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Sample records for cancer cells treated

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

    Directory of Open Access Journals (Sweden)

    Hu C

    2015-03-01

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

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

    International Nuclear Information System (INIS)

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

  3. Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer

    Science.gov (United States)

    2014-06-05

    Adult Langerhans Cell Histiocytosis; Childhood Langerhans Cell Histiocytosis; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

  4. Gene expression profile of colon cancer cell lines treated with SN-38

    DEFF Research Database (Denmark)

    Wallin, A; Francis, P; Nilbert, M;

    2010-01-01

    Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though...... the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor...... irinotecan which leads to cell cycle arrest and apoptosis....

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

    Science.gov (United States)

    2011-11-28

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

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

    Science.gov (United States)

    2013-03-25

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

  7. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease.

    Science.gov (United States)

    Lamb, Rebecca; Ozsvari, Bela; Lisanti, Camilla L; Tanowitz, Herbert B; Howell, Anthony; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2015-03-10

    Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect". Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent

  8. Raman confocal microscopy and AFM combined studies of cancerous cells treated with Paclitaxel

    Science.gov (United States)

    Derely, L.; Collart Dutilleul, P.-Y.; Michotte de Welle, Sylvain; Szabo, V.; Gergely, C.; Cuisinier, F. J. G.

    2011-03-01

    Paclitaxel interferes with the normal function of microtubule breakdown, induces apoptosis in cancer cells and sequesters free tubulin. As this drug acts also on other cell mechanisms it is important to monitor its accumulation in the cell compartments. The intracellular spreading of the drug was followed using a WITEC 300R confocal Raman microscope equipped with a CCD camera. Hence Atomic force microscopy (an MFP3D- Asylum Research AFM) in imaging and force mode was used to determine the morphological and mechanical modifications induced on living cells. These studies were performed on living epithelial MCF-7 breast cancer cells. Paclitaxel was added to cell culture media for 3, 6 and 9 hours. Among the specific paclitaxel Raman bands we selected the one at 1670 cm-1 because it is not superposed by the spectrum of the cells. Confocal Raman images are formed by monitoring this band, the NH2 and the PO4 band. Paclitaxel slightly accumulates in the nucleus forming patches. The drug is also concentrated in the vicinity of the cell membrane and in an area close to the nucleus where proteins accumulate. Our AFM images reveal that the treated cancerous MCF-7 cells keep the same size as the non treated ones, but their shape becomes more oval. Cell's elasticity is also modified: a difference of 2 kPa in the Young Modulus characterizes the treated MCF-7 mammary cancerous cell. Our observations demonstrate that paclitaxel acts not only on microtubules but accumulates also in other cell compartments (nucleus) where microtubules are absent.

  9. Gene expression profile of colon cancer cell lines treated with SN-38

    DEFF Research Database (Denmark)

    Wallin, A; Francis, P; Nilbert, M;

    2010-01-01

    the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor......Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though...

  10. Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer

    Science.gov (United States)

    2013-03-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Myelodysplastic Syndromes; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Disseminated Neuroblastoma; Malignant Neoplasm; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Immature Teratoma; Ovarian Mature Teratoma; Ovarian Mixed Germ Cell Tumor; Ovarian Monodermal and Highly Specialized Teratoma; Ovarian Polyembryoma; Ovarian Yolk Sac Tumor; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Neuroblastoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage II Ovarian Epithelial Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Multiple Myeloma; Stage III Ovarian Epithelial Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Seminoma; Testicular Choriocarcinoma and Teratoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular

  11. Two-dimensional polyacrylamide gel electrophoresis analysis of indomethacin-treated human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Yan-Li Cheng; Gui-Ying Zhang; Zhi-Qiang Xiao; Fa-Qing Tang

    2005-01-01

    AIM: To establish the two-dimensional gel electrophoresis (2-DE) profiles of indomethacin (IN)-treated human colon cancer cell line HCT116, and to provide a new way to study its anti-tumor molecular mechanism through analyzing a variety of protein maps.METHODS: Two-DE profiles of HCT116 were established in IN-treated and untreated groups. Total proteins were separated by immobilized pH gradient-based 2-DE. The gels were stained by silver, scanned by ImageScanner,and analyzed with Image Master software.RESULTS: Clear background, well-resolved and reproducible 2-DE patterns of HCT116 cells were acquired in IN-treated and untreated group. The average deviation of spot position was 0.896±0.177 mm in IEF direction and 1.106±0.289 mm in SDS-PAGE direction respectively. In IN-treated group,1 169±36 spots were detected and 1 061±32 spots were matched, the average matching rate was 90.6% in three gels. In untreated group, 1 256±50 spots were detected and 1 168±46 spots were matched, the average matching rate was 93.0% in three gels. Forty-five differential protein spots were displayed between IN-treated and untreated groups. Of which, 34 protein spots decreased and 9showed higher expression in IN-treated group, and only two protein spots showed an expression in untreated cells.CONCLUSION: Two-DE profiles of IN-treated and untreated HCT116 cells were established. Apparent 45 different protein spots were detected in IN-treated and untreated HCT116 cells. The analysis on differential protein spots may serve as a new way to study the molecule mechanism of IN-treated colon cancer.

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

    Science.gov (United States)

    2016-05-05

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

  13. Effects of Combined Chinese Drugs and Chemotherapy in Treating Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    陈衍智; 李占东; 高非; 张莹; 孙红; 李萍萍

    2009-01-01

    Objective:To evaluate the efficacy and side effects of combined Chinese drugs and chemotherapy in treating advanced non-small cell lung cancer(NSCLC).Methods:Sixty-three patients with stageⅢB andⅣNSCLC hospitalized from October 2001 to October 2008 were enrolled and assigned to two groups using a randomizing digital table,with 33 patients in the treatment group and 30 in the control group. They were all treated with the Navelbine and Cisplatin(NP) chemotherapy,but to the treatment group the Chinese drugs...

  14. Effect of hyperthermic CO2-treated dendritic cell-derived exosomes on the human gastric cancer AGS cell line

    OpenAIRE

    Wang, Jinlin; Wang, Zhiyong; MO, YANXIA; Zeng, Zhaohui; Wei, Pei; Li, Tao

    2015-01-01

    The aim of the present study was to determine the antitumor effects of hyperthermic CO2 (HT-CO2)-treated dendritic cell (DC)-derived exosomes (Dex) on human gastric cancer AGS cells. Mouse-derived DCs were incubated in HT-CO2 at 43°C for 4 h. The exosomes in the cell culture supernatant were then isolated. Cell proliferation was analyzed using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was observed using flow cytometry, Hoechst 33258 staining and the analysis of caspase-3 activity....

  15. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial

    DEFF Research Database (Denmark)

    Kim, E.S.; Hirsh, V.; Mok, T.;

    2008-01-01

    BACKGROUND: Two phase II trials in patients with previously-treated advanced non-small-cell lung cancer suggested that gefitinib was efficacious and less toxic than was chemotherapy. We compared gefitinib with docetaxel in patients with locally advanced or metastatic non-small-cell lung cancer wh...

  16. Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria Gry Gundgaard; Bandak, Mikkel;

    2016-01-01

    expiratory volume in 1 second and forced vital capacity remained unchanged after BEP but increased significantly to levels above pretreatment during follow-up. International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic group, mediastinal primary, pulmonary metastases, and smoking all......PURPOSE: For patients with germ cell cancer, various pulmonary toxicity risk factors have been hypothesized for treatment with bleomycin, etoposide, and cisplatin (BEP). Because existing studies have shortcomings, we present a large, unselected cohort of patients who have undergone close monitoring...... of lung function before, during, and after treatment with BEP to disclose valid pulmonary toxicity risk factors. PATIENTS AND METHODS: All patients who were treated with BEP at Rigshospitalet, Copenhagen, Denmark, from 1984 to 2007, were included. Pulmonary function tests (PFTs) that measured...

  17. 17 cases of advanced non-small cell lung cancer treated with paclitaxel liposome plus nedaplatin

    Institute of Scientific and Technical Information of China (English)

    Tao Suo; Wei Ge; Jinzhong Zhang; Yongfa Zheng; Shunxiang Luo

    2012-01-01

    Objective: The aim of this study was to evaluate the recent efficacy and adverse reactions of paclitaxel liposome plus nedaplatin in the treatment of advanced non-small cell lung cancer (NSCLC).Methods: Seventeen cases of NSCLC treated with paclitaxel liposome and nedaplatin for 2 to 6 cycles, by infusing paclitaxel liposome 135 mg/m2 for 3 h on d1 and nedaplatin 80 mg/m2 as infusion on d2.Results: Among 17 patients being evaluated for response to treatment, 1 achieved complete response (CR), 4 achieved partial response (PR), 3 achieved stable disease (SD), 9 achieved progress disease (PD).The main adverse reaction was haematological toxicities, especially leukopenia and thrombocytopenia.The non-haematological toxicities included nausea, vomiting, mild hepatic dysfunction, alopecia and so on.Conclusion: Paclitaxel liposome plus nedaplatin was effective and well tolerated for treating patients with advanced NSCLC.

  18. Mechanism of eliciting host immunity against cancer cells treated with silica-phthalocyanine-based near infrared photoimmunotherapy (Conference Presentation)

    Science.gov (United States)

    Kobayashi, Hisataka

    2016-03-01

    Near infrared (NIR) photoimmunotherapy (PIT) is a new type of molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IR700, to a monoclonal antibody (MAb) targeting cancer-specific cell-surface molecules. When exposed to NIR light, the conjugate induces a highly-selective necrotic/ immunogenic cell death (ICD) only in receptor-positive, MAb-IR700-bound cancer cells. This cell death occurs as early as 1 minute after exposure to NIR light. Meanwhile, immediately adjacent receptor-negative cells including immune cells are unharmed. Therefore, we hypothesized that NIR-PIT could efficiently elicit host immunity against treated cancer cells. Three-dimensional dynamic quantitative phase contrast microscopy and selective plane illumination microscopy of tumor cells undergoing PIT showed rapid swelling in treated cells immediately after light exposure suggesting rapid water influx into cells, followed by irreversible morphologic changes such as bleb formation, and rupture of vesicles. Furthermore, biological markers of ICD including relocation of HSP70/90 and calreticulin, and release of ATP and High Mobility Group Box 1 (HMGB1), were clearly detected immediately after NIR-PIT. When NIR-PIT was performed in a mixture of cancer cells and immature dendritic cells, maturation of immature dendritic cells was strongly induced rapidly after NIR-PIT. In summary, NIR-PIT can induce necrotic/ immunogenic cell death that promotes rapid maturation of immature dendritic cells adjacent to dying cancer cells. Therefore, NIR-PIT could efficiently initiate host immune response against NIR-PIT treated cancer cells growing in patients.

  19. Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung; Ro, Jungsil [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of); Yoon, Sungpil, E-mail: yoons@ncc.re.kr [Research Institute, National Cancer Center, Ilsan-gu, Goyang-si, Gyeonggi-do (Korea, Republic of)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitotic drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.

  20. Gene expression analysis in MCF-7 breast cancer cells treated with recombinant bromelain.

    Science.gov (United States)

    Fouz, Nour; Amid, Azura; Hashim, Yumi Zuhanis Has-Yun

    2014-08-01

    The contributing molecular pathways underlying the pathogenesis of breast cancer need to be better characterized. The principle of our study was to better understand the genetic mechanism of oncogenesis for human breast cancer and to discover new possible tumor markers for use in clinical practice. We used complimentary DNA (cDNA) microarrays to compare gene expression profiles of treated Michigan Cancer Foundation-7 (MCF-7) with recombinant bromelain and untreated MCF-7. SpringGene analysis was carried out of differential expression followed by Ingenuity Pathway Analysis (IPA), to understand the underlying consequence in developing disease and disorders. We identified 1,102 known genes differentially expressed to a significant degree (pbromelain produces a unique signature affecting different pathways, specific for each congener. The microarray results give a molecular mechanistic insight and functional effects, following recombinant bromelain treatment. The extent of changes in genes is related to and involved significantly in gap junction signaling, amyloid processing, cell cycle regulation by BTG family proteins, and breast cancer regulation by stathmin1 that play major roles. PMID:24928548

  1. Exploring cell apoptosis and senescence to understand and treat cancer: an interview with Scott Lowe

    Directory of Open Access Journals (Sweden)

    2015-11-01

    Full Text Available Scott W. Lowe is currently principal investigator at the Memorial Sloan-Kettering Cancer Center. After beginning his studies in chemical engineering, he decided to take another path and became fascinated by biochemistry, genetics and molecular biology, which ultimately led to an interest in human disease, particularly cancer. During his PhD at the Massachusetts Institute of Technology (MIT, Scott had the opportunity to benefit from the exceptional mentorship of Earl Ruley, David Housman and Tyler Jacks, and contributed to elucidating how the p53 (TP53 tumor suppressor gene limits oncogenic transformation and modulates the cytotoxic response to conventional chemotherapy. This important work earned him a fellowship from the Cold Spring Harbor Laboratory, which helped to launch his independent career. Scott is now a leading scientist in the cancer field and his work has helped to shed light on mechanisms of cell apoptosis and senescence to better understand and treat cancer. In this interview, he talks about this incredible scientific journey.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    2016-02-08

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

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

    Science.gov (United States)

    2015-09-28

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

  5. Prognostic cell biological markers in cervical cancer patients primarily treated with (chemo)radiation : a systematic review

    NARCIS (Netherlands)

    Noordhuis, Maartje G; Eijsink, Jasper J H; Roossink, Frank; de Graeff, Pauline; Pras, Elisabeth; Schuuring, Ed; Wisman, G Bea A; de Bock, Geertruida H; van der Zee, Ate G J

    2011-01-01

    The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell b

  6. Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Roberto Madeddu

    2013-08-01

    Full Text Available Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd, which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.

  7. Cadmium Modifies the Cell Cycle and Apoptotic Profiles of Human Breast Cancer Cells Treated with 5-Fluorouracil

    Science.gov (United States)

    Asara, Yolande; Marchal, Juan A.; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A.; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

    2013-01-01

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd. PMID:23941782

  8. Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil.

    Science.gov (United States)

    Asara, Yolande; Marchal, Juan A; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto

    2013-01-01

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd. PMID:23941782

  9. Gefitinib in Treating Patients With Metastatic or Unresectable Head and Neck Cancer or Non-Small Cell Lung Cancer

    Science.gov (United States)

    2013-01-11

    Anaplastic Thyroid Cancer; Insular Thyroid Cancer; Metastatic Parathyroid Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; 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 Parathyroid Cancer; Recurrent Salivary Gland 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 Thyroid Cancer; Recurrent Verrucous Carcinoma of the Larynx; Stage III Follicular Thyroid Cancer; Stage III Papillary Thyroid Cancer; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Larynx; Stage IIIB Non-small Cell Lung Cancer; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity; Stage IVA Basal Cell Carcinoma of the Lip; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Follicular Thyroid Cancer; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Lymphoepithelioma of the Oropharynx; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus

  10. Evaluation of Three Small Molecular Drugs for Targeted Therapy to Treat Nonsmall Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Ni; Li Zhang

    2016-01-01

    Objective: To guide the optimal selection among first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in clinical practice.This review attempted to provide a thorough comparison among three first-generation EGFR-TKIs, namely icotinib,erlotinib, and gefitinib, with regard to their molecular structure, pharmacokinetic parameters, clinical data, adverse reactions, and contraindications.Data Sources: An electronic literature search of the PubMed database and Google Scholar for all the available articles regarding gefitinib,icotinib, and erlotinib in the English language from January 2005 to December 2014 was used.Study Selection: The search terms or keywords included but not limited to "lung cancer", "nonsmall cell lung cancer (NSCLC)","epidemiology", "EGFR", "TKIs", and "optimal selection".Results: As suggested by this review, even though the three first-generation EGFR-TKIs share the quinazoline structure, erlotinib had the strongest apoptosis induction activity because of its use of a different side-chain.The pharmacokinetic parameters indicated that both erlotinib and icotinib are affected by food.The therapeutic window of erlotinib is narrow, and the recommended dosage is close to the maximum tolerable dosage.Icotinib enjoys a wider therapeutic window, and its concentration in the blood is within a safe dosage range even if it is administered with food.Based on multiple large-scale clinical trials, erlotinib is universally applied as the first-line treatment.In marked contrast, icotinib is available only in China as the second-or third-line therapeutic approach for treating advanced lung cancer.In addition, it exhibits a similar efficacy but better safety profile than gefitinib.Conclusions: Although there is a paucity of literature regarding whether icotinib is superior to erlotinib, its superior toxicity profile, noninferior efficacy, and lower cost indicate that it is a better alternative for Chinese patients living with

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

    Science.gov (United States)

    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

  12. Acute esophagitis for patients with local-regional advanced non small cell lung cancer treated with concurrent chemoradiotherapy

    DEFF Research Database (Denmark)

    Pan, Yi; Brink, Carsten; Knap, Marianne;

    2016-01-01

    PURPOSE: Esophagitis is common in patients treated with definitive radiotherapy for local-regional advanced non small cell lung cancer (NSCLC). The purpose of this study was to estimate the dose-effect relationship using clinical and dosimetric parameters in patients receiving intensity modulated...

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Activity of ABCG2 Is Regulated by Its Expression and Localization in DHT and Cyclopamine-Treated Breast Cancer Cells.

    Science.gov (United States)

    Chua, Vivian Y L; Larma, Irma; Harvey, Jennet; Thomas, Marc A; Bentel, Jacqueline M

    2016-10-01

    Elevated expression of the efflux transporter, ATP-binding cassette subfamily G isoform 2 (ABCG2) on the plasma membrane of cancer cells contributes to the development of drug resistance and is a key characteristic of cancer stem cells. In this study, gene expression analysis identified that treatment of the MCF-7 and T-47D breast cancer cell lines with the androgen, 5α-dihydrotestosterone (DHT), and the Hedgehog signaling inhibitor, cyclopamine downregulated ABCG2 mRNA levels. In MCF-7 cells, and in Hoechst 33342(lo) /CD44(hi) /CD24(lo) breast cancer stem-like cells isolated from MCF-7 cultures, ABCG2 was accumulated in cell-to-cell junction complexes and in large cytoplasmic aggresome-like vesicles. DHT treatments, which decreased cellular ABCG2 protein levels, led to diminished ABCG2 localization in both cell-to-cell junction complexes and in cytoplasmic vesicles. In contrast, cyclopamine, which did not alter ABCG2 protein levels, induced accumulation of ABCG2 in cytoplasmic vesicles, reducing its localization in cell-to-cell junction complexes. The reduced localization of ABCG2 at the plasma membrane of MCF-7 cells was associated with decreased efflux of the ABCG2 substrate, mitoxantrone, and increased sensitivity of cyclopamine-treated cultures to the cytotoxic effects of mitoxantrone. Together, these findings indicate that DHT and cyclopamine reduce ABCG2 activity in breast cancer cells by distinct mechanisms, providing evidence to advocate the adjunct use of analogous pharmaceutics to increase or prolong the efficacy of breast cancer treatments. J. Cell. Biochem. 117: 2249-2259, 2016. © 2016 Wiley Periodicals, Inc. PMID:26917208

  15. Tolerability and toxicity of adjuvant cisplatin and gemcitabine for treating non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    YANG Fan; LI Xiao; CHEN Ke-zhong; JIANG Guan-chao; WANG Jun

    2013-01-01

    Background The combination of cisplatin and vinorelbine is an evidence-supported regimen for adjuvant chemotherapy for treating non-small cell lung cancer (NSCLC).But this doublet has considerable toxicity and unfavorable tolerability,and results in poor compliance.The cisplatin and gemcitabine regimen is one of the most active and well-tolerated regimens against advanced NSCLC,but its toxicity and tolerability has not been adequately evaluated in the adjuvant setting.Methods From a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin (75 mg/m2) and gemcitabine (1250 mg/m2) between January 2005 and December 2011.Postoperative demographics,compliance to adjuvant therapy and toxicity were retrieved from medical records.Results A total of 132 patients met the criteria and were included in the study,96 were male (72.7%) and 36 were female (27.3%).Median age was 60.5 years old,range 29-75 years,and 41.7% of patients were ≥65 years old.Overall,68.2%patients received all four planned cycles,and the cumulative dose delivered for gemcitabine was 8333 mg (83.3% of the planned dose) and cisplatin 248 mg (82.7% of the planned dose).There were no treatment-related deaths.Grade 3/4neutropenia developed in 47 patients (35.6%) and was the predominant hematologic toxicity.Common grade 3/4 nonhematologic toxicities were nausea/vomiting (22.0%),infection (12.3%),and febrile neutropenia (11.4%).Conclusion Cisplatin and gemcitabine are feasible for use in the adjuvant setting with a favorable toxicity profile and superior tolerability compared with published data on cisplatin and vinorelbine.

  16. Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

    Science.gov (United States)

    2012-12-13

    Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  17. GPER1-mediated IGFBP-1 induction modulates IGF-1-dependent signaling in tamoxifen-treated breast cancer cells.

    Science.gov (United States)

    Vaziri-Gohar, Ali; Houston, Kevin D

    2016-02-15

    Tamoxifen, a selective estrogen receptor modulator, is a commonly prescribed adjuvant therapy for estrogen receptor-α (ERα)-positive breast cancer patients. To determine if extracellular factors contribute to the modulation of IGF-1 signaling after tamoxifen treatment, MCF-7 cells were treated with IGF-1 in conditioned medium (CM) obtained from 4-OHT-treated MCF-7 cells and the accumulation of phospho-Akt (S473) was measured. CM inhibited IGF-1-dependent cell signaling and suggesting the involvement of extracellular factors (ie. IGFBPs). A significant increase in IGFBP-1 mRNA and extracellular IGFBP-1 protein was observed in 4-OHT-treated MCF-7 cells. Knockdown experiments demonstrated that both GPER1 and CREB mediate IGFBP-1 induction. Furthermore, experiments showed that 4-OHT-dependent IGFBP-1 transcription is downstream of GPER1-activation in breast cancer cells. Additionally, neutralization and knockdown experiments demonstrated a role for IGFBP-1 in the observed inhibition of IGF-1 signaling. These results suggested that 4-OHT inhibits IGF-1 signaling via GPER1 and CREB mediated extracellular IGFBP-1 accumulation in breast cancer cells. PMID:26690777

  18. Variable NF-κB pathway responses in colon cancer cells treated with chemotherapeutic drugs

    OpenAIRE

    Samuel, Temesgen; Fadlalla, Khalda; Gales, Dominique N; Putcha, Balananda DK; Manne, Upender

    2014-01-01

    Background The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway is activated in cells exposed to various stimuli, including those originating on the cell surface or in the nucleus. Activated NF-κB signaling is thought to enhance cell survival in response to these stimuli, which include chemotherapy and radiation. In the present effort, we determined which anticancer drugs preferentially activate NF-κB in colon cancer cells. Methods NF-κB reporter cells ...

  19. Alterations in Cell Cycle and Induction of Apoptotic Cell Death in Breast Cancer Cells Treated with α-Mangostin Extracted from Mangosteen Pericarp

    Directory of Open Access Journals (Sweden)

    Hitomi Kurose

    2012-01-01

    Full Text Available The development of molecularly targeted drugs has greatly advanced cancer therapy, despite these drugs being associated with some serious problems. Recently, increasing attention has been paid to the anticancer effects of natural products. α-Mangostin, a xanthone isolated from the pericarp of mangosteen fruit, has been shown to induce apoptosis in various cancer cell lines and to exhibit antitumor activity in a mouse mammary cancer model. In this study, we investigated the influence of α-mangostin on apoptosis and cell cycle in the human breast cancer cell line MDA-MB231 (carrying a p53 mutation, and HER2, ER, and PgR negative in order to elucidate its anticancer mechanisms. In α-mangostin-treated cells, induction of mitochondria-mediated apoptosis was observed. On cell-cycle analysis, G1-phase arrest, increased p21cip1 expression and decreases in cyclins, cdc(s, CDKs and PCNA were observed. In conclusion, α-mangostin may be useful as a therapeutic agent for breast cancer carrying a p53 mutation and having HER2- and hormone receptor-negative subtypes.

  20. Clinical application of radiofrequency ablation combined with bronchial artery infusion of docetaxel in treating non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To discuss the clinical application of radiofrequency ablation combined with bronchial artery infusion of docetaxel in treating non-small cell lung cancer and to summarize the experience of using this therapy in clinical practice. Methods: Radiofrequency ablation was performed in twenty-one patients with lung cancer. The diagnosis was confirmed by CT-guided percutaneous needle biopsy or bronchoscopic biopsy in all patients. One week after radiofrequency ablation treatment, bronchial artery infusion of docetaxel was conducted. The therapeutic results were observed and evaluated. Results: After the treatment, the lesion's size was markedly reduced and the clinical symptoms were dramatically improved in all patients. Conclusion: Radiofrequency ablation combined with bronchial artery infusion of docetaxel is a safe, effective and simple technique with excellent therapeutic results for the treatment of non-small cell lung cancer. It is really worth popularizing this technique in clinical practice. (authors)

  1. Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways.

    Science.gov (United States)

    Dhillon, Harsharan; Mamidi, Sujan; McClean, Phillip; Reindl, Katie M

    2016-06-01

    Piperlongumine (PL), an alkaloid obtained from long peppers, displays antitumorigenic properties for a variety of human cell- and animal-based models. The aim of this study was to identify the underlying molecular mechanisms for PL anticancer effects on human pancreatic cancer cells. RNA sequencing (RNA-seq) was used to identify the effects of PL on the transcriptome of MIA PaCa-2 human pancreatic cancer cells. PL treatment of pancreatic cancer cells resulted in differential expression of 683 mRNA transcripts with known protein functions, 351 of which were upregulated and 332 of which were downregulated compared to control-treated cells. Transcripts associated with oxidative stress, endoplasmic reticulum (ER) stress, and unfolded protein response pathways were significantly overexpressed with PL treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to validate the RNA-seq results, which included upregulation of HO-1, IRE1α, cytochrome c, and ASNS. The results provide key insight into the mechanisms by which PL alters cancer cell physiology and identify that activation of oxidative stress and ER stress pathways is a critical avenue for PL anticancer effects. PMID:27119744

  2. Treating patients with ALK-positive non-small cell lung cancer: latest evidence and management strategy

    OpenAIRE

    Liao, Bin-Chi; Lin, Chia-Chi; Shih, Jin-Yuan; Yang, James Chih-Hsin

    2015-01-01

    Rearrangements in anaplastic lymphoma kinase (ALK) gene and echinoderm microtubule-associated protein-like 4 (EML4) gene were first described in a small portion of patients with non-small cell lung cancer (NSCLC) in 2007. Fluorescence in situ hybridization is used as the diagnostic test for detecting an EML4–ALK rearrangement. Crizotinib, an ALK inhibitor, is effective in treating advanced ALK-positive NSCLC, and the US Food and Drug Administration approved it for treating ALK-positive NSCLC ...

  3. Secondary oesophageal or gastric cancer in patients treated for head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Anja Rosenlund; Bjerring, Ole Steen; Godballe, Christian;

    2016-01-01

    SPM. CONCLUSION: In this study, we confirm that there is an elevated risk of developing oesophageal and gastric cancer in the Danish population of patients with a cancer in the supraglottic or hypopharyngeal region. Therefore, we recommend close follow-up of these patients and a low threshold......INTRODUCTION: Patients with head and neck squamous cell carcinoma (HNSCC) are at an elevated risk of developing second primary malignancies (SPM). Our objectives were to estimate the excess risk of oesophageal and gastric SPMs in patients with malignancies of the pharynx or larynx and, additionally.......004) and hypopharyngeal (OR = 3.9; p cancer compared with 3.4 years (95% CI: 3.1-4.3; range: 0.04-13.7) for patients without...

  4. Proteomic analysis of cervical cancer cells treated with suberonylanilide hydroxamic acid

    Indian Academy of Sciences (India)

    Jianxiong He; Canhua Huang; Aiping Tong; Bin Chen; Zhi Zeng; Peng Zhang; Chunting Wang; Yuquan Wei

    2008-12-01

    Suberonylanilide hydroxamic acid (SAHA) is an orally administered histone deacetylase inhibitor (HDACI) that has shown significant antitumour activity in a variety of tumour cells. To identify proteins involved in its antitumour activity, we utilized a proteomic approach to reveal protein expression changes in the human cervical cancer cell line HeLa following SAHA treatment. Protein expression profiles were analysed by 2-dimensional polyacrylamide gel electrophoresis (2-DE) and protein identification was performed on a MALDI-Q-TOF MS/MS instrument. As a result, a total of nine differentially expressed proteins were visualized by 2-DE and Coomassie brilliant blue (CBB) staining. Further, all the changed proteins were positively identified via mass spectrometry (MS)/MS analysis. Of these, PGAM1 was significantly downregulated in HeLa cells after treatment with SAHA. Moreover, PGAM1 has been proven to be downregulated in another cervical cancer cell line (CaSki) by western blot analysis. Together, using proteomic tools, we identified several differentially expressed proteins that underwent SAHA-induced apoptosis. These changed proteins may provide some clues to a better understanding of the molecular mechanisms underlying SAHA-induced apoptosis in cervical cancer.

  5. Successful Chemotherapy with Nab-Paclitaxel in a Heavily Treated Non-Small Cell Lung Cancer Patient: A Case Report

    Directory of Open Access Journals (Sweden)

    Mikiko Ishihara

    2014-06-01

    Full Text Available Non-small cell lung cancer (NSCLC accounts for the majority of all lung cancers. A 69-year-old female with postoperatively recurrent NSCLC was treated weekly with nanoparticle-albumin-bound paclitaxel (nab-paclitaxel monotherapy every 4 weeks as a tenth line chemotherapy, and stable disease was achieved by seven cycles of this regimen. The patient developed grade 4 neutropenia and grade 3 leukopenia, but none of the other toxicities, including febrile neutropenia and peripheral neuropathy, were severe, and thus she was able to tolerate this salvage chemotherapy. To our knowledge this is the first report of the efficacy of nab-paclitaxel monotherapy in a heavily treated NSCLC patient.

  6. Adenosquamous cell lung cancer successfully treated with gefitinib: A case report.

    Science.gov (United States)

    Kurishima, Koichi; Ohara, Gen; Kagohashi, Katsunori; Watanabe, Hiroko; Takayashiki, Norio; Ishibashi, Atsushi; Satoh, Hiroaki

    2014-03-01

    Although adenosquamous cell lung cancer (ASCLC) is included in the non-small-cell lung cancers (NSCLCs), the number of currently available studies on the response of this type of cancer to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is limited. This is the case report of a 66-year-old female who was referred to the Mito Medical Center (Mito, Japan) with hemoptysis and the chest computed tomography (CT) scan revealed a large cavitary mass in the lower lobe of the left lung. The patient underwent surgical resection of the lesion and the final pathological diagnosis was ASCLC staged as pT2bN2M0. Notably, an EGFR exon 19 deletion was identified in the adenocarcinomatous as well as the squamous cell carcinomatous components of the tumor. Despite adjuvant chemotherapy, the patient developed small cavitary metastases in the lungs bilaterally. Therefore, treatment with gefitinib was initiated. The chest CT scan revealed substantial regression of the metastatic cavitary tumors in both lungs, with thinning of the walls. The patient remains alive and recurrence-free 19 months following the initiation of gefitinib therapy. This case demonstrated an optimal clinical response to gefitinib treatment for EGFR mutation-positive ASCLC, suggesting that gefitinib is a therapeutic option for such a subset of patients with ASCLC. PMID:24649347

  7. Mortality in asymptomatic vs. symptomatic patients surgically treated for non-small cell lung cancer (NSCLC)

    DEFF Research Database (Denmark)

    Madsen, Kirsten Riis; Bødtger, Uffe

    Introduction: Compared to incidentally found lung cancer, the presence of symptoms (eg. cough, haemoptysis, pain, weight loss) at diagnosis is associated with a 50% reduction in median survival. In surgically treated patients, it is unknown whether presence of symptoms has prognostic significance....... Aim: We wanted to ascertain if symptoms at time of NSCLC diagnosis lowered 12-months mortality after surgery. Methods: Retrospective analysis of all patients with localised NSCLC referred from our department between 2009-2011 for intended curative surgery Data on age, sex, tobacco pack years, Charlson......, tobacco pack years, or FEV1. Former malignancy was significantly more prevalent among asymptomatic than symptomatic subjects (33 % vs. 11%), with insignificant differences in prevalence of other co-morbidities or in post-surgical TNM (82% vs 85% in stages IA-IIB). 12-months mortality was insignificantly...

  8. Outcome of 289 locally advanced non-small cell lung cancer treated with radiotherapy alone and radiotherapy combined with chemotherapy

    International Nuclear Information System (INIS)

    Objective: To retrospectively analyze the outcome of locally advanced non-small cell lung cancer patients treated with radiotherapy and chemoradiotherapy. Methods: 289 patients who were treated either by radiotherapy alone (168 patients) or radiotherapy plus chemotherapy (121 patients) from Dec. 1999 to Dec. 2002 were entered into the database for analysis. Pathological types: squamous cancer (152), adenocarcinoma(74), squamoadenocarcinoma(2) and other types (2). 24 showed cancer unclassificable and 35 were diagnosed without pathological proof. Stages: 74 had III A and 215 III B stage disease. Among the 121 patients treated with combined modality, 24 were treated with concurrent chemoradiotherapy, 78 radiotherapy after chemotherapy(C + R), and 19 radiotherapy followed by chemotherapy(R + C). In patients treated by concurrent chemoradiotherapy or C + R, 38 received consolidation chemotherapy after induction treatment. Results: The 1-, 3-, 5-year overall survival, and the median survival were: 45% , 16% , 8%, and 16.2 months for all patients; 57%, 27%, 11%, and 21.7 months for stage IIIA; 41%, 12%, 7%, and 15.3 months for IIIB. By logrank test, clinical stage, KPS performance, tumor volume, hemoglobin level before treatment, consolidation chemotherapy, radiation dose, and response to treatment showed statistically dramatic impact on overall survival. The overall survival rate and median survival time were slightly higher in the combined group than in the radiotherapy alone group, but the difference is statistically insignificant. In Cox multivariable regression, stage and consolidation chemotherapy were independent prognostic factors; KPS performance, radiation dose, and response to treatment were at the margin of statistical significance. Esophagitis and pneumonitis of Grade II or higher were 24% and 8%, respectively. Failure sites included in the thorax(41%), outside of thorax(48%), and both in and outside the thorax(11%). There was no difference between the

  9. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer

    Science.gov (United States)

    ... this page please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His ... Read More "Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His ...

  10. Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil

    OpenAIRE

    Roberto Madeddu; Cristiano Farace; Andrea Montella; Pasquale Bandiera; Garcia, Maria A.; Houria Boulaiz; Giuliana Solinas; Yolande Asara; Juan A. Marchal; Esther Carrasco

    2013-01-01

    Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of th...

  11. Endocrine Disorders in Childhood Cancer Survivors Treated with Haemopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Christina Wei

    2014-06-01

    Full Text Available The increasing number of haemopoietic stem cell transplantations (HSCT taking place worldwide has offered a cure to many high risk childhood malignancies with an otherwise very poor prognosis. However, HSCT is associated with an increased risk of morbidity and premature death, and patients who have survived the acute complications continue to face lifelong health sequelae as a result of the treatment. Endocrine dysfunction is well described in childhood HSCT survivors treated for malignancies. The endocrine system is highly susceptible to damage from the conditioning therapy, such as, alkylating agents and total body irradiation, which is given prior stem cell infusion. Although not immediately life-threatening, the impact of these abnormalities on the long term health and quality of life in these patients may be considerable. The prevalence, risk factors, clinical approaches to investigations and treatments, as well as the implications of ongoing surveillance of endocrine disorders in childhood HSCT survivors, are discussed in this review.

  12. Monoclonal antibodies for treating cancer

    International Nuclear Information System (INIS)

    The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

  13. A Case of Stage IV Non-Small Cell Lung Cancer Treated with Korean Medicine Therapy Alone

    Directory of Open Access Journals (Sweden)

    Dong-hyun Lee

    2013-11-01

    Full Text Available This report presents a case that shows a significant anticancer effect of Korean medicine therapy (KMT. A 79-year-old man, who was diagnosed as stage Ⅳ non-small cell lung cancer (NSCLC in December 2012, was treated with KMT including intravenous pharmacopunctures and oral herbal medicine from February 22, 2013, until September 2013 without any surgical intervention, chemotherapy or radiotherapy. The intravenous pharmacopunctures were the wild ginseng pharmacopuncture, Cordyceps sinensis pharmacopuncture and Trichosanthes kirilowii pharmacopuncture. The oral herbal medicine used was soramdan, made of cultivated wild ginseng. The effectiveness of this therapy was evaluated with computed tomography and the Eastern Cooperative Oncology Group (ECOG performance scale. The size of the tumor mass was markedly decreased and the ECOG performance scale was also improved. These results suggest that KMT alone can be an effective method to treat NSCLC.

  14. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India

    Science.gov (United States)

    Sridhar, Epari

    2016-01-01

    Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL) involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient's case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term. PMID:27597906

  15. Case Report of Diffuse Large B Cell Lymphoma of Uterine Cervix Treated at a Semiurban Cancer Centre in North India

    Directory of Open Access Journals (Sweden)

    Vibhor Sharma

    2016-01-01

    Full Text Available Lymphoma of the uterine cervix is very rare. We report a case of diffuse large B cell lymphoma (DLBCL involving the uterine cervix treated at a newly commissioned semiurban cancer centre in north India in 2015. Data for this study was obtained from the hospital electronic medical records and the patient’s case file. We also reviewed published case reports of uterine and cervical lymphoma involving forty-one patients. We treated a case of stage IV DLBCL cervix with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and intrathecal methotrexate followed by consolidation with radiotherapy. The patient showed complete response to chemotherapy. We conclude that, in advanced stage lymphoma involving uterus and cervix, combination of chemotherapy and radiotherapy is effective in short term.

  16. Pemetrexed in Previously Treated Non-small Cell Lung Cancer Patients with Poor Performance Status

    Institute of Scientific and Technical Information of China (English)

    Sun YoungJUNG; Su JinYOO; Ji Young SHIN; Ji Won PARK; Jeong Eun LEE; Hee Sun PARK; Ju Ock KIM; Sun Young KIM

    2011-01-01

    Background and objective Pemetrexed have been approved for the treatment of patients affected by advanced non-small cell lung cancner (NSCLC) in progression after first-line chemotherapy. We evaluated the activity and feasibility of pemetrexed in previously treated NSCLC.Methods Patients with histologically or cytologically confirmed NSCLC were evaluated from April 2007 to March 2009. The patients had relapsed or progressed after prior chemotherapy treatment. Pemetrexed (500 mg/m2) was administered intravenously once every 3 weeks after progression to prior chemotherapy. The tumor response was evaluated according to RECIST criteria by chest CT at every 2 cycles of chemotherapy.Results A total 61 patients were eligible for analysis. Performance status of them (100%) was over 2. The response rate and disease control rate were 14.7% and 37.7% respectively. Non-squamous cell carcinoma histology was significantly associated with a superior response rate (P=0.045) and disease control rate (P=0.008). The median survival time and the median progression free survival (PFS) time were 6.11 months and 2.17 months, respectively. Comparing the efficacy of pemetrexed in these two settings [second-line versus (12/61) more than third (49/61)], there was no significant difference in regard to median survival (11.18 months vs 11.46 months, P=0.922,S), but PFS was more longer in third- or further-line groups than second-line group (1.39 months vs 2.25 months, P=0.015,3).Conclusion Pemetrexed is a feasible regimen in previously treated NSCLC with poor performance status.

  17. Treating advanced non-small-cell lung cancer in Chinese patients: focus on icotinib

    Directory of Open Access Journals (Sweden)

    Liang JL

    2014-05-01

    Full Text Available Jun-Li Liang,1 Xiao-Cang Ren,2 Qiang Lin2 1Department of Radiation Oncology, Hebei Medical University Fourth Hospital, Shijiazhuang, People’s Republic of China; 2Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, Renqiu, Hebei Province, People’s Republic of China Abstract: Icotinib hydrochloride is an orally administered small-molecule reversible tyrosine kinase inhibitor that has been independently researched and developed and has independent intellectual property rights in the People’s Republic of China. Clinical trials have demonstrated that the response to icotinib among advanced non-small-cell lung cancer (NSCLC patients who received at least one platinum-based chemotherapy regimen was not inferior to gefitinib. Since being launched August 2011 in the People’s Republic of China, icotinib has been widely used in clinics, and has become an important treatment option for Chinese patients with advanced NSCLC. The present study presents the Phase I, II, and III clinical trials of icotinib and discusses current clinical applications in the People’s Republic of China and future research directions. Keywords: targeted therapy, EGFR-TKI, NSCLC

  18. Culture supernatants of breast cancer cell line MDA-MB-231 treated with parthenolide inhibit the proliferation, migration, and lumen formation capacity of human umbilical vein endothelial cells

    Institute of Scientific and Technical Information of China (English)

    LI Cai-juan; GUO Su-fen; SHI Tie-mei

    2012-01-01

    Background Parthenolide has been tested for anti-tumor activities,such as anti-proliferation and pro-apoptosis in recent studies.However,little is known about its role in the process of tumor angiogenesis.This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation,migration and lumen formation capacity of human umbilical vein endothelial cells.Methods Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells.After 24-hour incubation,the culture supematants were harvested and used to treat human umbilical vein endothelial cells for 24 hours.Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells.The secretion of vascular endothelial growth factor (VEGF),interleukin (IL)-8 and matrix metalloproteinases (MMP)-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay (ELISA) assays.Results Suppression of proliferation,migration,and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide.Parthenolide decreased the levels of the angiogenic factors MMP-9,VEGF,and IL-8secreted by the MDA-MB-231 cells.Conclusions Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation,migration and lumen-like structure formation of endothelial cells,thereby inhibiting tumor growth.It is a promising potential anti-angiogenic drug.

  19. Effect of Amifostine on Locally Advanced Non-small Cell Lung Cancer Patients Treated with Radiotherapy: A Meta-analysis of Randomized Controlled Trials

    OpenAIRE

    Wang, Shengye; Zhang, Yiping; Zhang, Suzhan; Ma, Shenglin

    2012-01-01

    Background and objective Controversy exists on whether amifostine can reduce the efficacy and decrease the side effects of non-small cell lung cancer (NSCLC) treated by radiotherapy. The aim of this meta-analysis is to evaluate the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy. Methods Open published randomized controlled trials on the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy were collected from Medline, Cochrane...

  20. Local failure in patients treated with radiotherapy and multidrug chemotherapy for small cell lung cancer

    International Nuclear Information System (INIS)

    Fifty-three patients with small cell carcinoma of the lung were treated with chemotherapy and radiotherapy, 40 Gy in the chest tumor. Intrathoracic failure occurred in 89% of the cases with extensive disease and in 60% of those with limited disease. Since 86% of all failures were localized within the target volume, one can conclude that in most cases the radiation dose was too low for eradication of the tumour. The treatment technique resulted in dose inhomogeneities of more than ±5% in 45% of the cases. The high local failure rate might indicate the need of improved radiotherapy, in the first place higher radiation dose. However, 82% of the patients with limited disease and local failure and 50% of those without local failure also developed distant metastases. This might indicate that the curative potential of improved thoracic radiotherapy probably is limited. Besides, lethal treatment toxicity affected particularly patients in whom local cure had been achieved, indicating the difficulty of increasing the treatment intensity without increasing the lethal toxicity in potentially curable cases. (orig.)

  1. Induction of apoptosis in colon cancer cells treated with isorhamnetin glycosides from Opuntia ficus-indica pads.

    Science.gov (United States)

    Antunes-Ricardo, Marilena; Moreno-García, Beatriz E; Gutiérrez-Uribe, Janet A; Aráiz-Hernández, Diana; Alvarez, Mario M; Serna-Saldivar, Sergio O

    2014-12-01

    (OFI) contains health-promoting compounds like flavonoids, being the isorhamnetin glycosides the most abundant. We evaluated the effect of OFI extracts with different isorhamnetin glycosides against two different human colon cancer cells (HT-29 and Caco2). The extracts were obtained by alkaline hydrolysis with NaOH at 40 °C during 15, 30 or 60 min. Tri and diglycosides were the most abundant isorhamnetin glycosides, therefore these compounds were isolated to compare their cytotoxic effect with the obtained from the extracts. The OFI extracts and purified isorhamnetin glycosides were more cytotoxic against HT-29 cells than Caco2 cells. OFI-30 exhibited the lowest IC50 value against HT-29 (4.9 ± 0.5 μg/mL) and against Caco2 (8.2 ± 0.3 μg/mL). Isorhamnetin diglycosides IG5 and IG6 were more cytotoxic than pure isorhamnetin aglycone or triglycosides when they were tested in HT-29 cells. Bioluminescent analysis revealed increased activity of caspase 3/7 in OFI extracts-treated cells, particularly for the extract with the highest concentration of isorhamnetin triglycosides. Flow cytometry analysis confirmed that OFI extract and isorhamnetin glycosides induced a higher percentage of apoptosis in HT-29 than in Caco2, while isorhamnetin was more apoptotic in Caco2. This research demonstrated that glycosilation affected antiproliferative effect of pure isorhamnetin glycosides or when they are mixed with other phytochemicals in an extract obtained from OFI.

  2. FoxO3a transcriptional regulation of bim controls apoptosis in paclitaxel-treated breast cancer cell lines

    NARCIS (Netherlands)

    Sunters, A; de Mattos, SF; Stahl, M; Brosens, JJ; Zoumpoulidou, G; Saunders, CA; Coffer, PJ; Medema, RH; Coombes, RC; Lam, EWF

    2003-01-01

    Paclitaxel is used to treat breast cancers, but the mechanisms by which it induces apoptosis are poorly understood. Consequently, we have studied the role of the FoxO transcription factors in determining cellular response to paclitaxel. Western blotting revealed that in a panel of nine breast cancer

  3. FoxO3a transcriptional regulation of Bim controls apoptosis in paclitaxel-treated breast cancer cell lines

    NARCIS (Netherlands)

    Sunters, A.; Fernandez de Mattos, S.; Stahl, M.; Brosens, J.J.; Zoumpoulidou, G.; Saunders, C.A.; Coffer, P.J.; Medema, R.H.; Coombes, R.C.; Lam, E.W.-F.

    2003-01-01

    Paclitaxel is used to treat breast cancers, but the mechanisms by which it induces apoptosis are poorly understood. Consequently, we have studied the role of the FoxO transcription factors in determining cellular response to paclitaxel. Western blotting revealed that in a panel of nine breast cancer

  4. PD-L1 Expression and Survival among Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Steffen Filskov Sorensen

    2016-02-01

    Full Text Available BACKGROUND: Recent clinical trial results have suggested that programmed cell death ligand 1 (PD-L1 expression measured by immunohistochemistry may predict response to anti–programmed cell death 1 (PD-1 therapy. Results on the association between PD-L1 expression and survival among patients with advanced non–small cell lung cancer (NSCLC treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD-L1 expression was measured using a prototype immunohistochemistry assay with the anti–PD-L1 22C3 antibody (Merck. PD-L1 strong positivity and weak positivity were defined to be traceable to the clinical trial version of the assay. RESULTS: Twenty-five percent of patients had PD-L1 strong-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9.8 months for the PD-L1 weak-positive group compared with the PD-L1–negative group (median OS, 7.5 months. No association was seen between PD-L1 expression and OS when PD-L1 expression levels were stratified by median or tertiles. CONCLUSIONS: In concordance with previous studies, we found PD-L1 measured by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy.

  5. Metastasis-Induced Acute Pancreatitis Successfully Treated with Chemotherapy and Radiotherapy in a Patient with Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kerem Okutur

    2015-01-01

    Full Text Available Although involvement of pancreas is a common finding in small cell lung cancer (SCLC, metastasis-induced acute pancreatitis (MIAP is very rare. A 50-year-old female with SCLC who had limited disease and achieved full response after treatment presented with acute pancreatitis during her follow-up. The radiologic studies revealed a small area causing obliteration of the pancreatic duct without mass in the pancreatic neck, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA confirmed the metastasis of SCLC. The patient was treated successfully with systemic chemotherapy and radiotherapy delivered to pancreatic field. In SCLC, cases of MIAP can be encountered with conventional computed tomography with no mass image, and positron emission tomography and EUS-FNA can be useful for diagnosis of such cases. Aggressive systemic and local treatment can prolong survival, especially in patients with good performance status.

  6. Prevalence and Predictors of Neoadjuvant Therapy for Stage IIIA Non-Small Cell Lung Cancer in the National Cancer Database: Importance of Socioeconomic Status and Treating Institution

    International Nuclear Information System (INIS)

    Purpose: The optimal locoregional therapy for stage IIIA non-small cell lung cancer (NSCLC) is controversial, with definitive chemoradiation therapy (CRT) and neoadjuvant therapy followed by surgery (NT-S) serving as competing strategies. In this study, we used the National Cancer Database to determine the prevalence and predictors of NT in a large, modern cohort of patients. Methods and Materials: Patients with stage IIIA NSCLC treated with CRT or NT-S between 2003 and 2010 at programs accredited by the Commission on Cancer were included. Predictors were categorized as clinical, time/geographic, socioeconomic, and institutional. In accord with the National Cancer Database, institutions were classified as academic/research program and as comprehensive and noncomprehensive community cancer centers. Logistic regression and random effects multilevel logistic regression were performed for univariable and multivariable analyses, respectively. Results: The cohort consisted of 18,581 patients, 3,087 (16.6%) of whom underwent NT-S (10.6% induction CRT, 6% induction chemotherapy). The prevalence of NT-S was constant over time, but there were significant relative 31% and 30% decreases in pneumonectomy and right-sided pneumonectomy, respectively, over time (P trend <.02). In addition to younger age, lower T stage, and favorable comorbidity score, indicators of higher socioeconomic status were strong independent predictors of NT-S, including white race, higher income, and private/managed insurance. The type of institution (academic/research program vs comprehensive or noncomprehensive community cancer centers, odds ratio 1.54 and 2.08, respectively) strongly predicted NT-S, but treatment volume did not. Conclusions: Neoadjuvant therapy followed by surgery was an uncommon treatment approach in Commission on Cancer programs, and the prevalence of postinduction pneumonectomy decreased over time. Higher socioeconomic status and treatment at academic institutions were significant

  7. Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

    Directory of Open Access Journals (Sweden)

    Steven M Yip

    2016-03-01

    Full Text Available Treatment of metastatic renal cell cancer (mRCC currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2, and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.

  8. The cost of treating advanced non-small cell lung cancer: estimates from the chinese experience.

    Directory of Open Access Journals (Sweden)

    Xiaohui Zeng

    Full Text Available BACKGROUND: Because of the potentially significant economic burden of healthcare costs associated with many diseases, it is critical that regulatory and medical insurance organisations collect and utilise data on the cost-effectiveness of care provision to make rational policy decisions. However, little is known about healthcare costs in China. METHODOLOGY/PRINCIPAL FINDINGS: Based on health expenditure data for 253 cases of advanced non-small cell lung cancer (NSCLC registered at the Second Xiangya Hospital of Central South University in China between 2006 and 2010, the cost of care provision was analysed. The monthly and aggregate annual medical costs were estimated for patients who were in either a progression-free state (PFS or a disease-progression state (DPS. Monthly healthcare costs accumulated during the terminal 3 months were collected separately. The mean cost of treatment for PFS and DPS patients over one year was approximately US$11,566 and $14,519, respectively. The monthly costs for all patients were higher initially than in the subsequent months (PFS: $2,490; DPS: $2,503. For PFS patients, healthcare expenditures stabilised after the 7th month, with a mean monthly medical expenditure of $82.49. For DPS patients, expenditures stabilised after the 9th month, and the mean expenditure during the 9th month was $307.9. Medical care costs in the three successive months prior to death were $3,754, $5,829 and $7,372, respectively. CONCLUSIONS/SIGNIFICANCE: The economic evaluation of health care technologies is becoming ever more important in China, especially in disease areas for which new and expensive therapies are being introduced on a regular basis. This is first paper to present empirically estimated China-specific costs associated with the treatment of NSCLC. The cost estimates are presented in a format that is specifically intended to inform cost-effectiveness analyses of treatments for NSCLC, and hence, contribute to the more

  9. Comparison of Survival Rate in Primary Non-Small-Cell Lung Cancer Among Elderly Patients Treated With Radiofrequency Ablation, Surgery, or Chemotherapy

    International Nuclear Information System (INIS)

    Purpose: We retrospectively compared the survival rate in patients with non-small-cell lung cancer (NSCLC) treated with radiofrequency ablation (RFA), surgery, or chemotherapy according to lung cancer staging. Materials and Methods: From 2000 to 2004, 77 NSCLC patients, all of whom had WHO performance status 0–2 and were >60 years old, were enrolled in a cancer registry and retrospectively evaluated. RFA was performed on patients who had medical contraindications to surgery/unsuitability for surgery, such as advanced lung cancer or refusal of surgery. In the RFA group, 40 patients with inoperable NSCLC underwent RFA under computed tomography (CT) guidance. These included 16 patients with stage I to II cancer and 24 patients with stage III to IV cancer who underwent RFA in an adjuvant setting. In the comparison group (n = 37), 13 patients with stage I to II cancer underwent surgery; 18 patients with stage III to IV cancer underwent chemotherapy; and 6 patients with stage III to IV cancer were not actively treated. The survival curves for RFA, surgery, and chemotherapy in these patients were calculated using Kaplan–Meier method. Results: Median survival times for patients treated with (1) surgery alone and (2) RFA alone for stage I to II lung cancer were 33.8 and 28.2 months, respectively (P = 0.426). Median survival times for patients treated with (1) chemotherapy alone and (2) RFA with chemotherapy for stage III to IV cancer were 29 and 42 months, respectively (P = 0.03). Conclusion: RFA can be used as an alternative treatment to surgery for older NSCLC patients with stage I to II inoperable cancer and can play a role as adjuvant therapy with chemotherapy for patients with stage III to IV lung cancer.

  10. Raman and coherent anti-Stokes Raman scattering microscopy studies of changes in lipid content and composition in hormone-treated breast and prostate cancer cells

    Science.gov (United States)

    Potcoava, Mariana C.; Futia, Gregory L.; Aughenbaugh, Jessica; Schlaepfer, Isabel R.; Gibson, Emily A.

    2014-11-01

    Increasing interest in the role of lipids in cancer cell proliferation and resistance to drug therapies has motivated the need to develop better tools for cellular lipid analysis. Quantification of lipids in cells is typically done by destructive chromatography protocols that do not provide spatial information on lipid distribution and prevent dynamic live cell studies. Methods that allow the analysis of lipid content in live cells are therefore of great importance. Using micro-Raman spectroscopy and coherent anti-Stokes Raman scattering (CARS) microscopy, we generated a lipid profile for breast (T47D, MDA-MB-231) and prostate (LNCaP, PC3) cancer cells upon exposure to medroxyprogesterone acetate (MPA) and synthetic androgen R1881. Combining Raman spectra with CARS imaging, we can study the process of hormone-mediated lipogenesis. Our results show that hormone-treated cancer cells T47D and LNCaP have an increased number and size of intracellular lipid droplets and higher degree of saturation than untreated cells. MDA-MB-231 and PC3 cancer cells showed no significant changes upon treatment. Principal component analysis with linear discriminant analysis of the Raman spectra was able to differentiate between cancer cells that were treated with MPA, R1881, and untreated.

  11. Cyclophosphamide or Denileukin Diftitox Followed By Expanding a Patient's Own T Cells in the Laboratory in Treating Patients With HER-2/Neu Overexpressing Metastatic Breast Cancer, Ovarian Cancer, or Non-Small Cell Lung Cancer Previously Treated With HER-2/Neu Vaccine

    Science.gov (United States)

    2014-11-07

    HER2-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage IV Breast Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

  12. The Effect of 217 Hz Magnetic Field of Cell Phone with Different Intensities on Apoptosis of Normal and Cancerous Cells Treated with Chemotherapy Drug

    Directory of Open Access Journals (Sweden)

    Mahsa Mansourian

    2012-03-01

    Full Text Available Background: According to the increasing development of home and business electronic equipment in today's world, the biological effects of ELF magnetic fields have been studied at two molecular-cellular and animal- human levels. Considering the therapeutic viewpoint of this study regarding the effects of low-frequency fields of mobile phone, the effect of acute exposure to this field on chemotherapy will be studied.Materials and Methods: In this experimental study, based on measurement of the intensity of the magnetic fields from mobile phones in another research, flux densities of magnetic field of 159.44, 93.25 and 120µ tesla with frequency of 217Hz was generated in magnetic field generator system, and the apoptosis level in K562 cancer cells and healthy cells of lymphocytes was assessed after exposure to field using flow cytometry method. This evaluation method was also performed for the cells treated with bleomycin after exposure to this field.Results: 217 Hz magnetic field exposure significantly increases the rate of apoptosis percentage (p > 0.05 in K562 cancer cells and in two intensities of 120 and 159.44µ tesla compared to the control group, but such effect is not observed in lymphocyte cells. Bleomycin-induced apoptosis percentage following exposure to the mentioned magnetic field shows no significant difference compared to the group of treatment with drug and without field exposure. This lack of significant difference is observed between the groups of drug after field exposure and field alone as well as between groups exposed to field and groups treated with bleomycin.Conclusion: Study results showed that 217 Hz magnetic field of mobile phone can induce apoptosis on cancer cells, but it has no effect on healthy cells. Thus, in order to use mobile phone as an effective factor in their treatment, some studies should be conducted at animal-human level.

  13. Endoplasmic reticulum vacuolation and unfolded protein response leading to paraptosis like cell death in cyclosporine A treated cancer cervix cells is mediated by cyclophilin B inhibition.

    Science.gov (United States)

    Ram, Babul Moni; Ramakrishna, Gayatri

    2014-11-01

    Cyclosporine A (CsA), a widely used immunosuppressant shows cytotoxic effects by either inducing apoptosis or redirecting the cell towards non-apoptotic cell death. However, there still remains a lacuna in understanding the mechanism of CsA induced non-apoptotic cell death. In the present study we investigated calcineurin dependent or independent cytotoxic effects of CsA, a calcineurin inhibitor, in cervical cancerous SiHa cells. Decreased cell viability and massive cytoplasmic vacuolations were observed in CsA treated SiHa cells, having increased calcineurin activity. Endoplasmic reticulum (ER) stress and unfolded protein response (UPR), accompanied by a decrease in cyclophilin B (ER resident PPIase), preceded the formation of the vacuoles. These vacuoles stained positive for many ER resident markers confirming their ER origin; but the absence of autophagosomal marker, LC3II, ruled out autophagy. Extensively vacuolated cells eventually undergo cell death which lacked the typical apoptotic features, but showed significant decrease in AIP (ALG2 interacting protein) as seen in paraptosis. ER-vacuolation was prevented by cycloheximide and salubrinal thereby indicating requirement of active protein synthesis. Inhibiting calcineurin activity by either Tacrolimus (FK506) or by knockdown of calcineurin B subunit did not result in either ER-stress or cellular vacuolation. However, knockdown of cyclophilin B by siRNA resulted in increased expression of Bip and IRE1α, together with cytoplasmic vacuolation. In conclusion, we report that persistent ER stress due to cyclophilin B inhibition in CsA treated cervical cancer cells caused cellular vacuolation which culminated in a non-apoptotic cell death response similar to paraptosis. Additionally, the paraptotic effects of CsA are independent of calcineurin inhibition. PMID:25003316

  14. Charlson Comorbidity Index predicts patient outcome, in cases of inoperable non-small cell lung cancer treated with radiofrequency ablation

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Tracey G.; Beland, Michael D. [Department of Diagnostic Imaging, Rhode Island Hospital/The Warren Alpert Medical School of Brown University, 593 Eddy Street, Providence, RI 02903 (United States); Machan, Jason T. [Department of Research Administration/Biostatistics, Rhode Island Hospital/The Warren Alpert Medical School of Brown University, 593 Eddy Street, Providence, RI 02903 (United States); DiPetrillo, Thomas [Department of Radiation Oncology, Rhode Island Hospital/The Warren Alpert Medical School of Brown University, 593 Eddy Street, Providence, RI 02903 (United States); Dupuy, Damian E., E-mail: ddupuy@lifespan.org [Department of Diagnostic Imaging, Rhode Island Hospital/The Warren Alpert Medical School of Brown University, 593 Eddy Street, Providence, RI 02903 (United States)

    2012-12-15

    Purpose: The Charlson Comorbidity Index (CCI) has been shown to be a significant prognostic indicator in the treatment of many types of cancer. The aim of this study is to evaluate the degree to which the CCI predicts survival in patients with inoperable non-small cell lung cancer (NSCLC) treated with radiofrequency ablation (RFA). Materials and methods: Eighty-two (34 men, 48 women) consecutive RFA treatments for medically inoperable NSCLC were performed at our institution from 1/1/2000 to 1/30/2009. With institutional IRB approval and in full HIPAA compliance, the medical records of these patients were examined for data relating to pre-treatment comorbid conditions, and a retrospective analysis was conducted. Survival curves were estimated by the Kaplan–Meier method. Risk factors for mortality were determined by single-factor comparisons of curves using Wilcoxon-weighted chi-square and multiple Cox regressions. Results: The patients ranged in age from 59 to 91 years (mean: 75.5). Eighty-eight percent (72 patients) were tumor stage IA or IB. Patients were followed for a total of five years; three-year overall survival was 50.6%. Hospital mortality was 0%. Gender, stage, histology and CCI score were each associated with significantly impaired survival (p < 0.001 in all cases). After covarying for age, tumor stage > IB, squamous histology and gender, multiple Cox regressions showed that an increasing CCI score was significantly associated with an increased risk of death (HR 1.3, 95% CI 25.5, 58.2). Conclusions: The CCI is validated as an important, independent predictor of patient survival, in cases of inoperable NSCLC treated with RFA.

  15. Dose distribution of IMRT and 3D-CRT on treating central non-small-cell lung cancer

    International Nuclear Information System (INIS)

    3D-CRT and IMRT were used in the radiation therapy of Central Non-small-cell lung cancer (NSCLC), and the dose difference of the methods was estimated. Thirty-two patients suffering with II class NSCLC were selected. Based on CT images, each patient was given 1 3D-CRT (3 dimensional conformal radiotherapy) and 2 IMRT(intensity modulated radiation therapy) treatment plans (5 fields and 7 fields), respectively, and the dose distribution was evaluated too. The results showed that PTVDmean and the PTVmax, PTVDmax (%) and CI of IMRT were both higher than those of 3D-CRT, but the uniformity was not as good as 3D-CRT. All indexes of lung and spinal cord treated with IMRT were lower than that treated with 3D-CRT. Moreover, there was no significance of the difference between 5 fields and 7 fields. In a conclusion, IMRT could not only decrease the target dose of NSCLC, but it can protect normal tissue from radiation damage effectively. And when IMRT was used, 5 fields might be enough. (authors)

  16. Efficacy and safety of albumin-bound paclitaxel in treating recurrent advanced non-small-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Pu-Yuan Xing; Jun-Ling Li; Yan Wang; Xue-Zhi Hao; Bin Wang; Lin Yang; Yuan-Kai Shi

    2013-01-01

    Objective:To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC).Methods:We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010.The treatment-related survival was also analyzed.Results:Of these 21 patients,the best overall response was partial response (PR) in 6 patients (28.6%),stable disease (SD) in 10 patients (47.6%),and progressive disease (PD) in 5 patients (23.8%).The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%.The median progression-free survival (PFS) was 4.0 months (95% CI,5.0-7.0 months).The main grade 3/4 toxicities included neutropenia (11.1%),peripheral nerve toxicity (5.6%),muscle and joint aches (5.6%),and fatigue (5.6%).Conclusions:The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.

  17. Metabolomics Reveals Metabolic Targets and Biphasic Responses in Breast Cancer Cells Treated by Curcumin Alone and in Association with Docetaxel

    OpenAIRE

    Bayet-Robert, Mathilde; Morvan, Daniel

    2013-01-01

    Background Curcumin (CUR) has deserved extensive research due to its anti-inflammatory properties, of interest in human diseases including cancer. However, pleiotropic even paradoxical responses of tumor cells have been reported, and the mechanisms of action of CUR remain uncompletely elucidated. Methodology/Principal Findings 1H-NMR spectroscopy-based metabolomics was applied to get novel insight into responses of MCF7 and MDA-MB-231 breast cancer cells to CUR alone, and MCF7 cells to CUR in...

  18. Proteomic profiling of human colon cancer cells treated with the histone deacetylase inhibitor belinostat

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Petersen, Jørgen; Nielsen, Søren Jensby;

    2010-01-01

    , and HSP90B that all were related to the proto-oncogene proteins p53, Myc, activator protein 1, and c-fos protein. The modulation of these proteins is consistent with the observations that belinostat is able to inhibit clonogenic cell growth of HCT116 cells and the biological role of these proteins...

  19. Induction of apoptosis in colon cancer cells treated with isorhamnetin glycosides from Opuntia ficus-indica pads.

    Science.gov (United States)

    Antunes-Ricardo, Marilena; Moreno-García, Beatriz E; Gutiérrez-Uribe, Janet A; Aráiz-Hernández, Diana; Alvarez, Mario M; Serna-Saldivar, Sergio O

    2014-12-01

    (OFI) contains health-promoting compounds like flavonoids, being the isorhamnetin glycosides the most abundant. We evaluated the effect of OFI extracts with different isorhamnetin glycosides against two different human colon cancer cells (HT-29 and Caco2). The extracts were obtained by alkaline hydrolysis with NaOH at 40 °C during 15, 30 or 60 min. Tri and diglycosides were the most abundant isorhamnetin glycosides, therefore these compounds were isolated to compare their cytotoxic effect with the obtained from the extracts. The OFI extracts and purified isorhamnetin glycosides were more cytotoxic against HT-29 cells than Caco2 cells. OFI-30 exhibited the lowest IC50 value against HT-29 (4.9 ± 0.5 μg/mL) and against Caco2 (8.2 ± 0.3 μg/mL). Isorhamnetin diglycosides IG5 and IG6 were more cytotoxic than pure isorhamnetin aglycone or triglycosides when they were tested in HT-29 cells. Bioluminescent analysis revealed increased activity of caspase 3/7 in OFI extracts-treated cells, particularly for the extract with the highest concentration of isorhamnetin triglycosides. Flow cytometry analysis confirmed that OFI extract and isorhamnetin glycosides induced a higher percentage of apoptosis in HT-29 than in Caco2, while isorhamnetin was more apoptotic in Caco2. This research demonstrated that glycosilation affected antiproliferative effect of pure isorhamnetin glycosides or when they are mixed with other phytochemicals in an extract obtained from OFI. PMID:25186940

  20. Prognostic importance of cell-free DNA in chemotherapy resistant ovarian cancer treated with bevacizumab

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Madsen, Christine Vestergaard; Andersen, Rikke Fredslund;

    2014-01-01

    AIM: Treatment of multiresistant epithelial ovarian cancer (EOC) is palliative and patients who have become resistant after multiple lines of chemotherapy often have an unmet need for further and less toxic treatment. Anti-angiogenic therapy has attracted considerable attention in the treatment...... of EOC in combination with chemotherapy. However, only a minor subgroup will benefit from the treatment and there is an obvious need for new markers to select such patients. The purpose of this study was to investigate the effect of single-agent bevacizumab in multiresistant EOC and the importance...

  1. Erlotinib dosing-to-rash: A phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer

    NARCIS (Netherlands)

    A. mita (Alain); K. Papadopoulos (K.); M.J.A. de Jonge (Maja); G. Schwartz (G.); J. Verweij (Jaap); A. Ricart (A.); Q.S.C. Chu (Q. S C); A.W. Tolcher (A. W.); L. Wood (Lori); S.W. McCarthy (Stanley); M. Hamilton; K.K. Iwata (Kenneth); B. Wacker; K. de Witte (Karel); E.K. Rowinsky (Eric Keith)

    2011-01-01

    textabstractBackground: To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacok

  2. Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy

    NARCIS (Netherlands)

    Wijsman, R.; Dankers, F.; Troost, E.G.; Hoffman, A.L.; Heijden, E. van der; Geus-Oei, L.F. de; Bussink, J.

    2015-01-01

    BACKGROUND AND PURPOSE: The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to d

  3. Inhibition of the epidermal growth factor receptor in bladder cancer cells treated with the DNA-damaging drug etoposide markedly increases apoptosis

    DEFF Research Database (Denmark)

    Munk, Mathias; Memon, Ashfaque Ahmed; Nexo, Ebba;

    2007-01-01

    : The bladder cancer cell lines RT4 and T24, representing low- and high-malignancy grades respectively, were treated with VP16 (10 or 50 microM) and the level of apoptosis determined using a commercial kit. EGFR receptor activity was determined by western blotting using antibodies against phosphorylated EGFR...

  4. Evaluation of the efficacyof aminolevulinic acid-dependent photodynamic therapy on melanoma cancer cells treated with tocopherol succinate (in-vitro

    Directory of Open Access Journals (Sweden)

    Homa Kouchesfahani

    2012-01-01

    Full Text Available Background: Photodynamic therapy (PDT using 5-aminolevulinic acid (ALA to produce an intracellular photo-sensitizer, a protoporphyrin molecule IX (PPIX which absorbs light and targets cells, is a promising cancer treatment. Unfortunately, treatment failures are still a common occurrence when ALA is used. In this study, in order to enhance the efficacy of ALA-dependent photodynamic therapy, the effects of photodynamic therapy on melanoma cancer cells were studied after treating them with tocopherol succinate.Materials and Methods: In this experimental study melanoma cells were cultured in RPMI 1640 medium for 24 h. then, cells were treated with tocopherol succinate (6μm/ml. After 48 and 72 hours, the mediums were replaced by serum-free medium in the darkness, with ALA, 0.1mg/ml and then cells incubated for 4h. After that, cells were irradiated by using Nd: YAG laser (532 nm. After 24h, cell survival was measured by the MTT assay.Results: Twenty-four hours after PDT, among compared groups, pretreated cells with tocopherol succinate showed significant lower cell viability than control group. Conclusion: Induction of differentiation by using tocopherol succinate augmented intracellular PPIX accumulation in cells treated with ALA. Therefore phototoxic cell death after exposure to 532nm light enhances significantly in tocopherol succinate-pretreated cells. This study suggests that tocopherol succinate may act as a biological enhancer of ALA based photodynamic therapy

  5. Survival Analysis of 121 Stage N2-IIIa Non-small Cell Lung Cancer Patients 
Treated with Surgery

    Directory of Open Access Journals (Sweden)

    Heli YANG

    2015-08-01

    Full Text Available Background and objective It has still been controversial to treat N2-IIIa non-small cell lung cancer (NSCLC patients by surgery or non-surgery. We retrospectively analysed the survival of 121 stage N2-IIIa NSCLC patients treated with surgery and explored their postoperatively long-term prognostic factors. Methods All of 1,290 patients in Beijing Cancer Hospital underwent resection by single-surgeon-team, among which 121 cases with stage N2-IIIa were enrolled in the study. We retrospectively analysed the impact of gender, age, smoking, perioperative chemotherapy, incision, histological type, vascular tumor emboli, pTstage and tumor size on survival of stage N2-IIIa patients, and compared the survival between patients with single-and multi-station N2 metastasis, and between intraoperatively or postoperatively pathological N2 (IIIa1/a2 and preoperative N2 (IIIa3/a4. Univariate analysis was conducted by Kaplan-Meier curve, and significance test was performed by Log-rank test and Cox regression factor analysis was applicated for multivariate analysis. Results The 5-yr of all the 121 cases was 43.6%, with a median survival time being 50.3 mo. Univariate analysis showed the 5-year survival rate in patients with single- and multi- station N2 metastasis were 58.3% and 25.5%, respectively (P=0.001, 5-year survival rate in patients with stage IIIa1/a2 and stag IIIa3/a4 were 52.7% and 38.4%, respectively (P=0.020. Multivariate analysis demonstrated that only single station N2 (HR=0.326, 95%CI: 0.186-0.572, P<0.001 and IIIa1/a2 (HR=0.494, 95%CI: 0.259-0.941, P=0.032 were independent prognostic factors for stage N2-IIIa lung cancer patients. Conclusion The prognosis of stage N2-IIIa NSCLC patients with single-station N2 metastasis were better than those with multi-station N2 metastasis. Besides, IIIa1/a2 patients had a better survival compared with stage IIIa3/a4 patients. A multi-disciplinary comprehensive treatment based on surgery may allow patients with

  6. Isolated Late Metastasis of a Renal Cell Cancer Treated by Radical Distal Pancreatectomy

    Directory of Open Access Journals (Sweden)

    J. P. Barras

    1996-01-01

    Full Text Available A 53–year-old man underwent right nephrectomy for a locally advanced renal cell carcinoma with concomitant resection of a solitary metastasis in the right lung. Ten years later, he presented with haematochezia caused by a tumour in the tail of pancreas, invading the transverse colon and the greater curvature of the stomach. The tumour was radically resected, and histological examination revealed a solitary metastasis of the previous renal cell carcinoma. This case illustrates a rare indication for pancreatic resection because of pancreatic metastasis.

  7. Chromophobe renal cell cancer - review of the literature and potential methods of treating metastatic disease

    Directory of Open Access Journals (Sweden)

    Bodnar Lubomir

    2009-10-01

    Full Text Available Abstract Chromophobe renal cell carcinoma (ChRCC is a subtype of renal cell carcinoma (RCC. ChRCC is diagnosed mainly in 6th decade of life. An incidence of ChRCC is similar in both men and woman. Eighty six percent of ChRCCs cases are diagnosed in stage 1 or 2. Prognosis of ChRCC is better than in other types of RCC. Five- and 10-year disease free survival (DFS for ChRCC was 83.9% and 77.9%, respectively. Expression of immunohistological markers: cytokeratins (CK, vimentin, epithelial membrane antigen (EMA, CD10 could be potentially helpful in diagnosis of different subtypes of RCC. From all conventional RCC, CD 117 was detected (overexpression in membrane of cells ChRCC. Overexpression of CD117 on cellular membranes of ChRCC could be a potential target for kinase inhibitors like: imatinib, dasatinib, nilotinib. The potential targets for other kinase inhibitors (sunitinib and sorafenib in ChRCC seem to be VEGFR and PDGFR. On the basis for formulating research hypotheses which should be verified by prospective studies.

  8. Biological Therapy in Treating Patients With Metastatic Cancer

    Science.gov (United States)

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  9. Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy.

    Directory of Open Access Journals (Sweden)

    Ming Yin

    Full Text Available The repair of DNA double-strand breaks (DSBs is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC patients treated with definitive radio(chemotherapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs (i.e., RAD51 -135G>C/rs1801320 and -172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794 and estimated their associations with overall survival (OS and radiation pneumonitis (RP in 228 NSCLC patients. We found a predictive role of RAD51 -135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31-0.86, P = 0.010 for CG/CC vs. GG. We also found that RAD51 -135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14-2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02-2.85, P = 0.043 for AG vs. GG, respectively and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 -135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemotherapy. Large studies are needed to confirm our findings.

  10. Curcumin-treated cancer cells show mitotic disturbances leading to growth arrest and induction of senescence phenotype.

    Science.gov (United States)

    Mosieniak, Grażyna; Sliwinska, Małgorzata A; Przybylska, Dorota; Grabowska, Wioleta; Sunderland, Piotr; Bielak-Zmijewska, Anna; Sikora, Ewa

    2016-05-01

    Cellular senescence is recognized as a potent anticancer mechanism that inhibits carcinogenesis. Cancer cells can also undergo senescence upon chemo- or radiotherapy. Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa, shows anticancer properties both in vitro and in vivo. Previously, we have shown that treatment with curcumin leads to senescence of human cancer cells. Now we identified the molecular mechanism underlying this phenomenon. We observed a time-dependent accumulation of mitotic cells upon curcumin treatment. The time-lapse analysis proved that those cells progressed through mitosis for a significantly longer period of time. A fraction of cells managed to divide or undergo mitotic slippage and then enter the next phase of the cell cycle. Cells arrested in mitosis had an improperly formed mitotic spindle and were positive for γH2AX, which shows that they acquired DNA damage during prolonged mitosis. Moreover, the DNA damage response pathway was activated upon curcumin treatment and the components of this pathway remained upregulated while cells were undergoing senescence. Inhibition of the DNA damage response decreased the number of senescent cells. Thus, our studies revealed that the induction of cell senescence upon curcumin treatment resulted from aberrant progression through the cell cycle. Moreover, the DNA damage acquired by cancer cells, due to mitotic disturbances, activates an important molecular mechanism that determines the potential anticancer activity of curcumin. PMID:26916504

  11. Addition of 2-deoxyglucose enhances growth inhibition but reverses acidification in colon cancer cells treated with phenformin.

    Science.gov (United States)

    Lea, Michael A; Chacko, Jerel; Bolikal, Sandhya; Hong, Ji Y; Chung, Ryan; Ortega, Andres; desbordes, Charles

    2011-02-01

    A report that effects of butyrate on some cells may be mediated by activation of AMP-activated protein kinase (AMPK) prompted this study which examines if other AMPK activators can induce differentiation and inhibit proliferation of colon cancer cells in a manner similar to butyrate. Using induction of alkaline phosphatase as a marker, it was observed that compound C, an AMPK inhibitor, is able to reduce the differentiating effect of butyrate on SW1116 and Caco-2 colon cancer cells. Metformin was observed to be less effective than butyrate in the induction of alkaline phosphatase but was more effective as a growth inhibitor. Phenformin was found to be a more potent growth inhibitor than metformin and both compounds cause acidification of the medium when incubated with colon cancer cells. Combined incubation of 2-deoxyglucose with either of the biguanides prevented the acidification of the medium but enhanced the growth inhibitory effects. PMID:21378320

  12. Functional Cross-Talking between Differentially Expressed and Alternatively Spliced Genes in Human Liver Cancer Cells Treated with Berberine

    OpenAIRE

    Zhen Sheng; Yi Sun; Ruixin Zhu; Na Jiao; Kailin Tang; Zhiwei Cao; Chao Ma

    2015-01-01

    Berberine has been identified with anti-proliferative effects on various cancer cells. Many researchers have been trying to elucidate the anti-cancer mechanisms of berberine based on differentially expressed genes. However, differentially alternative splicing genes induced by berberine might also contribute to its pharmacological actions and have not been reported yet. Moreover, the potential functional cross-talking between the two sets of genes deserves further exploration. In this study, R...

  13. A Clinical Study on Global TCM Therapy in Treating Senile Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To assess the clinical efficacy of global traditional Chinese medicine(TCM)therapy in treating senile advanced non-small cell lung cancer(NSCLC),with the aim of seeking a standardized,rational and economical way to treat advanced NSCLC in old patients.Methods:A retrospective analysis and comparison was carried out in 86 patients with senile advanced NSCLC,44 treated by global TCM(TCM group)and 42 by chemotherapy(control group)through dynamical observation on related indexes including tumor size,quality of life and the survival time,as well as on the fee for medical service at various time points in the course of the treatment.Results:The changes of tumor size,score of clinical main symptoms and behavior condition(by ZPS scoring),as well as survival rates in the two groups at corresponding time points,were not different significantly(P>0.05).The mean survival time in the TCM group was 13.20±1.52 months and that in the chemotherapy group was 13.45±1.94 months,showing insignificant difference between them.However,the median survival time in the TCM group(12 months)was actually longer than that in the chemotherapy group (9 months,P<0.05).The mean daily expense and the mean expense(RMB yuan)for each patient in the TCM group were significantly lower than that in the control group,which was 180.73±93.21 vs 825.84±329.63 for the mean daily expense and 34 077.21±14 638.04 vs 58 516.59±45 429.76 for the mean expense for each patient(both P<0.01).Conclusion:Treatment of senile advanced NSCLC with TCM alone has its apparent superiority in stabilizing tumor focus,improving clinical symptoms,elevating quality of life and prolonging the survival time.TCM is also less expensive,making it a good alternative therapeutic approach for this specific group of people.

  14. Risk factors of radiation-induced acute esophagitis in non-small cell lung cancer patients treated with concomitant chemoradiotherapy

    International Nuclear Information System (INIS)

    To analyze the clinical and dosimetric risk factors of acute esophagitis (AE) in non-small-cell lung cancer (NSCLC) patients treated with concomitant chemoradiotherapy. Seventy-six NSCLC patients treated with concomitant chemoradiotherapy were retrospectively analyzed. Forty-one patients received concomitant chemoradiotherapy with vinorelbine/cisplatin (VC), 35 with docetaxel/cisplatin (DC). AE was graded according to criteria of the Radiation Therapy Oncology Group (RTOG). The following clinical and dosimetric parameters were analyzed: gender, age, clinical stage, Karnofsky performance status (KPS), pretreatment weight loss, concomitant chemotherapy agents (CCA) (VC vs. DC), percentage of esophagus volume treated to ≥20 (V20), ≥30 (V30), ≥40 (V40), ≥50 (V50) and ≥60 Gy (V60), and the maximum (Dmax) and mean doses (Dmean) delivered to esophagus. Univariate and multivariate logistic regression analysis were used to test the association between the different factors and AE. Seventy patients developed AE (Grade 1, 19 patients; Grade 2, 36 patients; and Grade 3, 15 patients). By multivariate logistic regression analysis, V40 was the only statistically significant factor associated with Grade ≥2 AE (p<0.001, OR = 1.159). A V40 of <23% had a 33.3% (10/30) risk of Grade ≥2 AE, which increased to 89.1% (41/46) with a V40 of ≥23% (p<0.001). CCA (p =0.01; OR = 9.686) and V50 (p<0.001; OR = 1.122) were most significantly correlated with grade 3 AE. A V50 of <26.5% had a 6.7% (3/45) risk of Grade 3 AE, which increased to 38.7% (12/31) with a V50 of ≥26.5% (p = 0.001). On the linear regression analysis, V50 and CCA were significant independent factors affecting AE duration. Patients who received concomitant chemotherapy with VC had a decreased risk of grade 3 AE and shorter duration compared with DC. Concomitant chemotherapy agents have potential influence on AE. Concomitant chemotherapy with VC led to lower risk of AE compared with that using DC. V40 and V50

  15. A retrospective quality of life analysis using the lung cancer symptom scale in patients treated with palliative radiotherapy for advanced nonsmall cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: To measure symptom palliation in patients treated with radiation therapy for advanced nonsmall cell lung cancer (NSCLC). Methods and Materials: Five hundred thirty patients with NSCLC were treated at the Medical College of Virginia between 1988 and 1993. Sixty-three patients with the least favorable prognostic features received palliative radiation to 30 Gy in 10 or 12 fractions for symptoms related to the presence of intrathoracic tumor. The observer portion of the Lung Cancer Symptom Scale (LCSS) was employed in a retrospective chart review, scoring measures of appetite, fatigue, cough, dyspnea, hemoptysis, and pain. Results: In 54 evaluable patients, median survival was 4 months and was independent of age, stage, performance status, or histology. Ninety-six percent of the patients had at least one LCSS symptom at presentation. Fatigue was unaffected by therapy. Improvements in appetite (p = 0.68) and pain (p = 0.61) were not statistically significant. There was, however, a statistically significant reduction in cough (p = 0.01), hemoptysis (p = 0.001), and dyspnea (p 0.0003). Self-limiting acute side effects included transient esophagitis in 37% of patients, though no severe toxicities were noted. Conclusions: These results suggest symptomatic benefit from radiotherapy even in those NSCLC patients with advanced disease and a limited life expectancy. Treatment should be given to patients whose symptoms are most amenable to palliation. A site-specific quality of life instrument such as the LCSS should be included within any future clinical trial of NSCLC management so that symptom control may be scored as a treatment outcome in addition to disease-free survival

  16. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization

    International Nuclear Information System (INIS)

    Tumor-associated macrophages (TAM) play an important role in tumor microenvironment. Particularly, M2 macrophages contribute to tumor progression, depending on the expression of NF-κB. Tumor-derived exosomes can modulate tumor microenvironment by transferring miRNAs to immune cells. Epigallocatechin gallate (EGCG) has well known anti-tumor effects; however, no data are available on the influence of EGCG on communication with cancer cells and TAM. Murine breast cancer cell lines, 4T1, was used for in vivo and ex vivo studies. Exosome was extracted from EGCG-treated 4T1 cells, and the change of miRNAs was screened using microarray. Tumor cells or TAM isolated from murine tumor graft were incubated with exosomes derived from EGCG-treated and/or miR-16 inhibitor-transfected 4T1 cells. Chemokines for monocytes (CSF-1 and CCL-2), cytokines both with high (IL-6 and TGF-β) and low (TNF-α) expression in M2 macrophages, and molecules in NF-κB pathway (IKKα and Iκ-B) were evaluated by RT-qPCR or western blot. EGCG suppressed tumor growth in murine breast cancer model, which was associated with decreased TAM and M2 macrophage infiltration. Expression of chemokine for monocytes (CSF-1 and CCL-2) were low in tumor cells from EGCG-treated mice, and cytokines of TAM was skewed from M2- into M1-like phenotype by EGCG as evidenced by decreased IL-6 and TGF-β and increased TNF-α. Ex vivo incubation of isolated tumor cells with EGCG inhibited the CSF-1 and CCL-2 expression. Ex vivo incubation of TAM with exosomes from EGCG-treated 4T1 cells led to IKKα suppression and concomitant I-κB accumulation; increase of IL-6 and TGF-β; and, decrease of TNF-α. EGCG up-regulated miR-16 in 4T1 cells and in the exosomes. Treatment of tumor cells or TAM with exosomes derived from EGCG-treated and miR-16-knock-downed 4T1 cells restored the above effects on chemokines, cytokines, and NF-κB pathway elicited by EGCG-treated exosomes. Our data demonstrate that EGCG up-regulates miR-16 in

  17. P53-mediated cell cycle arrest and apoptosis through a caspase-3-independent, but caspase-9-dependent pathway in oridonin-treated MCF-7 human breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Qiao CUI; Jing-hua YU; Jin-nan WU; Shin-ichi TASHIRO; Satoshi ONODERA; Mutsuhiko MINAMI; Takashi IKEJIMA

    2007-01-01

    Aim: To study the caspase-3-independent mechanisms in oridonin-induced MCF-7 human breast cancer cell apoptosis in vitro. Methods: The viability of oridonin-treated MCF-7 cells was measured by MTT (thiazole blue) assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleoso-mal DNA fragmentation was assayed by agarose gel electrophoresis. The apoptotic ratio was determined by lactate dehydrogenase assay. Cell cycle alternation and mitochondrial membrane potential were measured by flow cytometric analysis. Bax, Bcl-2, caspase-3, caspase-9, heat shock protein (Hsp)90, p53, p-p53, p21, Poly (ADP-ribose) polymerase (PARP), and the inhibitor of caspase-activated Dnase (ICAD) protein expressions were detected by Western blot analysis. Results: Oridonin inhibited cell growth in a time- and dose-dependent manner. Cell cycle was altered through the upregulation of p53 and p21 protein expressions. Pan-caspase inhibitor Z-VAD-fmk and calpain inhibitor Ⅱ both decreased cell death ratio. Nucleosomal DNA fragmentation and the downregulation of △ψmit were detected in oridonin-induced MCF-7 cell apoptosis, which was involved in a postmitochondrial caspase-9-dependent pathway. Decreased Bcl-2 and Hsp90 expression levels and increased Bax and p21 expression levels were positively correlated with elevated levels of phosphorylated p53 phosphorylation. Moreover, PARP was partially cleaved by calpain rather than by capase-3. Conclusion: DNA damage provoked alternations in the mitochondrial and caspase-9 pathways as well as p53-mediated cell cycle arrest, but was not related to caspase-3 activity in oridonin-induced MCF-7 cells.

  18. Brachial Plexopathy in Apical Non-Small Cell Lung Cancer Treated With Definitive Radiation: Dosimetric Analysis and Clinical Implications

    Energy Technology Data Exchange (ETDEWEB)

    Eblan, Michael J.; Corradetti, Michael N.; Lukens, J. Nicholas; Xanthopoulos, Eric [Department of Radiation Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mitra, Nandita [Department of Biostatistics and Epidemiology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Christodouleas, John P.; Grover, Surbhi; Fernandes, Annemarie T. [Department of Radiation Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Langer, Corey J.; Evans, Tracey L.; Stevenson, James [Department of Medical Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Rengan, Ramesh [Department of Radiation Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Apisarnthanarax, Smith, E-mail: apisarns@uphs.upenn.edu [Department of Radiation Oncology, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

    2013-01-01

    Purpose: Data are limited on the clinical significance of brachial plexopathy in patients with apical non-small cell lung cancers (NSCLC) treated with definitive radiation therapy. We report the rates of radiation-induced brachial plexopathy (RIBP) and tumor-related brachial plexopathy (TRBP) and associated dosimetric parameters in apical NSCLC patients. Methods and Materials: Charts of NSCLC patients with primary upper lobe or superiorly located nodal disease who received {>=}50 Gy of definitive conventionally fractionated radiation or chemoradiation were retrospectively reviewed for evidence of brachial plexopathy and categorized as RIBP, TRBP, or trauma-related. Dosimetric data were gathered on ipsilateral brachial plexuses (IBP) contoured according to Radiation Therapy Oncology Group atlas guidelines. Results: Eighty patients were identified with a median follow-up and survival time of 17.2 and 17.7 months, respectively. The median prescribed dose was 66.6 Gy (range, 50.4-84.0), and 71% of patients received concurrent chemotherapy. RIBP occurred in 5 patients with an estimated 3-year rate of 12% when accounting for competing risk of death. Seven patients developed TRBP (estimated 3-year rate of 13%), comprising 24% of patients who developed locoregional failures. Grade 3 brachial plexopathy was more common in patients who experienced TRBP than RIBP (57% vs 20%). No patient who received {<=}78 Gy to the IBP developed RIBP. On multivariable competing risk analysis, IBP V76 receiving {>=}1 cc, and primary tumor failure had the highest hazard ratios for developing RIBP and TRBP, respectively. Conclusions: RIBP is a relatively uncommon complication in patients with apical NSCLC tumors receiving definitive doses of radiation, while patients who develop primary tumor failures are at high risk for developing morbid TRBP. These findings suggest that the importance of primary tumor control with adequate doses of radiation outweigh the risk of RIBP in this population of

  19. Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

    Directory of Open Access Journals (Sweden)

    Melissa Bersanelli

    2014-09-01

    Full Text Available The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group. The other 31 also received subcutaneous IL-2 (GIL-2 group: 1 MIU/m2 (Million International Unit/m2twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%, asthenia/anorexia (6% and diarrhea (7%; patients treated with IL-2 showed grade 2–3 fever (46%, fatigue (21% and arthralgia (13%. In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response and 5.1% (only partial response; a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8 and 4.1 (CI 95% = 2.6–5.7 months; a median overall survival of 20.1 (CI 95% = 5.1–35.1 and 6.9 (CI 95% = 4.9–8.9 months (p = 0.002; and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54 and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60 were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

  20. Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Bersanelli, Melissa, E-mail: melissa.bersanelli@alice.it; Buti, Sebastiano; Camisa, Roberta [Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy); Brighenti, Matteo; Lazzarelli, Silvia [Oncology Unit, Azienda Istituti Ospitalieri di Cremona, Largo Priori, 1, 26100 Cremona (Italy); Mazza, Giancarlo [Radiology Division, Spedali Civili di Brescia, P.le Spedali Civili,1, 25123 Brescia (Italy); Passalacqua, Rodolfo, E-mail: melissa.bersanelli@alice.it [1Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma (Italy)

    2014-09-30

    The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m{sup 2} (Million International Unit/m{sup 2})twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2–3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8) and 4.1 (CI 95% = 2.6–5.7) months; a median overall survival of 20.1 (CI 95% = 5.1–35.1) and 6.9 (CI 95% = 4.9–8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib.

  1. Efficacy of the smaller target volume for stage III non-small cell lung cancer treated with intensity-modulated radiotherapy

    OpenAIRE

    LIANG, XIANGCUN; Yu, Huiming; Yu, Rong; Xu, Gang; Guangying ZHU

    2015-01-01

    The present study reports the local recurrence, distant metastasis, progression-free survival, overall survival and radiation toxicity between two arms of stage III non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT); one arm with clinical target volume (CTV) and the other without CTV. The two arms of local recurrence, distant metastasis, progression-free survival, overall survival, grade 3–4 radiation esophagitis and hematological toxicity had no statistic...

  2. An Îto stochastic differential equations model for the dynamics of the MCF-7 breast cancer cell line treated by radiotherapy.

    Science.gov (United States)

    Oroji, Amin; Omar, Mohd; Yarahmadian, Shantia

    2016-10-21

    In this paper, a new mathematical model is proposed for studying the population dynamics of breast cancer cells treated by radiotherapy by using a system of stochastic differential equations. The novelty of the model is essentially in capturing the concept of the cell cycle in the modeling to be able to evaluate the tumor lifespan. According to the cell cycle, each cell belongs to one of three subpopulations G, S, or M, representing gap, synthesis and mitosis subpopulations. Cells in the M subpopulation are highly radio-sensitive, whereas cells in the S subpopulation are highly radio-resistant. Therefore, in the process of radiotherapy, cell death rates of different subpopulations are not equal. In addition, since flow cytometry is unable to detect apoptotic cells accurately, the small changes in cell death rate in each subpopulation during treatment are considered. Subsequently, the proposed model is calibrated using experimental data from previous experiments involving the MCF-7 breast cancer cell line. Consequently, the proposed model is able to predict tumor lifespan based on the number of initial carcinoma cells. The results show the effectiveness of the radiation under the condition of stability, which describes the decreasing trend of the tumor cells population. PMID:27457094

  3. Total-Body Irradiation and Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

    Science.gov (United States)

    2015-12-14

    Adult Acute Myeloid Leukemia in Remission; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndrome; Childhood Renal Cell Carcinoma; Chronic Myelomonocytic Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndrome; Metastatic Renal Cell Cancer; Previously Treated Myelodysplastic Syndrome; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Renal Medullary Carcinoma; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  4. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-10-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  5. Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer

    Science.gov (United States)

    2016-08-01

    Acute Undifferentiated Leukemia; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma

  6. Functional Cross-Talking between Differentially Expressed and Alternatively Spliced Genes in Human Liver Cancer Cells Treated with Berberine.

    Directory of Open Access Journals (Sweden)

    Zhen Sheng

    Full Text Available Berberine has been identified with anti-proliferative effects on various cancer cells. Many researchers have been trying to elucidate the anti-cancer mechanisms of berberine based on differentially expressed genes. However, differentially alternative splicing genes induced by berberine might also contribute to its pharmacological actions and have not been reported yet. Moreover, the potential functional cross-talking between the two sets of genes deserves further exploration. In this study, RNA-seq technology was used to detect the differentially expressed genes and differentially alternative spliced genes in BEL-7402 cancer cells induced by berberine. Functional enrichment analysis indicated that these genes were mainly enriched in the p53 and cell cycle signalling pathway. In addition, it was statistically proven that the two sets of genes were locally co-enriched along chromosomes, closely connected to each other based on protein-protein interaction and functionally similar on Gene Ontology tree. These results suggested that the two sets of genes regulated by berberine might be functionally cross-talked and jointly contribute to its cell cycle arresting effect. It has provided new clues for further researches on the pharmacological mechanisms of berberine as well as the other botanical drugs.

  7. Lung cancer - small cell

    Science.gov (United States)

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

  8. Lung cancer - small cell

    Science.gov (United States)

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

  9. Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy

    International Nuclear Information System (INIS)

    We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of 131I-A7, an IgG1 anti-colorectal monoclonal antibody, or 131I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P131I-A7 RIT displayed a marked therapeutic effect (n=8) (P131I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P131I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

  10. Identification of valid reference genes for the normalization of RT-qPCR expression studies in human breast cancer cell lines treated with and without transient transfection.

    Directory of Open Access Journals (Sweden)

    Lin-Lin Liu

    Full Text Available Reverse transcription-quantitative polymerase chain reaction (RT-qPCR is a powerful technique for examining gene expression changes during tumorigenesis. Target gene expression is generally normalized by a stably expressed endogenous reference gene; however, reference gene expression may differ among tissues under various circumstances. Because no valid reference genes have been documented for human breast cancer cell lines containing different cancer subtypes treated with transient transfection, we identified appropriate and reliable reference genes from thirteen candidates in a panel of 10 normal and cancerous human breast cell lines under experimental conditions with/without transfection treatments with two transfection reagents. Reference gene expression stability was calculated using four algorithms (geNorm, NormFinder, BestKeeper and comparative delta Ct, and the recommended comprehensive ranking was provided using geometric means of the ranking values using the RefFinder tool. GeNorm analysis revealed that two reference genes should be sufficient for all cases in this study. A stability analysis suggests that 18S rRNA-ACTB is the best reference gene combination across all cell lines; ACTB-GAPDH is best for basal breast cancer cell lines; and HSPCB-ACTB is best for ER+ breast cancer cells. After transfection, the stability ranking of the reference gene fluctuated, especially with Lipofectamine 2000 transfection reagent in two subtypes of basal and ER+ breast cell lines. Comparisons of relative target gene (HER2 expression revealed different expressional patterns depending on the reference genes used for normalization. We suggest that identifying the most stable and suitable reference genes is critical for studying specific cell lines under certain circumstances.

  11. Two Cases of Small Cell Cancer of the Maxillary Sinus Treated with Cisplatin plus Irinotecan and Radiotherapy

    Directory of Open Access Journals (Sweden)

    Kiyoaki Tsukahara

    2013-01-01

    Full Text Available Background. Small cell carcinoma (SmCC in the nasal cavity and paranasal sinuses is very rare, and definitive therapies have not yet been established. Methods. Chemoradiotherapy comprised 60 Gy of external radiation, with the administration of irinotecan intravenously at 60 mg/m2 on days 1, 8, and 15 and cisplatin at 60 mg/m2 on day 1. Results. Case 1 involved a 66-year-old woman with stage III cancer. Adverse events included decreased white blood cells, anemia, and oral mucositis, all Grade 2. The patient remained free of cancer as of 3 years and 6 months after completing the treatment. Case 2 involved a 60-year-old man with stage IV cancer. He also experienced adverse events of decreased white blood cells, anemia, and oral mucositis, all Grade 2. He died after 11 months due to metastases throughout the body. Conclusions. The results suggest that this regimen may be tolerable as a therapy for this type of carcinoma.

  12. Gene expression profiling and pathway analysis data in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin.

    Science.gov (United States)

    Aumsuwan, Pranapda; Khan, Shabana I; Khan, Ikhlas A; Walker, Larry A; Dasmahapatra, Asok K

    2016-09-01

    Microarray technology (Human OneArray microarray, phylanxbiotech.com) was used to compare gene expression profiles of non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells exposed to dioscin (DS), a steroidal saponin isolated from the roots of wild yam, (Dioscorea villosa). Initially the differential expression of genes (DEG) was identified which was followed by pathway enrichment analysis (PEA). Of the genes queried on OneArray, we identified 4641 DEG changed between MCF-7 and MDA-MB-231 cells (vehicle-treated) with cut-off log2 |fold change|≧1. Among these genes, 2439 genes were upregulated and 2002 were downregulated. DS exposure (2.30 μM, 72 h) to these cells identified 801 (MCF-7) and 96 (MDA-MB-231) DEG that showed significant difference when compared with the untreated cells (pMDA-MB-231 cells. Further comparison of DEG between MCF-7 and MDA-MB-231 cells exposed to DS identified 3626 DEG of which 1700 were upregulated and 1926 were down-regulated. Regarding to PEA, 12 canonical pathways were significantly altered between these two cell lines. However, there was no alteration in any of these pathways in MCF-7 cells, while in MDA-MB-231 cells only MAPK pathway showed significant alteration. When PEA comparison was made on DS exposed cells, it was observed that only 2 pathways were significantly affected. Further, we identified the shared DEG, which were targeted by DS and overlapped in both MCF-7 and MDA-MB-231 cells, by intersection analysis (Venn diagram). We found that 7 DEG were overlapped of which six are reported in the database. This data highlight the diverse gene networks and pathways in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin. PMID:27331101

  13. Metabolomics reveals metabolic targets and biphasic responses in breast cancer cells treated by curcumin alone and in association with docetaxel.

    Directory of Open Access Journals (Sweden)

    Mathilde Bayet-Robert

    Full Text Available BACKGROUND: Curcumin (CUR has deserved extensive research due to its anti-inflammatory properties, of interest in human diseases including cancer. However, pleiotropic even paradoxical responses of tumor cells have been reported, and the mechanisms of action of CUR remain uncompletely elucidated. METHODOLOGY/PRINCIPAL FINDINGS: (1H-NMR spectroscopy-based metabolomics was applied to get novel insight into responses of MCF7 and MDA-MB-231 breast cancer cells to CUR alone, and MCF7 cells to CUR in cotreatment with docetaxel (DTX. In both cell types, a major target of CUR was glutathione metabolism. Total glutathione (GSx increased at low dose CUR (≤ 10 mg.l(-1-28 µM- (up to +121% in MCF7 cells, P<0.01, and +138% in MDA-MB-231 cells, P<0.01, but decreased at high dose (≥ 25 mg.l(-1 -70 µM- (-49%, in MCF7 cells, P<0.02, and -56% in MDA-MB-231 cells, P<0.025. At high dose, in both cell types, GSx-related metabolites decreased, including homocystein, creatine and taurine (-60 to -80%, all, P<0.05. Together with glutathione-S-transferase actvity, data established that GSx biosynthesis was upregulated at low dose, and GSx consumption activated at high dose. Another major target, in both cell types, was lipid metabolism involving, at high doses, accumulation of polyunsaturated and total free fatty acids (between ×4.5 and ×11, P<0.025, and decrease of glycerophospho-ethanolamine and -choline (about -60%, P<0.025. Multivariate statistical analyses showed a metabolic transition, even a biphasic behavior of some metabolites including GSx, between low and high doses. In addition, CUR at 10 mg.l(-1 in cotreatment with DTX induced modifications in glutathione metabolism, lipid metabolism, and glucose utilization. Some of these changes were biphasic depending on the duration of exposure to CUR. CONCLUSIONS/SIGNIFICANCE: Metabolomics reveals major metabolic targets of CUR in breast cancer cells, and biphasic responses that challenge the widely accepted

  14. Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

    OpenAIRE

    Steven M Yip; Heng, Daniel Y. C.; Tang, Patricia A.

    2016-01-01

    Treatment of metastatic renal cell cancer (mRCC) currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR) pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium dat...

  15. Comparison of selected gene expression profiles in sensitive and resistant cancer cells treated with doxorubicin and Selol

    OpenAIRE

    Dudkiewicz-Wilczyńska, Jadwiga; Grabowska, Agnieszka; Książek, Iza; Sitarz, Karolina; Suchocki, Piotr; Anuszewska, Elżbieta

    2014-01-01

    Aim of the study Cellular resistance is strongly correlated with the risk of failure in doxorubicin (DOX) treatment, and the knowledge of the mechanisms of resistance and its possible modulation is still very limited. Material and methods In this study, we assessed the effect of 5% Selol and DOX on the expression of genes that affect cell proliferation in the resistant KB-V1 and sensitive HeLa cell lines, using RT2 ProfilerTM PCR Array matrix “Human Cancer Drug Resistance and Metabolism” (SAB...

  16. RIP kinase-mediated ROS production triggers XAF1 expression through activation of TAp73 in casticin-treated bladder cancer cells.

    Science.gov (United States)

    Chung, Yoon Hee; Kim, Daejin

    2016-08-01

    The p53 family protein p73 plays an important role in apoptosis induced by chemotherapeutic drugs. Transcriptionally active (TA) p73 (TAp73) substitutes for p53 in the response to stress. XIAP associated factor 1 (XAF1) is a novel predictive and prognostic factor in patients with bladder cancer, but the association between TAp73 and XAF1 expression in bladder cancer cells is poorly understood. Here, we investigated the status of TAp73 and XAF1 in T24 bladder cancer cells to identify molecular mechanisms in casticin‑exposed T24 cells. Casticin induced activation of JNK/p38 MAPK that preceded activation of the caspase cascade and disruption of the mitochondria membrane potential (∆ψm). Expression of XAF1 and TAp73 was also upregulated in casticin-treated T24 cells. Casticin treatment of T24 cells induced receptor-interacting protein (RIP) kinase expression and increased intracellular production of reactive oxygen species (ROS). Casticin-mediated ROS induced an increase in phosphorylated JNK/p38 MAPK, resulting in progressive upregulation of TAp73, which in turn led to XAF1 expression. Our data suggest that the apoptotic activity of casticin in T24 cells is mediated by activation of the TAp73-XAF1 signaling pathway through RIP kinase-mediated ROS production. PMID:27349281

  17. Biotin-targeted Pluronic(®) P123/F127 mixed micelles delivering niclosamide: A repositioning strategy to treat drug-resistant lung cancer cells.

    Science.gov (United States)

    Russo, Annapina; Pellosi, Diogo Silva; Pagliara, Valentina; Milone, Maria Rita; Pucci, Biagio; Caetano, Wilker; Hioka, Noboru; Budillon, Alfredo; Ungaro, Francesca; Russo, Giulia; Quaglia, Fabiana

    2016-09-10

    With the aim to develop alternative therapeutic tools for the treatment of resistant cancers, here we propose targeted Pluronic(®) P123/F127 mixed micelles (PMM) delivering niclosamide (NCL) as a repositioning strategy to treat multidrug resistant non-small lung cancer cell lines. To build multifunctional PMM for targeting and imaging, Pluronic(®) F127 was conjugated with biotin, while Pluronic(®) P123 was fluorescently tagged with rhodamine B, in both cases at one of the two hydroxyl end groups. This design intended to avoid any interference of rhodamine B on biotin exposition on PMM surface, which is a key fundamental for cell trafficking studies. Biotin-decorated PMM were internalized more efficiently than non-targeted PMM in A549 lung cancer cells, while very low internalization was found in NHI3T3 normal fibroblasts. Biotin-decorated PMM entrapped NCL with good efficiency, displayed sustained drug release in protein-rich media and improved cytotoxicity in A549 cells as compared to free NCL (P<0.01). To go in depth into the actual therapeutic potential of NCL-loaded PMM, a cisplatin-resistant A549 lung cancer cell line (CPr-A549) was developed and its multidrug resistance tested against common chemotherapeutics. Free NCL was able to overcome chemoresistance showing cytotoxic effects in this cell line ascribable to nucleolar stress, which was associated to a significant increase of the ribosomal protein rpL3 and consequent up-regulation of p21. It is noteworthy that biotin-decorated PMM carrying NCL at low doses demonstrated a significantly higher cytotoxicity than free NCL in CPr-A549. These results point at NCL-based regimen with targeted PMM as a possible second-line chemotherapy for lung cancer showing cisplatin or multidrug resistance.

  18. Targeting of cancer stem/progenitor cells plus stem cell-based therapies: the ultimate hope for treating and curing aggressive and recurrent cancers

    OpenAIRE

    MIMEAULT, M.; Batra, S K

    2008-01-01

    The rapid progression from aggressive primary cancers into locally advanced and invasive and/or metastatic diseases remains a big obstacle for an early diagnosis and curative therapeutic intervention for cancer patients. The late-stage leukemias and disseminated and metastatic sarcomas, melanomas, brain tumors and epithelial cancers are the devastating diseases associated with a high rate of recurrence after treatment with the conventional clinical therapies including surgery, ionizing radiat...

  19. A Phenolic Extract Obtained from Methyl Jasmonate-Treated Strawberries Enhances Apoptosis in a Human Cervical Cancer Cell Line.

    Science.gov (United States)

    Spagnuolo, Carmela; Flores, Gema; Russo, Gian Luigi; Ruiz Del Castillo, Maria Luisa

    2016-10-01

    In the present study, we evaluated the effect of methyl jasmonate (MeJA) treatment on strawberry phenolic composition. Strawberry extracts contain a mixture of phenolic compounds possessing several biological properties. We demonstrated that these extracts were more effective in inducing apoptosis in HeLa cells compared to phenolic preparations derived from untreated strawberries. Treatment of strawberries with 0.5% MeJA resulted in increased polyphenols content (from 7.4 to 8.6 mM quercetin equivalents) and antioxidant properties (from 3.9 to 4.6 mM quercetin equivalents). The identification and quantification of phenolic compounds by liquid chromatography-mass spectrometry in the strawberry extracts showed that cyanidin glucoside, pelargonidin glucoside, and ellagic glucoside acid were significantly higher in strawberries treated with MeJA. Phenolic extracts from MeJA-treated strawberries significantly decreased the cell viability in HeLa cells, compared to extracts derived from untreated fruits. We hypothesized that the enhanced apoptotic activity of MeJA-treated strawberries was due to a synergistic or additive effect of different phenolic compounds present in the extract, rather than the activity of a single molecule. PMID:27618150

  20. Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

    Science.gov (United States)

    2015-10-13

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Chronic Lymphocytic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Childhood Renal Cell Carcinoma; Chronic Phase Chronic Myelogenous Leukemia; Clear Cell Renal Cell Carcinoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer; T-cell Large Granular Lymphocyte Leukemia; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Waldenström Macroglobulinemia

  1. Clinical Effects for Patients with Recurrent Advanced Non-small Cell Lung Cancer Treated with Icotinib Hydrochloride

    Directory of Open Access Journals (Sweden)

    Jingying NONG

    2013-05-01

    Full Text Available Background and objective Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC. Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. Methods The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. Results The overall response rate (ORR was 45.0% and the disease control rate (DCR was 80.0%. The median progression-free survival (PFS time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively. RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively. RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, <0.001, 0.002, respectively . There was no statistical difference in RR and PFS between those age <65 and ≥65 or PS<2 and PS≥2. There was no statistical difference in RR and DCR between exon 19 deletion and exon 21 mutations, while the former had much longer PFS (P=0.020. EGFR mutation and exon 19 deletion are the independent prognostic factors to significantly improve the PFS (P=0.009, 0.012, respectively. The side effects were generally mild and consisted of rash and diarrhea. Conclusion Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

  2. The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis

    Directory of Open Access Journals (Sweden)

    Qun Liu

    2012-01-01

    Full Text Available Cervical cancer is one of the most common cancers among women in the world. 6-Shogaol is a natural compound isolated from the rhizome of ginger (Zingiber officinale. In this paper, we demonstrated that 6-shogaol induced apoptosis and G2/M phase arrest in human cervical cancer HeLa cells. Endoplasmic reticulum stress and mitochondrial pathway were involved in 6-shogaol-mediated apoptosis. Proteomic analysis based on label-free strategy by liquid chromatography chip quadrupole time-of-flight mass spectrometry was subsequently proposed to identify, in a non-target-biased manner, the molecular changes in cellular proteins in response to 6-shogaol treatment. A total of 287 proteins were differentially expressed in response to 24 h treatment with 15 μM 6-shogaol in HeLa cells. Significantly changed proteins were subjected to functional pathway analysis by multiple analyzing software. Ingenuity pathway analysis (IPA suggested that 14-3-3 signaling is a predominant canonical pathway involved in networks which may be significantly associated with the process of apoptosis and G2/M cell cycle arrest induced by 6-shogaol. In conclusion, this work developed an unbiased protein analysis strategy by shotgun proteomics and bioinformatics analysis. Data observed provide a comprehensive analysis of the 6-shogaol-treated HeLa cell proteome and reveal protein alterations that are associated with its anticancer mechanism.

  3. Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-06-17

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Lung Adenocarcinoma; Non-Small Cell Lung Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

  4. Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2016-09-07

    Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous 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

  5. Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-06-29

    Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Lung Adenocarcinoma; Malignant Pericardial Effusion; Malignant Pleural Effusion; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  6. Blood Samples From Patients With Cancer Treated on a Clinical Trial to Control Nausea and Vomiting During Donor Stem Cell Transplant

    Science.gov (United States)

    2016-02-11

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nausea and Vomiting; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  7. Stress associated gene expression in blood cells is related to outcome in radiotherapy treated head and neck cancer patients

    Directory of Open Access Journals (Sweden)

    Bøhn Siv K

    2012-09-01

    Full Text Available Abstract Background We previously observed that a radiotherapy-induced biochemical response in plasma was associated with favourable outcome in head and neck squamous carcinoma cancer (HNSCC patients. The aim of the present study was to compare stress associated blood cell gene expression between two sub-groups of HNSCC patients with different biochemical responses to radiotherapy. Methods Out of 87 patients (histologically verified, 10 biochemical ‘responders’ having a high relative increase in plasma oxidative damage and a concomitant decrease in plasma antioxidants during radiotherapy and 10 ‘poor-responders’ were selected for gene-expression analysis and compared using gene set enrichment analysis. Results There was a significant induction of stress-relevant gene-sets in the responders following radiotherapy compared to the poor-responders. The relevance of the involvement of similar stress associated gene expression for HNSCC cancer and radioresistance was verified using two publicly available data sets of 42 HNSCC cases and 14 controls (GEO GSE6791, and radiation resistant and radiation sensitive HNSCC xenografts (E-GEOD-9716. Conclusions Radiotherapy induces a systemic stress response, as revealed by induction of stress relevant gene expression in blood cells, which is associated to favourable outcome in a cohort of 87 HNSCC patients. Whether these changes in gene expression reflects a systemic effect or are biomarkers of the tumour micro-environmental status needs further study. Trial registration Raw data are available at ArrayExpress under accession number E-MEXP-2460.

  8. Cardiac toxicity and radiation dose to the heart in definitive treated non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schytte, Tine; Hansen, Olfred (Dept. of Oncology, Odense Univ. Hospital, 5000 Odense C (Denmark)), E-mail: tine.schytte@dadlnet.dk; Stolberg-Rohr, Thomine; Brink, Carsten (Radiophysic Laboratory, Odense Univ. Hospital, 5000 Odense C (Denmark))

    2010-10-15

    In this retrospective analysis of a consecutive series of NSCLC patients treated with definitive radiotherapy, we did not find a correlation between high mean-dose to three different volumes of the heart (left ventricle, both ventricles or whole heart) and cardiac toxicity defined as having an cardiac event after radiotherapy start. This is not as shown in studies with other diseases treated with radiotherapy. Darby et al. recently published a review concerning radiation related heart disease. They reported a significantly worse survival beyond ten years for breast cancer patients receiving radiotherapy. Some studies reported mortality from heart disease increased by 27%. In Hodgkin lymphoma patients an increased risk value of three to five for cardiac morbidity in general compared to general population and relative risk of death from myocardial infarction compared with general population in range 2 to 4. There may be several possible reasons why we did not experience a significant toxicity despite the high doses we delivered to the heart compared with patients receiving RT for breast cancer and lymphoma. Only relative few NSCLC patients live long enough to experience cardiac disease either due to lung cancer itself or comorbidity as a competitive risk factor. In our study the five year survival was 15% leaving very few patients at risk for developing cardiac disease. Without long-term survivors cardiac toxicity does not seem to be a problem, and this suggests that we should aim to increase tumour control by administrating larger doses of radiotherapy to the tumour and/or by adding concurrent chemotherapy. However, the latter may increase the risk of cardiac toxicity by itself, and the results given in present study, may not be extrapolated to this situation. Another reason might be that if NSCLC patients develop dyspnoea, chest pain, etc. it is interpreted as being due to a relapse of lung cancer and not cardiac disease. There are several studies indicating that

  9. Squamous cell skin cancer

    Science.gov (United States)

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

  10. Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe{sub 2}O{sub 3} nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Yan, S.Y.; Chen, M.M.; Fan, J.G.; Wang, Y.Q.; Hu, Y.; Xu, L.M., E-mail: leiming.xu@aliyun.com.cn, E-mail: huying@sohu.com [Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Du, Y.Q. [Department of Pathology, Cancer Hospital, Fudan University, Shanghai (China)

    2014-11-15

    This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe{sub 2}O{sub 3} nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe{sub 2}O{sub 3} nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe{sub 2}O{sub 3} MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe{sub 2}O{sub 3} MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe{sub 2}O{sub 3} nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (,24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe{sub 2}O{sub 3} MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe{sub 2}O{sub 3} MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells. (author)

  11. The effect of CyberKnife therapy on pulmonary function tests used for treating non-small cell lung cancer: a retrospective, observational cohort pilot study

    International Nuclear Information System (INIS)

    The current standard for treating operable early stage non-small cell lung cancer is surgical resection and for inoperable cases it is external beam radiotherapy. Lung functions are adversely affected with both the above treatments. CyberKnife treatment limits radiation damage by tracking targets moving with each breath. The effect of CyberKnife treatment on pulmonary function tests has not been well documented. Lung cancer patients who underwent CyberKnife treatment and had pre- and post-treatment pulmonary function tests were included. Paired t-tests were conducted. We also conducted subgroup analysis. Thirty-seven patients were included. Median age was 73 years. No statistical difference between mean pre- and post-CyberKnife pulmonary function tests was found. We observed that CyberKnife better preserves lung function status compared to current standards of care. It has shown to have very minimal side effects

  12. Perfusion CT allows prediction of therapy response in non-small cell lung cancer treated with conventional and anti-angiogenic chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Tacelli, Nunzia; Santangelo, Teresa; Remy, Jacques [University of Lille Nord de France, Department of Thoracic Imaging, Hospital Calmette (EA 2694), Lille (France); University of Lille Nord de France, Faculty of Medicine, Henri Warembourg, Lille (France); Scherpereel, Arnaud; Cortot, Alexis; Wallyn, Frederic [University of Lille Nord de France, Faculty of Medicine, Henri Warembourg, Lille (France); University of Lille Nord de France, Department of Pulmonary and Thoracic Oncology, Lille (France); Duhamel, Alain; Deken, Valerie [University of Lille Nord de France, Faculty of Medicine, Henri Warembourg, Lille (France); University of Lille Nord de France, Department of Medical Statistics, Lille (France); Klotz, Ernst [Siemens Healthcare, Computed Tomography Division, Forchheim (Germany); Lafitte, Jean-Jacques [University of Lille Nord de France, Faculty of Medicine, Henri Warembourg, Lille (France); University of Lille Nord de France, Department of Pulmonary and Thoracic Oncology, Lille (France); Pasteur Institute of Lille, INSERM unit 1019, CIIL, Lille (France); Remy-Jardin, Martine [University of Lille Nord de France, Department of Thoracic Imaging, Hospital Calmette (EA 2694), Lille (France); University of Lille Nord de France, Faculty of Medicine, Henri Warembourg, Lille (France); Hospital Calmette, Department of Thoracic Imaging, Lille cedex (France)

    2013-08-15

    To determine whether CT can depict early perfusion changes in lung cancer treated by anti-angiogenic drugs, allowing prediction of response. Patients with non-small cell lung cancer, treated by conventional chemotherapy with (Group 1; n = 17) or without (Group 2; n = 23) anti-vascular endothelial growth factor (anti-VEGF) drug (bevacizumab) underwent CT perfusion before (TIME 0) and after 1 (TIME 1), 3 (TIME 2) and 6 (TIME 3) cycles of chemotherapy. The CT parameters evaluated included: (1) total tumour vascular volume (TVV) and total tumour extravascular flow (TEF); (2) RECIST (Response Evaluation Criteria in Solid Tumours) measurements. Tumour response was also assessed on the basis of the clinicians' overall evaluation. In Group 1, significant reduction in perfusion was identified between baseline and: (1) TIME 1 (TVV, P = 0.0395; TEF, P = 0.015); (2) TIME 2 (TVV, P = 0.0043; TEF, P < 0.0001); (3) TIME 3 (TVV, P = 0.0034; TEF, P = 0.0005) without any significant change in Group 2. In Group 1: (1) the reduction in TVV at TIME 1 was significantly higher in responders versus non-responders at TIME 2 according to RECIST (P = 0.0128) and overall clinicians' evaluation (P = 0.0079); (2) all responders at TIME 2 had a concurrent decrease in TVV and TEF at TIME 1. Perfusion CT demonstrates early changes in lung cancer vascularity under anti-angiogenic chemotherapy that may help predict therapeutic response. (orig.)

  13. Micro-Raman spectroscopy studies of changes in lipid composition in breast and prostate cancer cells treated with MPA and R1881 hormones

    Science.gov (United States)

    Potcoava, Mariana C.; Futia, Gregory L.; Aughenbaugh, Jessica; Schlaepfer, Isabel; Gibson, Emily A.

    2014-03-01

    Increasing interest in the role of lipids in cancer cell proliferation or resistance to drug therapies has motivated the need to develop better tools for cellular lipid analysis. Quantification of lipids in cells is typically done by destructive chromatography protocols that do not provide spatial information on lipid distribution and prevent dynamic live cell studies. Methods that allow the analysis of lipid content in live cells is therefore of great importance for research. Using Raman micro-spectroscopy we investigated whether the female hormone medroxyprogesterone acetate (MPA) and the synthetic androgen R1881 affect the lipid expression in breast (T47D) and prostate (LNCaP) cancer cells. Differences were noted in the spectral regions at 830-1800 cm-1 and 2800-3000 cm-1 when comparing different drug treatments. Significant changes were noticed for saturated (1063 - 1125 cm-1, 1295 cm-1 and 1439 cm-1), unsaturated (1262 cm-1 and 1656 cm-1, and 1720 - 1748 cm-1) chemical bonds, suggesting that the composition of the lipid droplets was changed by the hormone treatments. Also, significant differences were observed in the high frequency regions of lipids and proteins at 2851 cm-1 and around 2890 cm-1. Principal component analysis with Linear Discriminant Analysis (PCA-LDA) of the Raman spectra was able to differentiate between cancer cells that were treated with MPA, R1881 or vehicle (P < 0.05). Future work includes analysis to determine exact lipid composition and concentrations as well as development of clinical techniques to characterize differences in patient tumor lipid profiles to determine response to drug treatment and prognosis.

  14. Development of Hemolytic Anemia in a Nivolumab-Treated Patient with Refractory Metastatic Squamous Cell Skin Cancer and Chronic Lymphatic Leukemia.

    Science.gov (United States)

    Schwab, K S; Heine, A; Weimann, T; Kristiansen, G; Brossart, P

    2016-01-01

    Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications. PMID:27462240

  15. Prognostic role of apoptosis-related gene functional variants in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

    Directory of Open Access Journals (Sweden)

    Tao KY

    2015-01-01

    >T polymorphisms are potential independent prognostic factors in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy. Keywords: lung cancer, FAS −670 A>G, survivin 9386 C>T, polymorphism, chemotherapy response

  16. Motexafin Gadolinium and Doxorubicin in Treating Patients With Advanced Cancer

    Science.gov (United States)

    2015-09-30

    Breast Cancer; Chronic Myeloproliferative Disorders; Colorectal Cancer; Head and Neck Cancer; Leukemia; Lung Cancer; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic/Myeloproliferative Diseases; Prostate Cancer; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  17. Predictive Immunohistochemical Markers Related to Drug Selection for Patients Treated with Sunitinib or Sorafenib for Metastatic Renal Cell Cancer

    Science.gov (United States)

    Ma, Xin; Wang, Lei; Li, Hongzhao; Zhang, Yu; Gao, Yu; Guo, Gang; Liu, Kan; Meng, Qingyu; Zhao, Chaofei; Wang, Dianjun; Song, Zhigang; Zhang, Xu

    2016-01-01

    Targeted drug decisions in metastatic renal cell carcinoma are exclusively made on the basis of clinical criteria. We investigated whether these biomarkers (HIF-1α, HIF-2α, CAIX, VEGF, VEGFR1, VEGFR2, VEGFR3, PDGFB, PDGFRA, PDGFRB, CD31, CD44, bcl-xL, KIT, p21, CXCR4, PTEN, (CSF)-1R, RET, and FLT-3) can predictive the different effects between sunitinib and sorafenib treatments and are available to guide targeted drug selection. We enrolled all patients who underwent nephrectomy with postoperative sunitinib- or sorafenib-treatment at our institution from 2007 to 2012. Immunohistochemical approach was applied to assess the potential differential effects of immunostainings between sunitinib- and sorafenib-treated groups. We found that patients with high HIF-2α, CD31 expression showed greater relative PFS and OS benefit and patients with high CAIX expression presented greater relative OS benefit from sunitinib than from sorafenib, patients with high VEGFR1 or PDGFRB expression levels exhibited worse relative PFS benefit from sunitinib than from sorafenib. Namely high HIF-2α, CD31, and CAIX expression levels along with low VEGFR1 and PDGFRB expression levels improved the benefit of sunitinib treatment compared with sorafenib treatment. These results can identify whether patients can benefit more from sunitinib or sorafenib for drug selection guidance, eventually with precision medicine. PMID:27488093

  18. Association of GWAS-identified lung cancer susceptibility loci with survival length in patients with small-cell lung cancer treated with platinum-based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Dong Li

    Full Text Available Genetic variants have been shown to affect length of survival in cancer patients. This study explored the association between lung cancer susceptibility loci tagged by single-nucleotide polymorphisms (SNPs identified in the genome-wide association studies and length of survival in small-cell lung cancer (SCLC. Eighteen SNPs were genotyped among 874 SCLC patients and Cox proportional hazards regression was used to examine the effects of genotype on survival length under an additive model with age, sex, smoking status and clinical stage as covariates. We identified 3 loci, 20q13.2 (rs4809957G >A, 22q12.2 (rs36600C >T and 5p15.33 (rs401681C >T, significantly associated with the survival time of SCLC patients. The adjusted hazard ratio (HR for patients with the rs4809957 GA or AA genotype was 0.80 (95% CI, 0.66-0.96; P = 0.0187 and 0.73 (95% CI, 0.55-0.96; P = 0.0263 compared with the GG genotype. Using the dominant model, the adjusted HR for patients carrying at least one T allele at rs36600 or rs401681 was 0.78 (95% CI, 0.63-0.96; P = 0.0199 and 1.29 (95% CI, 1.08-1.55; P = 0.0047, respectively, compared with the CC genotype. Stratification analyses showed that the significant associations of these 3 loci were only seen in smokers and male patients. The rs4809957 SNP was only significantly associated with length of survival of patients with extensive-stage but not limited-stage tumor. These results suggest that some of the lung cancer susceptibility loci might also affect the prognosis of SCLC.

  19. ATM Polymorphisms Predict Severe Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Huihua [Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan (China); Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Zhensheng [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Xu, Ting [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Qiming; Liu, Hongliang [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Komaki, Ritsuko; Gomez, Daniel [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Li-E [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Qingyi, E-mail: qwei@mdanderson.org [Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-03-15

    Purpose: The ataxia telangiectasia mutated (ATM) gene mediates detection and repair of DNA damage. We investigated associations between ATM polymorphisms and severe radiation-induced pneumonitis (RP). Methods and Materials: We genotyped 3 potentially functional single nucleotide polymorphisms (SNPs) of ATM (rs1801516 [D1853N/5557G>A], rs189037 [-111G>A] and rs228590) in 362 patients with non-small cell lung cancer (NSCLC), who received definitive (chemo)radiation therapy. The cumulative severe RP probabilities by genotypes were evaluated using the Kaplan-Meier analysis. The associations between severe RP risk and genotypes were assessed by both logistic regression analysis and Cox proportional hazard model with time to event considered. Results: Of 362 patients (72.4% of non-Hispanic whites), 56 (15.5%) experienced grade ≥3 RP. Patients carrying ATM rs189037 AG/GG or rs228590 TT/CT genotypes or rs189037G/rs228590T/rs1801516G (G-T-G) haplotype had a lower risk of severe RP (rs189037: GG/AG vs AA, adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI], 0.29-0.83, P=.009; rs228590: TT/CT vs CC, HR=0.57, 95% CI, 0.33-0.97, P=.036; haplotype: G-T-G vs A-C-G, HR=0.52, 95% CI, 0.35-0.79, P=.002). Such positive findings remained in non-Hispanic whites. Conclusions: ATM polymorphisms may serve as biomarkers for susceptibility to severe RP in non-Hispanic whites. Large prospective studies are required to confirm our findings.

  20. Analysis of long-term survival in patients treated with three-dimensional conformal radiotherapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the prognostic factors of locally advanced non-small cell lung cancer (LA-NSCLC) treated with three dimensional conformal radiation therapy (3D CRT). Methods: In 106 patients with stage IIIa/IIIb NSCLC treated with 3DCRT from Nov 2000 to Mar 2004, 46 of them were treated with radiotherapy alone, 41 by concurrent chemoradiation, and 19 by sequential chemoradiation. The influence of related prognostic factors on survival was evaluated by univariate and multivariate analysis. The treatment outcome was analyzed by prognostic index model. Results: The 1-, 3- and 5- year overall survival rate was 50.0%, 22.2% and 15.5%, respectively, and the median survival time was 12 months. The univariate analysis showed that the following factors were significantly associated with the longer survival: female, good kamofsky performance status (KPS), squamous cell carcinoma, absence of supraclavicular lymph nodes, no smoking history, hemoglobin ≥130 g/L before treatment, N stage, the maximum diameter of tumor ≤5 cm, the volume of tumor ≤90 cm3, GTV ≤150 cm3 and the radiotherapy efficacy. However, multivariate analysis revealed that no smoking history, hemoglobin ≥130 g/L and GTV ≤150 cm3 were the independent risk factors for predicting the survival. Conclusions: Three dimensional conformal radiation therapy could be effective in the treatment of locally advanced NSCLC. No smoking history, hemoglobin ≥130 g/L and GTV ≤150 cm3 might be the independent risk factors for predicting the survival. Prognostic index model could improve the potential of multivariate analysis in predicting the survival of patients treated with radiotherapy for NSCLC. (authors)

  1. Incidence and patterns of isolated brain failure in stage III non-small-cell lung cancer treated with concurrent chemoradiation therapy

    International Nuclear Information System (INIS)

    The incidence and patterns of isolated brain failure was examined in patients with stage III non-small-cell lung cancer (NSCLC) treated with concurrent chemoradiation (CCRT). Between 1996 and 2003, a total of 68 patients with stage III NSCLC were treated with radical CCRT. Among them, 63 patients were evaluable. Radiation therapy with a mean total dose of 61.4 Gy and chemotherapy (typically platinum-based) were administered concurrently. Other than locoregional failure, isolated brain failure was the most common failure pattern as the initial failure, occurring 2-37 months (median 6.5 months) after radical CCRT. The isolated brain failure rates as the initial failure at 1, 3, and 4 years were 9%, 13%, and 25%, respectively. Isolated brain failure as the initial failure occurred more frequently in T4 cases (39% at 4 years) compared to T1-3 cases (14% at 4 years) in our series (P=0.0099). Except for locoregional failure, isolated brain failure was the most common initial failure pattern of stage III NSCLCs treated with radical CCRT. Isolated brain failure as the initial failure occurred even after 3 years. Isolated brain failure as the initial failure occurred more frequently in T4 cases than in T1-3 cases. (author)

  2. The prognostic impact of soluble and vesicular HLA-G and its relationship to circulating tumor cells in neoadjuvant treated breast cancer patients.

    Science.gov (United States)

    König, Lisa; Kasimir-Bauer, Sabine; Hoffmann, Oliver; Bittner, Ann-Kathrin; Wagner, Bettina; Manvailer, Luis Felipe Santos; Schramm, Sabine; Bankfalvi, Agnes; Giebel, Bernd; Kimmig, Rainer; Horn, Peter A; Rebmann, Vera

    2016-09-01

    The non-classical human leukocyte antigen G (HLA-G) molecule and its soluble forms exert multiple immune suppressive regulatory functions in malignancy and in stem cells contributing to immune escape mechanisms. HLA-G can be secreted as free soluble HLA-G molecules or via extracellular vesicles (EVs). Here we evaluated these soluble HLA-G forms as prognostic marker for prediction of the clinical outcome of neoadjuvant chemotherapy (NACT) treated breast cancer (BC) patients. Plasma samples of BC patients procured before (n=142) and after (n=154) NACT were quantified for total soluble HLA-G (sHLA-Gtot) and HLA-G levels in ExoQuick™ derived EV fractions (sHLA-GEV) by ELISA. The corresponding increments were specified as free sHLA-G (sHLA-Gfree). Total and free sHLA-G were significantly increased in NACT treated BC patients compared to healthy controls (n=16). High sHLA-Gfree levels were exclusively associated to estrogen receptor expression before NACT. Importantly, high sHLA-GEV levels before NACT were related to disease progression and the detection of stem cell-like circulating tumor cells, but high sHLA-Gfree levels indicated an improved clinical outcome. Thus, this study demonstrates for the first time that the different sHLA-G subcomponents represent dissimilar qualitative prognostic impacts on the clinical outcome of NACT treated BC patients, whereas the total sHLA-G levels without separating into subcomponents are not related to clinical outcome.

  3. Effects of EGFR Gene Polymorphisms on Efficacy and Prognosis 
in Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs

    Directory of Open Access Journals (Sweden)

    Liangshan DA

    2013-03-01

    Full Text Available An increasing number of patients with advanced non-small cell lung cancer (NSCLC have been treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs. However, significant differences in response to EGFR-TKIs have been shown among advanced NSCLC patients. Recently, selection of patients was mainly based on EGFR gene mutation detection. Nevertheless, mutation detection is often limited by tumour tissues derivation, technique complexity, high cost, and so on. It is urgent to seek other biological markers to predict efficacy of EGFR-TKIs. Many studies have founded that the EGFR gene polymorphisms are also associated with clinical outcome and prognosis in treatment of advanced NSCLC with EGFR-TKIs. Here, we presented a review discussing the correlation between EGFR gene polymorphisms and the efficacy of EGFR-TKIs in advanced NSCLC.

  4. Analysis of 41 Cases of Primary Hypervascular Non-small Cell Lung Cancer Treated with Embolization of Emulsion of Chemotherapeutics and Iodized Oil

    Directory of Open Access Journals (Sweden)

    Yunzhi ZHOU

    2010-05-01

    Full Text Available Background and objective Transcatheter arterial chemotherapy and embolization is the main method in the treatment of lung cancer, but most of the reports do not study individually to small cell lung cancer (SCLC, non-small cell lung cancer (NSCLC, hypovascular and hypervascular lung cancer. The pre-embolization perfusion of hemotherapeutics is still being used routinely and seldom report to iodized oil embolization. The article summarized the quality of life after the treatment, clinical efficiency, survival time and complications to evaluate the clinical effect of primary hypervascular NSCLC treated with embolization of emulsion of chemotherapeutics and iodized oil. Methods The study totally analyzed 41 cases which confirmed by pathology and follow up study from January, 2008 to January 2009. The CT scan with IV contrast demonstrates over moderate enhanced lesion which indicate hypervascular. Within the 41 cases, 23 cases of central, 18 cases of peripheral. Suqamous carcinoma 21 cases, adenocarcinoma 15 cases and squamoadenocarcinoma 5 cases. Stage IIIb 34 cases, stage IV 7 cases. Superselective incubation with microcatheter under DSA, to embolize the capillary bed with liquefied iodized oil and the emulsion of pharmorubicin, to embolize the supply artery of the tumor with gelatin foam microparticle. The liquefied iodized oil 5 mL-10 mL, pharmorubicin 10 mg-30 mg. The longest follow up is 12 months and to compare with the references of 2007-2009. Results The KPS is widely acclaimed after the treatment (P < 0.05, no complete response (CR, 31 cases of partial response (PR, 7 cases of no change (NC and 3 cases of progressive disease (PD, the total efficiency (CR+PR is 75.6%. The clinical efficiency (CR+PR+NC is 92.68%. 33 cases of total survival tome over 12 months (80.48%, IIIb stage 29/34 (85.29%, IV stage 4/7 (57.14%. 1 case with severe complication-spinal injury. Conclusion To treat primary hypervascular NSCLC with simple embolization of

  5. Treating Cancer with Strong Magnetic Fields and Ultrasound

    CERN Document Server

    Winterberg, Dr Friedwardt

    2009-01-01

    It is proposed to treat cancer by the combination of a strong magnetic field with intense ultrasound. At the low electrical conductivity of tissue the magnetic field is not frozen into the tissue, and oscillates against the tissue which is brought into rapid oscillation by the ultrasound. As a result, a rapidly oscillating electric field is induced in the tissue, strong enough to disrupt cancer cell replication. Unlike radio frequency waves, which have been proposed for this purpose, ultrasound can be easily focused onto the regions to be treated. This method has the potential for the complete eradication of the tumor.

  6. GENE TECHNOLOGY: A NEW WAY TO TREAT CANCER

    Directory of Open Access Journals (Sweden)

    Prajapati P M.

    2012-06-01

    Full Text Available Gene therapy is the process of introducing genetic material RNA or DNA into a person's cells to fight disease. Gene therapy treats disease by either replacing damaged or missing genes with normal ones, or by providing new genes. The concept of gene therapy was born more than thirty years ago; however, new technology is opening the door to dramatically new possibilities in the treatment of cancers of all kinds. The long-term goal of cancer gene therapy is to develop treatments that attack only cancer cells, thereby eliminating adverse effects on the body and improving the possibility to cure disease. Gene therapy may someday soon make cancer a manageable disease with nominal side effects to the patients. Furthermore, since gene therapy has potential for other diseases such as cystic fibrosis, hemophilia, sickle-cell anemia, muscular dystrophy and Parkinson's, the value of research and discovery has broad applications.

  7. Variations in Cell Surfaces of Estrogen Treated Breast Cancer Cells Detected by A Combined Instrument for Far-Field and Near-Field Microscopy

    Directory of Open Access Journals (Sweden)

    P. Perner

    2002-01-01

    Full Text Available The response of single breast cancer cells (cell line T‐47D to 17β‐estradiol (E2 under different concentrations was studied by using an instrument that allows to combine far‐field light microscopy with high resolution scanning near‐field (AFM/SNOM microscopy on the same cell. Different concentrations of E2 induce clearly different effects as well on cellular shape (in classical bright‐field imaging as on surface topography (atomic force imaging and absorbance (near‐field light transmission imaging. The differences range from a polygonal shape at zero via a roughly spherical shape at physiological up to a spindle‐like shape at un‐physiologically high concentrations. The surface topography of untreated control cells was found to be regular and smooth with small overall height modulations. At physiological E2 concentrations the surfaces became increasingly jagged as detected by an increase in membrane height. After application of the un‐physiological high E2 concentration the cell surface structures appeared to be smoother again with an irregular fine structure. The general behaviour of dose dependent differences was also found in the near‐field light transmission images. In order to quantify the treatment effects, line scans through the normalised topography images were drawn and a rate of co‐localisation between high topography and high transmission areas was calculated. The cell biological aspects of these observations are, so far, not studied in detail but measurements on single cells offer new perspectives to be empirically used in diagnosis and therapy control of breast cancers.

  8. Effect of Amifostine on Locally Advanced Non-small Cell Lung Cancer Patients Treated with Radiotherapy: A Meta-analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Shengye WANG

    2012-09-01

    Full Text Available Background and objective Controversy exists on whether amifostine can reduce the efficacy and decrease the side effects of non-small cell lung cancer (NSCLC treated by radiotherapy. The aim of this meta-analysis is to evaluate the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy. Methods Open published randomized controlled trials on the efficacy and side effects of amifostine in NSCLC patients treated with radiotherapy were collected from Medline, Cochrane Central Register of Controlled Trials, EMBSE, CBM, CNKI, WANFANG, American Society of Clinical Oncology, and European Society of Medical Oncology databases. The pooled efficacy and side effects of amifostine in these patients were calculated using the statistics software Stata 11.0. Results Nine trials that included 769 (381 and 388 in each arm patients were analyzed. The pooled relative risk of complete, partial, and objective responses were 1.16 (95%CI: 0.90-1.50, Z=1.07, P=0.29, 1.02 (95%CI: 0.87-1.19, Z=0.21, P=0.83 and 1.06 (95%CI: 0.97-1.17, Z=1.31, P=0.20, respectively. The side effects in seven trials including 738 (367 and 371 in each arm patients were analyzed. The pooled relative risk of developing grades 3 to 4 esophagitis and pneumonitis were 0.51 (95%CI: 0.37-0.72, Z=3.88, P<0.001 and 0.51 (95%CI: 0.26-0.99, Z=1.98, P=0.04, respectively. Conclusion Amifostine can significantly decrease the risk of developing serious esophagitis and pneumonitis without reducing the response rate in NSCLC patients treated by radiotherapy.

  9. Clinical Observation on 271 Cases of Non-Small Cell Lung Cancer Treated with Yifei Kangliu Yin (益肺抗瘤饮)

    Institute of Scientific and Technical Information of China (English)

    刘嘉湘; 施志明; 李和根; 徐振晔; 朱晏伟; 赵丽红; 高虹; 刘苓霜; 朱惠蓉; 张晖

    2001-01-01

    To observe the effects of Yifei Kangliu Yin(YFKLY) in treating non-small cell lung cancer (NSCLC). Methods:Two hundred and seventy-one patients with NSCLC were randomly divided into three groups, Group A treated only by YFKLY, Group B treated by the combination of YFKLY and chemotherapy, and Group C treated only by chemotherapy as the control group for control. Results: (1) Of the 127 cases in Group A, 1 case got complete remission (CR), 13 got partial remission (PR), 89 had no change (NC), and 24 had progression of disease (PD), thus CR+PR+NC accounting for 81.10%; of the 80 patients in Group B, 17 got PR , 53 got NC, 10 got PD, PR+NC accounting for 87.50%; of the 64 cases of chemotherapy group, 7 cases got PR, 39 cases got NC, 18 cases got PD, PR+NC accounting for 71.88% (P<0.01). (2) The metastasis rate was 23.52% in Group A, 20.00% in Group B and 35.71% in Group C respectively after treatment. (3) The 1-, 2-, 3- and 4-year survival rate were 73.09%, 32.01%, 13.18% and 13.18% in Group A, 71.85%, 46.35%, 29.19% and 23.35% in Group B and 37.61%, 13.67%, 9.7% and 0% in Group C. The symptoms were improved, and Karnofsky score was elevated in Group A and B. Conclusion: YFKLY could increase survival rate and quality of life, decrease metastasis rate, and enhance the immune function in NSCLC patients.

  10. Risk factors for radiation induced lung toxicity in locally advanced non-small cell lung cancer treated with three-dimensional radiotherapy

    International Nuclear Information System (INIS)

    Objective: To investigate the patient and treatment related predictors for the development of radiation induced lung toxicity (RILT) in patients with locally advanced non-small cell lung cancer (NSCLC) receiving definitive three-dimensional radiotherapy. Methods: Data were retrospectively collected from inoperable or unresectable 253 patients with stage III NSCLC treated with definitive three-dimensional radiotherapy between January 2001 and April 2007. National cancer institute common toxicity criteria version 3.0 was employed to evaluate the classification of RILT and grade ≥2 toxicity served as the endpoint. The correlation between RILT and aforementioned factors was analyzed. Results: The grade ≥ 2 RILT was 26.5%. Univariate analysis showed age, FEV1%, DLCO%, contralateral lung (CL) V5 -V15, ipsilateral lung (IL) V5 -V40, total lung (TL) V5 -V50, IL and TL mean lung dose (MLD) were significantly correlated with the development of RILT (χ2 =4.46 - 23.99, P = 0.000 - 0.035). Multivariate analysis showed TL MLD >17.5 Gy and FEV1% ≥72% were significantly correlated with the development of RILT (χ2 = 17.49, 9.30, P = 0.000, 0.002). Patients were stratified into four groups according to MLD and FEV1%, corresponding to the RILT incidence of 9.3%, 24.7%, 38.5% and 63.6%, respectively (χ2 =25.27, P = 0.000). Conclusions: TL MLD and baseline FEV1% are significant factors correlated with the development of RILT in NSCLC patients treated with three-dimensional radiation therapy. The combination of TL MLD and FEV1% may help classify NSCLC patients per risk of RILT and subsequently direct risk-adaptive radiation therapy. Poor baseline pulmonary function does not increase the risk of RILT and may even be associated with lower RILT probability, which has yet to be validated in larger patient cohorts. (authors)

  11. Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

    Science.gov (United States)

    Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

    2015-10-01

    Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.

  12. Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Sharon R. Pine

    2008-01-01

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

  13. Cell phones and cancer

    Science.gov (United States)

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

  14. The survival outcomes and prognosis of stage IV non-small-cell lung cancer treated with thoracic three-dimensional radiotherapy combined with chemotherapy

    International Nuclear Information System (INIS)

    The impact of thoracic three-dimensional radiotherapy on the prognosis for stage IV non-small-cell lung cancer is unclear. This study is to investigate survival outcomes and prognosis in patients with stage IV non-small cell lung cancer (NSCLC) treated with thoracic three-dimensional radiotherapy and systemic chemotherapy. Ninety three patients with stage IV NSCLC had received at least four cycles of chemotherapy and thoracic three-dimensional radiotherapy of ≥40 Gy on primary tumors. The data from these patients were retrospectively analyzed. Of the 93 patients, the median survival time (MST) was 14.0 months, and the 1, 2, and 3-year survival rates were 54.8%, 20.4%, and 12.9%, respectively. The MST of patients received radiation dose to primary tumor ≥63Gy and <63 Gy for primary tumor were 15.0 and 8.0 months, respectively (P = 0.001). Patients had metastasis to a single site and lower tumor volume (<170 cm3) also produced longer overall survival time (P = 0.002, P = 0.020, respectively). For patients with metastasis at a single site, thoracic radiation dose ≥63 Gy remained a prognostic factor for better overall survival (P = 0.030); patients with metastases at multiple sites, radiation dose ≥63 Gy had a trend to improve overall survival (P = 0.062). A multivariate analysis showed that radiation dose ≥63 Gy (P = 0.017) and metastasis to a single site (P = 0.038) are associated with better overall survival, and the volume of primary tumor was marginally correlated with OS (P = 0.054). In combination with systemic chemotherapy, radiation dose ≥63 Gy on primary tumor and metastasis to a single site are significant factors for better OS, aggressive thoracic radiotherapy may have an important role in improving OS

  15. Donor Lymphocyte Infusion in Treating Patients With Persistent, Relapsed, or Progressing Cancer After Donor Hematopoietic Cell Transplant

    Science.gov (United States)

    2016-07-25

    Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma

  16. The influence of TLR4 agonist lipopolysaccharides on hepatocellular carcinoma cells and the feasibility of its application in treating liver cancer

    Directory of Open Access Journals (Sweden)

    Gu J

    2015-08-01

    Full Text Available Junsheng Gu, Ranran Sun, Shen Shen, Zujiang Yu Department of Infectious Diseases, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Objective: This study was designed to explore the influence of Toll-like receptor 4 (TLR4 agonist lipopolysaccharides (LPS on liver cancer cell and the feasibility to perform liver cancer adjuvant therapy. Methods: Human liver cancer cell lines HepG2, H7402, and PLC/PRF/5 were taken as models, and the expression of TLRs mRNA was detected by real time-polymerase chain reaction method semiquantitatively. WST-1 method was used to detect the influence of LPS on the proliferation ability of liver cancer cells; propidium iodide (PI single staining and Annexin V/PI double staining were used to test the influence of LPS on the cell cycle and apoptosis, respectively, on human liver cancer cell line H7402. Fluorescent quantitative polymerase chain reaction and Western blot method were used to determine the change of expression of Cyclin D1. Results: The results demonstrated that most TLRs were expressed in liver cancer cells; stimulating TLR4 by LPS could upregulate TLR4 mRNA and the protein level, activate NF-κB signaling pathway downstream of TLR4, and mediate the generation of inflammatory factors IL-6, IL-8, and TNF-α; LPS was found to be able to strengthen the proliferation ability of liver cancer cells, especially H7402 cells; the expression of Cyclin D1 rose and H7402 cells were promoted to transit from G1 stage to S stage under the stimulation of LPS, but cell apoptosis was not affected. It was also found that LPS was able to activate signal transducer and activator of transcription -3 (STAT3 signaling pathway in H7402 cells and meanwhile significantly increase the initiation activity of STAT3; proliferation promoting effect of LPS to liver cancer cells remarkably lowered once STAT3 was blocked or inhibited. Conclusion: Thus, TLR4 agonist LPS is proved to be able to

  17. Technical challenges of sparing infrahyoid swallowing organs at risk in oropharynx squamous cell cancer treated with IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Morley, Lyndon, E-mail: lyndon.morley@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Tsang, Shirley W.S. [Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Breen, Stephen L.; Waldron, John N. [Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Maganti, Manjula; Pintilie, Melania [Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Dawson, Laura A.; Ringash, Jolie [Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Huang, Shao Hui [Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Kim, John [Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

    2014-07-01

    This study reports clinical performance in the sparing of infrahyoid swallowing organs at risk (SWOARs) in oropharynx cancer intensity-modulated radiation therapy (IMRT) plans. Rates of meeting dose-volume planning goals are reported and compared with geometry-based estimates of what is achievable. This study also develops 3 measures of target-SWOAR geometry and tests their usefulness in providing geometry-based dose-volume planning goals. A total of 50 oropharynx cancer IMRT plans were reviewed. Success rates in meeting institutional dose-volume goals were determined for the glottic larynx (G), postcricoid pharynx (P), and esophagus (E). The following 3 measures of target-SWOAR geometry were investigated as methods of identifying geometry-based planning goals: presence of gross disease in neck levels 3 to 4, target-SWOAR overlap, and a 3-dimensional (3D) measure of target-SWOAR geometry. Locally advanced disease was predominant in this patient population with target volumes overlapping SWOARs in 68% to 98% of cases. Clinical rates of success in meeting dose-volume goals varied by SWOAR (16% to 82%) but compared well with estimated potentially achievable rates in most cases (14% average difference between clinical and potential). Cases grouped by the presence of levels 3 to 4 neck nodes or target-SWOAR overlap did not have significantly different SWOAR doses. Cases grouped using a 3D measure of target-SWOAR geometry differed significantly, providing useful geometry-based planning goals (e.g., mean Glottis dose <45 Gy was achieved 19%, 44%, or 81% of the time in each of 3 groups). This study describes the technical challenge of sparing SWOARs and investigates several potential methods for grouping cases to assist with treatment plan evaluation. Quantifying the 3-D relationship between the targets and SWOARs is a promising way of approaching this complex problem. Data presented in this paper may be useful to evaluate treatment plans using objective geometry

  18. Cancer Stem Cells

    OpenAIRE

    Katarzyna Wieczorek; Jolanta Niewiarowska

    2008-01-01

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

  19. Feasibility of omitting clinical target volume for limited-disease small cell lung cancer treated with chemotherapy and intensity-modulated radiotherapy

    International Nuclear Information System (INIS)

    To analyze the feasibility of omitting clinical target volume (CTV) for limited small cell lung cancer treated with chemotherapy and intensity modulated radiotherapy. 89 patients were treated from January 1, 2008 to August 31, 2011, 54 cases were irradiated with target volume without CTV, and 35 cases were irradiated with CTV. Both arms were irradiated post chemotherapy tumor extent and omitted elective nodal irradiation; dose prescription was 95% PTV56-63 Gy/28-35 F/5.6-7 weeks. In the arm without CTV and arm with CTV, the local relapse rates were 16.7% and 17.1% (p = 0.586) respectively. In the arm without CTV, of the 9 patients with local relapse, 6 recurred in-field, 2 recurred in margin, 1 recurred out of field. In the arm with CTV, of the 6 patients with local relapse, 4 recurred in-field, 1 recurred in margin, 1 recurred out of field. The distant metastases rates were 42.6% and 51.4% (p = 0.274) respectively. Grade 3-4 hematological toxicity and radiation esophagitis had no statistically significant, but grade 3-4 radiation pneumonia was observed in only 7.4% in the arm without CTV, compared 22.9% in the arm with CTV (p = 0.040). The median survival in the arm without CTV had not reached, compared with 38 months in the with CTV arm. The l- years, 2- years, 3- years survival rates of the arm without CTV and the arm with CTV were 81.0%, 66.2%, 61.5% and 88.6%, 61.7%, 56.6% (p = 0.517). The multivariate analysis indicated that the distant metastases (p = 0.000) and PCI factor (p = 0.004) were significantly related to overall survival. Target delineation omitting CTV for limited-disease small cell lung cancer received IMRT was feasible. The distant metastases and PCI factor were significantly related to overall survival

  20. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

    DEFF Research Database (Denmark)

    Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek;

    2010-01-01

    To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

  1. Exploiting replicative stress to treat cancer

    DEFF Research Database (Denmark)

    Dobbelstein, Matthias; Sørensen, Claus Storgaard

    2015-01-01

    DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms...

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

    Institute of Scientific and Technical Information of China (English)

    Guanghui Li; Donglin Wang

    2005-01-01

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

  3. Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

    Science.gov (United States)

    2016-02-15

    Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  4. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non–small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1–4 N2–3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients’ conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07–0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06–1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11–4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33–1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38–1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58–1.61]), and tumor size (HR: 1.04 [CI: 0.94–1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic

  5. The Impact of Extent and Location of Mediastinal Lymph Node Involvement on Survival in Stage III Non-Small Cell Lung Cancer Patients Treated With Definitive Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Annemarie T. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Mitra, Nandita [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA (United States); Xanthopoulos, Eric [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States); Evans, Tracey; Stevenson, James; Langer, Corey [Department of Medical Oncology, University of Pennsylvania, Philadelphia, PA (United States); Kucharczuk, John C. [Department of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA (United States); Lin, Lilie; Rengan, Ramesh [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA (United States)

    2012-05-01

    Purpose: Several surgical series have identified subcarinal, contralateral, and multilevel nodal involvement as predictors of poor overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive resection. This retrospective study evaluates the impact of extent and location of mediastinal lymph node (LN) involvement on survival in patients with Stage III NSCLC treated with definitive radiotherapy. Methods and Materials: We analyzed 106 consecutive patients with T1-4 N2-3 Stage III NSCLC treated with definitive radiotherapy at University of Pennsylvania between January 2003 and February 2009. For this analysis, mediastinal LN stations were divided into four mutually exclusive groups: supraclavicular, ipsilateral mediastinum, contralateral mediastinum, and subcarinal. Patients' conditions were then analyzed according to the extent of involvement and location of mediastinal LN stations. Results: The majority (88%) of patients received sequential or concurrent chemotherapy. The median follow-up time for survivors was 32.6 months. By multivariable Cox modeling, chemotherapy use (hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63]) was associated with improved overall survival. Increasing primary tumor [18F]-fluoro-2-deoxy-glucose avidity (HR: 1.11 [CI: 1.06-1.19]), and subcarinal involvement (HR: 2.29 [CI: 1.11-4.73]) were significant negative predictors of overall survival. On univariate analysis, contralateral nodal involvement (HR: 0.70 [CI: 0.33-1.47]), supraclavicular nodal involvement (HR: 0.78 [CI: 0.38-1.67]), multilevel nodal involvement (HR: 0.97 [CI: 0.58-1.61]), and tumor size (HR: 1.04 [CI: 0.94-1.14]) did not predict for overall survival. Patients with subcarinal involvement also had lower rates of 2-year nodal control (51.2% vs. 74.9%, p = 0.047) and 2-year distant control (28.4% vs. 61.2%, p = 0.043). Conclusions: These data suggest that the factors that determine oncologic outcome in Stage III

  6. Lung Cancer Stem Cells

    OpenAIRE

    Pine, Sharon R.; Blair Marshall; Lyuba Varticovski

    2008-01-01

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

  7. Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation

    International Nuclear Information System (INIS)

    Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT) followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients. We reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed. Median Progression-free survival (PFS) and Overall survival (OS) were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1- and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; p= 0.038). Patients with NSCLC and brain metastasis might benefit from treatment with WBRT and concurrent thoracic chemoradiotherapy. The subgroup of N0-N1 patients appears to achieve the greatest benefit. The result of this study warrants a prospective trial to confirm the benefit of this treatment

  8. Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy.

    Science.gov (United States)

    Valdes, Gilmer; Solberg, Timothy D; Heskel, Marina; Ungar, Lyle; Simone, Charles B

    2016-08-21

    To develop a patient-specific 'big data' clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm. PMID:27461154

  9. Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

    Science.gov (United States)

    Valdes, Gilmer; Solberg, Timothy D.; Heskel, Marina; Ungar, Lyle; Simone, Charles B., II

    2016-08-01

    To develop a patient-specific ‘big data’ clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm.

  10. Early treatment volume reduction rate as a prognostic factor in patients treated with chemoradiotherapy for limited stage small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo Hwan; Lee, Jeong Shin; Lee, Chang Geol; Cho, Jae Ho [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Choi, Jin Hyun; Kim, Jun Won [Dept. of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC). We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%). With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group. ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT.

  11. Anti-angiogenic-specific adverse events in patients with non-small cell lung cancer treated with nintedanib and docetaxel

    DEFF Research Database (Denmark)

    Reck, Martin; Mellemgaard, Anders; von Pawel, Joachim;

    2015-01-01

    were evaluated in all patients who received at least one dose of study medication (N=1307) and for the two main histologies: adenocarcinoma (n=653) and squamous cell carcinoma (SCC; n=553). AEs of special interest were analyzed by category, preferred term, and worst CTCAE grade and included perforation......OBJECTIVES: LUME-Lung 1 was a randomized, placebo-controlled, Phase III trial investigating nintedanib+docetaxel versus placebo+docetaxel in patients with advanced NSCLC progressing after first-line chemotherapy. Progression-free survival was significantly improved with nintedanib......, hypertension, bleeding, thromboembolic events, and skin disorders. RESULTS AND CONCLUSION: The incidence of patients with all-grade gastrointestinal (GI) perforations was low and balanced between arms (0.5% in both) and across histologies; the incidence of non-GI perforations was 1.2% with nintedanib...

  12. Three-year disease-free survivors of small cell lung cancer treated with combination chemotherapy with or without chest irradiation

    International Nuclear Information System (INIS)

    One hundred and seventy-four patients with small cell lung cancer (SCLC) treated with combination chemotherapy radiation, were analyzed. Fourteen patients (8%) survived for 3 years or more. Three-year disease-free survival continued for 12 of the 101 patients (12%) with limited disease, and one of 75 (1%) with extensive disease (P<0.05). Patients' sex and performance status were not important in achieving long-term survival. All disease-free survivors, except two who could not be evaluated, achieved a complete response. Although treatment had some influence on long-term survival rates (P<0.05), thoracic radiation did not have significant impact on long-term survival. Three of the 13 patients (23%) developed second malignancies and died; one of these patients also suffered from a progressive neurologic deterioration with dementia. Two other patients died free of SCLC. Eight have remained alive and free of disease. The last relapse was observed at 1.5 years from beginning of treatment. (author)

  13. Indium In 111 Pentetreotide in Treating Patients With Refractory Cancer

    Science.gov (United States)

    2014-07-01

    Brain and Central Nervous System Tumors; Childhood Langerhans Cell Histiocytosis; Gastrointestinal Carcinoid Tumor; Head and Neck Cancer; Intraocular Melanoma; Islet Cell Tumor; Kidney Cancer; Lung Cancer; Melanoma (Skin); Neoplastic Syndrome; Neuroendocrine Carcinoma of the Skin; Pheochromocytoma

  14. Breast cancer stem cells

    OpenAIRE

    Owens, Thomas W.; Naylor, Matthew J.

    2013-01-01

    Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumors are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs). Understanding how CSCs form and how they contribute to th...

  15. A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non-small-cell Lung Cancer Treated with HangAm-Plus

    Directory of Open Access Journals (Sweden)

    Bang Sun-Hwi

    2012-06-01

    Full Text Available Background and Objectives: Non-small-cell lung cancer (NSCLC represents approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis, most patients have advanced to unresectable disease with a very poor prognosis. The oriental herbal medicine HangAm-Plus (HAP has been developed for antitumor purposes, and several previous studies have reported its therapeutic effects. In this study, the efficacy of HAP was evaluated as a third-line treatment for advanced-stage IIIb/IV NSCLC. Methods: The study involved six patients treated at the East- West Cancer Center (EWCC from April 2010 to October 2011. Inoperable advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a daily basis over a 12-week period. Computed tomography (CT scans were obtained from the patients at the time of the initial administration and after 12 weeks of treatment. We observed and analyzed the patients overall survival (OS and progression-free survival (PFS. Results: Of the six patients, three expired during the study, and the three remaining patients were alive as of October 31, 2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment, three patients showed stable disease (SD, and the other three showed progressive disease (PD. The PFS of patients ranged from 88 to 512 days, the median PFS being 96 days. Longer OS and PFS were correlated with SD. Although not directly comparable, the OS and the PFS of this study were greater than those of the docetaxel or the best supportive care group in other studies. Conclusion: HAP may prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without significant adverse effects. In the future, more controlled clinical trials with larger samples from multi-centers should be conducted to evaluate the efficacy and the safety of HAP.

  16. Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

    Science.gov (United States)

    2011-07-08

    Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Inflammatory Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer

  17. Potential advantages of CUDC-101, a multitargeted HDAC, EGFR, and HER2 inhibitor, in treating drug resistance and preventing cancer cell migration and invasion.

    Science.gov (United States)

    Wang, Jing; Pursell, Natalie W; Samson, Maria Elena S; Atoyan, Ruzanna; Ma, Anna W; Selmi, Abdelkader; Xu, Wanlu; Cai, Xiong; Voi, Maurizio; Savagner, Pierre; Lai, Cheng-Jung

    2013-06-01

    CUDC-101 is a novel, small-molecule, anticancer agent targeting histone deacetylase (HDAC), EGF receptor (EGFR), and HER2. It is currently in phase I clinical development in patients with solid tumors. Previously, we reported that CUDC-101 has potent antiproliferative and proapoptotic activity in cultured tumor cells and in vivo xenograft models. We now show that cancer cells that have acquired resistance to single-target EGFR inhibitors through upregulation of AXL or loss of E-cadherin remain sensitive to CUDC-101, which inhibits MET- and AXL-mediated signaling, restores E-cadherin expression, and reduces cell migration. CUDC-101 also efficiently inhibited the proliferation of MET-overexpressing non-small cell lung cancer and gastric cancer cell lines and inhibited the migration and invasion of invasive tumor cells. Taken together, these results suggest that coupling HDAC and HER2 inhibitory activities to an EGFR inhibitor may potentially be effective in overcoming drug resistance and preventing cancer cell migration.

  18. Liver Cancer Stem Cells

    OpenAIRE

    Sameh Mikhail; Aiwu Ruth He

    2011-01-01

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

  19. Cancer stem cell metabolism

    OpenAIRE

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

    2016-01-01

    Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Deter...

  20. Gastric Cancer Stem Cells

    OpenAIRE

    Takaishi, Shigeo; Okumura, Tomoyuki; Timothy C Wang

    2008-01-01

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

  1. Stromal reengineering to treat pancreas cancer.

    Science.gov (United States)

    Stromnes, Ingunn M; DelGiorno, Kathleen E; Greenberg, Philip D; Hingorani, Sunil R

    2014-07-01

    Pancreatic ductal adenocarcinoma co-opts multiple cellular and extracellular mechanisms to create a complex cancer organ with an unusual proclivity for metastasis and resistance to therapy. Cell-autonomous events are essential for the initiation and maintenance of pancreatic ductal adenocarcinoma, but recent studies have implicated critical non-cell autonomous processes within the robust desmoplastic stroma that promote disease pathogenesis and resistance. Thus, non-malignant cells and associated factors are culprits in tumor growth, immunosuppression and invasion. However, even this increasing awareness of non-cell autonomous contributions to disease progression is tempered by the conflicting roles stromal elements can play. A greater understanding of stromal complexity and complicity has been aided in part by studies in highly faithful genetically engineered mouse models of pancreatic ductal adenocarcinoma. Insights gleaned from such studies are spurring the development of therapies designed to reengineer the pancreas cancer stroma and render it permissive to agents targeting cell-autonomous events or to reinstate immunosurveillance. Integrating conventional and immunological treatments in the context of stromal targeting may provide the key to a durable clinical impact on this formidable disease. PMID:24908682

  2. Converting redox signaling to apoptotic activities by stress-responsive regulators HSF1 and NRF2 in fenretinide treated cancer cells.

    Directory of Open Access Journals (Sweden)

    Kankan Wang

    Full Text Available BACKGROUND: Pharmacological intervention of redox balance in cancer cells often results in oxidative stress-mediated apoptosis, attracting much attention for the development of a new generation of targeted therapy in cancer. However, little is known about mechanisms underlying the conversion from oxidative signaling to downstream activities leading cells to death. METHODOLOGY/PRINCIPAL FINDINGS: We here report a systematic detection of transcriptome changes in response to oxidative signals generated in leukemia cells upon fenretinide treatment, implicating the occurrence of numerous stress-responsive events during the fenretinide induced apoptosis, such as redox response, endoplasmic reticulum stress/unfolded protein response, translational repression and proteasome activation. Moreover, the configuration of these relevant events is primarily orchestrated by stress responsive transcription factors, as typically highlighted by NF-E2-related factor-2 (NRF2 and heat shock factor 1 (HSF1. Several lines of evidence suggest that the coordinated regulation of these transcription factors and thus their downstream genes are involved in converting oxidative signaling into downstream stress-responsive events regulating pro-apoptotic and apoptotic activities at the temporal and spatial levels, typifying oxidative stress-mediated programmed death rather than survival in cancer cells. CONCLUSIONS/SIGNIFICANCE: This study provides a roadmap for understanding oxidative stress-mediated apoptosis in cancer cells, which may be further developed into more sophisticated therapeutic protocols, as implicated by synergistic induction of cell apoptosis using proteasome inhibitors with fenretinide.

  3. External validation of nomograms for predicting cancer-specific mortality in penile cancer patients treated with definitive surgery

    OpenAIRE

    Yao Zhu; Wei-Jie Gu; Ding-Wei Ye; Xu-Dong Yao; Shi-Lin Zhang; Bo Dai; Hai-Liang Zhang; Yi-Jun Shen

    2014-01-01

    Using a population-based cancer registry, Thuret et al. developed 3 nomograms for estimating cancer-specific mortality in men with penile squamous cell carcinoma. In the initial cohort, only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage. To generalize the prediction models in clinical practice, we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery. Clinicopathologic information was obt...

  4. 草酸铂处理人结肠癌细胞蛋白质组分析%Proteome analysis of human colon cancer cell line treated by oxaliplatin

    Institute of Scientific and Technical Information of China (English)

    陈家诚; 吴静; 钟亮玉; 郭伟; 陈远光

    2010-01-01

    目的 分析草酸铂处理后人结肠癌Lovo细胞系的差异表达蛋白,从蛋白质组学角度探讨草酸铂的作用机制.方法 Lovo细胞系按完全随机法分2组,即实验组(含草酸铂培养液培养)和对照组(无草酸铂培养液培养).培养后收集细胞依次进行二维电泳分离并选择差异点,采用质谱分析鉴定差异蛋白.结果 两组双向电泳图谱分辨率高、重复性好,匹配率分别为80.16%(812/1013)和81.19%(829/1021).获取重复差异点22个,质谱分析其中10个,成功鉴定出与结肠癌相关6种蛋白:β2微球蛋白、剪接因子SFRS3、尿嘧啶DNA糖基化酶表达上调;60S核糖体蛋白P2、甘油醛3磷酸脱氢酶、鸟苷酸结合蛋白β2多肽样1表达下调.结论 草酸铂作用人结肠癌Lovo细胞系后有多种差异蛋白表达,其与免疫增强、pre-mRNA转录修饰、DNA损伤修复、调控蛋白翻译及翻译后加工、能量代谢及信号传导通路等有关.%Objective To analyze differential expression proteins of human colon cancer Lovo cell line treated by oxaliplatin, and to explore the antitumor mechanism of oxaliplatin in the view of proteomics perspective. Methods The Lovo cells were randomly divided into two groups, including the experimental group (cultured in oxaliplatin- containing solution) and the control group (cultured in oxaliplatin-free solution). After culture, the both groups were processed by two-dimensional gel electrophoresis to select disparates, and differential proteins were identified by mass spectrometry analyses. Results High resolution and good reproducibility were observed on electrophoretograms of both groups, with matching rates at 80.16% (812/1013) and 81.19% (829/1021) respectively. Twenty-two repeated disparate points were obtained, ten of them were selected for mass spectrometry analyses. Six colorectal cancer related proteins were successfully identified, including 3 up-regulated proteins (β-2 microglobulin, splicing factor SFRS

  5. Reduced BCL2 and CCND1 mRNA expression in human cervical cancer HeLa cells treated with a combination of everolimus and paclitaxel

    OpenAIRE

    Yilmaz, Akin; Alp, Ebru; Onen, H. Ilke; MENEVSE, SEVDA

    2016-01-01

    Aim of the study Cervical cancer is the second most common malignancy in women worldwide. Everolimus displays direct effects on growth and proliferation of cancer cells via inhibition of mammalian target of rapamycin (mTOR) protein, which is known to be associated with drug resistance. In this study, we aimed to investigate the effects of everolimus, gemcitabine, and paclitaxel in terms of cell viability and mRNA expression levels of GRP78, CCND1, CASP2, and BCL2 genes. Material and methods H...

  6. Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

    Directory of Open Access Journals (Sweden)

    Ameer L. Elaimy

    2012-01-01

    Full Text Available Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient’s primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival.

  7. Classification and Regression Tree Analysis of Clinical Patterns to Predict the Survival of Patients with Advanced Non-small Cell Lung Cancer Treated with Erlotinib

    Directory of Open Access Journals (Sweden)

    Yutao LIU

    2011-10-01

    Full Text Available Background and objective Erlotinib is a targeted therapy drug for non-small cell lung cancer (NSCLC. It has been proven that, there was evidence of various survival benefits derived from erlotinib in patients with different clinical features, but the results are conflicting. The aim of this study is to identify novel predictive factors and explore the interactions between clinical variables as well as their impact on the survival of Chinese patients with advanced NSCLC heavily treated with erlotinib. Methods The clinical and follow-up data of 105 Chinese NSCLC patients referred to the Cancer Hospital and Institute, Chinese Academy of Medical Sciences from September 2006 to September 2009 were analyzed. Multivariate analysis of progressive-free survival (PFS was performed using recursive partitioning referred to as the classification and regression tree (CART analysis. Results The median PFS of 105 eligible consecutive Chinese NSCLC patients was 5.0 months (95%CI: 2.9-7.1. CART analysis was performed for the initial, second, and third split in the lymph node involvement, the time of erlotinib administration, and smoking history. Four terminal subgroups were formed. The longer values for the median PFS were 11.0 months (95%CI: 8.9-13.1 for the subgroup with no lymph node metastasis and 10.0 months (95%CI: 7.9-12.1 for the subgroup with lymph node involvement, but not over the second-line erlotinib treatment with a smoking history ≤35 packs per year. The shorter values for the median PFS were 2.3 months (95%CI: 1.6-3.0 for the subgroup with lymph node metastasis and over the second-line erlotinib treatment, and 1.3 months (95%CI: 0.5-2.1 for the subgroup with lymph node metastasis, but not over the second-line erlotinib treatment with a smoking history >35 packs per year. Conclusion Lymph node metastasis, the time of erlotinib administration, and smoking history are closely correlated with the survival of advanced NSCLC patients with first- to

  8. Interstitial lung disease in gefitinib-treated Japanese patients with non-small cell lung cancer – a retrospective analysis: JMTO LC03-02

    Directory of Open Access Journals (Sweden)

    Tada Harue

    2009-08-01

    Full Text Available Abstract Background In Japan, high incidences of interstitial lung disease (ILD and ILD-related deaths have been reported among gefitinib-treated patients with non-small cell lung cancer (NSCLC. We investigated the efficacy of gefitinib, the incidence of ILD and risk factors for ILD in these patients. Findings We obtained patient data retrospectively using questionnaires sent to 22 institutions. We asked for demographic and clinical data on NSCLC patients for whom gefitinib treatment had begun between July 2002 and February 2003. Data from a total of 526 patients were analyzed. The patient characteristics were as follows: 64% male, 69% with adenocarcinoma, 61% with a performance score of 0–1, and 5% with concurrent interstitial pneumonitis. The objective response proportion was 80/439 (18.2%; 95% CI: 14.7–22.0. ILD developed in 17 patients (3.2%; 95% CI 1.9–5.1%, of whom 7 died. According to multivariate analysis, female sex, history of prior chemotherapy, low absolute neutrophil count before gefitinib treatment, and adenocarcinoma histology were associated with response to gefitinib treatment. None of the factors we evaluated were associated with the development of ILD. Conclusion The results of this study are consistent with previously published values for treatment response proportions and incidence of ILD during gefitinib treatment in Japanese patients. Future studies should be aimed at identifying factors indicating that a patient has a high probability of receiving benefit from gefitinib and a low risk of developing ILD.

  9. Prospective evaluation of pulmonary function in cancer patients treated with total body irradiation, high-dose melphalan, and autologous hematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: (a) cyclophosphamide (7 g/m2); (b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); (c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed

  10. Functional dosimetric metrics for predicting radiation-induced lung injury in non-small cell lung cancer patients treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Radiation-induced lung injury (RILI) is an important dose-limiting toxicity during thoracic radiotherapy. The purpose of this study is to investigate single photon emission computed tomography (SPECT) perfusion-weighted functional dose-volume histogram (FDVH) for predicting RILI in non-small cell lung cancer (NSCLC) patients treated with definitive chemoradiotherapy. Fifty-seven locally advanced NSCLC patients receiving chemoradiotherapy were enrolled prospectively. Patients had treatment scans and dose calculations to provide a standard dose-volume histogram (DVH). Fusion of SPECT and computed tomography scans provided perfusion-weighted FDVH and associated functional dosimetric parameters (relative volumes of functional lung receiving more than a threshold dose of 5 – 60 Gy at increments of 5 Gy [FV5 – FV60]). The predictive abilities of FDVH and DVH were calculated and compared based on the area under receiver operating characteristic (ROC) curve (AUC). The accumulative incidence of ≥ 2 grade RILI was 19.3% with a median follow-up of 12 months. Univariate analysis showed that the functional (FV5 – FV60) and standard (V5 – V40) parameters were associated with RILI (all value of p < 0.05). Close correlations between a variety of functional and standard parameters were found. By ROC curve analysis, functional metrics (AUCs were 0.784 – 0.869) provided similarly (p value 0.233 – 1.000) predictive outcome to standard metrics (AUCs were 0.695 – 0.902) in lower – median dose level parameters (FV5 – FV40). However, FDVH seemed to add some predictive value in higher dose level, the best statistical significance for comparing FV60 with V60 was 0.693 vs. 0.511 (p = 0.055). Functional metrics are identified as reliable predictors for RILI, however, this observation still needs to be further verified using a larger sample size

  11. Clinical and dosimetric risk factors of acute radiation esophagitis in non-small cell lung cancer patients treated with three-dimensional conformal radiotherapy

    International Nuclear Information System (INIS)

    Objective: To analyze the clinical and dosimetric risk factors for acute radiation esophagitis (ARE) in non-small cell lung cancer (NSCLC) patients treated with three-dimensional conformal radiotherapy (3D-CRT), and to find significant risk factors for clinical therapy. Methods: A total of 102 NSCLC patients treated with 3D-CRT were retrospectively analyzed.ARE was scored according to the Radiation Therapy Oncology Group (RTOG) criteria with grade 2 or worse. Patients were divided into non-concurrent chemoradiotherapy group and concurrent chemoradiotherapy group. The clinical and dosimetric factors associated with grade 2 or worse ARE were analyzed using univariate logistic regression, multivariate logistic analysis and receiver operating characteristic (ROC) curve. Results: There were no grade 4 or 5 ARE observed in the 102 patients. Nineteen developed grade 2, 15 developed grade 3. In non-concurrent chemoradiotherapy group,multivariate analysis showed that V55 was the only risk factor of grade 2/3 ARE. For ROC curve analysis, the cut-off point of V55 was 16.0 while the area under ROC curve was 0.870 (95% CI: 0.782-0.957, P<0.05). In concurrent chemoradiotherapy group, multivariate analysis showed that V35 and chemotherapy regimens during radiotherapy were risk factors of grade 2/3 ARE. The cut-off point of V35 was 23.75 while the area under ROC curve was 0.782 (95% CI: 0.636-0.927, P<0.05). Vinorelbine and cisplatin regimen showed low incidence of ARE contrast with gemcitabine/docetaxel and cisplatin regimens (33.3% and 66.7%). Conclusions: V55 is the only statistically significant risk factor associated with grade 2 or worse ARE for patients who don't accepted concurrent chemotherapy. V35 and chemotherapy regimens during radiotherapy are statistically significant risk factors associated with grade 2 or worse ARE for patients who accept concurrent chemotherapy. Vinorelbine and cisplatin regimen during radiotherapy shows low incidence of ARE. (authors)

  12. Pro- and anti-apoptotic effects of p53 in cisplatin-treated human testicular cancer are cell context-dependent

    NARCIS (Netherlands)

    di Pietro, Alessandra; Koster, Roelof; Boersma-van Eck, Wytske; Dam, Wendy A.; Mulder, Nanno H.; Gietema, Jourik A.; de Vries, Elisabeth G. E.; de Jong, Steven

    2012-01-01

    In murine testicular cancer (TC) cells wild-type p53 contributes to sensitivity to DNA-damaging drugs in a dose-dependent way. In human TC, however, the role of wild-type p53 functionality in chemotherapeutic response remains elusive. We analyzed functionality of wild-type p53 in cisplatin sensitivi

  13. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1)

    DEFF Research Database (Denmark)

    Reck, Martin; Kaiser, Rolf; Mellemgaard, Anders;

    2014-01-01

    BACKGROUND: The phase 3 LUME-Lung 1 study assessed the efficacy and safety of docetaxel plus nintedanib as second-line therapy for non-small-cell lung cancer (NSCLC). METHODS: Patients from 211 centres in 27 countries with stage IIIB/IV recurrent NSCLC progressing after first-line chemotherapy...

  14. Prediction of outcome of non-small cell lung cancer patients treated with chemotherapy and bortezomib by time-course MALDI-TOF-MS serum peptide profiling

    NARCIS (Netherlands)

    Voortman, J.; Pham, T.V.; Knol, J.C.; Giaccone, G.; Jimenez, C.R.

    2009-01-01

    Background: Only a minority of patients with advanced non-small cell lung cancer (NSCLC) benefit from chemotherapy. Serum peptide profiling of NSCLC patients was performed to investigate patterns associated with treatment outcome. Using magnetic bead-assisted serum peptide capture coupled to matrix-

  15. Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

    Science.gov (United States)

    2016-06-13

    Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell

  16. High-dose OxyContin to treat pain associated with bone metastasis in patients with small-cell lung cancer: a case study report.

    Science.gov (United States)

    Zhou, Tao; Zhang, Xia; Dong, Yan; Zhuang, Feifei; Jiang, Fengquan; Yu, Jinming; Zhang, Bin

    2016-01-01

    Pain management is an important topic that has received extensive attention from clinical practitioners. Nearly all patients with malignant tumors suffer pain at the advanced stage of their disease. Oxycodone is a first-line choice for treating moderate-to-severe cancer-related pain, and OxyContin, a controlled-release oxycodone hydrochloride tablet, is internationally recognized as a safe and effective opioid analgesic. OxyContin has the characteristics of both immediate release and sustained release, with a time to onset and peak similar to those of immediate-release morphine. It acts on both μ and κ receptors and has been shown to be effective in treating different types of pain, especially neuropathic pain, theoretically without a dose cap. However, the dose is limited in clinical applications due to various factors that are likely to affect its analgesic effect and reduce patient quality of life. Cooperation with a patient's family members is required during the treatment of cancer pain. Chronic cancer pain has a long disease course, which could easily cause complex psychological symptoms due to their important role in the pain experience. Pain is controllable, and patients have a right to not experience pain. An optimal living state can be achieved through collaboration between physicians and patients. Rational personalized treatment of cancer pain can improve patient quality of life, relieve pain, and help prolong patient survival. This article reports the treatment procedure and adverse reactions in a patient who was treated with high-dose OxyContin, with the aim of providing a reference for other clinical practitioners. PMID:26855563

  17. Potential use of custirsen to treat prostate cancer

    Directory of Open Access Journals (Sweden)

    Higano CS

    2013-06-01

    Full Text Available Celestia S Higano Department of Medicine, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, WA, USA Abstract: Over the last few years, five agents have demonstrated a survival benefit over a comparator treatment or placebo in the treatment of metastatic castration-resistant prostate cancer and have been approved by the US Food and Drug Administration: sipuleucel-T (a dendritic cell immunotherapy; cabazitaxel; abiraterone acetate and enzalutamide (both hormonal agents; and radium 223 (an alpha emitter. The development of these agents pivoted on whether patients had been treated with docetaxel, which remains the first-line chemotherapy of choice. To date, no combination of docetaxel and another active agent has demonstrated superiority to docetaxel alone despite numerous Phase III trials. Clusterin is a cytoprotective chaperone protein that is upregulated in response to various anticancer therapies. When overexpressed, clusterin interferes with apoptotic signaling, thereby promoting cell survival and conferring broad-spectrum resistance in cancer cell lines. Custirsen (OGX-011 is a second-generation 2´-methoxyethyl modified phosphorothioate antisense oligonucleotide that inhibits expression of clusterin. This review presents the preclinical and clinical data that provided the rationale for the combination of custirsen with chemotherapy in ongoing Phase III trials. Keywords: castration-resistant prostate cancer, clusterin, custirsen, OGX-011, antisense, OGX-427, apoptosis

  18. High-dose OxyContin to treat pain associated with bone metastasis in patients with small-cell lung cancer: a case study report

    Directory of Open Access Journals (Sweden)

    Zhou T

    2016-01-01

    Full Text Available Tao Zhou,1,* Xia Zhang,2,* Yan Dong,1 Feifei Zhuang,1 Fengquan Jiang,3 Jinming Yu,4 Bin Zhang1,4 1Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, 2Department of Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, 3Laboratory of Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 4Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Abstract: Pain management is an important topic that has received extensive attention from clinical practitioners. Nearly all patients with malignant tumors suffer pain at the advanced stage of their disease. Oxycodone is a first-line choice for treating moderate-to-severe cancer-related pain, and OxyContin, a controlled-release oxycodone hydrochloride tablet, is internationally recognized as a safe and effective opioid analgesic. OxyContin has the characteristics of both immediate release and sustained release, with a time to onset and peak similar to those of immediate-release morphine. It acts on both µ and κ receptors and has been shown to be effective in treating different types of pain, especially neuropathic pain, theoretically without a dose cap. However, the dose is limited in clinical applications due to various factors that are likely to affect its analgesic effect and reduce patient quality of life. Cooperation with a patient’s family members is required during the treatment of cancer pain. Chronic cancer pain has a long disease course, which could easily cause complex psychological symptoms due to their important role in the pain experience. Pain is controllable, and patients have a right to not experience pain. An optimal living state can be achieved through collaboration between physicians and patients. Rational personalized treatment of cancer pain can improve

  19. Stem cell transplantation for treating Parkinson's disease

    OpenAIRE

    Li, Runhui

    2012-01-01

    OBJECTIVE: To identify global research trends of stem cell transplantation for treating Parkinson's disease using a bibliometric analysis of the Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of data retrievals for stem cell transplantation for treating Parkinson's disease from 2002 to 2011 using the Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed articles on stem cell transplantation for treating Parkinson's disease which were published and ind...

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

    OpenAIRE

    Vlashi, Erina; Pajonk, Frank

    2014-01-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be ...

  1. SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

    International Nuclear Information System (INIS)

    Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×107, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to explore the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 109 cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work is supported

  2. SU-D-BRB-06: Treating Glioblastoma Multiforme (GBM) as a Chronic Disease: Implication of Temporal-Spatial Dose Fractionation Optimization Including Cancer Stem Cell Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Yu, V; Nguyen, D; Pajonk, F; Kaprealian, T; Kupelian, P; Steinberg, M; Low, D; Sheng, K [Department of Radiation Oncology, UCLA, Los Angeles, CA (United States)

    2015-06-15

    Purpose: To explore the feasibility of improving GBM treatment outcome with temporal-spatial dose optimization of an ordinary differential equation (ODE) that models the differentiation and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC). Methods: The ODE was formulated into a non-convex optimization problem with the objective to minimize remaining total cancer cells 500 days from the onset of radiotherapy when the total cancer cell number was 3.5×10{sup 7}, while maintaining normal tissue biological effective dose (BED) of 100Gy resulted from standard prescription of 2Gyx30. Assuming spatially separated CSC and DCC, optimization was also performed to explore the potential benefit from dose-painting the two compartments. Dose escalation to a sub-cell-population in the GTV was also examined assuming that a 2 cm margin around the GTV allows sufficient dose drop-off to 100Gy BED. The recurrence time was determined as the time at which the total cancer cell number regrows to 10{sup 9} cells. Results: The recurrence time with variable fractional doses administered once per week, bi-week and month for one year were found to be 615, 593 and 570 days, superior to the standard-prescription recurrence time of 418 days. The optimal dose-fraction size progression for both uniform and dose-painting to the tumor is low and relatively constant in the beginning and gradually increases to more aggressive fractions at end of the treatment course. Dose escalation to BED of 200Gy to the whole tumor alongside with protracted weekly treatment was found to further delay recurrence to 733 days. Dose-painting of 200 and 500Gy BED to CSC on a year-long weekly schedule further extended recurrence to 736 and 1076 days, respectively. Conclusion: GBM treatment outcome can possibly be improved with a chronic treatment approach. Further dose escalation to the entire tumor or CSC targeted killing is needed to achieve total tumor control. This work

  3. Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer

    Science.gov (United States)

    2013-06-20

    Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Head and Neck Cancer; Kidney Cancer; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Retinoblastoma; Sarcoma; Testicular Germ Cell Tumor

  4. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Thomas W Owens

    2013-08-01

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

  5. Association between polymorphisms of BAG-1 and XPD and chemotherapy sensitivity in advanced non-small-cell lung cancer patients treated with vinorelbine combined cisplatin regimen.

    Science.gov (United States)

    Li, Ping; Wang, Ya-Di; Cheng, Jian; Chen, Jun-Chen; Ha, Min-Wen

    2015-12-01

    BCL-2 Associated athanogene 1 (BAG-1) and Xeroderma pigmentosum group D (XPD) are involved in the nucleotide excision repair pathway and DNA repair. We aimed to investigate whether polymorphisms in BAG-1 and XPD have effects on chemotherapy sensitivity and survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with vinorelbine combined cisplatin (NP) regimen. A total of 142 patients with diagnosed advanced NSCLC were recruited in the current study. NP regimen was applied for all eligible patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for BAG-1 (codon 324) and XPD (codons 312 and 751) genotyping. The treatment response was evaluated according to the RECIST guidelines. Progression-free survival (PFS) and overall survival (OS) were record as median and end point, respectively. As for BAG-1 codon 324, the chemotherapy sensitivity in NSCLC patients with CT genotype was 0.383 times of those with CC genotype (P < 0.05). With respect to XPD codon 751, the chemotherapy sensitivity in NSCLC patients with Lys/Gln genotype was 0.400 times of those with Lys/Lys genotype (P < 0.05). In addition, NSCLC patients carrying combined C/C genotype at codon 324 in BAG-1, Asp/Asp of XPD codon 312, and Lys/Lys of XPD codon 751 produced a higher efficacy of NP chemotherapy compared to those carrying mutation genotypes (all P < 0.05). Further, there were significant differences in PFS between patients with combined C/C genotype of BAG-1 codon 324, Lys/Lys genotype of XPD codon 751, and Asp/Asp genotype of XPD codon 312 and patients carrying BAG-1 codon 324 C/T genotype, XPD codon751 Lys/Gln genotype, and XPD codon312 Asp/Asn genotype (P < 0.05). Multivariate Cox regression analysis indicated that the combined wild-type of codon 324 XPD, codon 751 XPD, and codon 312 BAG-1 is the protective factor for OS and PFS, and clinical stages is the risk factor for OS and PFS. In conclusion, our research

  6. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Kim, Sinae [Division of Biometrics, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Biostatistics, School of Public Health, Rutgers University, New Brunswick, New Jersey (United States); Haider, Syed A. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Xu, Xiaoting [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow (China); Wu, Alson [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Surakanti, Sujani; Aisner, Joseph [Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Langenfeld, John [Division of Surgery, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States); Yue, Ning J.; Haffty, Bruce G.; Zou, Wei [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, New Brunswick, New Jersey (United States)

    2015-07-01

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.

  7. Determinants of Complications and Outcome in High-Risk Squamous Cell Head-and-Neck Cancer Treated With Perioperative High-Dose Rate Brachytherapy (PHDRB)

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Monge, Rafael, E-mail: rmartinezm@unav.es [Department of Oncology, Clinica Universitaria de Navarra, Pamplona (Spain); Pagola Divasson, Maria; Cambeiro, Mauricio; Gaztanaga, Miren; Moreno, Marta; Arbea, Leire [Department of Oncology, Clinica Universitaria de Navarra, Pamplona (Spain); Montesdeoca, Nestor [Department of Maxillofacial Surgery, Clinica Universitaria de Navarra, Pamplona (Spain); Alcalde, Juan [Department of Otolaryngology, Clinica Universitaria de Navarra, Pamplona (Spain)

    2011-11-15

    Purpose: To determine the impact of a set of patient, tumor, and treatment factors on toxicity and outcome in patients with head-and-neck squamous cell cancer treated with surgical resection and perioperative high-dose rate brachytherapy (PHDRB) alone (single-modality [SM] group) (n = 46) or PHDRB combined with postoperative radiation or chemoradiation (combined-modality [CM] group) (n = 57). Methods and Materials: From 2000 to 2008, 103 patients received PHDRB after complete macroscopic resection. SM patients received 32 or 40 Gy of PHDRB in 8 or 10 twice-daily treatments for R0 and R1 resections. CM patients received 16 or 24 Gy of PHDRB in 4 or 6 twice-daily treatments for R0 and R1 resections, followed by external radiation of 45 Gy in 25 fractions with or without concomitant chemotherapy. Results: Grade {>=}4 complications according to the Radiation Therapy Oncology Group were more frequent in the SM group than in the CM group (p = 0.024). Grade {>=}3 and {>=}4 complications increased with the antecedent of prior irradiation (p = 0.032 and p = 0.006, respectively) and with TV{sub 150} values of 13 mL or greater (p = 0.032 and p = 0.032, respectively). After a median follow-up of 34.8 and 60.8 months for SM and CM patients, respectively, patients with high-risk margins had a 9-year local control rate of 68.0% whereas patients with wider margins had a 9-year local control of 93.7% (p = 0.045). Patients with primary and recurrent tumors had 9-year actuarial locoregional control rates of 81.8% and 54.2%, respectively (p = 0.003). Patients with lymph-vascular space invasion (LVSI)-positive and LVSI-negative tumors had 9-year distant control rates of 62.8% and 81.6%, respectively (p = 0.034). Disease-free survival rates decreased in recurrent cases (p = 0.006) as well as in LVSI-positive patients (p = 0.035). Conclusions: The complications observed are largely attributable to the antecedent of prior irradiation but can possibly be minimized by meticulous mapping and

  8. Determinants of Complications and Outcome in High-Risk Squamous Cell Head-and-Neck Cancer Treated With Perioperative High–Dose Rate Brachytherapy (PHDRB)

    International Nuclear Information System (INIS)

    Purpose: To determine the impact of a set of patient, tumor, and treatment factors on toxicity and outcome in patients with head-and-neck squamous cell cancer treated with surgical resection and perioperative high–dose rate brachytherapy (PHDRB) alone (single-modality [SM] group) (n = 46) or PHDRB combined with postoperative radiation or chemoradiation (combined-modality [CM] group) (n = 57). Methods and Materials: From 2000 to 2008, 103 patients received PHDRB after complete macroscopic resection. SM patients received 32 or 40 Gy of PHDRB in 8 or 10 twice-daily treatments for R0 and R1 resections. CM patients received 16 or 24 Gy of PHDRB in 4 or 6 twice-daily treatments for R0 and R1 resections, followed by external radiation of 45 Gy in 25 fractions with or without concomitant chemotherapy. Results: Grade ≥4 complications according to the Radiation Therapy Oncology Group were more frequent in the SM group than in the CM group (p = 0.024). Grade ≥3 and ≥4 complications increased with the antecedent of prior irradiation (p = 0.032 and p = 0.006, respectively) and with TV150 values of 13 mL or greater (p = 0.032 and p = 0.032, respectively). After a median follow-up of 34.8 and 60.8 months for SM and CM patients, respectively, patients with high-risk margins had a 9-year local control rate of 68.0% whereas patients with wider margins had a 9-year local control of 93.7% (p = 0.045). Patients with primary and recurrent tumors had 9-year actuarial locoregional control rates of 81.8% and 54.2%, respectively (p = 0.003). Patients with lymph–vascular space invasion (LVSI)–positive and LVSI-negative tumors had 9-year distant control rates of 62.8% and 81.6%, respectively (p = 0.034). Disease-free survival rates decreased in recurrent cases (p = 0.006) as well as in LVSI-positive patients (p = 0.035). Conclusions: The complications observed are largely attributable to the antecedent of prior irradiation but can possibly be minimized by meticulous mapping and

  9. Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinical information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes

  10. Nomogram Predicting Clinical Outcomes in Non-small Cell Lung Cancer Patients Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

    OpenAIRE

    Keam, Bhumsuk; Kim, Dong-Wan; Park, Jin Hyun; Lee, Jeong-Ok; Kim, Tae Min; Lee, Se-Hoon; Chung, Doo Hyun; Heo, Dae Seog

    2014-01-01

    Purpose The aim of this study was to develop a pragmatic nomogram for prediction of progressionfree survival (PFS) for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in EGFR mutant non-small cell lung cancer (NSCLC). Materials and Methods A total of 306 recurred or metastatic NSCLC patients with EGFR mutation, who received EGFR TKIs, were enrolled in this study. We developed the nomogram, using a Cox proportional hazard regression model for PFS. Results The median...

  11. Effect of Radiation Therapy Techniques on Outcome in N3-positive IIIB Non-small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy

    OpenAIRE

    Noh, Jae Myoung; KIM, JIN MAN; Ahn, Yong Chan; Pyo, Hongryull; Kim, BoKyong; Oh, Dongryul; Ju, Sang Gyu; Kim, Jin Sung; Shin, Jung Suk; Hong, Chae-Seon; Park, Hyojung; Lee, Eonju

    2015-01-01

    Purpose This study was conducted to evaluate clinical outcomes following definitive concurrent chemoradiotherapy (CCRT) for patients with N3-positive stage IIIB (N3-IIIB) non-small cell lung cancer (NSCLC), with a focus on radiation therapy (RT) techniques. Materials and Methods From May 2010 to November 2012, 77 patients with N3-IIIB NSCLC received definitive CCRT (median, 66 Gy). RT techniques were selected individually based on estimated lung toxicity, with 3-dimensional conformal RT (3D-C...

  12. Development of chitosan graft pluronic®F127 copolymer nanoparticles containing DNA aptamer for paclitaxel delivery to treat breast cancer cells

    Science.gov (United States)

    Thach Nguyen, Kim; Le, Duc Vinh; Do, Dinh Ho; Huan Le, Quang

    2016-06-01

    HER-2/ErbB2/Neu(HER-2), a member of the epidermal growth factor receptor family, is specifically overexpressed on the surface of breast cancer cells and serves a therapeutic target for breast cancer. In this study, we aimed to isolate DNA aptamer (Ap) that specifically bind to a HER-2 overexpressing SK-BR-3 human breast cancer cell line, using SELEX strategy. We developed a novel multifunctional composite micelle with surface modification of Ap for targeted delivery of paclitaxel. This binary mixed system consisting of Ap modified pluronic®F127 and chitosan could enhance PTX loading capacity and increase micelle stability. Polymeric micelles had a spherical shape and were self-assemblies of block copolymers of approximately 86.22 ± 1.45 nm diameter. PTX could be loaded with high encapsulation efficiency (83.28 ± 0.13%) and loading capacity (9.12 ± 0.34%). The release profile were 29%-35% in the first 12 h and 85%-93% after 12 d at pH 7.5 of receiving media. The IC50 doses by MTT assay showed the greater activity of nanoparticles loaded paclitaxel over free paclitaxel and killed cells up to 95% after 6 h. These results demonstrated unique assembly with the capacity to function as an efficient detection and delivery vehicle in the biological living system.

  13. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    Directory of Open Access Journals (Sweden)

    Bonanno L

    2016-06-01

    Full Text Available Laura Bonanno,1 Giulia Zago,1 Giuseppe Marulli,2 Paola Del Bianco,3 Marco Schiavon,2 Giulia Pasello,1 Valentina Polo,1,4 Fabio Canova,1 Fabrizio Tonetto,5 Lucio Loreggian,5 Federico Rea,2 PierFranco Conte,1,4 Adolfo Favaretto1 1Medical Oncology Unit 2, Veneto Institute of Oncology IOV-IRCCS, 2Thoracic Surgery Department, University of Padova, 3Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, 4Department of Surgery, Oncology and Gastroenterology, University of Padova, 5Radiotherapy Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy Objectives: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs. No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1, paclitaxel (200 mg/m2, d1, and gemcitabine (1,000 mg/m2 d1, 8 for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS and overall survival (OS were correlated to response, surgery, and clinical features. Results: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system. A total of 36 (62% patients achieved partial response (PR, and six (10% progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62% cases. After chemotherapy, 37 (64% patients underwent surgery

  14. Effect of 4-methoxyindole-3-carbinol on the proliferation of colon cancer cells in vitro, when treated alone or in combination with indole-3-carbinol

    DEFF Research Database (Denmark)

    Kronbak, Remy; Duus, Fritz; Vang, Ole

    2010-01-01

    Consumption of cruciferous vegetables and cancer prevention seem to be positively associated. We present an easy two-step synthesis for 4-methoxyindole-3-carbinol (4MeOI3C), the expected breakdown product of 4-methoxyglucobrassicin during ingestion. 4MeOI3C inhibited the proliferation of human...... colon cancer cells DLD-1 and HCT 116 with IC(50) values of 116 microM and 96 microM, respectively, after 48 h in vitro, and is therefore a more potent inhibitor than indole-3-carbinol (I3C). 4MeOI3C and I3C combined in different molar ratios inhibited proliferation in a nearly additive to slightly...... synergistic manner. Proliferation was inhibited by 100 microM 4MeOI3C after 48 h without affecting cell cycle phase distribution, indicating an overall-slowdown effect on the cell cycle. However, 200 microM 4MeOI3C caused a very high level of cell death and an accumulation of living cells in the G(0)/G(1...

  15. The mechanisms of photodynamic action for treating of cancer patients

    Directory of Open Access Journals (Sweden)

    A. L. Akopov

    2015-01-01

    Full Text Available Current views on mechanisms of therapeutic effect of photodynamic therapy for treating of cancer patients are represented. The history of formation and development of the method is described. The main requirements for agents used as photosensitizers are listed. Detailed review of main photosensitizers used in clinical practice in Russia and in foreign countries with their chemical structure, main spectral characteristics was performed. Methods of its application, therapeutic dose ranges, indications, specifi c pharmacokinetic properties and side-effects are briefl y outlined. Advantages and disadvantages of the most popular modern photosensitizers, main mechanisms of entry of photosensitizers of different chemical structure into cancer cells are observed. Three main possible component of anti-tumor effect: direct damage of cancer cells, impairment of vascular stroma of tumor and elimination of tumor due to immune cells are shown and closely discussed. Necrosis and apotosis of neovascular net which are main development trends of anti-tumor action for photodynamic therapy are noticed. 

  16. Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer

    Science.gov (United States)

    2014-08-04

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

  17. Genetic association with overall survival of taxane-treated lung cancer patients - a genome-wide association study in human lymphoblastoid cell lines followed by a clinical association study

    International Nuclear Information System (INIS)

    Taxane is one of the first line treatments of lung cancer. In order to identify novel single nucleotide polymorphisms (SNPs) that might contribute to taxane response, we performed a genome-wide association study (GWAS) for two taxanes, paclitaxel and docetaxel, using 276 lymphoblastoid cell lines (LCLs), followed by genotyping of top candidate SNPs in 874 lung cancer patient samples treated with paclitaxel. GWAS was performed using 1.3 million SNPs and taxane cytotoxicity IC50 values for 276 LCLs. The association of selected SNPs with overall survival in 76 small or 798 non-small cell lung cancer (SCLC, NSCLC) patients were analyzed by Cox regression model, followed by integrated SNP-microRNA-expression association analysis in LCLs and siRNA screening of candidate genes in SCLC (H196) and NSCLC (A549) cell lines. 147 and 180 SNPs were associated with paclitaxel or docetaxel IC50s with p-values <10-4 in the LCLs, respectively. Genotyping of 153 candidate SNPs in 874 lung cancer patient samples identified 8 SNPs (p-value < 0.05) associated with either SCLC or NSCLC patient overall survival. Knockdown of PIP4K2A, CCT5, CMBL, EXO1, KMO and OPN3, genes within 200 kb up-/downstream of the 3 SNPs that were associated with SCLC overall survival (rs1778335, rs2662411 and rs7519667), significantly desensitized H196 to paclitaxel. SNPs rs2662411 and rs1778335 were associated with mRNA expression of CMBL or PIP4K2A through microRNA (miRNA) hsa-miR-584 or hsa-miR-1468. GWAS in an LCL model system, joined with clinical translational and functional studies, might help us identify genetic variations associated with overall survival of lung cancer patients treated paclitaxel

  18. Detecting and treating breast cancer resistance to EGFR inhibitors

    Science.gov (United States)

    Moonlee, Sun-Young; Bissell, Mina J.; Furuta, Saori; Meier, Roland; Kenny, Paraic A.

    2016-04-05

    The application describes therapeutic compositions and methods for treating cancer. For example, therapeutic compositions and methods related to inhibition of FAM83A (family with sequence similarity 83) are provided. The application also describes methods for diagnosing cancer resistance to EGFR inhibitors. For example, a method of diagnosing cancer resistance to EGFR inhibitors by detecting increased FAM83A levels is described.

  19. Preventing and Treating Prostate Cancer Spread to Bone

    Science.gov (United States)

    ... options Preventing and treating prostate cancer spread to bones If prostate cancer spreads to other parts of the body, it ... a vein and settle in areas of damaged bones (like those containing cancer spread). Once there, they give off radiation that ...

  20. Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

    Science.gov (United States)

    2016-05-05

    ; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Paroxysmal Nocturnal Hemoglobinuria; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage

  1. Prostate cancer stem cells

    OpenAIRE

    Tu, Shi-Ming; Lin, Sue-Hwa

    2011-01-01

    Stem cells have long been implicated in prostate glandular formation. The prostate undergoes regression after androgen deprivation and regeneration after testosterone replacement. Regenerative studies suggest that these cells are found in the proximal ducts and basal layer of the prostate. Many characteristics of prostate cancer indicate that it originates from stem cells. For example, the putative AR− status of prostate stem cells renders them inherently insensitive to androgen blockade ther...

  2. Vaccine Therapy in Treating Patients With Colon, Pancreatic, or Lung Cancer

    Science.gov (United States)

    2015-04-27

    Recurrent Colon Cancer; Extensive Stage Small Cell Lung Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Limited Stage Small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Stage III Non-small Cell Lung Cancer; Stage I Pancreatic Cancer; Stage II Non-small Cell Lung Cancer; Stage IVB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage IVA Pancreatic Cancer

  3. Malignant thrombosis of the superior vena cava caused by non-small-cell lung cancer treated with radiation and erlotinib: a case with complete and prolonged response over 3 years

    Directory of Open Access Journals (Sweden)

    Wang JY

    2013-07-01

    Full Text Available Jianyang Wang,1 Jun Liang,1 Wenqing Wang,1 Han Ouyang,2 Luhua Wang11Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Department of Diagnostic Radiology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of ChinaAbstract: Most cases of superior vena cava (SVC syndrome resulting from neoplasm, especially from lung cancer, remain a serious challenge to treat. Here, for the first time as far as we are aware, we report the case of a non-small-cell lung cancer patient with a massive SVC malignant thrombosis who was treated with thoracic irradiation and erlotinib. The treatment regimen consisted of erlotinib 150 mg/day and a total dose of 66 Gy/33 fractions delivered to the tumor, malignant thrombosis, and metastasis mediastinal lymph nodes. The malignant thrombosis responded dramatically and the combined regimen was well tolerated. After discharge, the erlotinib was prescribed as maintenance therapy. The patient was followed closely for the next 3 years. During this time, positron emission tomography/computed tomography scans and serum tumor marker screens were undertaken. By 6 months, the primary tumor showed complete response and by 9 months, the SVC thrombosis had disappeared. No sign of relapse has been found to date.Keywords: superior vena cava syndrome, radiotherapy, thoracic irradiation, neoplasm

  4. Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer

    Science.gov (United States)

    2015-08-28

    Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV Infection; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Central Nervous System Lymphoma; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma

  5. Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy

    OpenAIRE

    Han, Yang; Jia, Chengyou; Cong, Xianling; Yu, Fei; Cai, Haidong; Fang, Suyun; Cai, Li; Yang, Huiqiong; Sun, Yu; Li, Dan; Liu, Jin; Xie, Ruting; Yuan, Xueyu; Zhong, Xiaoming; LI Ming

    2015-01-01

    To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC) patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. T...

  6. Gene expression profiling and pathway analysis data in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin

    OpenAIRE

    Aumsuwan, Pranapda; Khan, Shabana I.; Khan, Ikhlas A.; Walker, Larry A.; Dasmahapatra, Asok K

    2016-01-01

    Microarray technology (Human OneArray microarray, phylanxbiotech.com) was used to compare gene expression profiles of non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells exposed to dioscin (DS), a steroidal saponin isolated from the roots of wild yam, (Dioscorea villosa). Initially the differential expression of genes (DEG) was identified which was followed by pathway enrichment analysis (PEA). Of the genes queried on OneArray, we identified 4641 DEG changed between MCF-7 and MDA-M...

  7. Cancer Stem Cells in Pancreatic Cancer

    International Nuclear Information System (INIS)

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

  8. Stem Cells and Cancer

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

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

  10. Histone deacetylase turnover and recovery in sulforaphane-treated colon cancer cells: competing actions of 14-3-3 and Pin1 in HDAC3/SMRT corepressor complex dissociation/reassembly

    Directory of Open Access Journals (Sweden)

    Williams David E

    2011-05-01

    Full Text Available Abstract Background Histone deacetylase (HDAC inhibitors are currently undergoing clinical evaluation as anti-cancer agents. Dietary constituents share certain properties of HDAC inhibitor drugs, including the ability to induce global histone acetylation, turn-on epigenetically-silenced genes, and trigger cell cycle arrest, apoptosis, or differentiation in cancer cells. One such example is sulforaphane (SFN, an isothiocyanate derived from the glucosinolate precursor glucoraphanin, which is abundant in broccoli. Here, we examined the time-course and reversibility of SFN-induced HDAC changes in human colon cancer cells. Results Cells underwent progressive G2/M arrest over the period 6-72 h after SFN treatment, during which time HDAC activity increased in the vehicle-treated controls but not in SFN-treated cells. There was a time-dependent loss of class I and selected class II HDAC proteins, with HDAC3 depletion detected ahead of other HDACs. Mechanism studies revealed no apparent effect of calpain, proteasome, protease or caspase inhibitors, but HDAC3 was rescued by cycloheximide or actinomycin D treatment. Among the protein partners implicated in the HDAC3 turnover mechanism, silencing mediator for retinoid and thyroid hormone receptors (SMRT was phosphorylated in the nucleus within 6 h of SFN treatment, as was HDAC3 itself. Co-immunoprecipitation assays revealed SFN-induced dissociation of HDAC3/SMRT complexes coinciding with increased binding of HDAC3 to 14-3-3 and peptidyl-prolyl cis/trans isomerase 1 (Pin1. Pin1 knockdown blocked the SFN-induced loss of HDAC3. Finally, SFN treatment for 6 or 24 h followed by SFN removal from the culture media led to complete recovery of HDAC activity and HDAC protein expression, during which time cells were released from G2/M arrest. Conclusion The current investigation supports a model in which protein kinase CK2 phosphorylates SMRT and HDAC3 in the nucleus, resulting in dissociation of the corepressor

  11. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

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

  12. Cancer Stem Cells in Breast Cancer

    OpenAIRE

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

    2011-01-01

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

  13. Primary Tumor Volume Is an Important Predictor of Clinical Outcomes Among Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck Treated With Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Purpose: The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy. Methods and Materials: A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis. Results: The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm3, and patients with a tumor volume 3 had a significantly better prognosis than those with a tumor volume >35 cm3 at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume 3 had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p = 3 larger than tumors without locoregional failure (p = .028) and 27.1-cm3 larger than tumors that recurred as distant metastases (p = .020). Conclusion: The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer of the head and neck undergoing definitive chemoradiotherapy and correlated with the treatment outcomes better than the T or N stage.

  14. Metallic taste in cancer patients treated with chemotherapy

    NARCIS (Netherlands)

    Ijpma, I.; Renken, R. J.; ter Horst, G. J.; Reyners, A. K. L.

    2015-01-01

    Background: Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic

  15. Genetic polymorphism in the epidermal growth factor receptor gene predicts outcome in advanced non-small cell lung cancer patients treated with erlotinib

    DEFF Research Database (Denmark)

    Winther-Larsen, Anne; Nissen, Peter H.; Jakobsen, Kristine Raaby;

    2015-01-01

    OBJECTIVES: Epidermal growth factor receptor (EGFR) mutations are important predictors of treatment response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). However, some patients with mutations do not respond and some patients without mutations show...... with advanced NSCLC. Genotypes were correlated with clinical characteristics, toxicity and outcome. A multivariate analysis was performed using Cox proportional hazards model while adjusting for clinically relevant factors including EGFR mutation status. RESULTS: 181946CT or TT genotypes showed an association...... response. We therefore need additional biomarkers to improve the selection of these patients for treatment. A promising candidate could be germline genetic variations in the EGFR gene that can alter protein expression or function and may influence the response to TKIs. Thus, the aim of this study...

  16. Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer

    Science.gov (United States)

    2015-05-14

    Childhood Hepatocellular Carcinoma; Papillary Thyroid Cancer; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Thyroid Cancer; Recurrent Wilms Tumor and Other Childhood Kidney Tumors

  17. Extragonadal Germ Cell Cancer (EGC)

    Science.gov (United States)

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

  18. Cancer Stem Cells in Pancreatic Cancer

    OpenAIRE

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

    2010-01-01

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

  19. Cancer stem cells in prostate cancer

    OpenAIRE

    Moltzahn, Felix; Thalmann, George N

    2013-01-01

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

  20. The Effects of Microwave Ablation and Surgical Resection on Hematogenous Dissemination of Cancer Cells in Treating Patients with Small Primary Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chaoyang Wen; Baowei Dong; Ping Liang; Xiaoling Yu; Li Su; Dejiang Yu; Hongtian Xia

    2006-01-01

    OBJECTIVE To conduct a comparative study of the effects of treatment using microwave ablation versus surgical resection on hematogenous dissemination of cancer cells, and on the level of immune cells of the peripheral blood in patients with small primary hepatocellular carcinoma (PHC, ≤5 cm).METHODS Forty patients with small PHC (maximal diameter ≤5 cm) were divided into a microwave group (19 cases) and a surgical operation group (21 cases). A real-time (RT) quantitative nested RT-PCR examination was performed for peripheral blood alpha-fetoprotein (AFP) mRNA. Studies were conducted to determine the level of CD3, CD4, CD8 and CD4/CD8 cells and for liver function at 30 min before, and 30 min,1 day and 3 days after the treatment.RESULTS Compared to the value before ablation, no obvious changes of CD3, CD4, CD8 and CD4/CD8 cells were found in patients of the microwave group within 7 days after ablation, but CD3, CD4 and CD4/CD8 cells in the operation group were lower compared to that before operatioh. The copy number of AFP mRNA in the peripheral blood samples of the patients of the 2 groups before operation was determined in 67.5% of the patients (27/40). There was an rise in the expression after treatment but no statistical difference was found in comparing the 2 groups. Follow-up of the patients was conducted for 1 to 16 months. For patients with continuous expression of peripheral blood AFP mRNA, the possibility of relapse and metastasis was increased.CONCLUSION Surgical resection or microwave ablation can cause more exfoliation of hepatoma carcinoma cells in the peripheral blood of patients with small PHC. The immune function of peripheral blood cells decreased in the patients after surgical resection, however, the immune function was better protected following microwave ablation. Microwave ablation causes minor reduction in liver function, and the treatment method presents a definite value for PHC therapy.

  1. Relationship Between Radiation Therapy Dose and Outcome in Patients Treated With Neoadjuvant Chemoradiation Therapy and Surgery for Stage IIIA Non-Small Cell Lung Cancer: A Population-Based, Comparative Effectiveness Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Sher, David J., E-mail: david_sher@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, Illinois (United States); Seder, Christopher W.; Liptay, Michael J. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, Illinois (United States); Koshy, Matthew [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)

    2015-06-01

    Purpose: To compare, using the National Cancer Database, survival, pathologic, and surgical outcomes in patients with stage IIIA non-small cell lung cancer treated with differential doses of neoadjuvant chemoradiation therapy, with the aim to discern whether radiation dose escalation was associated with a comparative effectiveness benefit and/or toxicity risk. Methods and Materials: Patients in the National Cancer Database with stage IIIA non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and surgery between 1998 and 2005 were analyzed. Dose strata were divided between 36 to 45 Gy (low-dose radiation therapy, LD-RT), 45 to 54 Gy (inclusive, standard-dose, SD-RT), and 54 to 74 Gy (high-dose, HD-RT). Outcomes included overall survival, residual nodal disease, positive surgical margin status, hospital length of stay, and adverse surgical outcomes (30-day mortality or readmission). Results: The cohort consisted of 1041 patients: 233 (22%) LD-RT, 584 (56%) SD-RT, and 230 (22%) HD-RT. The median, 3-year, and 5-year overall survival outcomes were 34.9 months, 48%, and 37%, respectively. On univariable analysis, patients treated with SD-RT experienced prolonged overall survival (median 38.3 vs 31.8 vs 29.0 months for SD-RT, LD-RT, and HD-RT, respectively, P=.0089), which was confirmed on multivariable analysis (hazard ratios 0.77 and 0.81 vs LD and HD, respectively). Residual nodal disease was seen less often after HD-RT (25.5% vs 31.8% and 37.5% for HD-RT, LD-RT, and SD-RT, respectively, P=.0038). Patients treated with SD-RT had fewer prolonged hospital stays. There were no differences in positive surgical margin status or adverse surgical outcomes between the cohorts. Conclusions: Neoadjuvant chemoradiation therapy between 45 and 54 Gy was associated with superior survival in comparison with doses above and below this threshold. Although this conclusion is limited by selection bias, clear candidates for trimodality therapy do not seem to

  2. Transcriptionally targeted gene therapy to detect and treat cancer

    OpenAIRE

    Wu, Lily; Johnson, Mai; Sato, Makoto

    2003-01-01

    The greatest challenge in cancer treatment is to achieve the highest levels of specificity and efficacy. Cancer gene therapy could be designed specifically to express therapeutic genes to induce cancer cell destruction. Cancer-specific promoters are useful tools to accomplish targeted expression; however, high levels of gene expression are needed to achieve therapeutic efficacy. Incorporating an imaging reporter gene in tandem with the therapeutic gene will allow tangible proof of principle t...

  3. Detection and Evaluation of EGFR Mutation Status in Serum of Patients with Advanced Non-small Cell Lung Cancer Treated with EGFR-TKIs

    Directory of Open Access Journals (Sweden)

    Ling MA

    2013-06-01

    Full Text Available Background and objective Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs has shown a high response rate in the treatment of lung cancer in patients with (EGFR mutation. The aim of this study is to evaluate the relationship between EGFR mutation status in serum and predicting benefit from EGFR-TKIs therapy in patients with advanced non-small cell lung cancer (NSCLC. Methods We examined EGFR mutation status in serum of 80 patients with advanced, EGFR-TKIs given as first-line therapy NSCLC. All patients were received long-term follow-up, and the drug efficacy were observed and evaluated. Results The EGFR mutation in serum was detected in 33.8% (27/80 of NSCLC patients examined, in which exon 19 deletion mutation was present at a frequency of 44.4% (12/27 and exon 21 point mutation was 55.6% (15/27; The response rate to EGFR-TKI in patients with EGFR mutation in serum was (55.6%, 15/27, which was remarkably higher than that in EGFR wild-type patients (17.0%, 9/53, the difference was statistically significant (χ2=0.370, P<0.001; The median progression free survival (PFS of patients with EGFR mutation in serum was remarkably better than that of EGFR wild-type patients (9.8 months vs 5.7 months, P=0.014. Conclusion In patients with advanced, EGFR-positive in serum NSCLC, EGFR-TKIs given as first-line therapy is associated with improved drug efficacy. The results suggest that it is feasible to use serum to detect EGFR mutation, which can predict a benefit from EGFR-TKIs given as first-line therapy.

  4. Patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. Data on potential cures, chronic toxicities, and late relapses after a five- to eleven-year follow-up

    International Nuclear Information System (INIS)

    The authors assessed the outcome in 252 patients with small-cell lung cancer 5 to 11 years after treatment with combination chemotherapy, with or without chest and cranial irradiation, in National Cancer Institute therapeutic trials from 1973 through 1978. Twenty-eight patients (11%) survived free of cancer for 30 months or more. Fourteen patients remain alive without evidence of cancer beyond 5 years, and 7 patients have returned to a lifestyle similar to that before diagnosis. The other 14 patients who were cancer-free at 30 months have developed cancer or died. A few patients with small-cell lung cancer (5.6%) may be cured. Thirty-month, cancer-free survival is insufficient to show a cure. Although late toxicities are troublesome, they do not outweigh the benefits of prolonged survival and potential for cure with modern aggressive therapy in small-cell lung cancer

  5. Influence of tumor response on the survival of patients with extensive-stage small-cell lung cancer treated with the etoposide plus cisplatin chemotherapy regimen

    Institute of Scientific and Technical Information of China (English)

    Guojing Zhang; Yaling Han; Xiaodong Xie; Yongye Liu; Chao Lin; Jianfei Guo; Long Xu; Junling Liu; Ying Piao; Guanzhong Zhang; Yuhui Liu

    2015-01-01

    Objective In this study, we evaluated the dif erence of progression-free survival (PFS) and overal surviv-al (OS) between extensive-stage smal-cel lung cancer (ES-SCLC) patients who acquired partial response (PR) or complete remission (CR) after two cycles of first-line chemotherapy with the etoposide plus cisplatin (EP) regimen and those who acquired PR or CR after four or six cycles. Methods A total of 106 eligible patients treated with the EP chemotherapy regimen for two to six cycles, at The General Hospital of Shenyang Military Region (China) between November 2004 and May 2011, were enrol ed in this study. RECIST version 1.1 was used for the evaluation of chemotherapy ef iciency. We fol owed up al eligible patients every 4 weeks. Al statistical data were analyzed by using SPSS 21.0 statistical package for Windows. Results After a median fol ow-up of 293 days (range, 62–1531 days), al patients had died by the cutof date. Fifty-one patients acquired PR or CR after two cycles of chemotherapy; the median PFS reached 6.0 months (95% CI, 5.1–6.9), and the median OS was 10.5 months (95% CI, 8.6–12.4). Twenty-eight patients acquired PR or CR after four or six cycles; the median PFS was 4.8 months (95% CI, 4.4–5.2), and the median OS was 7.5 months (95% CI, 6.8–8.2). Both PFS and OS showed a statistical dif erence between the two groups. Conclusion ES-SCLC patients who acquired PR or CR after two cycles of the EP regimen as first-line therapy had longer PFS and OS than those who acquired PR or CR after four or six cycles.

  6. Clinical outcomes of extensive stage small cell lung cancer patients treated with intensive modified radiotherapy%广泛期SCLC化疗后IMRT的疗效分析

    Institute of Scientific and Technical Information of China (English)

    张文珏; 周宗玫; 陈东福; 肖泽芬; 冯勤付; 吕纪马; 梁军; 董昕; 惠周光

    2016-01-01

    目的 回顾研究广泛期SCLC化疗后IMRT的疗效及预后.方法 回顾分析2007-2012年在本院放疗科接受化疗+IMRT的130例初治广泛期SCLC患者,化疗方案以EP、CE方案为主,放疗剂量32 Gy~63 Gy,35例患者进行了PCI.Kaplan-Meier法计算生存率,Logrank法单因素预后分析,Cox模型多因素预后分析.结果 随访率96.1%.全组治疗毒性轻微,≥2级血液学毒性及放射性食管炎发生率分别为22.3%、12.2%,≥2级RP发生率7.7%.放疗后达CR、PR、SD、PD者分别占4.6%、72.3%、6.2%、13.1%,疗效未能评价5例,客观有效率76.9%.中位生存期18个月(4~66个月),1、2年OS率分别为72.3%、38.3%.30例(23.1%)患者放疗后发生局部区域失败,83例(63.8%)发生远处失败.26例放疗计划可恢复的局部区域失败患者中,22例单纯照射野内失败,2例单纯野外失败,2例野内野外同时失败.单因素分析中年龄、LDH水平、放疗剂量、PCI是影响预后因素(P=0.014、0.049、0.043、0.003),多因素分析中放疗剂量、PCI是影响预后因素(P=0.021、0.007).初诊无脑转移患者PCI明显改善生存(HR=2.318,95% CI为1.388~3.871;P=0.003)并降低累积脑转移率(18.4%:37.2%,P=0.038).胸部放疗EQD2剂量达54 Gy可改善OS(HR=1.615,95% CI为1.016~2.567;P=0.043),并有改善PFS趋势(HR=1.49,95% CI为0.965~ 2.299,P=0.072).结论 化疗有效的广泛期SCLC行胸部放疗可提高LC率及OS率,适当提高胸部剂量可改善患者预后.PCI可显著改善OS并降低脑转移发生率.%Objective To determine the effect and the patterns of failure in extensive small cell lung cancer (SCLC) patients treated with thoracic intensive modified radiotherapy (IMRT).Methods A retrospective review was conducted on 130 extensive stage SCLC patients received thoracic IMRT from January 2007 to December 2012.Most patients received initial chemotherapy with carboplatin plus etoposide or chemotherapy with cisplatin plus

  7. Prediction of Candidate Drugs for Treating Pancreatic Cancer by Using a Combined Approach.

    Directory of Open Access Journals (Sweden)

    Yanfen Ma

    Full Text Available Pancreatic cancer is the leading cause of death from solid malignancies worldwide. Currently, gemcitabine is the only drug approved for treating pancreatic cancer. Developing new therapeutic drugs for this disease is, therefore, an urgent need. The C-Map project has provided a wealth of gene expression data that can be mined for repositioning drugs, a promising approach to new drug discovery. Typically, a drug is considered potentially useful for treating a disease if the drug-induced differential gene expression profile is negatively correlated with the differentially expressed genes in the target disease. However, many of the potentially useful drugs (PUDs identified by gene expression profile correlation are likely false positives because, in C-Map, the cultured cell lines to which the drug is applied are not derived from diseased tissues. To solve this problem, we developed a combined approach for predicting candidate drugs for treating pancreatic cancer. We first identified PUDs for pancreatic cancer by using C-Map-based gene expression correlation analyses. We then applied an algorithm (Met-express to predict key pancreatic cancer (KPC enzymes involved in pancreatic cancer metabolism. Finally, we selected candidates from the PUDs by requiring that their targets be KPC enzymes or the substrates/products of KPC enzymes. Using this combined approach, we predicted seven candidate drugs for treating pancreatic cancer, three of which are supported by literature evidence, and three were experimentally validated to be inhibitory to pancreatic cancer celllines.

  8. MAL-PDT for difficult to treat nonmelanoma skin cancer.

    Science.gov (United States)

    Stebbins, William G; Hanke, C William

    2011-01-01

    With an incidence of over 3.5 million nonmelanoma skin cancers (NMSCs) per year in the United States, there is an increasing need for effective, cost-effective treatments for NMSC. When surgical excision is impractical or not feasible, methyl aminolevulinate photodynamic therapy (MAL-PDT) has demonstrated consistently high long-term cure rates ranging from 70-90%, with superior cosmetic outcomes compared with other treatment modalities. With the exception of invasive squamous cell carcinoma, MAL-PDT has been successful in treating all types of NMSC, especially in patients with multiple comorbidities, field cancerization, and lesions in cosmetically sensitive locations. Herein, a step-by-step description of the procedure for MAL-PDT is provided, followed by a review of outcomes from large clinical trials performed over the past 15 years for each variant of NMSC. After reading this review, clinicians should have a thorough understanding of the benefits and limits of MAL-PDT, and should be able to add this valuable procedure to their armamentarium of therapies for NMSC.

  9. Factors associated with early progression of non-small-cell lung cancer treated by epidermal growth factor receptor tyrosine-kinase inhibitors

    International Nuclear Information System (INIS)

    Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKI) are a therapeutic option as second-line therapy in non-small-cell lung carcinoma (NSCLC), regardless of the EGFR gene status. Identifying patients with early progression during EGFR-TKI treatment will help clinicians to choose the best regimen, TKI or chemotherapy. From a prospective database, all patients treated with gefitinib or erlotinib between 2001 and 2010 were retrospectively reviewed. Patients were classified into two groups according to their tumor response by RECIST after 45 days of treatment, progressive disease (PD) or controlled disease (CD). Two hundred and sixty-eight patients were treated with EGFR-TKI, among whom 239 were classified as PD (n = 75) and CD (n = 164). Median overall survival was 77 days (95% CI 61–109) for PD and 385 days (95% CI 267–481) for CD. Patients with PD were of younger age (P = 0.004) and more frequently current smokers (P = 0.001) had more frequently a performance status ≥2 (P = 0.012), a weight loss ≥10% (P = 0.025), a shorter time since diagnosis (P < 0.0001), a pathological classification as non-otherwise-specified NSCLC (P = 0.01), and the presence of abdominal metastases (P = 0.008). In multivariate analysis, abdominal metastases were the only factor associated with early progression (odds ratio (OR) 2.17, 95% CI [1.12–4.19]; P = 0.021). Wild-type EGFR versus mutated EGFR was associated with early progression. The presence of abdominal metastasis was independently associated with early progression in metastatic NSCLC receiving EGFR-TKI

  10. Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Yang Han

    Full Text Available To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. TGFβR2 expression was also significantly correlated with other clinical parameters such as tumor differentiation, invasion of lung membrane, and chemotherapy. Moreover, overall survival (OS and disease free survival (DFS was increased in patients with low TGFβR2 expressing NSCLC and who had undergone chemotherapy. Thus, high expression of TGFβR2 is a significant risk factor for decreased OS and DFS in NSCLC patients. Thus, TGFβR2 is a potential prognostic tumor biomarker for chemotherapy.

  11. Increased Expression of TGFβR2 Is Associated with the Clinical Outcome of Non-Small Cell Lung Cancer Patients Treated with Chemotherapy

    Science.gov (United States)

    Yu, Fei; Cai, Haidong; Fang, Suyun; Cai, Li; Yang, Huiqiong; Sun, Yu; Li, Dan; Liu, Jin; Xie, Ruting; Yuan, Xueyu; Zhong, Xiaoming; Li, Ming; Wei, Qing; Lv, Zhongwei; Fu, Da; Ma, Yushui

    2015-01-01

    To investigate the prognostic significance of TGFβR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC) patients, TGFβR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFβR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. TGFβR2 expression was also significantly correlated with other clinical parameters such as tumor differentiation, invasion of lung membrane, and chemotherapy. Moreover, overall survival (OS) and disease free survival (DFS) was increased in patients with low TGFβR2 expressing NSCLC and who had undergone chemotherapy. Thus, high expression of TGFβR2 is a significant risk factor for decreased OS and DFS in NSCLC patients. Thus, TGFβR2 is a potential prognostic tumor biomarker for chemotherapy. PMID:26252213

  12. Is Huachansu Beneficial in Treating Advanced Non-Small-Cell Lung Cancer? Evidence from a Meta-Analysis of Its Efficacy Combined with Chemotherapy

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    Bingduo Zhou

    2015-01-01

    Full Text Available Background. Huachansu, the sterilized water extract of Bufo bufo gargarizans toad skin, is used in China to alleviate the side-effects and enhance the therapeutic effect of chemotherapy in advanced non-small-cell lung cancer (NSCLC. We conducted a meta-analysis to assess Huachansu’s efficacy. Methods. We extensively searched electronic databases (CENTRAL, EMBASE, MEDLINE, CBM, Cochrane Library, CNKI, CEBM, WFDP, CSCD, CSTD, and IPA for randomized controlled trials containing Huachansu plus chemotherapy as the test group and chemotherapy as the control group. Seventeen trials were selected based on the selection criteria. The pooled relative ratio (RR of indicators with 95% confidence interval (95% CI was calculated for efficacy evaluation. Results. The meta-analysis demonstrated a statistically significant improvement in objective tumor response, one-year survival, Karnofsky performance status, pain relief, and alleviation of severe side-effects (nausea and vomiting, leukocytopenia in the test group as compared to the control group, but no significant difference in thrombocytopenia. Conclusions. This study demonstrated the efficacy of Huachansu combined with chemotherapy in the treatment of advanced NSCLC. However, limitations exist and high-quality trials are needed for further verification.

  13. Urothelial Cancer Stem Cells

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    Irena Dimov

    2010-01-01

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

  14. How Taxol/paclitaxel kills cancer cells

    OpenAIRE

    Weaver, Beth A

    2014-01-01

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

  15. Yttrium-90 used to treat colon cancer: Awaiting investigational new drug approval

    International Nuclear Information System (INIS)

    A new radiation treatment takes just 14 to 21 days to shrink colorectal tumors in laboratory mice, is under review for clinical trials with human cancer patients. The treatment has succeeded in reducing the size of tumors by up to 95%. Colon cancer, the second leading cause of cancer deaths in the US, is extremely difficult to treat unless it is detected early enough for surgical procedures. In laboratory tests over the last 5 years, a team of researchers has developed the treatment using yttrium-90. The yttrium-90 is transported to the tumors by attaching it to monoclonal antibodies that seek out the cancer cells. Once the radioisotope has been targeted to the tumor, the radiation destroys many of the cells, dramatically reducing the size of the tumor. Since this treatment usually does not completely eliminate all the cancer cells, it cannot be called a cure, but it does seem to be an effective method of shrinking colorectal tumors

  16. New Paradigm in Treating Cancer: Right on Target.

    Science.gov (United States)

    Sutandyo, Noorwati

    2016-04-01

    Cancer prevalence is increasing every year and now cancer is the third highest cause of death in developing countries. Effective anticancer treatment can prolong life and improve the patient's quality of life. Targeted therapy is a new therapeutic modality which targets specific molecules in the cancer cell and disrupts dysregulated signaling pathways involved in carcinogenesis. Since targeted therapy does not attack normal cells, its side effects are considered low compared to chemotherapy. More than 15 drugs have been approved for treatment in various human cancers. These drugs can largely be grouped into tyrosine kinase inhibitors and monoclonal antibodies. This review will focus on the most common agents within both groups. PMID:27550884

  17. New modalities to treat laryngeal cancer.

    OpenAIRE

    Prgomet, Drago

    2012-01-01

    Early laryngeal cancer comprises T1 and T2 stages of the disease. Open functional operations achieve local control of the disease in 90–95% of T1 patients and in 70–90% of T2 patients. Primary RT achieves local control in 85–94% of T1 tumors and in 70–80% of patients with T2 tumors. Introduction of endoscopic laser surgery resulted in further popularization of preservation laryngeal surgery, whereby equally successful treatment results are achieved with minimal invasiveness. Quality of voice ...

  18. Combination Chemotherapy Plus Amifostine in Treating Patients With Metastatic or Unresectable Cancer

    Science.gov (United States)

    2009-02-06

    Bladder Cancer; Brain and Central Nervous System Tumors; Carcinoma of Unknown Primary; Extragonadal Germ Cell Tumor; Head and Neck Cancer; Kidney Cancer; Lung Cancer; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  19. Interleukin-12 in Treating Patients With Hematologic Cancers or Solid Tumors

    Science.gov (United States)

    2014-09-09

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

  20. 舒尼替尼治疗非小细胞肺癌的现状%The current situation of Sunitinib in treating non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Qingjie Yang; Xiaoyan Sun; Ming Guo

    2012-01-01

    Sunitinib malate is one of the multitargeted tyrosine kinase inhibitor, which are being used in clinic.It can inhibit more than 80 kinds of receptor`s tyrosine kinase, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptors, vascular endothelial growth factor receptors (VEGFR), etc.And tyrosine kinase inhibitor is involved in connection with the generation and progression of many kinds of cancer including lung cancer.Several studies have evaluated the effect of Sunitinib on non-small cell lung cancer (NSCLC), by single agent, continuous daily dosing or in combination with chemotherapeutics (with docetaxel or gemcitabine plus cisplatin), which all showed certain effect.The test of Sunitinib in combination with gemcitabine plus cisplatin for advanced NSCLC shown that at the maximum tolerated dose: oral Sunitinib 37.5 mg/day intermittently (Schedule 2/1: 2 weeks on treatment, 1 week off treatment) schedule with intravenous infusions of gemcitabine (1000 mg/m2 days 1, 8) and cisplatin (80 mg/m2 day 1), administered in 3-week cycles, 66.7% patients achieved partial responses.And adverse effects were mild to moderate in severity (grades 1 to 2).Therapy was generally well tolerated.In summary, all the evidence above suggests that Sunitinib may play an important role in the treating of NSCLC.

  1. EFFECT OF SOMATOSTATIN ON THE CELL CYCLE OF HUMAN GALLBLADDER CANCER CELL

    Institute of Scientific and Technical Information of China (English)

    李济宇; 全志伟; 张强; 刘建文

    2005-01-01

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

  2. [Basal cell carcinoma, squamous cell carcinoma and premalignant skin lesions--how to treat?].

    Science.gov (United States)

    Pitkänen, Sari; Jeskanen, Leila; Ylitalo, Leea

    2014-01-01

    Increasing exposure to UV radiation is considered the most important etiologic factor of nonmelanoma skin cancers. Consequently, exposed areas such as the scalp and face, are the primary areas for developing non-melanoma skin cancers. Once a patient has presented with one tumor, additional lesions are common. The diagnosis is based on typical clinical picture and biopsy or excision for histopathological analysis. Various non-surgical treatment options have been established. Superficial basal cell carcinoma, superficial carcinoma in situ and all actinic keratoses are preferentially treated non-surgically. Most other basal cell and squamous cell carcinomas should be surgically removed. PMID:24724463

  3. Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

    Science.gov (United States)

    2015-09-01

    Recurrent Large Cell Lung Carcinoma; Recurrent Lung Adenocarcinoma; Recurrent Squamous Cell Lung Carcinoma; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Squamous Cell Lung Carcinoma

  4. Dynamic contrast-enhanced CT in patients treated with sorafenib and erlotinib for non-small cell lung cancer: a new method of monitoring treatment?

    Energy Technology Data Exchange (ETDEWEB)

    Lind, Joline S.W.; Postmus, Pieter E.; Smit, Egbert F. [VU University Medical Center, Department of Pulmonary Diseases, Amsterdam (Netherlands); Meijerink, Martijn R.; Kuijk, Cornelis van [VU University Medical Center, Department of Radiology, De Boelelaan 1117, P.O. Box 7075, Amsterdam (Netherlands); Dingemans, Anne-Marie C. [Maastricht University, Medical Centre, Department of Pulmonary Diseases, Maastricht (Netherlands); Oellers, Michel C.; Ruysscher, Dirk de [Maastricht University, Medical Centre, Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands)

    2010-12-15

    We investigated the feasibility of serial dynamic contrast-enhanced computed tomography (DCE-CT) in patients with advanced/metastatic non-small cell lung cancer (NSCLC) receiving anti-angiogenic (sorafenib) and anti-EGFR (erlotinib) treatment, and correlated tumour blood flow (BF) with treatment outcome. DCE-CTs were performed at baseline and 3 and 6 weeks after starting treatment. Tumour BF, calculated with the maximum slope method, and percentage change were measured in 23 patients (14 male; median age 59 years). Tumour BF was compared at baseline and weeks 3 and 6; the relation with RECIST/Crabb response and progression-free survival (PFS) was assessed. Mean tumour perfusion decreased from 39.2 ml/100 g/min at baseline to 15.1 ml/100 g/min at week 3 (p < 0.001) and 9.4 ml/100 g/min at week 6 (p < 0.001). Tumour perfusion was lower in RECIST and Crabb responders versus non-responders at week 3 (4.2 versus 17.7 ml/100 g/min, p = 0.03) and week 6 (0 versus 13.4 ml/100 g/min, p = 0.04). Patients with a decrease larger than the median at week 6 tended to have a longer PFS (7.1 versus 5.7 months, p = 0.06). Serial DCE-CTs are feasible in patients with NSCLC and demonstrated a significant decrease in tumour BF following sorafenib/erlotinib therapy. Early changes in tumour BF correlated with objective response and showed a trend towards longer PFS. (orig.)

  5. Change in Diffusing Capacity After Radiation as an Objective Measure for Grading Radiation Pneumonitis in Patients Treated for Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Guerra, Jose Luis [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Department of Radiation Oncology, Hospitales Universitarios Virgen del Rocio, Seville (Spain); Gomez, Daniel, E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Zhuang Yan; Levy, Lawrence B. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Eapen, George [Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Liu Hongmei; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-08-01

    Purpose: Scoring of radiation pneumonitis (RP), a dose-limiting toxicity after thoracic radiochemotherapy, is subjective and thus inconsistent among studies. Here we investigated whether the extent of change in diffusing capacity of the lung for carbon monoxide (DLCO) after radiation therapy (RT) for non-small-cell lung cancer (NSCLC) could be used as an objective means of quantifying RP. Patients and Methods: We analyzed potential correlations between DLCO and RP in 140 patients who received definitive RT ({>=}60 Gy) with or without chemotherapy for primary NSCLC. All underwent DLCO analysis before and after RT. Post-RT DLCO values within 1 week of the RP diagnosis (Grade 0, 1, 2, or 3) were selected and compared with that individual's preradiation values. Percent reductions in DLCO and RP grade were compared by point biserial correlation in the entire patient group and in subgroups stratified according to various clinical factors. Results: Patients experiencing Grade 0, 1, 2, or 3 RP had median percentage changes in DLCO after RT of 10.7%, 13%, 22.1%, or 35.2%. Percent reduction in DLCO correlated with RP Grade {<=}1 vs. {>=}2 (p = 0.0004). This association held for the following subgroups: age {>=}65 years, advanced stage, smokers, use of chemotherapy, volume of normal lung receiving at least 20 Gy {>=}30%, and baseline DLCO or forced expiratory volume in 1 second {>=}60%. Conclusions: By correlating percent change in DLCO from pretreatment values at the time of diagnosis of RP with RP grade, we were able to identify categories of RP based on the change in DLCO. These criteria provide a basis for an objective scoring system for RP based on change in DLCO.

  6. Change in Diffusing Capacity After Radiation as an Objective Measure for Grading Radiation Pneumonitis in Patients Treated for Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: Scoring of radiation pneumonitis (RP), a dose-limiting toxicity after thoracic radiochemotherapy, is subjective and thus inconsistent among studies. Here we investigated whether the extent of change in diffusing capacity of the lung for carbon monoxide (DLCO) after radiation therapy (RT) for non-small-cell lung cancer (NSCLC) could be used as an objective means of quantifying RP. Patients and Methods: We analyzed potential correlations between DLCO and RP in 140 patients who received definitive RT (≥60 Gy) with or without chemotherapy for primary NSCLC. All underwent DLCO analysis before and after RT. Post-RT DLCO values within 1 week of the RP diagnosis (Grade 0, 1, 2, or 3) were selected and compared with that individual’s preradiation values. Percent reductions in DLCO and RP grade were compared by point biserial correlation in the entire patient group and in subgroups stratified according to various clinical factors. Results: Patients experiencing Grade 0, 1, 2, or 3 RP had median percentage changes in DLCO after RT of 10.7%, 13%, 22.1%, or 35.2%. Percent reduction in DLCO correlated with RP Grade ≤1 vs. ≥2 (p = 0.0004). This association held for the following subgroups: age ≥65 years, advanced stage, smokers, use of chemotherapy, volume of normal lung receiving at least 20 Gy ≥30%, and baseline DLCO or forced expiratory volume in 1 second ≥60%. Conclusions: By correlating percent change in DLCO from pretreatment values at the time of diagnosis of RP with RP grade, we were able to identify categories of RP based on the change in DLCO. These criteria provide a basis for an objective scoring system for RP based on change in DLCO.

  7. Prognosis of non-small cell lung cancer patients with bone oligometastases treated concurrently with thoracic three-dimensional radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    To evaluate the efficacy of three-dimensional radiotherapy for non-small cell lung cancer (NSCLC) patients with bone metastases. Clinical data for 95 NSCLC patients with bone metastases were collected and prognostic factors were analyzed. All patients received radiation to their thoracic primary tumor and ≥2 cycles of chemotherapy. Of these 95 patients, 47 patients had only bone metastases and 48 had both bone metastases and other organ metastases. Univariate analysis showed that factors that statistically significantly contributed to patients having longer overall survival (OS) included receiving a radiation dose to the primary tumor ≥63 Gy, responding to treatment and receiving ≥4 cycles of chemotherapy (p = 0.001, p = 0.037 and p = 0.009, respectively). A radiation dose to the primary tumor ≥63 Gy remained significant for patients with bone metastases only as well as those with bone and other organ metastases when they were analyzed separately (p = 0.045 and p = 0.012, respectively). For patients with bone metastases only, those with T1-2 tumors had longer OS than those with T3-4 (p = 0.048); and patients who received ≥4 cycles chemotherapy compared with those who received <4 cycles had similar OS (p = 0.385). On multivariate analysis, only a radiation dose ≥63 Gy (p = 0.028) and having only bone metastases (p = 0.006) were independent prognostic factors for better OS. A radiation dose to the primary tumor ≥63 Gy and having only bone metastases were associated with better OS in NSCLC patients with bone metastases. For patients with bone metastases only, besides radiation dose, T status was also correlated with OS, whereas the number of chemotherapy cycles was not. Therefore, aggressive thoracic radiation may play an important role in improving OS

  8. DNA methylation biomarkers predict progression-free and overall survival of metastatic renal cell cancer (mRCC treated with antiangiogenic therapies.

    Directory of Open Access Journals (Sweden)

    Inga Peters

    Full Text Available VEGF-targeted therapy increases both the progression-free (PFS and overall survival (OS of patients with metastasized renal cell cancer (mRCC. Identification of molecular phenotypes of RCC could improve risk-stratification and the prediction of the clinical disease course. We investigated whether gene-specific DNA hypermethylation can predict PFS and OS among patients undergoing anti-VEGF-based therapy. Primary tumor tissues from 18 patients receiving targeted therapy were examined retrospectively using quantitative methylation-specific PCR analysis of CST6, LAD1, hsa-miR-124-3, and hsa-miR-9-1 CpG islands. PFS and OS were analyzed for first-line and sequential antiangiogenic therapies using the log rank statistics. Sensitivity and specificity were determined for predicting first-line therapy failure. Hypermethylation of CST6 and LAD1 was associated with both a shortened PFS (log rank p = 0.009 and p = 0.004 and OS (p = 0.011 and p = 0.043. The median PFS observed for the high and low methylation groups of CST6 and LAD1 was 2.0 vs.11.4 months. LAD1 methylation had a specificity of 1.0 (95% CI 0.65-1.0 and a sensitivity of 0.73 (95% CI 0.43-0.90 for the prediction of first-line therapy. CST6 and LAD1 methylation are candidate epigenetic biomarkers showing unprecedented association with PFS and OS as well as specificity for the prediction of the response to therapy. DNA methylation markers should be considered for the prospective evaluation of larger patient cohorts in future studies.

  9. Differential Expression of Gene Profiles in MRGX-treated Lung Cancer

    OpenAIRE

    Kwon Yong-Kyun; Lee Seung-Yeul; Kang Hwan-Soo; Sung Jung-Suk; Cho Chong-Kwan; Yoo Hwa-Seung; Shin Seungjin; Choi Jong-Soon; Lee Yeon-Weol; Jang Ik-Soon

    2013-01-01

    Objectives: Modified regular ginseng extract (MRGX) has stronger anti-cancer activity-possessing gensenoside profiles. Methods: To investigate changes in gene expression in the MRGX-treated lung cancer cells (A549), we examined genomic data with cDNA microarray results. After completing the gene-ontology-based analysis, we grouped the genes into up-and down-regulated profiles and into ontology-related regulated genes and proteins through their interaction network. Results: One hundred n...

  10. Randomized Phase II Study of Docetaxel plus Personalized Peptide Vaccination versus Docetaxel plus Placebo for Patients with Previously Treated Advanced Wild Type EGFR Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Koichi Takayama

    2016-01-01

    Full Text Available Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC. Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m2 on Day 1 plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression-free survival (PFS. Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p=0.42. Interestingly, PFS and overall survival (OS in humoral immunological responder were significantly longer than those in nonresponder. Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed.

  11. Randomized Phase II Study of Docetaxel plus Personalized Peptide Vaccination versus Docetaxel plus Placebo for Patients with Previously Treated Advanced Wild Type EGFR Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Takayama, Koichi; Sugawara, Shunichi; Saijo, Yasuo; Maemondo, Makoto; Sato, Atsushi; Takamori, Shinzo; Harada, Taishi; Sasada, Tetsuro; Kakuma, Tatsuyuki; Kishimoto, Junji; Yamada, Akira; Noguchi, Masanori; Itoh, Kyogo; Nakanishi, Yoichi

    2016-01-01

    Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV) combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC). Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor) wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m(2) on Day 1) plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression-free survival (PFS). Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p = 0.42). Interestingly, PFS and overall survival (OS) in humoral immunological responder were significantly longer than those in nonresponder. Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed. PMID:27274999

  12. Chemoprevention gene therapy (CGT): novel combinatorial approach for preventing and treating pancreatic cancer.

    Science.gov (United States)

    Sarkar, S; Azab, B M; Das, S K; Quinn, B A; Shen, X; Dash, R; Emdad, L; Thomas, S; Dasgupta, S; Su, Z-Z; Wang, X-Y; Sarkar, D; Fisher, P B

    2013-08-01

    Pancreatic cancer remains one of the deadliest of all cancers despite aggressive surgical treatment combined with adjuvant radiotherapy and chemotherapy. Chemoresistance and radioresistance are the principal causes of failure of pancreatic cancer patients to respond to therapy. Conditionally replication competent adenovirus (CRCA)-based cancer gene therapy is an innovative strategy for treating cancers displaying inherent resistance to treatment. Limitations of current adenovirus (Ad)-based gene therapies for malignant tumors include lack of cancer-specificity, and effective and targeted delivery. To remedy this situation, CRCAs have been designed that express E1A, necessary for Ad replication, under the control of a cancer-specific progression elevated gene-3 promoter (PEG-Prom) with concomitant expression of an immunomodulatory cytokine, such as mda-7/IL-24 or interferon-γ (IFN-γ), under the control of a ubiquitous and strong cytomegalovirus promoter (CMV-Prom) from the E3 region. These bipartite CRCAs, when armed with a transgene, are called cancer terminator viruses (CTVs), i.e., Ad.PEG-E1A-CMV-mda-7 (CTV-M7) and Ad.PEG-E1A-CMV-IFN-γ (CTV-γ), because of their universal effectiveness in cancer treatment irrespective of p53/pRb/p16 or other genetic alterations in tumor cells. In addition to their selective oncolytic effects in tumor cells, the potent 'bystander antitumor' properties of MDA-7/IL-24 and IFN-γ embody the CTVs with expanded treatment properties for both primary and distant cancers. Pancreatic cancer cells display a "translational block" of mda-7/IL-24 mRNA, limiting production of MDA-7/IL-24 protein and cancer-specific apoptosis. Specific chemopreventive agents abrogate this "translational block" resulting in pancreatic cancer-specific killing. This novel chemoprevention gene therapy (CGT) strategy holds promise for both prevention and treatment of pancreatic cancers where all other strategies have proven ineffective.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

  15. Intrinsic fluorescence biomarkers in cells treated with chemopreventive drugs

    Science.gov (United States)

    Kirkpatrick, Nathaniel D.; Brands, William R.; Zou, Changping; Brewer, Molly A.; Utzinger, Urs

    2005-03-01

    Non-invasive monitoring of cellular metabolism offers promising insights into areas ranging from biomarkers for drug activity to cancer diagnosis. Fluorescence spectroscopy can be utilized in order to exploit endogenous fluorophores, typically metabolic co-factors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), and estimate the redox status of the sample. Fluorescence spectroscopy was applied to follow metabolic changes in epithelial ovarian cells as well as bladder epithelial cancer cells during treatment with a chemopreventive drug that initiates cellular quiescence. Fluorescence signals consistent with NADH, FAD, and tryptophan were measured to monitor cellular activity, redox status, and protein content. Cells were treated with varying concentrations of N-4-(hydroxyphenyl) retinamide (4-HPR) and measured in a stable environment with a sensitive fluorescence spectrometer. A subset of measurements was completed on a low concentration of cells to demonstrate feasibility for medical application such as in bladder or ovary washes. Results suggest that all of the cells responded with similar dose dependence but started at different estimated redox ratio baseline levels correlating with cell cycle, growth inhibition, and apoptosis assays. NADH and tryptophan related fluorescence changed significantly while FAD related fluorescence remained unaltered. Fluorescence data collected from approximately 1000 - 2000 cells, comparable to a bladder or ovary wash, was measurable and useful for future experiments. This study suggests that future intrinsic biomarker measurements may need to be most sensitive to changes in NADH and tryptophan related fluorescence while using FAD related fluorescence to help estimate the baseline redox ratio and predict response to chemopreventive agents.

  16. Early reduction in tumour [{sup 18}F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone

    Energy Technology Data Exchange (ETDEWEB)

    Trigonis, Ioannis; Tamal, Mahbubunnabi; Anton-Rodriguez, Jose; Jackson, Alan; Asselin, Marie-Claude [The University of Manchester, Institute of Population Health, Wolfson Molecular Imaging Centre, Manchester Academic Health Sciences Centre, Manchester (United Kingdom); Koh, Pek Keng [The University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester (United Kingdom); Taylor, Ben; Ryder, David; Earl, Mark [The Christie NHS Foundation Trust, Manchester (United Kingdom); Haslett, Kate; Faivre-Finn, Corinne; Blackhall, Fiona [The University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester (United Kingdom); The Christie NHS Foundation Trust, Manchester (United Kingdom); Young, Helen [AstraZeneca Pharmaceuticals, Macclesfield (United Kingdom)

    2014-04-15

    Changes in tumour 3'-deoxy-3'-[{sup 18}F]fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability. Sixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5-11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUV{sub mean} and SUV{sub max}) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions. In all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUV{sub mean} reproducibility in primary tumours (SD 8.9 %) was better than SUV{sub max} reproducibility (SD 12.6 %). In nodes, SUV{sub mean} and SUV{sub max} reproducibilities (SD 18.0 and 17.2 %) were comparable but worse than for primary tumours. After 5-11 RT fractions, primary tumour SUV{sub mean} decreased significantly by 25 % (p = 0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31 % (p = 0.020) with a larger SUV{sub mean} decrease of 40 % (p < 0.0001). Similar changes were found for SUV{sub max}. Across this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously

  17. Gemcitabine and capecitabine for heavily pre-treated metastatic colorectal cancer patients

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise G; Pallisgaard, Niels; Andersen, Rikke F;

    2014-01-01

    AIM: We investigated the efficacy and safety of capecitabine and gemcitabin (GemCap) in heavily pre-treated, therapy-resistant metastatic colorectal cancer (mCRC) patients and the clinical importance of cell-free DNA (cfDNA) measurement. PATIENTS AND METHODS: Patients' inclusion criteria included...

  18. Total-Body Irradiation With or Without Fludarabine Phosphate Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

    Science.gov (United States)

    2016-02-02

    Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Aggressive Non-Hodgkin Lymphoma; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Hematopoietic and Lymphoid Cell Neoplasm; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Waldenstrom Macroglobulinemia

  19. Psychological functioning in cancer patients treated with radiotherapy

    NARCIS (Netherlands)

    Stiegelis, HE; Ranchor, AV; Sanderman, R

    2004-01-01

    Although many side-effects of radiotherapy (RT) are physical, previous studies have shown that patients, when treated with RT, also experience psychological problems. This review describes the psychological functioning of cancer patients prior to, during, and after RT. Moreover, we examined whether

  20. General Information about Small Cell Lung Cancer

    Science.gov (United States)

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

  1. Stages of Small Cell Lung Cancer

    Science.gov (United States)

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

  2. Treatment Option Overview (Small Cell Lung Cancer)

    Science.gov (United States)

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

  3. Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs:a systemic review and meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Jie-Ying Chen; Ya-Nan Cheng; Lei Han; Feng Wei; Wen-Wen Yu; Xin-Wei Zhang; Shui Cao; Jin-Pu Yu

    2015-01-01

    Objective:A meta-analysis was performed to augment the insuffcient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical effciency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients. Methods:Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated. Results:Mutation in K-ras signiifcantly predicted poor ORR [OR=0.22;95%conifdence interval (CI), 0.13-0.35], shorter PFS (HR=1.56;95%CI, 1.27-1.92), and shorter OS (HR=1.59;95%CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA signiifcantly predicted shorter OS (HR=1.83;95%CI, 1.05-3.20), showed poor ORR (OR=0.70;95%CI, 0.22-2.18), and shorter PFS (HR=1.79;95%CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs. Conclusion:K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR-TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will beneift from EGFR-TKI treatment.

  4. Predictive value of K-ras and PIK3CA in non-small cell lung cancer patients treated with EGFR-TKIs: a systemic review and meta-analysis

    Science.gov (United States)

    Chen, Jie-Ying; Cheng, Ya-Nan; Han, Lei; Wei, Feng; Yu, Wen-Wen; Zhang, Xin-Wei; Cao, Shui; Yu, Jin-Pu

    2015-01-01

    Objective A meta-analysis was performed to augment the insufficient data on the impact of mutative EGFR downstream phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways on the clinical efficiency of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment of non-small cell lung cancer (NSCLC) patients. Methods Network databases were explored in April, 2015. Papers that investigated the clinical outcomes of NSCLC patients treated with EGFR-TKIs according to the status of K-ras and/or PIK3CA gene mutation were included. A quantitative meta-analysis was conducted using standard statistical methods. Odds ratios (ORs) for objective response rate (ORR) and hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were calculated. Results Mutation in K-ras significantly predicted poor ORR [OR =0.22; 95% confidence interval (CI), 0.13-0.35], shorter PFS (HR =1.56; 95% CI, 1.27-1.92), and shorter OS (HR =1.59; 95% CI, 1.33-1.91) in NSCLC patients treated with EGFR-TKIs. Mutant PIK3CA significantly predicted shorter OS (HR =1.83; 95% CI, 1.05-3.20), showed poor ORR (OR =0.70; 95% CI, 0.22-2.18), and shorter PFS (HR =1.79; 95% CI, 0.91-3.53) in NSCLC patients treated with EGFR-TKIs. Conclusion K-ras mutation adversely affected the clinical response and survival of NSCLC patients treated with EGFR-TKIs. PIK3CA mutation showed similar trends. In addition to EGFR, adding K-ras and PIK3CA as routine gene biomarkers in clinical genetic analysis is valuable to optimize the effectiveness of EGFR-TKI regimens and identify optimal patients who will benefit from EGFR-TKI treatment. PMID:26175928

  5. Gene expression profiling and pathway analysis in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin

    Science.gov (United States)

    The long-term goal of our study is to understand the genetic and epigenetic mechanisms of breast cancer metastasis in human and to discover new possible genetic markers for use in clinical practice. We have used microarray technology (Human OneArray microarray, phylanxbiotech.com) to compare gene ex...

  6. A peptide against soluble guanylyl cyclase α1: a new approach to treating prostate cancer.

    Directory of Open Access Journals (Sweden)

    Shuai Gao

    Full Text Available Among the many identified androgen-regulated genes, sGCα1 (soluble guanylyl cyclase α1 appears to play a pivotal role in mediating the pro-cancer effects of androgens and androgen receptor. The classical role for sGCα1 is to heterodimerize with the sGCβ1 subunit, forming sGC, the enzyme that mediates nitric oxide signaling by catalyzing the synthesis of cyclic guanosine monophosphate. Our published data show that sGCα1 can drive prostate cancer cell proliferation independent of hormone and provide cancer cells a pro-survival function, via a novel mechanism for p53 inhibition, both of which are independent of sGCβ1, NO, and cGMP. All of these properties make sGCα1 an important novel target for prostate cancer therapy. Thus, peptides were designed targeting sGCα1 with the aim of disrupting this protein's pro-cancer activities. One peptide (A-8R was determined to be strongly cytotoxic to prostate cancer cells, rapidly inducing apoptosis. Cytotoxicity was observed in both hormone-dependent and, significantly, hormone-refractory prostate cancer cells, opening the possibility that this peptide can be used to treat the usually lethal castration-resistant prostate cancer. In mouse xenograft studies, Peptide A-8R was able to stop tumor growth of not only hormone-dependent cells, but most importantly from hormone-independent cells. In addition, the mechanism of Peptide A cytotoxicity is generation of reactive oxygen species, which recently have been recognized as a major mode of action of important cancer drugs. Thus, this paper provides strong evidence that targeting an important AR-regulated gene is a new paradigm for effective prostate cancer therapy.

  7. Design of a nanoplatform for treating pancreatic cancer

    Science.gov (United States)

    Manawadu, Harshi Chathurangi

    Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA. Asymptomatic early cancer stages and late diagnosis leads to very low survival rates of pancreatic cancers, compared to other cancers. Treatment options for advanced pancreatic cancer are limited to chemotherapy and/or radiation therapy, as surgical removal of the cancerous tissue becomes impossible at later stages. Therefore, there's a critical need for innovative and improved chemotherapeutic treatment of (late) pancreatic cancers. It is mandatory for successful treatment strategies to overcome the drug resistance associated with pancreatic cancers. Nanotechnology based drug formulations have been providing promising alternatives in cancer treatment due to their selective targeting and accumulation in tumor vasculature, which can be used for efficient delivery of chemotherapeutic agents to tumors and metastases. The research of my thesis is following the principle approach to high therapeutic efficacy that has been first described by Dr. Helmut Ringsdorf in 1975. However, I have extended the use of the Ringsdorf model from polymeric to nanoparticle-based drug carriers by exploring an iron / iron oxide nanoparticle based drug delivery system. A series of drug delivery systems have been synthesized by varying the total numbers and the ratio of the tumor homing peptide sequence CGKRK and the chemotherapeutic drug doxorubicin at the surfaces of Fe/Fe3O 4-nanoparticles. The cytotoxicity of these nanoformulations was tested against murine pancreatic cancer cell lines (Pan02) to assess their therapeutic capabilities for effective treatments of pancreatic cancers. Healthy mouse fibroblast cells (STO) were also tested for comparison, because an effective chemotherapeutic drug has to be selective towards cancer cells. Optimal Experimental Design methodology was applied to identify the nanoformulation with the highest therapeutic activity. A statistical analysis method known as response

  8. Ovarian cancer: emerging concept on cancer stem cells

    OpenAIRE

    Ponnusamy Moorthy P; Batra Surinder K

    2008-01-01

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

  9. In vitro cytotoxic activity of Thai medicinal plants used traditionally to treat cancer.

    Science.gov (United States)

    Itharat, Arunporn; Houghton, Peter J; Eno-Amooquaye, E; Burke, P J; Sampson, Julia H; Raman, Amala

    2004-01-01

    The SRB assay was used to test cytotoxicity against three human cancer cell lines and one normal cell line of 11 Thai medicinal plant species used by traditional doctors in treating cancer patients. The extraction procedures used were similar to those practised by Thai traditional doctors (ethanolic and water extracts). Extracts were tested against the human large cell lung carcinoma cell line COR-L23, the human breast adenocarcinoma cell line MCF-7 and human colon adenocarcinoma cell line LS-174T and normal human keratinocytes SVK-14. The results showed that three plants; Dioscorea membranacea Pierre ex Prain & Burkill, Dioscorea birmanica Prain & Burkill (Dioscoreaceae) and Siphonodon celastrineus Griff. (Celastraceae), exhibited high cytotoxic activity showing a certain degree of selectivity against the different cell types. PMID:14698505

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

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

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

  11. High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

    Science.gov (United States)

    2016-08-17

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET); Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Plasma Cell Neoplasm; Primary Systemic Amyloidosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2

  12. Immunology of Stem Cells and Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Yang

    2007-01-01

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

  13. Indeterminate cell histiocytosis successfully treated with phototherapy.

    Science.gov (United States)

    Zerbini, Maria Claudia Nogueira; Sotto, Mirian Nacagami; de Campos, Fernando Peixoto Ferraz; Abdo, Andre Neder Ramires; Pereira, Juliana; Sanches, José Antônio; Martins, Jade Cury

    2016-01-01

    First described in 1985, intermediate cell histiocytosis is a rare disorder of the cutaneous dendritic cell group with a varied clinical presentation and evolution. The pathologic substrate is constituted by the proliferation of indeterminate cells (ICs) that are immunophenotypically characterized by the positivity of CD1a, CD68, and faint/focal S100, plus the negativity for CD207 (langerin). The authors present the case of a healthy elderly woman who presented generalized dome-shaped reddish cutaneous nodules over her trunk, neck, face, and extremities over a period of 18 months. A laboratory and imaging work-up ruled out internal involvement. The skin biopsy was consistent with IC histiocytosis. The patient was treated with narrowband ultraviolet B phototherapy, which resulted in an excellent short-term outcome. PMID:27547741

  14. Lung cancer - non-small cell

    Science.gov (United States)

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

  15. Prostate cancer stem cell biology

    OpenAIRE

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

    2012-01-01

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

  16. Differential Expression of Gene Profiles in MRGX-treated Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kwon Yong-Kyun

    2013-09-01

    Full Text Available Objectives: Modified regular ginseng extract (MRGX has stronger anti-cancer activity-possessing gensenoside profiles. Methods: To investigate changes in gene expression in the MRGX-treated lung cancer cells (A549, we examined genomic data with cDNA microarray results. After completing the gene-ontology-based analysis, we grouped the genes into up-and down-regulated profiles and into ontology-related regulated genes and proteins through their interaction network. Results: One hundred nine proteins that were up- and down-regulated by MRGX were queried by using IPA. IL8, MMP7 and PLAUR and were found to play a major role in the anti-cancer activity in MRGX-treated lung cancer cells. These results were validated using a Western blot analysis and a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR analysis. Conclusions: Most MRGX-responsive genes are up-regulated transiently in A549 cells, but down-regulated in a sustained manner in lung cancer cells.

  17. Sexual dysfunctions in men treated for testicular cancer

    DEFF Research Database (Denmark)

    Rosendal, Susanne; Kristensen, Ellids; Giraldi, Annamaria G E

    2008-01-01

    Patients treated for testicular cancer have increased risk of ejaculatory, orgasmic and erectile dysfunction compared with healthy men. The underlying relations are unclear. This review describes sexual dysfunctions that are associated with various treatment modalities. One meta-analysis and 11...... original works were examined. About one third of the patients experience one or more sexual problems in relation to the treatment. Only retroperitoneal surgery can cause a specific sexual dysfunction, namely loss of ejaculation ability or ejaculatory functioning. Psychosexual causes are important...... for understanding sexual dysfunctions in patients with testicular cancer....

  18. Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

    Science.gov (United States)

    2016-04-18

    Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

  19. Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy

    Directory of Open Access Journals (Sweden)

    Xu Bo

    2010-05-01

    Full Text Available Abstract Background To evaluate the association between the clinical, dosimetric factors and severe acute radiation pneumonitis (SARP in patients with locally advanced non-small cell lung cancer (LANSCLC treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT. Methods We analyzed 94 LANSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. SARP was defined as greater than or equal 3 side effects and graded according to Common Terminology Criteria for Adverse Events (CTCAE version 3.0. The clinical and dosimetric factors were analyzed. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between clinical, dosimetric factors and SARP. Results Median follow-up was 10.5 months (range 6.5-24. Of 94 patients, 11 (11.7% developed SARP. Univariate analyses showed that the normal tissue complication probability (NTCP, mean lung dose (MLD, relative volumes of lung receiving more than a threshold dose of 5-60 Gy at increments of 5 Gy (V5-V60, chronic obstructive pulmonary disease (COPD and Forced Expiratory Volume in the first second (FEV1 were associated with SARP (p p = 0.001 and V10 (p = 0.015 were the most significant factors associated with SARP. The incidences of SARP in the group with NTCP > 4.2% and NTCP ≤4.2% were 43.5% and 1.4%, respectively (p 50% were 5.7% and 29.2%, respectively (p Conclusions NTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT.

  20. Effect of PDT-treated apoptotic cells on macrophages

    Science.gov (United States)

    Song, Sheng; Xing, Da; Zhou, Fei-fan; Chen, Wei R.

    2009-02-01

    Recently, the long-term immunological effects of photodynamic therapy have attracted much attention. PDT induced immune response was mainly initiated through necrotic cells and apoptotic cells, as well as immune cells such as macrophages. Nitric oxide (NO) as an important regulatory factor in signal transfer between cells has been wildly studied for generation, development, and metastasis of tumors. NO synthase is a key enzyme in nitric oxide synthesis. However, inducible nitric oxide synthase (iNOS) is usually activated under pathological conditions, such as stress and cancer, which can produce high levels of nitric oxide and contribute to tumor cytotoxicity. In addition, increased NO production by iNOS has been associated with the host immune response and cell apoptosis, which play an important role in many carcinogenesis and anti-carcinoma mechanisms. This study focuses on the NO production in macrophages, induced by mouse breast carcinoma apoptotic cells treated by PDT in vitro, and on the effects of immune response induced by apoptotic cells in tumor cells growth.

  1. Importance of Molecular Features of Non–Small Cell Lung Cancer for Choice of Treatment

    OpenAIRE

    Moran, Cesar

    2011-01-01

    Lung cancer is the leading cause of cancer-related deaths in the United States. Approximately 85% of lung cancer is categorized as non–small cell lung cancer, and traditionally, non–small cell lung cancer has been treated with surgery, radiation, and chemotherapy. Targeted agents that inhibit the epidermal growth factor receptor pathway have been developed and integrated into the treatment regimens in non–small cell lung cancer. Currently, approved epidermal growth factor receptor inhibitors ...

  2. Small Cell Lung Cancer.

    Science.gov (United States)

    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

  3. Busulfan, Etoposide, and Intensity-Modulated Radiation Therapy Followed By Donor Stem Cell Transplant in Treating Patients With Advanced Myeloid Cancer

    Science.gov (United States)

    2016-10-07

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

  4. Treating asthma means treating airway smooth muscle cells

    NARCIS (Netherlands)

    Zuyderduyn, S; Sukkar, M B; Fust, A; Dhaliwal, S; Burgess, J K

    2008-01-01

    Asthma is characterised by airway hyperresponsiveness, airway inflammation and airway remodelling. Airway smooth muscle cells are known to be the main effector cells of airway narrowing. In the present paper, studies will be discussed that have led to a novel view of the role of airway smooth muscle

  5. Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

    Science.gov (United States)

    2011-07-14

    Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

  6. New Therapeutics to Treat Castrate-Resistant Prostate Cancer

    OpenAIRE

    Ömer Acar; Tarık Esen; Lack, Nathan A.

    2013-01-01

    Hindawi Publishing Corporation The ScientificWorld Journal Volume 2013, Article ID 379641, 8 pages http://dx.doi.org/10.1155/2013/379641 Review Article New Therapeutics to Treat Castrate-Resistant Prostate Cancer Ömer Acar,1 TarJk Esen,1,2 and Nathan A. Lack1 1 VKF American Hospital, Guzelbahce sokak, Nisantasi, Istanbul 34365, Turkey 2 School of Medicine, Koc¸ University, Rumelifeneri Yolu, Sariyer, Istanbul 34450, Turkey Correspondence should be addressed to Natha...

  7. SPATIAL DISTRUBITON OF CHILDREN TREATED BY CANCER IN ZONGULDAK, TURKEY

    OpenAIRE

    TOPAN, Aysel; Bayram, Dilek; Özendi, Mustafa; Cam, Ali; Öztürk, Cam; Kuzlu Ayyıldız, Tülay; Kulakçı, Hülya; Veren, Funda

    2016-01-01

    This research is focused on the examination of child cancer cases in Zonguldak (Turkey) descriptively in epidemiological aspect thanks to GIS. Universe of the study is composed of 60 children between 0-19 years old, treated in Children Oncology Clinic of Health Application and Research Center in BEU. Whole universe was reached without selecting a sample in the study. Data were collected by using a form prepared by obtaining expert advice and they were applied to children and their parents at ...

  8. Impact of pretreatment whole-tumor perfusion computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography measurements on local control of non–small cell lung cancer treated with stereotactic body radiotherapy

    Science.gov (United States)

    Aoki, Masahiko; Akimoto, Hiroyoshi; Sato, Mariko; Hirose, Katsumi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Seino, Hiroko; Kakehata, Shinya; Tsushima, Fumiyasu; Fujita, Hiromasa; Fujita, Tamaki; Fujioka, Ichitaro; Tanaka, Mitsuki; Miura, Hiroyuki; Ono, Shuichi; Takai, Yoshihiro

    2016-01-01

    This study aimed to investigate the correlation between the average iodine density (AID) detected by dual-energy computed tomography (DE-CT) and the maximum standardized uptake value (SUVmax) yielded by [18F] fluorodeoxyglucose positron emission tomography (18F-FDG PET) for non–small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Seventy-four patients with medically inoperable NSCLC who underwent both DE-CT and 18F-FDG PET/CT before SBRT (50‒60 Gy in 5‒6 fractions) were followed up after a median interval of 24.5 months. Kaplan–Meier analysis was used to determine associations between local control (LC) and variables, including AID, SUVmax, tumor size, histology, and prescribed dose. The median AID and SUVmax were 18.64 (range, 1.18–45.31) (100 µg/cm3) and 3.2 (range, 0.7–17.6), respectively. No correlation was observed between AID and SUVmax. Two-year LC rates were 96.2% vs 75.0% (P = 0.039) and 72.0% vs 96.2% (P = 0.002) for patients classified according to high vs low AID or SUVmax, respectively. Two-year LC rates for patients with adenocarcinoma vs squamous cell carcinoma vs unknown cancer were 96.4% vs 67.1% vs 92.9% (P = 0.008), respectively. Multivariate analysis identified SUVmax as a significant predictor of LC. The 2-year LC rate was only 48.5% in the subgroup of lower AID and higher SUVmax vs >90% (range, 94.4–100%) in other subgroups (P = 0.000). Despite the short follow-up period, a reduction in AID and subsequent increase in SUVmax correlated significantly with local failure in SBRT-treated NSCLC patients. Further studies involving larger populations and longer follow-up periods are needed to confirm these results. PMID:27296251

  9. Mouse models for cancer stem cell research

    OpenAIRE

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

    2009-01-01

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

  10. Ethanol extract of Innotus obliquus (Chaga mushroom) induces G1 cell cycle arrest in HT-29 human colon cancer cells

    OpenAIRE

    Lee, Hyun Sook; Kim, Eun Ji; Kim, Sun Hyo

    2015-01-01

    BACKGROUND/OBJECTIVES Inonotus obliquus (I. obliquus, Chaga mushroom) has long been used as a folk medicine to treat cancer. In the present study, we examined whether or not ethanol extract of I. obliquus (EEIO) inhibits cell cycle progression in HT-29 human colon cancer cells, in addition to its mechanism of action. MATERIALS/METHODS To examine the effects of Inonotus obliquus on the cell cycle progression and the molecular mechanism in colon cancer cells, HT-29 human colon cancer cells were...

  11. Combining Physical and Biologic Parameters to Predict Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, Matthew H. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Cai Xuwei [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Radiation Oncology, Shanghai Cancer Hospital, Fudan University, Shanghai (China); Shedden, Kerby [Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Hayman, James A. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Yuan Shuanghu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Radiation Oncology, Shangdong Cancer Hospital, Jinan (China); Ritter, Timothy [Veterans Affairs Medical Center, Ann Arbor, Michigan (United States); Ten Haken, Randall K.; Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Kong Fengming, E-mail: fengkong@med.umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Veterans Affairs Medical Center, Ann Arbor, Michigan (United States)

    2012-10-01

    Purpose: To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1{beta}), IL-6, IL-8, tumor necrosis factor alpha (TNF-{alpha}), and transforming growth factor beta1 (TGF-{beta}1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials: Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results: Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-ss1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-ss1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. Conclusions: Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

  12. Effect of daily administration of oral etoposide for patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent radiation therapy

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study is to explore the effect of daily administration of oral etoposide(25mg) for patients with stage III NSCLC treated with concurrent radiation therapy. Planned endpoints were response, survival and toxicities. Material and Methods: Between (8(92)) and (9(95)), 37 stage III NSCLC patients were randomized to daily oral etoposide(25mg) with concurrent radiation therapy group(ERT) in 21 and radiation therapy alone group(RT) in 16. Etoposide was administered in the morning throughout radiation therapy. Median total irradiated dose, fraction size and time were 61.9Gy, 34.2 fractions and 48.8 days, respectively. Results: TO Monovariate survival analysis between ERT and RT showed no significant difference(p=0.10), but multivariate analysis confirmed that administration of oral etoposide is independent prognostic factor (p=0.009), together with T factor and N factor. Conclusion: ERT was better in local response but poorer in survival than RT. We concluded that complications of ERT was severe enough to cause death in some patients. We should design some methods to decrease these complications to make use of good local response acquired with ERT

  13. Gemcitabine Hydrochloride and Cisplatin or High-Dose Methotrexate, Vinblastine, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Urothelial Cancer

    Science.gov (United States)

    2014-01-27

    Anterior Urethral Cancer; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Posterior Urethral Cancer; Recurrent Bladder Cancer; Recurrent Urethral Cancer; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage III Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Ureter Cancer; Urethral Cancer Associated With Invasive Bladder Cancer

  14. HS-4, a highly potent inhibitor of cell proliferation of human cancer cell

    Institute of Scientific and Technical Information of China (English)

    Gui-Lan Xing; Shu-Hong Tian; Xue-Li Xie; Jian Fu

    2015-01-01

    Objective:To investigate the antitumor activity of the compound HS-4 and the action mechanism.Methods:MTT method was used to testin vitroantitumor activity of the compound HS-4. Orthotopic xenotransplantation tumor model of liver cancer was established in nude mice, and,in vivoantitumor activity of compound HS-4 was tested with a small animal in-vivo imaging system. Sequencing of small RNA library and RNA library was performed in HS-4 treated tumor cell group and control group to investigate the anti-cancer mechanism of HS-4 at level of functional genomics, using high-throughput sequencing technology. Results:HS-4 was found to have relatively highin-vitro antitumor activity against liver cancer cells, gastric cancer cells, renal cancer cells, lung cancer cells, breast cancer cells and colon cancer cells. The IC50 values against SMMC-7721 and Bel-7402 of liver cancer cells were 0.14 and 0.13 nmol/L respectively, while the IC50 values against MGC-803 and SGC-7901 of gastric cancer cells were 0.19 and 0.21 nmol/L, respectively. It was demonstrated that HS- 4 possessed a better therapeutic effect in liver cancer.Conclusions: A new reliable orthotopic xenotransplantation tumor model of liver cancer in nude mice is established. The new compounds HS-4 was found to possess relatively highin vivo andin vitroantitumor activity against liver cancer cells.

  15. HS-4,a highly potent inhibitor of cell proliferation of human cancer cell

    Institute of Scientific and Technical Information of China (English)

    Gui-Lan; Xing; Shu-Hong; Tian; Xue-Li; Xie; Jian; Fu

    2015-01-01

    Objective:To investigate the antitumor activity of the compound HS-4 and the action mechanism.Methods:MTT method was used to test in vitro antitumor activity of the compound HS-4.Orthotopic xenotransplantation tumor model of liver cancer was established in nude mice,and.in vivo antitumor activity of compound HS-4 was tested with a small animal in-vivo imaging system.Sequencing of small RNA library and RNA library was performed in HS-4 treated tumor cell group and control group to investigate the anti-cancer mechanism of HS-4 at level of functional genomics,using high-throughput sequencing technology.Results:HS-4 was found to have relatively high in-vitro antitumor activity against liver cancer cells,gastric cancer cells,renal cancer cells,lung cancer cells,breast cancer cells and colon cancer cells.The IC50 values against SMMC-7721 and Bel-7402 of liver cancer cells were 0.14 and 0.13 nmol/L respectively,while the IC50 values against MGC-803 and SGC-7901 of gastric cancer cells were 0.19 and 0.21 nmol/L,respectively.It was demonstrated that HS- 4 possessed a betler therapeutic effect in liver cancer.Conclusions:A new reliable orthotopicxenotransplantation tumor model of liver cancer in nude mice is established.The new compounds HS-4 was found to possess relatively high in vivo and in vitro antitumor activity against liver cancer cells.

  16. An open-label phase 2 trial of dabrafenib plus trametinib in patients with previously treated BRAF V600E–mutant metastatic non-small cell lung cancer

    Science.gov (United States)

    Planchard, David; Besse, Benjamin; Groen, Harry J M; Souquet, Pierre-Jean; Quoix, Elisabeth; Baik, Christina S; Barlesi, Fabrice; Kim, Tae Min; Mazieres, Julien; Novello, Silvia; Rigas, James R; Upalawanna, Allison; D’Amelio, Anthony M; Zhang, Pingkuan; Mookerjee, Bijoyesh; Johnson, Bruce E

    2016-01-01

    Background BRAF mutations act as an oncogenic driver via the mitogen-activated protein kinase (MAPK) pathway in non-small cell lung cancer (NSCLC). BRAF inhibition has demonstrated antitumor activity in patients with BRAF V600E (Val600Glu)–mutant NSCLC. Dual MAPK pathway inhibition with BRAF and MEK inhibitors in BRAF V600E–mutant NSCLC may improve efficacy over BRAF-inhibitor monotherapy based on observations in BRAF V600–mutant melanoma. Methods In this phase 2, multicenter, nonrandomized, open-label study of patients with pretreated metastatic BRAF V600E–mutant NSCLC, antitumor activity and safety of oral dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) were evaluated. Adult patients (≥ 18 years) with documented progression following at least one prior platinum-based chemotherapy and no more than three prior systemic anticancer therapies were enrolled. Patients with prior BRAF or MEK inhibitor treatment were ineligible. Patients with brain metastases were permitted to enroll only if the lesions were asymptomatic, untreated (or stable > 3 weeks after local therapy if treated), and measured < 1 cm. The primary endpoint was investigator-assessed overall response, which was assessed by intention-to-treat in the protocol-defined population (≥ second-line); safety was also assessed in this population. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings Fifty-seven patients previously treated with systemic chemotherapy for metastatic BRAF V600E–mutant NSCLC were enrolled. The investigator-assessed overall response was 63·2% (36 of 57; 95% CI 49·3–75·6). Serious adverse events were reported in 32 (56%) of 57 patients and included pyrexia (16%; 9 of 57), anemia (5%; 3 of 57), confusional state (4%; 2 of 57), decreased appetite (4%; 2 of 57), hemoptysis (4%; 2 of 57), hypercalcemia (4%; 2 of 57), nausea (4%; 2 of 57), and cutaneous squamous cell

  17. External validation of nomograms for predicting cancer-specific mortality in penile cancer patients treated with definitive surgery

    Institute of Scientific and Technical Information of China (English)

    Yao Zhu; Wei-Jie Gu; Ding-Wei Ye; Xu-Dong Yao; Shi-Lin Zhang; Bo Dai; Hai-Liang Zhang; Yi-Jun Shen

    2014-01-01

    Using a population-based cancer registry, Thuret et al. developed 3 nomograms for estimating cancer-specific mortality in men with penile squamous cell carcinoma. In the initial cohort, only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage. To generalize the prediction models in clinical practice, we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery. Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008. The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade. Discrimination, calibration, and clinical usefulness were assessed to compare model performance. The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging (Harrell’s concordance index = 0.817 and 0.832, respectively), whereas it was inferior for the Surveillance, Epidemiology and End Results staging (Harrel ’s concordance index = 0.728). Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade, which also achieved favorable clinical net benefit, with a threshold probability in the range of 0 to 42%. The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery. Our data support the integration of this model in decision-making and trial design.

  18. Head and Neck Cancer Stem Cells

    OpenAIRE

    Krishnamurthy, S.; Nör, J.E.

    2012-01-01

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

  19. Cell of origin of lung cancer

    OpenAIRE

    Hanna, Jennifer M.; Onaitis, Mark W.

    2013-01-01

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

  20. Antacid Use and De Novo Brain Metastases in Patients with Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer Who Were Treated Using First-Line First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

    Directory of Open Access Journals (Sweden)

    Yu-Mu Chen

    Full Text Available Antacid treatments decrease the serum concentrations of first-generation epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKIs, although it is unknown whether antacids affect clinical outcomes. As cerebrospinal fluid concentrations of TKIs are much lower than serum concentrations, we hypothesized that this drug-drug interaction might affect the prognosis of patients with de novo brain metastases.This retrospective study evaluated 269 patients with EGFR-mutant non-small cell lung cancer (NSCLC who had been diagnosed between December 2010 and December 2013, and had been treated using first-line first-generation EGFR-TKIs. Among these patients, we identified patients who concurrently used H2 receptor antagonists (H2RAs and proton pump inhibitors (PPIs as antacids. Patients who exhibited >30% overlap between the use of TKIs and antacids were considered antacid users.Fifty-seven patients (57/269, 21.2% were antacid users, and antacid use did not significantly affect progression-free survival (PFS; no antacids: 11.2 months, H2RAs: 9.4 months, PPIs: 6.7 months; p = 0.234. However, antacid use significantly reduced overall survival (OS; no antacids: 25.0 months, H2RAs: 15.5 months, PPIs: 11.3 months; p = 0.002. Antacid use did not affect PFS for various metastasis sites, although antacid users with de novo brain metastases exhibited significantly shorter OS, compared to non-users (11.8 vs. 16.3 months, respectively; p = 0.041. Antacid use did not significantly affect OS in patients with bone, liver, or pleural metastases.Antacid use reduced OS among patients with EGFR-mutant NSCLC who were treated using first-line first-generation EGFR-TKIs, and especially among patients with de novo brain metastases.

  1. The Relationship Between THE PATHOLOGICAL CHANGES AND Response Rate (RR) IN Non-small Cell Lung Cancer Treated by Neoadjuvant Chemotherapy with Mitomycin (MMC), Vindesine (VDS) and Cisplatin (DDP) Combination

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To explore the change of pathology and the clinical response rate treated by neoadjuvant chemotherapy with MVP regimen for non-small cell lung cancer. Methods: This is a randomized study in patients with stage I-lIIa. Among them, 46 patients enrolled in neoadjuvant chemotherapy treated by 1-2 course MVP regimen. MMC was given 6 mg/M2 by intravenous (I.V.) infusion on day1, VDS 2.5-3 mg/M2 I.V. on day1, 8 and/or day15, DDP 90 mg/M2 I.V. on day1. The treatment was recycled every 28 days. The clinical RR evaluated with WHO criteria. All surgical samples were classified with pathology. Results: The overall response rate in 2 courses chemotherapy is better than that in 1 course (P<0.01). The number of patient with pathology grade I-II in 2 course chemotherapy is higher than that in 1 course (P<0.01). But the RR can not completely translated into pathology grade I-II. The pathology grade I-II is closely related with tumor involvement (T) (P<0.01) but not closely related with regional lymph node metastasis (N). It is reasonable to use RR together with PCR to judge the chemotherapy response. NR patients can not be regard as chemotherapy failure. No serve toxicities and surgical mortality were observed. Conclusion: MVP regimen is an effective neoadjuvant treatment regimen for I-IIIa NSCLC.

  2. Cancer Stem Cells: Biological Functions and Therapeutically Targeting

    Directory of Open Access Journals (Sweden)

    Marius Eugen Ciurea

    2014-05-01

    Full Text Available Almost all tumors are composed of a heterogeneous cell population, making them difficult to treat. A small cancer stem cell population with a low proliferation rate and a high tumorigenic potential is thought to be responsible for cancer development, metastasis and resistance to therapy. Stem cells were reported to be involved in both normal development and carcinogenesis, some molecular mechanisms being common in both processes. No less controversial, stem cells are considered to be important in treatment of malignant diseases both as targets and drug carriers. The efforts to understand the role of different signalling in cancer stem cells requires in depth knowledge about the mechanisms that control their self-renewal, differentiation and malignant potential. The aim of this paper is to discuss insights into cancer stem cells historical background and to provide a brief review of the new therapeutic strategies for targeting cancer stem cells.

  3. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

    Directory of Open Access Journals (Sweden)

    Ziping WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variables and their impact on the survival of Chinese patients with advanced NSCLC who were heavily treated with gefitinib in the second- or third-line setting. Methods The clinical and follow-up data of 127 advanced NSCLC patients referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from March 2005 to March 2010 were analyzed. Multivariate analysis of progression-free survival (PFS was performed using recursive partitioning, which is referred to as the classification and regression tree (CART analysis. Results The median PFS of 127 eligible consecutive advanced NSCLC patients was 8.0 months (95%CI: 5.8-10.2. CART was performed with an initial split on first-line chemotherapy outcomes and a second split on patients’ age. Three terminal subgroups were formed. The median PFS of the three subsets ranged from 1.0 month (95%CI: 0.8-1.2 for those with progressive disease outcome after the first-line chemotherapy subgroup, 10 months (95%CI: 7.0-13.0 in patients with a partial response or stable disease in first-line chemotherapy and age <70, and 22.0 months for patients obtaining a partial response or stable disease in first-line chemotherapy at age 70-81 (95%CI: 3.8-40.1. Conclusion Partial response, stable disease in first-line chemotherapy and age ≥ 70 are closely correlated with long-term survival treated by gefitinib as a second- or third-line setting in advanced NSCLC. CART can be used to identify previously unappreciated patient

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

    Science.gov (United States)

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

    2016-04-25

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

  5. Prostate cancer treated with HIFU: A 10-year experience

    Science.gov (United States)

    Chapelon, Jean-Yves; Curiel, Laura; Gelet, Albert

    2001-05-01

    Objectives: To evaluate our overall experience in HIFU in the prostate cancer application, for its two main indications: as a primary care and as a salvage therapy after radiation. Material and method: Group 1: patients treated with HIFU as primary care for localized prostate cancer, with a baseline PSA level lower than 30 ng/ml, and with at least 1 year of follow-up were included in this analysis. Group 2: patients with a local recurrence after radiation. They were all treated using the Ablatherm HIFU device (EDAP S.A., France). Results: Group 1: n=242 patients. The mean nadir PSA was 0.63 sd 1.30 ng/ml, and further follow-up evidenced a 81% negative biopsy rate. These results are influenced by the usual prognostic factors (clinical stage, baseline PSA, Gleason score), and, as for the other treatment option, the nadir allows prediction of the patient outcome. Group 2: n=71 patients. After HIFU treatment, 80% of the patients presented negative biopsies, and 61% had a nadir PSA level lower than 0.5 ng/ml, obtained within 3 months. No rectal injury occurred since the use of specific parameters. Conclusion: Transrectal HIFU is a valuable option for prostate cancer, for primary care as well as for salvage therapy.

  6. Spatial Distrubiton of Children Treated by Cancer in Zonguldak, Turkey

    Science.gov (United States)

    Topan, Aysel; Bayram, Dilek; Özendi, Mustafa; Cam, Ali; Öztürk, Cam; Kuzlu Ayyıldız, Tülay; Kulakçı, Hülya; Veren, Funda

    2016-06-01

    This research is focused on the examination of child cancer cases in Zonguldak (Turkey) descriptively in epidemiological aspect thanks to GIS. Universe of the study is composed of 60 children between 0-19 years old, treated in Children Oncology Clinic of Health Application and Research Center in BEU. Whole universe was reached without selecting a sample in the study. Data were collected by using a form prepared by obtaining expert advice and they were applied to children and their parents at study dates. Results were expressed as percentages. Chi-Square test was used in intergroup comparisons, results were assessed within 95% confidence interval and pmaps were produced. When disease diagnosis of the children participated in the study were evaluated, it was observed that 33.3% (n=20) were being treated for ALL, 13.3% (n=8) for Medullablastoma and 11.7% (n=7) for Hodgkin-nonHodgkin Lymphoma. It was detected that 31.7% (n=19) were in Ereğli, 31.7% (n=19) were in Central district and 18.3% (n=11) were in Çaycuma, when the places where children were living were evaluated. Statistically significant difference was found (p=0.016) comparing disease diagnosis with living place, and overall distribution map of the number of cancer cases was produced in this context. This is the first research subjecting the distribution of cancer cases for Zonguldak province.

  7. Metformin and prostate cancer stem cells: a novel therapeutic target.

    Science.gov (United States)

    Mayer, M J; Klotz, L H; Venkateswaran, V

    2015-12-01

    Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies. PMID:26215782

  8. Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Topkan Erkan

    2012-10-01

    Full Text Available Abstract Background Glutamine (Gln supplementation during concurrent chemoradiotherapy (C-CRT effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE. However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC. We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities. Methods The study included 104 patients: 56 (53.8% received prophylactic powdered Gln (Gln+ orally at a dose of 10 g/8 h and 48 (46.2% did not receive Gln (Gln- and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS, local/regional progression-free survival (LRPFS, and overall survival (OS were correlated with status of Gln supplementation. Results Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0% patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02 and late-RIE (0% vs. 6.3%; p=0.06, a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04, and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002. At a median follow-up of 24.2 months (range 9.2-34.4 the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35, 14.2 vs.11.3 (p=0.16, and 10.2 vs. 9.0 months (p=0.11, respectively. Conclusion In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial

  9. Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

    International Nuclear Information System (INIS)

    Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities. The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation. Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively. In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss

  10. Genetic polymorphisms in the endothelial nitric oxide synthase gene correlate with overall survival in advanced non-small-cell lung cancer patients treated with platinum-based doublet chemotherapy

    Directory of Open Access Journals (Sweden)

    Mio Tadashi

    2010-11-01

    Full Text Available Abstract Background Nitric oxide (NO is a free radical that is involved in carcinogenesis. Endothelial NO, synthesized from L-arginine by endothelial NO synthase (eNOS, inhibits apoptosis and promotes angiogenesis, tumor cell proliferation and metastasis. The aim of this study was to evaluate the influence of polymorphisms in the eNOS gene on prognosis of patients with advanced stage non-small-cell lung cancer (NSCLC. Methods Unresectable, chemotherapy naïve stage III or IV NSCLC patients who were treated with standard platinum-containing doublet regimens were analyzed. All individuals were genotyped for the single-nucleotide polymorphism G894T in exon 7 of the eNOS gene and for a variable number of tandem repeats (VNTR polymorphism in intron 4 that results in a rare smaller allele (a and a common larger allele (b, to investigate the association between these polymorphisms and clinical outcomes. The primary endpoint was correlation with overall survival. Results From October 2004 to December 2007, 108 patients (male/female, 66/42; Stage IIIA/IIIB/IV, 6/30/72 aged 29-77 years (median 63 with good performance status were consecutively enrolled in this study. Using Kaplan-Meier estimates, we showed that 5-year overall survival was significantly increased in patients carrying the VNTR a-allele compared with VNTR b/b patients (P = 0.015. In multivariate Cox proportional hazard analysis, the VNTR polymorphism was an independent prognostic factor for survival. Conclusions The results support the role of the VNTR polymorphism in intron 4 as a marker for survival in patients with advanced stage NSCLC who are candidates for standard chemotherapy.

  11. Psychological distress and intervention in cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Background. Common side effects of treatment with radiation therapy (RT) often cause psychophysical distress in cancer patients. Anxiety, adjustment disorders and depression (which are according to many studies experienced in about half of the oncological population) might originate some serious psychiatric forms of mood disorders and can even culminate in suicide, if not treated appropriately. There are some groups of cancer patients who are especially vulnerable and among them are cancer patients undergoing RT - they should receive special attention from medical staff. The purpose of this review is to present a variety of psychosocial interventions and illustrate some methods that are (or could be) used in psycho-oncology practice. Conclusions. A large body of literature suggests that the first intervention step should be effective screening for patients in distress. In regard to these proposals the development of (computerized) screening programmes is the first measure that ought to be taken. Moreover, further systematical research of traditional, non-traditional and complementary intervention strategies in cancer patients in distress would be necessary in order to provide reliable empirical results about the effectiveness of different approaches. (author)

  12. Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer

    Science.gov (United States)

    2016-06-07

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma; Previously Treated Myelodysplastic Syndrome; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

  13. Prostate Cancer Stem Cells: Research Advances

    OpenAIRE

    Dagmara Jaworska; Wojciech Król; Ewelina Szliszka

    2015-01-01

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

  14. How Is Sickle Cell Disease Treated?

    Science.gov (United States)

    ... sickle cell disease, go to the Health Topics Sickle Cell Anemia article. Living With and Managing Sickle Cell Disease ( ... the most severe form of sickle cell disease, sickle cell anemia, Tiffany has lived with the symptoms and complications ...

  15. Mathematical models in cell biology and cancer chemotherapy

    CERN Document Server

    Eisen, Martin

    1979-01-01

    The purpose of this book is to show how mathematics can be applied to improve cancer chemotherapy. Unfortunately, most drugs used in treating cancer kill both normal and abnormal cells. However, more cancer cells than normal cells can be destroyed by the drug because tumor cells usually exhibit different growth kinetics than normal cells. To capitalize on this last fact, cell kinetics must be studied by formulating mathematical models of normal and abnormal cell growth. These models allow the therapeutic and harmful effects of cancer drugs to be simulated quantitatively. The combined cell and drug models can be used to study the effects of different methods of administering drugs. The least harmful method of drug administration, according to a given criterion, can be found by applying optimal control theory. The prerequisites for reading this book are an elementary knowledge of ordinary differential equations, probability, statistics, and linear algebra. In order to make this book self-contained, a chapter on...

  16. GP方案引起NSCLC患者糖耐量异常的临床研究%Clinical Study of Glucose Levels in Patients with Advanced Non-small Cell Lung Cancer Treated by GP Regimen

    Institute of Scientific and Technical Information of China (English)

    姚兰; 蒋成霞; 徐勇; 叶序卷; 贾钰铭; 雷开键; 唐元英

    2015-01-01

    Objective To evaluate blood glucose differences before and after three cycles of chemotherapy in patients with advanced non-small cell lung cancer. Methods 44 patients with advanced non-small cell lung cancer conducted blood routine,bi-ochemical,and C-reactive protein test;Normal blood glucose group treated chemotherapy with GP 3 cycles,high blood sugar groups measured blood glucose by oral glucose tolerance test,then were on diets,exercised or injected insulin. After GP regimen of 3 cy-cles,blood analysis,biochemical,C-reactive protein,oral glucose tolerance test,c-peptide and insulin release test were measured. Results After 3 cycles of GP,25%(8/32) of patients with normal glucose appears abnormal,and half of patients with abnormal glucose tolerance turn into diabetic. After chemotherapy,aspartate aminotransferase and C-reactive protein were significantly differ-ent from the patients with increased blood glucose and normal blodd glucose,the difference was statistically significant(P<0. 05). Conclusion GP regimen could cause glucose metabolism disorders in some patients with advanced non-small cell lung cancer and even induce diabetes. Patients with abnormal aspartate aminotransferase and C-reactive protein are susceptible to elevate blood glu-cose.%目的:分析非小细胞肺癌晚期患者GP方案化疗3周期前后血糖的差异。方法将44名非小细胞肺癌晚期患者根据血糖情况分为血糖正常组和血糖升高组:血糖正常组32例患者直接用GP方案化疗3周期,血糖升高组12例患者予以饮食、运动及胰岛素干预后,再进行GP方案化疗3周期,化疗前后行口服葡萄糖耐量试验、C肽及胰岛素释放试验。结果化疗前血糖正常者经GP方案化疗3周期后25%(8/32)的患者出现血糖升高,而糖调节受损患者化疗后出现一半的患者转变为糖尿病患者。化疗后血糖升高者与血糖正常者比较谷草转氨酶及C反应蛋白差异有统计学意义(P<0.05)

  17. Cisplatin and Radiation Therapy With or Without Triapine in Treating Patients With Previously Untreated Stage IB-IVA Cervical Cancer or Stage II-IVA Vaginal Cancer

    Science.gov (United States)

    2016-03-25

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB2 Cervical Cancer; Stage II Vaginal Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage III Vaginal Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Vaginal Adenocarcinoma; Vaginal Adenosquamous Carcinoma; Vaginal Squamous Cell Carcinoma

  18. Oxidative phosphorylation in cancer cells.

    Science.gov (United States)

    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. Cancer stem cell markers in common cancers - therapeutic implications

    DEFF Research Database (Denmark)

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

    2008-01-01

    Rapid advance in the cancer stem cell field warrants optimism for the development of more reliable cancer therapies within the next 2-3 decades. Below, we characterize and compare the specific markers that are present on stem cells, cancer cells and cancer stem cells (CSC) in selected tissues......, the last part of the review discusses future directions of this intriguing new research field in the context of new diagnostic and therapeutic opportunities....

  20. Albendazole sensitizes cancer cells to ionizing radiation

    International Nuclear Information System (INIS)

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

  1. Cryotherapy in Treating Patients With Lung Cancer That Has Spread to the Other Lung or Parts of the Body

    Science.gov (United States)

    2012-03-16

    Advanced Malignant Mesothelioma; Extensive Stage Small Cell Lung Cancer; Lung Metastases; Recurrent Malignant Mesothelioma; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  2. Stem cells in human breast cancer

    OpenAIRE

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

    2010-01-01

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

  3. Innate Lymphoid Cells in Cancer.

    Science.gov (United States)

    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. Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vulvar Cancer

    Science.gov (United States)

    2016-10-28

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Vulvar Cancer; Stage IB2 Cervical Cancer; Stage II Vulvar Cancer; Stage IIA1 Cervical Cancer; Stage IIA2 Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Cervical Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVA Cervical Cancer; Stage IVA Vulvar Cancer; Vulvar Adenocarcinoma; Vulvar Squamous Cell Carcinoma

  5. Stem cell transplantation for treating Duchenne muscular dystrophy

    OpenAIRE

    Yang, Xiaofeng

    2012-01-01

    OBJECTIVE: To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy in...

  6. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    Science.gov (United States)

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  7. Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E;

    2007-01-01

    with parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment.......Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor-positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance...... for future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells...

  8. Molecular advances to treat cancer of the brain.

    Science.gov (United States)

    Fathallah-Shaykh, H M; Zhao, L J; Mickey, B; Kafrouni, A I

    2000-06-01

    Malignant primary and metastatic brain tumours continue to be associated with poor prognosis. Nevertheless, recent advances in molecular medicine, specifically in the strategies of gene therapy, targeting tumour cells, anti-angiogenesis and immunotherapy, have created novel tools that may be of therapeutic value. To date, gene therapy trials have not yet demonstrated clinical efficacy because of inherent defects in vector design. Despite this, advances in adenoviral technology, namely the helper-dependent adenoviral constructs (gutless) and the uncovering of brain parenchymal cells as effective and necessary targets for antitumour benefits of adenoviral-mediated gene transfer, suggest that developments in vector design may be approaching the point of clinical utility. Targeting tumour cells refers to strategies that destroy malignant but spare normal cells. A new assortment of oncolytic viruses have emerged, capable of specific lysis of cancer tissue while sparing normal cells and propagating until they reach the tumour borders. Furthermore, peptides have been transformed into bullets that specifically seek and destroy cancer cells. The concept of tumour angiogenesis has been challenged by new but still very controversial findings that tumour cells themselves may form blood channels. These results may lead to the redirecting of the molecular targets toward anti-angiogenesis in some tumours including glioblastoma multiform. Unfortunately, our knowledge regarding the immunological ignorance of the tumour is still limited. Even so, newly discovered molecules have shed light on novel pathways leading to the escape of the tumour from the immune system. Finally, significant limitations in our current experimental tumour models may soon be overcome by firstly, the development of models of reproducible organ-specific tumours in non-inbred animals and secondly applying genomics to individualize therapy for a particular tumour in a specific patient.

  9. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells

    OpenAIRE

    Smith, Tim A. D.; Phyu, Su M.

    2016-01-01

    Introduction The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined. Methods MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14...

  10. Apoptosis of human pancreatic cancer cells induced by Triptolide

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  11. Resveratrol Sensitizes Selectively Thyroid Cancer Cell to 131-Iodine Toxicity

    Directory of Open Access Journals (Sweden)

    Seyed Jalal Hosseinimehr

    2014-01-01

    Full Text Available Background. In this study, the radiosensitizing effect of resveratrol as a natural product was investigated on cell toxicity induced by 131I in thyroid cancer cell. Methods. Human thyroid cancer cell and human nonmalignant fibroblast cell (HFFF2 were treated with 131I and/or resveratrol at different concentrations for 48 h. The cell proliferation was measured by determination of the percent of the survival cells using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Results. Findings of this study show that resveratrol enhanced the cell death induced by 131I on thyroid cancer cell. Also, resveratrol exhibited a protective effect on normal cells against 131I toxicity. Conclusion. This result indicates a promising effect of resveratrol on improvement of cellular toxicity during iodine therapy.

  12. Induction of G1 cell cycle arrest and apoptosis by berberine in bladder cancer cells.

    Science.gov (United States)

    Yan, Keqiang; Zhang, Cheng; Feng, Jinbo; Hou, Lifang; Yan, Lei; Zhou, Zunlin; Liu, Zhaoxu; Liu, Cheng; Fan, Yidon; Zheng, Baozhong; Xu, Zhonghua

    2011-07-01

    Bladder cancer is the ninth most common type of cancer, and its surgery is always followed by chemotherapy to prevent recurrence. Berberine is non-toxic to normal cells but has anti-cancer effects in many cancer cell lines. This study was aimed to determine whether berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87 and T24 bladder cancer cell line. The superficial bladder cancer cell line BIU-87 and invasive T24 bladder cancer cells were treated with different concentrations of berberine. MTT assay was used to determine the effects of berberine on the viability of these cells. The cell cycle arrest was detected through propidium iodide (PI) staining. The induction of apoptosis was determined through Annexin V-conjugated Alexa Fluor 488 (Alexa488) staining. Berberine inhibited the viability of BIU-87 and T24 cells in a dose- and time-dependent manner. It also promoted cell cycle arrest at G0/G1 in a dose-dependent manner and induced apoptosis. We observed that H-Ras and c-fos mRNA and protein expressionswere dose-dependently and time-dependently decreased by berberine treatment. Also, we investigated the cleaved caspase-3 and caspase-9 protein expressions increased in a dose-dependent manner. Berberine inhibits the cell proliferation and induces cell cycle arrest and apoptosis in BIU-87, bladder cancer cell line and T24, invasive bladder cancer cell line. Berberine can inhibit the oncogentic H-Ras and c-fos in T24 cells, and can induce the activation of the caspase-3 and caspase-9 apoptosis. Therefore, berberine has the potential to be a novel chemotherapy drug to treat the bladder cancer by suppressing tumor growth.

  13. Cetuximab, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

    Science.gov (United States)

    2014-12-29

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  14. Hair cortisol measurement in mitotane-treated adrenocortical cancer patients.

    Science.gov (United States)

    Manenschijn, L; Quinkler, M; van Rossum, E F C

    2014-04-01

    The only approved drug for the treatment of adrenocortical cancer (ACC) is mitotane. Mitotane is adrenolytic and therefore, hydrocortisone replacement therapy is necessary. Since mitotane increases cortisol binding globulin (CBG) and induces CYP3A4 activity, high doses of hydrocortisone are thought to be required. Evaluation of hydrocortisone therapy in mitotane-treated patients has been difficult since there is no good marker to evaluate hydrocortisone therapy. Measurement of cortisol in scalp hair is a novel method that offers the opportunity to measure long-term cortisol levels. Our aim was to evaluate whether hair cortisol measurements could be useful in evaluating recent hydrocortisone treatment in mitotane-treated ACC patients. Hair cortisol levels were measured in 15 mitotane-treated ACC patients on hydrocortisone substitution and 96 healthy individuals. Cortisol levels were measured in 3 cm hair segments, corresponding to a period of 3 months. Hair cortisol levels were higher in ACC patients compared to healthy individuals (pcortisol levels above the reference range. None of the patients had hair cortisol levels below normal. In contrast to hydrocortisone doses (β=0.03, p=0.93), hair cortisol levels were associated with BMI (β=0.53, p=0.042). There was no correlation between hair cortisol levels and hydrocortisone doses (β=0.41, p=0.13). Almost half of the ACC patients had high hair cortisol levels, suggesting long-term over-substitution of hydrocortisone in some of the patients, whereas none of the patients was under-substituted. Hair cortisol measurements might be useful in long-term monitoring hydrocortisone treatment in mitotane-treated ACC patients.

  15. A Prospective Study of the Associations Between Treated Diabetes and Cancer Outcomes

    OpenAIRE

    Yeh, Hsin-Chieh; Platz, Elizabeth A.; Wang, Nae-Yuh; Visvanathan, Kala; Helzlsouer, Kathy J.; Brancati, Frederick L.

    2011-01-01

    OBJECTIVE To quantify the association of treated diabetes with cancer incidence and cancer mortality as well as cancer case fatality and all-cause mortality in adults who subsequently develop cancer and to calculate attributable fractions due to diabetes on various cancer outcomes. RESEARCH DESIGN AND METHODS Prospective data on 599 diabetic and 17,681 nondiabetic adults from the CLUE II (Give Us a Clue to Cancer and Heart Disease) cohort in Washington County, Maryland, were analyzed. Diabete...

  16. The effects of phenoxodiol on the cell cycle of prostate cancer cell lines

    OpenAIRE

    Mahoney, Simon; Arfuso, Frank; Millward, Michael; Dharmarajan, Arun

    2014-01-01

    Background Prostate cancer is associated with a poor survival rate. The ability of cancer cells to evade apoptosis and exhibit limitless replication potential allows for progression of cancer from a benign to a metastatic phenotype. The aim of this study was to investigate in vitro the effect of the isoflavone phenoxodiol on the expression of cell cycle genes. Methods Three prostate cancer cell lines-LNCaP, DU145, and PC3 were cultured in vitro, and then treated with phenoxodiol (10 μM and 30...

  17. Cisplatin and Radiation Therapy Followed by Paclitaxel and Carboplatin in Treating Patients With Stage IB-IVA Cervical Cancer

    Science.gov (United States)

    2016-03-16

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage IIIA Cervical Cancer; Stage IIIB Cervical Cancer; Stage IVA Cervical Cancer

  18. Role of cancer stem cells in hepatocarcinogenesis

    OpenAIRE

    Wang, Bo; Jacob, Samson T.

    2011-01-01

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

  19. Clozapine Induces Autophagic Cell Death in Non-Small Cell Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yu-Chun Yin

    2015-02-01

    Full Text Available Background/Aims: Previous studies have shown that patients with schizophrenia have a lower incidence of cancer than the general population, and several antipsychotics have been demonstrated to have cytotoxic effects on cancer cells. However, the mechanisms underlying these results remain unclear. The present study aimed to investigate the effect of clozapine, which is often used to treat patients with refractory schizophrenia, on the growth of non-small cell lung carcinoma cell lines and to examine whether autophagy contributes to its effects. Methods: A549 and H1299 cells were treated with clozapine, and cell cytotoxicity, cell cycle and autophagy were then assessed. The autophagy inhibitor bafilomycin A1 and siRNA-targeted Atg7 were used to determine the role of autophagy in the effect of clozapine. Results: Clozapine inhibited A549 and H1299 proliferation and increased p21 and p27 expression levels, leading to cell cycle arrest. Clozapine also induced a high level of autophagy, but not apoptosis, in both cell lines, and the growth inhibitory effect of clozapine was blunted by treatment with the autophagy inhibitor bafilomycin A1 or with an siRNA targeting atg7. Conclusions: Clozapine inhibits cell proliferation by inducing autophagic cell death in two non-small cell lung carcinoma cell lines. These findings may provide insights into the relationship between clozapine use and the lower incidence of lung cancer among patients with schizophrenia.

  20. Hormone profiles in women treated for cervical cancer

    International Nuclear Information System (INIS)

    Some investigators believe that the protective effect of radiotherapy is hormonally mediated. To determine whether ovarian radiation affects serum hormone levels differently from surgical removal of the ovaries, serum estradiol, estrone, testosterone and androstenedione were evaluated by radioimmunoassay in 320 women (203 irradiated and 117 nonirradiated) from six US clinics participating in a large international cohort study of women treated for cervical cancer since the 1960's. Overall, estradiol levels were similar for both treatment groups, while estrone, testosterone and androstenedione levels were somewhat lower in irradiated women than in nonirradiated women after adjustment for year of birth. Notably, among women in both groups whose treatment included bilateral oophorectomy, irradiated women consistently had lower levels of androstenedione, testosterone and estrone but similar levels of estradiol

  1. Cell proliferation and apoptosis in stage III inoperable non-small cell lung carcinoma treated by radiotherapy

    NARCIS (Netherlands)

    Langendijk, H; Thunnissen, E; Arends, JW; de Jong, J; ten Velde, G; Lamers, R; Guinee, D; Holden, J; Wouters, M

    2000-01-01

    Purpose: The purpose of this study was to assess the prognostic value of the expression of p53 and bcl-2, the apoptotic index and the expression of topoisomerase II alpha in patients with inoperable non-small cell lung cancer (NSCLC) treated with high dose radiotherapy. Patients and methods: A numbe

  2. Do Cell Phones Cause Cancer?

    CERN Document Server

    Leikind, Bernard

    2010-01-01

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

  3. Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hye Kyung; Kim, Mi Sook; Jeong, Jae Hoon [Korea Institute of Radiologicaland Medical Sciences, Seoul (Korea, Republic of)

    2010-11-15

    To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

  4. Oridonin phosphate-induced autophagy effectively enhances cell apoptosis of human breast cancer cells.

    Science.gov (United States)

    Li, Yue; Wang, Ying; Wang, Suihai; Gao, Yanjun; Zhang, Xuefeng; Lu, Chunhua

    2015-01-01

    Oridonin is an active diterpenoid, which was extracted from traditional Chinese herbs and had been widely used in clinical treatment nowadays. Oridonin phosphate is one of the derivatives of oridonin. In the present study, we explored its anti-tumor effect and investigated the molecular mechanism of oridonin phosphate in breast cancer cell lines. Firstly, cell viability was analyzed by MTT assay. The breast cancer cells were treated with increasing concentrations of oridonin phosphate for 24, 48 and 72 h, respectively. The results demonstrated that oridonin phosphate inhibited the proliferation of MDA-MB-436 and MDA-MB-231 cells in a dose- and time-dependent manner. Next, cell apoptosis rate was detected in oridonin phosphate-treated breast cancer cells by Annexin V-FITC/PI dual staining analysis and the data demonstrated that oridonin phosphate induced cell apoptosis of breast cancer cells in time- and dose-dependent manner. Moreover, apoptosis-related proteins were detected by Western blotting analysis. The results showed that the expression level of Bax was up-regulated and the expression level of Bcl-2 was down-regulated. Meanwhile, the level of cleaved caspase-9 was significantly increased when the cells were treated with 40 μM of oridonin phosphate for 48 h, although the expression level of pro-caspase-9 was not obviously changed. All of the data revealed that mitochondrial apoptosis pathway may be involved in the cell apoptosis induced by oridonin phosphate in breast cancer cells. Importantly, the expression levels of autophagy-related protein beclin-1 and LC3-II were significantly higher in oridonin phosphate-treated breast cancer cell lines MDA-MB-436 and MDA-MB-231 for 48 h. Additionally, we further explored the relationship between apoptosis and autophagy specifically induced by oridonin phosphate in breast cancer cells. The result showed that inhibition of autophagy suppressed the cell apoptosis in oridonin phosphate-treated MDA-MB-436 cells. Taken

  5. Exercise echocardiography in asymptomatic survivors of childhood cancer treated with anthracyclines

    DEFF Research Database (Denmark)

    Sieswerda, Elske; Kremer, Leontien C M; Vidmar, Suzanna;

    2010-01-01

    BACKGROUND: Exercise echocardiography reveals abnormalities in asymptomatic childhood cancer survivors who previously have been treated with anthracyclines. We determined the added value of monitoring childhood cancer survivors with exercise echocardiography compared to monitoring with resting ec...

  6. Losartan sensitizes selectively prostate cancer cell to ionizing radiation.

    Science.gov (United States)

    Yazdannejat, H; Hosseinimehr, S J; Ghasemi, A; Pourfallah, T A; Rafiei, A

    2016-01-11

    Losartan is an angiotensin II receptor (AT-II-R) blocker that is widely used by human for blood pressure regulation. Also, it has antitumor property. In this study, we investigated the radiosensitizing effect of losartan on cellular toxicity induced by ionizing radiation on prostate cancer and non-malignant fibroblast cells. Human prostate cancer (DU-145) and human non-malignant fibroblast cells (HFFF2) were treated with losartan at different concentrations (0.5, 1, 10, 50 and 100 µM) and then these cells were exposed to ionizing radiation. The cell proliferation was determined using MTT assay. Our results showed that losartan exhibited antitumor effect on prostate cancer cells; it was reduced cell survival to 66% at concentration 1 µM. Losartan showed an additive killing effect in combination with ionizing radiation on prostate cancer cell. The cell proliferation was reduced to 54% in the prostate cancer cells treated with losartan at concentration 1 µM in combination with ionizing radiation. Losartan did not exhibit any toxicity on HFFF2 cell. This result shows a promising effect of losartan on enhancement of therapeutic effect of ionizing radiation in patients during therapy.

  7. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

    Science.gov (United States)

    Pathak, Sen; Multani, Asha S; Banerji, Pratip; Banerji, Prasanta

    2003-10-01

    Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.

  8. Cancer stem cells and metastasis.

    Science.gov (United States)

    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.

  9. Chromosome inversions in lymphocytes of prostate cancer patients treated with X-rays and carbon ions

    International Nuclear Information System (INIS)

    Background and purpose: To investigate the cytogenetic damage of the intrachange type in peripheral blood lymphocytes of patients treated for prostate cancer with different radiation qualities. Material and methods: Prostate cancer patients were enrolled in a clinical trial based at the Heidelberg University Hospital and at the GSI Helmholtz Centre for Heavy Ion Research in 2006. Patients were treated either with intensity-modulated radiation therapy (IMRT) alone or with a carbon-ion boost followed by IMRT. Blood samples were collected at the end of the therapy and the mBAND technique was used to investigate the cytogenetic damage of the inter and intrachange types. Moreover, the mBAND analysis was performed on healthy donor cells irradiated in vitro with X-rays or C-ions. Results: Our results show no statistically significant differences in the yield and the spectrum of chromosome aberrations among patients treated only with IMRT and patients receiving the combined treatment when similar target volumes and doses to the target are compared. Conclusion: The study suggests that the risks of normal tissue late effects and second malignancies in prostate cancer patients are comparable when heavy ions or IMRT radiotherapy are applied

  10. Treatment Option Overview (Renal Cell Cancer)

    Science.gov (United States)

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

  11. Treatment Options for Renal Cell Cancer

    Science.gov (United States)

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

  12. Inhibition of Gli/hedgehog signaling in prostate cancer cells by "cancer bush" Sutherlandia frutescens extract.

    Science.gov (United States)

    Lin, Hui; Jackson, Glenn A; Lu, Yuan; Drenkhahn, Sara K; Brownstein, Korey J; Starkey, Nicholas J; Lamberson, William R; Fritsche, Kevin L; Mossine, Valeri V; Besch-Williford, Cynthia L; Folk, William R; Zhang, Yong; Lubahn, Dennis B

    2016-02-01

    Sutherlandia frutescens is a medicinal plant, traditionally used to treat various types of human diseases, including cancer. Previous studies of several botanicals link suppression of prostate cancer growth with inhibition of the Gli/hedgehog (Gli/Hh) signaling pathway. Here we hypothesized the anti-cancer effect of S. frutescens was linked to its inhibition of the Gli/Hh signaling in prostate cancer. We found a dose- and time-dependent growth inhibition in human prostate cancer cells, PC3 and LNCaP, and mouse prostate cancer cell, TRAMP-C2, treated with S. frutescens methanol extract (SLE). We also observed a dose-dependent inhibition of the Gli-reporter activity in Shh Light II and TRAMP-C2QGli cells treated with SLE. In addition, SLE can inhibit Gli/Hh signaling by blocking Gli1 and Ptched1 gene expression in the presence of a Gli/Hh signaling agonist (SAG). A diet supplemented with S. frutescens suppressed the formation of poorly differentiated carcinoma in prostates of TRAMP mice. Finally, we found Sutherlandioside D was the most potent compound in the crude extract that could suppress Gli-reporter in Shh Light II cells. Together, this suggests that the S. frutescens extract may exert anti-cancer effect by targeting Gli/Hh signaling, and Sutherlandioside D is one of the active compounds. PMID:26377232

  13. Cell Membrane Softening in Cancer Cells

    Science.gov (United States)

    Schmidt, Sebastian; Händel, Chris; Käs, Josef

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

  14. Heterologous mesenchymal stem cells successfully treat femoral pseudarthrosis in rats

    OpenAIRE

    Ferreira Manoel; Silva Paulo; Alvarez Silva Lucas; Bonfim Danielle; Conilho Macedo Müller Lucas; Espósito Christiano; Schanaider Alberto

    2012-01-01

    Abstract Background This study evaluated the effectiveness of treating pseudarthrosis in rats by using bone marrow cell suspensions or cultures of bone marrow mesenchymal stromal cells Methods Thirty-eight specific pathogen-free (SPF) animals were randomly assigned to four groups: Group 1, Control, without surgical intervention; Group 2 (Placebo), experimental model of femoral pseudarthrosis treated only with saline solution; Group 3, experimental model of femoral pseudarthrosis treated with ...

  15. Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells

    Science.gov (United States)

    Montgomery, Amanda; Adeyeni, Temitope; San, KayKay; Heuertz, Rita M.; Ezekiel, Uthayashanker R.

    2016-01-01

    We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer. PMID:27390600

  16. Multiple effects of electroporation on the adhesive behaviour of breast cancer cells and fibroblasts

    OpenAIRE

    Pehlivanova Viktoria N; Tsoneva Iana H; Tzoneva Rumiana D

    2012-01-01

    Abstract Background Recently electroporation using biphasic pulses was successfully applied in clinical developments for treating tumours in humans and animals. We evaluated the effects of electrical treatment on cell adhesion behaviour of breast cancer cells and fibroblasts. By applying bipolar electrical pulses we studied short- and long-lived effects on cell adhesion and survival, actin cytoskeleton and cell adhesion contacts in adherent cancer cells and fibroblasts. Methods Two cancer cel...

  17. Invasive cancer cells and metastasis

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

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

  18. Inhalable self-assembled albumin nanoparticles for treating drug-resistant lung cancer.

    Science.gov (United States)

    Choi, Seong Ho; Byeon, Hyeong Jun; Choi, Ji Su; Thao, Lequang; Kim, Insoo; Lee, Eun Seong; Shin, Beom Soo; Lee, Kang Choon; Youn, Yu Seok

    2015-01-10

    Direct pulmonary delivery of anti-cancer agents is viewed as an effective way of treating lung cancer. Here, we fabricated inhalable nanoparticles made of human serum albumin (HSA) conjugated with doxorubicin and octyl aldehyde and adsorbed with apoptotic TRAIL protein (TRAIL/Dox HSA-NP). The octyl aldehyde and doxorubicin endowed HSA with significant hydrophobicity that facilitated self-assembly. TRAIL/Dox HSA-NP was found to have excellent particle size (~340nm), morphology, dispersability, and aerosolization properties. TRAIL/Dox HSA-NP displayed synergistic cytotoxicity and apoptotic activity in H226 lung cancer cells vs. HSA-NP containing TRAIL or Dox alone. TRAIL/Dox HSA-NP was well deposited in the mouse lungs using an aerosolizer, and TRAIL and Dox-HSA were found to be gradually released over 3days. The anti-tumor efficacy of pulmonary administered TRAIL/Dox HSA-NP was evaluated in BALB/c nu/nu mice bearing H226 cell-induced metastatic tumors. It was found that the tumors of H226-implanted mice treated with TRAIL/Dox HSA-NP were remarkably smaller and lighter than those of mice treated with TRAIL or Dox HSA-NP alone (337.5±7.5; 678.2±51.5; and 598.9±24.8mg, respectively). Importantly, this improved anti-tumor efficacy was found to be due to the synergistic apoptotic effects of Dox and TRAIL. In the authors' opinion, TRAIL/Dox HSA-NP offers a potential inhalable anti-lung cancer drug delivery system. Furthermore, the synergism displayed by combined use of Dox and TRAIL could be used to markedly reduce doxorubicin doses and minimize its side effects. PMID:25445703

  19. What makes cancer stem cell markers different?

    OpenAIRE

    Karsten, Uwe; Goletz, Steffen

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lu Han

    2013-04-01

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

  1. Where do patients treated for oral cancer die? A 20-year cohort study 1992-2011.

    Science.gov (United States)

    Kamisetty, A; Magennis, P; Mayland, C; Jack, B; Lowe, D; Rogers, S N

    2015-12-01

    Of 1290 consecutive patients treated between 1992 and 2011 for primary squamous cell carcinoma of the oral cavity at a regional centre, 750 had died by August 2013. About half of them (n=373) died in hospital, 113 (15%) in a hospice, 180 (24%) at home, 57 (8%) in a care home, and 22 (3%) elsewhere. Cancer was the underlying cause of death in 64%, and of them, 56% were oral cancers. The place of death was strongly associated with the age at death and cancer being the underlying cause. The percentage of people who died from cancer at home or in a hospice rose over time across all age groups and, from 2010, accounted for two-thirds. In contrast, less than 1 in 5 who did not die from cancer, died at home or in a hospice, and in this there has been no discernible change over the last 20 years. The percentage of deaths from cancer in hospital and hospice ranged from 32%-38% and 20%-29%, respectively, across age groups. An increase in the number of deaths from cancer in care homes in those aged 75 years and over was mirrored by fewer at home. Most of those who did not die from cancer, died in hospital, two-thirds were under 65 years, 85% were aged 65-84, and 56% were older. This was mirrored by fewer deaths at home in those under 85 and more in care homes in those over 75. In conclusion, our findings suggest that patients' preferences not to die in hospital are being realised. However, at the end of their lives, patients and their carers need more support at home, and more research is required.

  2. Clinical Usefulness of 18F-FDG PET/CT in the Detection of Early Recurrence in Treated Cervical Cancer Patients with Unexplained Elevation of Serum Tumor Markers

    OpenAIRE

    Chong, Ari; Ha, Jung-Min; Jeong, Shin Young; Song, Ho-Chun; Min, Jung Joon; Bom, Hee-Seung; Choi, Ho-Sun

    2013-01-01

    We investigated the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for restaging of treated uterine cervix squamous cell cancer with tumor maker elevation that was not explained by other conventional evaluation. We enrolled 32 cases who underwent PET/CT for the restaging of treated cervical cancer with tumor marker elevation that was not explained by recent conventional evaluation. All enrolled cases had squamous cell carcinoma. Increased ...

  3. Targeting the Checkpoint to Kill Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jan Benada

    2015-08-01

    Full Text Available 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.

  4. Astragalus extract inhibits destruction of gastric cancer cells to mesothelial cells by anti-apoptosis

    Institute of Scientific and Technical Information of China (English)

    Di Na; Fu-Nan Liu; Zhi-Feng Miao; Zong-Min Du; Hui-Mian Xu

    2009-01-01

    AIM: To determine the inhibitory effect of Astragalus memebranaceushas on gastric cancer cell supernatantinduced apoptosis of human peritoneal mesothelial cells. METHODS: Human peritoneal mesothelial cell (HPMC) line HMrSV5 was co-incubated with gastric cancer cell supernatant (MKN45) and/or Astragalus memebranaceushas. Morphological changes in gastric cancer cells were observed under phase-contrast microscope. Quantitative cell damage was determined by MTT assay. Apoptosis was determined under transmission electron microscope and quantified by detecting acridine orange/ethidium bromide-stained (AO/EB) condensed nuclei under fluorescent microscope or by flow cytometry. Expressions of Bcl-2 and Bax were evaluated with immunostaining. RESULTS: Morphological changes and exfoliation occurred and naked areas appeared in cultured HMrSV5 cells 24 h after they were treated with gastric cancer cell supernatant. Cell supernatant from MKN45 gastric cancer cells induced apoptosis of HMrSV5 cells in a time-dependent manner. Obvious morphological changes were observed in cell apoptosis, such as condensation of chromatin, nuclear fragmentations and apoptotic bodies. Astragalus memebranaceus could partly suppress these changes and regulate the expressions of Bcl-2 and Bax in HMrSV5 cells. CONCLUSION: Gastric cancer cells induce apoptosis of HPMCs through the supernatant. Astragalus memebranaceushas inhibits this phenomenon and can be used an adjuvant chemothera-peutic agent in gastric cancer therapy.

  5. Fourier transform infrared spectroscopy for the distinction of MCF-7 cells treated with different concentrations of 5-fluorouracil

    OpenAIRE

    WU, BI-BO; Gong, Yi-Ping; Wu, Xin-Hong; Chen, Yuan-Yuan; Chen, Fang-Fang; Jin, Li-Ting; Cheng, Bo-Ran; Hu, Fen; Xiong, Bin

    2015-01-01

    Background In order to provide personalized treatment to patients with breast cancer, an accurate, reliable and cost-efficient analytical technique is needed for drug screening and evaluation of tumor response to chemotherapy. Methods Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was used as a tool to assess cancer cell response to chemotherapy. MCF-7 cells (human breast adenocarcinoma cell line) were treated with different concentrations of 5-fluorouracil (5...

  6. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk ... day and for how long you have smoked. Being around the smoke ...

  7. Stem Cell Therapy to Treat Diabetes Mellitus

    OpenAIRE

    Liew, Chee Gee; Andrews, Peter W.

    2008-01-01

    Transplantation of pancreatic islets offers a direct treatment for type 1 diabetes and in some cases, insulin-dependent type 2 diabetes. However, its widespread use is hampered by a shortage of donor organs. Many extant studies have focused on deriving β-cell progenitors from pancreas and pluripotent stem cells. Efforts to generate β-cells in vitro will help elucidate the mechanisms of β-cell formation and thus provide a versatile in vivo system to evaluate the therapeutic potential of these ...

  8. Prognostic factors analysis in EGFR mutation-positive non-small cell lung cancer with brain metastases treated with whole brain-radiotherapy and EGFR-tyrosine kinase inhibitors

    OpenAIRE

    WEI, HANGPING; Su, Meng; LIN, RUIFANG; Li, Huifang; ZOU, CHANGLIN

    2016-01-01

    The survival time of non-small cell lung cancer (NSCLC) patients with brain metastases has been previously reported to be 6.5–10.0 months, even with systematic treatment. Patients that possess a certain epidermal growth factor receptor (EGFR) mutation alongside NSCLC with brain metastases also have a short survival rate, and a reliable prognostic model for these patients demonstrates a strong correlation between the outcome and treatment recommendations. The Cox proportional hazards regressio...

  9. Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

    OpenAIRE

    Wang, Ziping; Guo, Jihong; Wang, Yan; Yutao LIU; Juan YANG

    2011-01-01

    Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC) patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variable...

  10. Advanced Merkel cell cancer and the elderly.

    LENUS (Irish Health Repository)

    Bird, B R

    2012-02-03

    BACKGROUND: Merkel cell cancer (MCC) is an uncommon neuroendocrine skin cancer occurring predominantly in elderly Caucasians. It tends to metastasize to regional lymph nodes and viscera and is sensitive to chemotherapy but recurs rapidly. AIM: To report one such case, its response to chemotherapy and briefly review the literature. METHODS: A 73-year-old male with a fungating primary lesion on his left knee and ulcerated inguinal lymph nodes was diagnosed with MCC and treated with chemotherapy. The two largest case series and reviews of case reports were summarised. RESULTS: His ulcer healed after two cycles of carboplatin and etoposide with improvement in quality of life. Overall response rates of nearly 60% to chemotherapy are reported but median survival is only nine months with metastatic disease. CONCLUSIONS: Chemotherapy should be considered for fit elderly patients with MCC who have recurrent or advanced disease.

  11. How Taxol/paclitaxel kills cancer cells.

    Science.gov (United States)

    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.

  12. The relationship of cancer stem cells in urological cancers

    Directory of Open Access Journals (Sweden)

    Marta Pokrywczyńska

    2013-08-01

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

  13. Colorectal Cancer Stem Cells and Cell Death

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-11

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

  14. Interleukin-12 and Trastuzumab in Treating Patients With Cancer That Has High Levels of HER2/Neu

    Science.gov (United States)

    2013-02-27

    Advanced Adult Primary Liver Cancer; Anaplastic Thyroid Cancer; Bone Metastases; Carcinoma of the Appendix; Distal Urethral Cancer; Fallopian Tube Cancer; Gastrinoma; Glucagonoma; Inflammatory Breast Cancer; Insulinoma; Liver Metastases; Localized Unresectable Adult Primary Liver Cancer; Lung Metastases; Male Breast Cancer; Malignant Pericardial Effusion; Malignant Pleural Effusion; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Parathyroid Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Newly Diagnosed Carcinoma of Unknown Primary; Occult Non-small Cell Lung Cancer; Pancreatic Polypeptide Tumor; Primary Peritoneal Cavity Cancer; Proximal Urethral Cancer; Pulmonary Carcinoid Tumor; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adrenocortical Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Carcinoma of Unknown Primary; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Endometrial Carcinoma; Recurrent Esophageal Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Pancreatic Cancer; Recurrent Parathyroid Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; 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 Thyroid Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Vaginal

  15. Glutathione in Cancer Cell Death

    Directory of Open Access Journals (Sweden)

    Jose M. Estrela

    2011-03-01

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

  16. Glutathione in Cancer Cell Death

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-03-11

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

  17. Thoughts about cancer stem cells in solid tumors.

    Science.gov (United States)

    La Porta, Caterina Am

    2012-03-26

    Cancer chemotherapy efficacy is frequently impaired by either intrinsic or acquired tumor resistance. A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. In recent years, the cancer stem cell (CSC) theory has changed the classical view of tumor growth and therefore the therapeutic perspective. Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. On the other hand, the identification of CSCs in vivo and in vitro relies on specific surface markers that should allow the sorting cancer cells into phenotypically distinct subpopulations. In the present review, recent papers published on CSCs in solid tumors (breast, prostate, brain and melanoma) are discussed, highlighting critical points such as the choice of markers to sort CSCs and mouse models to demonstrate that CSCs are able to replicate the original tumor. A discussion of the possible role of aldehyde dehydrogenase and CXCR6 biomarkers as signaling molecules in CSCs and normal stem cells is also discussed. The author believes that efforts have to be made to investigate the functional and biological properties of putative CSCs in cancer. Developing diagnostic/prognostic tools to follow cancer development is also a challenge. In this connection it would be useful to develop a multidisciplinary approach combining mathematics, physics and biology which merges experimental approaches and theory. Biological models alone are probably unable to resolve the problem completely.

  18. [Dendritic cells in cancer immunotherapy].

    Science.gov (United States)

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

    2015-01-01

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

  19. Understanding the cancer stem cell

    OpenAIRE

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

    2010-01-01

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

  20. Effect of vitamin E on protein bound carbhohydrate complexes in radiation treated oral squamous cell carcinoma patients

    OpenAIRE

    S. Chitra; Shyamala Devi, C. S.

    2008-01-01

    Serum glycoproteins were evaluated in oral squamous cell carcinoma patients treated with radiotherapy and also the effect of vitamin E was studied. Cell surface glycoconjugates are important parameters in the detection of malignancy. Thus, the objective of the present study is to evaluate the efficacy of vitamin E on glycoproteins in oral cavity cancer patients treated with radiotherapy. The study includes 26 age and sex matched normal healthy individuals and 26 patients with squamous cell ca...

  1. A cancer-favoring oncolytic vaccinia virus shows enhanced suppression of stem-cell like colon cancer

    Science.gov (United States)

    Yoo, So Young; Bang, Seo Young; Jeong, Su-Nam; Kang, Dae Hwan; Heo, Jeong

    2016-01-01

    Stem cell-like colon cancer cells (SCCs) pose a major challenge in colon cancer treatment because of their resistance to chemotherapy and radiotherapy. Oncolytic virus-based therapy has shown promising results in uncured cancer patients; however, its effects on SCCs are not well studied yet. Here, we engineered a cancer-favoring oncolytic vaccinia virus (CVV) as a potent biotherapeutic and investigated its therapeutic efficacy in terms of killing SCCs. CVV is an evolved Wyeth strain vaccinia virus (EVV) lacking the viral thymidine kinase. SCC models were established using human or mouse colon cancer spheres, which continuously expressed stemness markers. The cancer-favoring characteristics and different cytotoxic pathways for killing cancer cells successfully overrode general drug resistance, thereby killing colon cancer cells regardless of the presence of SCCs. Subcutaneously injected HT29 spheres showed lower growth in CVV-treated models than in 5-Fu-treated models. Intraperitoneally injected CT26 spheres induced tumor masses in the abdominal region. CVV-treated groups showed higher survival rates and smaller tumor mass formation, compared to 5-Fu-treated groups. Interestingly, the combined treatment of CVV with 5-Fu showed improved survival rates and complete suppression of tumor mass. The CVV developed in this study, thus, effectively suppresses SCCs, which can be synergistically enhanced by simultaneous treatment with the anticancer drug 5-Fu. Our novel CVV is highly advantageous as a next-generation therapeutic for treating colon cancer. PMID:26918725

  2. Prostate Cancer Stem Cells: Research Advances.

    Science.gov (United States)

    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.

  3. Prostate Cancer Stem Cells: Research Advances

    Directory of Open Access Journals (Sweden)

    Dagmara Jaworska

    2015-11-01

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

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

    OpenAIRE

    Gao, Jian-Xin

    2007-01-01

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

  5. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer.

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-14

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients. PMID:27182156

  6. KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine | Office of Cancer Genomics

    Science.gov (United States)

    Decitabine, a cancer therapeutic that inhibits DNA methylation, produces variable antitumor response rates in patients with solid tumors that might be leveraged clinically with identification of a predictive biomarker. In this study, we profiled the response of human ovarian, melanoma, and breast cancer cells treated with decitabine, finding that RAS/MEK/ERK pathway activation and DNMT1 expression correlated with cytotoxic activity. Further, we showed that KRAS genomic status predicted decitabine sensitivity in low-grade and high-grade serous ovarian cancer cells.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  8. Extinction Models for Cancer Stem Cell Therapy

    OpenAIRE

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

    2009-01-01

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

  9. 非小细胞肺癌脑转移调强放射治疗可行性研究%Feasibity study for brain metastases of non-small cell lung cancer treated with IMRT

    Institute of Scientific and Technical Information of China (English)

    王靖; 卢冰; 胡银祥; 欧阳伟炜; 苏胜发; 王刚; 龙金华; 栗蕙芹

    2013-01-01

    OBJECTIVE:To investigate the feasibility of clinical prospective study for brain metastases from non-small cell lung cancer (NSCLC) treated with intensity modulated radiotherapy (IMRT).METHODS:Thirty NSCLC untreated patients with brain metastases treated with IMRT.Through evaluating the response,quality of life before and after treatment,toxicity and normal brain tissue adjacent to the tumor dose-volume parameters,the advantages of IMRT was analyzed and compared to redesigned three-dimesional conformal radiation therapy (3D-CRT) or stereotactic radiotherapy (SRT) plans.RESULTS:Complete remission was 16.7% (5/30),partial remission was 33.3% (10/30).Minimental state examination score (all patients 25.67 ±2.73,three to five metastases patients 24.77 ±3.24) and activities of daily living score (all patients 79.00 ±14.82,three to five metastases patients 72.31 ±15.63) after treatment were higher than that before treatment(the former all patients 22.9 ±4.94,three to five metastases patients 19.23± 4.64; the later all patients 68.67 ± 19.60,three to five metastases patients 55.77 ±19.13),especially with three to five brain metastases lesions (P<0.05).Acute injury of grade Ⅱ was 10%(3/30) and late injury of grade Ⅱ,Ⅳ was in one patient.Dose volume V35 (147.56±80.77),V40 (50.86±32.33) and V45 (22.32± 15.40) in normal tissue adjacent to the brain tumor was obviously decreased in IMRT,especially within three to five metastases lesions(V35 214.56±58.09,V40 79.29 ± 22.76,V45 34.17±12.64,P<0.05).CONCLUSIONS:IMRT treatment of NSCLC brain metastases is effective and the toxicity can be tolerated.For the patients with 3-5 brain metastases lesions selecting IMRT may be a better choice.%目的:探讨调强放射治疗(intensity modulated radiation therapy,IMRT)非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移的可行性.方法:选择NSCLC脑转移初治患者30例,分析近期疗效、治疗前后生活质量和毒副作用,与重新设计

  10. Stem cell biology in thyroid cancer: Insights for novel therapies

    Institute of Scientific and Technical Information of China (English)

    Parisha; Bhatia; Koji; Tsumagari; Zakaria; Y; Abd; Elmageed; Paul; Friedlander; Joseph; F; Buell; Emad; Kandil

    2014-01-01

    Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.

  11. Stem cell biology in thyroid cancer: Insights for novel therapies

    Science.gov (United States)

    Bhatia, Parisha; Tsumagari, Koji; Abd Elmageed, Zakaria Y; Friedlander, Paul; Buell, Joseph F; Kandil, Emad

    2014-01-01

    Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review. PMID:25426258

  12. Steroidogenesis in amlodipine treated purified Leydig cells

    Energy Technology Data Exchange (ETDEWEB)

    Latif, Rabia, E-mail: rabialatif08@hotmail.com [Department of Physiology, Army Medical College, National University of Sciences and Technology, Islamabad (Pakistan); Lodhi, Ghulam Mustafa, E-mail: drmustafa786@gmail.com [Department of Physiology, Wah Medical College, Wah (Pakistan); Hameed, Waqas, E-mail: waqham@hotmail.com [Department of Physiology, Rehman Medical College, Peshawar (Pakistan); Aslam, Muhammad, E-mail: professormaslam@yahoo.com [Department of Physiology, Shifa College of Medicine, Islamabad (Pakistan)

    2012-01-01

    Drugs have been shown to adversely affect male fertility and recently anti-hypertensive drugs were added to the list. The anti-fertility effects of amlodipine, a calcium channel blocker, are well-illustrated in in vivo experiments but lack an in vitro proof. The present study was designed to experimentally elucidate the effects of amlodipine on Leydig cell steroidogenesis and intracellular calcium in vitro. Leydig cells of Sprague–Dawley rats were isolated and purified by Percoll. Cells were incubated for 3 h with/without amlodipine in the presence/absence of LH, dbcAMP, Pregnenolone and 25-Hydroxycholesterol. Cytosolic calcium was measured in purified Leydig cells by fluorometric technique. The results showed significantly reduced (P < 0.05) steroidogenesis and intracellular calcium in amlodipine exposed rats. The site of amlodipine induced steroidogenic inhibition seems to be prior to the formation of Pregnenolone at the level of StAR protein. -- Highlights: ► Inhibition of steroidogenesis in isolated and purified Leydig cells by amlodipine. ► Site of inhibition was before Pregnenolone formation, at the level of StAR protein. ► Inhibition of LH stimulated rise in cytosolic calcium by amlodipine.

  13. Stem cell therapy to treat heart ischaemia

    DEFF Research Database (Denmark)

    Qayyum, Abbas Ali; Mathiasen, Anders Bruun; Kastrup, Jens

    2014-01-01

    Diabetes mellitus is a well-known risk factor for coronary artery disease (CAD), which can lead to acute myocardial infarction, chronic myocardial ischaemia and heart failure. Despite the advantages in medical treatment, percutaneous coronary intervention (PCI) and coronary artery bypass grafting...... of cardiomyocytes. Recently published clinical trials and meta-analysis of stem cell studies have shown encouraging results with increased left ventricle ejection fraction and reduced symptoms in patients with CAD and heart failure. There is some evidence of mesenchymal stem cell being more effective compared...

  14. Cancer immunotherapy using γδT cells : dealing with diversity

    NARCIS (Netherlands)

    Schepers, W.A.

    2015-01-01

    The broad and potent tumour-reactivity of innate-like γδT cells makes them valuable additions to current cancer immunotherapeutic concepts based on adaptive immunity, such as monoclonal antibodies and αβT cells. Nevertheless, clinical success using γδT cells to treat cancer has so far fallen short h

  15. In vitro study on effect of germinated wheat on human breast cancer cells

    Science.gov (United States)

    This research investigated the possible anti-cancer effects of germinated wheat flours (GWF) on cell growth and apoptosis of human breast cancer cells. In a series of in vitro experiments, estrogen receptor-positive (MCF-7) and negative (MDA-MB-231) cells were cultured and treated with GWF that wer...

  16. A suicide gene therapy approach to treat epidermolysis bullosa-associated skin cancer

    International Nuclear Information System (INIS)

    Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited disease causing extensive blister formation within the basal membrane zone (BMZ) of the skin and mucous membranes. It is caused by premature STOP mutations in the COL7A1 gene, which is indispensable for proper skin assembling. RDEB is associated with the development of a highly malignant skin cancer (squamous cell carcinoma, SCC) in early adulthood that displays a life threatening complication within this patient group. To date, neither chemo- nor radiotherapies showed successful results and due to the high metastatic potential of RDEB SCC wide surgical excision is still favoured. In this study we could reveal a new promising cancer treatment using spliceosome mediated RNA trans-splicing (SMaRT) using a suicide gene therapy approach. First we identified the tumour marker gene MMP-9 expressed by RDEB SCC cells in cell culture which was used to generate various pre-mRNA trans-splicing molecules (PTM). PTMs are able to facilitate trans-splicing between a tumour target gene and a cell death inducing peptide/toxin, encoded by the PTM. As a consequence the toxin is expressed in cancer cells leading to the induction of cell death. This technique offers high specificity in cancer cell targeting compared to other conventional cDNA expression studies. Various trans-splicing molecules were pre-evaluated in a fluorescence screening model for their best trans-splicing efficiency with the target molecule. Herein we identified two potent PTMs (PTM BD0 and PTM BD6), that were further adapted for endogenous suicide studies by inserting the toxin streptolysin O. In two independent in vitro cell culture assays we were able to confirm that the trans-splicing molecules are able to induce expression of the toxin resulting in cell membrane permeabilization and increased cell death induction. The results indicate that SMaRT technology offers a new platform for a suicide gene therapy approach to treat malignant squamous cell

  17. Dendritic-tumor fusion cells in cancer immunotherapy.

    Science.gov (United States)

    Takakura, Kazuki; Kajihara, Mikio; Ito, Zensho; Ohkusa, Toshifumi; Gong, Jianlin; Koido, Shigeo

    2015-03-01

    A promising area of clinical investigation is the use of cancer immunotherapy to treat cancer patients. Dendritic cells (DCs) operate as professional antigen-presenting cells (APCs) and play a critical role in the induction of antitumor immune responses. Thus, DC-based cancer immunotherapy represents a powerful strategy. One DC-based cancer immunotherapy strategy that has been investigated is the administration of fusion cells generated with DCs and whole tumor cells (DC-tumor fusion cells). The DC-tumor fusion cells can process a broad array of tumor-associated antigens (TAAs), including unidentified molecules, and present them through major histocompatibility complex (MHC) class I and II pathways in the context of co-stimulatory signals. Improving the therapeutic efficacy of DC-tumor fusion cell-based cancer immunotherapy requires increased immunogenicity of DCs and whole tumor cells. We discuss the potential ability of DC-tumor fusion cells to activate antigen-specific T cells and strategies to improve the immunogenicity of DC-tumor fusion cells as anticancer vaccines.

  18. Mortality of patients with clinically localized prostate cancer treated with observation for 10 years or longer

    DEFF Research Database (Denmark)

    Brasso, Klaus; Friis, S; Juel, K;

    1999-01-01

    We studied the outcome in patients with early and probably organ confined prostate cancer who were considered candidates for curative therapy and treated expectantly.......We studied the outcome in patients with early and probably organ confined prostate cancer who were considered candidates for curative therapy and treated expectantly....

  19. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models......There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...

  20. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells

    Science.gov (United States)

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji

    2015-01-01

    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A–nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells. PMID:25775533

  1. Comorbidity-Adjusted Survival in Early Stage Lung Cancer Patients Treated with Hypofractionated Proton Therapy

    Directory of Open Access Journals (Sweden)

    Sharon Y. Do

    2010-01-01

    Full Text Available Objective. To determine the influence of comorbidity on survival in early-stage lung cancer patients treated with proton radiotherapy, using the Charlson Comorbidity Index. Study Design and Setting. Fifty-four non-small-cell lung cancer patients, treated prospectively in a phase II clinical trial with hypofractionated proton therapy, were analyzed retrospectively to assess their burden of comorbid disease as expressed by Charlson Comorbidity Index. Using the Charlson Comorbidity Index method, a predicted survival curve based on comorbidity was formulated and compared to the observed mortality from causes other than lung cancer in the study population. Results. The study population had an average age score of 2.8 and an average Charlson Comorbidity Index of 4.7. Predicted survival was calculated to be 67% and 50% at 2 and 4 years, respectively. Actual comorbidity-specific survival at 2 and 4 years was 64% and 45%, respectively. The observed survival fell within the 95% confidence intervals of the predicted survival at all time points up to 5 years. Conclusion. Predicted mortality from concurrent disease, based on Charlson Comorbidity Index, correlated well with observed comorbidity-specific mortality. This helps substantiate the accuracy of the data coding in cause of death and strengthens previously reported disease-specific survival rates.

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

    OpenAIRE

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

    2014-01-01

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

  3. Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach

    Science.gov (United States)

    Pizzolato, Nicola; Valenti, Davide; Adorno, Dominique; Spagnolo, Bernardo

    2009-09-01

    The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a statistical approach. Cancer progression is explored by applying a Monte Carlo method to simulate the stochastic behavior of cell reproduction and death in a population of blood cells which can experience genetic mutations. In CML front line therapy is represented by the tyrosine kinase inhibitor imatinib which strongly affects the reproduction of leukemic cells only. In this work, we analyze the effects of a targeted therapy on the evolutionary dynamics of normal, first-mutant and cancerous cell populations. Several scenarios of the evolutionary dynamics of imatinib-treated leukemic cells are described as a consequence of the efficacy of the different modelled therapies. We show how the patient response to the therapy changes when a high value of the mutation rate from healthy to cancerous cells is present. Our results are in agreement with clinical observations. Unfortunately, development of resistance to imatinib is observed in a fraction of patients, whose blood cells are characterized by an increasing number of genetic alterations. We find that the occurrence of resistance to the therapy can be related to a progressive increase of deleterious mutations.

  4. Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?

    OpenAIRE

    Ravindran, Jayaraj; Prasad, Sahdeo; Aggarwal, Bharat B.

    2009-01-01

    Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one ...

  5. Mechanical properties of normal versus cancerous breast cells.

    Science.gov (United States)

    Smelser, Amanda M; Macosko, Jed C; O'Dell, Adam P; Smyre, Scott; Bonin, Keith; Holzwarth, George

    2015-11-01

    A cell's mechanical properties are important in determining its adhesion, migration, and response to the mechanical properties of its microenvironment and may help explain behavioral differences between normal and cancerous cells. Using fluorescently labeled peroxisomes as microrheological probes, the interior mechanical properties of normal breast cells were compared to a metastatic breast cell line, MDA-MB-231. To estimate the mechanical properties of cell cytoplasms from the motions of their peroxisomes, it was necessary to reduce the contribution of active cytoskeletal motions to peroxisome motion. This was done by treating the cells with blebbistatin, to inhibit myosin II, or with sodium azide and 2-deoxy-D-glucose, to reduce intracellular ATP. Using either treatment, the peroxisomes exhibited normal diffusion or subdiffusion, and their mean squared displacements (MSDs) showed that the MDA-MB-231 cells were significantly softer than normal cells. For these two cell types, peroxisome MSDs in treated and untreated cells converged at high frequencies, indicating that cytoskeletal structure was not altered by the drug treatment. The MSDs from ATP-depleted cells were analyzed by the generalized Stokes-Einstein relation to estimate the interior viscoelastic modulus G* and its components, the elastic shear modulus G' and viscous shear modulus G", at angular frequencies between 0.126 and 628 rad/s. These moduli are the material coefficients that enter into stress-strain relations and relaxation times in quantitative mechanical models such as the poroelastic model of the interior regions of cancerous and non-cancerous cells. PMID:25929519

  6. Prevalence and predictors of cognitive dysfunction in opioid-treated patients with cancer: a multinational study

    DEFF Research Database (Denmark)

    Kurita, Geana P; Sjøgren, Per; Ekholm, Ola;

    2011-01-01

    PURPOSE To identify prevalence and associated factors of cognitive dysfunction in opioid-treated patients with cancer. PATIENTS AND METHODS EPOS (European Pharmacogenetic Opioid Study) is a prospective cross-sectional multicenter study in which adult patients with cancer who received treatment wi......-treated patients with cancer had possible or definite cognitive dysfunction. Lung cancer, daily opioid doses of 400 mg or more (oral morphine equivalents), older age, low KPS, shorter time since cancer diagnosis, and absence of BTP were predictors for cognitive dysfunction.......PURPOSE To identify prevalence and associated factors of cognitive dysfunction in opioid-treated patients with cancer. PATIENTS AND METHODS EPOS (European Pharmacogenetic Opioid Study) is a prospective cross-sectional multicenter study in which adult patients with cancer who received treatment...... with opioids for moderate or severe pain for at least 3 days were included. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). MMSE scores were categorized into definite cognitive dysfunction (scores

  7. Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients

    International Nuclear Information System (INIS)

    CD20, a membrane protein highly expressed on most B-cell lymphomas, is an effective target demonstrated in clinical practice for treating B-cell non-Hodgkin's lymphoma (NHL). Rituximab is a monoclonal antibody against CD20. In this work, we applied atomic force microscopy (AFM) to map the nanoscale distribution of CD20 molecules on the surface of cancer cells from clinical B-cell NHL patients under the assistance of ROR1 fluorescence recognition (ROR1 is a specific cell surface marker exclusively expressed on cancer cells). First, the ROR1 fluorescence labeling experiments showed that ROR1 was expressed on cancer cells from B-cell lymphoma patients, but not on normal cells from healthy volunteers. Next, under the guidance of ROR1 fluorescence, the rituximab-conjugated AFM tips were moved to cancer cells to image the cellular morphologies and detect the CD20-rituximab interactions on the cell surfaces. The distribution maps of CD20 on cancer cells were constructed by obtaining arrays of (16×16) force curves in local areas (500×500 nm2) on the cell surfaces. The experimental results provide a new approach to directly investigate the nanoscale distribution of target protein on single clinical cancer cells. - Highlights: • Cancer cells were recognized from healthy cells by ROR1 fluorescence labeling. • The nanoscale distribution of CD20 on cancer cells was characterized. • The distribution of CD20 was non-uniform on the surface of cancer cells

  8. Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning, E-mail: xin@egr.msu.edu [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong (China); Wang, Yuechao; Dong, Zaili [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

    2013-11-01

    CD20, a membrane protein highly expressed on most B-cell lymphomas, is an effective target demonstrated in clinical practice for treating B-cell non-Hodgkin's lymphoma (NHL). Rituximab is a monoclonal antibody against CD20. In this work, we applied atomic force microscopy (AFM) to map the nanoscale distribution of CD20 molecules on the surface of cancer cells from clinical B-cell NHL patients under the assistance of ROR1 fluorescence recognition (ROR1 is a specific cell surface marker exclusively expressed on cancer cells). First, the ROR1 fluorescence labeling experiments showed that ROR1 was expressed on cancer cells from B-cell lymphoma patients, but not on normal cells from healthy volunteers. Next, under the guidance of ROR1 fluorescence, the rituximab-conjugated AFM tips were moved to cancer cells to image the cellular morphologies and detect the CD20-rituximab interactions on the cell surfaces. The distribution maps of CD20 on cancer cells were constructed by obtaining arrays of (16×16) force curves in local areas (500×500 nm{sup 2}) on the cell surfaces. The experimental results provide a new approach to directly investigate the nanoscale distribution of target protein on single clinical cancer cells. - Highlights: • Cancer cells were recognized from healthy cells by ROR1 fluorescence labeling. • The nanoscale distribution of CD20 on cancer cells was characterized. • The distribution of CD20 was non-uniform on the surface of cancer cells.

  9. Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy

    OpenAIRE

    Xuanbin Wang; Yibin Feng; Ning Wang; Fan Cheung; Hor Yue Tan; Sen Zhong; Charlie Li; Seiichi Kobayashi

    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...

  10. Cancer stem cells and brain tumors

    OpenAIRE

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

    2008-01-01

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

  11. Cancer stem cells, tumor dormancy, and metastasis

    OpenAIRE

    EmilyChen

    2012-01-01

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

  12. Cancer Immunotherapy Using Engineered Hematopoietic Stem Cells

    OpenAIRE

    Gschweng, Eric Hans

    2015-01-01

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

  13. Third-line chemotherapy for small cell lung cancer

    NARCIS (Netherlands)

    de Jong, WK; ten Hacken, NHT; Groen, HJM

    2006-01-01

    Efficacy of third-line chemotherapy treatment for small cell lung cancer (SCLC) is unknown. We present our experience with third-tine chemotherapy for recurrent SCLC. Between January 1996 and July 2004 all. consecutive patients treated for SCLC were retrospectively studied. We recorded patient chara

  14. Different impact of excision repair cross-complementation group 1 on survival in male and female patients with inoperable non-small-cell lung cancer treated with carboplatin and gemcitabine

    DEFF Research Database (Denmark)

    Holm, Bente; Mellemgaard, Anders; Skov, Torsten;

    2009-01-01

    PURPOSE: The excision repair cross-complementation group 1 (ERCC1) status was assessed in patients receiving carboplatin and gemcitabine for inoperable non-small-cell lung cancer (NSCLC). We analyzed the association between the ERCC1 status and the overall survival after the chemotherapy. PATIENTS...... mainly seen in men, where those with ERCC1-negative tumors had a significantly increased survival compared to men with ERCC1-positive tumors (median survival, 11.8 months v 7.9 months; P = .005). Conversely, women who were ERCC1 negative did not have a survival advantage over ERCC1-positive women...

  15. Successful management of elderly breast cancer patients treated without radiotherapy

    Directory of Open Access Journals (Sweden)

    Robertson John FR

    2007-06-01

    Full Text Available Abstract Background Breast cancer in the elderly may follow a less aggressive course. There are data suggesting that radiotherapy (RT following breast conserving surgery (BCS for invasive carcinoma may not be necessary in some elderly patients. The addition of RT to surgery might constitute an imposition to such patients due to age-related factors. The aim of this study was to assess the efficacy of BCS without adjuvant RT in this group of patients. Patients and methods A retrospective review of 92 elderly (median age 75 years; range: 70 – 87 years patients (analysed as 93 'patients' due to one patient having bilateral cancers managed in a dedicated breast clinic and who underwent BCS for invasive carcinoma was carried out. Eighty-three patients did not receive postoperative RT to the breast (no-RT group whereas the remaining 10 had RT (RT-group. Results The median age in this group was 75 (range 70 – 87 years. The mean tumour size was 18 mm with a median follow-up of 37 (range 6 – 142 months. In the no RT group, adjuvant endocrine therapy with tamoxifen was given to 40/53 patients. No patients in the oestrogen receptor (ER negative group received tamoxifen. The local recurrence (LR rate in this group was 8.4% (2.4% per year, n = 7/83, with median time to LR of 17 months. In this no-RT group LR was correlated to ER status (2/53 ER+, 5/26ER-, p = 0.024 and margins of excision (n = 1/54 >5 mm, 2/17 1–5 mm, 4/12 Conclusion It would appear that omission of RT following successful BCS in elderly patients with ER positive tumours receiving adjuvant tamoxifen may be acceptable. The LR rate as shown in this retrospective study is highly comparable to that of younger patients treated by conventional therapy. This concept is now being evaluated prospectively following a change in treatment practice.

  16. How I treat Langerhans cell histiocytosis

    Science.gov (United States)

    Allen, Carl E.; Ladisch, Stephan

    2015-01-01

    “Langerhans cell histiocytosis” (LCH) describes a spectrum of clinical presentations ranging from a single bone lesion or trivial skin rash to an explosive disseminated disease. Regardless of clinical severity, LCH lesions share the common histology of CD1a+/CD207+ dendritic cells with characteristic morphology among an inflammatory infiltrate. Despite historical uncertainty defining LCH as inflammatory vs neoplastic and incomplete understanding of mechanisms of pathogenesis, clinical outcomes have improved markedly over the past decades through cooperative randomized clinical trials based on empiric therapeutic strategies. Significant advances include recognition of high- and low-risk clinical groups defined by hematopoietic and/or hepatic involvement, and of the importance of optimal intensity and of duration of chemotherapy. Nevertheless, mortality of high-risk patients, disease recurrence, lack of robustly tested salvage strategies, and significant disease morbidity of both high- and low-risk patients remain challenges. Recent discovery of recurrent somatic mutations in mitogen-activated protein kinase pathway genes at critical stages of myeloid hematopoietic differentiation in LCH patients supports redefinition of the disease as a myeloproliferative disorder and provides opportunities to develop novel approaches to diagnosis and therapy. PMID:25827831

  17. Head and neck cancer stem cells.

    Science.gov (United States)

    Krishnamurthy, S; Nör, J E

    2012-04-01

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

  18. Anti-Cancer Activity of Solanum nigrum (AESN through Suppression of Mitochondrial Function and Epithelial-Mesenchymal Transition (EMT in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ying-Jang Lai

    2016-04-01

    Full Text Available Chemotherapy is the main approach for treating advanced and recurrent carcinoma, but the clinical performance of chemotherapy is limited by relatively low response rates, drug resistance, and adverse effects that severely affect the quality of life of patients. An association between epithelial-mesenchymal transition (EMT and chemotherapy resistance has been investigated in recent studies. Our recent studies have found that the aqueous extract of Solanum nigrum (AESN is a crucial ingredient in some traditional Chinese medicine formulas for treating various types of cancer patients and exhibits antitumor effects. We evaluated the suppression of EMT in MCF-7 breast cancer cells treated with AESN. The mitochondrial morphology was investigated using Mitotracker Deep-Red FM stain. Our results indicated that AESN markedly inhibited cell viability of MCF-7 breast cancer cells through apoptosis induction and cell cycle arrest mediated by activation of caspase-3 and production of reactive oxygen species. Furthermore, mitochondrial fission was observed in MCF-7 breast cancer cells treated with AESN. In addition to elevation of E-cadherin, downregulations of ZEB1, N-cadherin, and vimentin were found in AESN-treated MCF-7 breast cancer cells. These results suggested that AESN could inhibit EMT of MCF-7 breast cancer cells mediated by attenuation of mitochondrial function. AESN could be potentially beneficial in treating breast cancer cells, and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells.

  19. Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer

    Science.gov (United States)

    2016-05-02

    HER2-positive Breast Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

  20. Nifedipine promotes the proliferation and migration of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Dong-Qing Guo

    Full Text Available Nifedipine is widely used as a calcium channel blocker (CCB to treat angina and hypertension,but it is controversial with respect the risk of stimulation of cancers. In this study, we demonstrated that nifedipine promoted the proliferation and migration of breast cancer cells both invivo and invitro. However, verapamil, another calcium channel blocker, didn't exert the similar effects. Nifedipine and high concentration KCl failed to alter the [Ca2+]i in MDA-MB-231 cells, suggesting that such nifedipine effect was not related with calcium channel. Moreover, nifedipine decreased miRNA-524-5p, resulting in the up-regulation of brain protein I3 (BRI3. Erk pathway was consequently activated and led to the proliferation and migration of breast cancer cells. Silencing BRI3 reversed the promoting effect of nifedipine on the breast cancer. In a summary, nifedipine stimulated the proliferation and migration of breast cancer cells via the axis of miRNA-524-5p-BRI3-Erk pathway independently of its calcium channel-blocking activity. Our findings highlight that nifedipine but not verapamil is conducive for breast cancer growth and metastasis, urging that the caution should be taken in clinic to prescribe nifedipine to women who suffering both hypertension and breast cancer, and hypertension with a tendency in breast cancers.

  1. Sunitinib Malate in Treating HIV-Positive Patients With Cancer Receiving Antiretroviral Therapy

    Science.gov (United States)

    2014-03-14

    -transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Renal Cell Cancer; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Stage IV Renal Cell Cancer; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  2. Activation of TIM1 induces colon cancer cell apoptosis via modulating Fas ligand expression.

    Science.gov (United States)

    Wang, Hao; Zhang, Xueyan; Sun, Wenjing; Hu, Xiaocui; Li, Xiaolin; Fu, Songbin; Liu, Chen

    2016-04-29

    The pathogenesis of colon cancer is unclear. It is proposed that TIM1 has an association with human cancer. The present study aims to investigate the role of TIM1 activation in the inhibition of human colon cancer cells. In this study, human colon cancer cell line, HT29 and T84 cells were cultured. The expression of TIM1 was assessed by real time RT-PCR and Western blotting. The TIM1 on the cancer cells was activated in the culture by adding recombinant TIM4. The chromatin structure at the FasL promoter locus was assessed by chromatin immunoprecipitation. The apoptosis of the cancer cells was assessed by flow cytometry. The results showed that human colon cancer cell lines, HT29 cells and T84 cells, expressed TIM1. Activation of TIM1 by exposing the cells to TIM4 significantly increased the frequency of apoptotic colon cancer cells. The expression of FasL was increased in the cancer cells after treating by TIM4. Blocking Fas or FasL abolished the exposure to TIM4-induced T84 cell apoptosis. In conclusion, HT29 cells and T84 cells express TIM1; activation TIM1 can induce the cancer cell apoptosis. TIM1 may be a novel therapeutic target of colon cancer.

  3. Telomere shortening and cell senescence induced by perylene derivatives in A549 human lung cancer cells.

    Science.gov (United States)

    Taka, Thanachai; Huang, Liming; Wongnoppavich, Ariyaphong; Tam-Chang, Suk-Wah; Lee, T Randall; Tuntiwechapikul, Wirote

    2013-02-15

    Cancer cells evade replicative senescence by re-expressing telomerase, which maintains telomere length and hence chromosomal integrity. Telomerase inhibition would lead cancer cells to senesce and therefore prevent cancer cells from growing indefinitely. G-quadruplex ligands can attenuate telomerase activity by inducing G-quadruplex formation at the 3'-overhang of telomere and at the human telomerase reverse transcriptase (hTERT) promoter; the former prevents telomerase from accessing the telomere, and the latter acts as a transcriptional silencer. The present investigation found that perylene derivatives PM2 and PIPER induced G-quadruplex formation from both telomeric DNA and the hTERT promoter region in vitro. Further, TRAP assay showed that these compounds inhibited telomerase in a dose-dependent manner. When A549 human lung cancer cells were treated with these compounds, hTERT expression was down-regulated. Moreover, the crude protein extract from these treated cells exhibited less telomerase activity. In the long-term treatment of A549 lung cancer cells with sub-cytotoxic dose of these perylenes, telomere shortening, reduction of cell proliferation and tumorigenicity, and cell senescence were observed. The results of this study indicate that perylene derivatives warrant further consideration as effective agents for cancer therapy.

  4. Study on Tongkuaixiao Babu Plaster(痛块消巴布剂)in Treating Cancer Pain

    Institute of Scientific and Technical Information of China (English)

    万冬桂; 李佩文

    2004-01-01

    Objective: To explore the efficacy of Tongkuaixiao Babu plaster (痛块消巴剂, TKXBBP)in treating cancer pain. Methods: In the clinical observation, sixty-five patients with moderate or severe cancer pain were randomly divided into two groups: 32 in the treated group (TKXBBP group) and 33 in the control group (Bucinnazine group). The therapeutic effects in relieving pain, improving quality of life (QOL),and the rate of satisfaction the patients felt of the two groups were compared respectively. Results: TKXBBP was effective in treating cancer pain. There wasn't any statistically significant difference in total effective rate (P>0.05), but the statistical difference was significant in obvious remission rate (P<0.05) between the treated and control group, and the effect on serious pain shown in the treated group was better than that of the control group (P<0.05). The difference in the initiation time of relieving cancer pain was insignificant (P>0.05), while in the remission period, the treated group showed its treatment was obviously superior to that of the control group (P<0.05). TKXBBP showed better effect in the improvement of QOL (P<0.05)and satisfaction rate, with significant difference between the treated and the control groups (P<0.01). Conclusion: TKXBBP's effect in treating cancer pain was obvious, its application was safe and convenient. It was shown that the external treatment with this kind of Chinese medicine had great advantage in treating cancer pain.

  5. Resveratrol and STAT inhibitor enhance autophagy in ovarian cancer cells.

    Science.gov (United States)

    Zhong, L-X; Zhang, Y; Wu, M-L; Liu, Y-N; Zhang, P; Chen, X-Y; Kong, Q-Y; Liu, J; Li, H

    2016-01-01

    Autophagic activity reflects cellular response to drug treatment and can be regulated by STAT3 signaling. Resveratrol inhibits STAT3 activation and causes remarkable growth arrest and cell death of ovarian cancer (OC) cells. However, the autophagic status and its relevance with resveratrol's anti-OC effects remain unclear. We analyzed the states of autophagic activities, the nature of autophagosomes and the levels of autophagy-related proteins (LC-3, Beclin 1 and STAT3) in resveratrol-treated CAOV-3 and OVCAR-3 OC cells using multiple approaches. We elucidated the correlation of STAT3 inhibition with autophagic activity by treating OC cells with an upstream inhibitor of STAT proteins, AG490. Resveratrol efficiently suppressed growth, induced apoptosis and inactivated STAT3 signaling of the two OC cell lines. We found enhanced autophagic activity accompanied with Beclin-1 upregulation and LC3 enzymatic cleavage in resveratrol-treated OC cells. Immunofluorescent (IF) microscopic and IF-based confocal examinations demonstrated the accumulation of cytoplasmic granules co-labeled with LC3 and cytochrome C in resveratrol- or AG490-treated OC cells. Using electron microscopy, we confirmed an increase in autophagosomes and mitochondrial spheroids in either resveratrol- or AG490-treated OC cells. This study demonstrates the abilities of resveratrol to enhance apoptotic and autophagic activities in OC cells, presumably via inactivating STAT3 signaling. Resveratrol or the selective JAK2 inhibitor also leads to mitochondrial turnover, which would be unfavorable for OC cell survival and sensitize OC cells to resveratrol. PMID:27551495

  6. Mitochondria, cholesterol and cancer cell metabolism.

    Science.gov (United States)

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

    2016-12-01

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

  7. Cell of origin of lung cancer

    Directory of Open Access Journals (Sweden)

    Jennifer M Hanna

    2013-01-01

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

  8. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Tim A D Smith

    Full Text Available The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined.MDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK, CTP:phosphocholine cytidylyl transferase (CCT and PtdCho-phospholipase C (PLC were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography.Metformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U]glucose.This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.

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

    OpenAIRE

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

    2015-01-01

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

  10. Cancer Cell Fusion: Mechanisms Slowly Unravel

    Science.gov (United States)

    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

  11. The biology of cancer stem cells.

    Science.gov (United States)

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

    2007-01-01

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

  12. Lung Cancer

    Science.gov (United States)

    ... spreads in different ways, and each is treated differently. Non-small cell lung cancer is more common than small cell lung cancer. Small cell lung cancer grows more quickly and is more likely to spread to other organs in the body. Learn more about non-small cell lung cancer. Learn ...

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

    OpenAIRE

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

    2010-01-01

    Abstract Background Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced b...

  14. The Implications of Cancer Stem Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wenjing Jiang

    2012-12-01

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

  15. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    Energy Technology Data Exchange (ETDEWEB)

    Salama, Joseph K., E-mail: joseph.salama@duke.edu [Duke University Medical Center, Durham, NC (United States); Stinchcombe, Thomas E. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Gu Lin; Wang Xiaofei [CALGB Statistical Center, Duke University Medical Center, Durham, NC (United States); Morano, Karen [Quality Assurance Review Center, Lincoln, RI (United States); Bogart, Jeffrey A. [State University of New York Upstate Medical University, Syracuse, NY (United States); Crawford, Jeffrey C. [Duke University Medical Center, Durham, NC (United States); Socinski, Mark A. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Blackstock, A. William [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Vokes, Everett E. [University of Chicago, Chicago, IL (United States)

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  16. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    International Nuclear Information System (INIS)

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non–small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  17. Cold atmospheric plasma for selectively ablating metastatic breast cancer cells.

    Science.gov (United States)

    Wang, Mian; Holmes, Benjamin; Cheng, Xiaoqian; Zhu, Wei; Keidar, Michael; Zhang, Lijie Grace

    2013-01-01

    Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atmospheric plasma (CAP) is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, the objective of this research is to investigate a novel CAP-based therapy for selectively bone metastatic breast cancer treatment. For this purpose, human metastatic breast cancer (BrCa) cells and bone marrow derived human mesenchymal stem cells (MSCs) were separately treated with CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture. With different treatment times, different BrCa and MSC cell responses were observed. Our results showed that BrCa cells were more sensitive to these CAP treatments than MSCs under plasma dose conditions tested. It demonstrated that CAP can selectively ablate metastatic BrCa cells in vitro without damaging healthy MSCs at the metastatic bone site. In addition, our study showed that CAP treatment can significantly inhibit the migration and invasion of BrCa cells. The results suggest the great potential of CAP for breast cancer therapy.

  18. Cold atmospheric plasma for selectively ablating metastatic breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Mian Wang

    Full Text Available Traditional breast cancer treatments such as surgery and radiotherapy contain many inherent limitations with regards to incomplete and nonselective tumor ablation. Cold atmospheric plasma (CAP is an ionized gas where the ion temperature is close to room temperature. It contains electrons, charged particles, radicals, various excited molecules, UV photons and transient electric fields. These various compositional elements have the potential to either enhance and promote cellular activity, or disrupt and destroy them. In particular, based on this unique composition, CAP could offer a minimally-invasive surgical approach allowing for specific cancer cell or tumor tissue removal without influencing healthy cells. Thus, the objective of this research is to investigate a novel CAP-based therapy for selectively bone metastatic breast cancer treatment. For this purpose, human metastatic breast cancer (BrCa cells and bone marrow derived human mesenchymal stem cells (MSCs were separately treated with CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture. With different treatment times, different BrCa and MSC cell responses were observed. Our results showed that BrCa cells were more sensitive to these CAP treatments than MSCs under plasma dose conditions tested. It demonstrated that CAP can selectively ablate metastatic BrCa cells in vitro without damaging healthy MSCs at the metastatic bone site. In addition, our study showed that CAP treatment can significantly inhibit the migration and invasion of BrCa cells. The results suggest the great potential of CAP for breast cancer therapy.

  19. A Case of Orbital Metastasis as Disease Progression of Anaplastic Lymphoma Kinase-Positive Lung Cancer Treated with Crizotinib

    Directory of Open Access Journals (Sweden)

    Yoshihiko Sakata

    2015-01-01

    Full Text Available Orbital metastasis of lung cancer is rare. It often causes visual disorder. To date, there are only a few case reports. Crizotinib is an anaplastic lymphoma kinase (ALK tyrosine kinase inhibitor that leads to responses in most patients with ALK-positive non-small-cell lung cancer. Visual disorder is one of the popular adverse events of crizotinib, but the symptom almost decreases over time. We report a case of orbital metastasis as the disease progression of ALK-positive lung cancer treated with crizotinib. It should be kept in mind that orbital metastasis can be the disease progression of lung adenocarcinoma with ALK translocation treated with crizotinib. When physicians encounter a patient receiving crizotinib with visual disorder, we must distinguish between adverse events and orbital metastasis.

  20. Gene expression alterations associated with outcome in aromatase inhibitor-treated ER+ early-stage breast cancer patients

    DEFF Research Database (Denmark)

    Gravgaard Thomsen, Karina Hedelund; Lyng, Maria Bibi; Elias, Daniel;

    2015-01-01

    Aromatase inhibitors (AI), either alone or together with chemotherapy, have become the standard adjuvant treatment for postmenopausal, estrogen receptor-positive (ER+) breast cancer. Although AIs improve overall survival, resistance is still a major clinical problem, thus additional biomarkers...... predictive of outcome of ER+ breast cancer patients treated with AIs are needed. Global gene expression analysis was performed on ER+ primary breast cancers from patients treated with adjuvant AI monotherapy; half experienced recurrence (median follow-up 6.7 years). Gene expression alterations were validated...... by qRT-PCR, and functional studies evaluating the effect of siRNA-mediated gene knockdown on cell growth were performed. Twenty-six genes, including TFF3, DACH1, RGS5, and GHR, were shown to exhibit altered expression in tumors from patients with recurrence versus non-recurrent (fold change ≥1.5, p

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

    Science.gov (United States)

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

  2. Metformin Hydrochloride and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2016-05-18

    Brenner Tumor; Malignant Ascites; Malignant Pleural Effusion; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

  3. Influenza vaccination in children being treated with chemotherapy for cancer

    NARCIS (Netherlands)

    G.M. Goossen; L.C.M. Kremer; M.D. van de Wetering

    2009-01-01

    Background Influenza infection is a potential cause of severe morbidity in children with cancer, therefore vaccination against influenza is recommended. However, there are conflicting data concerning the immune response to influenza vaccination in children with cancer and the value of vaccination re

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

    Institute of Scientific and Technical Information of China (English)

    Niansong Qian; Nobuko Kawaguchi-Sakita; Masakazu Toi

    2010-01-01

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

  5. Cancer Stem Cells in Lung Tumorigenesis

    OpenAIRE

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

    2010-01-01

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

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

    Science.gov (United States)

    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. PMID:23603476

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

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2015-01-01

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

  8. Baseline and Trend of Lymphocyte-to-Monocyte Ratio as Prognostic Factors in Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer Patients Treated with First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

    Directory of Open Access Journals (Sweden)

    Yu-Mu Chen

    Full Text Available Patients with early-stage lung cancer who have a high baseline lymphocyte-to-monocyte ratio (LMR have a favorable prognosis. However, the prognostic significance of LMR in patients with advanced-stage EGFR-mutant non-small cell lung cancer (NSCLC receiving first-line epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKIs has not been established. We conducted a retrospective analysis to investigate the influence of LMR on clinical outcomes including progression-free survival (PFS and overall survival (OS in EGFR-mutant patients with NSCLC.Of 1310 lung cancer patients diagnosed between January 2011 and October 2013, 253 patients receiving first-line EGFR-TKIs for EGFR-mutant NSCLC were included. The cut-off values for baseline and the 1-month-to-baseline ratio of LMR (MBR, determined by using receiver operating characteristic curves, were 3.29 and 0.63, respectively. Patients were divided into 3 prognostic groups: high LMR and MBR, high LMR or MBR, and low LMR and MBR.The mean patient age was 65.2 years, and 41% were men. The median PFS and OS were 10.3 and 22.0 months, respectively. The PFS in patients with high LMR and MBR, high LMR or MBR, and low LMR and MBR were 15.4, 7.1, and 2.0 months, respectively (p < 0.001, whereas the OS were 32.6, 13.7, and 5.1 months, respectively (p < 0.001.A combination of baseline and trend of LMR can be used to identify patients with a high mortality risk in EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs.

  9. SOMATOSTATIN MAY ENHANCE CYTOTOXIC EFFECT OF DOXORUBICIN ON GALLBLADDER CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    李济宇; 全志伟; 张强; 刘建文

    2004-01-01

    Objective: To explore the change of chemosensitivity of gallbladder cancer cells pre-treated with somatostatin. Methods: Twenty-four hours after somatostatin treatment, gradient concentrated Doxorubicin was added and growth curve of gallbladder cancer cells was investigated to measure IC50, I.e., concentration of Doxorubicin at 50% cell viability. Results: Somatostatin ccould induce gallbladder cancer cell growth arrest in S phase. Inhibition of growth of cancer cell line was detected by Doxorubicin concentration- dependently (P<0.05). IC50 value was significantly lower by combined-treating with somatostatin and Doxorubicin compared with by Doxorubicin alone (P<0.05). Conclusion: Somatostatin could increase the cytotoxic effect of Doxorubicin on gallbladder cancer cell by modulating its cell cycle.

  10. Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yallapu Murali M

    2010-04-01

    Full Text Available Abstract Background Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells. Methods Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-co-glycolic acid (PLGA nanoparticle formulation of curcumin (Nano-CUR was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods. Results Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre

  11. Induction of apoptosis in lung cancer cells by isorhamnetin

    Institute of Scientific and Technical Information of China (English)

    LingZHU; Li-mingZHOU; Chun-leiYANG; Zun-zhenZHANG; JingXIAO; Zheng-rongWANG

    2005-01-01

    AIM The aim of the present study was to explore cytotoxic activity and the mechanism of tumor cell killing by isorhamnetin and to investigate the effect of isorhamnetin on tumor growth, cell prolification and apoptosis in transplantation tumor of lung cancer of Lewis cell line in C57BL/6 mice. METHODS Human A549 cells were treated with 10-320(g/ml isorhamnetin, C57BL/6 mice were subcutaneously inoculated Lewis cells 0.2ml/each (1×107cells/ml) below the right forelimb armpit and were treated with 50 (g/ml isorhamnetin isorhamnetin.The results were observed and analyzed under light-microscope, electronic microscopy, growth inhibition was analyzed by MTT, clonogenic asssays and growth curve;the apoptosis and the expression-associated genes peaks were detected with flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay,

  12. Modern oncologic and operative outcomes for oesophageal cancer treated with curative intent.

    LENUS (Irish Health Repository)

    Reynolds, J V

    2011-09-01

    The curative approach to oesophageal cancer carries significant risks and a cure is achieved in approximately 20 per cent. There has been a recent trend internationally to observe improved operative and oncological outcomes. This report audits modern outcomes from a high volume centre with a prospective database for the period 2004-08. 603 patients were referred and 310 (52%) were treated with curative intent. Adenocarcinoma represented 68% of the cohort, squamous cell cancer 30%. Of the 310 cases, 227 (73%) underwent surgery, 105 (46%) underwent surgery alone, and 122 (54%) had chemotherapy or combination chemotherapy and radiation therapy. The postoperative mortality rate was 1.7%. The median and 5-year survival of the 310 patients based on intention to treat was 36 months and 36%, respectively, and of the 181 patients undergoing R0 resection, 52 months and 42%, respectively. An in-hospital postoperative mortality rate of less than 2 per cent, and 5-year survival of between 35 and 42% is consistent with benchmarks from international series.

  13. DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis.

    Directory of Open Access Journals (Sweden)

    Patrizia Vici

    Full Text Available Cervical cancer cells commonly harbour a defective G1/S checkpoint owing to the interaction of viral oncoproteins with p53 and retinoblastoma protein. The activation of the G2/M checkpoint may thus become essential for protecting cancer cells from genotoxic insults, such as chemotherapy. In 52 cervical cancer patients treated with neoadjuvant chemotherapy, we investigated whether the levels of phosphorylated Wee1 (pWee1, a key G2/M checkpoint kinase, and γ-H2AX, a marker of DNA double-strand breaks, discriminated between patients with a pathological complete response (pCR and those with residual disease. We also tested the association between pWee1 and phosphorylated Chk1 (pChk1, a kinase acting upstream Wee1 in the G2/M checkpoint pathway. pWee1, γ-H2AX and pChk1 were retrospectively assessed in diagnostic biopsies by immunohistochemistry. The degrees of pWee1 and pChk1 expression were defined using three different classification methods, i.e., staining intensity, Allred score, and a multiplicative score. γ-H2AX was analyzed both as continuous and categorical variable. Irrespective of the classification used, elevated levels of pWee1 and γ-H2AX were significantly associated with a lower rate of pCR. In univariate and multivariate analyses, pWee1 and γ-H2AX were both associated with reduced pCR. Internal validation conducted through a re-sampling without replacement procedure confirmed the robustness of the multivariate model. Finally, we found a significant association between pWee1 and pChk1. The message conveyed by the present analysis is that biomarkers of DNA damage and repair may predict the efficacy of neoadjuvant chemotherapy in cervical cancer. Further studies are warranted to prospectively validate these encouraging findings.

  14. DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis.

    Science.gov (United States)

    Vici, Patrizia; Buglioni, Simonetta; Sergi, Domenico; Pizzuti, Laura; Di Lauro, Luigi; Antoniani, Barbara; Sperati, Francesca; Terrenato, Irene; Carosi, Mariantonia; Gamucci, Teresa; Dattilo, Rosanna; Bartucci, Monica; Vincenzoni, Cristina; Mariani, Luciano; Vizza, Enrico; Sanguineti, Giuseppe; Gadducci, Angiolo; Vitale, Ilio; Barba, Maddalena; De Maria, Ruggero; Mottolese, Marcella; Maugeri-Saccà, Marcello

    2016-01-01

    Cervical cancer cells commonly harbour a defective G1/S checkpoint owing to the interaction of viral oncoproteins with p53 and retinoblastoma protein. The activation of the G2/M checkpoint may thus become essential for protecting cancer cells from genotoxic insults, such as chemotherapy. In 52 cervical cancer patients treated with neoadjuvant chemotherapy, we investigated whether the levels of phosphorylated Wee1 (pWee1), a key G2/M checkpoint kinase, and γ-H2AX, a marker of DNA double-strand breaks, discriminated between patients with a pathological complete response (pCR) and those with residual disease. We also tested the association between pWee1 and phosphorylated Chk1 (pChk1), a kinase acting upstream Wee1 in the G2/M checkpoint pathway. pWee1, γ-H2AX and pChk1 were retrospectively assessed in diagnostic biopsies by immunohistochemistry. The degrees of pWee1 and pChk1 expression were defined using three different classification methods, i.e., staining intensity, Allred score, and a multiplicative score. γ-H2AX was analyzed both as continuous and categorical variable. Irrespective of the classification used, elevated levels of pWee1 and γ-H2AX were significantly associated with a lower rate of pCR. In univariate and multivariate analyses, pWee1 and γ-H2AX were both associated with reduced pCR. Internal validation conducted through a re-sampling without replacement procedure confirmed the robustness of the multivariate model. Finally, we found a significant association between pWee1 and pChk1. The message conveyed by the present analysis is that biomarkers of DNA damage and repair may predict the efficacy of neoadjuvant chemotherapy in cervical cancer. Further studies are warranted to prospectively validate these encouraging findings. PMID:26930412

  15. Thalidomide in Treating Patients With Recurrent or Persistent Endometrial Cancer

    Science.gov (United States)

    2013-01-23

    Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma

  16. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, M.J. van; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, P.J. van; Aarts, J.M.M.J.G.; Ommen, B. van

    2004-01-01

    Background. Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an a

  17. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Van Erk, Marjan J; Teuling, Eva; Staal, Yvonne CM; Huybers, Sylvie; Van Bladeren, Peter J; Aarts, Jac MMJG; Van Ommen, Ben

    2004-01-01

    BACKGROUND: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an a

  18. Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells

    NARCIS (Netherlands)

    Erk, van M.J.; Teuling, E.; Staal, Y.C.M.; Huybers, S.; Bladeren, van P.J.; Aarts, J.M.M.J.G.; Ommen, van B.

    2004-01-01

    Background: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an a

  19. Breathless cancer cells get fat on glutamine

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Anastasiou; Lewis C Cantley

    2012-01-01

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

  20. CYLD Promotes TNF-α-Induced Cell Necrosis Mediated by RIP-1 in Human Lung Cancer Cells

    Science.gov (United States)

    Lin, Xing; Chen, Qianshun; Huang, Chen

    2016-01-01

    Lung cancer is one of the most common cancers in the world. Cylindromatosis (CYLD) is a deubiquitination enzyme and contributes to the degradation of ubiquitin chains on RIP1. The aim of the present study is to investigate the levels of CYLD in lung cancer patients and explore the molecular mechanism of CYLD in the lung cancer pathogenesis. The levels of CYLD were detected in human lung cancer tissues and the paired paracarcinoma tissues by real-time PCR and western blotting analysis. The proliferation of human lung cancer cells was determined by MTT assay. Cell apoptosis and necrosis were determined by FACS assay. The results demonstrated that low levels of CYLD were detected in clinical lung carcinoma specimens. Three pairs of siRNA were used to knock down the endogenous CYLD in lung cancer cells. Knockdown of CYLD promoted cell proliferation of lung cancer cells. Otherwise overexpression of CYLD induced TNF-α-induced cell death in A549 cells and H460 cells. Moreover, CYLD-overexpressed lung cancer cells were treated with 10 μM of z-VAD-fmk for 12 hours and the result revealed that TNF-α-induced cell necrosis was significantly enhanced. Additionally, TNF-α-induced cell necrosis in CYLD-overexpressed H460 cells was mediated by receptor-interacting protein 1 (RIP-1) kinase. Our findings suggested that CYLD was a potential target for the therapy of human lung cancers.

  1. A survey on anticancer effects of artemisinin, iron, miconazole, and butyric acid on 5637 (bladder cancer and 4T1 (Breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Amir Ali Shahbazfar

    2014-01-01

    The groups treated with miconazole showed identical changes, with less severity compared to combination therapy groups. In butyric acid-treated groups, the only detectable changes were, mild cell swelling, few apoptosis, and rare necrosis. Conclusions: A combination therapy with artemisinin can be more effective against cancer cells than monotherapy with that. Butyric acid was not effective on cancer cells. Miconazole deviated the nature of cell death from apoptosis to necrosis and it must be used under caution.

  2. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

    Directory of Open Access Journals (Sweden)

    Abdulrahman Khazim Al-Asmari

    Full Text Available In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90% in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for

  3. Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

    Science.gov (United States)

    Al-Asmari, Abdulrahman Khazim; Albalawi, Sulaiman Mansour; Athar, Md Tanwir; Khan, Abdul Quaiyoom; Al-Shahrani, Hamoud; Islam, Mozaffarul

    2015-01-01

    In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast

  4. Deferasirox for Treating Patients Who Have Undergone Allogeneic Stem Cell Transplant and Have Iron Overload

    Science.gov (United States)

    2012-07-16

    Iron Overload; Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult

  5. Radiofrequency treatment alters cancer cell phenotype

    Science.gov (United States)

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

    2015-07-01

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

  6. Gadolinium uptake by brain cancer cells: Quantitative analysis with X-PEEM spectromicroscopy for cancer therapy

    Science.gov (United States)

    De Stasio, Gelsomina; Gilbert, B.; Perfetti, P.; Margaritondo, G.; Mercanti, D.; Ciotti, M. T.; Casalbore, P.; Larocca, L. M.; Rinelli, A.; Pallini, R.

    2000-05-01

    We present the first X-PEEM spectromicroscopy semi-quantitative data, acquired on Gd in glioblastoma cell cultures from human brain cancer. The cells were treated with a Gd compound for the optimization of GdNCT (Gadolinium Neutron Capture Therapy). We analyzed the kinetics of Gd uptake as a function of exposure time, and verified that a quantitative analytical technique gives the same results as our MEPHISTO X-PEEM, demonstrating the feasibility of semi-quantitative spectromicroscopy.

  7. Approach for mechanism of BH3 domain counterpart BH3I-2′ inducing colorectal cancer cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    FENG Wan-yu; LIU Yang; ZHANG Zhi-cheng

    2008-01-01

    Objective To discuss mechanism of BH3 domain counterpart BH3I-2' inducing colorectal cancer cell apoptosis. Methods Detected inhibition ratio and apoptosis of colorectal cancer cells HCT-116, which were treated by BH3I-2', with microplate reader and flow cytometry. Results Inhibition ratio of colorectal cancer cells, which were treated by BH3I-2', could reach about 50 %. Ratio of viable apoptotic cell decreased and that of non-viable apoptotie cell increased as time went. Conclusions BH3I-2' can induce colorectal cancer cell apoptosis.

  8. The regulatory effects of radiation and histone deacetylase inhibitor on liver cancer cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Ho; Choi, Hyung Seok; Jang, Dong Gun; Lee, Hong Je; Yang, Seoung Oh [Dept. Nuclear Medicine, Dongnam Institute of Radiological and Medicine Sciences Cancer Center, Busan (Korea, Republic of)

    2013-11-15

    Radiation has been an effective tool for treating cancer for a long time. Radiation therapy induces DNA damage within cancer cells and destroys their ability to reproduce. Radiation therapy is often combined with other treatments, like surgery and chemotherapy. Here, we describe the effects of radiation and histone deacetylase inhibitor, Trichostain A, on cell cycle regulation in hepatoma cells. Results demonstrate that the treatment of radiation TSA induces cell cycle arrest, thereby stimulating cell death in hepatoma cells. In addition, since different cells or tissues have different reactivity to radiation and TSA, these results might be an indicator for the combination therapy with radiation and drugs in diverse cancers.

  9. Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil

    DEFF Research Database (Denmark)

    Ording, Anne Gulbech; Cronin Fenton, Deirdre; Christensen, Mariann;

    2013-01-01

    Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil......Manganese Superoxide Dismtase Polymorphism and Breast Cancer Recurrence: A Danish Population-Based Case-Control Study of Breast Cancer Patients Treated with Cyclophosphamide Epirubicin and 5-fluorouracil...

  10. Prolongation of life by adoptive cell therapy with cascade primed immune cells in four patients with non-small cell lung cancer stages IIIB and IV and a pancoast tumor: a case series

    OpenAIRE

    Laumbacher, Barbara; GU, SONGHAI; Wank, Rudolf

    2013-01-01

    Introduction Despite newer treatment modalities, few patients with non-small cell lung cancer in stages IIIB and IV survive the median of one year. We present four patients with non-small cell lung cancer treated with an adjuvant therapy with cascade primed immune cells. The in vitro stimulated expression of cancer information on the patients’ monocytes matures and activates T lymphocytes to destroy cancer cells. The cascade primed immune cell therapy significantly improved the quality of lif...

  11. Troglitazone reverses the multiple drug resistance phenotype in cancer cells

    Directory of Open Access Journals (Sweden)

    Gerald F Davies

    2009-03-01

    Full Text Available Gerald F Davies1, Bernhard HJ Juurlink2, Troy AA Harkness11Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada; 2College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi ArabiaAbstract: A major problem in treating cancer is the development of drug resistance. We previously demonstrated doxorubicin (DOX resistance in K562 human leukemia cells that was associated with upregulation of glyoxalase 1 (GLO-1 and histone H3 expression. The thiazolidinedione troglitazone (TRG downregulated GLO-1 expression and further upregulated histone H3 expression and post-translational modifications in these cells, leading to a regained sensitivity to DOX. Given the pleiotropic effects of epigenetic changes in cancer development, we hypothesized that TRG may downregulate the multiple drug resistance (MDR phenotype in a variety of cancer cells. To test this, MCF7 human breast cancer cells and K562 cells were cultured in the presence of low-dose DOX to establish DOX-resistant cell lines (K562/DOX and MCF7/DOX. The MDR phenotype was confirmed by Western blot analysis of the 170 kDa P-glycoprotein (Pgp drug efflux pump multiple drug resistance protein 1 (MDR-1, and the breast cancer resistance protein (BCRP. TRG markedly decreased expression of both MDR-1 and BCRP in these cells, resulting in sensitivity to DOX. Silencing of MDR-1 expression also sensitized MCF7/DOX cells to DOX. Use of the specific and irreversible peroxisome proliferator-activated receptor gamma (PPARγ inhibitor GW9662 in the nanomolar range not only demonstrated that the action of TRG on MCF/DOX was PPARγ-independent, but indicated that PPARγ may play a role in the MDR phenotype, which is antagonized by TRG. We conclude that TRG is potentially a useful adjunct therapy in chemoresistant cancers. Keywords: chemotherapy, doxorubicin, breast cancer resistance protein-1, multiple drug resistance, multiple drug resistance protein 1

  12. Understanding and Managing Erectile Dysfunction in Patients Treated for Cancer.

    Science.gov (United States)

    Annam, Kiran; Voznesensky, Maria; Kreder, Karl J

    2016-04-01

    Cancer can cause sexual adverse effects by direct and indirect pathways. It can involve sexual organs, indirectly affect body image, or cause fatigue or depression with subsequent effects on libido. Erectile dysfunction (ED), the inability to obtain or maintain an erection firm enough for sexual intercourse, can also result from adverse effects of cancer treatment, such as fatigue, pain, or anxiety about therapy. In addition, depressed feelings about having cancer can affect sexuality, causing a range of signs and symptoms that can lead to ED. Chemotherapy, hormone therapy, surgery, and radiation can all cause sexual adverse effects. Additional factors that play a role include patient age and degree of ED before starting cancer treatment. In this article, we discuss how chemotherapy, hormone therapy, surgery, and radiation affect erectile function as well as possible treatment options for ED. PMID:27072383

  13. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Science.gov (United States)

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  14. Treatment of prostate cancer cell lines and primary cells using low temperature plasma

    Science.gov (United States)

    O'Connell, Deborah; Hirst, Adam; Frame, Fiona F.; Maitland, Norman J.

    2014-10-01

    The mechanisms of cell death after plasma treatment of both benign and cancerous prostate epithelial cells are investigated. Prostate cancer tissue was obtained with patient consent from targeted needle core biopsies following radical prostatectomy. Primary cells were cultured from cancer tissue and plated onto a chamber slide at a density of 10,000 cells per well in 200 microliter of stem cell media (SCM). The treated sample was previously identified as Gleason grade 7 cancer through tissue histo-pathology. A dielectric barrier discharge (DBD) jet configuration, with helium as a carrier gas, and 0.3% O2 admixture was used for treating the cells. Reactive oxygen and nitrogen species (RONS) produced by the plasma are believed to be the main mediators of the plasma-cell interaction and response. We found the concentration of reactive oxygen species (ROS) induced inside the cells increased with plasma exposure. Exposure to the plasma for >3 minutes showed high levels of DNA damage compared to untreated and hydrogen peroxide controls. Cell viability and cellular recovery are also investigated and will be presented. All findings were common to both cell lines, suggesting the potential of LTP therapy for both benign and malignant disease.

  15. Markers of small cell lung cancer

    OpenAIRE

    Sharma SK; Taneja Tarvinder

    2004-01-01

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

  16. Dr. Wu Liangcun's Experience in Treating Primary Liver Cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Having been engaged in clinical treatment of tumors and cancers for more than 40 years, Dr. Wu Liangcun (吴良村),professor of Zhejiang Provincial Hospital of Traditional Chinese Medicine, has put forward a unique method for treatment of liver cancer. His academic thought is to nourish yin, clear away heat, soothe the liver and strengthen the spleen, and clinically, he has obtained good therapeutic results as introduced in the following.

  17. Integrative Nanomedicine: Treating Cancer With Nanoscale Natural Products

    OpenAIRE

    Bell, Iris R; Sarter, Barbara; Koithan, Mary; Banerji, Prasanta; Banerji, Pratip; Jain, Shamini; Ives, John

    2014-01-01

    Finding safer and more effective treatments for specific cancers remains a significant challenge for integrative clinicians and researchers worldwide. One emerging strategy is the use of nanostructured forms of drugs, vaccines, traditional animal venoms, herbs, and nutraceutical agents in cancer treatment. The recent discovery of nanoparticles in traditional homeopathic medicines adds another point of convergence between modern nanomedicine and alternative interventional strategies. A way in ...

  18. Resveratrol induces apoptosis in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  19. Interfacial geometry dictates cancer cell tumorigenicity

    Science.gov (United States)

    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.

  20. Chronic fatigue in cancer patients treated with radiotherapy

    International Nuclear Information System (INIS)

    Fatigue is one of the most prevalent and profound symptoms related to both malignancy and anti-neoplastic treatment. It is being reported in 60% to 80% of cancer patients. We review the correlation between the cancer-related fatigue syndrome and radiotherapy. In patients undergoing radiotherapy, fatigue is often cumulative and may reach its peak during the last weeks of treatment. The presence of fatigue prior to therapy initiation is the most important predictive factor of the occurrence of radiotherapy-related cancer fatigue syndrome. Occasionally, fatigue persists for a prolonged period of months and even years beyond radiotherapy. Anemia may be one of major causative factors responsible for the development of the cancer-related fatigue syndrome. Fatigue has an enormous physical, mental, emotional, and economic impact on cancer patients, their families and care-providers. The treatment of radiation-related fatigue remains unknown. The initial approach should cover efforts aimed at the correction of potential etiologies, especially anemia. Education concerning fatigue greatly benefits some patients. It seems that exercise may be beneficial in relieving fatigue, bearing in mind that the exercise program for cancer patients should be initiated gradually and significantly individualized. (author)