecules and 'oncogenes' that were proposed to drive uncontrolled cell proliferation. The rise of cell biology and new imaging and culturing technologies led to the idea that disruptions in the extracellular environment prime cells for transformation. In the current genomics era, cancer is most commonly seen as a genetic disorder where an unstable genome gives rise to a variety of different cell variants that are selected for proliferation and survival. All of these views are partially correct, of course, and are simply different ways of saying that genetic alterations in cancer cells result in a loss of growth homeostasis. They also take the view that molecular changes 'drive' a cell to grow uncontrollably, rather than tip the balance from one normal state (quiescence) to another (proliferation). Underlying this oversimplification is a profound ignorance of what controls homeostatic cell growth in the first place and how specific mutations impact it. Normal, proliferation-competent cells can accurately monitor their environment and respond appropriately to perturbation, whether it is a loss of neighbors or an inflammatory stimulus. Cancer cells either proliferate or refuse to die where and when they should not, which clearly indicates that they have problems in detecting or responding to their environment. Thus, an enormous amount of effort has gone into defining the signaling pathways that can trigger a proliferative response and the biochemical mechanisms underlying these pathways. Far less work has focused on understanding the higher-order logic of these pathways and the roles played by all of the components as part of an integrated system. In other words, we do not really understand how cells process

  7. Dielectrophoretic Separation of Cancer Cells from Blood

    PubMed Central

    Gascoyne, Peter R. C.; Wang, Xiao-Bo; Huang, Ying; Becker, Frederick F.

    2009-01-01

    Recent measurements have demonstrated that the dielectric properties of cells depend on their type and physiological status. For example, MDA-231 human breast cancer cells were found to have a mean plasma membrane specific capacitance of 26 mF/m2, more than double the value (11 mF/m2) observed for resting T-lymphocytes. When an inhomogeneous ac electric field is applied to a particle, a dielectrophoretic (DEP) force arises that depends on the particle dielectric properties. Therefore, cells having different dielectric characteristics will experience differential DEP forces when subjected to such a field. In this article, we demonstrate the use of differential DEP forces for the separation of several different cancerous cell types from blood in a dielectric affinity column. These separations were accomplished using thin, flat chambers having microelectrode arrays on the bottom wall. DEP forces generated by the application of ac fields to the electrodes were used to influence the rate of elution of cells from the chamber by hydrodynamic forces within a parabolic fluid flow profile. Electrorotation measurements were first made on the various cell types found within cell mixtures to be separated, and theoretical modeling was used to derive the cell dielectric parameters. Optimum separation conditions were then predicted from the frequency and suspension conductivity dependencies of cell DEP responses defined by these parameters. Cell separations were then undertaken for various ratios of cancerous to normal cells at different concentrations. Eluted cells were characterized in terms of separation efficiency, cell viability, and separation speed. For example, 100% efficiency was achieved for purging MDA-231 cells from blood at the tumor to normal cell ratio 1:1 × 105 or 1:3 × 105, cell viability was not compromised, and separation rates were at least 103 cells/s. Theoretical and experimental criteria for the design and operation of such separators are presented. PMID

  8. Nano-discs Destroy Cancer Cells

    SciTech Connect

    2010-01-01

    A new technique, designed with the potential to treat brain cancers, is under study at Argonne National Laboratory and the University of Chicago Medical Center. The micron-sized magnetic materials, with vortex-like arrangements of spins, were successfully interfaced with Glioblastoma multiforme (GBM) cancer cells. The microdisks are gold-coated and biofunctionalized with a cancer-targeting antibody. The antibody recognizes unique receptors on the cancer cells and attaches to them (and them alone), leaving surrounding healthy cells unaffected during treatment. Under application of an alternative magnetic field, the magnetic vortices shift, leading to oscillatory motion of the disks and causing the magneto-mechanic stimulus to be transmitted directly to the cancer cell. Probably because of the damage to the cancer cell membrane, this results in cellular signal transduction and amplification, causing initiation of apoptosis (programmed cell death or "cell suicide"). Manifestation of apoptosis is of clinical significance because the malignant cells are known to be almost "immortal" (due to suppressed apoptosis), and, consequently, highly resistant to conventional (chemo- and radio-) therapies. Due to unique properties of the vortex microdisks, an extremely high spin-vortex-induced cytotoxicity effect can be caused by application of unprecedentedly weak magnetic fields. An alternative magnetic field as slow as about 10s Hertz (for comparison, 60 Hertz in a electrical outlet) and as small as less than 90 Oersteds (which is actually less than the field produced by a magnetized razor blade) applied only for 10 minutes was sufficient to cause ~90% cancer cell destruction in vitro. The study has only been conducted in cells in a laboratory; animal trials are being planned. Watch a news clip of the story from ABC-7 News: http://abclocal.go.com/wls/story?section=news/health&id=7245605 More details on this study can be found in the original research paper: Biofunctionalized

  9. Access to cancer drugs in Medicare Part D: formulary placement and beneficiary cost sharing in 2006.

    PubMed

    Bowman, Jennifer; Rousseau, Amy; Silk, David; Harrison, Catherine

    2006-01-01

    The Medicare Part D benefit expands the universe of cancer drugs and biologics that Medicare may cover. Individual Part D plans have discretion to determine their formularies and cost sharing for drugs within federal guidelines. This paper analyzes differences in coverage and cost sharing for cancer drugs among these plans. We find that many cancer drugs, including brand-name products, are covered by almost all plans, although prior authorization might limit access to some. In addition, many plans charge a relatively low copayment for most cancer drugs. These findings suggest that Part D could greatly expand beneficiaries' access to cancer treatments.

  10. Cancer-Associated Myeloid Regulatory Cells

    PubMed Central

    De Vlaeminck, Yannick; González-Rascón, Anna; Goyvaerts, Cleo; Breckpot, Karine

    2016-01-01

    Myeloid cells are critically involved in the pathophysiology of cancers. In the tumor microenvironment (TME), they comprise tumor-associated macrophages (TAMs), neutrophils (TANs), dendritic cells, and myeloid-derived suppressor cells, which are further subdivided into a monocytic subset and a granulocytic subset. Some of these myeloid cells, in particular TAMs and TANs, are divided into type 1 or type 2 cells, according to the paradigm of T helper type 1 or type 2 cells. Type 1-activated cells are generally characterized as cells that aid tumor rejection, while all other myeloid cells are shown to favor tumor progression. Moreover, these cells are often at the basis of resistance to various therapies. Much research has been devoted to study the biology of myeloid cells. This endeavor has proven to be challenging, as the markers used to categorize myeloid cells in the TME are not restricted to particular subsets. Also from a functional and metabolic point of view, myeloid cells share many features. Finally, myeloid cells are endowed with a certain level of plasticity, which further complicates studying them outside their environment. In this article, we challenge the exclusive use of cell markers to unambiguously identify myeloid cell subsets in the TME. We further propose to divide myeloid cells into myeloid regulatory or stimulatory cells according to their pro- or antitumor function, because we contend that for therapeutic purposes it is not targeting the cell subsets but rather targeting their protumor traits; hence, myeloid regulatory cells will push antitumor immunotherapy to the next level. PMID:27065074

  11. Cancer cells in the circulating blood

    PubMed Central

    Sato, Haruo

    1962-01-01

    The author discusses the relation between the presence of cancer cells in the circulating blood and the development of metastasis, as demonstrated by studies on animals with experimentally induced tumours, by post-mortem studies on fatal human cases of cancer, and by studies on patients operated upon for stomach cancer. Although the correlation between the presence of tumour cells in the blood and the occurrence of metastatic lesions was found to be less close in the human cases of cancer than in the experimental animals, the author considers that it was sufficiently marked to justify the assumption that the appearance of tumour cells in the circulating blood is an important link in the chain of processes leading to cancer metastasis. In conclusion, the author puts forward the suggestion, based on the results of animal experiments, that chemotherapy might have an inhibitory effect on the liberated tumour cells in the blood, particularly if these cells are present only in small numbers, and thus be instrumental in halting the course of metastasis. PMID:14497407

  12. Cell Membrane Softening in Cancer Cells

    NASA Astrophysics Data System (ADS)

    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.

  13. Hypoxic stellate cells of pancreatic cancer stroma regulate extracellular matrix fiber organization and cancer cell motility.

    PubMed

    Sada, Masafumi; Ohuchida, Kenoki; Horioka, Kohei; Okumura, Takashi; Moriyama, Taiki; Miyasaka, Yoshihiro; Ohtsuka, Takao; Mizumoto, Kazuhiro; Oda, Yoshinao; Nakamura, Masafumi

    2016-03-28

    Desmoplasia and hypoxia in pancreatic cancer mutually affect each other and create a tumor-supportive microenvironment. Here, we show that microenvironment remodeling by hypoxic pancreatic stellate cells (PSCs) promotes cancer cell motility through alteration of extracellular matrix (ECM) fiber architecture. Three-dimensional (3-D) matrices derived from PSCs under hypoxia exhibited highly organized parallel-patterned matrix fibers compared with 3-D matrices derived from PSCs under normoxia, and promoted cancer cell motility by inducing directional migration of cancer cells due to the parallel fiber architecture. Microarray analysis revealed that procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) in PSCs was the gene that potentially regulates ECM fiber architecture under hypoxia. Stromal PLOD2 expression in surgical specimens of pancreatic cancer was confirmed by immunohistochemistry. RNA interference-mediated knockdown of PLOD2 in PSCs blocked parallel fiber architecture of 3-D matrices, leading to decreased directional migration of cancer cells within the matrices. In conclusion, these findings indicate that hypoxia-induced PLOD2 expression in PSCs creates a permissive microenvironment for migration of cancer cells through architectural regulation of stromal ECM in pancreatic cancer.

  14. The role of mast cells in cancers

    PubMed Central

    Maciel, Thiago T.; Moura, Ivan C.

    2015-01-01

    Mast cells are immune cells that accumulate in the tumors and their microenvironment during disease progression. Mast cells are armed with a wide array of receptors that sense environment modifications and, upon stimulation, they are able to secrete several biologically active factors involved in the modulation of tumor growth. For example, mast cells are able to secrete pro-angiogenic and growth factors but also pro- and anti-inflammatory mediators. Recent studies have allowed substantial progress in understanding the role of mast cells in tumorigenesis/disease progression but further studies are necessary to completely elucidate their impact in the pathophysiology of cancer. Here we review observations suggesting that mast cells could modulate tumor growth in humans. We also discuss the drawbacks related to observations from mast cell-deficient mouse models, which could have consequences in the determination of a potential causative relationship between mast cells and cancer. We believe that the understanding of the precise role of mast cells in tumor development and progression will be of critical importance for the development of new targeted therapies in human cancers. PMID:25705392

  15. Opioids and differentiation in human cancer cells.

    PubMed

    Zagon, Ian S; McLaughlin, Patricia J

    2005-10-01

    This study was designed to examine the role of opioids on cell differentiation, with an emphasis on the mechanism of opioid growth factor (OGF, [Met5]-enkephalin)-dependent growth inhibition. Three human cancer cell lines (SK-N-SH neuroblastoma and SCC-1 and CAL-27 squamous cell carcinoma of the head and neck), along with OGF and the opioid antagonist naltrexone (NTX) at a dosage (10(-6) M) known to repress or increase, respectively, cell replication, were utilized. The effects on differentiation (neurite formation, process lengths, betaIII-tubulin, involucrin) were investigated in cells exposed to OGF or NTX for up to 6 days. In addition, the influence of a variety of other natural and synthetic opioids on differentiation was examined. OGF, NTX, naloxone, [D-Pen2,5]-enkephalin, dynorphin A1-8, beta-endorphin, endomorphin-1 and -2, [D-Ala2, MePhe4, Glycol5]-enkephalin (DAMGO), morphine, and U69,593 at concentrations of 10(-6) M did not alter cell differentiation of any cancer cell line. In NTX-treated SK-N-SH cells, cellular area was increased 23%, and nuclear area was decreased 17%, from control levels; no changes in cell or nuclear area were recorded in OGF-exposed cells. F-actin concentration was increased 40% from control values in SK-N-SH cells subjected to NTX, whereas alpha-tubulin was decreased 53% in OGF-treated cells. These results indicate that the inhibitory or stimulatory actions of OGF and NTX, respectively, on cell growth in tissue culture are not due to alterations in differentiation pathways. However, exposure to OGF and NTX modified some aspects of cell structure, but this was independent of differentiation. The absence of effects on cancer cell differentiation by a variety of other opioids supports the previously reported lack of growth effects of these compounds.

  16. The metabolic landscape of cancer stem cells.

    PubMed

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

    2015-09-01

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

  17. Hydrogen Fuel Cells: Part of the Solution

    ERIC Educational Resources Information Center

    Busby, Joe R.; Altork, Linh Nguyen

    2010-01-01

    With the decreasing availability of oil and the perpetual dependence on foreign-controlled resources, many people around the world are beginning to insist on alternative fuel sources. Hydrogen fuel cell technology is one answer to this demand. Although modern fuel cell technology has existed for over a century, the technology is only now becoming…

  18. ICAM1 Is a Potential Cancer Stem Cell Marker of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Tsai, Sheng-Ta; Wang, Po-Jen; Liou, Nia-Jhen; Lin, Pei-Shan; Chen, Chung-Hsuan; Chang, Wei-Chao

    2015-01-01

    Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC) is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1) was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC. PMID:26571024

  19. Cancer Vaccine by Fusions of Dendritic and Cancer Cells

    PubMed Central

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

    2009-01-01

    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. PMID:20182533

  20. Activation of ERK signaling and induction of colon cancer cell death by piperlongumine.

    PubMed

    Randhawa, H; Kibble, K; Zeng, H; Moyer, M P; Reindl, K M

    2013-09-01

    Piperlongumine (PPLGM) is a bioactive compound isolated from long peppers that shows selective toxicity towards a variety of cancer cell types including colon cancer. The signaling pathways that lead to cancer cell death in response to PPLGM exposure have not been previously identified. Our objective was to identify the intracellular signaling mechanisms by which PPLGM leads to enhanced colon cancer cell death. We found that PPLGM inhibited the growth of colon cancer cells in time- and concentration-dependent manners, but was not toxic toward normal colon mucosal cells at concentrations below 10 μM. Acute (0-60 min) and prolonged (24h) exposure of HT-29 cells to PPLGM resulted in phosphorylation of ERK. To investigate whether ERK signaling was involved in PPLGM-mediated cell death, we treated HT-29 cells with the MEK inhibitor U0126, prior to treating with PPLGM. We found that U0126 attenuated PPLGM-induced activation of ERK and partially protected against PPLGM-induced cell death. These results suggest that PPLGM works, at least in part, through the MEK/ERK pathway to result in colon cancer cell death. A more thorough understanding of the molecular mechanisms by which PPLGM induces colon cancer cell death will be useful in developing therapeutic strategies to treat colon cancer.

  1. Cancer Stem Cells: Plasticity Works against Therapy

    PubMed Central

    Vinogradova, T. V.; Chernov, I. P.; Monastyrskaya, G. S.; Kondratyeva, L. G.; Sverdlov, E. D.

    2015-01-01

    Great successes in identification and deciphering of mechanisms of the adult stem cells regulation have given rise to the idea that stem cells can also function in tumors as central elements of their development, starting from the initial stage and continuing until metastasis. Such cells were called cancer stem cells (CSCs). Over the course of intense discussion, the CSCs hypothesis gradually began to be perceived as an obvious fact. Recently, the existence of CSCs has been indeed confirmed in a number of works. However, when are CSCs universal prerequisites of tumors and to what extent their role is essential for tumor evolution remains an issue far from resolved. Likewise, the problem of potential use of CSCs as therapeutic targets remains unsolved. The present review attempts to analyze the issue of cancer stem cells and the potential of targeting them in tumor therapy. PMID:26798491

  2. An update on the biology of cancer stem cells in breast cancer.

    PubMed

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

    2008-12-01

    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.

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

    PubMed Central

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

    2015-01-01

    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 prevent certain cancers. Here, we show that simvastatin decreases the SASP of senescent human fibroblasts by inhibiting protein prenylation, without affecting the senescent growth arrest. The Rho family GTPases Rac1 and Cdc42 were activated in senescent cells, and simvastatin reduced both activities. Further, geranylgeranyl transferase, Rac1 or Cdc42 depletion reduced IL-6 secretion by senescent cells. We also show that simvastatin mitigates the effects of senescent conditioned media on breast cancer cell proliferation and endocrine resistance. Our findings identify a novel activity of simvastatin and mechanism of SASP regulation. They also suggest that senescent cells, which accumulate after radio/chemo therapy, promote endocrine resistance in breast cancer and that simvastatin might suppress this resistance. PMID:26658759

  4. [Cancer cell plasticity and metastatic dissemination].

    PubMed

    Moyret-Lalle, Caroline; Pommier, Roxane; Bouard, Charlotte; Nouri, Ebticem; Richard, Geoffrey; Puisieux, Alain

    Metastatic dissemination consists of a sequence of events resulting in the invasion by cancer cells of tissues located away from the primary tumour. This process is highly inefficient, since each event represents an obstacle that only a limited number of cells can overcome. However, two biological phenomena intrinsically linked with tumour development facilitate the dissemination of cancer cells throughout the body and promote the formation of metastases, namely the genetic diversity of cancer cells within a given tumour, which arises from their genetic instability and from successive clonal expansions, and cellular plasticity conveyed to the cells by micro-environmental signals. Genetic diversity increases the probability of selecting cells that are intrinsically resistant to biological and physical constraints encountered during metastatic dissemination, whereas cellular plasticity provides cells with the capacity to adapt to stressful conditions and to changes in the microenvironment. The epithelial-mesenchymal transition, an embryonic trans-differentiation process frequently reactivated during tumour development, plays an important role in that context by endowing tumor cells with a unique capacity of motility, survival and adaptability to the novel environments and stresses encountered during the invasion-metastasis cascade. PMID:27615180

  5. Comprehensive genomic characterization of squamous cell lung cancers.

    PubMed

    2012-09-27

    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. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers. PMID:22960745

  6. Natural Compounds as Regulators of the Cancer Cell Metabolism

    PubMed Central

    Cerella, Claudia; Radogna, Flavia; Dicato, Mario

    2013-01-01

    Even though altered metabolism is an “old” physiological mechanism, only recently its targeting became a therapeutically interesting strategy and by now it is considered an emerging hallmark of cancer. Nevertheless, a very poor number of compounds are under investigation as potential modulators of cell metabolism. Candidate agents should display selectivity of action towards cancer cells without side effects. This ideal favorable profile would perfectly overlap the requisites of new anticancer therapies and chemopreventive strategies as well. Nature represents a still largely unexplored source of bioactive molecules with a therapeutic potential. Many of these compounds have already been characterized for their multiple anticancer activities. Many of them are absorbed with the diet and therefore possess a known profile in terms of tolerability and bioavailability compared to newly synthetized chemical compounds. The discovery of important cross-talks between mediators of the most therapeutically targeted aberrancies in cancer (i.e., cell proliferation, survival, and migration) and the metabolic machinery allows to predict the possibility that many anticancer activities ascribed to a number of natural compounds may be due, in part, to their ability of modulating metabolic pathways. In this review, we attempt an overview of what is currently known about the potential of natural compounds as modulators of cancer cell metabolism. PMID:23762063

  7. Wnt signaling in cancer stem cells and colon cancer metastasis

    PubMed Central

    Ben-Ze'ev, Avri

    2016-01-01

    Overactivation of Wnt signaling is a hallmark of colorectal cancer (CRC). The Wnt pathway is a key regulator of both the early and the later, more invasive, stages of CRC development. In the normal intestine and colon, Wnt signaling controls the homeostasis of intestinal stem cells (ISCs) that fuel, via proliferation, upward movement of progeny cells from the crypt bottom toward the villus and differentiation into all cell types that constitute the intestine. Studies in recent years suggested that cancer stem cells (CSCs), similar to ISCs of the crypts, consist of a small subpopulation of the tumor and are responsible for the initiation and progression of the disease. Although various ISC signature genes were also identified as CRC markers and some of these genes were even demonstrated to have a direct functional role in CRC development, the origin of CSCs and their contribution to cancer progression is still debated. Here, we describe studies supporting a relationship between Wnt-regulated CSCs and the progression of CRC. PMID:27134739

  8. Piperlongumine induces gastric cancer cell apoptosis and G2/M cell cycle arrest both in vitro and in vivo.

    PubMed

    Duan, Chaoqin; Zhang, Bin; Deng, Chao; Cao, Yu; Zhou, Fan; Wu, Longyun; Chen, Min; Shen, Shanshan; Xu, Guifang; Zhang, Shu; Duan, Guihua; Yan, Hongli; Zou, Xiaoping

    2016-08-01

    Recently, several studies have shown that piperlongumine (PL) can selectively kill cancer cells by targeting reactive oxygen species (ROS). However, the potential therapeutic effects and detailed mechanism of PL in gastric cancer are still not clear. In the current report, we found that PL significantly suppressed gastric cancer both in vitro and in vivo. PL obviously increased ROS generation in gastric cancer cells. Anti-oxidant glutathione (GSH) and N-acetyl-L-cysteine (NAC) can abrogate PL-induced gastric cancer cell death and proliferation inhibition. GADD45α was induced in PL-treated cancer cells and led to G2/M phase arrest, whereas genetic depletion of GADD45α by small interfering RNAs (siRNAs) could partly reverse PL-induced cell cycle arrest in gastric cancer cells. Interestingly, we also found that PL treatment decreased the expression of telomerase reverse transcriptase (TERT) gene, which plays an essential role in cancer initiation and progression. Our findings thus revealed a potential anti-tumor effect of PL on gastric cancer cells and may have therapeutic implications.

  9. Circulating Tumor Cell and Cell-free Circulating Tumor DNA in Lung Cancer.

    PubMed

    Nurwidya, Fariz; Zaini, Jamal; Putra, Andika Chandra; Andarini, Sita; Hudoyo, Achmad; Syahruddin, Elisna; Yunus, Faisal

    2016-09-01

    Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer. PMID:27689025

  10. Circulating Tumor Cell and Cell-free Circulating Tumor DNA in Lung Cancer

    PubMed Central

    Zaini, Jamal; Putra, Andika Chandra; Andarini, Sita; Hudoyo, Achmad; Syahruddin, Elisna; Yunus, Faisal

    2016-01-01

    Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer. PMID:27689025

  11. Circulating Tumor Cell and Cell-free Circulating Tumor DNA in Lung Cancer

    PubMed Central

    Zaini, Jamal; Putra, Andika Chandra; Andarini, Sita; Hudoyo, Achmad; Syahruddin, Elisna; Yunus, Faisal

    2016-01-01

    Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer.

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

    SciTech Connect

    Maneckjee, R.; Minna, J.D. Uniformed Services Univ. of the Health Sciences, Bethesda, MD )

    1990-05-01

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

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

    ClinicalTrials.gov

    2013-01-15

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

  14. Translational potential of cancer stem cells: A review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment.

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2012-01-01

    AIM: To investigate whether the side population (SP) cells possess cancer stem cell-like characteristics in vitro and the role of SP cells in tumorigenic process in gastric cancer. METHODS: We analyzed the presence of SP cells in different human gastric carcinoma cell lines, and then isolated and identified the SP cells from the KATO III human gastric cancer cell line by flow cytometry. The clonogenic ability and self-renewal were evaluated by clone and sphere formation assays. The related genes were determined by reverse transcription polymerase chain reaction. To compare tumorigenic ability, SP and non-side population (NSP) cells from the KATO III human gastric cancer cell line were subcutaneously injected into nude mice. RESULTS: SP cells from the total population accounted for 0.57% in KATO III, 1.04% in Hs-746T, and 0.02% in AGS (CRL-1739). SP cells could grow clonally and have self-renewal capability in conditioned media. The expression of ABCG2, MDRI, Bmi-1 and Oct-4 was different between SP and NSP cells. However, there was no apparent difference between SP and NSP cells when they were injected into nude mice. CONCLUSION: SP cells have some cancer stem cell-like characteristics in vitro and can be used for studying the tumorigenic process in gastric cancer. PMID:22969237

  16. Cancer Cell Colonisation in the Bone Microenvironment

    PubMed Central

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

    2016-01-01

    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

  17. Treatment options for small cell lung cancer.

    PubMed

    Wolf, Todd; Gillenwater, Heidi H

    2004-07-01

    Lung cancer remains the leading cause of cancer-related death in the United States. Small cell lung cancer (SCLC) comprises 15% to 25% of all lung cancers. The leading cause of lung cancer remains smoking, and rates of smoking continue to rise in women, whereas rates in other subgroups have slowed. In this article we review recent advances in the treatment of limited-stage as well as extensive-stage small cell lung cancer. In limited-stage disease, the best survival results are observed when patients are treated with twice-daily thoracic radiotherapy given concurrently with chemotherapy. Patients who have been successful in smoking cessation during therapy for limited-stage disease may have a survival benefit over those who are unable to quit smoking during treatment. In extensive-stage disease, the most significant trial is one comparing irinotecan plus cisplatin and etoposide plus cisplatin, showing a survival advantage for the irinotecan arm. This trial may change the standard of care for patients with extensive-stage disease. A similar ongoing trial in the United States is attempting to confirm these results.

  18. Targeting Lung Cancer Stem Cells with Antipsychological Drug Thioridazine

    PubMed Central

    Yue, Haiying; Huang, Dongning; Qin, Li; Zheng, Zhiyong; Hua, Li; Wang, Guodong; Huang, Jian

    2016-01-01

    Lung cancer stem cells are a subpopulation of cells critical for lung cancer progression, metastasis, and drug resistance. Thioridazine, a classical neurological drug, has been reported with anticancer ability. However, whether thioridazine could inhibit lung cancer stem cells has never been studied. In our current work, we used different dosage of thioridazine to test its effect on lung cancer stem cells sphere formation. The response of lung cancer stem cells to chemotherapy drug with thioridazine treatment was measured. The cell cycle distribution of lung cancer stem cells after thioridazine treatment was detected. The in vivo inhibitory effect of thioridazine was also measured. We found that thioridazine could dramatically inhibit sphere formation of lung cancer stem cells. It sensitized the LCSCs to chemotherapeutic drugs 5-FU and cisplatin. Thioridazine altered the cell cycle distribution of LCSCs and decreased the proportion of G0 phase cells in lung cancer stem cells. Thioridazine inhibited lung cancer stem cells initiated tumors growth in vivo. This study showed that thioridazine could inhibit lung cancer stem cells in vitro and in vivo. It provides a potential drug for lung cancer therapy through targeting lung cancer stem cells. PMID:27556038

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

    SciTech Connect

    Li, Tao; Li, Dong; Sha, Jianjun; Sun, Peng; Huang, Yiran

    2009-06-05

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

  20. Proteomic analysis of cancer stem cells in human prostate cancer cells

    SciTech Connect

    Lee, Eun-Kyung; Cho, Hyungdon; Kim, Chan-Wha

    2011-08-26

    Highlights: {yields} DU145 prostate cancer cell line was isolated into CD44+ or CD44- cells. {yields} We confirmed CD44+ DU145 cells are more proliferative and tumorigenic than CD44- DU145 cells. {yields} We analyzed and identified proteins that were differentially expressed between CD44+ and CD44- DU145 cells. {yields} Cofilin and Annexin A5 associated with cancer were found to be positively correlated with CD44 expression. -- Abstract: Results from recent studies support the hypothesis that cancer stem cells (CSCs) are responsible for tumor initiation and formation. Here, we applied a proteome profiling approach to investigate the mechanisms of CSCs and to identify potential biomarkers in the prostate cancer cell line DU145. Using MACS, the DU145 prostate cancer cell line was isolated into CD44+ or CD44- cells. In sphere culture, CD44+ cells possessed stem cell characteristics and highly expressed genes known to be important in stem cell maintenance. In addition, they showed strong tumorigenic potential in the clonogenic assay and soft agar colony formation assay. We then analyzed and identified proteins that were differentially expressed between CD44+ and CD44- using two-dimensional gel electrophoresis and LC-MS/MS. Cofilin and Annexin A5, which are associated with proliferation or metastasis in cancer, were found to be positively correlated with CD44 expression. These results provide information that will be important to the development of new cancer diagnostic tools and understanding the mechanisms of CSCs although a more detailed study is necessary to investigate the roles of Cofilin and Annexin A5 in CSCs.

  1. Circulating tumor cells in lung cancer.

    PubMed

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

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  3. Immune cell functions in pancreatic cancer.

    PubMed

    Plate, J M; Harris, J E

    2000-01-01

    Pancreatic cancer kills nearly 29,000 people in the United States annually-as many people as are diagnosed with the disease. Chemotherapeutic treatment is ineffective in halting progression of the disease. Yet, specific immunity to pancreatic tumor cells in subjects with pancreatic cancer has been demonstrated repeatedly during the last 24 years. Attempts to expand and enhance tumor-specific immunity with biotherapy, however, have not met with success. The question remains, "Why can't specific immunity regulate pancreatic cancer growth?" The idea that tumor cells have evolved protective mechanisms against immunity was raised years ago and has recently been revisited by a number of research laboratories. In pancreatic cancer, soluble factors produced by and for the protection of the tumor environment have been detected and are often distributed to the victim's circulatory system where they may effect a more generalized immunosuppression. Yet the nature of these soluble factors remains controversial, since some also serve as tumor antigens that are recognized by the same T cells that may become inactivated by them. Unless the problem of tumor-derived immunosuppressive products is addressed directly through basic and translational research studies, successful biotherapeutic treatment for pancreatic cancer may not be forthcoming.

  4. Circulating Tumor Cells in Breast Cancer Patients.

    PubMed

    Hall, Carolyn; Valad, Lily; Lucci, Anthony

    2016-01-01

    Breast cancer is the most commonly diagnosed cancer among women, resulting in an estimated 40,000 deaths in 2014.1 Metastasis, a complex, multi-step process, remains the primary cause of death for these patients. Although the mechanisms involved in metastasis have not been fully elucidated, considerable evidence suggests that metastatic spread is mediated by rare cells within the heterogeneous primary tumor that acquire the ability to invade into the bloodstream. In the bloodstream, they can travel to distant sites, sometimes remaining undetected and in a quiescent state for an extended period of time before they establish distant metastases in the bone, lung, liver, or brain. These occult micrometastatic cells (circulating tumor cells, CTCs) are rare, yet their prognostic significance has been demonstrated in both metastatic and non-metastatic breast cancer patients. Because repeated tumor tissue collection is typically not feasible and peripheral blood draws are minimally invasive, serial CTC enumeration might provide "real-time liquid biopsy" snapshots that could be used to identify early-stage breast cancer patients with micrometastatic disease who are at risk for disease progression and monitor treatment response in patients with advanced disease. In addition, characterizing CTCs might aid in the development of novel, personalized therapies aimed at eliminating micrometastases. This review describes current CTC isolation, detection, and characterization strategies in operable breast cancer. PMID:27481009

  5. Apoptotic Death of Cancer Stem Cells for Cancer Therapy

    PubMed Central

    He, Ying-Chun; Zhou, Fang-Liang; Shen, Yi; Liao, Duan-Fang; Cao, Deliang

    2014-01-01

    Cancer stem cells (CSCs) play crucial roles in tumor progression, chemo- and radiotherapy resistance, and recurrence. Recent studies on CSCs have advanced understanding of molecular oncology and development of novel therapeutic strategies. This review article updates the hypothesis and paradigm of CSCs with a focus on major signaling pathways and effectors that regulate CSC apoptosis. Selective CSC apoptotic inducers are introduced and their therapeutic potentials are discussed. These include synthetic and natural compounds, antibodies and recombinant proteins, and oligonucleotides. PMID:24823879

  6. An ecosystem of cancer cell line factories to support a cancer dependency map.

    PubMed

    Boehm, Jesse S; Golub, Todd R

    2015-07-01

    Jesse Boehm and Todd Golub call for an international effort to establish >10,000 cancer cell line models as a community resource. Cancer cell line factories will facilitate the creation of a cancer dependency map, connecting cancer genomics to therapeutic dependencies.

  7. Modeling Selective Elimination of Quiescent Cancer Cells from Bone Marrow

    PubMed Central

    Cavnar, Stephen P.; Rickelmann, Andrew D.; Meguiar, Kaille F.; Xiao, Annie; Dosch, Joseph; Leung, Brendan M.; Cai Lesher-Perez, Sasha; Chitta, Shashank; Luker, Kathryn E.; Takayama, Shuichi; Luker, Gary D.

    2015-01-01

    Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer. PMID:26408255

  8. Therapeutic strategies impacting cancer cell glutamine metabolism

    PubMed Central

    Lukey, Michael J; Wilson, Kristin F; Cerione, Richard A

    2014-01-01

    The metabolic adaptations that support oncogenic growth can also render cancer cells dependent on certain nutrients. Along with the Warburg effect, increased utilization of glutamine is one of the metabolic hallmarks of the transformed state. Glutamine catabolism is positively regulated by multiple oncogenic signals, including those transmitted by the Rho family of GTPases and by c-Myc. The recent identification of mechanistically distinct inhibitors of glutaminase, which can selectively block cellular transformation, has revived interest in the possibility of targeting glutamine metabolism in cancer therapy. Here, we outline the regulation and roles of glutamine metabolism within cancer cells and discuss possible strategies for, and the consequences of, impacting these processes therapeutically. PMID:24047273

  9. Targeting angiogenesis in small cell lung cancer

    PubMed Central

    Matikas, Alexios; Voutsina, Alexandra; Mavroudis, Dimitrios; Georgoulias, Vassilis

    2016-01-01

    Small cell lung cancer (SCLC) is a highly aggressive and lethal malignancy. Despite high initial response rates to systemic chemotherapy, the disease eventually relapses; further treatment only modestly improves outcomes and overall survival (OS) for patients with extensive stage disease is less than one year. Little progress has been made during the past decades, with no new drugs approved. Consequently, the development of novel strategies is an unmet need. The inhibition of angiogenesis, a defining characteristic of cancer, has demonstrated modest efficacy in several human malignancies, including non-small cell lung cancer (NSCLC). However, results from clinical trials in SCLC have been disappointing, and no anti-angiogenic agent has received regulatory approval due to lack of clinical efficacy. The elucidation of underlying mechanisms responsible for tumor resistance to angiogenic therapy and the simultaneous blockade of multiple elements that play a role in angiogenesis need to be further explored. PMID:27652203

  10. Targeting angiogenesis in small cell lung cancer

    PubMed Central

    Matikas, Alexios; Voutsina, Alexandra; Mavroudis, Dimitrios; Georgoulias, Vassilis

    2016-01-01

    Small cell lung cancer (SCLC) is a highly aggressive and lethal malignancy. Despite high initial response rates to systemic chemotherapy, the disease eventually relapses; further treatment only modestly improves outcomes and overall survival (OS) for patients with extensive stage disease is less than one year. Little progress has been made during the past decades, with no new drugs approved. Consequently, the development of novel strategies is an unmet need. The inhibition of angiogenesis, a defining characteristic of cancer, has demonstrated modest efficacy in several human malignancies, including non-small cell lung cancer (NSCLC). However, results from clinical trials in SCLC have been disappointing, and no anti-angiogenic agent has received regulatory approval due to lack of clinical efficacy. The elucidation of underlying mechanisms responsible for tumor resistance to angiogenic therapy and the simultaneous blockade of multiple elements that play a role in angiogenesis need to be further explored.

  11. Targeting angiogenesis in small cell lung cancer.

    PubMed

    Stratigos, Michalis; Matikas, Alexios; Voutsina, Alexandra; Mavroudis, Dimitrios; Georgoulias, Vassilis

    2016-08-01

    Small cell lung cancer (SCLC) is a highly aggressive and lethal malignancy. Despite high initial response rates to systemic chemotherapy, the disease eventually relapses; further treatment only modestly improves outcomes and overall survival (OS) for patients with extensive stage disease is less than one year. Little progress has been made during the past decades, with no new drugs approved. Consequently, the development of novel strategies is an unmet need. The inhibition of angiogenesis, a defining characteristic of cancer, has demonstrated modest efficacy in several human malignancies, including non-small cell lung cancer (NSCLC). However, results from clinical trials in SCLC have been disappointing, and no anti-angiogenic agent has received regulatory approval due to lack of clinical efficacy. The elucidation of underlying mechanisms responsible for tumor resistance to angiogenic therapy and the simultaneous blockade of multiple elements that play a role in angiogenesis need to be further explored. PMID:27652203

  12. EXAFS studies of prostate cancer cell lines

    NASA Astrophysics Data System (ADS)

    Czapla, J.; Kwiatek, W. M.; Lekki, J.; Kisiel, A.; Steininger, R.; Goettlicher, J.

    2013-04-01

    Sulphur plays a vital role in every human organism. It is known, that sulphur-bearing compounds, such as for example cysteine and glutathione, play critical roles in development and progression of many diseases. Any alteration in sulphur's biochemistry could become a precursor of serious pathological conditions. One of such condition is prostate cancer, the most frequently diagnosed malignancy in the western world and the second leading cause of cancer related death in men. The purpose of presented studies was to examine what changes occur in the nearest chemical environment of sulphur in prostate cancer cell lines in comparison to healthy cells. The Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy was used, followed by theoretical calculations. The results of preliminary analysis is presented.

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

    PubMed

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

    2012-04-01

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

  14. Human Colon Cancer Cells Cultivated in Space

    NASA Technical Reports Server (NTRS)

    1995-01-01

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

  15. The African-American cancer crisis, Part II: A prescription.

    PubMed

    Byrd, W M; Clayton, L A

    1993-01-01

    To appreciate the causes of the African-American cancer crisis, contemporary myths and perceptual gaps regarding cancer in blacks must be analyzed and placed in historical context. Since ancient times, racism has permeated western scientific, medical, and social cultures. Yet contemporary analysts typically frame a 370-year-old African-American health deficit in nonracial terms, and ignore both the metamorphosis of racism and the impact of racism on the prevention, diagnosis, and treatment of cancer; exposure to cancer-causing industrial pollutants; educational opportunities for black health professionals and policymakers, and other factors. If the African-American cancer crisis is to be halted, the growing divergence between urgent needs and meager resources devoted to preventing, detecting, and treating cancer in blacks must be sharply reversed.

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

    PubMed

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

    2016-04-25

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

  17. Chordin-Like 1 Suppresses Bone Morphogenetic Protein 4-Induced Breast Cancer Cell Migration and Invasion

    PubMed Central

    Cyr-Depauw, Chanèle; Northey, Jason J.; Tabariès, Sébastien; Annis, Matthew G.; Dong, Zhifeng; Cory, Sean; Hallett, Michael; Rennhack, Jonathan P.; Andrechek, Eran R.

    2016-01-01

    ShcA is an important mediator of ErbB2- and transforming growth factor β (TGF-β)-induced breast cancer cell migration, invasion, and metastasis. We show that in the context of reduced ShcA levels, the bone morphogenetic protein (BMP) antagonist chordin-like 1 (Chrdl1) is upregulated in numerous breast cancer cells following TGF-β stimulation. BMPs have emerged as important modulators of breast cancer aggressiveness, and we have investigated the ability of Chrdl1 to block BMP-induced increases in breast cancer cell migration and invasion. Breast cancer-derived conditioned medium containing elevated concentrations of endogenous Chrdl1, as well as medium containing recombinant Chrdl1, suppresses BMP4-induced signaling in multiple breast cancer cell lines. Live-cell migration assays reveal that BMP4 induces breast cancer migration, which is effectively blocked by Chrdl1. We demonstrate that BMP4 also stimulated breast cancer cell invasion and matrix degradation, in part, through enhanced metalloproteinase 2 (MMP2) and MMP9 activity that is antagonized by Chrdl1. Finally, high Chrdl1 expression was associated with better clinical outcomes in patients with breast cancer. Together, our data reveal that Chrdl1 acts as a negative regulator of malignant breast cancer phenotypes through inhibition of BMP signaling. PMID:26976638

  18. Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

    ClinicalTrials.gov

    2016-10-18

    Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

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

    SciTech Connect

    Felthaus, O.; Ettl, T.; Gosau, M.; Driemel, O.; Brockhoff, G.; Reck, A.; Zeitler, K.; Hautmann, M.; Reichert, T.E.; Schmalz, G.; Morsczeck, C.

    2011-04-01

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

  20. How does cancer cell metabolism affect tumor migration and invasion?

    PubMed

    Han, Tianyu; Kang, De; Ji, Daokun; Wang, Xiaoyu; Zhan, Weihua; Fu, Minggui; Xin, Hong-Bo; Wang, Jian-Bin

    2013-01-01

    Cancer metastasis is the major cause of cancer-associated death. Accordingly, identification of the regulatory mechanisms that control whether or not tumor cells become "directed walkers" is a crucial issue of cancer research. The deregulation of cell migration during cancer progression determines the capacity of tumor cells to escape from the primary tumors and invade adjacent tissues to finally form metastases. The ability to switch from a predominantly oxidative metabolism to glycolysis and the production of lactate even when oxygen is plentiful is a key characteristic of cancer cells. This metabolic switch, known as the Warburg effect, was first described in 1920s, and affected not only tumor cell growth but also tumor cell migration. In this review, we will focus on the recent studies on how cancer cell metabolism affects tumor cell migration and invasion. Understanding the new aspects on molecular mechanisms and signaling pathways controlling tumor cell migration is critical for development of therapeutic strategies for cancer patients.

  1. The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms

    PubMed Central

    Abdal Dayem, Ahmed; Choi, Hye Yeon; Yang, Gwang-Mo; Kim, Kyeongseok; Saha, Subbroto Kumar; Cho, Ssang-Goo

    2016-01-01

    The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The interplay between autophagy and apoptosis in the anti-cancer activity of polyphenols will also be highlighted. In addition, the potential of polyphenols to target cancer stem cells (CSCs) via various mechanisms will be explained. Recently, the use of natural products as chemotherapeutics and chemopreventive drugs to overcome the side effects and resistance that arise from using chemical-based agents has garnered the attention of the scientific community. Polyphenol research is considered a promising field in the treatment and prevention of breast cancer. PMID:27657126

  2. What Is Kidney Cancer (Renal Cell Carcinoma)?

    MedlinePlus

    ... the key statistics 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 ...

  3. Knockdown of Legumain Suppresses Cervical Cancer Cell Migration and Invasion.

    PubMed

    Meng, Fei; Liu, Wei

    2016-01-01

    Cervical cancer is the second leading type of cancer in women living in less developed countries. The pathological and molecular mechanisms of cervical cancer are not comprehensively known. Though legumain has been found to be highly expressed in various types of solid tumors, its expression and biological function in cervical cancer remain unknown. In this study, we aimed to investigate legumain expression and functions in cervical cancer. We found that legumain was highly expressed in cervical cancer cells. When knocked down, legumain expression in HeLa and SiHa cells significantly reduced its migration and invasion abilities compared with control cells. Furthermore, legumain silencing suppressed the activation of matrix metalloproteases (MMP2 and MMP3) in cervical cancer cells. This study indicates that legumain might play an important role in cervical cancer cell migration and invasion. Legumain might be a potential therapeutic target for cervical cancer therapy.

  4. Mouth Cancer for Clinicians Part 5: Risk Factors (Other).

    PubMed

    Kalavrezos, Nicholas; Scully, Crispian

    2015-10-01

    A MEDLINE search early in 2015 revealed more than 250,000 papers on head and neck cancer; over 100,000 on oral cancer; and over 60,000 on mouth cancer. Not all publications contain robust evidence. We endeavour to encapsulate the most important of the latest information and advances now employed in practice, in a form comprehensible to healthcare workers, patients and their carers. This series offers the primary care dental team, in particular, an overview of the aetiopathogenesis, prevention, diagnosis and multidisciplinary care of mouth cancer, the functional and psychosocial implications, and minimization of the impact on the quality of life of patient and family. Clinical Relevance: This article offers the dental team an overview of other cancer risk factors agents, such as human papilloma viruses (HPV) and irradiation. PMID:26685475

  5. Mouth Cancer for Clinicians Part 3: Risk Factors (Traditional: Tobacco).

    PubMed

    Kalavrezos, Nicholas; Scully, Crispian

    2015-06-01

    A MEDLINE search early in 2015 revealed more than 250,000 papers on head and neck cancer; over 100,000 on oral cancer; and over 60,000 on mouth cancer. Not all publications contain robust evidence. We endeavour to encapsulate the most important of the latest information and advances now employed in practice, in a form comprehensible to healthcare workers, patients and their carers. This series offers the primary care dental team, in particular, an overview of the aetiopathogenesis, prevention, diagnosis and multidisciplinary care of mouth cancer, the functional and psychosocial implications, and minimization of the impact on the quality of life of patient and family. CPD/CLINICAL RELEVANCE: This article offers the dental team an overview of the main cancer risk factors, tobacco and alcohol, betel and other chewing habits, and environmental factors. PMID:26964449

  6. Circulating tumor cells in colorectal cancer patients.

    PubMed

    Torino, Francesco; Bonmassar, Enzo; Bonmassar, Laura; De Vecchis, Liana; Barnabei, Agnese; Zuppi, Cecilia; Capoluongo, Ettore; Aquino, Angelo

    2013-11-01

    The availability of sensitive methods has allowed the detailed study of circulating tumor cells only recently. Evolving evidence support the prognostic and predictive role of these cells in patients affected by several solid tumors, including colorectal cancer. Ongoing studies are aimed at confirming that the molecular characterization of circulating tumor cells in peripheral blood and in bone marrow of patients is a powerful tool to improve the patient risk-stratification, to monitor activity of the drugs, to develop more appropriate targeted therapies and tailored treatments. In parallel, results from these correlative studies promise to gain a better biological understanding of the metastatic process. The clinical utility of the detection of circulating tumor cells in patients affected by colorectal cancer is still hampered by a number of specific hurdles. Improvement in sensitivity and specificity of the available methods of detection, standardization of these methods and functional characterization of circulating tumor cells in well designed and statistically well powered studies are the key steps to reach these ambitious objectives in colorectal cancer patients as well.

  7. Squamous cell lung cancer: from tumor genomics to cancer therapeutics.

    PubMed

    Gandara, David R; Hammerman, Peter S; Sos, Martin L; Lara, Primo N; Hirsch, Fred R

    2015-05-15

    Squamous cell lung cancer (SCC) represents an area of unmet need in lung cancer research. For the past several years, therapeutic progress in SCC has lagged behind the now more common non-small cell lung cancer histologic subtype of adenocarcinoma. However, recent efforts to define the complex biology underlying SCC have begun to bear fruit in a multitude of ways, including characterization of previously unknown genomic and signaling pathways, delineation of new, potentially actionable molecular targets, and subsequent development of a large number of agents directed against unique SCC-associated molecular abnormalities. For the first time, SCC-specific prognostic gene signatures and predictive biomarkers of new therapeutic agents are emerging. In addition, recent and ongoing clinical trials, including the Lung-MAP master protocol, have been designed to facilitate approval of targeted therapy-biomarker combinations. In this comprehensive review, we describe the current status of SCC therapeutics, recent advances in the understanding of SCC biology and prognostic gene signatures, and the development of innovative new clinical trials, all of which offer new hope for patients with advanced SCC.

  8. Principles of adoptive T cell cancer therapy

    PubMed Central

    June, Carl H.

    2007-01-01

    The transfusion of T cells, also called adoptive T cell therapy, is an effective treatment for viral infections and has induced regression of cancer in early-stage clinical trials. However, recent advances in cellular immunology and tumor biology are guiding new approaches to adoptive T cell therapy. For example, use of engineered T cells is being tested as a strategy to improve the functions of effector and memory T cells, and manipulation of the host to overcome immunotoxic effects in the tumor microenvironment has led to promising results in early-stage clinical trials. Challenges that face the field and must be addressed before adoptive T cell therapy can be translated into routine clinical practice are discussed. PMID:17476350

  9. Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer

    ClinicalTrials.gov

    2013-03-25

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

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

    ClinicalTrials.gov

    2011-11-28

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

  11. Hazard function for cancer patients and cancer cell dynamics.

    PubMed

    Horová, Ivana; Pospísil, Zdenek; Zelinka, Jirí

    2009-06-01

    The aim of the paper is to develop a procedure for an estimate of an analytical form of a hazard function for cancer patients. Although a deterministic approach based on cancer cell population dynamics yields the analytical expression, it depends on several parameters which should be estimated. On the other hand, a kernel estimate is an effective nonparametric method for estimating hazard functions. This method provides the pointwise estimate of the hazard function. Our procedure consists of two steps: in the first step we find the kernel estimate of the hazard function and in the second step the parameters in the deterministic model are obtained by the least squares method. A simulation study with different types of censorship is carried out and the developed procedure is applied to real data. PMID:18634801

  12. Hazard function for cancer patients and cancer cell dynamics.

    PubMed

    Horová, Ivana; Pospísil, Zdenek; Zelinka, Jirí

    2009-06-01

    The aim of the paper is to develop a procedure for an estimate of an analytical form of a hazard function for cancer patients. Although a deterministic approach based on cancer cell population dynamics yields the analytical expression, it depends on several parameters which should be estimated. On the other hand, a kernel estimate is an effective nonparametric method for estimating hazard functions. This method provides the pointwise estimate of the hazard function. Our procedure consists of two steps: in the first step we find the kernel estimate of the hazard function and in the second step the parameters in the deterministic model are obtained by the least squares method. A simulation study with different types of censorship is carried out and the developed procedure is applied to real data.

  13. Single-Cell-Precision Microplasma-Induced Cancer Cell Apoptosis

    PubMed Central

    Lu, Xinpei; He, Guangyuan; Ostrikov, Kostya

    2014-01-01

    The issue of single-cell control has recently attracted enormous interest. However, in spite of the presently achievable intracellular-level physiological probing through bio-photonics, nano-probe-based, and some other techniques, the issue of inducing selective, single-cell-precision apoptosis, without affecting neighbouring cells remains essentially open. Here we resolve this issue and report on the effective single-cell-precision cancer cell treatment using the reactive chemistry of the localized corona-type plasma discharge around a needle-like electrode with the spot size ∼1 µm. When the electrode is positioned with the micrometer precision against a selected cell, a focused and highly-localized micro-plasma discharge induces apoptosis in the selected individual HepG2 and HeLa cancer cells only, without affecting any surrounding cells, even in small cell clusters. This is confirmed by the real-time monitoring of the morphological and structural changes at the cellular and cell nucleus levels after the plasma exposure. PMID:24971517

  14. Stem cells: tissue regeneration and cancer.

    PubMed

    Tataria, Monika; Perryman, Scott V; Sylvester, Karl G

    2006-11-01

    Regenerative medicine is the promised paradigm of replacement and repair of damaged or senescent tissues. As the building blocks for organ development and tissue repair, stem cells have unique and wide-ranging capabilities, thus delineating their potential application to regenerative medicine. The recognition that consistent patterns of molecular mechanisms drive organ development and postnatal tissue regeneration has significant implications for a variety of pediatric diseases beyond replacement biology. The observation that organ-specific stem cells derive all of the differentiated cells within a given tissue has led to the acceptance of a stem cell hierarchy model for tissue development, maintenance, and repair. Extending the tissue stem cell hierarchical model to tissue carcinogenesis may revolutionize the manner in which we conceptualize cancer therapeutics. In this review, the clinical promise of these technologies and the emerging concept of "cancer stem cells" are examined. A basic understanding of stem cell biology is paramount to stay informed of this emerging technology and the accompanying research in this area with the potential for clinical application. PMID:17055959

  15. Light induced drug delivery into cancer cells.

    PubMed

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

    2011-02-01

    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. PMID:21074848

  16. Light induced drug delivery into cancer cells.

    PubMed

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

    2011-02-01

    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.

  17. Lycopene and apo-12'-lycopenal reduce cell proliferation and alter cell cycle progression in human prostate cancer cells.

    PubMed

    Ford, Nikki A; Elsen, Amy C; Zuniga, Krystle; Lindshield, Brian L; Erdman, John W

    2011-01-01

    Lycopene is associated with a reduced risk of prostate cancer. However, lycopene may not be wholly responsible for the effects seen in vivo or in cell culture systems. Apo-lycopenals or other lycopene metabolites, whether produced by cleavage enzymes within the body or consumed with tomato products, can be found in tissues at concentrations equivalent to physiological retinoid concentrations. Therefore, it is plausible that lycopenoids, like retinoids, are bioactive within tissues. Androgen-independent DU145 prostate cancer cells were treated with lycopene, apo-8'-lycopenal, or apo-12'-lycopenal. DU145 cell proliferation was significantly reduced by supra-physiological levels of lycopene and apo-12'-lycopenal, in part, through alteration of the normal cell cycle. Levels of the gap junction protein, connexin 43, were unaltered by lycopene or apo-lycopenal treatment while cell apoptosis rates significantly decreased. We further confirmed that connexin 43 protein levels were unaltered by lycopene treatment in mouse embryonic fibroblasts, or in Dunning R3327-H rat prostate tumor. The present data indicate that lycopene and apo-12'-lycopenal reduce the proliferation of prostate cancer cells, in part, by inhibiting normal cell cycle progression. PMID:21207319

  18. A novel steroidal saponin glycoside from Fagonia indica induces cell-selective apoptosis or necrosis in cancer cells.

    PubMed

    Waheed, Abdul; Barker, James; Barton, Stephen J; Owen, Caroline P; Ahmed, Sabbir; Carew, Mark A

    2012-09-29

    Fagonia indica is a small spiny shrub of great ethnopharmacological importance in folk medicine. The aqueous decoction of aerial parts is a popular remedy against various skin lesions, including cancer. We used a biological activity-guided fractionation approach to isolate the most potent fraction of the crude extract on three cancer cell lines: MCF-7 oestrogen-dependent breast cancer, MDA-MB-468 oestrogen-independent breast cancer, and Caco-2 colon cancer cells. A series of chromatographic and spectroscopic procedures were utilised on the EtOAc fraction, which resulted in the isolation of a new steroidal saponin glycoside. The cytotoxic activity of the saponin glycoside was determined in cancer cells using the MTT and neutral red uptake assays. After 24h treatment, the observed IC(50) values of the saponin glycoside were 12.5 μM on MDA-MB-468 and Caco-2 cells, but 100 μM on MCF-7 cells. Several lines of evidence: PARP cleavage, caspase-3 cleavage, DNA ladder assays, and reversal of growth inhibition with the pan-caspase inhibitor Z-VAD-fmk, suggested stimulation of apoptosis in MDA-MB-468 and Caco-2 cells, but not in MCF-7 cells, which do not express caspase-3. The haemolytic activity of the saponin glycoside was confirmed in sheep red blood cells, with cell lysis observed at >100 μM, suggesting that, at this concentration, the saponin glycoside caused necrosis through cell lysis in MCF-7 cells. Using the DNA ladder assay, the saponin glycoside (12.5 μM) was not toxic to HUVEC (human umbilical vein endothelial cells) or U937 cells, indicating some selectivity between malignant and normal cells. We conclude that the steroidal saponin glycoside isolated from F. indica is able to induce apoptosis or necrosis in cancer cells depending on the cell type. PMID:22800968

  19. Hypoxia and metabolic adaptation of cancer cells

    PubMed Central

    Eales, K L; Hollinshead, K E R; Tennant, D A

    2016-01-01

    Low oxygen tension (hypoxia) is a pervasive physiological and pathophysiological stimulus that metazoan organisms have contended with since they evolved from their single-celled ancestors. The effect of hypoxia on a tissue can be either positive or negative, depending on the severity, duration and context. Over the long-term, hypoxia is not usually consistent with normal function and so multicellular organisms have had to evolve both systemic and cellular responses to hypoxia. Our reliance on oxygen for efficient adenosine triphosphate (ATP) generation has meant that the cellular metabolic network is particularly sensitive to alterations in oxygen tension. Metabolic changes in response to hypoxia are elicited through both direct mechanisms, such as the reduction in ATP generation by oxidative phosphorylation or inhibition of fatty-acid desaturation, and indirect mechanisms including changes in isozyme expression through hypoxia-responsive transcription factor activity. Significant regions of cancers often grow in hypoxic conditions owing to the lack of a functional vasculature. As hypoxic tumour areas contain some of the most malignant cells, it is important that we understand the role metabolism has in keeping these cells alive. This review will outline our current understanding of many of the hypoxia-induced changes in cancer cell metabolism, how they are affected by other genetic defects often present in cancers, and how these metabolic alterations support the malignant hypoxic phenotype. PMID:26807645

  20. Anal Cancer Rates Rising in Many Parts of The World

    MedlinePlus

    ... Services, or federal policy. More Health News on: Health Disparities HPV Recent Health News Related MedlinePlus Health Topics Anal Cancer Health Disparities HPV About MedlinePlus Site Map FAQs Contact Us ...

  1. Cancer cell labeling and tracking using fluorescent and magnetic nanodiamond.

    PubMed

    Lien, Zhi-Yi; Hsu, Tzu-Chia; Liu, Kuang-Kai; Liao, Wei-Siang; Hwang, Kuo-Chu; Chao, Jui-I

    2012-09-01

    Nanodiamond, a promising carbon nanomaterial, develops for biomedical applications such as cancer cell labeling and detection. Here, we establish the nanodiamond-bearing cancer cell lines using the fluorescent and magnetic nanodiamond (FMND). Treatment with FMND particles did not significantly induce cytotoxicity and growth inhibition in HFL-1 normal lung fibroblasts and A549 lung cancer cells. The fluorescence intensities and particle complexities were increased in a time- and concentration-dependent manner by treatment with FMND particles in lung cancer cells; however, the existence of FMND particles inside the cells did not alter cellular size distribution. The FMND-bearing lung cancer cells could be separated by the fluorescent and magnetic properties of FMNDs using the flow cytometer and magnetic device, respectively. The FMND-bearing cancer cells were identified by the existence of FMNDs using flow cytometer and confocal microscope analysis. More importantly, the cell morphology, viability, growth ability and total protein expression profiles in the FMND-bearing cells were similar to those of the parental cells. The separated FMND-bearing cells with various generations were cryopreservation for further applications. After re-thawing the FMND-bearing cancer cell lines, the cells still retained the cell survival and growth ability. Additionally, a variety of human cancer types including colon (RKO), breast (MCF-7), cervical (HeLa), and bladder (BFTC905) cancer cells could be used the same strategy to prepare the FMND-bearing cancer cells. These results show that the FMND-bearing cancer cell lines, which reserve the parental cell functions, can be applied for specific cancer cell labeling and tracking.

  2. Stem cells in normal mammary gland and breast cancer.

    PubMed

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

    2010-04-01

    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.

  3. Synergistic Effect and Molecular Mechanisms of Traditional Chinese Medicine on Regulating Tumor Microenvironment and Cancer Cells.

    PubMed

    Xu, Jingnan; Song, Zhuo; Guo, Qiujun; Li, Jie

    2016-01-01

    The interaction of tumor cells with the microenvironment is like a relationship between the "seeds" and "soil," which is a hotspot in recent cancer research. Targeting at tumor microenvironment as well as tumor cells has become a new strategy for cancer treatment. Conventional cancer treatments mostly focused on single targets or single mechanism (the seeds or part of the soil); few researches intervened in the whole tumor microenvironment and achieved ideal therapeutic effect as expected. Traditional Chinese medicine displays a broad range of biological effects, and increasing evidence has shown that it may relate with synergistic effect on regulating tumor microenvironment and cancer cells. Based on literature review and our previous studies, we summarize the synergistic effect and the molecular mechanisms of traditional Chinese medicine on regulating tumor microenvironment and cancer cells.

  4. Synergistic Effect and Molecular Mechanisms of Traditional Chinese Medicine on Regulating Tumor Microenvironment and Cancer Cells

    PubMed Central

    Song, Zhuo; Li, Jie

    2016-01-01

    The interaction of tumor cells with the microenvironment is like a relationship between the “seeds” and “soil,” which is a hotspot in recent cancer research. Targeting at tumor microenvironment as well as tumor cells has become a new strategy for cancer treatment. Conventional cancer treatments mostly focused on single targets or single mechanism (the seeds or part of the soil); few researches intervened in the whole tumor microenvironment and achieved ideal therapeutic effect as expected. Traditional Chinese medicine displays a broad range of biological effects, and increasing evidence has shown that it may relate with synergistic effect on regulating tumor microenvironment and cancer cells. Based on literature review and our previous studies, we summarize the synergistic effect and the molecular mechanisms of traditional Chinese medicine on regulating tumor microenvironment and cancer cells. PMID:27042656

  5. Plasma membrane calcium channels in cancer: Alterations and consequences for cell proliferation and migration.

    PubMed

    Déliot, Nadine; Constantin, Bruno

    2015-10-01

    The study of calcium channels in molecular mechanisms of cancer transformation is still a novel area of research. Several studies, mostly conducted on cancer cell lines, however support the idea that a diversity of plasma membrane channels participates in the remodeling of Ca2+ homeostasis, which regulates various cancer hallmarks such as uncontrolled multiplication and increase in migration and invasion abilities. However few is still understood concerning the intracellular signaling cascades mobilized by calcium influx participating to cancer cell behavior. This review intends to gather some of these pathways dependent on plasma membrane calcium channels and described in prostate, breast and lung cancer cell lines. In these cancer cell types, the calcium channels involved in calcium signaling pathways promoting cancer behaviors are mostly non-voltage activated calcium channels and belong to the TRP superfamily (TRPC, TPRPV and TRPM families) and the Orai family. TRP and Orai channels are part of many signaling cascades involving the activation of transmembrane receptors by extracellular ligand from the tumor environment. TRPV can sense changes in the physical and chemical environment of cancer cells and TRPM7 are stretch activated and sensitive to cholesterol. Changes in activation and or expression of plasma-membrane calcium channels affect calcium-dependent signaling processes relevant to tumorigenesis. The studies cited in this review suggest that an increase in plasma membrane calcium channel expression and/or activity sustain an elevated calcium entry (constitutive or under the control of extracellular signals) promoting higher cell proliferation and migration in most cases. A variety of non-voltage-operated calcium channels display change expression and/or activity in a same cancer type and cooperate to the same process relevant to cancer cell behavior, or can be involved in a different sequence of events during the tumorigenesis. This article is part of a

  6. The Colon Cancer Stem Cell Microenvironment Holds Keys to Future Cancer Therapy

    PubMed Central

    Huang, Emina H.

    2014-01-01

    Background Colorectal cancer remains the most common gastrointestinal cancer. While screening combined with effective surgical treatment has reduced its mortality, we still do not have effective means to prevent recurrence nor to treat metastatic disease. What we know about cancer biology has gone through revolutionary changes in recent decades. The advent of the cancer stem cell theory has accelerated our understanding of the cancer cell. However, there is increasing evidence that cancer cells are influenced by their surrounding microenvironment. Purpose This review divides the tumor microenvironment into four functional components—the stem cell niche, cancer stroma, immune cells, and vascular endothelia—and examines their individual and collective influence on the growth and metastasis of the colon cancer stem cell. The discussion will highlight the need to fully exploit the tumor microenvironment when designing future prognostic tools and therapies. PMID:24643495

  7. Integromic analysis of the NCI-60 cancer cell lines.

    PubMed

    Weinstein, John N

    2004-01-01

    Microarray-based transcript profiling has become exceedingly popular, particularly for breast cancer. However, other 'omic' profiling technologies at the DNA, RNA, protein, functional, and pharmacological levels are also becoming increasingly practical. We define 'integromics' as the melding of such diverse types of data from different experimental platforms. The whole can sometimes be more than the sum of its parts. We describe here a set of integromic studies in which we have profiled the 60 human cancer cell lines (the NCI-60) used by the National Cancer Institute to screen >100,000 chemical compounds over the last 13 years. Patterns of potency in the screen can be mapped into molecular structures of the compounds or into molecular characteristics of the cells. Here we discuss conceptual and experimental aspects of the profiling, as well as a number of bioinformatic computer programs (CIMminer, MedMiner, MatchMiner, and GoMiner) that we have developed for biological interpretation of the profiles. As briefly reviewed here, we have used the combination of NCI-60 data types to identify markers for distinguishing tumor types and to obtain pharmacogenomic clues for possible individualization of a cancer therapy. PMID:15687693

  8. Drug insight: cancer therapy strategies based on restoration of endogenous cell death mechanisms.

    PubMed

    Reed, John C

    2006-07-01

    Cell death is a normal facet of human physiology, ensuring tissue homeostasis by offsetting cell production with cell demise. Neoplasms arise in part because of defects in physiological cell death mechanisms, contributing to pathological cell expansion. Defects in normal cell death pathways also contribute to cancer progression by permitting progressively aberrant cell behaviors, while also desensitizing tumor cells to immune-mediated attack, radiation, and chemotherapy. Through basic research, much has been learned about the molecular mechanisms responsible for cell turnover and how tumors escape cell death. By exploiting this knowledge base, several innovative strategies for eradicating malignancies have materialized that are based on restoration of natural pathways for cell autodestruction. Some of these strategies have advanced into human clinical trials. Several of the current strategies based on targeting core components of the cell death machinery for cancer therapy are reviewed here, and a summary of progress toward clinical applications is provided. PMID:16826219

  9. Tumoral stem cell reprogramming as a driver of cancer: Theory, biological models, implications in cancer therapy.

    PubMed

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

    2015-06-01

    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.

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

    PubMed

    Hu, Chenxia; Niestroj, Martin; Yuan, Daniel; Chang, Steven; Chen, Jie

    2015-01-01

    Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain). Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension) form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs) with thio-PEG (polyethylene glycol) and thio-glucose, the resulting functionalized GNPs (Glu-GNPs) were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients) was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells' elevated glucose consumption over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line) were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design

  11. Heat induces gene amplification in cancer cells

    SciTech Connect

    Yan, Bin; Ouyang, Ruoyun; Huang, Chenghui; Liu, Franklin; Neill, Daniel; Li, Chuanyuan; Dewhirst, Mark

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer This study discovered that heat exposure (hyperthermia) results in gene amplification in cancer cells. Black-Right-Pointing-Pointer Hyperthermia induces DNA double strand breaks. Black-Right-Pointing-Pointer DNA double strand breaks are considered to be required for the initiation of gene amplification. Black-Right-Pointing-Pointer The underlying mechanism of heat-induced gene amplification is generation of DNA double strand breaks. -- Abstract: Background: Hyperthermia plays an important role in cancer therapy. However, as with radiation, it can cause DNA damage and therefore genetic instability. We studied whether hyperthermia can induce gene amplification in cancer cells and explored potential underlying molecular mechanisms. Materials and methods: (1) Hyperthermia: HCT116 colon cancer cells received water-submerged heating treatment at 42 or 44 Degree-Sign C for 30 min; (2) gene amplification assay using N-(phosphoacetyl)-L-aspartate (PALA) selection of cabamyl-P-synthetase, aspartate transcarbarmylase, dihydro-orotase (cad) gene amplified cells; (3) southern blotting for confirmation of increased cad gene copies in PALA-resistant cells; (4) {gamma}H2AX immunostaining to detect {gamma}H2AX foci as an indication for DNA double strand breaks. Results: (1) Heat exposure at 42 or 44 Degree-Sign C for 30 min induces gene amplification. The frequency of cad gene amplification increased by 2.8 and 6.5 folds respectively; (2) heat exposure at both 42 and 44 Degree-Sign C for 30 min induces DNA double strand breaks in HCT116 cells as shown by {gamma}H2AX immunostaining. Conclusion: This study shows that heat exposure can induce gene amplification in cancer cells, likely through the generation of DNA double strand breaks, which are believed to be required for the initiation of gene amplification. This process may be promoted by heat when cellular proteins that are responsible for checkpoints, DNA replication, DNA repair and

  12. Telomeres, stem cells, senescence, and cancer

    PubMed Central

    Sharpless, Norman E.; DePinho, Ronald A.

    2004-01-01

    Mammalian aging occurs in part because of a decline in the restorative capacity of tissue stem cells. These self-renewing cells are rendered malignant by a small number of oncogenic mutations, and overlapping tumor suppressor mechanisms (e.g., p16INK4a-Rb, ARF-p53, and the telomere) have evolved to ward against this possibility. These beneficial antitumor pathways, however, appear also to limit the stem cell life span, thereby contributing to aging. PMID:14722605

  13. Identification of Replication Competent Murine Gammaretroviruses in Commonly Used Prostate Cancer Cell Lines

    PubMed Central

    Sfanos, Karen Sandell; Aloia, Amanda L.; Hicks, Jessica L.; Esopi, David M.; Steranka, Jared P.; Shao, Wei; Sanchez-Martinez, Silvia; Yegnasubramanian, Srinivasan; Burns, Kathleen H.; Rein, Alan; De Marzo, Angelo M.

    2011-01-01

    A newly discovered gammaretrovirus, termed XMRV, was recently reported to be present in the prostate cancer cell line CWR22Rv1. Using a combination of both immunohistochemistry with broadly-reactive murine leukemia virus (MLV) anti-sera and PCR, we determined if additional prostate cancer or other cell lines contain XMRV or MLV-related viruses. Our study included a total of 72 cell lines, which included 58 of the 60 human cancer cell lines used in anticancer drug screens and maintained at the NCI-Frederick (NCI-60). We have identified gammaretroviruses in two additional prostate cancer cell lines: LAPC4 and VCaP, and show that these viruses are replication competent. Viral genome sequencing identified the virus in LAPC4 and VCaP as nearly identical to another known xenotropic MLV, Bxv-1. We also identified a gammaretrovirus in the non-small-cell lung carcinoma cell line EKVX. Prostate cancer cell lines appear to have a propensity for infection with murine gammaretroviruses, and we propose that this may be in part due to cell line establishment by xenograft passage in immunocompromised mice. It is unclear if infection with these viruses is necessary for cell line establishment, or what confounding role they may play in experiments performed with these commonly used lines. Importantly, our results suggest a need for regular screening of cancer cell lines for retroviral “contamination”, much like routine mycoplasma testing. PMID:21698104

  14. Targeting cancer cell metabolism in pancreatic adenocarcinoma

    PubMed Central

    Cohen, Romain; Neuzillet, Cindy; Tijeras-Raballand, Annemilaï; Faivre, Sandrine; de Gramont, Armand; Raymond, Eric

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer death by 2030. Current therapeutic options are limited, warranting an urgent need to explore innovative treatment strategies. Due to specific microenvironment constraints including an extensive desmoplastic stroma reaction, PDAC faces major metabolic challenges, principally hypoxia and nutrient deprivation. Their connection with oncogenic alterations such as KRAS mutations has brought metabolic reprogramming to the forefront of PDAC therapeutic research. The Warburg effect, glutamine addiction, and autophagy stand as the most important adaptive metabolic mechanisms of cancer cells themselves, however metabolic reprogramming is also an important feature of the tumor microenvironment, having a major impact on epigenetic reprogramming and tumor cell interactions with its complex stroma. We present a comprehensive overview of the main metabolic adaptations contributing to PDAC development and progression. A review of current and future therapies targeting this range of metabolic pathways is provided. PMID:26164081

  15. Inside the 2016 American Society of Clinical Oncology Genitourinary Cancers Symposium: part 2 - prostate and bladder cancer.

    PubMed

    Buti, Sebastiano; Ciccarese, Chiara; Iacovelli, Roberto; Bersanelli, Melissa; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo; Tortora, Giampaolo; Massari, Francesco

    2016-09-01

    The American Society of Clinical Oncology Genitourinary Cancers Symposium, Moscone West Building, San Francisco, CA, USA, 7-9 January 2016 The American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held in San Francisco (CA, USA), from 7 to 9 January 2016, focused on 'patient-centric care: translating research to results'. Every year, this meeting is a must for anyone studying genitourinary tumors to keep abreast of the most recent innovations in this field, exchange views on behaviors customarily adopted in daily clinical practice and discuss future topics of scientific research. This two-part report highlights the key themes presented at the 2016 ASCO Genitourinary Cancers Symposium, with part 1 reporting the main novelties of kidney cancer and part 2 discussing the most relevant issues which have emerged for bladder and prostate tumors.

  16. Disseminated prostate cancer cells can instruct hematopoietic stem and progenitor cells to regulate bone phenotype.

    PubMed

    Joseph, Jeena; Shiozawa, Yusuke; Jung, Younghun; Kim, Jin Koo; Pedersen, Elisabeth; Mishra, Anjali; Zalucha, Janet Linn; Wang, Jingcheng; Keller, Evan T; Pienta, Kenneth J; Taichman, Russell S

    2012-03-01

    Prostate cancer metastases and hematopoietic stem cells (HSC) frequently home to the bone marrow, where they compete to occupy the same HSC niche. We have also shown that under conditions of hematopoietic stress, HSCs secrete the bone morphogenetic proteins (BMP)-2 and BMP-6 that drives osteoblastic differentiation from mesenchymal precursors. As it is not known, we examined whether metastatic prostate cancer cells can alter regulation of normal bone formation by HSCs and hematopoietic progenitor cells (HPC). HSC/HPCs isolated from mice bearing nonmetastatic and metastatic tumor cells were isolated and their ability to influence osteoblastic and osteoclastic differentiation was evaluated. When the animals were inoculated with the LNCaP C4-2B cell line, which produces mixed osteoblastic and osteolytic lesions in bone, HPCs, but not HSCs, were able to induced stromal cells to differentiate down an osteoblastic phenotype. Part of the mechanism responsible for this activity was the production of BMP-2. On the other hand, when the animals were implanted with PC3 cells that exhibits predominantly osteolytic lesions in bone, HSCs derived from these animals were capable of directly differentiating into tartrate-resistant acid phosphatase-positive osteoclasts through an interleukin-6-mediated pathway. These studies for the first time identify HSC/HPCs as novel targets for future therapy involved in the bone abnormalities of prostate cancer.

  17. Mutations in ribosomal proteins: Apoptosis, cell competition, and cancer.

    PubMed

    Baker, Nicholas E; Kale, Abhijit

    2016-01-01

    Mutations affecting multiple ribosomal proteins are implicated in cancer. Using genetic mosaics in the fruit fly Drosophila, we describe 3 apoptotic mechanisms that affect Rp/Rp homozygous mutant cells, Rp/+ heterozygous cells, or Rp/+ heterozygous cells in competition with nearby wild type cells, and discuss how apoptosis might be related to cancer predisposition. PMID:27308545

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  19. Differential effects of bisphosphonates on breast cancer cell lines.

    PubMed

    Verdijk, R; Franke, H R; Wolbers, F; Vermes, I

    2007-02-01

    Bisphosphonates may induce direct anti-tumor effects in breast cancer cells in vitro. In this study, six bisphosphonates were administered to three breast cancer cell lines. Cell proliferation was measured by quantification of the expression of Cyclin D1 mRNA. Apoptosis was determined by flow cytometry of a DNA fragmentation assay. We demonstrated that bisphosphonates have direct effects on cell proliferation and apoptosis in different breast cancer cell lines. However, not all bisphosphonates act equally on breast cancer cells in vitro. Zoledronate seems to be the most potent of the six bisphosphonates. This in vitro study showed that bisphosphonates possess promising anti-tumor potential.

  20. Therapeutic Effectiveness of Anticancer Phytochemicals on Cancer Stem Cells

    PubMed Central

    Oh, Jisun; Hlatky, Lynn; Jeong, Yong-Seob; Kim, Dohoon

    2016-01-01

    Understanding how to target cancer stem cells (CSCs) may provide helpful insights for the development of therapeutic or preventive strategies against cancers. Dietary phytochemicals with anticancer properties are promising candidates and have selective impact on CSCs. This review summarizes the influence of phytochemicals on heterogeneous cancer cell populations as well as on specific targeting of CSCs. PMID:27376325

  1. LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

    PubMed

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

    2013-04-01

    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.

  2. Open questions: The disrupted circuitry of the cancer cell

    DOE PAGES

    Wiley, H. Steven

    2014-10-18

    Every new decade of biology brings with it a change in outlook driven by new technologies and fresh perspectives. Such is the case for cancer and how we consider the disease. The advent of molecular biology led to the identification of altered signaling molecules and 'oncogenes' that were proposed to drive uncontrolled cell proliferation. The rise of cell biology and new imaging and culturing technologies led to the idea that disruptions in the extracellular environment prime cells for transformation. In the current genomics era, cancer is most commonly seen as a genetic disorder where an unstable genome gives rise tomore » a variety of different cell variants that are selected for proliferation and survival. All of these views are partially correct, of course, and are simply different ways of saying that genetic alterations in cancer cells result in a loss of growth homeostasis. They also take the view that molecular changes 'drive' a cell to grow uncontrollably, rather than tip the balance from one normal state (quiescence) to another (proliferation). Underlying this oversimplification is a profound ignorance of what controls homeostatic cell growth in the first place and how specific mutations impact it. Normal, proliferation-competent cells can accurately monitor their environment and respond appropriately to perturbation, whether it is a loss of neighbors or an inflammatory stimulus. Cancer cells either proliferate or refuse to die where and when they should not, which clearly indicates that they have problems in detecting or responding to their environment. Thus, an enormous amount of effort has gone into defining the signaling pathways that can trigger a proliferative response and the biochemical mechanisms underlying these pathways. Far less work has focused on understanding the higher-order logic of these pathways and the roles played by all of the components as part of an integrated system. In other words, we do not really understand how cells process

  3. [Case of heterochronous triple urogenital cancer (renal cell carcinoma, bladder cancer, prostatic cancer)].

    PubMed

    Okumura, Akiou; Tsuritani, Shinji; Takagawa, Kiyoshi; Fuse, Hideki

    2013-11-01

    We report a case of a 73-year-old male with heterochronous triple urogenital cancer. The patient was referred to our hospital because serum PSA was elevated (7.0 ng/ml) in 1998. Prostatic needle biopsy revealed prostatic cancer in the right lobe, and total prostatectomy was performed. The histopathological diagnosis was moderately differentiated adenocarcinoma (TlcNOMO). Non-muscle invasive bladder cancer (NMIBC) was detected during an examination for microhematuria in 2002. Transurethral resection of the bladder tumor (TURBT) procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). A right renal mass was detected incidentally on follow-up CT for bladder cancer in 2008. Renal enucleation was performed in 2009. The histopathological diagnosis was grade 2 clear cell renal cell carcinoma (pTlaNXMO). NMIBC was detected on follow-up urethrocystoscopy in 2011. The TURBT procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). On follow-up for urogenital cancer patients, it is important to investigate recurrence of the primary cancer and also heterochronous canceration of other urogenital organs.

  4. Hepatocellular carcinoma cells cause different responses in expressions of cancer-promoting genes in different cancer-associated fibroblasts.

    PubMed

    Lin, Zu-Yau; Chuang, Wan-Long

    2013-06-01

    Cancer-associated fibroblast (CAF) is one of the most crucial components of the tumor microenvironment to promote the invasiveness of cancer cells. The interactions between cancer cells and CAFs are bidirectional. Our recent study showed that up-regulations of chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 26 (CCL26), interleukin 6 (IL6), and lysyl oxidase-like 2 (LOXL2) genes in cancer cells were parts of the common effects of CAFs on hepatocellular carcinoma (HCC) cells to promote proliferation, migration and invasion of cancer cells. However, the subject of how HCC cells to influence the gene expressions of CAFs still needs to be clarified. The purpose of this study was to investigate this issue. Two human HCC (HCC24/KMUH, HCC38/KMUH) and two human CAF cell lines (F26/KMUH, F28/KMUH) were studied. Influence of HCC38/KMUH cancer cells on differential expressions of genes in F28/KMUH CAFs was detected by microarray to select target genes for further analysis. Both HCC cell lines increased proliferation (all p < 0.005) and migration (all p < 0.0001) of two CAF cell lines. HCC24/KMUH cancer cells had stronger ability to promote migration of F26/KMUH CAFs than HCC38/KMUH cancer cells did (p < 0.0001). Eleven up-regulated cancer-promoting genes, including apelin (APLN), CCL2, CCL26, fibroblast growth factor 1 (FGF1), fibroblast growth factor 2 (FGF2), IL6, mucin 1 (MUC1), LOXL2, platelet-derived growth factor alpha polypeptide (PDGFA), phosphoglycerate kinase 1 (PGK1), and vascular endothelial growth factor A (VEGFA) detected by microarray showed good correlation with results of quantitative reverse transcriptase-polymerase chain reaction study. Among these genes, HCC24/KMUH cancer cells had same tendency of effects on differential expressions of genes in F28/KMUH CAFs as HCC38/KMUH cancer cells did. However, the responses of F26/KMUH CAFs to different HCC cell lines were variable. Only PGK1 gene was consistently up-regulated and PDGFA gene

  5. Hepatocellular carcinoma cells cause different responses in expressions of cancer-promoting genes in different cancer-associated fibroblasts.

    PubMed

    Lin, Zu-Yau; Chuang, Wan-Long

    2013-06-01

    Cancer-associated fibroblast (CAF) is one of the most crucial components of the tumor microenvironment to promote the invasiveness of cancer cells. The interactions between cancer cells and CAFs are bidirectional. Our recent study showed that up-regulations of chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 26 (CCL26), interleukin 6 (IL6), and lysyl oxidase-like 2 (LOXL2) genes in cancer cells were parts of the common effects of CAFs on hepatocellular carcinoma (HCC) cells to promote proliferation, migration and invasion of cancer cells. However, the subject of how HCC cells to influence the gene expressions of CAFs still needs to be clarified. The purpose of this study was to investigate this issue. Two human HCC (HCC24/KMUH, HCC38/KMUH) and two human CAF cell lines (F26/KMUH, F28/KMUH) were studied. Influence of HCC38/KMUH cancer cells on differential expressions of genes in F28/KMUH CAFs was detected by microarray to select target genes for further analysis. Both HCC cell lines increased proliferation (all p < 0.005) and migration (all p < 0.0001) of two CAF cell lines. HCC24/KMUH cancer cells had stronger ability to promote migration of F26/KMUH CAFs than HCC38/KMUH cancer cells did (p < 0.0001). Eleven up-regulated cancer-promoting genes, including apelin (APLN), CCL2, CCL26, fibroblast growth factor 1 (FGF1), fibroblast growth factor 2 (FGF2), IL6, mucin 1 (MUC1), LOXL2, platelet-derived growth factor alpha polypeptide (PDGFA), phosphoglycerate kinase 1 (PGK1), and vascular endothelial growth factor A (VEGFA) detected by microarray showed good correlation with results of quantitative reverse transcriptase-polymerase chain reaction study. Among these genes, HCC24/KMUH cancer cells had same tendency of effects on differential expressions of genes in F28/KMUH CAFs as HCC38/KMUH cancer cells did. However, the responses of F26/KMUH CAFs to different HCC cell lines were variable. Only PGK1 gene was consistently up-regulated and PDGFA gene

  6. Stacking the DEK: from chromatin topology to cancer stem cells.

    PubMed

    Privette Vinnedge, Lisa M; Kappes, Ferdinand; Nassar, Nicolas; Wells, Susanne I

    2013-01-01

    Stem cells are essential for development and tissue maintenance and display molecular markers and functions distinct from those of differentiated cell types in a given tissue. Malignant cells that exhibit stem cell-like activities have been detected in many types of cancers and have been implicated in cancer recurrence and drug resistance. Normal stem cells and cancer stem cells have striking commonalities, including shared cell surface markers and signal transduction pathways responsible for regulating quiescence vs. proliferation, self-renewal, pluripotency and differentiation. As the search continues for markers that distinguish between stem cells, progenitor cells and cancer stem cells, growing evidence suggests that a unique chromatin-associated protein called DEK may confer stem cell-like qualities. Here, we briefly describe current knowledge regarding stem and progenitor cells. We then focus on new findings that implicate DEK as a regulator of stem and progenitor cell qualities, potentially through its unusual functions in the regulation of local or global chromatin organization.

  7. [Advances in Lung Stem Cells and Lung Cancer Stem Cells].

    PubMed

    Yin, Huijing; Deng, Jiong

    2015-10-20

    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.

  8. Wnt/{beta}-catenin signaling regulates cancer stem cells in lung cancer A549 cells

    SciTech Connect

    Teng, Ying; Wang, Xiuwen; Wang, Yawei; Ma, Daoxin

    2010-02-12

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

  9. Cell-ECM Interactions During Cancer Invasion

    NASA Astrophysics Data System (ADS)

    Jiang, Yi

    The extracellular matrix (ECM), a fibrous material that forms a network in a tissue, significantly affects many aspects of cellular behavior, including cell movement and proliferation. Transgenic mouse tumor studies indicate that excess collagen, a major component of ECM, enhances tumor formation and invasiveness. Clinically, tumor associated collagen signatures are strong markers for breast cancer survival. However, the underlying mechanisms are unclear since the properties of ECM are complex, with diverse structural and mechanical properties depending on various biophysical parameters. We have developed a three-dimensional elastic fiber network model, and parameterized it with in vitro collagen mechanics. Using this model, we study ECM remodeling as a result of local deformation and cell migration through the ECM as a network percolation problem. We have also developed a three-dimensional, multiscale model of cell migration and interaction with ECM. Our model reproduces quantitative single cell migration experiments. This model is a first step toward a fully biomechanical cell-matrix interaction model and may shed light on tumor associated collagen signatures in breast cancer. This work was partially supported by NIH-U01CA143069.

  10. The health of healthcare, Part II: patient healthcare has cancer.

    PubMed

    Waldman, Deane

    2013-01-01

    In this article, we make the etiologic diagnosis for a sick patient named Healthcare: the cancer of greed. When we explore the two forms of this cancer--corporate and bureaucratic--we find the latter is the greater danger to We the Patients. The "treatments" applied to patient Healthcare by the Congressional "doctors" have consistently made the patient worse, not better. At the core of healthcare's woes is the government's diversion of money from healthcare services to healthcare bureaucracy. As this is the root cause, it is what we must address in order to cure, not sedate or palliate, patient Healthcare. PMID:24236323

  11. An Easy-to-Assemble Three-Part Galvanic Cell

    ERIC Educational Resources Information Center

    Eggen, Per-Odd; Skaugrud, Brit

    2015-01-01

    The galvanic cell presented in this article is made of only three parts, is easy to assemble, and can light a red light emitting diode (LED). The three cell components consist of a piece of paper with copper sulfate, a piece of paper with sodium sulfate, and a piece of magnesium ribbon. Within less than 1 h, students have time to discuss the…

  12. Cavitary lung cancer lined with normal bronchial epithelium and cancer cells.

    PubMed

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

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells. PMID:21980325

  13. General Information about Non-Small Cell Lung Cancer

    MedlinePlus

    ... most patients with non-small cell lung cancer, current treatments do not cure the cancer. If lung ... professional versions have detailed information written in technical language. The patient versions are written in easy-to- ...

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. [Study of cancer cells fluorescence lifetime based on picosecond time resolution].

    PubMed

    Chen, Bi-Fang; Liu, Tian-Fu

    2006-08-01

    The object of the present study was the ultrafast photodynamic processes of hematoporphyrin derivative (HPD) for diagnosis and therapy of cancer. Time-resolved fluorescence spectra of cancerous and normal cells were measured using an ultrashort pulse laser spectral technique and picosecond time-correlated single-photon counting system. The fast part of cancerous and normal cells fluorescence decay was approximately 150 and 300 ps, the fluorescence peak intensity of cancerous and normal cells decayed about 10% and 55% in 12 hour, the lifetime of cancerous and normal cells was about 824 and 1 798 ps by calculating date of fluorescence decay, and HPD stay time was about 17 and 6 days in the cancerous and normal cells sample respectively. The data show that cancerous cells were greatly intimate with HPD. The results obtained can be used as an important basis for the diagnosis of cancer based on ultrashort pulse laser spectral technique. The results will contribute to feebleness ultrafast fluorescence of biology sample for real time measurement. PMID:17058959

  17. Can Nanomedicines Kill Cancer Stem Cells?

    PubMed Central

    Zhao, Yi; Alakhova, Daria Y.; Kabanov, Alexander V.

    2014-01-01

    Most tumors are heterogeneous and many cancers contain small population of highly tumorigenic and intrinsically drug resistant cancer stem cells (CSCs). Like normal stem cell, CSCs have ability to self-renew and differentiate to other tumor cell types. They are believed to be a source for drug resistance, tumor recurrence and metastasis. CSCs often overexpress drug efflux transporters, spend most of their time in non-dividing G0 cell cycle state, and therefore, can escape the conventional chemotherapies. Thus, targeting CSCs is essential for developing novel therapies to prevent cancer relapse and emerging of drug resistance. Nanocarrier-based therapeutic agents (nanomedicines) have been used to achieve longer circulation times, better stability and bioavailability over current therapeutics. Recently, some groups have successfully applied nanomedicines to target CSCs to eliminate the tumor and prevent its recurrence. These approaches include 1) delivery of therapeutic agents (small molecules, siRNA, antibodies) that affect embryonic signaling pathways implicated in self-renewal and differentiation in CSCs, 2) inhibiting drug efflux transporters in an attempt to sensitize CSCs to therapy, 3) targeting metabolism in CSCs through nanoformulated chemicals and field-responsive magnetic nanoparticles and carbon nanotubes, and 4) disruption of multiple pathways in drug resistant cells using combination of chemotherapeutic drugs with amphiphilic Pluronic block copolymers. Despite clear progress of these studies the challenges of targeting CSCs by nanomedicines still exist and leave plenty of room for improvement and development. This review summarizes biological processes that are related to CSCs, overviews the current state of anti-CSCs therapies, and discusses state-of-the-art nanomedicine approaches developed to kill CSCs. PMID:24120657

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

    PubMed

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

    2005-01-01

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

  19. Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2016-05-26

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  20. Fusion of bone marrow-derived cells with cancer cells: metastasis as a secondary disease in cancer

    PubMed Central

    Pawelek, John M.

    2014-01-01

    This perspective article highlights the leukocyte-cancer cell hybrid theory as a mechanism for cancer metastasis. Beginning from the first proposal of the theory more than a century ago and continuing today with the first proof for this theory in a human cancer, the hybrid theory offers a unifying explanation for metastasis. In this scenario, leukocyte fusion with a cancer cell is a secondary disease superimposed upon the early tumor, giving birth to a new, malignant cell with a leukocyte-cancer cell hybrid epigenome. PMID:24589183

  1. Integrin Signaling in Cancer Cell Survival and Chemoresistance

    PubMed Central

    Aoudjit, Fawzi; Vuori, Kristiina

    2012-01-01

    Resistance to apoptosis and chemotherapy is a hallmark of cancer cells, and it is a critical factor in cancer recurrence and patient relapse. Extracellular matrix (ECM) via its receptors, the integrins, has emerged as a major pathway contributing to cancer cell survival and resistance to chemotherapy. Several studies over the last decade have demonstrated that ECM/integrin signaling provides a survival advantage to various cancer cell types against numerous chemotherapeutic drugs and against antibody therapy. In this paper, we will discuss the major findings on how ECM/integrin signaling protects tumor cells from drug-induced apoptosis. We will also discuss the potential role of ECM in malignant T-cell survival and in cancer stem cell resistance. Understanding how integrins and their signaling partners promote tumor cell survival and chemoresistance will likely lead to the development of new therapeutic strategies and agents for cancer treatment. PMID:22567280

  2. Targeting Cell Survival Proteins for Cancer Cell Death

    PubMed Central

    Pandey, Manoj K.; Prasad, Sahdeo; Tyagi, Amit Kumar; Deb, Lokesh; Huang, Jiamin; Karelia, Deepkamal N.; Amin, Shantu G.; Aggarwal, Bharat B.

    2016-01-01

    Escaping from cell death is one of the adaptations that enable cancer cells to stave off anticancer therapies. The key players in avoiding apoptosis are collectively known as survival proteins. Survival proteins comprise the Bcl-2, inhibitor of apoptosis (IAP), and heat shock protein (HSP) families. The aberrant expression of these proteins is associated with a range of biological activities that promote cancer cell survival, proliferation, and resistance to therapy. Several therapeutic strategies that target survival proteins are based on mimicking BH3 domains or the IAP-binding motif or competing with ATP for the Hsp90 ATP-binding pocket. Alternative strategies, including use of nutraceuticals, transcriptional repression, and antisense oligonucleotides, provide options to target survival proteins. This review focuses on the role of survival proteins in chemoresistance and current therapeutic strategies in preclinical or clinical trials that target survival protein signaling pathways. Recent approaches to target survival proteins-including nutraceuticals, small-molecule inhibitors, peptides, and Bcl-2-specific mimetic are explored. Therapeutic inventions targeting survival proteins are promising strategies to inhibit cancer cell survival and chemoresistance. However, complete eradication of resistance is a distant dream. For a successful clinical outcome, pretreatment with novel survival protein inhibitors alone or in combination with conventional therapies holds great promise. PMID:26927133

  3. Chemotherapy for Advanced Non-small Cell Lung Cancer.

    PubMed

    Dietrich, Martin F; Gerber, David E

    2016-01-01

    Non-small cell lung cancer has seen an unprecedented augmentation of therapeutic options over the last couple of years. Improved understanding of molecular drivers and the role of the immune system in cancer therapy have brought new drugs to the armamentarium. Despite these advances, cytotoxic chemotherapy remains a substantial part of therapy for most patients in locally advanced and metastatic stage. Initially thought to be a chemotherapy-resistant entity, meta-analyses in the mid-1990s demonstrated modest efficacy of platinum-based therapy. Further combination trials demonstrated enhanced efficacy for several regimen in first and second lines, including the introduction of antimetabolites, taxanes, and anti-angiogenic agents. Maintenance chemotherapy has been another novel, successful approach for management of metastatic disease. Herein, we summarize the current concepts of chemotherapy, its applicability to the different histologies, and novel concepts of therapy. PMID:27535392

  4. Verrucous Squamous Cell Cancer in the Esophagus: An Obscure Diagnosis

    PubMed Central

    Egeland, Charlotte; Achiam, Michael P.; Federspiel, Birgitte; Svendsen, Lars Bo

    2016-01-01

    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 with dysphagia, weight loss, and an endoscopically malignant tumor, but surgery was not performed until after 9 and 10 months, respectively, and then in order to get a diagnosis. At the last follow-up, both patients were without any recurrence of the disease. PMID:27721734

  5. Niche construction game cancer cells play

    NASA Astrophysics Data System (ADS)

    Bergman, Aviv; Gligorijevic, Bojana

    2015-10-01

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

  6. Niche construction game cancer cells play*

    PubMed Central

    Bergman, Aviv; Gligorijevic, Bojana

    2016-01-01

    Niche construction concept was originally defined in evolutionary biology as the continuous interplay between natural selection via environmental conditions and the modification of these conditions by the organism itself. Processes unraveling during cancer metastasis include construction of niches, which cancer cells use towards more efficient survival, transport into new environments and preparation of the remote sites for their arrival. Many elegant experiments were done lately illustrating, for example, the premetastatic niche construction, but there is practically no mathematical modeling done which would apply the niche construction framework. To create models useful for understanding niche construction role in cancer progression, we argue that a) genetic, b) phenotypic and c) ecological levels are to be included. While the model proposed here is phenomenological in its current form, it can be converted into a predictive outcome model via experimental measurement of the model parameters. Here we give an overview of an experimentally formulated problem in cancer metastasis and propose how niche construction framework can be utilized and broadened to model it. Other life science disciplines, such as host-parasite coevolution, may also benefit from niche construction framework adaptation, to satisfy growing need for theoretical considerations of data collected by experimental biology. PMID:27656339

  7. Alterations in Cell Signaling Pathways in Breast Cancer Cells after Environmental Exposure

    SciTech Connect

    Kulp, K; McCutcheon-Maloney, S M; Bennett, L M

    2003-02-01

    Recent human epidemiological studies suggest that up to 75% of human cancers can be attributed to environmental exposures. Understanding the biologic impact of being exposed to a lifetime of complex environmental mixtures that may not be fully characterized is currently a major challenge. Functional endpoints may be used to assess the gross health consequences of complex mixture exposures from groundwater contamination, superfund sites, biologic releases, or nutritional sources. Such endpoints include the stimulation of cell growth or the induction of a response in an animal model. An environmental exposure that upsets normal cell growth regulation may have important ramifications for cancer development. Stimulating cell growth may alter an individual's cancer risk by changing the expression of genes and proteins that have a role in growth regulatory pathways within cells. Modulating the regulation of these genes and their products may contribute to the initiation, promotion or progression of disease in response to environmental exposure. We are investigating diet-related compounds that induce cell proliferation in breast cancer cell lines. These compounds, PhIP, Flor-Essence{reg_sign} and Essiac{reg_sign}, may be part of an everyday diet. PhIP is a naturally occurring mutagen that is formed in well-cooked muscle meats. PhIP consistently causes dose-dependent breast tumor formation in rats and consumption of well-done meat has been linked to increased risk of breast cancer in women. Flor-Essence{reg_sign} and Essiac{reg_sign} herbal tonics are complementary and alternative medicines used by women who have been diagnosed with breast cancer as an alternative therapy for disease treatment and prevention. The long-term goal of this work is to identify those cellular pathways that are altered by a chemical or biologic environmental exposure and understand how those changes correlate with and or predict changes in human health risk. This project addressed this goal by

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

    ClinicalTrials.gov

    2015-09-28

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

  9. Biomarkers and targeted systemic therapies in advanced non-small cell lung cancer.

    PubMed

    Kumar, Mukesh; Ernani, Vinicius; Owonikoko, Taofeek K

    2015-11-01

    The last decade has witnessed significant growth in therapeutic options for patients diagnosed with lung cancer. This is due in major part to our improved technological ability to interrogate the genomics of cancer cells, which has enabled the development of biologically rational anticancer agents. The recognition that lung cancer is not a single disease entity dates back many decades to the histological subclassification of malignant neoplasms of the lung into subcategories of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). While SCLC continues to be regarded as a single histologic and therapeutic category, the NSCLC subset has undergone additional subcategorizations with distinct management algorithms for specific histologic and molecular subtypes. The defining characteristics of these NSCLC subtypes have evolved into important tools for prognosis and for predicting the likelihood of benefit when patients are treated with anticancer agents.

  10. Reactive Oxygen Species: The Achilles' Heel of Cancer Cells?

    PubMed Central

    2012-01-01

    Abstract Cancer development, progression, and metastasis are multistep processes. Accumulating evidence suggests that reactive oxygen species (ROS) are critically involved in cancer cell functions. This Forum reviews our current understanding of the important and paradoxical role of ROS in the regulation of tumor-associated cell properties, genes, and signaling pathways. The six reviews in this Forum showcase the up-to-date knowledge on how ROS modulate or interact with the p53 protein, epithelial–mesenchymal transition, tumor stromal cells, angiogenesis, and cancer stem cells, which are essential factors in cancer development and metastasis. The contributions demonstrate that ROS levels in cancer cells are tightly controlled, which brings promises and challenges in the development of novel ROS-targeted anticancer therapies. Further understanding of the biological mechanisms underlying the effects of oxidative stress on tumor growth and metastasis will contribute to the advancement of cancer biology and cancer treatment. Antioxid. Redox Signal. 16, 1212–1214. PMID:22304673

  11. Argininosuccinate synthetase 1 suppression and arginine restriction inhibit cell migration in gastric cancer cell lines.

    PubMed

    Shan, Yan-Shen; Hsu, Hui-Ping; Lai, Ming-Derg; Yen, Meng-Chi; Chen, Wei-Ching; Fang, Jung-Hua; Weng, Tzu-Yang; Chen, Yi-Ling

    2015-01-01

    Gastric cancer metastasis remains a major cause of cancer-related deaths. There is an urgent need to develop new therapeutic approaches targeting metastatic gastric cancer. Argininosuccinate synthetase 1 (ASS1) expression is increased in gastric cancer. We detected the protein expression of ASS1 in human gastric cancer cell lines (AGS, NCI-N87, and MKN45) and in murine gastric cancer cell lines (3I and 3IB2). We used vector-mediated short hairpin RNA (shRNA) expression to silence ASS1 expression in the MKN45 and 3IB2 cell lines, and analyzed the effects of this protein on cell migration and metastasis. We demonstrated that ASS1 silencing suppressed cell migration in the MKN45 and 3IB2 cell lines. ASS1 knockdown significantly reduced liver metastasis in mice after the intrasplenic implantation of 3IB2 cancer cell clones. To determine whether arginine restriction may represent a therapeutic approach to treat gastric cancer, the sensitivity of tumor cells to arginine depletion was determined in gastric cancer cells. Arginine depletion significantly inhibited cell migration in the gastric cancer cell line. The silencing of ASS1 expression in MKN45 and 3IB2 gastric cancer cells markedly decreased STAT3 protein expression. In conclusion, our results indicate that the ASS1 protein is required for cell migration in gastric cancer cell lines. PMID:25928182

  12. Oncolytic viral therapy: targeting cancer stem cells

    PubMed Central

    Smith, Tyrel T; Roth, Justin C; Friedman, Gregory K; Gillespie, G Yancey

    2014-01-01

    Cancer stem cells (CSCs) are defined as rare populations of tumor-initiating cancer cells that are capable of both self-renewal and differentiation. Extensive research is currently underway to develop therapeutics that target CSCs for cancer therapy, due to their critical role in tumorigenesis, as well as their resistance to chemotherapy and radiotherapy. To this end, oncolytic viruses targeting unique CSC markers, signaling pathways, or the pro-tumor CSC niche offer promising potential as CSCs-destroying agents/therapeutics. We provide a summary of existing knowledge on the biology of CSCs, including their markers and their niche thought to comprise the tumor microenvironment, and then we provide a critical analysis of the potential for targeting CSCs with oncolytic viruses, including herpes simplex virus-1, adenovirus, measles virus, reovirus, and vaccinia virus. Specifically, we review current literature regarding first-generation oncolytic viruses with their innate ability to replicate in CSCs, as well as second-generation viruses engineered to enhance the oncolytic effect and CSC-targeting through transgene expression. PMID:24834430

  13. Expression of pleiotrophin in small cell lung cancer.

    PubMed

    Wang, H Q; Wang, J

    2015-01-01

    Pleiotrophin (PTN) is a kind of heparin binding growth factor closely related to tumor progression. This study aimed to discuss the significance of the expression of PTN in benign and malignant lung cancer tissues, especially small cell lung cancer. Lung cancer samples were collected for study and lung tissue samples with benign lesions were taken as controls. The expression of PTN was detected using tissue chip combined with the immunohistochemical method, and the differences of small cell lung cancer with non-small cell lung cancer and benign lesion tissue were compared. It was found that PTN expression was mainly located in the cytoplasm and membrane of cells; PTN expression in the lung cancer group was higher than that in the control group (p < 0.01), and PTN expression in the small cell cancer group was higher than that in the squamous carcinoma group and glandular cancer group (p < 0.05). In addition, PTN expression quantity in patients with lung cancer were in close correlation with TNM staging, pathological type and tumor differentiation degree (p < 0.05). PTN was found to express abnormally high in lung cancer, especially small cell lung cancer tissue. PTN is most likely to be a new tumor marker for diagnosis and prognosis of lung cancer. PMID:25864755

  14. Nanomaterials for regulating cancer and stem cell fate

    NASA Astrophysics Data System (ADS)

    Shah, Birju P.

    The realm of nanomedicine has grown exponentially over the past few decades. However, there are several obstacles that need to be overcome, prior to the wide-spread clinical applications of these nanoparticles, such as (i) developing well-defined nanoparticles of varying size, morphology and composition to enable various clinical applications; (ii) overcome various physiological barriers encountered in order to deliver the therapeutics to the target location; and (iii) real-time monitoring of the nano-therapeutics within the human body for tracking their uptake, localization and effect. Hence, this dissertation focuses on developing multimodal nanotechnology-based approaches to overcome the above-mentioned challenges and thus enable regulation of cancer and stem cell fate. The initial part of this dissertation describes the development of multimodal magnetic core-shell nanoparticles (MCNPs), comprised of a highly magnetic core surrounded by a thin gold shell, thus combining magnetic and plasmonic properties. These nanoparticles were utilized for mainly two applications: (i) Magnetically-facilitated delivery of siRNA and plasmid DNA for effective stem cell differentiation and imaging and (ii) Combined hyperthermia and targeted delivery of a mitochondria-targeting peptide for enhancing apoptosis in cancer cells. The following part of this dissertation presents the generation of a multi-functional cyclodextrin-conjugated polymeric delivery platform (known as DexAMs), for co-delivery of anticancer drugs and siRNAs in a target-specific manner to brain tumor cells. This combined delivery of chemotherapeutics and siRNA resulted in a synergistic effect on the apoptosis of brain tumor cells, as compared to the individual treatments. The final part of this thesis presents development of stimuli-responsive uorescence resonance energy transfer (FRET)-based mesoporous silica nanoparticles for real-time monitoring of drug release in cells. The stimuli-responsive behavior of

  15. Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling.

    PubMed

    Chai, Xinqun; Chu, Hongpeng; Yang, Xuan; Meng, Yuanpu; Shi, Pengfei; Gou, Shanmiao

    2015-01-01

    The prognosis of pancreatic cancer remains dismal, with little advance in chemotherapy because of its high frequency of chemoresistance. Metformin is widely used to treat type II diabetes, and was shown recently to inhibit pancreatic cancer stem cell proliferation. In the present study, we investigated the role of metformin in chemoresistance of pancreatic cancer cells to gemcitabine, and its possible cellular and molecular mechanisms. Metformin increases sensitivity of pancreatic cancer cells to gemcitabine. The mechanism involves, at least in part, the inhibition of CD133(+) cells proliferation and suppression of P70S6K signaling activation via inhibition of ERK phosphorylation. Studies of primary tumor samples revealed a relationship between P70S6K signaling activation and the malignancy of pancreatic cancer. Analysis of clinical data revealed a trend of the benefit of metformin for pancreatic cancer patients with diabetes. The results suggested that metformin has a potential clinical use in overcoming chemoresistance of pancreatic cancer. PMID:26391180

  16. Microchimeric Cells, Sex Chromosome Aneuploidies and Cancer.

    PubMed

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

    2015-09-01

    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 < 0.0001). The frequencies of SCAs were higher in the tumoral tissues than in the blood (p < 0.0001). There was a significant difference in the frequencies of SCAs between the tumor and blood tissues, and this was higher in the tumor tissue (p < 0.0001). In general, 78.9 % (41) of the 52 patients with LC and BC had X and Y 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 < 0.0001). XY cells were identified in the lung and bladder tissues of the women who had been pregnant with boys, but not in those who had not. There was a significant difference in the frequencies of McCs between the LC and BC patients

  17. A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer

    ClinicalTrials.gov

    2014-04-21

    HER2 + Breast Cancer, HER2 + Gastric Cancer, Squamous Cell Carcinoma of Head and Neck, Esophageal Squamous Cell Carcinoma; HER2 + Breast Cancer; HER2 + Gastric Cancer; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma

  18. Spheroid body-forming cells in the human gastric cancer cell line MKN-45 possess cancer stem cell properties.

    PubMed

    Liu, Jianming; Ma, Lilin; Xu, Junfei; Liu, Chun; Zhang, Jianguo; Liu, Jie; Chen, Ruixin; Zhou, Youlang

    2013-02-01

    The cancer stem cell theory hypothesizes that cancer stem cells (CSCs), which possess self-renewal and other stem cell properties, are regarded as the cause of tumor formation, recurrence and metastasis. The isolation and identification of CSCs could help to develop novel therapeutic strategies specifically targeting CSCs. In this study, we enriched gastric cancer stem cells through spheroid body formation by cultivating the human gastric cancer cell line MKN-45 in defined serum-free medium. The stemness characteristics of spheroid body-forming cells, including self-renewal, proliferation, chemoresistance, tumorigenicity of the MKN-45 spheroid body-forming cells were evaluated, and the expression levels of stemness genes and related proteins in the MKN-45 spheroid body-forming cells were assessed. Furthermore, immunofluorescence staining for the stem cell markers on spheroid body-forming cells was examined to evaluate the association between stemness factors (Oct4, Sox2, Nanog) and the proposed CSC marker CD44. Our data demonstrated that non-adherent spheroid body-forming cells from the gastric cancer cell line MKN-45 cultured in stem cell-conditioned medium possessed gastric CSC properties, such as persistent self-renewal, extensive proliferation, drug resistance, high tumorigenic capacity and overexpression of CSC-related genes and proteins (Oct4, Sox2, Nanog and CD44), compared with the parental cells. More importantly, CD44-positive cells co-expressing the pluripotency genes Oct4, Sox2 and Nanog may represent gastric CSCs. Further experiments using more refined selection criteria such as a combination of two or multiple markers would be useful to specifically identify and purify CSCs.

  19. Combination therapy targeting both cancer stem-like cells and bulk tumor cells for improved efficacy of breast cancer treatment.

    PubMed

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

    2016-06-01

    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. PMID:27259361

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

    PubMed

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

    2016-06-01

    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. Chinese medicine and biomodulation in cancer patients—Part one

    PubMed Central

    Sagar, S.M.; Wong, R.K.

    2008-01-01

    Traditional Chinese Medicine (tcm) may be integrated with conventional Western medicine to enhance the care of patients with cancer. Although tcm is normally implemented as a whole system, recent reductionist research suggests mechanisms for the effects of acupuncture, herbs, and nutrition within the scientific model of biomedicine. The health model of Chinese medicine accommodates physical and pharmacologic interventions within the framework of a body–mind network. A Cartesian split does not occur within this model, but to allow for scientific exploration within the restrictions of positivism, reductionism, and controls for confounding factors, the components must necessarily be separated. Still, whole-systems research is important to evaluate effectiveness when applying the full model in clinical practice. Scientific analysis provides a mechanistic understanding of the processes that will improve the design of clinical studies and enhance safety. Enough preliminary evidence is available to encourage quality clinical trials to evaluate the efficacy of integrating tcm into Western cancer care. PMID:18317584

  2. Cancer Stem Cell Biomarker Discovery Using Antibody Array Technology.

    PubMed

    Burgess, Rob; Huang, Ruo-Pan

    2016-01-01

    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.

  3. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin.

    PubMed

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

    2015-04-01

    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.

  4. T Cell Receptor Gene Therapy for Cancer

    PubMed Central

    Schmitt, Thomas M.; Ragnarsson, Gunnar B.

    2009-01-01

    Abstract T cell-based adoptive immunotherapy has been shown to be a promising treatment for various types of cancer. However, adoptive T cell therapy currently requires the custom isolation and characterization of tumor-specific T cells from each patient—a process that can be not only difficult and time-consuming but also often fails to yield high-avidity T cells, which together have limited the broad application of this approach as a clinical treatment. Employing T cell receptor (TCR) gene therapy as a component of adoptive T cell therapy strategies can overcome many of these obstacles, allowing autologous T cells with a defined specificity to be generated in a much shorter time period. Initial studies using this approach have been hampered by a number of technical difficulties resulting in low TCR expression and acquisition of potentially problematic specificities due to mispairing of introduced TCR chains with endogenous TCR chains. The last several years have seen substantial progress in our understanding of the multiple facets of TCR gene therapy that will have to be properly orchestrated for this strategy to succeed. Here we outline the challenges of TCR gene therapy and the advances that have been made toward realizing the promise of this approach. PMID:19702439

  5. Harnessing Dendritic Cells to Generate Cancer Vaccines

    PubMed Central

    Palucka, Karolina; Ueno, Hideki; Fay, Joseph; Banchereau, Jacques

    2009-01-01

    Passive immunotherapy of cancer, i.e., transfer of T cells or antibodies, can lead to some objective clinical responses, thus demonstrating that the immune system can reject tumors. However, passive immunotherapy is not expected to yield memory T cells that might control tumor outgrowth. Active immunotherapy with dendritic cell (DCs) vaccines has the potential to induce tumor-specific effector and memory T cells. Clinical trials testing first generation DC vaccines pulsed with tumor antigens provided a proof-of-principle that therapeutic immunity can be elicited. Newer generation DC vaccines are build on the increased knowledge of the DC system including the existence of distinct DC subsets and their plasticity all leading to generation of distinct types of immunity. Rather than the quantity of IFN-γ secreting CD8+ T cells, we should aim at generating high quality high avidity poly-functional effector CD8+ T cells able to reject tumors and long-lived memory CD8+ T cells able to prevent relapse. PMID:19769741

  6. Stiffness nanotomography of human epithelial cancer cells

    NASA Astrophysics Data System (ADS)

    Staunton, Jack R.; Doss, Bryant L.; Gilbert, C. Michael; Kasas, Sandor; Ros, Robert

    2012-02-01

    The mechanical stiffness of individual cells is important in both cancer initiation and metastasis. We present atomic force microscopy (AFM) based nanoindentation experiments on various human mammary and esophagus cell lines covering the spectrum from normal immortalized cells to highly metastatic ones. The combination of an AFM with a confocal fluorescence lifetime imaging microscope (FLIM) in conjunction with the ability to move the sample and objective independently allow for precise alignment of AFM probe and laser focus with an accuracy down to a few nanometers. This enables us to correlate the mechanical properties with the point of indentation in the FLIM image. We are using force-volume measurements as well as force indentation curves on distinct points on the cells to compare the elastic moduli of the nuclei, nucleoli, and the cytoplasm, and how they vary within and between individual cells and cell lines. Further, a detailed analysis of the force-indentation curves allows study of the cells' mechanical properties at different indentation depths and to generate 3D elasticity maps.

  7. How Taxol/paclitaxel kills cancer cells.

    PubMed

    Weaver, Beth A

    2014-09-15

    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.

  8. Pediatric cancer gone viral. Part I: strategies for utilizing oncolytic herpes simplex virus-1 in children

    PubMed Central

    Cripe, Timothy P; Chen, Chun-Yu; Denton, Nicholas L; Haworth, Kellie B; Hutzen, Brian; Leddon, Jennifer L; Streby, Keri A; Wang, Pin-Yi; Markert, James M; Waters, Alicia M; Gillespie, George Yancey; Beierle, Elizabeth A; Friedman, Gregory K

    2015-01-01

    Progress for improving outcomes in pediatric patients with solid tumors remains slow. In addition, currently available therapies are fraught with numerous side effects, often causing significant life-long morbidity for long-term survivors. The use of viruses to kill tumor cells based on their increased vulnerability to infection is gaining traction, with several viruses moving through early and advanced phase clinical testing. The prospect of increased efficacy and decreased toxicity with these agents is thus attractive for pediatric cancer. In part I of this two-part review, we focus on strategies for utilizing oncolytic engineered herpes simplex virus (HSV) to target pediatric malignancies. We discuss mechanisms of action, routes of delivery, and the role of preexisting immunity on antitumor efficacy. Challenges to maximizing oncolytic HSV in children are examined, and we highlight how these may be overcome through various arming strategies. We review the preclinical and clinical evidence demonstrating safety of a variety of oncolytic HSVs. In Part II, we focus on the antitumor efficacy of oncolytic HSV in pediatric tumor types, pediatric clinical advances made to date, and future prospects for utilizing HSV in pediatric patients with solid tumors. PMID:26436135

  9. S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2015-08-11

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  10. Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-06-28

    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

  11. Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-02-08

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Bronchoalveolar Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

  12. Stem cells and lung cancer: future therapeutic targets?

    PubMed

    Alison, Malcolm R; Lebrenne, Arielle C; Islam, Shahriar

    2009-09-01

    In both the UK and USA more people die of lung cancer than any other type of cancer. Lung cancer's high mortality rate is also reflected on a global scale, with lung cancer accounting for more than 1 million deaths per year. In tissues with ordered structure such a lung epithelia, it is likely that the cancers have their origins in normal adult stem cells, and then the tumours themselves are maintained by a population of malignant stem cells - so-called cancer stem cells. This review examines both these postulates in animal models and in the clinical setting, noting that stem cell niches appear to foster tumour development, and that drug resistance can often be attributed to malignant cells with stem cell properties. PMID:19653862

  13. Targeting the cancer cell cycle by cold atmospheric plasma

    NASA Astrophysics Data System (ADS)

    Volotskova, O.; Hawley, T. S.; Stepp, M. A.; Keidar, M.

    2012-09-01

    Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating S-phase damage, is enhanced specifically within CAP treated cells in the S phase of the cell cycle. Together with a significant decrease in EdU-incorporation after CAP, these data suggest that tumorigenic cancer cells are more susceptible to CAP treatment.

  14. New Findings on Breast Cancer Stem Cells: A Review.

    PubMed

    Bozorgi, Azam; Khazaei, Mozafar; Khazaei, Mohammad Rasool

    2015-12-01

    Since the introduction of the "cancer stem cell" theory, significant developments have been made in the understanding of cancer and the heterogenic structure of tumors. In 2003, with the isolation of cancer stem cells from the first solid tumor, breast cancer, and recognition of the tumorigenicity of these cells, this theory suggested that the main reason for therapy failure might be the presence of cancer stem cells. This review article describes breast cancer stem cell origin, the related cellular and molecular characteristics, signaling pathways, and therapy resistance mechanisms. The databases PubMed, SCOPUS, and Embase were explored, and articles published on these topics between 1992 and 2015 were investigated. It appears that this small subpopulation of cells, with the capacity for self-renewal and a high proliferation rate, originate from normal stem cells, are identified by specific markers such as CD44(+)/CD24(-/low), and enhance a tumor's capacity for metastasis, invasion, and therapy resistance. Cancer stem cell characteristics depend on their interactions with their microenvironment as well as on the inducing factors and elements. Although uncertainties about breast cancer stem cells exist, many of researchers believe that cancer stem cells should be considered as possible therapeutic targets.

  15. New Findings on Breast Cancer Stem Cells: A Review

    PubMed Central

    Bozorgi, Azam; Khazaei, Mohammad Rasool

    2015-01-01

    Since the introduction of the "cancer stem cell" theory, significant developments have been made in the understanding of cancer and the heterogenic structure of tumors. In 2003, with the isolation of cancer stem cells from the first solid tumor, breast cancer, and recognition of the tumorigenicity of these cells, this theory suggested that the main reason for therapy failure might be the presence of cancer stem cells. This review article describes breast cancer stem cell origin, the related cellular and molecular characteristics, signaling pathways, and therapy resistance mechanisms. The databases PubMed, SCOPUS, and Embase were explored, and articles published on these topics between 1992 and 2015 were investigated. It appears that this small subpopulation of cells, with the capacity for self-renewal and a high proliferation rate, originate from normal stem cells, are identified by specific markers such as CD44+/CD24-/low, and enhance a tumor's capacity for metastasis, invasion, and therapy resistance. Cancer stem cell characteristics depend on their interactions with their microenvironment as well as on the inducing factors and elements. Although uncertainties about breast cancer stem cells exist, many of researchers believe that cancer stem cells should be considered as possible therapeutic targets. PMID:26770236

  16. Use of Cancer Stem Cells to Investigate the Pathogenesis of Colitis-associated Cancer

    PubMed Central

    Davies, Julie M.; Santaolalla, Rebeca

    2016-01-01

    Abstract: Colitis-associated cancer (CAC) can develop in patients with inflammatory bowel disease with long-term uncontrolled inflammation. The mutational history and tumor microenvironment observed in CAC patients is distinct from that observed in sporadic colon cancer and suggests a different etiology. Recently, much attention has been focused on understanding the cellular origin of cancer and the cancer stem cells, which is key to growth and progression. Cancer stem cells are often chemo-resistant making them attractive targets for improving patient outcomes. New techniques have rapidly been evolving allowing for a better understanding of the normal intestinal stem cell function and behavior in the niche. Use of these new technologies will be crucial to understanding cancer stem cells in both sporadic and CAC. In this review, we will explore emerging methods related to the study of normal and cancer stem cells in the intestine, and examine potential avenues of investigation and application to understanding the pathogenesis of CAC. PMID:26963566

  17. Skeletal Health Part 1: Overview Of Bone Health and Management In the Cancer Setting.

    PubMed

    Turner, Bruce; Ali, Sacha; Drudge-Coates, Lawrence; Pati, Jhumur; Nargund, Vinod; Wells, Paula

    2016-01-01

    Cancer-induced bone disease and cancer therapy-induced bone loss are significant skeletal problems related to the treatment for urological and other cancers. Our team of specialists and nurse practitioners developed a nurse practitioner-led Bone Support Clinic for urologic cancer patients at a university hospital in London, England, United Kingdom, to address this issue. The clinic has been well-accepted, has made a positive impact on the patient journey, helps to ensure continuity of care, and highlights patients who require assessment or treatment for impending skeletal-related events in a timely fashion. This article has been divided into two parts for improved readability. PMID:27093759

  18. Skeletal Health Part 1: Overview Of Bone Health and Management In the Cancer Setting.

    PubMed

    Turner, Bruce; Ali, Sacha; Drudge-Coates, Lawrence; Pati, Jhumur; Nargund, Vinod; Wells, Paula

    2016-01-01

    Cancer-induced bone disease and cancer therapy-induced bone loss are significant skeletal problems related to the treatment for urological and other cancers. Our team of specialists and nurse practitioners developed a nurse practitioner-led Bone Support Clinic for urologic cancer patients at a university hospital in London, England, United Kingdom, to address this issue. The clinic has been well-accepted, has made a positive impact on the patient journey, helps to ensure continuity of care, and highlights patients who require assessment or treatment for impending skeletal-related events in a timely fashion. This article has been divided into two parts for improved readability.

  19. Method for restoration of normal phenotype in cancer cells

    DOEpatents

    Bissell, Mina J.; Weaver, Valerie M.

    2000-01-01

    A method for reversing expression of malignant phenotype in cancer cells is described. The method comprises applying .beta..sub.1 integrin function-blocking antibody to the cells. The method can be used to assess the progress of cancer therapy. Human breast epithelial cells were shown to be particularly responsive.

  20. The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy

    PubMed Central

    Legut, Mateusz; Cole, David K; Sewell, Andrew K

    2015-01-01

    γδ T cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of human γδ T cell receptors (TCRs) remain largely unknown, but recent studies have confirmed the recognition of phosphorylated prenyl metabolites, lipids in complex with CD1 molecules and markers of cellular stress. All of these molecules are upregulated on various cancer types, highlighting the potential importance of the γδ T cell compartment in cancer immunosurveillance and paving the way for the use of γδ TCRs in cancer therapy. Ligand recognition by the γδ TCR often requires accessory/co-stimulatory stress molecules on both T cells and target cells; this cellular stress context therefore provides a failsafe against harmful self-reactivity. Unlike αβ T cells, γδ T cells recognise their targets irrespective of HLA haplotype and therefore offer exciting possibilities for off-the-shelf, pan-population cancer immunotherapies. Here, we present a review of known ligands of human γδ T cells and discuss the promise of harnessing these cells for cancer treatment. PMID:25864915

  1. Liver cancer stem cell markers: Progression and therapeutic implications.

    PubMed

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

    2016-04-01

    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. Liver cancer stem cell markers: Progression and therapeutic implications

    PubMed Central

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

    2016-01-01

    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

  3. Atractylenolide I-mediated Notch pathway inhibition attenuates gastric cancer stem cell traits

    SciTech Connect

    Ma, Li; Mao, Rurong; Shen, Ke; Zheng, Yuanhong; Li, Yueqi; Liu, Jianwen; Ni, Lei

    2014-07-18

    Highlights: • This paper supports the anti-tumor effects of AT-I on gastric cancer in vitro. • AT-I attenuates gastric cancer stem cell traits. • It is the systematic study regarding AT-I suppression of Notch pathway in GC and GCSLCs. - Abstract: Atractylenolide I (AT-I), one of the main naturally occurring compounds of Rhizoma Atractylodis Macrocephalae, has remarkable anti-cancer effects on various cancers. However, its effects on the treatment of gastric cancer remain unclear. Via multiple cellular and molecular approaches, we demonstrated that AT-I could potently inhibit cancer cell proliferation and induce apoptosis through inactivating Notch pathway. AT-I treatment led to the reduction of expressions of Notch1, Jagged1, and its downstream Hes1/ Hey1. Our results showed that AT-I inhibited the self-renewal capacity of gastric stem-like cells (GCSLCs) by suppression of their sphere formation capacity and cell viability. AT-I attenuated gastric cancer stem cell (GCSC) traits partly through inactivating Notch1, leading to reducing the expressions of its downstream target Hes1, Hey1 and CD44 in vitro. Collectively, our results suggest that AT-I might develop as a potential therapeutic drug for the treatment of gastric cancer.

  4. Squamous Cell Lung Cancer: From Tumor Genomics to Cancer Therapeutics

    PubMed Central

    Gandara, David R.; Hammerman, Peter S.; Sos, Martin L.; Lara, Primo N.; Hirsch, Fred R.

    2016-01-01

    Squamous cell lung cancer (SCC) represents an area of unmet need in lung cancer research. For the last several years, therapeutic progress in SCC has lagged behind the now more common NSCLC histologic subtype of adenocarcinoma. However, recent efforts to define the complex biology underlying SCC have begun to bear fruit in a multitude of ways, including characterization of previously unknown genomic and signaling pathways, delineation of new potentially actionable molecular targets, and subsequent development of a large number of agents directed against unique SCC-associated molecular abnormalities. For the first time, SCC-specific prognostic gene signatures and predictive biomarkers of new therapeutic agents are emerging. In addition, recent and ongoing clinical trials, including the Lung-MAP master protocol, have been designed to facilitate approval of targeted therapy-biomarker combinations. In this comprehensive review we describe the current status of SCC therapeutics, recent advances in the understanding of SCC biology and prognostic gene signatures, and the development of innovative new clinical trials, all of which offer new hope for patients with advanced SCC. PMID:25979930

  5. Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells.

    PubMed

    Yongsanguanchai, Nuttida; Pongrakhananon, Varisa; Mutirangura, Apiwat; Rojanasakul, Yon; Chanvorachote, Pithi

    2015-01-15

    Even though tremendous advances have been made in the treatment of cancers during the past decades, the success rate among patients with cancer is still dismal, largely because of problems associated with chemo/radioresistance and relapse. Emerging evidence has indicated that cancer stem cells (CSCs) are behind the resistance and recurrence problems, but our understanding of their regulation is limited. Rapid reversible changes of CSC-like cells within tumors may result from the effect of biological mediators found in the tumor microenvironment. Here we show how nitric oxide (NO), a key cellular modulator whose level is elevated in many tumors, affects CSC-like phenotypes of human non-small cell lung carcinoma H292 and H460 cells. Exposure of NO gradually altered the cell morphology toward mesenchymal stem-like shape. NO exposure promoted CSC-like phenotype, indicated by increased expression of known CSC markers, CD133 and ALDH1A1, in the exposed cells. These effects of NO on stemness were reversible after cessation of the NO treatment for 7 days. Furthermore, such effect was reproducible using another NO donor, S-nitroso-N-acetylpenicillamine. Importantly, inhibition of NO by the known NO scavenger 2-(4-carboxy-phenyl)-4,4,5,5 tetramethylimidazoline-1-oxy-3-oxide strongly inhibited CSC-like aggressive cellular behavior and marker expression. Last, we unveiled the underlying mechanism of NO action through the activation of caveolin-1 (Cav-1), which is upregulated by NO and is responsible for the aggressive behavior of the cells, including anoikis resistance, anchorage-independent cell growth, and increased cell migration and invasion. These findings indicate a novel role of NO in CSC regulation and its importance in aggressive cancer behaviors through Cav-1 upregulation.

  6. Defining cancer-risk, and assessing diagnostic usefulness of myositis serology, in dermatomyositis- Part 2

    PubMed Central

    Madan, V; Chinoy, H; Griffiths, C E M; Cooper, R G

    2015-01-01

    Summary In the first part of this review we examined the evidence behind the association between idiopathic inflammatory myopathies (IIM) and cancers. In view of the well-recognised association between cancer and myositis (hence the term cancer-associated myositis, or CAM) clinicians responsible for the management of patients with myositis must make important decisions regarding how intensively they undertake searches for malignancy. Clinicians must also decide how often such searches are repeated, and again how intensively, so as to optimise both cancer detection and treatment, and thus patient survival. As the risks of CAM are greatest in dermatomyositis, this is an issue of obvious importance to dermatologists. In this second of the two part review we examine the role of autoantibodies as potential predictors of cancer risk in IIM. PMID:19508476

  7. Delivery of therapeutics using nanocarriers for targeting cancer cells and cancer stem cells.

    PubMed

    Krishnamurthy, Sangeetha; Ke, Xiyu; Yang, Yi Yan

    2015-01-01

    Development of cancer resistance, cancer relapse and metastasis are attributed to the presence of cancer stem cells (CSCs). Eradication of this subpopulation has been shown to increase life expectancy of patients. Since the discovery of CSCs a decade ago, several strategies have been devised to specifically target them but with limited success. Nanocarriers have recently been employed to deliver anti-CSC therapeutics for reducing the population of CSCs at the tumor site with great success. This review discusses the different therapeutic strategies that have been employed using nanocarriers, their advantages, success in targeting CSCs and the challenges that are to be overcome. Exploiting this new modality of cancer treatment in the coming decade may improve outcomes profoundly with promise of effective treatment response and reducing relapse and metastasis.

  8. Cancer microenvironment, inflammation and cancer stem cells: A hypothesis for a paradigm change and new targets in cancer control

    PubMed Central

    Blaylock, Russell L.

    2015-01-01

    Since President Nixon officially declared a war on cancer with the National Cancer Act, billions of dollars have been spent on research in hopes of finding a cure for cancer. Recent reviews have pointed out that over the ensuing 42 years, cancer death rates have barely changed for the major cancers. Recently, several researchers have questioned the prevailing cancer paradigm based on recent discoveries concerning the mechanism of carcinogenesis and the origins of cancer. Over the past decade we have learned a great deal concerning both of these central issues. Cell signaling has taken center stage, particularly as regards the links between chronic inflammation and cancer development. It is now evident that the common factor among a great number of carcinogenic agents is activation of genes controlling inflammation cell-signaling pathways and that these signals control all aspects of the cancer process. Of these pathways, the most important and common to all cancers is the NFκB and STAT3 pathways. The second discovery of critical importance is that mutated stem cells appear to be in charge of the cancer process. Most chemotherapy agents and radiotherapy kill daughter cells of the cancer stem cell, many of which are not tumorigenic themselves. Most cancer stem cells are completely resistant to conventional treatments, which explain dormancy and the poor cure rate with metastatic tumors. A growing number of studies are finding that several polyphenol extracts can kill cancer stem cells as well as daughter cells and can enhance the effectiveness and safety of conventional treatments. These new discoveries provide the clinician with a whole new set of targets for cancer control and cure. PMID:26097771

  9. Nitric oxide and cell death in liver cancer cells.

    PubMed

    Muntané, Jordi; De la Rosa, Angel J; Marín, Luís M; Padillo, Francisco J

    2013-05-01

    Nitric oxide (NO) is a lipophillic, highly diffusible, and short-lived physiological messenger which regulates a variety of physiopathological responses. NO may exert its cellular action through cGMP-dependent and cGMP-independent pathways which includes different postranslational modifications. The effect of NO in cancer depends on the activity and localization of NOS isoforms, concentration and duration of NO exposure, cellular sensitivity, and hypoxia/re-oxygenation process. NO regulates critical factors such as the hypoxia inducible factor-1 (HIF-1) and p53 generally leading to growth arrest, apoptosis or adaptation. NO sensitizes hepatoma cells to chemotherapeutic compounds probably through increased p53 and cell death receptor expressions.

  10. Cell Death and Deubiquitinases: Perspectives in Cancer

    PubMed Central

    Bhattacharya, Seemana

    2014-01-01

    The process of cell death has important physiological implications. At the organism level it is mostly involved in maintenance of tissue homeostasis. At the cellular level, the strategies of cell death may be categorized as either suicide or sabotage. The mere fact that many of these processes are programmed and that these are often deregulated in pathological conditions is seed to thought. The various players that are involved in these pathways are highly regulated. One of the modes of regulation is via post-translational modifications such as ubiquitination and deubiquitination. In this review, we have first dealt with the different modes and pathways involved in cell death and then we have focused on the regulation of several proteins in these signaling cascades by the different deubiquitinating enzymes, in the perspective of cancer. The study of deubiquitinases is currently in a rather nascent stage with limited knowledge both in vitro and in vivo, but the emerging roles of the deubiquitinases in various processes and their specificity have implicated them as potential targets from the therapeutic point of view. This review throws light on another aspect of cancer therapeutics by targeting the deubiquitinating enzymes. PMID:25121098

  11. TAK1 regulates Paneth cell integrity partly through blocking necroptosis

    PubMed Central

    Simmons, A N; Kajino-Sakamoto, R; Ninomiya-Tsuji, J

    2016-01-01

    Paneth cells reside at the base of crypts of the small intestine and secrete antimicrobial factors to control gut microbiota. Paneth cell loss is observed in the chronically inflamed intestine, which is often associated with increased reactive oxygen species (ROS). However, the relationship between Paneth cell loss and ROS is not yet clear. Intestinal epithelial-specific deletion of a protein kinase Tak1 depletes Paneth cells and highly upregulates ROS in the mouse model. We found that depletion of gut bacteria or myeloid differentiation factor 88 (Myd88), a mediator of bacteria-derived cell signaling, reduced ROS but did not block Paneth cell loss, suggesting that gut bacteria are the cause of ROS accumulation but bacteria-induced ROS are not the cause of Paneth cell loss. In contrast, deletion of the necroptotic cell death signaling intermediate, receptor-interacting protein kinase 3 (Ripk3), partially blocked Paneth cell loss. Thus, Tak1 deletion causes Paneth cell loss in part through necroptotic cell death. These results suggest that TAK1 participates in intestinal integrity through separately modulating bacteria-derived ROS and RIPK3-dependent Paneth cell loss. PMID:27077812

  12. Cancer stem cell: fundamental experimental pathological concepts and updates.

    PubMed

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

    2015-04-01

    Cancer stem cells (CSCs) are a subset of cancer cells which play a key role in predicting the biological aggressiveness of cancer due to its ability of self-renewal and multi-lineage differentiation (stemness). The CSC model is a dynamic one with a functional subpopulation of cancer cells rather than a stable cell population responsible for tumour regeneration. Hypotheses regarding the origins of CSCs include (1) malignant transformation of normal stem cells; (2) mature cancer cell de-differentiation with epithelial-mesenchymal transition and (3) induced pluripotent cancer cells. Surprisingly, the cancer stem cell hypothesis originated in the late nineteenth century and the existence of haematopoietic stem cells was demonstrated a century later, demonstrating that the concept was possible. In the last decade, CSCs have been identified and isolated in different cancers. The hallmark traits of CSCs include their heterogeneity, interaction with microenvironments and plasticity. Understanding these basic concepts of CSCs is important for translational applications using CSCs in the management of patients with cancer. PMID:25659759

  13. Stem Cell Transplantation in Treating Patients With Hematologic Cancer

    ClinicalTrials.gov

    2012-05-31

    Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous/Nonmalignant Condition; Small Intestine Cancer

  14. Cytotoxic Effects of Loperamide Hydrochloride on Canine Cancer Cells

    PubMed Central

    REGAN, Rebecca Cohen; GOGAL, Robert Michael; BARBER, James Perry; TUCKFIELD, Richard Cary; HOWERTH, Elizabeth Wynne; LAWRENCE, Jessica Ann

    2014-01-01

    Loperamide is a peripheral opiate agonist that can cause apoptosis and G2/M arrest in human cancer cell lines and may sensitize cells to chemotherapy. The objectives of this study were to investigate the effects of loperamide on viability, apoptosis and cell cycle kinetics in canine cancer cells and to establish whether the drug sensitizes cells to doxorubicin. Cell viability was assessed using Alamar Blue. Cell death and cell cycle were studied using flow cytometry with 7-Aminoactinomycin-D (7-AAD) and propidium iodide (PI), respectively. Loperamide decreased cell viability in a dose-dependent fashion and was most effective against canine osteosarcoma cells. In all cell lines, it induced a dose and time dependent apoptosis and resulted in accumulation in G0/G1. When co-incubated with doxorubicin, loperamide induced a synergistic cell kill in canine carcinoma cells. Investigation is warranted into the role of loperamide in the treatment of canine cancer. PMID:25649936

  15. The marine-derived fungal metabolite, terrein, inhibits cell proliferation and induces cell cycle arrest in human ovarian cancer cells.

    PubMed

    Chen, Yi-Fei; Wang, Shu-Ying; Shen, Hong; Yao, Xiao-Fen; Zhang, Feng-Li; Lai, Dongmei

    2014-12-01

    The difficulties faced in the effective treatment of ovarian cancer are multifactorial, but are mainly associated with relapse and drug resistance. Cancer stem-like cells have been reported to be an important contributor to these hindering factors. In this study, we aimed to investigate the anticancer activities of a bioactive fungal metabolite, namely terrein, against the human epithelial ovarian cancer cell line, SKOV3, primary human ovarian cancer cells and ovarian cancer stem-like cells. Terrein was separated and purified from the fermentation metabolites of the marine sponge-derived fungus, Aspergillus terreus strain PF26. Its anticancer activities against ovarian cancer cells were investigated by cell proliferation assay, cell migration assay, cell apoptosis and cell cycle assays. The ovarian cancer stem-like cells were enriched and cultured in a serum-free in vitro suspension system. Terrein inhibited the proliferation of the ovarian cancer cells by inducing G2/M phase cell cycle arrest. The underlying mechanisms involved the suppression of the expression of LIN28, an important marker gene of stemness in ovarian cancer stem cells. Of note, our study also demonstrated the ability of terrein to inhibit the proliferation of ovarian cancer stem-like cells, in which the expression of LIN28 was also downregulated. Our findings reveal that terrein (produced by fermention) may prove to be a promising drug candidate for the treatment of ovarian cancer by inhibiting the proliferation of cancer stem-like cells.

  16. Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer

    ClinicalTrials.gov

    2016-08-25

    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

  17. Arctigenin induces cell cycle arrest by blocking the phosphorylation of Rb via the modulation of cell cycle regulatory proteins in human gastric cancer cells.

    PubMed

    Jeong, Jin Boo; Hong, Se Chul; Jeong, Hyung Jin; Koo, Jin Suk

    2011-10-01

    Gastric cancer is a leading cause of cancer-related deaths, worldwide being second only to lung cancer as a cause of death. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms of arctigenin for anti-tumor effect on gastric cancer have not been examined. This study examined the biological effects of arctigenin on the human gastric cancer cell line SNU-1 and AGS. Cell proliferation was determined by MTT assay. In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by arctigenin in a time and dose dependent manner, as compared with SNU-1 and AGS cells cultured in the absence of arctigenin. Inhibition of cell proliferation by arctigenin was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bcl-2 to Bax by arctigenin. Also, arctigenin blocked cell cycle arrest from G(1) to S phase by regulating the expression of cell cycle regulatory proteins such as Rb, cyclin D1, cyclin E, CDK4, CDK2, p21Waf1/Cip1 and p15 INK4b. The antiproliferative effect of arctigenin on SNU-1 and AGS gastric cancer cells revealed in this study suggests that arctigenin has intriguing potential as a chemopreventive or chemotherapeutic agent.

  18. Side population cells from long-term passage non-small cell lung cancer cells display loss of cancer stem cell-like properties and chemoradioresistance

    PubMed Central

    Gu, Hao; Wu, Xin-Yu; Fan, Rui-Tai; Wang, Xin; Guo, You-Zhong; Wang, Rui

    2016-01-01

    The side population (SP) assay is a widely used method for isolating stem cell-like cells from cancer cell lines and primary cells. The cancer cells used in different laboratories have been passaged for different generations. Emerging evidence revealed that repeated passaging of cell lines for multiple generations frequently leads to change of characteristics. Thus, it is worth investigating the effects of repeated passaging on the biological and functional properties of the enriched SP fraction from early- and late-passage cells. The present study reports that the cancer stem cell (CSC) characteristics, including increased frequency of tumor-initiating and self-renewal capacity, and resistance to the chemotherapy agent doxorubicin and ionizing radiation, was diminished in SP cells from late-passage non-small cell lung cancer (NSCLC) cells. This finding revealed that the SP from long-term passage NSCLC cells was not consistently enriched for stem cell-like cancer cells, and low-passage cell lines and primary cancer cells are therefore recommended in the CSCs field.

  19. Metabolomic profiling of cultured cancer cells.

    PubMed

    Scoazec, Marie; Durand, Sylvere; Chery, Alexis; Galluzzi, Lorenzo; Kroemer, Guido

    2014-01-01

    Quantitative proteomics approaches have been developed-and now begin to be implemented on a high-throughput basis-to fill-in the large gap between the genomic/transcriptomic setup of (cancer) cells and their phenotypic/behavioral traits, reflecting a significant degree of posttranscriptional regulation in gene expression as well as a robust posttranslational regulation of protein function. However, proteomic profiling assays not only fail to detect labile posttranslational modifications as well as unstable protein-to-protein interactions but also are intrinsically incapable of assessing the enzymatic activity, as opposed to the mere abundance, of a given protein. Thus, determining the abundance of theoretically all the metabolites contained in a cell/tissue/organ/organism may significantly improve the informational value of proteomic approaches. Several techniques have been developed to this aim, including high-performance liquid chromatography (HPLC) coupled to quadrupole time-of-flight (Q-TOF) high-resolution mass spectrometry (HRMS). This approach is particularly advantageous for metabolomic profiling as it offers elevated accuracy and improved sensitivity. Here, we describe a simple procedure to determine the complete complement of intracellular metabolites in cultured malignant cells by HPLC coupled to Q-TOF HRMS. According to this method, (1) cells are collected and processed to minimize contaminations as well as fluctuations in their metabolic profile; (2) samples are separated by HPLC and analyzed on a Q-TOF spectrometer; and (3) data are extracted, normalized, and deconvoluted according to refined mathematical methods. This protocol constitutes a simple approach to determine the intracellular metabolomic profile of cultured cancer cells. With minimal variations (mostly related to sample collection and processing), this method is expected to provide reliable metabolomic data on a variety of cellular samples.

  20. Aptamer-Mediated Delivery of Chemotherapy to Pancreatic Cancer Cells

    PubMed Central

    Ray, Partha; Cheek, Marcus A.; Sharaf, Mariam L.; Li, Na; Ellington, Andrew D.; Sullenger, Bruce A.; Shaw, Barbara Ramsay

    2012-01-01

    Gemcitabine is a nucleoside analog that is currently the best available single-agent chemotherapeutic drug for pancreatic cancer. However, efficacy is limited by our inability to deliver sufficient active metabolite into cancer cells without toxic effects on normal tissues. Targeted delivery of gemcitabine into cancer cells could maximize effectiveness and concurrently minimize toxic side effects by reducing uptake into normal cells. Most pancreatic cancers overexpress epidermal growth factor receptor (EGFR), a trans-membrane receptor tyrosine kinase. We utilized a nuclease resistant RNA aptamer that binds and is internalized by EGFR on pancreatic cancer cells to deliver gemcitabine-containing polymers into EGFR-expressing cells and inhibit cell proliferation in vitro. This approach to cell type–specific therapy can be adapted to other targets and to other types of therapeutic cargo. PMID:23030589

  1. Adhesion between peptides/antibodies and breast cancer cells

    NASA Astrophysics Data System (ADS)

    Meng, J.; Paetzell, E.; Bogorad, A.; Soboyejo, W. O.

    2010-06-01

    Atomic force microscopy (AFM) techniques were used to measure the adhesion forces between the receptors on breast cancer cells specific to human luteinizing hormone-releasing hormone (LHRH) peptides and antibodies specific to the EphA2 receptor. The adhesion forces between LHRH-coated AFM tips and human MDA-MB-231 cells (breast cancer cells) were shown to be about five times greater than those between LHRH-coated AFM tips and normal Hs578Bst breast cells. Similarly, those between EphA2 antibody-coated AFM tips and breast cancer cells were over five times greater than those between EphA2 antibody-coated AFM tips and normal breast cells. The results suggest that AFM can be used for the detection of breast cancer cells in biopsies. The implications of the results are also discussed for the early detection and localized treatment of cancer.

  2. Involvement of aquaporin-5 in differentiation of human gastric cancer cells.

    PubMed

    Watanabe, Tomoko; Fujii, Takuto; Oya, Takeshi; Horikawa, Naoki; Tabuchi, Yoshiaki; Takahashi, Yuji; Morii, Magotoshi; Takeguchi, Noriaki; Tsukada, Kazuhiro; Sakai, Hideki

    2009-03-01

    Litttle is known about the function of aquaporin (AQP) water channels in human gastric cancer. In the upper or middle part of human stomach, we found that expression level of AQP5 protein in intestinal type of adenocarcinoma was significantly higher than that in accompanying normal mucosa. AQP5 was localized in the apical membrane of the cancer cells. On the other hand, both AQP3 and AQP4 were not up-regulated in the adenocarcinoma. To elucidate the role of AQP5 in cancer cells, AQP5 was exogenously expressed in a cell line of poorly differentiated human gastric adenocarcinoma (MKN45). The AQP5 expression significantly increased the proportion of differentiated cells with a spindle shape, the activity of alkaline phosphatase, a marker for the intestinal epithelial cell type of cancer cells, and the expression level of laminin, an epithelial cell marker. Treatment of the MKN45 cells stably expressing AQP5 with HgCl(2), an inhibitor of aquaporins, significantly decreased the proportion of differentiated cells and the activity of alkaline phosphatase. Our results suggest that up-regulation of AQP5 may be involved in differentiation of human gastric cancer cells.

  3. Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment

    PubMed Central

    Justus, Calvin R.; Sanderlin, Edward J.; Yang, Li V.

    2015-01-01

    Cancer cells preferentially utilize glycolysis, instead of oxidative phosphorylation, for metabolism even in the presence of oxygen. This phenomenon of aerobic glycolysis, referred to as the “Warburg effect”, commonly exists in a variety of tumors. Recent studies further demonstrate that both genetic factors such as oncogenes and tumor suppressors and microenvironmental factors such as spatial hypoxia and acidosis can regulate the glycolytic metabolism of cancer cells. Reciprocally, altered cancer cell metabolism can modulate the tumor microenvironment which plays important roles in cancer cell somatic evolution, metastasis, and therapeutic response. In this article, we review the progression of current understandings on the molecular interaction between cancer cell metabolism and the tumor microenvironment. In addition, we discuss the implications of these interactions in cancer therapy and chemoprevention. PMID:25988385

  4. Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care

    ClinicalTrials.gov

    2016-03-01

    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

  5. Cancer

    MedlinePlus

    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 ...

  6. How Are Squamous and Basal Cell Skin Cancers Diagnosed?

    MedlinePlus

    ... often enough to cure basal and squamous cell skin cancers without further treatment. There are different types of skin biopsies. The ... and Prevention Early Detection, Diagnosis, and Staging Treating Skin Cancer - ... Your Doctor After Treatment What`s New in Skin Cancer - Basal and Squamous ...

  7. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  8. Ultraviolet carcinogenesis in nonmelanoma skin cancer. Part I: incidence rates in relation to geographic locations and in migrant populations.

    PubMed

    Almahroos, Mona; Kurban, Amal K

    2004-01-01

    Over the past two decades a worldwide increase in the incidence of skin cancer to near epidemic proportions has led to increased morbidity and appreciating cost. Well known risk factors include UV radiation, x or gamma irradiation, chemical carcinogens, genetic aberrations, and immunosuppression. This article reviews and analyzes the evidence for UV radiations role in the pathogenesis of nonmelanoma skin cancer (NMSC). Observations on the incidence of NMSC among migrants to temperate regions show an increase in both basal cell carcinoma and squamous cell carcinoma. There is also an increase in NMSC in areas with lower latitudes. Irradiation of human skin grafted to animals and animal models that develop NMSC lend further support to the role of UV radiation in the pathogenesis of NMSC. In the forthcoming Part II of this review, epidemiologic evidence will be presented attesting to the relationship between UV radiation and NMSC.

  9. Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy

    PubMed Central

    D’Eliseo, Donatella; Velotti, Francesca

    2016-01-01

    Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, possibly improving their efficacy especially against cancers resistant to treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on studies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing the molecular mechanisms underlying this effective and selective activity. Here, we highlight the multiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis can allow a better comprehension of the potential cytotoxic therapeutic role of n-3 PUFAs against cancer, providing specific information and support to design future pre-clinical and clinical studies for a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy. PMID:26821053

  10. Metabolic profiling of breast cancer: Differences in central metabolism between subtypes of breast cancer cell lines.

    PubMed

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

    2015-09-01

    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. PMID:26218769

  11. Cancer Stem Cell Plasticity Drives Therapeutic Resistance.

    PubMed

    Doherty, Mary R; Smigiel, Jacob M; Junk, Damian J; Jackson, Mark W

    2016-01-01

    The connection between epithelial-mesenchymal (E-M) plasticity and cancer stem cell (CSC) properties has been paradigm-shifting, linking tumor cell invasion and metastasis with therapeutic recurrence. However, despite their importance, the molecular pathways involved in generating invasive, metastatic, and therapy-resistant CSCs remain poorly understood. The enrichment of cells with a mesenchymal/CSC phenotype following therapy has been interpreted in two different ways. The original interpretation posited that therapy kills non-CSCs while sparing pre-existing CSCs. However, evidence is emerging that suggests non-CSCs can be induced into a transient, drug-tolerant, CSC-like state by chemotherapy. The ability to transition between distinct cell states may be as critical for the survival of tumor cells following therapy as it is for metastatic progression. Therefore, inhibition of the pathways that promote E-M and CSC plasticity may suppress tumor recurrence following chemotherapy. Here, we review the emerging appreciation for how plasticity confers therapeutic resistance and tumor recurrence. PMID:26742077

  12. Cancer Stem Cell Plasticity Drives Therapeutic Resistance

    PubMed Central

    Doherty, Mary R.; Smigiel, Jacob M.; Junk, Damian J.; Jackson, Mark W.

    2016-01-01

    The connection between epithelial-mesenchymal (E-M) plasticity and cancer stem cell (CSC) properties has been paradigm-shifting, linking tumor cell invasion and metastasis with therapeutic recurrence. However, despite their importance, the molecular pathways involved in generating invasive, metastatic, and therapy-resistant CSCs remain poorly understood. The enrichment of cells with a mesenchymal/CSC phenotype following therapy has been interpreted in two different ways. The original interpretation posited that therapy kills non-CSCs while sparing pre-existing CSCs. However, evidence is emerging that suggests non-CSCs can be induced into a transient, drug-tolerant, CSC-like state by chemotherapy. The ability to transition between distinct cell states may be as critical for the survival of tumor cells following therapy as it is for metastatic progression. Therefore, inhibition of the pathways that promote E-M and CSC plasticity may suppress tumor recurrence following chemotherapy. Here, we review the emerging appreciation for how plasticity confers therapeutic resistance and tumor recurrence. PMID:26742077

  13. GTI-2040 and Docetaxel in Treating Patients With Recurrent, Metastatic, or Unresectable Locally Advanced Non-Small Cell Lung Cancer, Prostate Cancer, or Other Solid Tumors

    ClinicalTrials.gov

    2013-01-23

    Recurrent Non-small Cell Lung Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  14. Concentration of Cd, Pb, Hg, and Se in Different Parts of Human Breast Cancer Tissues

    PubMed Central

    Mohammadi, Mehrnoosh; Riyahi Bakhtiari, Alireza; Khodabandeh, Saber

    2014-01-01

    Breast cancer is the major cause of cancer morbidity and mortality between women in the world. Metals involved in environmental toxicology are closely related to tumor growth and cancer. On the other hand, some metals such as selenium have anticarcinogenic properties. The aim of this study is to determine the concentration of cadmium, lead, mercury, and selenium in separated parts of tegmen, tumor, tumor adiposity, and tegmen adiposity of 14 breast cancer tissues which have been analyzed by graphite furnace atomic absorption (AA-670) and ICP-OES (ULTIMA 2CE). Our results show that Se and Hg have maximum and minimum concentration, respectively. Statistical analysis reveals no significant differences between metal accumulations in different parts of cancer tissues (P > 0.05) and this observation might be due to the close relation of separated parts of fatty breast organ. Thus, we could conclude that a high level of these heavy metals is accumulated in Iranian cancerous breasts and their presence can be one of the reasons of cancer appearance. PMID:24659998

  15. The Interconnectedness of Cancer Cell Signaling

    PubMed Central

    Rehemtulla, Alnawaz

    2011-01-01

    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 database 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. PMID:22241964

  16. Reconstruction of a generic metabolic network model of cancer cells.

    PubMed

    Hadi, Mahdieh; Marashi, Sayed-Amir

    2014-11-01

    A promising strategy for finding new cancer drugs is to use metabolic network models to investigate the essential reactions or genes in cancer cells. In this study, we present a generic constraint-based model of cancer metabolism, which is able to successfully predict the metabolic phenotypes of cancer cells. This model is reconstructed by collecting the available data on tumor suppressor genes. Notably, we show that the activation of oncogene related reactions can be explained by the inactivation of tumor suppressor genes. We show that in a simulated growth medium similar to the body fluids, our model outperforms the previously proposed model of cancer metabolism in predicting expressed genes.

  17. Delirium: assessment and treatment of patients with cancer. PART 2.

    PubMed

    Brown, Michelle; Hardy, Kersten

    Delirium at the end of life may present significant ethical dilemmas in clinical practice: whether to simply treat it in order to maximise symptom relief, with the resulting side effect being palliative sedation, or to attempt to reverse delirium and risk prolonging suffering. Determining whether the delirium can be reversed involves comprehensive assessment using established tools, which may or may not provide the answer to the question posed. This article examines the evidence surrounding several assessment tools that have been suggested as effective in identifying delirium, and the consequences of various approaches to the management of delirium in a patient with a cancer diagnosis. It also considers the impact delirium may have on the health professional and those close to the patient.

  18. Delirium: assessment and treatment of patients with cancer. PART 2.

    PubMed

    Brown, Michelle; Hardy, Kersten

    Delirium at the end of life may present significant ethical dilemmas in clinical practice: whether to simply treat it in order to maximise symptom relief, with the resulting side effect being palliative sedation, or to attempt to reverse delirium and risk prolonging suffering. Determining whether the delirium can be reversed involves comprehensive assessment using established tools, which may or may not provide the answer to the question posed. This article examines the evidence surrounding several assessment tools that have been suggested as effective in identifying delirium, and the consequences of various approaches to the management of delirium in a patient with a cancer diagnosis. It also considers the impact delirium may have on the health professional and those close to the patient. PMID:26911180

  19. Breast cancer and racial disparity between Caucasian and African American women, part 1 (BRCA-1).

    PubMed

    Tariq, Khurram; Latif, Naeem; Zaiden, Robert; Jasani, Nick; Rana, Fauzia

    2013-08-01

    Breast cancer is a commonly diagnosed malignancy and the second leading cause of cancer-related death among American women today. Despite the lower incidence of breast cancer among African American women, they are more likely to die from the disease each year than their white counterparts. We present a retrospective cohort study of the tumor registry data from electronic medical records of patients diagnosed with breast cancer at the University of Florida Health, Jacksonville from 2000 to 2005. A total of 907 patients were diagnosed with breast cancer; 445 patients with invasive breast cancer had complete medical records and were selected for this review. Much like previously published research, we found that African American patients presented with a more advanced stage and aggressive subtype of breast cancer than white patients, and were less likely to have health insurance. However, we have yet to determine if universal health care insurance can lead to improved health care access, better breast cancer awareness, and an enhanced attitude toward breast cancer screenings. Such factors would ultimately lead to an earlier diagnosis and better outcomes in both African American and white patients. We plan to investigate this critical issue in a follow-up study (BRCA-2; Breast Cancer and Racial Disparity Between Caucasian and African American Women, Part 2), which will begin a few years after the complete implementation of the universal health care law enacted by President Obama in 2010. The higher frequency of aggressive tumor subtypes in African American women warrants more attention. We suggest further research to determine whether decreasing the initial age for screening or increasing the frequency of mammograms in African American women would improve breast cancer outcomes. This study underscores the importance of identifying and preventing obstacles in routine breast cancer screening, as well as increasing breast cancer awareness.

  20. Overexpression of ankyrin1 promotes pancreatic cancer cell growth

    PubMed Central

    Omura, Noriyuki; Mizuma, Masamichi; MacGregor, Anne; Hong, Seung-Mo; Ayars, Michael; Almario, Jose Alejandro; Borges, Michael; Kanda, Mitsuro; Li, Ang; Vincent, Audrey; Maitra, Anirban; Goggins, Michael

    2016-01-01

    The methylation status of a promoter influences gene expression and aberrant methylation during tumor development has important functional consequences for pancreatic and other cancers. Using methylated CpG island amplification and promoter microarrays, we identified ANK1 as hypomethylated in pancreatic cancers. Expression analysis determined ANK1 as commonly overexpressed in pancreatic cancers relative to normal pancreas. ANK1 was co-expressed with miR-486 in pancreatic cancer cells. Stable knockdown of ANK1 in the pancreatic cancer cell line AsPC1 led to changes in cell morphology, and decreases in colony formation. Stable knockdown of ANK1 also marked reduced the growth of tumors in athymic nude mice. Among patients undergoing pancreaticoduodenectomy, those with pancreatic cancers expressing ANK1 had a poorer prognosis than those without ANK1 expression. These findings indicate a role for ANK1 overexpression in mediating pancreatic cancer tumorigenicity. PMID:27144336

  1. Personalized Therapy of Small Cell Lung Cancer.

    PubMed

    Schneider, Bryan J; Kalemkerian, Gregory P

    2016-01-01

    Small cell lung cancer (SCLC) is an aggressive, poorly differentiated neuroendocrine carcinoma with distinct clinical, pathological and molecular characteristics. Despite robust responses to initial chemotherapy and radiation, the prognosis of patients with SCLC remains poor with an overall 5-year survival rate of less than 10 %. Despite the fact that numerous molecularly targeted approaches have thus far failed to demonstrate clinical utility in SCLC, further advances will rely on better definition of the biological pathways that drive survival, proliferation and metastasis. Recent next-generation, molecular profiling studies have identified many new therapeutic targets in SCLC, as well as extreme genomic instability which explains the high degree of resistance. A wide variety of anti-angiogenic agents, growth factor inhibitors, pro-apoptotic agents, and epigenetic modulators have been evaluated in SCLC and many studies of these strategies are on-going. Perhaps the most promising approaches involve agents targeting cancer stem cell pathways and immunomodulatory drugs that interfere with the PD1 and CTLA-4 pathways. SCLC offers many barriers to the development of successful therapy, including limited tumor samples, inadequate preclinical models, high mutational burden, and aggressive tumor growth which impairs functional status and hampers enrollment on clinical trials. PMID:26703804

  2. Treatment of small cell lung cancer patients.

    PubMed

    Zöchbauer-Müller, S; Pirker, R; Huber, H

    1999-01-01

    Small cell lung cancers, comprising approximately 20% of lung cancers, are rapidly growing and disseminating carcinomas which are initially chemosensitive but acquire drug resistance during the course of disease. Thus, outcome is poor with median survival of 10-16 months for patients with limited and 7-11 months for patients with extensive disease. Polychemotherapy with established drugs (platins, etoposide, anthracyclines, cyclophosphamide, ifosfamide and Vinca alkaloids) plays the major role in the treatment of this disease and results in overall response rates between 80%-95% for limited disease and 60%-80% for extensive disease. Dose-intensified chemotherapy and high-dose chemotherapy with peripheral blood progenitor cell support were tested in several trials but their exact impact on outcome remains to be determined. New drugs including the taxanes (paclitaxel, docetaxel), the topoisomerase I inhibitors (topotecan, irinotecan), vinorelbine and gemcitabine are currently evaluated in clinical trials. In limited disease, thoracic radiotherapy improves survival and prophylactic cranial irradiation should be administered to those with a reasonable chance of cure. PMID:10676558

  3. Adipose microenvironment promotes triple negative breast cancer cell invasiveness and dissemination by producing CCL5

    PubMed Central

    D’Esposito, Vittoria; Liguoro, Domenico; Ambrosio, Maria Rosaria; Collina, Francesca; Cantile, Monica; Spinelli, Rosa; Raciti, Gregory Alexander; Miele, Claudia; Valentino, Rossella; Campiglia, Pietro; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Formisano, Pietro

    2016-01-01

    Growing evidence indicates that adiposity is associated with raised cancer incidence, morbidity and mortality. In a subset of tumors, cancer cell growth and/or metastasis predominantly occur in adipocyte-rich microenvironment. Indeed, adipocytes represent the most abundant cell types surrounding breast cancer cells. We have studied the mechanisms by which peritumoral human adipose tissue contributes to Triple Negative Breast Cancer (TNBC) cell invasiveness and dissemination. Co-culture with human adipocytes enhanced MDA-MB231 cancer cell invasiveness. Adipocytes cultured in high glucose were 2-fold more active in promoting cell invasion and motility compared to those cultured in low glucose. This effect is induced, at least in part, by the CC-chemokine ligand 5 (CCL5). Indeed, CCL5 inhibition by specific peptides and antibodies reduced adipocyte-induced breast cancer cell migration and invasion. CCL5 immuno-detection in peritumoral adipose tissue of women with TNBC correlated with lymph node (p-value = 0.04) and distant metastases (p-value = 0.001). A positive trend was also observed between CCL5 expression and glycaemia. Finally, Kaplan-Meier curves showed a negative correlation between CCL5 staining in the peritumoral adipose tissue and overall survival of patients (p-value = 0.039). Thus, inhibition of CCL5 in adipose microenvironment may represent a novel approach for the therapy of highly malignant TNBC. PMID:27027351

  4. Chinese medicines induce cell death: the molecular and cellular mechanisms for cancer therapy.

    PubMed

    Wang, Xuanbin; Feng, Yibin; Wang, Ning; Cheung, Fan; Tan, Hor Yue; Zhong, Sen; Li, Charlie; Kobayashi, Seiichi

    2014-01-01

    Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and Methods. Chinese medicines (including Chinese medicinal herbs, animal parts, and minerals) were used in the study. The key words including "cancer", "cell death", "apoptosis", "autophagy," "necrosis," and "Chinese medicine" were used in retrieval of related information from PubMed and other databases. Results. The cell death induced by Chinese medicines is described as apoptotic, autophagic, or necrotic cell death and other types with an emphasis on their mechanisms of anticancer action. The relationship among different types of cell death induced by Chinese medicines is critically reviewed and discussed. Conclusions. This review summarizes that CMs treatment could induce multiple pathways leading to cancer cell death, in which apoptosis is the dominant type. To apply these preclinical researches to clinic application will be a key issue in the future.

  5. 3D cancer cell migration in a confined matrix

    NASA Astrophysics Data System (ADS)

    Alobaidi, Amani; Sun, Bo

    Cancer cell migration is widely studied in 2D motion, which does not mimic the invasion processes in vivo. More recently, 3D cell migration studies have been performed. The ability of cancer cells to migrate within the extracellular matrix depends on the physical and biochemical features of the extracellular matrix. We present a model of cell motility in confined matrix geometry. The aim of the study is to study cancer migration in collagen matrix, as a soft tissue, to investigate their motility within the confined and surrounding collagen environment. Different collagen concentrations have been used to show the ability of these cancer cells to move through such a complex structure by measuring Cancer cell migration velocity as well as the displacement. Graduate student physics department.

  6. Glutaminolysis: supplying carbon or nitrogen or both for cancer cells?

    PubMed

    Dang, Chi V

    2010-10-01

    A cancer cell comprising largely of carbon, hydrogen, oxygen, phosphorus, nitrogen and sulfur requires not only glucose, which is avidly transported and converted to lactate by aerobic glycolysis or the Warburg effect, but also glutamine as a major substrate. Glutamine and essential amino acids, such as methionine, provide energy through the TCA cycle as well as nitrogen, sulfur and carbon skeletons for growing and proliferating cancer cells. The interplay between utilization of glutamine and glucose is likely to depend on the genetic make-up of a cancer cell. While the MYC oncogene induces both aerobic glycolysis and glutaminolysis, activated β-catenin induces glutamine synthesis in hepatocellular carcinoma. Cancer cells that have elevated glutamine synthetase can use glutamate and ammonia to synthesize glutamine and are hence not addicted to glutamine. As such, cancer cells have many degrees of freedom for re-programming cell metabolism, which with better understanding will result in novel therapeutic approaches.

  7. Phototheranostics of CD44-positive cell populations in triple negative breast cancer

    PubMed Central

    Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Kobayashi, Hisataka; Bhujwalla, Zaver M.

    2016-01-01

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44high/CD24low, and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC. PMID:27302409

  8. Osteosarcoma: mouse models, cell of origin and cancer stem cell

    PubMed Central

    Guijarro, Maria V.

    2016-01-01

    Osteosarcoma (OS) is the most common non-hematologic primary tumor of bone in children and adults. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for non-metastatic disease approaching 70%. However, most OS tumors are high grade and tend to rapidly develop pulmonary metastases. Despite clinical advances, patients with metastatic disease or relapse have a poor prognosis. Here the cell biology of OS is reviewed with a special emphasis on mouse models as well as the roles of the cell of origin and cancer stem cells. A better understanding of the molecular pathogenesis of human OS is essential for the development of improved prognostic and diagnostic markers as well as targeted therapies for both primary and metastatic OS.

  9. Activated leukocyte cell adhesion molecule regulates the interaction between pancreatic cancer cells and stellate cells

    PubMed Central

    Zhang, Wei-Wei; Zhan, Shu-Hui; Geng, Chang-Xin; Sun, Xin; Erkan, Mert; Kleeff, Jörg; Xie, Xiang-Jun

    2016-01-01

    Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a transmembrane glycoprotein that is involved in tumor progression and metastasis. In the present study, the expression and functional role of ALCAM in pancreatic cancer cells and pancreatic stellate cells (PSCs) was investigated. Tissue specimens were obtained from patients with pancreatic ductal adenocarcinoma (n=56) or chronic pancreatitis (CP; n=10), who underwent pancreatic resection, and from normal pancreatic tissue samples (n=10). Immunohistochemistry was used to analyze the localization and expression of ALCAM in pancreatic tissues. Subsequently, reverse transcription-quantitative polymerase chain reaction and immunoblotting were applied to assess the expression of ALCAM in pancreatic cancer Panc-1 and T3M4 cells, as well as in PSCs. An enzyme-linked immunosorbent assay was used to measure ALCAM levels in cell culture medium stimulated by hypoxia, tumor necrosis factor (TNF)-α and transforming growth factor-β. Silencing of ALCAM was performed using ALCAM small interfering (si)RNA and immunocytochemistry was used to analyze the inhibition efficiency. An invasion assay and a cell interaction assay were performed to assess the invasive ability and co-cultured adhesive potential of Panc-1 and T3M4 cells, as well as PSCs. Histologically, ALCAM expression was generally weak or absent in pancreatic cancer cells, but was markedly upregulated in PSCs in pancreatic cancer tissues. ALCAM was highly expressed in PSCs from CP tissues and PSCs surrounding pancreatic intraepithelial neoplasias, as well as in pancreatic cancer cells. ALCAM mRNA was highly expressed in PSCs, with a low to moderate expression in T3M4 and Panc-1 cells. Similar to the mRNA expression, immunoblotting demonstrated that ALCAM protein levels were high in PSCs and T3M4 cells, but low in Panc-1 cells. The expression of TNF-α increased, while hypoxia decreased the secretion of ALCAM in pancreatic cancer Panc-1 and T3M4 cells, and also in

  10. Exometabolom analysis of breast cancer cell lines: Metabolic signature

    PubMed Central

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

    2015-01-01

    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. PMID:26293811

  11. How to target small cell lung cancer

    PubMed Central

    Hamilton, Gerhard; Rath, Barbara; Ulsperger, Ernst

    2015-01-01

    Small cell lung cancer (SCLC) is a highly malignant disease with dismal prognosis. Although great progress has been made in investigating genetic aberrations and putative drivers of this tumor entity, the mechanisms of rapid dissemination and acquisition of drug resistance are not clear. The majority of SCLC cases are characterized by inactivation of the tumor suppressors p53 and retinoblastoma (Rb) and, therefore, interchangeable drivers will be difficult to target successfully. Access to pure cultures of SCLC circulating tumor cells (CTCs) and study of their tumor biology has revealed a number of new potential targets. Most important, expression of chitinase-3-like-1/YKL-40 (CHI3L1) which controls expression of vascular epithelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9) was newly described in these cells. The process switching CHI3L1-negative SCLC cells to CHI3L1-positive CTCs seems to be associated with cytokines released by inflammatory immune cells. Furthermore, these CTCs were found to promote monocyte-macrophage differentiation, most likely of the M2 tumor-promoting type, recently described to express PD-1 immune checkpoint antigen in SCLC. In conclusion, dissemination of SCLC seems to be linked to conversion of regular tumor cells to highly invasive CHI3L1-positive CTCs, which are protected by immune system suppression. Besides the classical targets VEGF, MMP-9 and PD-1, CHI3L1 constitutes a new possibly drugable molecule to retard down dissemination of SCLC cells, which may be similarly relevant for glioblastoma and other tumor entities. PMID:26425658

  12. Comparative proteomics analysis of oral cancer cell lines: identification of cancer associated proteins

    PubMed Central

    2014-01-01

    Background A limiting factor in performing proteomics analysis on cancerous cells is the difficulty in obtaining sufficient amounts of starting material. Cell lines can be used as a simplified model system for studying changes that accompany tumorigenesis. This study used two-dimensional gel electrophoresis (2DE) to compare the whole cell proteome of oral cancer cell lines vs normal cells in an attempt to identify cancer associated proteins. Results Three primary cell cultures of normal cells with a limited lifespan without hTERT immortalization have been successfully established. 2DE was used to compare the whole cell proteome of these cells with that of three oral cancer cell lines. Twenty four protein spots were found to have changed in abundance. MALDI TOF/TOF was then used to determine the identity of these proteins. Identified proteins were classified into seven functional categories – structural proteins, enzymes, regulatory proteins, chaperones and others. IPA core analysis predicted that 18 proteins were related to cancer with involvements in hyperplasia, metastasis, invasion, growth and tumorigenesis. The mRNA expressions of two proteins – 14-3-3 protein sigma and Stress-induced-phosphoprotein 1 – were found to correlate with the corresponding proteins’ abundance. Conclusions The outcome of this analysis demonstrated that a comparative study of whole cell proteome of cancer versus normal cell lines can be used to identify cancer associated proteins. PMID:24422745

  13. Protective mechanism against cancer found in progeria patient cells

    Cancer.gov

    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

  14. [Circulating tumor cells in head and neck cancer].

    PubMed

    Guntinas-Lichius, O; Pachmann, K

    2015-06-01

    Circulating tumor cells are defined as tumor cells which are circulating in the peripheral blood of the cancer patient. While several large studies have investigated the role of circulating tumor cells in other solid tumors, the importance of these tumor cells in patients with head and neck cancer was turned into the focus not until the recent years. In other solid tumor the presence of circulating tumor cells often seems to be a negative prognostic marker and seems to be a marker for therapy response. The present article wants to give an overview about the knowledge on circulating tumor cells and their clinical relevance in head and neck cancer. The methodology to detect circulating tumor cells will be critically reflected. The future potential of the detection of circulating tumor cells in head and neck cancer patients will be discussed.

  15. Systems microscopy approaches to understand cancer cell migration and metastasis

    PubMed Central

    Le Dévédec, Sylvia E.; Yan, Kuan; de Bont, Hans; Ghotra, Veerander; Truong, Hoa; Danen, Erik H.; Verbeek, Fons

    2010-01-01

    Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially, invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding the molecular mechanisms that define cancer cell migration. PMID:20556632

  16. Ki-67 is required for maintenance of cancer stem cells but not cell proliferation

    PubMed Central

    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

    2016-01-01

    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

  17. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells.

    PubMed

    Lawson, Devon A; Bhakta, Nirav R; Kessenbrock, Kai; Prummel, Karin D; Yu, Ying; Takai, Ken; Zhou, Alicia; Eyob, Henok; Balakrishnan, Sanjeev; Wang, Chih-Yang; Yaswen, Paul; Goga, Andrei; Werb, Zena

    2015-10-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are initiated

  18. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells

    PubMed Central

    Lawson, Devon A.; Bhakta, Nirav R.; Kessenbrock, Kai; Prummel, Karin D.; Yu, Ying; Takai, Ken; Zhou, Alicia; Eyob, Henok; Balakrishnan, Sanjeev; Wang, Chih-Yang; Yaswen, Paul; Goga, Andrei; Werb, Zena

    2015-01-01

    Despite major advances in understanding the molecular and genetic basis of cancer, metastasis remains the cause of >90% of cancer-related mortality1. Understanding metastasis initiation and progression is critical to developing new therapeutic strategies to treat and prevent metastatic disease. Prevailing theories hypothesize that metastases are seeded by rare tumour cells with unique properties, which may function like stem cells in their ability to initiate and propagate metastatic tumours2–5. However, the identity of metastasis-initiating cells in human breast cancer remains elusive, and whether metastases are hierarchically organized is unknown2. Here we show at the single-cell level that early stage metastatic cells possess a distinct stem-like gene expression signature. To identify and isolate metastatic cells from patient-derived xenograft models of human breast cancer, we developed a highly sensitive fluorescence-activated cell sorting (FACS)-based assay, which allowed us to enumerate metastatic cells in mouse peripheral tissues. We compared gene signatures in metastatic cells from tissues with low versus high metastatic burden. Metastatic cells from low-burden tissues were distinct owing to their increased expression of stem cell, epithelial-to-mesenchymal transition, pro-survival, and dormancy-associated genes. By contrast, metastatic cells from high-burden tissues were similar to primary tumour cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have considerable tumour-initiating capacity, and can differentiate to produce luminal-like cancer cells. Progression to high metastatic burden was associated with increased proliferation and MYC expression, which could be attenuated by treatment with cyclin-dependent kinase (CDK) inhibitors. These findings support a hierarchical model for metastasis, in which metastases are

  19. Myeloid derived suppressor cells - a new therapeutic target in the treatment of cancer.

    PubMed

    Wesolowski, Robert; Markowitz, Joseph; Carson, William E

    2013-01-01

    Myeloid Derived Suppressor Cells (MDSC) are a heterogeneous population of immature myeloid cells that are increased in states of cancer, inflammation and infection. In malignant states, MDSC are induced by tumor secreted growth factors. MDSC play an important part in suppression of host immune responses through several mechanisms such as production of arginase 1, release of reactive oxygen species and nitric oxide and secretion of immune-suppressive cytokines. This leads to a permissive immune environment necessary for the growth of malignant cells. MDSC may also contribute to angiogenesis and tumor invasion. This review focuses on currently available strategies to inhibit MDSC in the treatment of cancer.

  20. Myeloid derived suppressor cells – a new therapeutic target in the treatment of cancer

    PubMed Central

    2013-01-01

    Myeloid Derived Suppressor Cells (MDSC) are a heterogeneous population of immature myeloid cells that are increased in states of cancer, inflammation and infection. In malignant states, MDSC are induced by tumor secreted growth factors. MDSC play an important part in suppression of host immune responses through several mechanisms such as production of arginase 1, release of reactive oxygen species and nitric oxide and secretion of immune-suppressive cytokines. This leads to a permissive immune environment necessary for the growth of malignant cells. MDSC may also contribute to angiogenesis and tumor invasion. This review focuses on currently available strategies to inhibit MDSC in the treatment of cancer. PMID:24829747

  1. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness.

    PubMed

    Giannoni, Elisa; Bianchini, Francesca; Masieri, Lorenzo; Serni, Sergio; Torre, Eugenio; Calorini, Lido; Chiarugi, Paola

    2010-09-01

    Although cancer-associated fibroblasts (CAF) are key determinants in the malignant progression of cancer, their functional contribution to this process is still unclear. Analysis of the mutual interplay between prostate carcinoma cells and CAFs revealed a mandatory role of carcinoma-derived interleukin-6 in fibroblast activation. In turn, activated fibroblasts through secretion of metalloproteinases elicit in cancer cells a clear epithelial-mesenchymal transition (EMT), as well as enhancement of tumor growth and development of spontaneous metastases. CAF-induced EMT leads prostate carcinoma cells to enhance expression of stem cell markers, as well as the ability to form prostaspheres and to self-renew. Hence, the paracrine interplay between CAFs and cancer cells leads to an EMT-driven gain of cancer stem cell properties associated with aggressiveness and metastatic spread.

  2. The metabolic state of cancer stem cells-a valid target for cancer therapy?

    PubMed

    Vlashi, Erina; Pajonk, Frank

    2015-02-01

    In the 1920s Otto Warburg first described high glucose uptake, aerobic glycolysis, and high lactate production in tumors. Since then high glucose uptake has been utilized in the development of PET imaging for cancer. However, despite a deepened understanding of the molecular underpinnings of glucose metabolism in cancer, this fundamental difference between normal and malignant tissue has yet to be employed in targeted cancer therapy in the clinic. In this review, we highlight attempts in the recent literature to target cancer cell metabolism and elaborate on the challenges and controversies of these strategies in general and in the context of tumor cell heterogeneity in cancer.

  3. The Metabolic State of Cancer Stem Cells – A Valid Target for Cancer Therapy?

    PubMed Central

    Vlashi, Erina; Pajonk, Frank

    2014-01-01

    In the 1920s Otto Warburg first described high glucose uptake, aerobic glycolysis and high lactate production in tumors. Since then high glucose uptake has been utilized in the development of PET imaging for cancer. However, despite a deepened understanding of the molecular underpinnings of glucose metabolism in cancer, this fundamental difference between normal and malignant tissue has yet to be employed intargeted cancer therapy in the clinic. In this review, we highlight attempts in the recent literature to target cancer cell metabolism and elaborate on the challenges and controversies of these strategies in general, and in the context of tumor cell heterogeneity in cancer. PMID:25450330

  4. What's New in Research and Treatment of Basal and Squamous Cell Skin Cancers?

    MedlinePlus

    ... for basal and squamous cell skin cancers What’s new in basal and squamous cell skin cancer research? ... cancer cells. Researchers are working to apply this new information to strategies for preventing and treating skin ...

  5. Lgr5-positive cells are cancer stem cells in skin squamous cell carcinoma.

    PubMed

    Liu, Shunli; Gong, Zhenyu; Chen, Mingrui; Liu, Benli; Bian, Donghui; Wu, Kai

    2014-11-01

    Cancer stem cells (CSCs) in most human tumors are commonly identified and enriched using similar strategies for identifying normal stem cells, including flow cytometry assays for side population, high aldehyde dehydrogenase (ALDH) activity, and CD133 positivity. Thus, development of a method for isolating a specific cancer using cancer-specific characteristic appears to be potentially important. Here, we reported extremely high Lgr5 levels in the specimen from skin squamous cell carcinoma (SCC) in patients. Using SCC cell line A431, we detected high Lgr5 and CD133 levels in ALDH-high or side population from these cancer cells. To figure out whether Lgr5 is a marker of CSCs in SCC, we transfected A431 cells with a Lgr5-creERT-2A-DTR/Cag-Loxp-GFP-STOP-Loxp-RFP plasmid and purified transfected cells (tA431) based on GFP by flow cytometry. 4-Hydroxytamoxifen (4-OHT) was given to label Lgr5-positive cells with RFP, for comparison to GFP-positive Lgr5-negative cells. Lgr5-positive cells grew significantly faster than Lgr5-negative cells, and the fold increase in growth of Lgr5-positive vs Lgr5-negative cells is significantly higher than SP vs non-SP, or ALDH-high vs ALDH-low, or CD133-positive vs CD133-negative cells. Moreover, in Lgr5-negative population, Lgr5-positive re-appeared in culture with time, suggesting that Lgr5-positive cells can be regenerated from Lgr5-negative cells. Furthermore, the growth of tA431 cells significantly decreased upon a single dose of diphtheria toxin (DT)/4-OHT to eliminate Lgr5-positive cell lineage, while multiple doses of DT/4-OHT nearly completely inhibited tA431 cell growth. Taken together, our data provide compelling data to demonstrate that Lgr5-positive cells are CSCs in skin SCC.

  6. Exploring Cancer Therapeutics with Natural Products from African Medicinal Plants, Part II: Alkaloids, Terpenoids and Flavonoids.

    PubMed

    Nwodo, Justina N; Ibezim, Akachukwu; Simoben, Conrad V; Ntie-Kang, Fidele

    2016-01-01

    Cancer stands as second most common cause of disease-related deaths in humans. Resistance of cancer to chemotherapy remains challenging to both scientists and physicians. Medicinal plants are known to contribute significantly to a large population of Africa, which is to a very large extent linked to folkloric claims which is part of their livelihood. In this review paper, the potential of naturally occurring anti-cancer agents from African flora has been explored, with suggested modes of action, where such data is available. Literature search revealed plant-derived compounds from African flora showing anti-cancer and/or cytotoxic activities, which have been tested in vitro and in vivo. This corresponds to 400 compounds (from mildly active to very active) covering various compound classes. However, in this part II, we only discussed the three major compound classes which are: flavonoids, alkaloids and terpenoids.

  7. Evolution and Phenotypic Selection of Cancer Stem Cells

    PubMed Central

    Poleszczuk, Jan; Hahnfeldt, Philip; Enderling, Heiko

    2015-01-01

    Cells of different organs at different ages have an intrinsic set of kinetics that dictates their behavior. Transformation into cancer cells will inherit these kinetics that determine initial cell and tumor population progression dynamics. Subject to genetic mutation and epigenetic alterations, cancer cell kinetics can change, and favorable alterations that increase cellular fitness will manifest themselves and accelerate tumor progression. We set out to investigate the emerging intratumoral heterogeneity and to determine the evolutionary trajectories of the combination of cell-intrinsic kinetics that yield aggressive tumor growth. We develop a cellular automaton model that tracks the temporal evolution of the malignant subpopulation of so-called cancer stem cells(CSC), as these cells are exclusively able to initiate and sustain tumors. We explore orthogonal cell traits, including cell migration to facilitate invasion, spontaneous cell death due to genetic drift after accumulation of irreversible deleterious mutations, symmetric cancer stem cell division that increases the cancer stem cell pool, and telomere length and erosion as a mitotic counter for inherited non-stem cancer cell proliferation potential. Our study suggests that cell proliferation potential is the strongest modulator of tumor growth. Early increase in proliferation potential yields larger populations of non-stem cancer cells(CC) that compete with CSC and thus inhibit CSC division while a reduction in proliferation potential loosens such inhibition and facilitates frequent CSC division. The sub-population of cancer stem cells in itself becomes highly heterogeneous dictating population level dynamics that vary from long-term dormancy to aggressive progression. Our study suggests that the clonal diversity that is captured in single tumor biopsy samples represents only a small proportion of the total number of phenotypes. PMID:25742563

  8. Analysis of non-thermal plasma-induced cell injury in human lung cancer cell lines

    NASA Astrophysics Data System (ADS)

    Kurita, Hirofumi; Sano, Kaori; Wada, Motoi; Mizuno, Kazue; Ono, Ryo; Yasuda, Hachiro; Takashima, Kazunori; Mizuno, Akira

    2015-09-01

    Recent progress of biomedical application of atmospheric pressure plasma shows that the biological effects are mainly due to reactive oxygen and nitrogen species (RONS) in liquid produced by the plasma exposure. To elucidate the cellular responses induced by exposure to the plasma, we focused on identification and quantification of reactive chemical species in plasma-exposed cell culture medium, and cell injury in mammalian cells after treatment of the plasma-exposed medium. In this study, we examined human lung cancer cell lines. The contribution of H2O2 to the cellular responses was considered. Here, an atmospheric pressure plasma jet (APPJ) sustained by a pulsed power supply in argon was used. After APPJ exposure to cell culture medium, RONS detection in liquid was conducted. It showed that OH radical, ONOO-, NO2-, NO3-, and H2O2 were produced in the plasma-exposed medium. Cellular responses of human lung cancer cell lines to the plasma-exposed medium in a concentration-dependence manner were also studied. It showed that the plasma-exposed medium and the H2O2 treatment gave similar reduction in viability and induction of apoptosis. This work was partly supported by MEXT KAKENHI Grant Number 24108005 and JSPS KAKENHI Grant Number 26390096.

  9. Pitavastatin suppressed liver cancer cells in vitro and in vivo

    PubMed Central

    You, He-Yi; Zhang, Wei-Jian; Xie, Xue-Meng; Zheng, Zhi-Hai; Zhu, Heng-Liang; Jiang, Fei-Zhao

    2016-01-01

    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.

  10. Dynamics of Cancer Cell near Collagen Fiber Chain

    NASA Astrophysics Data System (ADS)

    Kim, Jihan; Sun, Bo

    Cell migration is an integrated process that is important in life. Migration is essential for embryonic development as well as homeostatic processes such as wound healing and immune responses. When cell migrates through connective extracellular matrix (ECM), it applies cellular traction force to ECM and senses the rigidity of their local environment. We used human breast cancer cell (MDA-MB-231) which is highly invasive and applies strong traction force to ECM. As cancer cell applies traction force to type I collage-based ECM, it deforms collagen fibers near the surface. Patterns of deforming collagen fibers are significantly different with pairs of cancer cells compared to a single cancer cell. While a pair of cancer cells within 60 um creates aligned collagen fiber chains between them permanently, a single cancer cell does not form any fiber chains. In this experiment we measured a cellular response and an interaction between a pair of cells through the chain. Finally, we analyzed correlation of directions between cancer cell migration and the collagen chain alignment.

  11. Pitavastatin suppressed liver cancer cells in vitro and in vivo.

    PubMed

    You, He-Yi; Zhang, Wei-Jian; Xie, Xue-Meng; Zheng, Zhi-Hai; Zhu, Heng-Liang; Jiang, Fei-Zhao

    2016-01-01

    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

  12. How does metabolism affect cell death in cancer?

    PubMed

    Villa, Elodie; Ricci, Jean-Ehrland

    2016-07-01

    In cancer research, identifying a specificity of tumor cells compared with 'normal' proliferating cells for targeted therapy is often considered the Holy Grail for researchers and clinicians. Although diverse in origin, most cancer cells share characteristics including the ability to escape cell death mechanisms and the utilization of different methods of energy production. In the current paradigm, aerobic glycolysis is considered the central metabolic characteristic of cancer cells (Warburg effect). However, recent data indicate that cancer cells also show significant changes in other metabolic pathways. Indeed, it was recently suggested that Kreb's cycle, pentose phosphate pathway intermediates, and essential and nonessential amino acids have key roles. Renewed interest in the fact that cancer cells have to reprogram their metabolism in order to proliferate or resist treatment must take into consideration the ability of tumor cells to adapt their metabolism to the local microenvironment (low oxygen, low nutrients). This variety of metabolic sources might be either a strength, resulting in infinite possibilities for adaptation and increased ability to resist chemotherapy-induced death, or a weakness that could be targeted to kill cancer cells. Here, we discuss recent insights showing how energetic metabolism may regulate cell death and how this might be relevant for cancer treatment.

  13. Pitavastatin suppressed liver cancer cells in vitro and in vivo

    PubMed Central

    You, He-Yi; Zhang, Wei-Jian; Xie, Xue-Meng; Zheng, Zhi-Hai; Zhu, Heng-Liang; Jiang, Fei-Zhao

    2016-01-01

    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

  14. In situ recognition of cell-surface glycans and targeted imaging of cancer cells

    PubMed Central

    Xu, Xiao-Ding; Cheng, Han; Chen, Wei-Hai; Cheng, Si-Xue; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2013-01-01

    Fluorescent sensors capable of recognizing cancer-associated glycans, such as sialyl Lewis X (sLex) tetrasaccharide, have great potential for cancer diagnosis and therapy. Studies on water-soluble and biocompatible sensors for in situ recognition of cancer-associated glycans in live cells and targeted imaging of cancer cells are very limited at present. Here we report boronic acid-functionalized peptide-based fluorescent sensors (BPFSs) for in situ recognition and differentiation of cancer-associated glycans, as well as targeted imaging of cancer cells. By screening BPFSs with different structures, it was demonstrated that BPFS1 with a FRGDF peptide could recognize cell-surface glycan of sLex with high specificity and thereafter fluorescently label and discriminate cancer cells through the cooperation with the specific recognition between RGD and integrins. The newly developed peptide-based sensor will find great potential as a fluorescent probe for cancer diagnosis. PMID:24042097

  15. Lidocaine inhibits the invasion and migration of TRPV6-expressing cancer cells by TRPV6 downregulation

    PubMed Central

    Jiang, Yuan; Gou, Hui; Zhu, Jiang; Tian, Si; Yu, Lehua

    2016-01-01

    It is well known that local anesthetics have a broad spectrum of pharmacological actions, acting as nerve blocks, and treating pain and cardiac arrhythmias via blocking of the sodium channel. The use of local anesthetics could reduce the possibility of cancer metastasis and recurrence following surgical tumor excision. The purpose of the present study was to investigate the inhibitory effect of lidocaine upon the invasion and migration of transient receptor potential cation channel subfamily V member 6 (TRPV6)-expressing cancer cells. Human breast cancer MDA-MB-231 cells, prostatic cancer PC-3 cells and ovarian cancer ES-2 cells were treated with lidocaine. Cell viability was quantitatively determined by MTT assay. The migration of the cells was evaluated using the wound healing assay, and the invasion of the cells was assessed using a Transwell assay. Calcium (Ca2+) measurements were performed using a Fluo-3 AM fluorescence kit. The expression of TRPV6 mRNA and protein in the cells was determined by quantitative-polymerase chain reaction and western blot analysis, respectively. The results suggested that lidocaine inhibits the cell invasion and migration of MDA-MB-231, PC-3 and ES-2 cells at lower than clinical concentrations. The inhibitory effect of lidocaine on TRPV6-expressing cancer cells was associated with a reduced rate of calcium influx, and could occur partly as a result of the downregulation of TRPV6 expression. The use of appropriate local anesthetics may confer potential benefits in clinical practice for the treatment of patients with TRPV6-expressing cancer. PMID:27446413

  16. Chemoprevention of Low-Molecular-Weight Citrus Pectin (LCP) in Gastrointestinal Cancer Cells

    PubMed Central

    Wang, Shi; Li, Pei; Lu, Sheng-Min; Ling, Zhi-Qiang

    2016-01-01

    Background & Aims: Low-molecular-weight citrus pectin (LCP) is a complex polysaccharide that displays abundant galactosyl (i.e., sugar carbohydrate) residues. In this study, we evaluated the anti-tumor properties of LCP that lead to Bcl-xL -mediated dampening of apoptosis in gastrointestinal cancer cells. Methods: We used AGS gastric cancer and SW-480 colorectal cancer cells to elucidate the effects of LCP on cell viability, cell cycle and apoptosis in cultured cells and tumor xenografts. Results: Significantly decreased cell viabilities were observed in LCP treated AGS and SW-480 cells (P<0.05). Cell cycle-related protein expression, such as Cyclin B1, was also decreased in LCP treated groups as compared to the untreated group. The AGS or SW-480 cell-line tumor xenografts were significantly smaller in the LCP treated group as compared the untreated group (P<0.05). LCP treatment decreased Galectin-3 (GAL-3) expression levels, which is an important gene in cancer metastasis that results in reversion of the epithelial-mesenchymal transition (EMT), and increased suppression of Bcl-xL and Survivin to promote apoptosis. Moreover, results demonstrated synergistic tumor suppressor activity of LCP and 5-FU against gastrointestinal cancer cells both in vivo and in vitro. Conclusions: LCP effectively inhibits the growth and metastasis of gastrointestinal cancer cells, and does so in part by down-regulating Bcl-xL and Cyclin B to promote apoptosis, and suppress EMT. Thus, LCP alone or in combination with other treatments has a high potential as a novel therapeutic strategy to improve the clinical therapy of gastrointestinal cancer. PMID:27194951

  17. Molecular markers in prostate cancer. Part I: predicting lethality

    PubMed Central

    Agrawal, Sachin; Dunsmuir, William D.

    2009-01-01

    Assessing the lethality of 'early,' potentially organ-confined prostate cancer (PCa) is one of the central controversies in modern-day urological clinical practice. Such cases are often considered for radical 'curative' treatment, although active surveillance may be equally appropriate for many men. Moreover, the balance between judicious intervention and overtreatment can be difficult to judge. The patient's age, comorbidities, family history and philosophy of self-health care can be weighed against clinical features such as the palpability of disease, the number and percentage of biopsy cores involved with the disease, histological grade, presenting prostate-specific antigen (PSA) and possible previous PSA kinetics. For many years, scientists and physicians have sought additional molecular factors that may be predictive for disease stage, progression and lethality. Usually, claims for a 'new' unique marker fall short of true clinical value. More often than not, such molecular markers are useful only in multivariate models. This review summarizes relevant molecular markers and models reported up to and including 2008. PMID:19050690

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

    PubMed Central

    2015-01-01

    Chemoresistance is a primary cause of treatment failure in cancer and a common property of tumor-initiating cancer stem cells. Overcoming mechanisms of chemoresistance, particularly in cancer stem cells, can markedly enhance cancer therapy and prevent recurrence and metastasis. This study demonstrates that the delivery of Epirubicin by nanodiamonds is a highly effective nanomedicine-based approach to overcoming chemoresistance in hepatic cancer stem cells. The potent physical adsorption of Epirubicin to nanodiamonds creates a rapidly synthesized and stable nanodiamond–drug complex that promotes endocytic uptake and enhanced tumor cell retention. These attributes mediate the effective killing of both cancer stem cells and noncancer stem cells in vitro and in vivo. Enhanced treatment of both tumor cell populations results in an improved impairment of secondary tumor formation in vivo compared with treatment by unmodified chemotherapeutics. On the basis of these results, nanodiamond-mediated drug delivery may serve as a powerful method for overcoming chemoresistance in cancer stem cells and markedly improving overall treatment against hepatic cancers. PMID:25437772

  19. Multiple Cancer Cell Population Dynamics in a Complex Ecology

    NASA Astrophysics Data System (ADS)

    Lin, Ke-Chih; Targa, Gonzalo; Pienta, Kenneth; Sturm, James; Austin, Robert

    We have developed a technology for study of complex ecology cancer population dynamics. The technology includes complex drug gradients, full bright field/dark field/fluorescence imaging of areas of several square millimeters and thin gas-permable membranes which allow single cell extraction and analysis. We will present results of studies of prostate cancer cell dynamics.

  20. Induction of pyroptosis in colon cancer cells by LXRβ

    PubMed Central

    Rébé, Cédric; Derangère, Valentin; Ghiringhelli, François

    2015-01-01

    Liver X receptors (LXRs) have been proposed to have some anticancer properties. We recently identified a new non-genomic role of LXRβ in colon cancer cells. Under LXR agonist treatment, LXRβ induces pyroptosis of these cells in vitro and in vivo, raising the possibility of targeting this isoform in cancer treatment. PMID:27308405

  1. The Traditional Chinese Medicine Baicalein Potently Inhibits Gastric Cancer Cells

    PubMed Central

    Mu, Jiasheng; Liu, Tianrun; Jiang, Lin; Wu, Xiangsong; Cao, Yang; Li, Maolan; Dong, Qian; Liu, Yingbin; Xu, Haineng

    2016-01-01

    Baicalein, a traditional Chinese medicine, is a member of the flavone subclass of flavonoids. It has been reported to have anticancer activities in several human cancer cell lines in vitro. However, the therapeutic effects of baicalein on human gastric cancer and the mechanisms of action of baicalein have not been extensively studied. In the present study, we utilized a cell viability assay and an in vivo tumor growth assay to test the inhibitory effects of baicalein on gastric cancer. Analyses of the cell cycle, apoptosis and alterations in protein levels were performed to elucidate how baicalein functions in gastric cancer. We found that baicalein could potently inhibit gastric cancer cell growth and colony formation. Baicalein robustly induced arrest at the S phase in the gastric cancer cell line SGC-7901. It induced SGC-7901 cell apoptosis and disrupted the mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Analysis of protein expression levels in SGC-7901 cells showed downregulation of Bcl-2 and upregulation of Bax in response to baicalein treatment. These results indicate that baicalein induces apoptosis of gastric cancer cells through the mitochondrial pathway. In an in vivo subcutaneous xenograft model, baicalein exhibited excellent tumor inhibitory effects. These results indicate that baicalein may be a potential drug for gastric cancer therapy. PMID:26918059

  2. The Traditional Chinese Medicine Baicalein Potently Inhibits Gastric Cancer Cells.

    PubMed

    Mu, Jiasheng; Liu, Tianrun; Jiang, Lin; Wu, Xiangsong; Cao, Yang; Li, Maolan; Dong, Qian; Liu, Yingbin; Xu, Haineng

    2016-01-01

    Baicalein, a traditional Chinese medicine, is a member of the flavone subclass of flavonoids. It has been reported to have anticancer activities in several human cancer cell lines in vitro. However, the therapeutic effects of baicalein on human gastric cancer and the mechanisms of action of baicalein have not been extensively studied. In the present study, we utilized a cell viability assay and an in vivo tumor growth assay to test the inhibitory effects of baicalein on gastric cancer. Analyses of the cell cycle, apoptosis and alterations in protein levels were performed to elucidate how baicalein functions in gastric cancer. We found that baicalein could potently inhibit gastric cancer cell growth and colony formation. Baicalein robustly induced arrest at the S phase in the gastric cancer cell line SGC-7901. It induced SGC-7901 cell apoptosis and disrupted the mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Analysis of protein expression levels in SGC-7901 cells showed downregulation of Bcl-2 and upregulation of Bax in response to baicalein treatment. These results indicate that baicalein induces apoptosis of gastric cancer cells through the mitochondrial pathway. In an in vivo subcutaneous xenograft model, baicalein exhibited excellent tumor inhibitory effects. These results indicate that baicalein may be a potential drug for gastric cancer therapy.

  3. A multicenter blinded study evaluating EGFR and KRAS mutation testing methods in the clinical non-small cell lung cancer setting--IFCT/ERMETIC2 Project Part 1: Comparison of testing methods in 20 French molecular genetic National Cancer Institute platforms.

    PubMed

    Beau-Faller, Michèle; Blons, Hélène; Domerg, Caroline; Gajda, Dorota; Richard, Nicolas; Escande, Fabienne; Solassol, Jérôme; Denis, Marc G; Cayre, Anne; Nanni-Metellus, Isabelle; Olschwang, Sylviane; Lizard, Sarab; Piard, Fabienne; Pretet, Jean-Luc; de Fraipont, Florence; Bièche, Ivan; de Cremoux, Patricia; Rouquette, Isabelle; Bringuier, Pierre-Paul; Mosser, Jean; Legrain, Michèle; Voegeli, Anne-Claire; Saulnier, Patrick; Morin, Franck; Pignon, Jean-Pierre; Zalcman, Gérard; Cadranel, Jacques

    2014-01-01

    Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors have limited use as first-line treatment for mutated EGFR metastatic non-small cell lung cancer. The French National Cancer Institute has installed molecular genetics platforms implementing EGFR and KRAS testing. However, there is considerable uncertainty as to which detection methods should be applied for routine diagnosis. This study aimed to compare the EGFR and KRAS genotyping methods developed by the IFCT/ERMETIC2 network platforms in two blind panels: 25 samples of serial dilutions of cell line DNA (20 centers) and 74 FFPE lung tumor samples (10 centers). The best threshold of mutation detection on cell lines was obtained using allele-specific amplification-based technologies. Nonamplifiable tissue samples were significantly less common when using alternative testing versus direct sequencing [15%; 95% confidence interval (CI), 14%-16% versus 40%; 95% CI, 39%-42%; P < 0.001]. Mutated cases increased from 42% (95% CI, 31%-54%) to 53% (95% CI, 41%-64%), with three supplementary EGFR mutations (p.G179A at exon 18 and p.L858R and p.L861Q at exon 21) and five supplementary KRAS mutations, when using alternative testing instead of direct sequencing. False-positive results were observed when using a PCR-based sizing assay, high-resolution melting, or pyrosequencing. Concordance analysis returned good kappa test scores for EGFR exon 19 and KRAS analysis when comparing sequencing with alternative methods and revealed no difference between alternative techniques themselves.

  4. Project for the National Program of Early Diagnosis of Endometrial Cancer Part II

    PubMed Central

    Bohîlțea, RE; Ancăr, V; Rădoi, V; Furtunescu, F; Bohîlțea, LC

    2015-01-01

    Rationale: Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania. Since 2013, an increased trend of endometrial cancer occurrence has been registered in urban areas as compared with rural ones. Unfortunately, most of the cancer cases are diagnosed too late, in an advanced stage of the disease, resulting into diminished lifetime expectancy. The first part of the article concentrated on issues such as: the description of the study, results, and discussions regarding the study, definitions and terms, risk factors specific for endometrial carcinomas, presentation of the activities of the Program, etc. Objective: Drafting a national program that will serve as an early diagnosis method of endometrial cancer. This second part of the study continues with the presentation of the activities of the Program, analyzes the human resources and materials needed to implement the Program, presents the strategies and the indicators specific for the implementation of the project. Methods and Results: A standardization of the diagnostic steps was proposed and the focus was on 4 key elements for the early diagnosis of endometrial cancer: The first steps were approached in the first part of the study and the second part of the study investigated the proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Discussion: Improving medical practice based on diagnostic algorithms and programs improves and increases the lifetime expectancy, due to the fact that endometrial cancer is early diagnosed and treated before it causes serious health problems or even death. Abbreviations: ASCCP = American Society for Colposcopy and Cervical Pathology, CT = Computerized Tomography, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, MSI = Microsatellites instability, MSI-H/ MSI-L = high (positive test)/ low (negative test

  5. [Biology of cancer cell-stroma interaction in carcinogenesis and cancer progression].

    PubMed

    Fujita, S; Sugihara, H; Ito, R; Tsuchihashi, Y

    1984-03-01

    Cancer cells are dependent on physical and chemical supports of stroma no less than non-cancerous cells and tissues are. The role of stroma should, therefore, be important in genesis and progression of cancers growing in vivo. But this aspect underlying carcinogenesis and manifestation of human cancers has long been neglected or attracted less attention in the investigations of oncology. Focusing particular attention on parenchyma-stromal interaction in gastrointestinal mucosa, the authors have found that, quite unexpectedly, in normal gastric as well as intestinal mucosa of all the animal species so for studied, vascularity is always poorly developed in the generative cell zones. Cross-sectional area of vascular bed is markedly reduced in this zone. Application of Hagen-Poiseulle law revealed that the reduced total cross-sectional area, resulting in a rapid drop in hydrostatic pressure, creates here a situation particularly favorable for proliferating cell population. Since the transport of water soluble material together with tissue fluid through the capillary wall is driven by the hydrostatic pressure, the generative cell zones are found to be present at the site where the turnover of the material is the most active. Before the zone of the rapid pressure drop, there appears zone of relatively high intravascular hydrostatic pressure, where secretory function seems to be facilitated. This zone, as is well known, corresponds to glandular portion of the mucosa. After the zone of the rapid pressure drop (in surface of the mucosa), zone of a low intravascular hydrostatic pressure appears, where absorptive function is to be facilitated. Within such zones, in gastric mucosa surface epithelium and in intestinal mucosa absorptive villi cells are located. It is likely that architecture of gastrointestinal epithelium and vascular pattern in the stroma is closely correlated and that the former is determined, at least partly, by the latter. When human gastric mucosa shows

  6. [Energy metabolism of Ehrlich ascites cancer cells].

    PubMed

    del Pozo, A M; Valladares, Y; Alvarez Rodríguez, Y

    1983-01-01

    Cell respiration (CR) and glycolysis (GL) are the main sources cell energy, since along their metabolic pathways ATP is produced. Expressed as microM/100 mg/h, normal cells produce 63 by CR, 0.2 by aerobic GL, and 9.37 by anaerobic GL, while cancer cells produce 35 by CR, 18 by aerobic GL, and 29 by anaerobic GL. The ascites fluid from EAC increases the anaerobic GL to 38, while it does not change the aerobic GL to 7 and diminishes the CR to 26. Insulin produces a lowering of CR to 26, aerobic GL to 26 and anaerobic GL to 22. Glucose inhibits CR and stimulates GL. Ribose does not modify CR and inhibits GL. Mannose inhibits both CR and GL. Ribonuclease increases GL in the presence of glucose but not of ribose. Glucose-phosphate and ribose-phosphate have no action because they do not enter into the cell. Expressed as QLN2/100 mg, the main localization of GL is the cytosol (480), but it is significant in the nucleus (170), and diminishes in microsomes (100) and mitochondria (52). Mitochondria inhibit the cytosol glycolytic activity when they are either in the usual proportion they have in the cell or in a higher proportion. It is curious the observation that a diminution of the relative concentration of mitochondria with regard to cytosol (1/100 to 1/1000) produces a marked increase of GL. The addition of nuclear fraction stabilizes the cytosol-mitochondria complex and modifies the metabolic pathway of the CO2 that is produced during the GL.

  7. MiR-221 promotes stemness of breast cancer cells by targeting DNMT3b

    PubMed Central

    Roscigno, Giuseppina; Quintavalle, Cristina; Donnarumma, Elvira; Puoti, Ilaria; Diaz-Lagares, Angel; Iaboni, Margherita; Fiore, Danilo; Russo, Valentina; Todaro, Matilde; Romano, Giulia; Thomas, Renato; Cortino, Giuseppina; Gaggianesi, Miriam; Esteller, Manel; Croce, Carlo M.; Condorelli, Gerolama

    2016-01-01

    Cancer stem cells (CSCs) are a small part of the heterogeneous tumor cell population possessing self-renewal and multilineage differentiation potential as well as a great ability to sustain tumorigenesis. The molecular pathways underlying CSC phenotype are not yet well characterized. MicroRNAs (miRs) are small noncoding RNAs that play a powerful role in biological processes. Early studies have linked miRs to the control of self-renewal and differentiation in normal and cancer stem cells. We aimed to study the functional role of miRs in human breast cancer stem cells (BCSCs), also named mammospheres. We found that miR-221 was upregulated in BCSCs compared to their differentiated counterpart. Similarly, mammospheres from T47D cells had an increased level of miR-221 compared to differentiated cells. Transfection of miR-221 in T47D cells increased the number of mammospheres and the expression of stem cell markers. Among miR-221's targets, we identified DNMT3b. Furthermore, in BCSCs we found that DNMT3b repressed the expression of various stemness genes, such as Nanog and Oct 3/4, acting on the methylation of their promoters, partially reverting the effect of miR-221 on stemness. We hypothesize that miR-221 contributes to breast cancer tumorigenicity by regulating stemness, at least in part through the control of DNMT3b expression. PMID:26556862

  8. ccmGDB: a database for cancer cell metabolism genes

    PubMed Central

    Kim, Pora; Cheng, Feixiong; Zhao, Junfei; Zhao, Zhongming

    2016-01-01

    Accumulating evidence has demonstrated that rewiring of metabolism in cells is an important hallmark of cancer. The percentage of patients killed by metabolic disorder has been estimated to be 30% of the advanced-stage cancer patients. Thus, a systematic annotation of cancer cell metabolism genes is imperative. Here, we present ccmGDB (Cancer Cell Metabolism Gene DataBase), a comprehensive annotation database for cell metabolism genes in cancer, available at http://bioinfo.mc.vanderbilt.edu/ccmGDB. We assembled, curated, and integrated genetic, genomic, transcriptomic, proteomic, biological network and functional information for over 2000 cell metabolism genes in more than 30 cancer types. In total, we integrated over 260 000 somatic alterations including non-synonymous mutations, copy number variants and structural variants. We also integrated RNA-Seq data in various primary tumors, gene expression microarray data in over 1000 cancer cell lines and protein expression data. Furthermore, we constructed cancer or tissue type-specific, gene co-expression based protein interaction networks and drug-target interaction networks. Using these systematic annotations, the ccmGDB portal site provides 6 categories: gene summary, phenotypic information, somatic mutations, gene and protein expression, gene co-expression network and drug pharmacological information with a user-friendly interface for browsing and searching. ccmGDB is developed and maintained as a useful resource for the cancer research community. PMID:26519468

  9. Epidemiologic characteristics and risk factors for renal cell cancer

    PubMed Central

    Lipworth, Loren; Tarone, Robert E; Lund, Lars; McLaughlin, Joseph K

    2009-01-01

    Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches, including evaluation of gene–environment interactions and epigenetic mechanisms of inherited and acquired increased risk, are needed to explain the increasing incidence of renal cell cancer. PMID:20865085

  10. Epidemiologic characteristics and risk factors for renal cell cancer.

    PubMed

    Lipworth, Loren; Tarone, Robert E; Lund, Lars; McLaughlin, Joseph K

    2009-08-09

    Incidence rates of renal cell cancer, which accounts for 85% of kidney cancers, have been rising in the United States and in most European countries for several decades. Family history is associated with a two- to four-fold increase in risk, but the major forms of inherited predisposition together account for less than 4% of renal cell cancers. Cigarette smoking, obesity, and hypertension are the most consistently established risk factors. Analgesics have not been convincingly linked with renal cell cancer risk. A reduced risk of renal cell cancer among statin users has been hypothesized but has not been adequately studied. A possible protective effect of fruit and vegetable consumption is the only moderately consistently reported dietary finding, and, with the exception of a positive association with parity, evidence for a role of hormonal or reproductive factors in the etiology of renal cell cancer in humans is limited. A recent hypothesis that moderate levels of alcohol consumption may be protective for renal cell cancer is not strongly supported by epidemiologic results, which are inconsistent with respect to the categories of alcohol consumption and the amount of alcohol intake reportedly associated with decreased risk. For occupational factors, the weight of the evidence does not provide consistent support for the hypotheses that renal cell cancer may be caused by asbestos, gasoline, or trichloroethylene exposure. The established determinants of renal cell cancer, cigarette smoking, obesity, and hypertension, account for less than half of these cancers. Novel epidemiologic approaches, including evaluation of gene-environment interactions and epigenetic mechanisms of inherited and acquired increased risk, are needed to explain the increasing incidence of renal cell cancer.

  11. Transferrin synthesis by small cell lung cancer cells acts as an autocrine regulator of cellular proliferation.

    PubMed Central

    Vostrejs, M; Moran, P L; Seligman, P A

    1988-01-01

    Since transferrin is required for cellular proliferation, we investigated transferrin synthesis by a small cell lung cancer line (NCI-H510) that survives in serum-free media without added transferrin. Immunoassays for human transferrin demonstrated that these cells contained immunoreactive human transferrin. Immunofluorescence studies showed that the protein is expressed on the surface of cells, presumably bound to transferrin receptor. Media conditioned by NCI-H510 cells support proliferation of human leukemic cells that would not survive in media lacking transferrin. [35S]Methionine incorporation documented transferrin synthesis by NCI-H510 cells as well as three other small cell lines. Transferrin synthesis by NCI-H510 cells increased more than 10-fold when cells entered active phases of the cell cycle, and this increase was seen before large increases in transferrin-receptor expression. Further experiments examining the effects of agents that affect iron metabolism show that the addition of transferrin-iron or hemin to the media is associated with a more rapid initial rate of proliferation and lower rates of transferrin synthesis than control cells. Gallium salts, which inhibit iron uptake, inhibited proliferation of these cells. If the cells recovered from this effect, transferrin synthesis remained greatly increased compared to control. We conclude that transferrin synthesis by these malignant cells is ultimately related to an iron requirement for cellular proliferation. It appears that this synthesized transferrin acts as part of an important autocrine mechanism permitting proliferation of these cells, and perhaps permitting tumor cell growth in vivo in areas not well vascularized. Images PMID:2839550

  12. Identification of drugs that restore primary cilium expression in cancer cells.

    PubMed

    Khan, Niamat Ali; Willemarck, Nicolas; Talebi, Ali; Marchand, Arnaud; Binda, Maria Mercedes; Dehairs, Jonas; Rueda-Rincon, Natalia; Daniels, Veerle W; Bagadi, Muralidhararao; Thimiri Govinda Raj, Deepak Balaji; Vanderhoydonc, Frank; Munck, Sebastian; Chaltin, Patrick; Swinnen, Johannes V

    2016-03-01

    The development of cancer is often accompanied by a loss of the primary cilium, a microtubule-based cellular protrusion that functions as a cellular antenna and that puts a break on cell proliferation. Hence, restoration of the primary cilium in cancer cells may represent a novel promising approach to attenuate tumor growth. Using a high content analysis-based approach we screened a library of clinically evaluated compounds and marketed drugs for their ability to restore primary cilium expression in pancreatic ductal cancer cells. A diverse set of 118 compounds stimulating cilium expression was identified. These included glucocorticoids, fibrates and other nuclear receptor modulators, neurotransmitter regulators, ion channel modulators, tyrosine kinase inhibitors, DNA gyrase/topoisomerase inhibitors, antibacterial compounds, protein inhibitors, microtubule modulators, and COX inhibitors. Certain compounds also dramatically affected the length of the cilium. For a selection of compounds (Clofibrate, Gefitinib, Sirolimus, Imexon and Dexamethasone) their ability to restore ciliogenesis was confirmed in a panel of human cancer cell line models representing different cancer types (pancreas, lung, kidney, breast). Most compounds attenuated cell proliferation, at least in part through induction of the primary cilium, as demonstrated by cilium removal using chloral hydrate. These findings reveal that several commonly used drugs restore ciliogenesis in cancer cells, and warrant further investigation of their antineoplastic properties. PMID:26862738

  13. Identification of drugs that restore primary cilium expression in cancer cells

    PubMed Central

    Khan, Niamat Ali; Willemarck, Nicolas; Talebi, Ali; Marchand, Arnaud; Binda, Maria Mercedes; Dehairs, Jonas; Rueda-Rincon, Natalia; Daniels, Veerle W.; Bagadi, Muralidhararao; Raj, Deepak Balaji Thimiri Govinda; Vanderhoydonc, Frank; Munck, Sebastian; Chaltin, Patrick; Swinnen, Johannes V.

    2016-01-01

    The development of cancer is often accompanied by a loss of the primary cilium, a microtubule-based cellular protrusion that functions as a cellular antenna and that puts a break on cell proliferation. Hence, restoration of the primary cilium in cancer cells may represent a novel promising approach to attenuate tumor growth. Using a high content analysis-based approach we screened a library of clinically evaluated compounds and marketed drugs for their ability to restore primary cilium expression in pancreatic ductal cancer cells. A diverse set of 118 compounds stimulating cilium expression was identified. These included glucocorticoids, fibrates and other nuclear receptor modulators, neurotransmitter regulators, ion channel modulators, tyrosine kinase inhibitors, DNA gyrase/topoisomerase inhibitors, antibacterial compounds, protein inhibitors, microtubule modulators, and COX inhibitors. Certain compounds also dramatically affected the length of the cilium. For a selection of compounds (Clofibrate, Gefitinib, Sirolimus, Imexon and Dexamethasone) their ability to restore ciliogenesis was confirmed in a panel of human cancer cell line models representing different cancer types (pancreas, lung, kidney, breast). Most compounds attenuated cell proliferation, at least in part through induction of the primary cilium, as demonstrated by cilium removal using chloral hydrate. These findings reveal that several commonly used drugs restore ciliogenesis in cancer cells, and warrant further investigation of their antineoplastic properties. PMID:26862738

  14. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    SciTech Connect

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  15. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest

    PubMed Central

    Ujiki, Michael B; Ding, Xian-Zhong; Salabat, M Reza; Bentrem, David J; Golkar, Laleh; Milam, Ben; Talamonti, Mark S; Bell, Richard H; Iwamura, Takeshi; Adrian, Thomas E

    2006-01-01

    Background Many chemotherapeutic agents have been used to treat pancreatic cancer without success. Apigenin, a naturally occurring flavonoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit pancreatic cancer cell growth in vitro. Results Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis and cell proliferation in four pancreatic cancer cell lines. Apigenin induced G2/M phase cell cycle arrest. Apigenin reduced levels of cyclin A, cyclin B, phosphorylated forms of cdc2 and cdc25, which are all proteins required for G2/M transition. Conclusion Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest, and may be a valuable drug for the treatment or prevention of pancreatic cancer. PMID:17196098

  16. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2015-03-17

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  17. Xylitol induces cell death in lung cancer A549 cells by autophagy.

    PubMed

    Park, Eunjoo; Park, Mi Hee; Na, Hee Sam; Chung, Jin

    2015-05-01

    Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells.

  18. Role of Natural Radiosensitizers and Cancer Cell Radioresistance: An Update

    PubMed Central

    Sultana, Misbah; Qazi, Aamer; Qazi, Mahmood Husain; Parveen, Gulshan; Waquar, Sulayman; Ashraf, Abdul Basit; Rasool, Mahmood

    2016-01-01

    Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds. PMID:26998418

  19. Cancer: An Oxidative Crosstalk between Solid Tumor Cells and Cancer Associated Fibroblasts

    PubMed Central

    Arcucci, Alessandro; Ruocco, Maria Rosaria; Granato, Giuseppina; Sacco, Anna Maria

    2016-01-01

    Redox balance is associated with the regulation of several cell signalling pathways and functions. In fact, under physiological conditions, cells maintain a balance between oxidant and antioxidant systems, and reactive oxygen species (ROS) can act as second messengers to regulate cell proliferation, cell death, and other physiological processes. Cancer tissues usually contain higher levels of ROS than normal tissues, and this ROS overproduction is associated with tumor development. Neoplastic tissues are very heterogeneous systems, composed of tumor cells and microenvironment that has a critical role in tumor progression. Cancer associated fibroblasts (CAFs) represent the main cell type of tumor microenvironment, and they contribute to tumor growth by undergoing an irreversible activation process. It is known that ROS can be transferred from cancer cells to fibroblasts. In particular, ROS affect the behaviour of CAFs by promoting the conversion of fibroblasts to myofibroblasts that support tumor progression and dissemination. Furthermore, the wrecking of redox homeostasis in cancer cells and tumor microenvironment induces a metabolic reprogramming in tumor cells and cancer associated fibroblasts, giving advantage to cancer growth. This review describes the role of ROS in tumor growth, by focusing on CAFs activation and metabolic interactions between cancer cells and stromal fibroblasts. PMID:27595103

  20. Cancer: An Oxidative Crosstalk between Solid Tumor Cells and Cancer Associated Fibroblasts

    PubMed Central

    Arcucci, Alessandro; Ruocco, Maria Rosaria; Granato, Giuseppina; Sacco, Anna Maria

    2016-01-01

    Redox balance is associated with the regulation of several cell signalling pathways and functions. In fact, under physiological conditions, cells maintain a balance between oxidant and antioxidant systems, and reactive oxygen species (ROS) can act as second messengers to regulate cell proliferation, cell death, and other physiological processes. Cancer tissues usually contain higher levels of ROS than normal tissues, and this ROS overproduction is associated with tumor development. Neoplastic tissues are very heterogeneous systems, composed of tumor cells and microenvironment that has a critical role in tumor progression. Cancer associated fibroblasts (CAFs) represent the main cell type of tumor microenvironment, and they contribute to tumor growth by undergoing an irreversible activation process. It is known that ROS can be transferred from cancer cells to fibroblasts. In particular, ROS affect the behaviour of CAFs by promoting the conversion of fibroblasts to myofibroblasts that support tumor progression and dissemination. Furthermore, the wrecking of redox homeostasis in cancer cells and tumor microenvironment induces a metabolic reprogramming in tumor cells and cancer associated fibroblasts, giving advantage to cancer growth. This review describes the role of ROS in tumor growth, by focusing on CAFs activation and metabolic interactions between cancer cells and stromal fibroblasts.

  1. Cancer: An Oxidative Crosstalk between Solid Tumor Cells and Cancer Associated Fibroblasts.

    PubMed

    Arcucci, Alessandro; Ruocco, Maria Rosaria; Granato, Giuseppina; Sacco, Anna Maria; Montagnani, Stefania

    2016-01-01

    Redox balance is associated with the regulation of several cell signalling pathways and functions. In fact, under physiological conditions, cells maintain a balance between oxidant and antioxidant systems, and reactive oxygen species (ROS) can act as second messengers to regulate cell proliferation, cell death, and other physiological processes. Cancer tissues usually contain higher levels of ROS than normal tissues, and this ROS overproduction is associated with tumor development. Neoplastic tissues are very heterogeneous systems, composed of tumor cells and microenvironment that has a critical role in tumor progression. Cancer associated fibroblasts (CAFs) represent the main cell type of tumor microenvironment, and they contribute to tumor growth by undergoing an irreversible activation process. It is known that ROS can be transferred from cancer cells to fibroblasts. In particular, ROS affect the behaviour of CAFs by promoting the conversion of fibroblasts to myofibroblasts that support tumor progression and dissemination. Furthermore, the wrecking of redox homeostasis in cancer cells and tumor microenvironment induces a metabolic reprogramming in tumor cells and cancer associated fibroblasts, giving advantage to cancer growth. This review describes the role of ROS in tumor growth, by focusing on CAFs activation and metabolic interactions between cancer cells and stromal fibroblasts. PMID:27595103