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Sample records for brain cancer combination

  1. A Phase I trial of dose escalation of topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaohui Ge; Wenyan Zhao; Xiaocang Ren; Yongqiang Wang; Zhigang Li; Yanqi Li; Yuee Liu; Qiang Lin

    2012-01-01

    Objective: The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer. Methods: Patients with brain metastasis of lung cancer received conventional fractionation radiotherapy, with 5 daily fractions of 2 Gy per week, the total radiation dose was 40 Gy, while the larger lesions were boosted to 50-60 Gy. The initial dose of topotecan was 1.0 mg/m2. Escalation dose was 0.25 mg/m2. Every cohort contained at least 3 patients.If no dose-limiting toxicity (DLT) was observed,the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: Eighteen patients were recruited. Two cases of grade 3 leucopenia/neutropenia was observed as DLT at the level of topotecan 2.0 mg/m2. MTD of topotecan was defined as 1.75 mg/m2.The major side effects were leucopenia/neutropenia, nausea and vomiting. Conclusion: Topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer is well tolerated. Maximum-tolerated dose of topotecan is 1.75 mg/m2, once a week of a total of four.

  2. Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer

    OpenAIRE

    Xinhong Wu; Bo Luo; Shaozhong Wei; Yan Luo; Yaojun Feng; Juan Xu; Wei Wei

    2013-01-01

    Aim: To investigate the treatment efficiency of whole brain irradiation combined with precise radiotherapy on triple-negative (TN) phenotype breast cancer patients with brain metastases and their survival times. Materials and Methods : A total of 112 metastatic breast cancer patients treated with whole brain irradiation and intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT) were analyzed. Thirty-seven patients were of TN phenotype. Objective response rates were co...

  3. Combination chemotherapy in the treatment of breast cancer patients with metastatic brain involvement and a poor prognosis

    Directory of Open Access Journals (Sweden)

    D. R. Naskhletashvili

    2011-01-01

    Full Text Available Radiotherapy (RT is a standard treatment for breast cancer (BC patients with metastatic brain involvement. All patients (n = 15 had already received chemotherapy (CT for the underlying disease when they were found to have brain metastases. To develop effective CT regimens for patients with recurrent brain metastases, who have received RT to the brain, is a serious problem. Combination CT with gemcitabine and cisplatin showed a high efficacy (complete and partial regressions were achieved in 47.7% of cases and fair survival rates (median 10 months in a group of patients with BC brain metastases and a poor prognosis.

  4. Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

    2016-03-01

    Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

  5. Gene Therapy for Brain Cancer: Combination Therapies Provide Enhanced Efficacy and Safety

    OpenAIRE

    Candolfi, Marianela; Kroeger, Kurt M.; Muhammad, A K M G; Yagiz, Kader; Farrokhi, Catherine; Pechnick, Robert N; Pedro R Lowenstein; Castro, Maria G

    2009-01-01

    Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults. Despite significant advances in treatment and intensive research, the prognosis for patients with GBM remains poor. Therapeutic challenges for GBM include its invasive nature, the proximity of the tumor to vital brain structures often preventing total resection, and the resistance of recurrent GBM to conventional radiotherapy and chemotherapy. Gene therapy has been proposed as a useful adjuvant for GBM, to be use...

  6. Eribulin Mesylate Combined with Local Treatment for Brain Metastasis from Breast Cancer: Two Case Reports.

    Science.gov (United States)

    Byun, Kyung-Do; Ahn, Sung Gwe; Baik, Hyung Joo; Lee, Anbok; Bae, Ki Beom; An, Min Sung; Kim, Kwang Hee; Shin, Jae Ho; Park, Ha Kyoung; Cho, Heunglae; Jeong, Joon; Kim, Tae Hyun

    2016-06-01

    The prognosis associated with brain metastasis arising from breast cancer is very poor. Eribulin is a microtubule dynamic inhibitor synthesized from halichondrin B, a natural marine product. In a phase III study (EMBRACE), eribulin improved overall survival in patients with heavily pretreated metastatic breast cancers. However, these studies included few patients with brain metastases. Metastatic brain tumors (MBT) were detected during first-line palliative chemotherapy in a 43-year-old woman with breast cancer metastasis to the lung and mediastinal nodes; the genetic subtype was luminal B-like human epidermal growth factor receptor 2 (HER2)-negative. Whole brain radiotherapy (WBRT) followed by eribulin treatment continuously decreased the size, and induced regression, of the MBT with systemic disease stability for 12 months. Another 48-year-old woman with metastatic breast cancer (HER2+ subtype) presented with MBT. Following surgical resection of the tumor, eribulin with concurrent WBRT showed regression of the MBT without systemic progression for 18 months. PMID:27382400

  7. Brain cancer spreads

    DEFF Research Database (Denmark)

    Perryman, Lara; Erler, Janine Terra

    2014-01-01

    The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue).......The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue)....

  8. Successful outcome after combined chemotherapeutic and surgical management in a case of esophageal cancer with breast and brain relapse

    Institute of Scientific and Technical Information of China (English)

    Davide Adriano Santeufemia; Antonio Farris; Gianfranca Piredda; Giovanni Maria Fadda; Paolo Cossu Rocca; Salvatore Costantino; Giovanni Sanna; Maria Giuseppa Sarobba; Maria Antonietta Pinna; Carlo Putzu

    2006-01-01

    Esophageal cancer (EC) is a highly lethal disease. Approximately 50% of patients present with metastatic EC and most patients with localized EC will have local recurrence or develop metastases, despite potentially curative local therapy. The most common sites of distant recurrence are represented by lung, liver and bone while brain and breast metastases are rare. Usually patients with advanced disease are not treated aggressively and their median survival is six months. We report a woman patient who developed breast and brain metastases after curative surgery. We treated her with a highly aggressive chemotherapeutic and surgical combination resulting in a complete remission of the disease even after 11-year follow-up. We think that in super selected patients with more than one metastasis, when functional status is good and metastases are technically resectable, a surgical excision may be considered as a salvage option and chemotherapy should be delivered to allow a systemic control.

  9. A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases.

    Science.gov (United States)

    Chen, Xilin; Han, Jianfeng; Chu, Jianhong; Zhang, Lingling; Zhang, Jianying; Chen, Charlie; Chen, Luxi; Wang, Youwei; Wang, Hongwei; Yi, Long; Elder, J Bradley; Wang, Qi-En; He, Xiaoming; Kaur, Balveen; Chiocca, E Antonio; Yu, Jianhua

    2016-05-10

    Breast cancer brain metastases (BCBMs) are common in patients with metastatic breast cancer and indicate a poor prognosis. These tumors are especially resistant to currently available treatments due to multiple factors. However, the combination of chimeric antigen receptor (CAR)-modified immune cells and oncolytic herpes simplex virus (oHSV) has not yet been explored in this context. In this study, NK-92 cells and primary NK cells were engineered to express the second generation of EGFR-CAR. The efficacies of anti-BCBMs of EGFR-CAR NK cells, oHSV-1, and their combination were tested in vitro and in a breast cancer intracranial mouse model. In vitro, compared with mock-transduced NK-92 cells or primary NK cells, EGFR-CAR-engineered NK-92 cells and primary NK cells displayed enhanced cytotoxicity and IFN-γ production when co-cultured with breast cancer cell lines MDA-MB-231, MDA-MB-468, and MCF-7. oHSV-1 alone was also capable of lysing and destroying these cells. However, a higher cytolytic effect of EGFR-CAR NK-92 cells was observed when combined with oHSV-1 compared to the monotherapies. In the mice intracranially pre-inoculated with EGFR-expressing MDA-MB-231 cells, intratumoral administration of either EGFR-CAR-transduced NK-92 cells or oHSV-1 mitigated tumor growth. Notably, the combination of EGFR-CAR NK-92 cells with oHSV-1 resulted in more efficient killing of MDA-MB-231 tumor cells and significantly longer survival of tumor-bearing mice when compared to monotherapies. These results demonstrate that regional administration of EGFR-CAR NK-92 cells combined with oHSV-1 therapy is a potentially promising strategy to treat BCBMs.

  10. BRAIN CANCER IMMUNOTHERAPY (REVIEW)

    OpenAIRE

    Yashin К.S.; Medyanik I.А.

    2014-01-01

    The review analyzes Russian and foreign reports concerned with a rapidly developing brain cancer treatment technique — immunotherapy. There has been presented a current view on the basic concept of antitumor immunity, on the problem of immune system interaction with a tumor in general and under the conditions of an immunologically privileged nervous system, shown the theoretical background of efficiency of immunotherapy used against brain cancer (the capability of tumor antigens and activated...

  11. Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

    Directory of Open Access Journals (Sweden)

    Poujol Sylvain

    2010-06-01

    Full Text Available Abstract Background Since 1999, patients presenting with brain metastases (BM from breast cancer (BC are treated in our institution with a carmustine (BCNU - methotrexate (MTX combination. We report here our clinical experience regarding this combination. Patients and Methods Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity. Results 50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5. Median number of cycles was 3 (1-20. There were 11 objective responses (23% [95%CI 12-37] among 48 evaluable patients. Median progression-free survival and overall survival (OS were 4.2 (95%CI: 2.8-5.3 and 6.9 (4.2-10.7 months respectively, with a one-year OS rate of 32% (20-46. Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1 and 0.96 (0.57-1.66 respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis. Conclusions This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.

  12. Treatment of Brain Metastasis from Lung Cancer

    International Nuclear Information System (INIS)

    Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, functional performance status, age, and number of brain metastases. Patients with good prognosis may benefit from more aggressive treatment because of the potential for prolonged survival for some of them. In this review, we will comprehensively discuss the therapeutic options for treating brain metastases, which arise mostly from a lung cancer primary. In particular, we will focus on the patient selection for combined modality treatment of brain metastases, such as surgical resection or stereotactic radiosurgery (SRS) combined with whole brain irradiation; the use of radiosensitizers; and the neurocognitive deficits after whole brain irradiation with or without SRS. The benefit of prophylactic cranial irradiation (PCI) and its potentially associated neuro-toxicity for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are also discussed, along with the combined treatment of intrathoracic primary disease and solitary brain metastasis. The roles of SRS to the surgical bed, fractionated stereotactic radiotherapy, WBRT with an integrated boost to the gross brain metastases, as well as combining WBRT with epidermal growth factor receptor (EGFR) inhibitors, are explored as well

  13. Immunotherapy of Brain Cancer.

    Science.gov (United States)

    Roth, Patrick; Preusser, Matthias; Weller, Michael

    2016-01-01

    The brain has long been considered an immune-privileged site precluding potent immune responses. Nevertheless, because of the failure of conventional anti-cancer treatments to achieve sustained control of intracranial neoplasms, immunotherapy has been considered as a promising strategy for decades. However, several efforts aimed at exploiting the immune system as a therapeutic weapon were largely unsuccessful. The situation only changed with the introduction of the checkpoint inhibitors, which target immune cell receptors that interfere with the activation of immune effector cells. Following the observation of striking effects of drugs that target CTLA-4 or PD-1 against melanoma and other tumor entities, it was recognized that these drugs may also be active against metastatic tumor lesions in the brain. Their therapeutic activity against primary brain tumors is currently being investigated within clinical trials. In parallel, other immunotherapeutics such as peptide vaccines are at an advanced stage of clinical development. Further immunotherapeutic strategies currently under investigation comprise adoptive immune cell transfer as well as inhibitors of metabolic pathways involved in the local immunosuppression frequently found in brain tumors. Thus, the ongoing implementation of immunotherapeutic concepts into clinical routine may represent a powerful addition to the therapeutic arsenal against various brain tumors. PMID:27260656

  14. Increased survival with the combination of stereotactic radiosurgery and gefitinib for non-small cell lung cancer brain metastasis patients: a nationwide study in Taiwan

    International Nuclear Information System (INIS)

    Whole brain irradiation (WBRT) either with or without resection has historically been the treatment for brain metastases from non-small cell lung cancer (NSCLC). The effect of gamma knife (GK) radiosurgery, chemotherapy, or the combination remains incompletely defined. In this study, we assessed the outcome of brain metastases from non-small cell lung cancer treated by WBRT followed by GK, gefitinib, or the combination of GK and gefitinib. We retrieved the records of NSCLC patients with brain metastases from the National Health Insurance Research Database (NHIRD) of Taiwan from 2004 to 2010. WBRT either with or without resection was the first line treatment for nearly all patients. The decision to add GK and/or gefitinib treatment was at the discretion of the treating physician and based upon a patient’s medical records and imaging data. These patients were classified into four groups including WBRT, WBRT + gefitinib, WBRT + GK, WBRT + gefitinib + GK. These data was evaluated for difference in survival and factors that portended an extended survival from the time of brain metastasis diagnosis. Of the 60194 patients with newly diagnosed NSCLC, 23874 (39.6 %) developed brain metastases. The distribution of patients for the groups was WBRT for 20241, WBRT + gefitinib for 3379, WBRT + GK for 155, and WBRT+ gefitinib + GK for 99 patients. The median survival for the time of brain metastasis diagnosis for WBRT, WBRT+ gefitinib, WBRT+ GK, WBRT+ gefitinib + GK groups was 0.53, 1.01, 1.46, and 2.25 years, respectively (p < 0.0001). The hazard ratio (95 % CI) for survival was 1, 0.56, 0.43, and 0.40, respectively (p < 0.001). The adjusted hazard ratio (95 % CI) by age, sex and Charlson comorbidity index (CCI) was 1, 0.73, 0.49, and 0.42, respectively (p < 0.001). Patients with brain metastases from NSCLC receiving GK or gefitinib demonstrated extended survival. The improved survival seen with GK and gefitinib suggests a survival benefit in selected patients receiving the

  15. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  16. Brain metastases of breast cancer.

    Science.gov (United States)

    Palmieri, Diane; Smith, Quentin R; Lockman, Paul R; Bronder, Julie; Gril, Brunilde; Chambers, Ann F; Weil, Robert J; Steeg, Patricia S

    Central nervous system or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. The development of brain metastases has been associated with young age, and tumors that are estrogen receptor negative, Her-2+ or of the basal phenotype. Treatment typically includes whole brain irradiation, or either stereotactic radiosurgery or surgery with whole brain radiation, resulting in an approximately 20% one year survival. The blood-brain barrier is a formidable obstacle to the delivery of chemotherapeutics to the brain. Mouse experimental metastasis model systems have been developed for brain metastasis using selected sublines of human MDA-MB-231 breast carcinoma cells. Using micron sized iron particles and MRI imaging, the fate of MDA-MB-231BR cells has been mapped: Approximately 2% of injected cells form larger macroscopic metastases, while 5% of cells remain as dormant cells in the brain. New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells. PMID:17473372

  17. Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with Lapatinib and Capecitabine after Whole Brain Irradiation

    Directory of Open Access Journals (Sweden)

    Esin Oktay

    2013-01-01

    Full Text Available Trastuzumab treatment does not prevent intracranial seeding and is largely ineffective for established central nervous system metastasis in HER2 overexpressing breast cancer patients. Combination therapy of lapatinib and capecitabine may be an effective treatment option for brain metastasis of HER2-positive breast cancer. We report a patient with breast cancer overexpressing HER-2 where brain metastases were successfully treated with radiation and a combination of lapatinib and capecitabine.

  18. Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged Non-Small Cell Lung Cancer with brain metastases

    Science.gov (United States)

    Subbiah, Vivek; Berry, Jenny; Roxas, Michael; Guha-Thakurta, Nandita; Subbiah, Ishwaria Mohan; Ali, Siraj M.; McMahon, Caitlin; Miller, Vincent; Cascone, Tina; Pai, Shobha; Tang, Zhenya; Heymach, John V.

    2016-01-01

    In-frame fusion KIF5B (the-kinesin-family-5B-gene)-RET transcripts have been characterized in 1–2% of non-small cell lung cancers and are known oncogenic drivers. The RET tyrosine kinase inhibitor, vandetanib, suppresses fusion-induced, anchorage-independent growth activity. In vitro studies have shown that vandetanib is a high-affinity substrate of breast cancer resistance protein (Bcrp1/Abcg2) but is not transported by P-glycoprotein (P-gp), limiting its blood-brain barrier penetration. A co-administration strategy to enhance the brain accumulation of vandetanib by modulating P-gp/Abcb1- and Bcrp1/Abcg2-mediated efflux with mTOR inhibitors, specifically everolimus, was shown to increase the blood-brain barrier penetration. We report the first bench to bed-side evidence that RET inhibitor combined with an mTOR inhibitor is active against brain-metastatic RET-rearranged lung cancer and the first evidence of blood-brain barrier penetration. A 74 year old female with progressive adenocarcinoma of the lung (wild-type EGFR and no ALK rearrangement) presented for therapy options. A deletion of 5’RET was revealed by FISH assay, indicating RET-gene rearrangement. Because of progressive disease in the brain, she was enrolled in a clinical trial with vandetanib and everolimus (NCT01582191). Comprehensive genomic profiling revealed fusion of KIF5B (the-kinesin-family-5B-gene) and RET, in addition to AKT2 gene amplification. After 2 cycles of therapy a repeat MRI brain showed a decrease in the intracranial disease burden and PET /CT showed systemic response as well. Interestingly, AKT2 amplification seen is a critical component of the PI3K/mTOR pathway, alterations of which has been associated with both de novo and acquired resistance to targeted therapy. The addition of everolimus may have both overcome the AKT2 amplification to produce a response in addition to its direct effects on the RET gene. Our case report forms the first evidence of blood-brain

  19. Neuroanatomical automatic segmentation in brain cancer patients

    OpenAIRE

    D’Haese, P.; Niermann, K; Cmelak, A.; Donnelly, E.; Duay, V.; Li, R; Dawant, B.

    2003-01-01

    Conformally prescribed radiation therapy for brain cancer requires precisely defining the target treatment area, as well as delineating vital brain structures which must be spared from radiotoxicity. The current clinical practice of manually segmenting brain structures can be complex and exceedingly time consuming. Automatic computeraided segmentation methods have been proposed to increase efficiency and reproducibility in developing radiation treatment plans. Previous studies have establishe...

  20. A brain cancer pathway in clinical practice

    DEFF Research Database (Denmark)

    Laursen, Emilie Lund; Rasmussen, Birthe Krogh

    2012-01-01

    Danish healthcare seeks to improve cancer survival through improved diagnostics, rapid treatment and increased focus on cancer prevention and early help-seeking. In neuro-oncology, this has resulted in the Integrated Brain Cancer Pathway (IBCP). The paper explores how the pathway works...

  1. A brain cancer pathway in clinical practice

    DEFF Research Database (Denmark)

    Laursen, Emilie Lund; Rasmussen, Birthe Krogh

    2012-01-01

    Danish healthcare seeks to improve cancer survival through improved diagnostics, rapid treatment and increased focus on cancer prevention and early help-seeking. In neuro-oncology, this has resulted in the Integrated Brain Cancer Pathway (IBCP). The paper explores how the pathway works in the...

  2. Curcumin in combined cancer therapy.

    Science.gov (United States)

    Troselj, Koraljka Gall; Kujundzic, Renata Novak

    2014-01-01

    The mechanisms of beneficial preventive and therapeutic effects achieved by traditional and complementary medicine are currently being deciphered in molecular medicine. Curcumin, a yellow-colored polyphenol derived from the rhizome of turmeric (Curcuma longa), influences a wide variety of cellular processes through the reshaping of many molecular targets. One of them, nuclear factor kappa B (NF-κB), represents a strong mediator of inflammation and, in a majority of systems, supports the pro-proliferative features of cancer cells. The application of various anticancer drugs, cytostatics, triggers signals which lead to an increase in cellular NF-κB activity. As a consequence, cancer cells often reshape their survival signaling pathways and, over time, become resistant to applied therapy. Curcumin was shown to be a strong inhibitor of NF-κB activity and its inhibitory effect on NF-κB related pathways often leads to cellular apoptotic response. All these facts, tested and confirmed in many different biological systems, have paved the way for research aimed to elucidate the potential beneficial effects of combining curcumin and various anti-cancer drugs in order to establish more efficient and less toxic cancer treatment modalities. This review addresses certain aspects of NF-κB-related inflammatory response, its role in carcinogenesis and therapy benefits that may be gained through silencing NF-κB by selectively combining curcumin and various anticancer drugs.

  3. 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 ...

  4. Differential Reactions of Microglia to Brain Metastasis of Lung Cancer

    OpenAIRE

    He, Bei Ping; Wang, Jian Jun; Zhang, Xian; Wu, Yan; Wang, Miao; Bay, Boon-Huat; Chang, Alex Yuang-Chi

    2006-01-01

    The brain is a common metastatic site for various types of cancers, especially lung cancer. Patients with brain metastases have a poor prognosis in spite of radiotherapy and/or chemotherapy. It is postulated that immune cells in the brain may play a major role in cancer metastasis, dormancy, and relapse. Although microglia may serve as a major component in the brain immune system, the interaction between metastatic cancer cells and microglia is still largely unknown and remains to be elucidat...

  5. Small Vessel Ischemic Disease of the Brain and Brain Metastases in Lung Cancer Patients

    OpenAIRE

    Mazzone, Peter J.; Marchi, Nicola; Fazio, Vince; Taylor, J. Michael; Masaryk, Thomas; Bury, Luke; Mekhail, Tarek; Janigro, Damir

    2009-01-01

    Background Brain metastases occur commonly in patients with lung cancer. Small vessel ischemic disease is frequently found when imaging the brain to detect metastases. We aimed to determine if the presence of small vessel ischemic disease (SVID) of the brain is protective against the development of brain metastases in lung cancer patients. Methodology/Principal Findings A retrospective cohort of 523 patients with biopsy confirmed lung cancer who had received magnetic resonance imaging of the ...

  6. Computational systems biology in cancer brain metastasis.

    Science.gov (United States)

    Peng, Huiming; Tan, Hua; Zhao, Weiling; Jin, Guangxu; Sharma, Sambad; Xing, Fei; Watabe, Kounosuke; Zhou, Xiaobo

    2016-01-01

    Brain metastases occur in 20-40% of patients with advanced malignancies. A better understanding of the mechanism of this disease will help us to identify novel therapeutic strategies. In this review, we will discuss the systems biology approaches used in this area, including bioinformatics and mathematical modeling. Bioinformatics has been used for identifying the molecular mechanisms driving brain metastasis and mathematical modeling methods for analyzing dynamics of a system and predicting optimal therapeutic strategies. We will illustrate the strategies, procedures, and computational techniques used for studying systems biology in cancer brain metastases. We will give examples on how to use a systems biology approach to analyze a complex disease. Some of the approaches used to identify relevant networks, pathways, and possibly biomarkers in metastasis will be reviewed into details. Finally, certain challenges and possible future directions in this area will also be discussed.

  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. Parental Exposure to Pesticides and Childhood Brain Cancer: U.S. Atlantic Coast Childhood Brain Cancer Study

    OpenAIRE

    Shim, Youn K.; Mlynarek, Steven P.; van Wijngaarden, Edwin

    2009-01-01

    Background The etiology of childhood brain cancer remains largely unknown. However, previous studies have yielded suggestive associations with parental pesticide use. Objectives We aimed to evaluate parental exposure to pesticides at home and on the job in relation to the occurrence of brain cancer in children. Methods We included 526 one-to-one–matched case–control pairs. Brain cancer cases were diagnosed at < 10 years of age, and were identified from statewide cancer registries of four U.S....

  9. Lung cancer brain metastases – the role of neurosurgery

    Directory of Open Access Journals (Sweden)

    V. A. Aleshin

    2016-01-01

    Full Text Available Lung cancer is mostly common occurring oncological disease in the developed countries. Currently lung cancers are subdivided into nonsmall-cell (adenocarcinoma, large-cell, squamous cell and small-cell. The difference in the clinical and morphological picture leads to the necessity of choosing therapeutic approaches to patients of various groups.Lung cancer should be referred to encephalotropic diseases since metastatic lesion of the central nervous system is sufficiently common complication. Successes of complex treatment of primary tumor result in increase of total longlivety currently ther is ageing of patients suffering lung cancer. These factors increase the risk of metastatic lesions of the brain.Interest to the problem of neurosurgical treatment of patients suffering lung cancer is determined by frequency of lesion, varicosity of morphological variants of the disease, requiring various algorithms of treatment and diagnosis.The main role of neurosurgical intervention in cerebral metastases of lung cancer consist in creation of the paled of carrying out combined therapy. Ideally, a neurosurgical operation should be carried out with clearcut observance of oncological principles of ablasty.Adequate comprehensive approach to treatment or patients with cerebral metastases of various forms of lung cancer with the developed of optimal tactics of and stages of treatment would make it possible to increase duration and quality of life of patients.

  10. Cancer of the Brain and Other Nervous System

    Science.gov (United States)

    ... Show More Cancer and the Brain Figure: Brain Anatomy Click to enlarge. There are many types of brain and spinal cord tumors. Together, the brain and spinal cord make up the central nervous system (CNS). The tumors may be either benign (not ...

  11. Researchers Find 8 Immune Genes in Aggressive Brain Cancer

    Science.gov (United States)

    ... 159031.html Researchers Find 8 Immune Genes in Aggressive Brain Cancer Discovery might eventually lead to better ... tissue samples from 170 people with a less aggressive type of brain tumor. This led to the ...

  12. Extensive Surgery Best for an Aggressive Brain Cancer

    Science.gov (United States)

    ... fullstory_159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more ... News) -- When it comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may ...

  13. Novel Brain Cancer Treatment Taps into Sound Waves

    Science.gov (United States)

    ... html Novel Brain Cancer Treatment Taps Into Sound Waves Experimental device seems to help more chemotherapy reach ... When the so-called SonoCloud was activated, sound waves opened the blood-brain barrier, letting in more ...

  14. Management of solitary and multiple brain metastases from breast cancer

    Directory of Open Access Journals (Sweden)

    Addison Willett

    2015-01-01

    Full Text Available As local and systemic control of breast cancer improves, metastasis to the brain remains a common event requiring a specialized management approach. Women diagnosed with breast cancer who develop brain metastases have superior overall survival compared to patients with other forms of metastatic carcinoma. This article summarizes some of the unique aspects of care for patients with breast cancer metastases to the brain.

  15. CHEMO- AND TARGET THERAPY OF PATIENTS WITH BREAST CANCER WITH METASTATIC BRAIN LESIONS

    OpenAIRE

    D. R. Naskhletashvili; V. A. Gorbunova; E. A. Moskvina

    2014-01-01

    Results of studies performed have shown high efficiency of drug therapy for treatment of patients with breast cancer (BC) with brain metastases. The best results regarding survival rate have been achieved for treatment of BC patients with brain metastases and HER2 hyperexpression. At present, studies are performed regarding examination of new anticancer drugs and their use in combination with radiotherapy for treatment of BC patients with brain metastases. It is necessary to perform studies o...

  16. Mathematical optimization of the combination of radiation and differentiation therapies of cancer

    Directory of Open Access Journals (Sweden)

    Jeff W.N. Bachman

    2013-03-01

    Full Text Available Cancer stem cells (CSC are considered to be a major driver of cancer progression and successful therapies must control CSCs. However, CSC are often less sensitive to treatment and they might survive radiation and/or chemotherapies. In this paper we combine radiation treatment with differentiation therapy. During differentiation therapy, a differentiation promoting agent is supplied (e.g. TGF-beta such that CSCs differentiate and become more radiosensitive. Then radiation can be used to control them. We consider three types of cancer: head and neck cancer, brain cancers (primary tumors and metastatic brain cancers, and breast cancer; and we use mathematical modelling to show that combination therapy of the above type can have a large beneficial effect for the patient; increasing treatment success and reducing side effects.

  17. Combined radiotherapy and chemotherapy for high-grade brain tumours

    Science.gov (United States)

    Barazzuol, Lara

    Glioblastoma (GBM) is the most common primary brain tumour in adults and among the most aggressive of all tumours. For several decades, the standard care of GBM was surgical resection followed by radiotherapy alone. In 2005, a landmark phase III clinical trial coordinated by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) demonstrated the benefit of radiotherapy with concomitant and adjuvant temozolomide (TMZ) chemotherapy. With TMZ, the median life expectancy in optimally managed patients is still only 12-14 months, with only 25% surviving 24 months. There is an urgent need for new therapies in particular in those patients whose tumour has an unmethylated methylguanine methyltransferase gene (MGMT) promoter, which is a predictive factor of benefit from TMZ. In this dissertation, the nature of the interaction between TMZ and radiation is investigated using both a mathematical model, based on in vivo population statistics of survival, and in vitro experimentation on a panel of human GBM cell lines. The results show that TMZ has an additive effect in vitro and that the population-based model may be insufficient in predicting TMZ response. The combination of TMZ with particle therapy is also investigated. Very little preclinical data exists on the effects of charged particles on GBM cell lines as well as on the concomitant application of chemotherapy. In this study, human GBM cells are exposed to 3 MeV protons and 6 MeV alpha particles in concomitance with TMZ. The results suggest that the radiation quality does not affect the nature of the interaction between TMZ and radiation, showing reproducible additive cytotoxicity. Since TMZ and radiation cause DNA damage in cancer cells, there has been increased attention to the use of poly(ADP-ribose) polymerase (PARP) inhibitors. PARP is a family of enzymes that play a key role in the repair of DNA breaks. In this study, a novel PARP inhibitor, ABT-888

  18. Brain Cancer in Workers Employed at a Laboratory Research Facility.

    Directory of Open Access Journals (Sweden)

    James J Collins

    Full Text Available An earlier study of research facility workers found more brain cancer deaths than expected, but no workplace exposures were implicated.Adding four additional years of vital-status follow-up, we reassessed the risk of death from brain cancer in the same workforce, including 5,284 workers employed between 1963, when the facility opened, and 2007. We compared the work histories of the brain cancer decedents in relationship to when they died and their ages at death.As in most other studies of laboratory and research workers, we found low rates of total mortality, total cancers, accidents, suicides, and chronic conditions such as heart disease and diabetes. We found no new brain cancer deaths in the four years of additional follow-up. Our best estimate of the brain cancer standardized mortality ratio (SMR was 1.32 (95% confidence interval [95% CI] 0.66-2.37, but the SMR might have been as high as 1.69. Deaths from benign brain tumors and other non-malignant diseases of the nervous system were at or below expected levels.With the addition of four more years of follow-up and in the absence of any new brain cancers, the updated estimate of the risk of brain cancer death is smaller than in the original study. There was no consistent pattern among the work histories of decedents that indicated a common causative exposure.

  19. Work-up times in an integrated brain cancer pathway

    DEFF Research Database (Denmark)

    Lund Laursen, Emilie; Rasmussen, Birthe Krogh

    2012-01-01

    The integrated brain cancer pathway (IBCP) aims to ensure fast-track diagnostics and treatment for brain cancers in Denmark. This paper focuses on the referral pattern and the time frame of key pathway elements during the first two years following implementation of the IBCP in a regional neurolog...

  20. Small vessel ischemic disease of the brain and brain metastases in lung cancer patients.

    Directory of Open Access Journals (Sweden)

    Peter J Mazzone

    Full Text Available BACKGROUND: Brain metastases occur commonly in patients with lung cancer. Small vessel ischemic disease is frequently found when imaging the brain to detect metastases. We aimed to determine if the presence of small vessel ischemic disease (SVID of the brain is protective against the development of brain metastases in lung cancer patients. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort of 523 patients with biopsy confirmed lung cancer who had received magnetic resonance imaging of the brain as part of their standard initial staging evaluation was reviewed. Information collected included demographics, comorbidities, details of the lung cancer, and the presence of SVID of the brain. A portion of the cohort had the degree of SVID graded. The primary outcome measure was the portion of study subjects with and without SVID of the brain who had evidence of brain metastases at the time of initial staging of their lung cancer.109 patients (20.8% had evidence of brain metastases at presentation and 345 (66.0% had evidence of SVID. 13.9% of those with SVID and 34.3% of those without SVID presented with brain metastases (p<0.0001. In a model including age, diabetes mellitus, hypertension, hyperlipidemia, and tobacco use, SVID of the brain was found to be the only protective factor against the development of brain metastases, with an OR of 0.31 (0.20, 0.48; p<0.001. The grade of SVID was higher in those without brain metastases. CONCLUSIONS/SIGNIFICANCE: These findings suggest that vascular changes in the brain are protective against the development of brain metastases in lung cancer patients.

  1. [Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer 
with Brain Metastasis].

    Science.gov (United States)

    Song, Qi; Jiao, Shunchang; Li, Fang

    2016-08-20

    Brain metastasis, a common complication of non-small cell lung cancer (NSCLC) with an incidence rate of 30%-50%, significantly affects the patients' quality of life. The prognosis of patients of NSCLC with brain metastasis is extremely poor, the average median survival is only 1 m-2 m without treatment. The targeted therapy based on lung cancer driven gene is a new treatment. Besides, the immunotherapy which can enhance the effect of anti-cancer by simulating the immune system is a new approach. The combination of targeted therapy and immunotherapy can greatly benefit patients in clinical work. PMID:27561803

  2. CHEMO- AND TARGET THERAPY OF PATIENTS WITH BREAST CANCER WITH METASTATIC BRAIN LESIONS

    Directory of Open Access Journals (Sweden)

    D. R. Naskhletashvili

    2014-01-01

    Full Text Available Results of studies performed have shown high efficiency of drug therapy for treatment of patients with breast cancer (BC with brain metastases. The best results regarding survival rate have been achieved for treatment of BC patients with brain metastases and HER2 hyperexpression. At present, studies are performed regarding examination of new anticancer drugs and their use in combination with radiotherapy for treatment of BC patients with brain metastases. It is necessary to perform studies of efficiency of various schemes of drug therapy depending on biological properties of the primary tumor. The issue of sequence of application of drug therapy and radiotherapy for metastatic brain lesions also remains actual.

  3. Non-coding RNAs in cancer brain metastasis.

    Science.gov (United States)

    Wu, Kerui; Sharma, Sambad; Venkat, Suresh; Liu, Keqin; Zhou, Xiaobo; Watabe, Kounosuke

    2016-01-01

    More than 90% of cancer death is attributed to metastatic disease, and the brain is one of the major metastatic sites of melanoma, colon, renal, lung and breast cancers. Despite the recent advancement of targeted therapy for cancer, the incidence of brain metastasis is increasing. One reason is that most therapeutic drugs can't penetrate blood-brain-barrier and tumor cells find the brain as sanctuary site. In this review, we describe the pathophysiology of brain metastases to introduce the latest understandings of metastatic brain malignancies. This review also particularly focuses on non-coding RNAs and their roles in cancer brain metastasis. Furthermore, we discuss the roles of the extracellular vesicles as they are known to transport information between cells to initiate cancer cell-microenvironment communication. The potential clinical translation of non-coding RNAs as a tool for diagnosis and for treatment is also discussed in this review. At the end, the computational aspects of non-coding RNA detection, the sequence and structure calculation and epigenetic regulation of non-coding RNA in brain metastasis are discussed. PMID:26709907

  4. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S;

    2011-01-01

    Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...

  5. Small RNA combination therapy for lung cancer

    Science.gov (United States)

    Xue, Wen; Dahlman, James E.; Tammela, Tuomas; Khan, Omar F.; Sood, Sabina; Dave, Apeksha; Cai, Wenxin; Chirino, Leilani M.; Yang, Gillian R.; Bronson, Roderick; Crowley, Denise G.; Sahay, Gaurav; Schroeder, Avi; Langer, Robert; Anderson, Daniel G.; Jacks, Tyler

    2014-01-01

    MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but their effective delivery to most solid tumors has been difficult. Here, we show that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically engineered mouse model of lung cancer based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a levels in lung tumors, specifically down-regulated miR-34a target genes, and slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene expression and MAPK signaling, increased apoptosis, and inhibited tumor growth. The combination of miR-34a and siRNA targeting Kras improved therapeutic responses over those observed with either small RNA alone, leading to tumor regression. Furthermore, nanoparticle-mediated small RNA delivery plus conventional, cisplatin-based chemotherapy prolonged survival in this model compared with chemotherapy alone. These findings demonstrate that RNA combination therapy is possible in an autochthonous model of lung cancer and provide preclinical support for the use of small RNA therapies in patients who have cancer. PMID:25114235

  6. Brain Cancer Treatment Shows Promise in Early Trial

    Science.gov (United States)

    ... 2016 WEDNESDAY, June 1, 2016 (HealthDay News) -- An experimental viral treatment may extend the lives of patients with a hard-to-treat brain cancer, researchers say. For the phase 1 study, patients ...

  7. Metabolic Imaging of Breast Cancer and the Normal Brain

    DEFF Research Database (Denmark)

    Asghar Butt, Sadia

    biological systems - breast cancer and normal brain. Breast cancer metabolism was longitudinally monitored in a mouse model using MRS of hyperpolirized pyruvate. The results demonstrated that we could monitor the changes in metabolism with increasing disease severity. The normal cerebral metabolism of α......-ketoisocaproate (KIC) was studied in the rat brain. The findings showed that hyperpolarized KIC is a promising substrate for in vivo evaluation of specific enzymatic activity....

  8. A Case of Brain Metastases from Breast Cancer Treated with Whole-Brain Radiotherapy and Eribulin Mesylate

    Directory of Open Access Journals (Sweden)

    Carsten Nieder

    2012-01-01

    Full Text Available Patients with triple receptor-negative breast cancer often develop aggressive metastatic disease, which also might involve the brain. In many cases, systemic and local treatment is needed. It is important to consider the toxicity of chemo- and radiotherapy, especially when newly approved drugs become available. Randomised studies leading to drug approval often exclude patients with newly diagnosed brain metastases. Here we report our initial experience with eribulin mesylate and whole-brain radiotherapy (WBRT in a heavily pretreated patient with multiple brain, lung, and bone metastases from triple receptor-negative breast cancer. Eribulin mesylate was given after 4 previous lines for metastatic disease. Two weeks after the initial dose, that is, during the first cycle, the patient was diagnosed with 5 brain metastases with a maximum size of approximately 4.5 cm. She continued chemotherapy and received concomitant WBRT with 10 fractions of 3 Gy. After 3 cycles of eribulin mesylate, treatment was discontinued because of newly diagnosed liver metastases and progression in the lungs. No unexpected acute toxicity was observed. The only relevant adverse reactions were haematological events after the third cycle (haemoglobin 9.5 g/dL, leukocytes 3.1×109/L. The patient died from respiratory failure 18.5 months from diagnosis of metastatic disease, and 2.7 months from diagnosis of brain metastases. To the best of our knowledge, this is the first report on combined WBRT and eribulin mesylate.

  9. Radiotherapy combined with Tegafur (FT-207s) for brain tumors

    International Nuclear Information System (INIS)

    5-Fluorouracil (5-FU) has anti-tumor effects as an anti-metabolite, but it cannot pass the Blood-Brain-Barrier (BBB). FT-207 a masked-compound of 5-FU, is easily lipid soluble and is able to pass the BBB. Twenty eight patients of primary brain tumor and 8 patients of metastatic brain tumor were treated with irradiation combined with 750 mg of FT-207 suppository. Twenty four patients of primary brain tumor were treated only with irradiation as control. The mean survival time was 20.4 +- 11.8 months for the combined therapy group and 17.6 +- 8.6 months for the control. The concentration of FT-207 and 5-FU in serum and in cerebrospinal fluid (CSF) was investigated after administration of 750 mg of FT-207 suppository per annum. The maximum concentration of FT-207 and of 5-FU in serum was 20.4 +- 11.8 mcg/ml and 0.06 +- 0.02 mcg/ml, respectively. There were observed several side effects, such as anorexia, nausea, exanthema and etc. These side effects were not so great as to interrupt the therapy at the dose level of 750 mg of FT-207. However, at the dose of 1500 mg, one case showed disturbance of consciousness, to which attention should be called. (author)

  10. 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

  11. Brain metastases free survival differs between breast cancer subtypes

    Science.gov (United States)

    Berghoff, A; Bago-Horvath, Z; De Vries, C; Dubsky, P; Pluschnig, U; Rudas, M; Rottenfusser, A; Knauer, M; Eiter, H; Fitzal, F; Dieckmann, K; Mader, R M; Gnant, M; Zielinski, C C; Steger, G G; Preusser, M; Bartsch, R

    2012-01-01

    Background: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. Methods: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan–Meier method and compared with the log-rank test. Results: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34–16.66) compared with 18 months (95% CI: 14.46–21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71–44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). Conclusion: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes. PMID:22233926

  12. Combining multi-atlas segmentation with brain surface estimation

    Science.gov (United States)

    Huo, Yuankai; Carass, Aaron; Resnick, Susan M.; Pham, Dzung L.; Prince, Jerry L.; Landman, Bennett A.

    2016-03-01

    Whole brain segmentation (with comprehensive cortical and subcortical labels) and cortical surface reconstruction are two essential techniques for investigating the human brain. The two tasks are typically conducted independently, however, which leads to spatial inconsistencies and hinders further integrated cortical analyses. To obtain self-consistent whole brain segmentations and surfaces, FreeSurfer segregates the subcortical and cortical segmentations before and after the cortical surface reconstruction. However, this "segmentation to surface to parcellation" strategy has shown limitation in various situations. In this work, we propose a novel "multi-atlas segmentation to surface" method called Multi-atlas CRUISE (MaCRUISE), which achieves self-consistent whole brain segmentations and cortical surfaces by combining multi-atlas segmentation with the cortical reconstruction method CRUISE. To our knowledge, this is the first work that achieves the reliability of state-of-the-art multi-atlas segmentation and labeling methods together with accurate and consistent cortical surface reconstruction. Compared with previous methods, MaCRUISE has three features: (1) MaCRUISE obtains 132 cortical/subcortical labels simultaneously from a single multi-atlas segmentation before reconstructing volume consistent surfaces; (2) Fuzzy tissue memberships are combined with multi-atlas segmentations to address partial volume effects; (3) MaCRUISE reconstructs topologically consistent cortical surfaces by using the sulci locations from multi-atlas segmentation. Two data sets, one consisting of five subjects with expertly traced landmarks and the other consisting of 100 volumes from elderly subjects are used for validation. Compared with CRUISE, MaCRUISE achieves self-consistent whole brain segmentation and cortical reconstruction without compromising on surface accuracy. MaCRUISE is comparably accurate to FreeSurfer while achieving greater robustness across an elderly population.

  13. Combination immunotherapy and photodynamic therapy for cancer

    Science.gov (United States)

    Hamblin, Michael R.; Castano, Ana P.; Mroz, Pawel

    2006-02-01

    Cancer is a leading cause of death among modern people largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity towards normal tissue. This is best accomplished by priming the body's immune system to recognize the tumor antigens so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species leading to vascular shutdown and tumor cell death. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens using PDT and immunostimulating treatments are likely to even further enhance post-PDT immunity. These immunostimulants are likely to include products derived from pathogenic microorganisms that are effectively recognized by Toll-like receptors and lead to upregulation of transcription factors for cytokines and inflammatory mediators. The following cascade of events causes activation of macrophages, dendritic and natural killer cells. Exogenous cytokine administration can be another way to increase PDT-induced immunity as well as treatment with a low dose of cyclophosphamide that selectively reduces T-regulatory cells. Although so far these combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration.

  14. Targeted Therapies for Brain Metastases from Breast Cancer

    Science.gov (United States)

    Venur, Vyshak Alva; Leone, José Pablo

    2016-01-01

    The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways. PMID:27649142

  15. Targeted Therapies for Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Vyshak Alva Venur

    2016-09-01

    Full Text Available The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2 and epidermal growth factor receptor (EGFR, vascular endothelial growth factor (VEGF receptor, mechanistic target of rapamycin (mTOR pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6 pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

  16. Three-Dimensional Magnetic Resonance Spectroscopic Imaging of Brain and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    John Kurhanewicz

    2000-01-01

    Full Text Available Clinical applications of magnetic resonance spectroscopic imaging (MRSI for the study of brain and prostate cancer have expanded significantly over the past 10 years. Proton MRSI studies of the brain and prostate have demonstrated the feasibility of noninvasively assessing human cancers based on metabolite levels before and after therapy in a clinically reasonable amount of time. MRSI provides a unique biochemical “window” to study cellular metabolism noninvasively. MRSI studies have demonstrated dramatic spectral differences between normal brain tissue (low choline and high N-acetyl aspartate, NAA and prostate (low choline and high citrate compared to brain (low NAA, high choline and prostate (low citrate, high choline tumors. The presence of edema and necrosis in both the prostate and brain was reflected by a reduction of the intensity of all resonances due to reduced cell density. MRSI was able to discriminate necrosis (absence of all metabolites, except lipids and lactate from viable normal tissue and cancer following therapy. The results of current MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy as well as the magnitude and time course of metabolic changes after therapy can improve our understanding of cancer aggressiveness and mechanisms of therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the potential for improved diagnosis, staging and treatment planning of brain and prostate cancer. Additionally, studies are under way to determine the accuracy of anatomic and metabolic parameters in providing an objective quantitative basis for assessing disease progression and response to therapy.

  17. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Junker, Niels; Ellebaek, Eva; Svane, Inge Marie;

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...... of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...... can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma....

  18. Combinations of genetic data in a study of oral cancer

    DEFF Research Database (Denmark)

    Mellerup, Erling Thyge; Møller, Gert Lykke; Mondal, Pinaki;

    2015-01-01

    for a polygenic disorder will not occur in in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients. In a previous study of oral cancer and leukoplakia 325 SNPs were analyzed. This study has been supplemented...... with an analysis of combinations of two SNP genotypes from among the 325 SNPs. Two clusters of combinations containing 95 patient specific combinations were significantly associated with oral cancer or leukoplakia. Of 373 patients with oral cancer 205 patients had a number of these 95 combinations in their genome......, whereas none of 535 control persons had any of these combinations in their genome....

  19. Combined local blood–brain barrier opening and systemic methotrexate for the treatment of brain tumors

    OpenAIRE

    Cooper, Itzik; Last, David; Guez, David; Sharabi, Shirley; Elhaik Goldman, Shirin; Lubitz, Irit; Daniels, Dianne; Salomon,Sharona; Tamar, Gregory; Tamir, Tzur; Mardor, Ronni; Fridkin, Mati; Shechter, Yoram; Mardor, Yael

    2015-01-01

    Despite aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme patients, in part due to poor penetration of most drugs across the blood–brain barrier (BBB). We propose a minimal-invasive combined treatment approach consisting of local BBB disruption in the tumor in parallel to systemic drug administration. Local BBB disruption is obtained by convection-enhanced delivery of a novel BBB disruption agent, enabling efficient/targeted delivery of the systemically ...

  20. Experience on breast cancer with brain metastasis in Kanagawa Cancer Center

    International Nuclear Information System (INIS)

    We studied the relationship between clinicopathologic findings and effect of adjuvant therapy on brain metastasis in breast cancer in order to clarify risk factors for brain metastasis in breast cancer patients. We divided patients into a group treated up until December 1999 (Group 1) and a group treated after January 2000 (Group 2), in whom adjuvant therapy was not generalized. Estrogen receptor-negative patients and cases more advanced than T2 showed a high risk of brain metastasis. The time interval to brain metastasis in Group 1 and 2 were 25 and 49.6 months, respectively, showing a significant difference. Taxan derivatives were used in 1.6% of Group 1 and 76% of Group 2. Estrogen receptor negativity, cancer more advanced than T2, and adjuvant therapy are risk factors for brain metastasis. (author)

  1. Brain cancer probed by native fluorescence and stokes shift spectroscopy

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-hui; He, Yong; Pu, Yang; Li, Qingbo; Wang, Wei; Alfano, Robert R.

    2012-12-01

    Optical biopsy spectroscopy was applied to diagnosis human brain cancer in vitro. The spectra of native fluorescence, Stokes shift and excitation spectra were obtained from malignant meningioma, benign, normal meningeal tissues and acoustic neuroma benign tissues. The wide excitation wavelength ranges were used to establish the criterion for distinguishing brain diseases. The alteration of fluorescence spectra between normal and abnormal brain tissues were identified by the characteristic fluorophores under the excitation with UV to visible wavelength range. It was found that the ratios of the peak intensities and peak position in both spectra of fluorescence and Stokes shift may be used to diagnose human brain meninges diseases. The preliminary analysis of fluorescence spectral data from cancer and normal meningeal tissues by basic biochemical component analysis model (BBCA) and Bayes classification model based on statistical methods revealed the changes of components, and classified the difference between cancer and normal human brain meningeal tissues in a predictions accuracy rate is 0.93 in comparison with histopathology and immunohistochemistry reports (gold standard).

  2. Combined doxorubicin and paclitaxel in advanced breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T;

    1996-01-01

    BACKGROUND: Paclitaxel has shown activity in metastatic breast cancer, including anthracycline-resistant breast cancer. The efficacy, toxicity and optimal scheduling of the combination of the two drugs needs to be defined. PATIENTS AND METHODS: Thirty women with advanced breast cancer who had...

  3. Environmental effects on molecular biomarkers expression in pancreatic and brain cancer

    Science.gov (United States)

    Mensah, Lawrence; Mallidi, Srivalleesha; Massodi, Iqbal; Anbil, Sriram; Mai, Zhiming; Hasan, Tayyaba

    2013-03-01

    A complete understanding of the biological mechanisms regulating devastating disease such as cancer remains elusive. Pancreatic and brain cancers are primary among the cancer types with poor prognosis. Molecular biomarkers have emerged as group of proteins that are preferentially overexpressed in cancers and with a key role in driving disease progression and resistance to chemotherapy. The epidermal growth factor receptor (EGFR), a cell proliferative biomarker is particularly highly expressed in most cancers including brain and pancreatic cancers. The ability of EGFR to sustain prolong cell proliferation is augmented by biomarkers such as Bax, Bcl-XL and Bcl-2, proteins regulating the apoptotic process. To better understand the role and effect of the microenvironment on these biomarkers in pancreatic cancer (PaCa); we analysed two pancreatic tumor lines (AsPc-1 and MiaPaCa-2) in 2D, 3D in-vitro cultures and in orthotopic tumors at different growth stages. We also investigated in patient derived glioblastoma (GBM) tumor cultures, the ability to utilize the EGFR expression to specifically deliver photosensitizer to the cells for photodynamic therapy. Overall, our results suggest that (1) microenvironment changes affect biomarker expression; thereby it is critical to understand these effects prior to designing combination therapies and (2) EGFR expression in tumor cells indeed could serve as a reliable and a robust biomarker that could be used to design targeted and image-guided photodynamic therapy.

  4. Dye-Enhanced Multimodal Confocal Imaging of Brain Cancers

    Science.gov (United States)

    Wirth, Dennis; Snuderl, Matija; Sheth, Sameer; Curry, William; Yaroslavsky, Anna

    2011-04-01

    Background and Significance: Accurate high resolution intraoperative detection of brain tumors may result in improved patient survival and better quality of life. The goal of this study was to evaluate dye enhanced multimodal confocal imaging for discriminating normal and cancerous brain tissue. Materials and Methods: Fresh thick brain specimens were obtained from the surgeries. Normal and cancer tissues were investigated. Samples were stained in methylene blue and imaged. Reflectance and fluorescence signals were excited at 658nm. Fluorescence emission and polarization were registered from 670 nm to 710 nm. The system provided lateral resolution of 0.6 μm and axial resolution of 7 μm. Normal and cancer specimens exhibited distinctively different characteristics. H&E histopathology was processed from each imaged sample. Results and Conclusions: The analysis of normal and cancerous tissues indicated clear differences in appearance in both the reflectance and fluorescence responses. These results confirm the feasibility of multimodal confocal imaging for intraoperative detection of small cancer nests and cells.

  5. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    International Nuclear Information System (INIS)

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings

  6. Clinical Observation and Basic Study of Erlotinib Combined Radiotherapy in the Treatment of Non-Small Cell Lung Cancer with Brain Metastasis%厄洛替尼联合放疗治疗肺癌脑转移的临床及基础研究

    Institute of Scientific and Technical Information of China (English)

    张清琴; 靳彩玲; 崔艳慧; 苗战会; 寇小格; 李小瑞

    2011-01-01

    Objective To study the efficacy of erlotinib combined with whole brain radiotherapy(WBRT) for non-small cell lung cancer(NSCLC) patients with brain metastasis and investigate gene mutations of EGFR and erlotinib efficacy. Methods Forty NSCLC patients with brain metastasis received conventional WBRT of 30 Gy concurrently with 150 mg oral doses of erlotinib once daily until disease progression. Gene sequencing was used to detect the EGFR of all patients, MRI was evaluated 3 months after radiation. Results In NSCLC patients with brain metastasis, the overall response rate and clinical benefit rate of erlotinib combined with WBRT were 90.0% and 100% respectively( complete response, CR in 4 patients, partial response, PR in 30 patients ,and stable disease SD in 6patients). Overall median survival was 10.2 months. Its efficacy in exon 19 and 21 of EGFR was 90.3%. Conclusion Erlotinib combined with radiotherapy was effective for Non-small cell lung cancer patients with multiple brain metastasis,especially patients with 19 and 21 of EGFR.%目的 观察厄洛替尼联合全脑放疗(WBRT)治疗非小细胞肺癌(non-small cell lung cancer,NSCLC)的有效性,并探讨其与表皮生长因子(epidermal growth factor receptor,EGFR)基因突变的关系.方法 40例均为不能接受化疗或化疗失败的NSCLC脑转移患者,接受全脑放疗(whole brain radi otherapy,WBRT)30 Gy/10 Fx,共2周,同时口服厄洛替尼150 mg,1次/d,直至疾病进展,所有患者均经基因测序法检查EGFR突变.放疗结束后3个月复查脑MRI,每3个月复查1次,进行临床疗效评价,直至疾病进展,并统计1年生存情况.结果 厄洛替尼联合WBRT对NSCLC脑转移的客观缓解率(完全缓解+部分缓解)为85.0%,临床症状缓解率100%,中位生存时间10.2月,EGFR突变的外显子19和2l突变的有效率为90.3%.结论 厄洛替尼联合WBRT对NSCLC脑转移EGFR突变的患者有较好的疗效,尤其是外显子19和2l突变的患者.生存期明显延

  7. Development of Combination Therapy with Anti-Cancer Drugs

    NARCIS (Netherlands)

    Leijen, S.

    2013-01-01

    This thesis describes early clinical trials with anti-cancer drugs in combination with commonly applied and registered chemotherapy and single agent studies with compounds that are intended for use in combination with registered or other targeted anti-cancer drugs. Gemcitabine is a prodrug that fi

  8. No increase in brain cancer rates during period of expanding cell phone use

    Science.gov (United States)

    In a new examination of United States cancer incidence data, investigators at the National Cancer Institute (NCI) reported that incidence trends have remained roughly constant for glioma, the main type of brain cancer hypothesized to be related to cell ph

  9. Brain metastases from breast cancer during pregnancy

    Directory of Open Access Journals (Sweden)

    Ashish Sharma

    2016-01-01

    Conclusion: There is a lack of guidelines and clinical consensus on medical and surgical treatment for breast cancer metastases in pregnant patients. Treatment usually varies based upon underlying tumor burden, location, gestational age of the fetus, and patient′s preference and symptomatology.

  10. Dietary acrylamide intake and brain cancer risk

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2009-01-01

    Background: Acrylamide is a probable human carcinogen, which is present in several heat-treatedfood s. In epidemiologic studies, positive associations with endometrial, ovarian, and renal cell cancer risk have been observed. The incidence of central nervous system tumors was increased upon acrylamid

  11. Treatment for brain metastasis from lung cancer in the era of radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, Kazuhiro; Iwai, Yoshiyasu; Nakajima, Hideki [Osaka City General Hospital (Japan)] (and others)

    2001-07-01

    The treatment for brain metastasis has undergone remarkable changes since the development of radiosurgery. We investigated the results of treatment for brain metastasis from lung cancer since the initiation of gamma knife radiosurgery (GKRS) and we discuss the usefulness of GKRS combined with other treatments in cases with recurrence. We treated 142 patients with brain metastasis from lung cancer. Sixteen patients were treated surgically, 11 patients were treated with whole brain radiation therapy (WBRT), and 115 patients were treated with GKRS. Our treatment plan is to use GKRS in cases with less than 5 lesions and lesions less than 3 cm in mean diameter. We use WBRT in cases with 5 or more lesions, and surgery in cases with lesions 3 cm or larger. If new lesions or tumor regrowth appeared after the initial treatment, we retreated them with one of the methods mentioned above. Twice or three-time treatments were performed in 30 patients. Median survival including all cases was 10 months and the number of deaths due to local treatment failure was only 5 (6.5%) out of the total 77 deaths which occurred. We were able to carry out less invasive treatment for brain metastasis from lung cancer by utilizing GKRS. Though we have to consider the indications for other treatments, we can say that radiosurgery is usually the treatment of first choice for brain metastasis from lung caner. When new lesions appear in cases where a particular initial treatment was used, it is possible to maintain or improve the quality of life by retreatment, using a combination of GKRS, surgery or WBRT, to prolong the patient's life. (author)

  12. Gamma knife radiosurgery for multiple brain metastases from non-small cell lung cancer. Comparison with whole brain radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Serizawa, Toru; Ono, Junichi [Chiba Cardiovascular Center (Japan); Iuchi, Toshihiko; Osato, Katsunobu

    2001-04-01

    The purpose of this retrospective study is to compare the effectiveness of gamma knife radiosurgery (GKS) with that of whole-brain radiation therapy (WBRT) for multiple cerebral metastases from non-small cell lung cancer. Among 302 cases with cerebral metastases from non-small cell lung cancer treated at the Chiba Cardiovascular Center and Chiba Cancer Center between 1990 and 1999, 100 consecutive patients filling the following 4 entry criteria were analyzed in this study: Up to 10 multiple brain lesions at initial MRI study; No surgically inaccessible tumors with more than 30 mm in diameter; No carcinomatous meningitis; More than 3 months of life expectancy. The patients were divided into two groups: the GKS group (66 patients) and the WBRT group (34 patients). In the GKS group, large lesions ({>=}30mm) were removed microsurgically and all other small lesions (<30 mm) were treated by GKS. New distant lesions were treated by repeated GKS without prophylactic WBRT. In the WBRT group, the patients were treated by the traditional combined therapy of WBRT and surgery. In both groups, chemotherapy was administered according to the primary physician's protocol. The two groups did not differ in terms of age, gender, initial Karnofsky Performance Scale (KPS) score, pathology of lung caner, number, and size of brain lesion, systemic control, and chemotherapy. Overall survival (OS), neurological survival (NS) and qualitative survival (QS) of the GKS group were longer than those of the WBRT group according to Kaplan-Meier's method. In a multivariate analysis the WBRT group also had significant poor prognostic factors for OS, NS and QS. GKS without prophylactic WBRT could be a primary choice of treatment method for patients with as many as 10 cerebral metastases from non-small cell lung cancer. (author)

  13. Gamma knife radiosurgery for multiple brain metastases from non-small cell lung cancer. Comparison with whole brain radiation therapy

    International Nuclear Information System (INIS)

    The purpose of this retrospective study is to compare the effectiveness of gamma knife radiosurgery (GKS) with that of whole-brain radiation therapy (WBRT) for multiple cerebral metastases from non-small cell lung cancer. Among 302 cases with cerebral metastases from non-small cell lung cancer treated at the Chiba Cardiovascular Center and Chiba Cancer Center between 1990 and 1999, 100 consecutive patients filling the following 4 entry criteria were analyzed in this study: Up to 10 multiple brain lesions at initial MRI study; No surgically inaccessible tumors with more than 30 mm in diameter; No carcinomatous meningitis; More than 3 months of life expectancy. The patients were divided into two groups: the GKS group (66 patients) and the WBRT group (34 patients). In the GKS group, large lesions (≥30mm) were removed microsurgically and all other small lesions (<30 mm) were treated by GKS. New distant lesions were treated by repeated GKS without prophylactic WBRT. In the WBRT group, the patients were treated by the traditional combined therapy of WBRT and surgery. In both groups, chemotherapy was administered according to the primary physician's protocol. The two groups did not differ in terms of age, gender, initial Karnofsky Performance Scale (KPS) score, pathology of lung caner, number, and size of brain lesion, systemic control, and chemotherapy. Overall survival (OS), neurological survival (NS) and qualitative survival (QS) of the GKS group were longer than those of the WBRT group according to Kaplan-Meier's method. In a multivariate analysis the WBRT group also had significant poor prognostic factors for OS, NS and QS. GKS without prophylactic WBRT could be a primary choice of treatment method for patients with as many as 10 cerebral metastases from non-small cell lung cancer. (author)

  14. Combinational strategies of metformin and chemotherapy in cancers.

    Science.gov (United States)

    Zhang, Hui-Hui; Guo, Xiu-Li

    2016-07-01

    Chemotherapeutic regimens are the most common treatment to inhibit tumor growth, but there is great variability in clinical responses of cancer patients; cancer cells often develop resistance to chemotherapeutics which results in tumor recurrence and further progression. Metformin, an extensively prescribed and well-tolerated first-line therapeutic drug for type 2 diabetes mellitus, has recently been identified as a potential and attractive anticancer adjuvant drug combined with chemotherapeutic drugs to improve treatment efficacy and lower doses. In this review, we summarized the molecular mechanisms underlying anticancer effects of metformin, which included insulin- and AMPK-dependent effects, selectively targeting cancer stem cells, reversing multidrug resistance, inhibition of the tumor metastasis and described the antineoplastic effects of metformin combined with chemotherapeutic agents in digestive system cancers (colorectal, gastric, hepatic and pancreatic cancer), reproductive system cancers (ovarian and endometrial cancer), prostate cancer, breast cancer, lung cancer, etc. Moreover, the clinical trials regarding metformin in combination of chemotherapeutic drugs were presented and the clinical obstacle or limitation related to the potential role of metformin in cancer treatment was also discussed in this review. PMID:27118574

  15. Treatment options in patients with small-cell lung cancer and brain metastases

    International Nuclear Information System (INIS)

    Small cell lung cancer (SCLC) accounts for some 20-25% of all lung cancers, with some 60-70% of patients presenting with the extensive stage (ES) of SCLC at the time of the diagnosis. Brain metastases are observed in 10-35% patients with ES SCLC, and 33% of them are asymptomatic. The main method of treatment in case of ES SCLC patients is cisplatin-containing systemic therapy. Radiotherapy is used as palliative treatment (primary tumour in chest, metastases localized in bones, brain or spinal cord) or as a prophylactic procedure (prophylactic cranial irradiation).The purpose of paper is to present the treatment possibilities in case of ES SCLC patients with brain metastases. Between 1995 and 2005 at the Oncology Centre in Krakow we evaluated 170 patients with SCLC in order to establish the stage of the disease recognising 39 cases (22.9%) with the extensive stage of the disease. The most frequent localizations of distant metastases were: the brain (11 patients, of whom 3 developed brain metastases without clinical symptoms), liver (10 patients), and bones (10 patients). Further analysis has been performed in the group of patients with brain metastases. In these patients treatment based on palliative irradiation of the whole brain and on chemotherapy according to the EP (etoposide and cisplatine) regimen. For cranial irradiation the dose of 20 Gy was given in 5 fractions. In 3 patients with brain metastases without clinical symptoms radiotherapy of brain was repeated after a 4-week interruption. These patients received 5-6 cycles of EP chemotherapy, followed by consolidation radiotherapy of the primary tumour region in the chest. Overall survival was estimated at 2 to 19 months (median: 8.9 months). In the subgroup of 3 patients with brain metastases without clinical symptoms we observed complete regression within the primary tumour region and of the brain metastases. These results were confirmed radiologically. In these patients disease-free survival of 5-9 months

  16. Appropriate Contrast Enhancement Measures for Brain and Breast Cancer Images

    Directory of Open Access Journals (Sweden)

    Suneet Gupta

    2016-01-01

    Full Text Available Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests the most appropriate measures for two of the medical images, namely, brain cancer images and breast cancer images.

  17. Evolving synergistic combinations of targeted immunotherapies to combat cancer.

    Science.gov (United States)

    Melero, Ignacio; Berman, David M; Aznar, M Angela; Korman, Alan J; Pérez Gracia, José Luis; Haanen, John

    2015-08-01

    Immunotherapy has now been clinically validated as an effective treatment for many cancers. There is tremendous potential for synergistic combinations of immunotherapy agents and for combining immunotherapy agents with conventional cancer treatments. Clinical trials combining blockade of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) may serve as a paradigm to guide future approaches to immuno-oncology combination therapy. In this Review, we discuss progress in the synergistic design of immune-targeting combination therapies and highlight the challenges involved in tailoring such strategies to provide maximal benefit to patients. PMID:26205340

  18. Common astrocytic programs during brain development, injury and cancer

    OpenAIRE

    Silver, Daniel J.; Steindler, Dennis A.

    2009-01-01

    In addition to radial glial cells of neurohistogenesis, immature astrocytes with stem-cell-like properties cordon off emerging functional patterns in the developing brain. Astrocytes also can be stem cells during adult neurogenesis, and a proposed potency of injury-associated reactive astrocytes has recently been substantiated. Astrocytic cells might additionally be involved in cancer stem cell-associated gliomagenesis. Thus, there are distinguishing roles for stem-cell-like astrocytes during...

  19. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    Science.gov (United States)

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

  20. Metabolic therapy: a new paradigm for managing malignant brain cancer.

    Science.gov (United States)

    Seyfried, Thomas N; Flores, Roberto; Poff, Angela M; D'Agostino, Dominic P; Mukherjee, Purna

    2015-01-28

    Little progress has been made in the long-term management of glioblastoma multiforme (GBM), considered among the most lethal of brain cancers. Cytotoxic chemotherapy, steroids, and high-dose radiation are generally used as the standard of care for GBM. These procedures can create a tumor microenvironment rich in glucose and glutamine. Glucose and glutamine are suggested to facilitate tumor progression. Recent evidence suggests that many GBMs are infected with cytomegalovirus, which could further enhance glucose and glutamine metabolism in the tumor cells. Emerging evidence also suggests that neoplastic macrophages/microglia, arising through possible fusion hybridization, can comprise an invasive cell subpopulation within GBM. Glucose and glutamine are major fuels for myeloid cells, as well as for the more rapidly proliferating cancer stem cells. Therapies that increase inflammation and energy metabolites in the GBM microenvironment can enhance tumor progression. In contrast to current GBM therapies, metabolic therapy is designed to target the metabolic malady common to all tumor cells (aerobic fermentation), while enhancing the health and vitality of normal brain cells and the entire body. The calorie restricted ketogenic diet (KD-R) is an anti-angiogenic, anti-inflammatory and pro-apoptotic metabolic therapy that also reduces fermentable fuels in the tumor microenvironment. Metabolic therapy, as an alternative to the standard of care, has the potential to improve outcome for patients with GBM and other malignant brain cancers. PMID:25069036

  1. Signaling the Unfolded Protein Response in primary brain cancers.

    Science.gov (United States)

    Le Reste, Pierre-Jean; Avril, Tony; Quillien, Véronique; Morandi, Xavier; Chevet, Eric

    2016-07-01

    The Unfolded Protein Response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress in the Endoplasmic Reticulum (ER). During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply; exposure to chemotherapies) challenges, with which they must cope to survive. Primary brain tumors are relatively rare but deadly and present a significant challenge in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain. As such surgery, radiation and chemotherapy options carry potentially lasting patient morbidity and incomplete tumor cure. Some of these tumors, such as glioblastoma, were reported to present features of ER stress and to depend on UPR activation to sustain growth, but to date there is no clear general representation of the ER stress status in primary brain tumors. In this review, we describe the key molecular mechanisms controlling the UPR and their implication in cancers. Then we extensively review the literature reporting the status of ER stress in various primary brain tumors and discuss the potential impact of such observation on patient stratification and on the possibility of developing appropriate targeted therapies using the UPR as therapeutic target. PMID:27016056

  2. Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England

    International Nuclear Information System (INIS)

    Aim: To determine current practice regarding brain imaging for newly diagnosed lung cancer patients without symptoms of brain metastases. Materials and methods: A survey questionnaire was sent by e-mail to all the lung cancer lead clinicians in England currently on the National Cancer Intelligence Network database. The survey asked whether brain imaging was used in new lung cancer patients without symptoms or signs to suggest brain metastases; and if so, which patient subgroups were imaged according to cell type, stage of disease, and intention to treat, and which techniques were used to image these patients. Responses were received between February and May 2014. Results: Fifty-nine of 154 centres replied to the survey (38%). Thirty of the 59 centres (51%) did not image the brain in these patients. Twenty-nine of the 59 (49%) centres imaged the brain in at least certain subgroups. Of those centres that did image the brain 21 (72%) used CT as the first-line imaging technique and six (20%) used MRI. Twenty-five of 59 (42%) centres stated that the 2011 NICE guidelines had led to a change in their practice. Conclusion: There is wide variation in practice regarding brain imaging in this patient group in England, with no brain imaging at all in approximately half of centres and a spectrum of imaging in the other half. When the brain is imaged, CT is the technique most commonly used. The 2011 NICE guidelines have led to some change in practice but not to national uniformity. - Highlights: • Ascertain current practice in brain imaging for staging asymptomatic lung cancer patients. • Survey questionnaire sent to all the lung cancer lead clinicians in England. • Wide variation in practice with regard to brain imaging in this patient group. • No brain imaging at all in approximately half of centres and a spectrum of imaging in the other half • The 2011 NICE guidelines have led to some change in practice but not to national uniformity

  3. 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.

  4. In vitro study of combined cilengitide and radiation treatment in breast cancer cell lines

    International Nuclear Information System (INIS)

    Brain metastasis from breast cancer poses a major clinical challenge. Integrins play a role in regulating adhesion, growth, motility, and survival, and have been shown to be critical for metastatic growth in the brain in preclinical models. Cilengitide, an αvβ3/αvβ5 integrin inhibitor, has previously been studied as an anti-cancer drug in various tumor types. Previous studies have shown additive effects of cilengitide and radiation in lung cancer and glioblastoma cell lines. The ability of cilengitide to enhance the effects of radiation was examined preclinically in the setting of breast cancer to assess its possible efficacy in the setting of brain metastasis from breast cancer. Our panel of breast cells was composed of four cell lines: T-47D (ER/PR+, Her2-, luminal A), MCF-7 (ER/PR+, Her2-, luminal A), MDA-MB-231 (TNBC, basal B), MDA-MB-468 (TNBC, basal A). The presence of cilengitide targets, β3 and β5 integrin, was first determined. Cell detachment was determined by cell counting, cell proliferation was determined by MTS proliferation assay, and apoptosis was measured by Annexin V staining and flow cytometry. The efficacy of cilengitide treatment alone was analyzed, followed by assessment of combined cilengitide and radiation treatment. Integrin β3 knockdown was performed, followed by cilengitide and radiation treatment to test for incomplete target inhibition by cilengitide, in high β3 expressing cells. We observed that all cell lines examined expressed both β3 and β5 integrin and that cilengitide was able to induce cell detachment and reduced proliferation in our panel. Annexin V assays revealed that a portion of these effects was due to cilengitide-induced apoptosis. Combined treatment with cilengitide and radiation served to further reduce proliferation compared to either treatment alone. Following β3 integrin knockdown, radiosensitization in combination with cilengitide was observed in a previously non-responsive cell line (MDA-MB-231

  5. CAPECITABINE IN THE TREATMENT OF BRAIN METASTATIC LESION IN PATIENTS WITH BREAST CANCER

    Directory of Open Access Journals (Sweden)

    E. A. Moskvina

    2012-01-01

    Full Text Available The paper considers the experience with capecitabine in 67 patients with brain metastatic lesion from breast cancer. The immediate efficacy of capecitabine and the results of therapy with the agent were analyzed in the groups of its use alone and in combination with radiotherapy both for therapeutic purposes and as an adjuvant regimen. In the chemoradiation therapy group, the objective effects in the brain were 73 %. The median time to progression was 12.27 months. In the monochemotherapy group, the objective effects were 30 %. The median time to progression was 4 months. The results of the investigation show that capecitabine has pronounced antitumor activity and moderate toxicity. Combination treatment is the method of choice. 

  6. Nanoparticle Based Combination Treatments for Targeting Multiple Hallmarks of Cancer

    Science.gov (United States)

    VanDyke, D; Kyriacopulos, P; Yassini, B; Wright, A; Burkhart, E; Jacek, S; Pratt, M; Peterson, CR; Rai, P

    2016-01-01

    Treatment of cancer remains one of the most challenging tasks facing the healthcare system. Cancer affects the lives of millions of people and is often fatal. Current treatment methods include surgery, chemotherapy, radiation therapies or some combinations of these. However, recurrence is a major problem. These treatments can be invasive with severe side effects. Inefficacies in treatments are a result of the complex and variable biology of cancerous cells. Malignant tumor cells and normal functioning cells share many of the same biological characteristics but the main difference is that in cancer cells there is in an overuse and over expression of these biological characteristics. These pertinent characteristics can be grouped into eight hallmarks, as illustrated by Hanahan and Weinberg. These characteristics include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, reprogramming energy metabolism, and evading immune destruction. In order to provide a noninvasive, effective treatment, delivery methods must be explored in order to transport cytotoxic agents used for targeting the hallmarks of cancer in a safer and more effective fashion. The use of nanoparticles as drug delivery carriers provides an effective method in which multiple cytotoxic agents can be safely delivered to cancer tissue to simultaneously target multiple hallmarks. By targeting multiple hallmarks of cancer at once, the efficacy of cancer treatments could be improved drastically. This review explores the uses and efficacy of combination therapies using nanoparticles that can simultaneously target multiple hallmarks of cancer. PMID:27547592

  7. Prognostic factors to predict survival in non-small-cell lung cancer with brain metastasis

    Institute of Scientific and Technical Information of China (English)

    Tiantian Li; Xuezhen Ma; Yuan Yao

    2014-01-01

    Objective:The purpose of the study was to assess prognostic factors to predict overal survival (OS) and progres-sion-free survival (PFS) in non-smal-celllung cancer (NSCLC) with brain metastasis (BM). Methods:From November 2011 to March 2013, the clinical data of 31 NSCLC cases with BM treated with multiple modalities including brain radiotherapy alone, systemic chemotherapy, whole brain radiotherapy (WBRT) combined with tyrosine kinase inhibitor (TKIs). The ef icacy and adverse reaction were evaluated after treatment. Results:In terms of intracranial lesions, the objective response rate (ORR) and the disease control rate (DCR) were 22.6%and 90.3%, respectively. As for systemic disease, ORR and DCR were 32.3%and 93.5%, respectively. The median time to progression-free survival (PFS) was 298 days (95%CI:258.624-337.376 days), whereas in the epidermal growth factor receptor (EGFR) mutation patients was 331 days. Patients who received EGFR-TKIs combined with brain radiation had better response rate (RR) than those only brain radiation. Univariate analysis showed that the EGFR-mutations could predictive factors for PFS, and not to other clinical pathological features. The most common toxici-ties were rash and diarrhea, but al were wel-tolerated. Conclusion:EGFR-mutations is the independent prognostic factors af ecting the survival rates of NSCLC patients with BM. Through the clinical observation, icotinib combined with WBRT may be ef ective on brain metastases in NSCLC patients, and toxicities are tolerable, which worth further study.

  8. Monocarboxylate transporters in the brain and in cancer.

    Science.gov (United States)

    Pérez-Escuredo, Jhudit; Van Hée, Vincent F; Sboarina, Martina; Falces, Jorge; Payen, Valéry L; Pellerin, Luc; Sonveaux, Pierre

    2016-10-01

    Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1-4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. PMID:26993058

  9. Drug combination may be highly effective in recurrent ovarian cancer

    Science.gov (United States)

    Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. The trial compared the activity of a combination of the dru

  10. Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury

    DEFF Research Database (Denmark)

    Jin, Guang; Duggan, Michael; Imam, Ayesha;

    2012-01-01

    We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival after hemorrhagic shock (HS), protect neurons from hypoxia-induced apoptosis, and attenuate the inflammatory response. We have also shown that administration of 6% hetastarch (Hextend [...... [Hex]) after traumatic brain injury (TBI) decreases brain swelling, without affecting size of the lesion. This study was performed to determine whether addition of VPA to Hex would decrease the lesion size in a clinically relevant large animal model of TBI + HS....

  11. Vitamin D in combination cancer treatment

    Science.gov (United States)

    Ma, Yingyu; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    As a steroid hormone that regulates mineral homeostasis and bone metabolism, 1α, 25-dihydroxycholecalciferol (calcitriol) also has broad spectrum anti-tumor activities as supported by numerous epidemiological and experimental studies. Calcitriol potentiates the anti-tumor activities of multiple chemotherapeutics agents including DNA-damaging agents cisplatin, carboplatin and doxorubicin; antimetabolites 5-fluorouracil, cytarabine, hydroxyurea, cytarabine and gemcitabine; and microtubule-disturbing agents paclitaxel and docetaxel. Calcitriol elicits anti-tumor effects mainly through the induction of cancer cell apoptosis, cell cycle arrest, differentiation, angiogenesis and the inhibition of cell invasiveness by a number of mechanisms. Calcitriol enhances the cytotoxic effects of gamma irradiation and certain antioxidants and naturally derived compounds. Inhibition of calcitriol metabolism by 24-hydroxylase promotes growth inhibition effect of calcitriol. Calcitriol has been used in a number of clinical trials and it is important to note that sufficient dose and exposure to calcitriol is critical to achieve anti-tumor effect. Several trials have demonstrated that safe and feasible to administer high doses of calcitriol through intermittent regimen. Further well designed clinical trials should be conducted to better understand the role of calcitriol in cancer therapy. PMID:20842231

  12. Vitamin D in combination cancer treatment

    Directory of Open Access Journals (Sweden)

    Yingyu Ma, Donald L. Trump, Candace S. Johnson

    2010-01-01

    Full Text Available As a steroid hormone that regulates mineral homeostasis and bone metabolism, 1α, 25-dihydroxycholecalciferol (calcitriol also has broad spectrum anti-tumor activities as supported by numerous epidemiological and experimental studies. Calcitriol potentiates the anti-tumor activities of multiple chemotherapeutics agents including DNA-damaging agents cisplatin, carboplatin and doxorubicin; antimetabolites 5-fluorouracil, cytarabine, hydroxyurea, cytarabine and gemcitabine; and microtubule-disturbing agents paclitaxel and docetaxel. Calcitriol elicits anti-tumor effects mainly through the induction of cancer cell apoptosis, cell cycle arrest, differentiation, angiogenesis and the inhibition of cell invasiveness by a number of mechanisms. Calcitriol enhances the cytotoxic effects of gamma irradiation and certain antioxidants and naturally derived compounds. Inhibition of calcitriol metabolism by 24-hydroxylase promotes growth inhibition effect of calcitriol. Calcitriol has been used in a number of clinical trials and it is important to note that sufficient dose and exposure to calcitriol is critical to achieve anti-tumor effect. Several trials have demonstrated that safe and feasible to administer high doses of calcitriol through intermittent regimen. Further well designed clinical trials should be conducted to better understand the role of calcitriol in cancer therapy.

  13. βIII-Tubulin Regulates Breast Cancer Metastases to the Brain.

    Science.gov (United States)

    Kanojia, Deepak; Morshed, Ramin A; Zhang, Lingjiao; Miska, Jason M; Qiao, Jian; Kim, Julius W; Pytel, Peter; Balyasnikova, Irina V; Lesniak, Maciej S; Ahmed, Atique U

    2015-05-01

    Brain metastases occur in about 10% to 30% of breast cancer patients, which culminates in a poor prognosis. It is, therefore, critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brain-predominant markers and found an elevation of several neuronal markers (βIII-tubulin, Nestin, and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of βIII-tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2, and MDA-MB-468), which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells.

  14. Simultaneous laparoscopic multi-organ resection combined with colorectal cancer: Comparison with non-combined surgery

    Institute of Scientific and Technical Information of China (English)

    Hye Jin Kim; Gyu-Seog Choi; Jun Seok Park; Soo Yeun Park; Soo Han Jun

    2012-01-01

    AIM:To access the short-term outcomes of simultaneous laparoscopic surgery combined with resection for synchronous lesions in patients with colorectal cancer.METHODS:Between March 1996 and April 2010 prospectively collected data were reviewed from 93 consecutive patients who had colorectal cancer and underwent simultaneous multiple organ resection (combined group) and 1090 patients who underwent conventional laparoscopic right hemicolectomy or laparoscopic low/anterior resection for colorectal cancer (non-combined group).In the combined group,there were nine gastric resections,three nephrectomies,nine adrenalectomies,56 cholecystectomies,and 21 gynecologic resections.In addition,five patients underwent simultaneous laparoscopic resection for three organs.The patient demographics,intra-operative outcomes,surgical morbidity,and short-term outcomes were compared between the two groups (the combined and non-combined groups).RESULTS:There were no significant differences in the clinicopathological variables between the two groups.The operating time was significantly longer in the combined group than in the non-combined group,regardless of tumor location (laparoscopic right hemicolectomy and laparoscopic low/anterior resection groups; P =0.048 and P < 0.001,respectively).The other intraoperative outcomes,such as the complications and open conversion rate,were similar in both groups.The rate of post-operative morbidity in the combined group was similar to the non-combined group (combined vs non-combined,15.1% vs 13.5%,P =0.667).Oncological safety for the colon and synchronous lesions were obtained in the combined group.CONCLUSION:Simultaneous laparoscopic multiple organ resection combined with colorectal cancer is a safe and feasible option in selected patients.

  15. Crizotinib Treatment Combined with Resection and Whole-brain Radiation Therapy 
in A ROS1 Rearranged Lung Adenocarcinoma with Brain Metastasis: 
Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Min ZHANG

    2016-08-01

    Full Text Available Background and objective Lung cancer with brain metastasis had poor prognosis. Crizotinib had been confirmed to be used in ROS1 (C-ros oncogene 1 receptor tyrosine kinase rearranged lung adenocarcinoma, but its efficacy in lung cancer with brain metastasis was poor due to the blood brain barrier. In the present study, we reported one case of ROS1 fusion lung adenocarcinoma with symptomatic brain matastasis, who was treated with brain metastases resection, crizotinib, and whole brain radiotherapy plus boost to residual brain metastasis. The safety and efficacy was summarized. Methods At first, surgical resection was used to relive mass effect and to biopsy. Then crizotinib (250 mg, bid was chosen for the existence of ROS1 fusion gene. Whole brain radiotherapy plus boost to residual brain metastasis were used after surgery. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours (RECIST v1.1 and brain metastasis were evaluated by computer tomography (CT/magnetic resonance imaging (MRI image. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTC AE v4.0. Results After taking crizotinib for 3 months, the lung lesions were close to complete response (CR, the brain metastasis were partial response (PR, the abdomen metastasis were CR and the symptom of blurred vision relieved. Conclusion Crizotinib combined with palliative operation and radiation therapy (WBRT plus boost to residual brain metastasis in the treatment of ROS1 fusion gene positive lung adenocarcinoma with symptomatic brain metastases, can effectively control intracranial lesions with good tolerance.

  16. Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer

    OpenAIRE

    Papademetriou, Iason T.; Porter, Tyrone

    2015-01-01

    Brain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood–brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development. Targeting to receptors enabling transport across the BBB offers non...

  17. Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for enhanced cancer cell apoptosis.

    Science.gov (United States)

    Shah, Birju P; Pasquale, Nicholas; De, Gejing; Tan, Tao; Ma, Jianjie; Lee, Ki-Bum

    2014-09-23

    Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core-shell nanoparticle (MCNP)-mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail-anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis. PMID:25133971

  18. Human brain cancer studied by resonance Raman spectroscopy

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-Hui; Sun, Yi; Pu, Yang; Boydston-White, Susie; Liu, Yulong; Alfano, Robert R.

    2012-11-01

    The resonance Raman (RR) spectra of six types of human brain tissues are examined using a confocal micro-Raman system with 532-nm excitation in vitro. Forty-three RR spectra from seven subjects are investigated. The spectral peaks from malignant meningioma, stage III (cancer), benign meningioma (benign), normal meningeal tissues (normal), glioblastoma multiforme grade IV (cancer), acoustic neuroma (benign), and pituitary adenoma (benign) are analyzed. Using a 532-nm excitation, the resonance-enhanced peak at 1548 cm-1 (amide II) is observed in all of the tissue specimens, but is not observed in the spectra collected using the nonresonance Raman system. An increase in the intensity ratio of 1587 to 1605 cm-1 is observed in the RR spectra collected from meningeal cancer tissue as compared with the spectra collected from the benign and normal meningeal tissue. The peak around 1732 cm-1 attributed to fatty acids (lipids) are diminished in the spectra collected from the meningeal cancer tumors as compared with the spectra from normal and benign tissues. The characteristic band of spectral peaks observed between 2800 and 3100 cm-1 are attributed to the vibrations of methyl (-CH3) and methylene (-CH2-) groups. The ratio of the intensities of the spectral peaks of 2935 to 2880 cm-1 from the meningeal cancer tissues is found to be lower in comparison with that of the spectral peaks from normal, and benign tissues, which may be used as a distinct marker for distinguishing cancerous tissues from normal meningeal tissues. The statistical methods of principal component analysis and the support vector machine are used to analyze the RR spectral data collected from meningeal tissues, yielding a diagnostic sensitivity of 90.9% and specificity of 100% when two principal components are used.

  19. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.;

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...... with chemotherapy may lead to improved clinical efficacy by clearing suppressor cells, reboot of the immune system, by rendering tumor cells more susceptible to immune mediated killing, or by activation of cells of the immune system. In addition, a range of tumor antigens have been characterized to allow targeting...... of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...

  20. Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Nagla Abdel Karim

    2015-01-01

    Full Text Available Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%–14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%–80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.

  1. Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

    International Nuclear Information System (INIS)

    An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. Fifty-eight patients with 1–3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. The treatment regimen had no significant impact on local control in the univariate analysis (p = 0.59). Age ≤59 years showed a trend towards improved local control on univariate (p = 0.066) and multivariate analysis (p = 0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p = 0.040) and ECOG 0–1 (p = 0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p = 0.039) and performance status (p = 0.028) maintained significance on multivariate analysis. ECOG 0–1 was positively correlated with survival on univariate analysis (p < 0.001); age ≤59 years showed a strong trend (p = 0.054). On multivariate analysis, performance status (p < 0.001) and age (p = 0.041) were significant. In breast cancer patients with few brain metastases, radiosurgery plus whole-brain

  2. Pancreatic cancer: systemic combination therapies for a heterogeneous disease.

    Science.gov (United States)

    Melisi, Davide; Calvetti, Lorenzo; Frizziero, Melissa; Tortora, Giampaolo

    2014-01-01

    Pancreatic cancer is the only human malignancy for which patients' survival has not improved substantially during the past 30 years. Despite advances in the comprehension of the molecular mechanisms underlying pancreatic carcinogenesis, current systemic treatments offer only a modest benefit in tumor-related symptoms and survival. Over the past decades, gemcitabine and its combination with other standard cytotoxic agents have been the reference treatments for advanced pancreatic cancer patients. The recent introduction of the three-drug combination regimen FOLFIRINOX or the new taxane nab-paclitaxel represent key advances for a better control of the disease. Novel agents targeting molecular mechanisms involved in cancer development and maintenance are currently under clinical investigation. This review describes the most important findings in the field of systemic combination therapies for the treatment of pancreatic cancer. We discuss the emerging evidences for the clinical activity of combination treatments with standard chemotherapy plus novel agents targeting tumor cell-autonomous and tumor microenvironment signaling pathways. We present some of the most important advances in the comprehension of the molecular mechanisms responsible for the chemoresistance of pancreatic cancer and the emerging therapeutic targets to overcome this resistance.

  3. Altered resting brain connectivity in persistent cancer related fatigue

    Directory of Open Access Journals (Sweden)

    Johnson P. Hampson

    2015-01-01

    Full Text Available There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI. Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected. This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52 and poor sleep quality (P = 0.04, r = 0.52 in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected. Mental fatigue scores were associated with greater default mode network (DMN connectivity to the superior frontal gyrus (P = 0.05 FDR corrected among fatigued subjects (r = 0.82 and less connectivity in the non-fatigued group (r = −0.88. These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent

  4. THE MANAGEMENT OF BRAIN METASTASES IN NON-SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Scott eOwen

    2014-09-01

    Full Text Available Brain metastases (BM are a common and lethal complication of non-small cell lung cancer (NSCLC which portend a poor prognosis. In addition, their management implies several challenges including preservation of neurological and neuro-cognitive function during surgery or radiation -therapy, minimizing iatrogenic complications of supportive medications, and optimizing drug delivery across the blood brain barrier (BBB. Despite these challenges, advancements in combined modality approaches can deliver hope of improved overall survival and quality of life for a subset of NSCLC patients with BM. Moreover, new drugs harnessing our greater understanding of tumour biology promise to build on this hope. In this mini-review, we revised the management of BM in NSCLC including advancements in neurosurgery, radiation therapy, as well as systemic and supportive therapy.

  5. Combining EEG source connectivity and network similarity: Application to object categorization in the human brain

    OpenAIRE

    Mheich, Ahmad; Hassan, Mahmoud; Dufor, Olivier; Khalil, Mohamad; Wendling, Fabrice

    2016-01-01

    A major challenge in cognitive neuroscience is to evaluate the ability of the human brain to categorize or group visual stimuli based on common features. This categorization process is very fast and occurs in few hundreds of millisecond time scale. However, an accurate tracking of the spatiotemporal dynamics of large-scale brain networks is still an unsolved issue. Here, we show the combination of recently developed method called dense-EEG source connectivity to identify functional brain netw...

  6. Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs

    Directory of Open Access Journals (Sweden)

    Thirugnanam Sivasakthivel

    2013-02-01

    Full Text Available Abstract Background The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. Presentation of the hypothesis Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs, which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. Testing the hypothesis The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. Expected outcome The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. Implications of the hypothesis Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and

  7. Epigenetic therapy in gastrointestinal cancer: the right combination.

    Science.gov (United States)

    Abdelfatah, Eihab; Kerner, Zachary; Nanda, Nainika; Ahuja, Nita

    2016-07-01

    Epigenetics is a relatively recent field of molecular biology that has arisen over the past 25 years. Cancer is now understood to be a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. The development of drugs targeting these processes has rapidly progressed; with several drugs already FDA approved as first-line therapy in hematological malignancies. Gastrointestinal (GI) cancers possess high degrees of epigenetic dysregulation, exemplified by subtypes such as CpG island methylator phenotype (CIMP), and the potential benefit of epigenetic therapy in these cancers is evident. The application of epigenetic drugs in solid tumors, including GI cancers, is just emerging, with increased understanding of the cancer epigenome. In this review, we provide a brief overview of cancer epigenetics and the epigenetic targets of therapy including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. We discuss the epigenetic drugs currently in use, with a focus on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and explain the pharmacokinetic and mechanistic challenges in their application. We present the strategies employed in incorporating these drugs into the treatment of GI cancers, and explain the concept of the cancer stem cell in epigenetic reprogramming and reversal of chemo resistance. We discuss the most promising combination strategies in GI cancers including: (1) epigenetic sensitization to radiotherapy, (2) epigenetic sensitization to cytotoxic chemotherapy, and (3) epigenetic immune modulation and priming for immune therapy. Finally, we present preclinical and clinical trial data employing these strategies thus far in various GI cancers including colorectal, esophageal, gastric, and pancreatic cancer. PMID:27366224

  8. Epigenetic therapy in gastrointestinal cancer: the right combination

    Science.gov (United States)

    Abdelfatah, Eihab; Kerner, Zachary; Nanda, Nainika; Ahuja, Nita

    2016-01-01

    Epigenetics is a relatively recent field of molecular biology that has arisen over the past 25 years. Cancer is now understood to be a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. The development of drugs targeting these processes has rapidly progressed; with several drugs already FDA approved as first-line therapy in hematological malignancies. Gastrointestinal (GI) cancers possess high degrees of epigenetic dysregulation, exemplified by subtypes such as CpG island methylator phenotype (CIMP), and the potential benefit of epigenetic therapy in these cancers is evident. The application of epigenetic drugs in solid tumors, including GI cancers, is just emerging, with increased understanding of the cancer epigenome. In this review, we provide a brief overview of cancer epigenetics and the epigenetic targets of therapy including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. We discuss the epigenetic drugs currently in use, with a focus on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and explain the pharmacokinetic and mechanistic challenges in their application. We present the strategies employed in incorporating these drugs into the treatment of GI cancers, and explain the concept of the cancer stem cell in epigenetic reprogramming and reversal of chemo resistance. We discuss the most promising combination strategies in GI cancers including: (1) epigenetic sensitization to radiotherapy, (2) epigenetic sensitization to cytotoxic chemotherapy, and (3) epigenetic immune modulation and priming for immune therapy. Finally, we present preclinical and clinical trial data employing these strategies thus far in various GI cancers including colorectal, esophageal, gastric, and pancreatic cancer. PMID:27366224

  9. Predicting brain metastases of breast cancer based on serum S100B and serum HER2

    DEFF Research Database (Denmark)

    Bechmann, Troels; Madsen, Jonna Skov; Brandslund, Ivan;

    2013-01-01

    Brain metastases are a major cause of morbidity and mortality in breast cancer. The aim of the current study was to evaluate the prediction of brain metastases based on serum S100B and human epidermal growth factor receptor 2 (HER2). A total of 107 breast cancer patients were included...

  10. Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation.

    Directory of Open Access Journals (Sweden)

    Navjot Shah

    Full Text Available Ashwagandha, a traditional Indian herb, has been known for its variety of therapeutic activities. We earlier demonstrated anticancer activities in the alcoholic and water extracts of the leaves that were mediated by activation of tumor suppressor functions and oxidative stress in cancer cells. Low doses of these extracts were shown to possess neuroprotective activities in vitro and in vivo assays.We used cultured glioblastoma and neuroblastoma cells to examine the effect of extracts (alcoholic and water as well as their bioactive components for neuroprotective activities against oxidative stress. Various biochemical and imaging assays on the marker proteins of glial and neuronal cells were performed along with their survival profiles in control, stressed and recovered conditions. We found that the extracts and one of the purified components, withanone, when used at a low dose, protected the glial and neuronal cells from oxidative as well as glutamate insult, and induced their differentiation per se. Furthermore, the combinations of extracts and active component were highly potent endorsing the therapeutic merit of the combinational approach.Ashwagandha leaf derived bioactive compounds have neuroprotective potential and may serve as supplement for brain health.

  11. Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives

    DEFF Research Database (Denmark)

    Bergmann, Til Ole; Karabanov, Anke; Hartwigsen, Gesa;

    2016-01-01

    and "offline" NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed. Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS. In this paper, we will provide a conceptual framework...

  12. Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer

    International Nuclear Information System (INIS)

    Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer. Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT). From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups. Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent

  13. The results of combination therapy for local cervical cancer

    International Nuclear Information System (INIS)

    Administration of the developed technique os combination treatment based on split course of combination radiotherapy against a background of neoadjuvant chemotherapy to 275 patients with stage II-III cervical cancer allowed to transfer an immobile tumor process to the respectable in 46.0% og cases, which was followed by the uterus and appendages removal, while with traditional course of radiotherapy operability index was only 6.9%

  14. Combined therapy of radiotherapy and chemotherapy on brain tumor

    International Nuclear Information System (INIS)

    The subjects were 52 patients (5-78 years, average 51.4 years) with primary brain tumor treated in 4 institutes in Chugoku and Shikoku districts during 3 years from April 1991. Histopathologically, the subject diseases were glioblastoma in 16, well differentiated glioblastoma in 19, brain primary lymphoma in 9, and malignant meningioma in 5. In the glioblastoma group, 14 received surgery, radiotherapy, and chemotherapy at the first admission. Three patients who survived more than 1 year and 6 patients who died within 1 year were compared. No significant difference was observed in terms of radiotherapy between the both groups. In the astrocytoma and oligodendroglioma groups, 16 patients received radiotherapy and chemotherapy as the initial treatment, and 14 underwent several course of maintenance therapy. In the comparison between 7 patients who died within 3 years from the first treatment and 9 patients surviving more than 3 years, no significant difference was observed in terms of radiation doses. (S.Y.)

  15. 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.

  16. Combining chemotherapy and targeted therapies in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.

  17. Cancer treatment: the combination of vaccination with other therapies

    DEFF Research Database (Denmark)

    Andersen, M.H.; Sorensen, R.B.; Schrama, D.;

    2008-01-01

    Harnessing of the immune system by the development of 'therapeutic' vaccines, for the battle against cancer has been the focus of tremendous research efforts over the past two decades. As an illustration of the impressive amounts of data gathered over the past years, numerous antigens expressed...... their escape from cytotoxic therapies represent prime vaccination candidates. The characterization of a high number of tumor antigens allow the concurrent or serial immunological targeting of different proteins associated with such cancer traits. Moreover, while vaccination in itself is a promising new...... approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending...

  18. Partnership to Explore New Drug Combination for Pancreatic Cancer | Poster

    Science.gov (United States)

    By Frank Blanchard, Staff Writer Scientists at NCI and Frederick National Laboratory for Cancer Research (FNLCR) are partnering with the Lustgarten Foundation to test whether a vitamin D derivative will make a difference when combined with a conventional anticancer drug in treating tumors of the pancreas.

  19. Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances

    Directory of Open Access Journals (Sweden)

    Simpson GR

    2016-01-01

    Full Text Available Guy R Simpson,1 Kate Relph,1 Kevin Harrington,2 Alan Melcher,3 Hardev Pandha1 1Department of Clinical and Experimental Medicine, Targeted Cancer Therapy, Faculty of Health and Medical Sciences, University of Surrey, Guildford, 2Targeted Therapy, The Institute of Cancer Research/The Royal Marsden NIHR Biomedical Research Centre, London, 3Targeted and Biological Therapies,Oncology and Clinical Research, Leeds Institute of Cancer and Pathology, Faculty of Medicine and Health, University of Leeds, Leeds, UK Abstract: Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors. Similarly to oncolytic viruses, the benefits of chemotherapeutic agents may be that they induce systemic antitumor immunity through the induction of immunogenic cell death of cancer cells. Combining these two treatment modalities has to date resulted in significant potential in vitro and in vivo synergies through various mechanisms without any apparent additional toxicities. Chemotherapy has been and will continue to be integral to the management of advanced cancers. This review therefore focuses on the potential for a number of common cytotoxic agents to be combined with clinically relevant oncolytic viruses. In many cases, this combined approach has already advanced to the clinical trial arena. Keywords: oncolytic virotherapy, chemotherapy, immunogenic cell death

  20. Novel Combinations for the Treatment of Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Linda T. Vahdat

    2010-01-01

    Full Text Available Anthracyclines and taxanes represent the mainstay of first-line cytotoxic therapy for metastatic breast cancer (MBC, but most patients eventually develop resistance to these agents. Consequently, alternative combinations for MBC therapy are the subject of much ongoing research. Capecitabine and ixabepilone is the only chemotherapy combination specifically approved for MBC after failure of anthracyclines and taxanes. Other options have limited data to support their use in this setting but are commonly used in practice. Future MBC therapies will likely combine alternative chemotherapies and novel biologic agents, and numerous ongoing trials should help to further define the proper use of these regimens.

  1. The Effects of Nimesulide Combined with Cisplatin on Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    邢丽华; 张珍祥; 徐永健; 张惠兰; 刘剑波

    2004-01-01

    To study the effects of cyclooxygenase 2 selective inhibitor Nimesulide (NIM) combined with Cisplatin (DDP) on human lung cancer and the possible mechanisms, the proliferation and apoptosis of human lung cancer cell line A549 were evaluated by MTT reduction assay and flow cytometry respectively. The inhibitory effect on neoplasia in vivo was tested on nude mice subcutaneously implanted tumor. Our results showed that NIM and DDP could inhibit A549 cell proliferation in a concentration dependent pattern; this action was enhanced when NIM (25 μmol/L) was given in combination with DDP and they worked in a synergistic or additive pattern as DDP concentration ≥ 1 μg/ml. NIM and DDP could induce A549 cells apoptosis and the action was augmented when used in combination (P<0.01). NIM and DDP could inhibit the growth of subcutaneously implan ted tumors on nude mice (P<0.05,P<0.01) and the inhibitory rate of NIM combined with DDP was significantly higher than that of NIM orDDPgroup (P<0.01, P<0.01). It is concluded that combined usc of NIM and DDP has significant synergistic antitumor effects on lung cancer cell line A549 and in animals in vivo. The synergy may be achieved by growth inhibition and apoptosis induction.

  2. Advances in Diagnosis and Treatment of Brain Metastases from the Primary Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yi LIU

    2013-07-01

    Full Text Available Lung cancer with brain metastasis was 23% to 65%, and is the most common type in brain metastasis tumors with the poor prognosis. At present, diagnosis and treatment of brain metastases from lung carcinoma and its molecular mechanism have become one hot spot of amount researches. Here, we made a systematic review of the progress of the clinical features, diagnosis and treatment of brain metastases from lung and its molecular mechanism.

  3. 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.

  4. Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives.

    Science.gov (United States)

    Bergmann, Til Ole; Karabanov, Anke; Hartwigsen, Gesa; Thielscher, Axel; Siebner, Hartwig Roman

    2016-10-15

    Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures or neuronal activity patterns for a given brain function. It is nowadays feasible to combine NTBS, either consecutively or concurrently, with a variety of neuroimaging and electrophysiological techniques. Here we discuss what kind of information can be gained from combined approaches, which often are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both "online" NTBS effects immediately following the stimulation and "offline" NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed. Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS. In this paper, we will provide a conceptual framework, emphasizing principal strategies and highlighting promising future directions to exploit the benefits of combining NTBS with neuroimaging or electrophysiology. PMID:26883069

  5. 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.

  6. Neural networks improve brain cancer detection with Raman spectroscopy in the presence of light artifacts

    Science.gov (United States)

    Jermyn, Michael; Desroches, Joannie; Mercier, Jeanne; St-Arnaud, Karl; Guiot, Marie-Christine; Petrecca, Kevin; Leblond, Frederic

    2016-03-01

    It is often difficult to identify cancer tissue during brain cancer (glioma) surgery. Gliomas invade into areas of normal brain, and this cancer invasion is frequently not detected using standard preoperative magnetic resonance imaging (MRI). This results in enduring invasive cancer following surgery and leads to recurrence. A hand-held Raman spectroscopy is able to rapidly detect cancer invasion in patients with grade 2-4 gliomas. However, ambient light sources can produce spectral artifacts which inhibit the ability to distinguish between cancer and normal tissue using the spectral information available. To address this issue, we have demonstrated that artificial neural networks (ANN) can accurately classify invasive cancer versus normal brain tissue, even when including measurements with significant spectral artifacts from external light sources. The non-parametric and adaptive model used by ANN makes it suitable for detecting complex non-linear spectral characteristics associated with different tissues and the confounding presence of light artifacts. The use of ANN for brain cancer detection with Raman spectroscopy, in the presence of light artifacts, improves the robustness and clinical translation potential for intraoperative use. Integration with the neurosurgical workflow is facilitated by accounting for the effect of light artifacts which may occur, due to operating room lights, neuronavigation systems, windows, or other light sources. The ability to rapidly detect invasive brain cancer under these conditions may reduce residual cancer remaining after surgery, and thereby improve patient survival.

  7. COMBINED TREATMENT OF LOCALLY-ADVANCED BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    I. V. Chernyshev

    2015-01-01

    Full Text Available Bladder cancer (BC is an important clinical and scientific challenge. In 2013, in Russia, the absolute number of patients with first-ever diagnosis of bladder cancer was 12 992 people. There is an increasing proportion of detection of bladder cancer stage I–II disease patterns: 2003–50.8% in 2013–69.6%, while the number of newly diagnosed patients in III and IV clinical stages remains at 30%. The proportion of individuals who completed the treatment of the number of newly diagnosed patients with bladder cancer in 2013, was as follows: only surgical method — 65.4%, 33.5% combined. Purpose. Improvement of the results of treatment of patients with locally advanced bladder cancer. Materials and methods. The main treatment for muscle-invasive bladder cancer is radical cystectomy. In the combined treatment of bladder cancer chemotherapy is the component that systemic exposure to the tumor, the way of regional and distant metastases. The study included 132 patients with locally advanced bladder cancer who were treated for 2005–2013, divided into four groups: NACT + CE — 27 people (20.5%, CE + ACT — 21 (15.9%, NACT + CE + ACT — 21 (15.9% only CE — 63 (47.7%. An important component of treatment has been the use of platinum (cisplatin or carboplatin in Schemes M–VAC and GP. An objective response is possible in 44.7%, and the stabilization process in 40.4% of patients.Results. The clinical effect is evaluated in all patients. In the group of NACT 21% of patients survived for more than 4 years, but did not survive the 5‑year mark. In the group of CE + ACT the indicator achieved only 3‑year survival rate, which amounted to 43%. In the group of CE — none of the patients did not live up to 3 years, with 2‑year survival rate was 30%. In the group of ACT + NCT + CE 3 patients (15% were alive at the time, passed the threshold of the 5‑year survival rate, there is no progression of cancer.Conclusion. Combined treatment mode NACT

  8. Combining gene signatures improves prediction of breast cancer survival.

    Directory of Open Access Journals (Sweden)

    Xi Zhao

    Full Text Available BACKGROUND: Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123 and test set (n = 81, respectively. Gene sets from eleven previously published gene signatures are included in the study. PRINCIPAL FINDINGS: To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014. Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001. The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. CONCLUSION: Combining the predictive strength of multiple gene signatures improves

  9. Brain cancer mortality rates increase with Toxoplasma gondii seroprevalence in France

    Science.gov (United States)

    Vittecoq, Marion; Elguero, Eric; Lafferty, Kevin D.; Roche, Benjamin; Brodeur, Jacques; Gauthier-Clerc, Michel; Missé, Dorothée; Thomas, Frédéric

    2012-01-01

    The incidence of adult brain cancer was previously shown to be higher in countries where the parasite Toxoplasma gondii is common, suggesting that this brain protozoan could potentially increase the risk of tumor formation. Using countries as replicates has, however, several potential confounding factors, particularly because detection rates vary with country wealth. Using an independent dataset entirely within France, we further establish the significance of the association between T. gondii and brain cancer and find additional demographic resolution. In adult age classes 55 years and older, regional mortality rates due to brain cancer correlated positively with the local seroprevalence of T. gondii. This effect was particularly strong for men. While this novel evidence of a significant statistical association between T. gondii infection and brain cancer does not demonstrate causation, these results suggest that investigations at the scale of the individual are merited.

  10. Substance use and the adolescent brain: a toxic combination?

    Science.gov (United States)

    Lubman, Dan I; Yücel, Murat; Hall, Wayne D

    2007-11-01

    Early onset substance use has consistently been associated with increased risk for a range of adverse outcomes in late adolescence and early adulthood. However, the mechanisms that underlie this relationship are not fully understood. Recent advances in developmental neuro-science, together with emerging literature on early onset substance use, suggest that the adolescent brain may be more vulnerable to the effects of addictive substances because of the extensive neuromaturational processes that are occurring during this period. Such findings are suggestive of disrupted developmental trajectories in early onset users, although there is growing evidence that high-risk youths have premorbid neurobiological vulnerabilities. Prospective studies investigating neurobiological correlates and sequelae of early adolescent drug use are urgently required to inform appropriate public health responses. PMID:17984159

  11. Whole brain radiotherapy for brain metastases from breast cancer: estimation of survival using two stratification systems

    International Nuclear Information System (INIS)

    Brain metastases (BM) are the most common form of intracranial cancer. The incidence of BM seems to have increased over the past decade. Recursive partitioning analysis (RPA) of data from three Radiation Therapy Oncology Group (RTOG) trials (1200 patients) has allowed three prognostic groups to be identified. More recently a simplified stratification system that uses the evaluation of three main prognostics factors for radiosurgery in BM was developed. To analyze the overall survival rate (OS), prognostic factors affecting outcomes and to estimate the potential improvement in OS for patients with BM from breast cancer, stratified by RPA class and brain metastases score (BS-BM). From January 1996 to December 2004, 174 medical records of patients with diagnosis of BM from breast cancer, who received WBRT were analyzed. The surgery followed by WBRT was used in 15.5% of patients and 84.5% of others patients were submitted at WBRT alone; 108 patients (62.1%) received the fractionation schedule of 30 Gy in 10 fractions. Solitary BM was present in 37.9 % of patients. The prognostic factors evaluated for OS were: age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, neurosurgery, chemotherapy, absence extracranial disease, RPA class, BS-BM and radiation doses and fractionation. The OS in 1, 2 and 3 years was 33.4 %, 16.7%, and 8.8 %, respectively. The RPA class analysis showed strong relation with OS (p < 0.0001). The median survival time by RPA class in months was: class I 11.7, class II 6.2 and class III 3.0. The significant prognostic factors associated with better OS were: higher KPS (p < 0.0001), neurosurgery (P < 0.0001), single metastases (p = 0.003), BS-BM (p < 0.0001), control primary tumor (p = 0.002) and absence of extracranial metastases (p = 0.001). In multivariate analysis, the factors associated positively with OS were: neurosurgery (p < 0.0001), absence of extracranial metastases (p <0.0001) and RPA class I (p < 0.0001). Our

  12. Stimuli-sensitive nanopreparations for combination cancer therapy.

    Science.gov (United States)

    Jhaveri, Aditi; Deshpande, Pranali; Torchilin, Vladimir

    2014-09-28

    Nanocarriers have revolutionized drug delivery practices over the past couple of decades, primarily due to the advances in materials chemistry, nanotechnology and nanomedicine. This in turn, has spurred the development of a number of novel nanocarrier-based platforms and treatment strategies for cancer. It is now clear that to manage a disease as complex as cancer, a single or stand-alone treatment strategy may not suffice. Present day drug delivery strategies progressively lean towards "multi-pronged" combination approaches to make cancer treatments more effective. To that end, nanocarriers which simultaneously incorporate multiple drugs that affect different pathways and act through different mechanisms, or combinations of drugs with biological therapeutics like genes, antibodies, proteins or siRNAs have been the focus of recent active research. Furthermore, nanocarriers which respond to a variety of intrinsic cues afforded by the tumor microenvironment like low pH, elevated redox potential, over-expressed enzymes and hyperthermia as well as to externally applied stimuli such as magnetic field, ultrasound or light have been developed to trigger site-specific drug release. In this review, we focus specifically on nanocarriers that simultaneously exhibit stimuli-sensitivity and incorporate various combinations of conventional small molecule chemotherapeutic agents and biologics. We provide an overview of the different internal and external stimuli most relevant to cancer, and discuss selected examples of stimuli-sensitive combination nanopreparations from the recent literature with respect to each stimulus. Finally, we discuss multifunctional stimuli-sensitive nanopreparations which incorporate various combinations of drugs, biologics and targeting ligands within a single carrier that form so-called "smart" nanopreparations. PMID:24818767

  13. A placebo-controlled, randomized phase II study of maintenance enzastaurin following whole brain radiation therapy in the treatment of brain metastases from lung cancer

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Ciuleanu, Tudor; Fløtten, Øystein;

    2012-01-01

    Enzastaurin is a protein kinase C inhibitor with anti-tumor activity. This study was designed to determine if maintenance enzastaurin improved the outcome of whole brain radiotherapy (WBRT) in lung cancer (LC) patients with brain metastases (BMs).......Enzastaurin is a protein kinase C inhibitor with anti-tumor activity. This study was designed to determine if maintenance enzastaurin improved the outcome of whole brain radiotherapy (WBRT) in lung cancer (LC) patients with brain metastases (BMs)....

  14. Combined clinical and genetic testing algorithm for cervical cancer diagnosis

    OpenAIRE

    Liou, Yu-Ligh; Zhang, Tao-Lan; Yan, Tian; Yeh, Ching-Tung; Kang, Ya-Nan; Cao, Lanqin; Wu, Nayiyuan; Chang, Chi-Feng; Wang, Huei-Jen; Yen, Carolyn; Chu, Tang-Yuan; Zhang, Yi; Zhang, Yu; Zhou, Honghao

    2016-01-01

    Background Opportunistic screening in hospitals is widely used to effectively reduce the incidence rate of cervical cancer in China and other developing countries. This study aimed to identify clinical risk factor algorithms that combine gynecologic examination and molecular testing (paired box gene 1 (PAX1) or zinc finger protein 582 (ZNF582) methylation or HPV16/18) results to improve diagnostic accuracy. Methods The delta Cp of methylated PAX1 and ZNF582 was obtained via quantitative methy...

  15. Response of breast cancer cells and cancer stem cells to metformin and hyperthermia alone or combined.

    Directory of Open Access Journals (Sweden)

    Hyemi Lee

    Full Text Available Metformin, the most widely prescribed drug for treatment of type 2 diabetes, has been shown to exert significant anticancer effects. Hyperthermia has been known to kill cancer cells and enhance the efficacy of various anti-cancer drugs and radiotherapy. We investigated the combined effects of metformin and hyperthermia against MCF-7 and MDA-MB-231 human breast cancer cell, and MIA PaCa-2 human pancreatic cancer cells. Incubation of breast cancer cells with 0.5-10 mM metformin for 48 h caused significant clonogenic cell death. Culturing breast cancer cells with 30 µM metformin, clinically relevant plasma concentration of metformin, significantly reduced the survival of cancer cells. Importantly, metformin was preferentially cytotoxic to CD44(high/CD24(low cells of MCF-7 cells and, CD44(high/CD24(high cells of MIA PaCa-2 cells, which are known to be cancer stem cells (CSCs of MCF-7 cells and MIA PaCa-2 cells, respectively. Heating at 42°C for 1 h was slightly toxic to both cancer cells and CSCs, and it markedly enhanced the efficacy of metformin to kill cancer cells and CSCs. Metformin has been reported to activate AMPK, thereby suppressing mTOR, which plays an important role for protein synthesis, cell cycle progression, and cell survival. For the first time, we show that hyperthermia activates AMPK and inactivates mTOR and its downstream effector S6K. Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K. Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR. It is conclude that the effects of metformin against cancer cells including CSCs can be markedly enhanced by hyperthermia.

  16. Effect of progesterone combined with chemotherapy on epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    陈晓军; 丰有吉

    2003-01-01

    Objective To identify an effective auxiliary therapy for epithelial ovarian cancer. Methods Progesterone acetate given at 250 mg intramuscularly twice a week for 1 month followed by increased administration to 500 mg intramuscularly every two weeks for 3 years was used in combination with platinum based chemotherapy to treat patients with epithelial ovarian cancer as a first-line therapy. Prognoses of the patients receiving progesterone combined with chemotherapy (progesterone group) and those receiving chemotherapy only (control group) were compared. Results Three-year recurrence and survival conditions of the progesterone and control groups were as follows. Stage Ⅰa: no patient relapsed or died in either group. Stage Ⅰb-Ⅰc: three-year recurrence rates were 14.2% and 37.5%, respectively (P=0.2845); three-year survival rates were 92.3% and 87.5% (P=0.7221). Stage Ⅱ: 1 patient relapsed and died among the 3 patients in the progesterone group; among the 4 patients in the control group, 1 patient relapsed, none died. Stage Ⅲ: three-year recurrence rates were 30.8% and 64.3%, respectively (P=0.1170); three-year survival rates were 85.7% and 42.9%, respectively (P=0.005). Stage Ⅳ: 4 patients relapsed and 1 patient died among the 7 patients in the progesterone group; both the patients in the control group relapsed and died. Conclusions The results indicated that progesterone combined with platinum based chemotherapy as a first-line therapy may improve the prognosis of advanced epithelial ovarian cancer, but would not change the prognosis of early stage epithelial ovarian cancer.

  17. Combination treatment of tamoxifen with risperidone in breast cancer.

    Directory of Open Access Journals (Sweden)

    Wei-Lan Yeh

    Full Text Available Tamoxifen has long been used and still is the most commonly used endocrine therapy for treatment of both early and advanced estrogen receptor-positive breast cancer in pre- and post-menopause women. Tamoxifen exerts its cytotoxic effect primarily through cytostasis which is associated with the accumulation of cells in the G0/G1 phase of the cell cycle. Apoptotic activity can also be exerted by tamoxifen which involves cleavage of caspase 9, caspase 7, caspase 3, and poly-ADP-ribose polymerase (PARP. Down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulation of pro-apoptotic proteins Bax and Bak have also been observed. In addition, stress response protein of GRP 94 and GRP 78 have also been induced by tamoxifen in our study. However, side effects occur during tamoxifen treatment in breast cancer patients. Researching into combination regimen of tamoxifen and drug(s that relieves tamoxifen-induced hot flushes is important, because drug interactions may decrease tamoxifen efficacy. Risperidone has been shown to be effective in reducing or eliminating hot flushes on women with hormonal variations. In this present study, we demonstrated that combination of tamoxifen with risperidone did not interfered tamoxifen-induced cytotoxic effects in both in vitro and in vivo models, while fluoxetine abrogated the effects of tamoxifen. This is the first paper suggesting the possibility of combination treatment of tamoxifen with risperidone in breast cancer patients, providing a conceivable resolution of tamoxifen-induced side effects without interfering the efficacy of tamoxifen against breast cancer.

  18. A pilot case-cohort study of brain cancer in poultry and control workers.

    Science.gov (United States)

    Gandhi, S; Felini, M J; Ndetan, H; Cardarelli, K; Jadhav, S; Faramawi, M; Johnson, E S

    2014-01-01

    We conducted an exploratory study to investigate which exposures (including poultry oncogenic viruses) are associated with brain cancer in poultry workers. A total of 46,819 workers in poultry and nonpoultry plants from the same union were initially followed for mortality. Brain cancer was observed to be in excess among poultry workers. Here we report on a pilot case-cohort study with cases consisting of 26 (55%) of the 47 brain cancer deaths recorded in the cohort, and controls consisting of a random sample of the cohort (n = 124). Exposure information was obtained from telephone interviews, and brain cancer mortality risk estimated by odds ratios. Increased risk of brain cancer was associated with killing chickens, odds ratio (OR) = 5.8 (95% confidence interval, 1.2-28.3); working in a shell-fish farm, OR = 13.0 (95% CI, 1.9-84.2); and eating uncooked fish, OR = 8.2 (95% CI, 1.8-37.0). Decreased risks were observed for chicken pox illness, OR = 0.2 (95% CI, 0.1-0.6), and measles vaccination, OR = 0.2 (95% CI, 0.1-0.6). Killing chickens, an activity associated with the highest occupational exposure to poultry oncogenic viruses, was associated with brain cancer mortality, as were occupational and dietary shellfish exposures. These findings are novel. PMID:24564367

  19. TENIPOSIDE FOR BRAIN METASTASES OF SMALL-CELL LUNG-CANCER - A PHASE-II STUDY

    NARCIS (Netherlands)

    POSTMUS, PE; SMIT, EF; HAAXMAREICHE, H; VANZANDWIJK, N; ARDIZZONI, A; QUOIX, E; KIRKPATRICK, A; SAHMOUD, T; GIACCONE, G

    1995-01-01

    Purpose: Here we report the results of a phase II study of teniposide, one of the most active drugs against small-cell lung cancer (SCLC), in patients with brain metastases. Patients and Methods: Patients with SCLC who presented with brain metastases at diagnosis (n = 11) or during follow-up evaluat

  20. Admission criteria to the Danish Brain Cancer Program are moderately associated with magnetic resonance imaging findings

    DEFF Research Database (Denmark)

    Hill, Thomas Winther; Nielsen, Mie Kiszka; Nepper-Rasmussen, Jørgen

    2013-01-01

    The objective of this study was to evaluate the Danish Brain Cancer Program by examining the criteria for admission to the program and the results of magnetic resonance imaging (MRI) of the brain in 359 patients referred to the program at the Odense University Hospital during one year...

  1. The taxonomy of brain cancer stem cells: what's in a name?

    OpenAIRE

    Gutmann, David H.

    2014-01-01

    With the increasing recognition that stem cells play vital roles in the formation, maintenance, and potential targeted treatment of brain tumors, there has been an exponential increase in basic laboratory and translational research on these cell types. However, there are several different classes of stem cells germane to brain cancer, each with distinct capabilities and functions. In this perspective, we discuss the types of stem cells relevant to brain tumor pathogenesis, and suggest a nomen...

  2. Targeting Neuronal Networks with Combined Drug and Stimulation Paradigms Guided by Neuroimaging to Treat Brain Disorders.

    Science.gov (United States)

    Faingold, Carl L; Blumenfeld, Hal

    2015-10-01

    Improved therapy of brain disorders can be achieved by focusing on neuronal networks, utilizing combined pharmacological and stimulation paradigms guided by neuroimaging. Neuronal networks that mediate normal brain functions, such as hearing, interact with other networks, which is important but commonly neglected. Network interaction changes often underlie brain disorders, including epilepsy. "Conditional multireceptive" (CMR) brain areas (e.g., brainstem reticular formation and amygdala) are critical in mediating neuroplastic changes that facilitate network interactions. CMR neurons receive multiple inputs but exhibit extensive response variability due to milieu and behavioral state changes and are exquisitely sensitive to agents that increase or inhibit GABA-mediated inhibition. Enhanced CMR neuronal responsiveness leads to expression of emergent properties--nonlinear events--resulting from network self-organization. Determining brain disorder mechanisms requires animals that model behaviors and neuroanatomical substrates of human disorders identified by neuroimaging. However, not all sites activated during network operation are requisite for that operation. Other active sites are ancillary, because their blockade does not alter network function. Requisite network sites exhibit emergent properties that are critical targets for pharmacological and stimulation therapies. Improved treatment of brain disorders should involve combined pharmacological and stimulation therapies, guided by neuroimaging, to correct network malfunctions by targeting specific network neurons.

  3. Combined modality preoperative therapy for unresectable rectal cancer.

    Science.gov (United States)

    Percarpio, B; Bitterman, J; Sabbath, K; Alfano, F; Ruszkowski, R; Bowen, J

    1992-01-01

    Locally advanced rectal cancer has been a surgical challenge because of fixation of the primary tumor to the boney pelvis or to other pelvic soft tissues. During a 12-month period seven patients with locally advanced adenocarcinoma of the rectum were treated preoperatively with simultaneous pelvic irradiation (4500-5040 cGy) and infusion chemotherapy (5-fluorouracil 1000 mg per m2 per day over 96 hours and mitomycin 10 mg per m2. Tolerance was reasonable and all patients underwent successful resection of the primary lesion. Two patients had a complete response to preoperative combined modality therapy with no cancer found in the surgical specimen. With a short follow-up period, all patients have experienced satisfactory healing and none have suffered local or distant recurrence. The results of this limited series are encouraging for future clinical trials.

  4. Combining stereotactic radiosurgery and systemic therapy for brain metastases: a potential role for temozolomide

    Directory of Open Access Journals (Sweden)

    Matthew E Hardee

    2012-08-01

    Full Text Available Brain metastases are unfortunately very common in the natural history of many solid tumors and remain a life-threatening condition, associated with a dismal prognosis, despite many clinical trials aimed at improving outcomes. Radiation therapy options for brain metastases include whole brain radiotherapy (WBRT and stereotactic radiosurgery (SRS. SRS avoids the potential toxicities of WBRT and is associated with excellent local control rates. However, distant intracranial failure following SRS remains a problem, suggesting that untreated intracranial micrometastatic disease is responsible for failure of treatment. The oral alkylating agent temozolomide (TMZ, which has demonstrated efficacy in primary malignant central nervous system tumors such as glioblastoma, has been used in early phase trials in the treatment of established brain metastases. Although results of these studies in established, macroscopic metastatic disease have been modest at best, there is clinical and preclinical data to suggest that TMZ is more efficacious at treating and controlling clinically undetectable intracranial micrometastatic disease. We review the available data for the primary management of brain metastases with SRS, as well as the use of TMZ in treating established brain metastases and undetectable micrometastatic disease, and suggest the role for a clinical trial with the aims of treating macroscopically visible brain metastases with SRS combined with TMZ to address microscopic, undetectable disease.

  5. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

    Directory of Open Access Journals (Sweden)

    Zhiwei Zheng

    2015-01-01

    Full Text Available Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age.

  6. Pesticides and brain cancer linked in orchard farmers of Kashmir

    Directory of Open Access Journals (Sweden)

    Bhat Abdul

    2010-12-01

    338 were unrelated to pesticides. Out of 389 patients, 71.7% (279 out of 389 were males and 28.3% (110 out of 389 including 7 members of three families, 6 were females and 1 male. Conclusion: All orchard-related 389 patients had high grade tumors as compared to the non-pesticide tumors. Mortality in pesticide exposed tumors was 12%. Higher levels of SCE were found in 31.9% (124 out of 389 patients and decreased levels in only 45.3% (176 out of 389 orchard-related patients. The significant case/control odds ratio (OR of 0.28, hospital control SCE OR of 1.1 and family control SCE OR of 1.5, points the finger of suspicion toward the link between pesticides and brain cancer.

  7. Combined liquid and solid-phase extraction improves quantification of brain estrogen content

    Directory of Open Access Journals (Sweden)

    Andrew eChao

    2011-09-01

    Full Text Available Accuracy in quantifying brain-derived steroid hormones (‘neurosteroids’ has become increasingly important for understanding the modulation of neuronal activity, development, and physiology. Relative to other neuroactive compounds and classical neurotransmitters, steroids pose particular challenges with regard to isolation and analysis, owing to their lipid solubility. Consequently, anatomical studies of the distribution of neurosteroids have relied primarily on the expression of neurosteroid synthesis enzymes. To evaluate the distribution of synthesis enzymes vis-à-vis the actual steroids themselves, traditional steroid quantification assays, including radioimmunoassays (RIA, have successfully employed liquid extraction methods (e.g., ether, dichloromethane or methanol to isolate steroids from microdissected brain tissue. Due to their sensitivity, safety and reliability, the use of commercial enzyme immunoassays (EIA for laboratory quantification of steroids in plasma and brain has become increasingly widespread. However, EIAs rely on enzymatic reactions in vitro, making them sensitive to interfering substances in brain tissue and thus producing unreliable results. Here, we evaluate the effectiveness of a protocol for combined, two-stage liquid/solid phase extraction as compared to conventional liquid extraction alone for the isolation of estradiol (E2 from brain tissue. We employ the songbird model system, in which brain steroid production is pronounced and linked to neural mechanisms of learning and plasticity. This study outlines a combined liquid-solid phase extraction protocol that improves the performance of a commercial EIA for the quantification of brain E2 content. We demonstrate the effectiveness of our optimized method for evaluating the region specificity of brain E2 content, compare these results to established anatomy of the estrogen synthesis enzyme and estrogen receptor, and discuss the nature of potential EIA interfering

  8. Combined androgen blockade in the treatment of advanced prostate cancer--an overview. The Scandinavian Prostatic Cancer Group

    DEFF Research Database (Denmark)

    Iversen, P

    1997-01-01

    The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed.......The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed....

  9. Preoperative staging of lung cancer with combined PET-CT

    DEFF Research Database (Denmark)

    Fischer, Barbara; Lassen, Ulrik; Mortensen, Jann;

    2009-01-01

    BACKGROUND: Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC...... one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause...

  10. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    Directory of Open Access Journals (Sweden)

    Couraud Pierre-Olivier

    2009-07-01

    Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

  11. Family history of cancer in benign brain tumor subtypes versus gliomas

    Directory of Open Access Journals (Sweden)

    Quinn eOstrom

    2012-02-01

    Full Text Available Purpose: Family history is associated with gliomas, but this association has not ben established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study (OBTS. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%, 78 meningioma (65%, 49 pituitary adenoma (73.1% and 152 glioma patients (58.2%. The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs and 95% confidence intervals (95% CI. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusions: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  12. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    Science.gov (United States)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  13. Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Imam, Ayesha M; Jin, Guang; Sillesen, Martin;

    2013-01-01

    Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the assoc......Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well...

  14. Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain.

    Science.gov (United States)

    Palmieri, Diane; Bronder, Julie L; Herring, Jeanne M; Yoneda, Toshiyuki; Weil, Robert J; Stark, Andreas M; Kurek, Raffael; Vega-Valle, Eleazar; Feigenbaum, Lionel; Halverson, Douglas; Vortmeyer, Alexander O; Steinberg, Seth M; Aldape, Kenneth; Steeg, Patricia S

    2007-05-01

    Retrospective studies of breast cancer patients suggest that primary tumor Her-2 overexpression or trastuzumab therapy is associated with a devastating complication: the development of central nervous system (brain) metastases. Herein, we present Her-2 expression trends from resected human brain metastases and data from an experimental brain metastasis assay, both indicative of a functional contribution of Her-2 to brain metastatic colonization. Of 124 archival resected brain metastases from breast cancer patients, 36.2% overexpressed Her-2, indicating an enrichment in the frequency of tumor Her-2 overexpression at this metastatic site. Using quantitative real-time PCR of laser capture microdissected epithelial cells, Her-2 and epidermal growth factor receptor (EGFR) mRNA levels in a cohort of 12 frozen brain metastases were increased up to 5- and 9-fold, respectively, over those of Her-2-amplified primary tumors. Co-overexpression of Her-2 and EGFR was also observed in a subset of brain metastases. We then tested the hypothesis that overexpression of Her-2 increases the colonization of breast cancer cells in the brain in vivo. A subclone of MDA-MB-231 human breast carcinoma cells that selectively metastasizes to brain (231-BR) overexpressed EGFR; 231-BR cells were transfected with low (4- to 8-fold) or high (22- to 28-fold) levels of Her-2. In vivo, in a model of brain metastasis, low or high Her-2-overexpressing 231-BR clones produced comparable numbers of micrometastases in the brain as control transfectants; however, the Her-2 transfectants yielded 3-fold greater large metastases (>50 microm(2); P < 0.001). Our data indicate that Her-2 overexpression increases the outgrowth of metastatic tumor cells in the brain in this model system. PMID:17483330

  15. Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells.

    Science.gov (United States)

    Cirone, Pasquale; Bourgeois, Jacqueline M; Shen, Feng; Chang, Patricia L

    2004-10-01

    An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to pass by diffusion. This strategy was applied to the treatment of cancer with some success by delivering either interleukin 2 or angiostatin. However, as cancer is a complex, multifactorial disease, a multipronged approach is now being developed to attack tumorigenesis via multiple pathways in order to improve treatment efficacy. A combination of immunotherapy with angiostatic therapy was investigated by treating B16-F0/neu melanoma-bearing mice with intraperitoneally implanted, microencapsulated mouse myoblasts (C2C12) genetically modified to deliver angiostatin and an interleukin 2 fusion protein (sFvIL-2). The combination treatment resulted in improved survival, delayed tumor growth, and increased histological indices of antitumor activity (apoptosis and necrosis). In addition to improved efficacy, the combination treatment also ameliorated some of the undesirable side effects from the individual treatments that have led to the previous failure of the single treatments, for example, inflammatory response to IL-2 or vascular mimicry due to angiostatin. In conclusion, the combination of immuno- and antiangiogenic therapies delivered by immunoisolated cells was superior to individual treatments for antitumorigenesis activity, not only because of their known mechanisms of action but also because of unexpected protection against the adverse side effects of the single treatments. Thus, the concept of a "cocktail" strategy, with microencapsulation delivering multiple antitumor recombinant molecules to improve efficacy, is validated. PMID:15585110

  16. A case of leukoencephalopathy caused by radiation and chemotherapy for brain metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Shigeru; Sonoo, Hiroshi; Nomura, Tsunehisa; Ohkubo, Sumiko; Yamamoto, Yutaka; Tanaka, Katsuhiro; Kurebayashi, Junichi; Hiratsuka, Junichi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    2002-08-01

    A case of treatment-related leukoencephalopathy is presented. A patient with breast cancer metastasis to the brain, liver, bone and distant lymph nodes was treated with whole brain radiation and docetaxcel. Eleven months after radiation, magnetic resonance imaging showed diffuse leukoencephalopathy. Twenty-two months after radiation, the patient had gait disturbance, parkinsonism, dementia and urinary incontinence. From this experience, stereotactic radiosurgery such as cyber knife and gamma knife therapy, representing a new modality for delivering intense focal radiation, should be come preferred techniques for treating patients with brain metastases, to avoid the potential cognitive side effects of fractionated whole-brain radiotherapy. (author)

  17. High risk factors of brain metastases in 295 patients with advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    YAN Min; L(U) Hui-min; LIU Zhen-zhen; LIU Hui; ZHANG Meng-wei; SUN Xi-bin; CUI Shu-de

    2013-01-01

    Background The incidence of brain metastases in patients with breast cancer is approximately 10%-16%,and survival after diagnosis of brain metastases is usually short.This study was designed to evaluate the risk factors associated with brain metastases in advanced breast cancer patients,with a view to help predict patient groups with high risk of brain metastases.Methods In total,295 patients with advanced breast cancer were evaluated.All patients were pathologically confirmed and metastatic lesions were confirmed pathologically or by imaging.All patients were examined at least once every 6 months with head CT or MRI.Patients showing symptoms underwent immediate inspection,and brain metastatic lesions were confirmed by head CT and/or MRI.Results At a median follow-up of 12 months from the occurrence of metastases,brain metastases had occurred in 49 patients (16.6%).In our univariate analysis,variables significantly related to increased risk of brain metastases were hormone receptor-negative tumors,epidermal growth factor receptor 2 (HER2)-positive tumors,and multiple distant metastases.Patients with dominant tumor sites in soft tissue,or defined as Luminal A subtype,tended to have a lower risk of brain metastases than patients with visceral metastases,Luminal B subtype,triple-negative subtype or HER2-enriched subtype tumors.Conclusions Our results strongly suggest that factors such as Luminal B,triple-negative,and HER2-enriched subtypes are high risk factors for brain metastases.These data,therefore,provide pivotal clinical evidence towards a comprehensive understanding of the risk factors of brain metastases in advanced breast cancer patients.

  18. Intensity-based registration and combined visualization of multimodal brain images for noninvasive epilepsy surgery planning

    Science.gov (United States)

    Hong, Helen; Shin, Yeong G.

    2003-05-01

    To visualize the brain anatomy, seizure focus location and grid and strip electrode in 3-dimensional space provides improved planning information for focus localization and margin determination pre- and intra-operatively. However given the relatively poor spatial resolution and structural detail of the PET images, it can be difficult to recognize precise anatomic localization of the site of increased activation during seizure. In this paper, we present an intensity-based registration and combined visualization of CT, MR and PET brain images to provide both critical functional information and the structural details.

  19. Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1-3 brain metastasis: a multi institutional study

    International Nuclear Information System (INIS)

    To determine the outcome of patients with brain metastasis (BM) from lung cancer treated with an external beam radiotherapy boost (RTB) after whole brain radiotherapy (WBRT). A total of 53 BM patients with lung cancer were treated sequentially with WBRT and RTB between 1996 and 2008 according to our institutional protocol. Mean age was 58.8 years. The median KPS was 90. Median recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) grouping were 2 and 2.5, respectively. Surgery was performed on 38 (71%) patients. The median number of BM was 1 (range, 1-3). Median WBRT and RTB combined dose was 39 Gy (range, 37.5 - 54). Median follow-up was 12.0 months. During the period of follow-up, 37 (70%) patients died. The median overall survival (OS) was 14.5 months. Only 13 patients failed in the brain. The majority of patients (n = 29) failed distantly. The 1-year OS, -local control, extracranial failure rates were 61.2%, 75.2% and 60.8%, respectively. On univariate analysis, improved OS was found to be significantly associated with total dose (≤ 39 Gy vs. > 39 Gy; p < 0.01), age < 65 (p < 0.01), absence of extracranial metastasis (p < 0.01), GPA ≥ 2.5 (p = 0.01), KPS ≥ 90 (p = 0.01), and RPA < 2 (p = 0.04). On multivariate analysis, total dose (p < 0.01) and the absence of extracranial metastasis (p = 0.03) retained statistical significance. The majority of lung cancer patients treated with WBRT and RTB progressed extracranially. There might be a subgroup of younger patients with good performance status and no extracranial disease who may benefit from dose escalation after WBRT to the metastatic site

  20. Relaxins enhance growth of spontaneous murine breast cancers as well as metastatic colonization of the brain.

    Science.gov (United States)

    Binder, Claudia; Chuang, Eugenia; Habla, Christina; Bleckmann, Annalen; Schulz, Matthias; Bathgate, Ross; Einspanier, Almuth

    2014-01-01

    Relaxins are known for their tissue remodeling capacity which is also a hallmark of cancer progression. However, their role in the latter context is still unclear, particularly in breast cancer. In a mouse model with spontaneously arising breast cancer due to erbB2-overexpression we show that exposure to porcine relaxin results in significantly enhanced tumour growth as compared to control animals. This is accompanied by increased serum concentrations of progesterone and estradiol as well as elevated expression of the respective receptors and the relaxin receptor RXFP1 in the tumour tissue. It is also associated with enhanced infiltration by tumour-associated macrophages which are known to promote tumour progression. Additionally, we show in an ex vivo model of metastatic brain colonization that porcine relaxin as well as human brain-specific relaxin-3 promotes invasion into the brain tissue and enhance interaction of breast cancer cells with the resident brain macrophages, the microglia. Relaxin signaling is mediated via RXFP1, since R 3/I5, a specific agonist of the relaxin-3 receptor RXFP3 in the brain, does not significantly enhance invasion. Taken together, these findings strongly support a role of relaxins in the progression of breast cancer where they foster primary tumour growth as well as metastatic colonization by direct and indirect means. PMID:23963762

  1. Combined compared to dissociated oral and intestinal sucrose stimuli induce different brain hedonic processes

    Directory of Open Access Journals (Sweden)

    Caroline eClouard

    2014-08-01

    Full Text Available The characterization of brain networks contributing to the processing of oral and/or intestinal sugar signals in a relevant animal model might help to understand the neural mechanisms related to the control of food intake in humans and suggest potential causes for impaired eating behaviors. This study aimed at comparing the brain responses triggered by oral and/or intestinal sucrose sensing in pigs. Seven animals underwent brain single photon emission computed tomography (99mTc-HMPAO further to oral stimulation with neutral or sucrose artificial saliva paired with saline or sucrose infusion in the duodenum, the proximal part of the intestine. Oral and/or duodenal sucrose sensing induced differential cerebral blood flow (CBF changes in brain regions known to be involved in memory, reward processes and hedonic (i.e. pleasure evaluation of sensory stimuli, including the dorsal striatum, prefrontal cortex, cingulate cortex, insular cortex, hippocampus and parahippocampal cortex. Sucrose duodenal infusion only and combined sucrose stimulation induced similar activity patterns in the putamen, ventral anterior cingulate cortex and hippocampus. Some brain deactivations in the prefrontal and insular cortices were only detected in the presence of oral sucrose stimulation. Finally, activation of the right insular cortex was only induced by combined oral and duodenal sucrose stimulation, while specific activity patterns were detected in the hippocampus and parahippocampal cortex with oral sucrose dissociated from caloric load. This study sheds new light on the brain hedonic responses to sugar and has potential implications to unravel the neuropsychological mechanisms underlying food pleasure and motivation.

  2. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    International Nuclear Information System (INIS)

    Research highlights: → The most important therapeutic tool in brain metastasis is radiation therapy. → Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. → Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. → Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  3. Extremely low frequency electromagnetic fields (EMF) and brain cancer in adults and children: review and comment.

    Science.gov (United States)

    Gurney, J. G.; van Wijngaarden, E.

    1999-01-01

    Epidemiologic and experimental research on the potential carcinogenic effects of extremely low frequency electromagnetic fields (EMF) has now been conducted for over two decades. Cancer epidemiology studies in relation to EMF have focused primarily on brain cancer and leukemia, both from residential sources of exposure in children and adults and from occupational exposure in adult men. Because genotoxic effects of EMF have not been shown, most recent laboratory research has attempted to show biological effects that could be related to cancer promotion. In this report, we briefly review residential and occupational EMF studies on brain cancer. We also provide a general review of experimental studies as they relate both to the biological plausibility of an EMF-brain cancer relation and to the insufficiency of such research to help guide exposure assessment in epidemiologic studies. We conclude from our review that no recent research, either epidemiologic or experimental, has emerged to provide reasonable support for a causal role of EMF on brain cancer. PMID:11550314

  4. Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Heekyoung [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Cancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Yoon, Su Jin [Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Jin, Juyoun [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Cancer Stem Cell Research Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Choi, Seung Ho [Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); Seol, Ho Jun; Lee, Jung-Il [Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of); and others

    2011-03-04

    Research highlights: {yields} The most important therapeutic tool in brain metastasis is radiation therapy. {yields} Radiosensitivity of cancer cells was enhanced with treatment of Chk1 inhibitor. {yields} Depletion of Chk1 in cancer cells showed an enhancement of sensitivity to radiation. {yields} Chk1 can be a good target for enhancement of radiosensitivity. -- Abstract: The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, signal pathways about DNA damage checkpoints after irradiation have been noticed. We investigated the radiosensitivity can be enhanced with treatment of Chk1 inhibitor, AZD7762 in lung cancer cell lines and xenograft models of lung cancer brain metastasis. Clonogenic survival assays showed enhancement of radiosensitivity with AZD7762 after irradiation of various doses. AZD7762 increased ATR/ATM-mediated Chk1 phosphorylation and stabilized Cdc25A, suppressed cyclin A expression in lung cancer cell lines. In xenograft models of lung cancer (PC14PE6) brain metastasis, AZD7762 significantly prolonged the median survival time in response to radiation. Depletion of Chk1 using shRNA also showed an enhancement of sensitivity to radiation in PC14PE6 cells. The results of this study support that Chk1 can be a good target for enhancement of radiosensitivity.

  5. Molecular Genetics Techniques to Develop New Treatments for Brain Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Jacob; Fathallan-Shaykh, Hassan

    2006-09-22

    The objectives of this report are: (1) to devise novel molecular gene therapies for malignant brain tumors, (2) advance our understanding of the immune system in the central nervous system; and (3) apply genomics to find molecular probes to diagnose brain tumors, predict prognosis, biological behavior and their response to treatment.

  6. Brain

    Science.gov (United States)

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  7. New and emerging combination therapies for esophageal cancer

    International Nuclear Information System (INIS)

    Esophageal cancer comprises two different histological forms – squamous cell carcinoma (SCC) and adenocarcinoma (AC). While the incidence of AC has increased steeply in Western countries during the last few years, the incidence of SCC is fairly stable. Both forms differ in pathogenesis and response to chemotherapy and radiation therapy. Plenty of studies have evaluated new chemotherapy combination regimens in the neoadjuvant, adjuvant, and palliative setting. In addition, new radiation and chemoradiation protocols have been investigated. Finally, molecular-targeted therapy has been included in several new randomized prospective trials. Therefore, this review presents new data on this topic and critically discusses promising approaches towards a more effective treatment in a disease with a grim prognosis

  8. Optimal Multitrial Prediction Combination and Subject-Specific Adaptation for Minimal Training Brain Switch Designs.

    Science.gov (United States)

    Spyrou, Loukianos; Blokland, Yvonne; Farquhar, Jason; Bruhn, Jorgen

    2016-06-01

    Brain-Computer Interface (BCI) systems are traditionally designed by taking into account user-specific data to enable practical use. More recently, subject independent (SI) classification algorithms have been developed which bypass the subject specific adaptation and enable rapid use of the system. A brain switch is a particular BCI system where the system is required to distinguish from two separate mental tasks corresponding to the on-off commands of a switch. Such applications require a low false positive rate (FPR) while having an acceptable response time (RT) until the switch is activated. In this work, we develop a methodology that produces optimal brain switch behavior through subject specific (SS) adaptation of: a) a multitrial prediction combination model and b) an SI classification model. We propose a statistical model of combining classifier predictions that enables optimal FPR calibration through a short calibration session. We trained an SI classifier on a training synchronous dataset and tested our method on separate holdout synchronous and asynchronous brain switch experiments. Although our SI model obtained similar performance between training and holdout datasets, 86% and 85% for the synchronous and 69% and 66% for the asynchronous the between subject FPR and TPR variability was high (up to 62%). The short calibration session was then employed to alleviate that problem and provide decision thresholds that achieve when possible a target FPR=1% with good accuracy for both datasets. PMID:26529768

  9. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    Directory of Open Access Journals (Sweden)

    Picano Eugenio

    2012-04-01

    Full Text Available Abstract Background According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906, the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Results Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of Conclusions At this point, a systematic assessment of brain (cancer and non-cancer effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed.

  10. Combining Object Detection And Brain Computer Interfacing: Towards A New Way Of Subject-Environment Interaction

    OpenAIRE

    Robben, Arne; Chumerin, Nikolay; Manyakov, Nikolay V.; Combaz, Adrien; van Vliet, Marijn; Hulle, Marc van

    2011-01-01

    In this paper we propose an application which combines two research disciplines: object detection and brain-computer interfacing. It is in particular useful for patients suffering from a severe motor impairment which prevents them to interact with their surrounding environment. The application shows an image of e.g., the room of the patient, on a computer screen and searches for instances of certain objects in the image. When these are found, a flashing dot appears on top of them, flickering ...

  11. Subject Combination and Electrode Selection in Cooperative Brain-Computer Interface Based on Event Related Potentials

    OpenAIRE

    Hubert Cecotti; Bertrand Rivet

    2014-01-01

    New paradigms are required in Brain-Computer Interface (BCI) systems for the needs and expectations of healthy people. To solve this issue, we explore the emerging field of cooperative BCIs, which involves several users in a single BCI system. Contrary to classical BCIs that are dependent on the unique subject’s will, cooperative BCIs are used for problem solving tasks where several people shall be engaged by sharing a common goal. Similarly as combining trials over time improves performance,...

  12. MAP training: combining meditation and aerobic exercise reduces depression and rumination while enhancing synchronized brain activity

    OpenAIRE

    Alderman, B L; Olson, R L; Brush, C J; Shors, T. J.

    2016-01-01

    Mental and physical (MAP) training is a novel clinical intervention that combines mental training through meditation and physical training through aerobic exercise. The intervention was translated from neuroscientific studies indicating that MAP training increases neurogenesis in the adult brain. Each session consisted of 30 min of focused-attention (FA) meditation and 30 min of moderate-intensity aerobic exercise. Fifty-two participants completed the 8-week intervention, which consisted of t...

  13. Effect of combined naltrexone and bupropion therapy on the brain's reactivity to food cues

    OpenAIRE

    Wang, G-J; Tomasi, D; Volkow, N. D.; R. Wang; Telang, F.; Caparelli, E. C.; Dunayevich, E

    2013-01-01

    Objective: The significant weight loss observed with combination naltrexone-sustained release (SR) 32 mg and bupropion SR 360 mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment. Methods: Forty women (31...

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

    OpenAIRE

    Kong, Doo-Sik

    2012-01-01

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

  15. MicroRNAs Linked to Trastuzumab Resistance, Brain Metastases | Division of Cancer Prevention

    Science.gov (United States)

    Researchers have tied increased levels of a microRNA (miRNA) to resistance to the targeted therapy trastuzumab (Herceptin) in women with HER2-positive breast cancer. Another research team has discovered a “signature” of miRNAs in brain metastases in patients with melanoma—a signature that is also present in the primary tumor and could identify melanoma patients at increased risk of brain metastases. |

  16. New Breast Cancer Recursive Partitioning Analysis Prognostic Index in Patients With Newly Diagnosed Brain Metastases

    International Nuclear Information System (INIS)

    Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4 months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of ≤60. Class II included all other cases. Conclusions: The breast cancer RPA prognostic index is an easy and valuable tool for use in clinical practice. It can select patients who require aggressive treatment and those in whom whole-brain radiotherapy or symptomatic therapy is the most reasonable option. An individual approach is required for patients from prognostic Class II.

  17. Intracranial arterial infusion chemotherapy for lung cancer complicated by brain metastases: a clinical observation

    International Nuclear Information System (INIS)

    Objective: T evaluate the efficacy of intracranial arterial infusion chemotherapy in treating advanced lung cancer with brain metastases and to discuss the factors influencing prognosis. Methods: From September 2007 to August 2008, a total of 27 patients of lung cancer with brain metastases received intracranial arterial infusion chemotherapy. This procedure was performed every 4 weeks for three times in succession. Follow-up brain MRI was regularly performed at intervals of eight weeks after the treatment in order to evaluate the therapeutic efficacy, which was conducted until the disease became worse or the patient could tolerate the drug toxicity no longer. Results: All 27 cases were treated 3 times at least, and one case received 7 times. Of the 27 cases, partial response was obtained in 15 (55.6%), stable condition in 8 (29.6%) and deterioration in 4 (14.8%), although no one showed complete alleviation. The effective rate for intracranial lesions was 55.6% (15/27) and the 85.2% of lesions (23/27) were brought under control. Overall median survival time was 7 months. The 6-month survival rate and 1-year survival rate were 81.5% and 14.8%, respectively. Conclusion: Intracranial arterial infusion chemotherapy is one of the most effective methods for the treatment of lung cancer associated with brain metastases. Karnofsky performance status ≥ 60 and absent of extra cranial metastases are good prognostic factors for lung cancer patients with brain metastases. (authors)

  18. Micronucleus formation induced by dielectric barrier discharge plasma exposure in brain cancer cells

    Science.gov (United States)

    Kaushik, Nagendra K.; Uhm, Hansup; Ha Choi, Eun

    2012-02-01

    Induction of micronucleus formation (cytogenetic damage) in brain cancer cells upon exposure of dielectric barrier discharge plasma has been investigated. We have investigated the influence of exposure and incubation times on T98G brain cancer cells by using growth kinetic, clonogenic, and micronucleus formation assay. We found that micronucleus formation rate directly depends on the plasma exposure time. It is also shown that colony formation capacity of cells has been inhibited by the treatment of plasma at all doses. Cell death and micronucleus formation are shown to be significantly elevated by 120 and 240 s exposure of dielectric barrier discharge plasma.

  19. Hemorrhage of brain metastasis from non-small cell lung cancer post gefitinib therapy: two case reports and review of the literature

    Directory of Open Access Journals (Sweden)

    Liao Xin-Biao

    2010-02-01

    Full Text Available Abstract Background Gefitinib is one of the small molecule inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR TKIs. Clinical trials have demonstrated it is effective for treatment of a subset of patients with advanced non-small cell lung cancer (NSCLC. Gefitinib has been generally considered to be a relatively safe agent. Besides a small proportion of fatal interstitial pneumonia, the common adverse drug reactions of gefitinib include diarrhea and skin rash, which are generally mild and reversible. Herein, we report the first two cases of brain metastasis hemorrhage that might be involved with the use of gefitinib. Case presentation Two patients with brain metastasis from NSCLC developed brain hemorrhage after gefitinib therapy. The hemorrhage in one case occurred one month after gefitinib combined with whole brain radiation therapy (WBRT, and in the another case hemorrhage developed slowly within brain metastases eight months post gefitinib monotherapy for diffuse pulmonary metastasis from a lung cancer undergone surgical removal previously. Conclusion We speculate brain hemorrhage could be one of the adverse drug reactions of gefitinib treatment for NSCLC and suggest clinicians be aware of this possible rare entity. More data are needed to confirm our findings, especially when gefitinib is used in the settings of brain metastases from NSCLC or other origins.

  20. Systemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: an overview of the literature.

    Science.gov (United States)

    Lombardi, Giuseppe; Di Stefano, Anna Luisa; Farina, Patrizia; Zagonel, Vittorina; Tabouret, Emeline

    2014-09-01

    The frequency of metastatic brain tumors has increased over recent years; the primary tumors most involved are breast cancer, lung cancer, melanoma and renal cell carcinoma. While radiation therapy and surgery remain the mainstay treatment in selected patients, new molecular drugs have been developed for brain metastases. Studies so far report interesting results. This review focuses on systemic cytotoxic drugs and, in particular, on new targeted therapies and their clinically relevant activities in brain metastases from solid tumors in adults.

  1. Long-term outcome of gamma knife radiosurgery for metastatic brain tumors  originating from lung cancer

    OpenAIRE

    Bir, Shyamal C.; Sudheer Ambekar; Papireddy Bollam; Anil Nanda

    2014-01-01

    Background: Gamma knife radiosurgery (GKRS) has emerged as an important treatment option for metastasis brain tumors (MBTs). However, the long-term outcome of GKRS on MBTs originating from lung carcinoma is not well understood. The treatment of MBTs derived from lung cancer with GKRS at our institution is reviewed. Methods: We performed a retrospective review (2000-2013) of 173 patients with MBTs from lung cancer who received GKRS. Out of 173 patients, 38 patients had recurrent tumors aft...

  2. Role of infectious agents in the carcinogenesis of brain and head and neck cancers

    Directory of Open Access Journals (Sweden)

    Alibek Kenneth

    2013-02-01

    Full Text Available Abstract This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV in distinct types of brain tumour, namely glioblastoma multiforme (GBM and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV and nasopharyngeal carcinoma (NPC. Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV and head and neck squamous cell carcinoma (HNSCC; specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90% and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of

  3. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

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

    Science.gov (United States)

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

    2016-06-01

    Many types of tumors are organized in a hierarchy of heterogeneous cell populations. The cancer stem-like cells (CSCs) hypothesis suggests that tumor development and metastasis are driven by a minority population of cells, which are responsible for tumor initiation, growth and recurrences. The inability to efficiently eliminate CSCs during chemotherapy, together with CSCs being highly tumorigenic and invasive, may result in treatment failure due to cancer relapse and metastases. CSCs are emerging as a promising target for the development of translational cancer therapies. Ideal panacea for cancer would kill all malignant cells, including CSCs and bulk tumor cells. Since both chemotherapy and CSCs-specific therapy are insufficient to cure cancer, we propose combination therapy with CSCs-targeted agents and chemotherapeutics for improved breast cancer treatment. We generated in vitro mammosphere of 2 breast cancer cell lines, and demonstrated ability of mammospheres to grow and enrich cancer cells with stem-like properties, including self-renewal, multilineage differentiation and enrichment of cells expressing breast cancer stem-like cell biomarkers CD44(+)/CD24(-/low). The formation of mammospheres was significantly inhibited by salinomycin, validating its pharmacological role against the cancer stem-like cells. In contrast, paclitaxel showed a minimal effect on the proliferation and growth of breast cancer stem-like cells. While combination therapies of salinomycin with conventional chemotherapy (paclitaxel or lipodox) showed a potential to improve tumor cell killing, different subtypes of breast cancer cells showed different patterns in response to the combination therapies. While optimization of combination therapy is warranted, the design of combination therapy should consider phenotypic attributes of breast cancer types. PMID:27259361

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

    Science.gov (United States)

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

    2016-06-01

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

  6. A multimodality imaging model to track viable breast cancer cells from single arrest to metastasis in the mouse brain

    Science.gov (United States)

    Parkins, Katie M.; Hamilton, Amanda M.; Makela, Ashley V.; Chen, Yuanxin; Foster, Paula J.; Ronald, John A.

    2016-01-01

    Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i.e., iron-loaded cells) on day 0 significantly correlated with BLI signal. Both BLI and MRI signals decreased from day 0 to day 8, indicating a loss of viable cells rather than a loss of iron label. Total brain MR tumour volume on day 28 also correlated with BLI signal. Overall, BLI complemented our sensitive cellular MRI technologies well, allowing us for the first time to screen animals for successful injections, and, in addition to MR measures of cell arrest and tumor burden, provided longitudinal measures of cancer cell viability in individual animals. We predict this novel multimodality molecular imaging framework will be useful for evaluating the efficacy of emerging anti-cancer drugs at different stages of the metastatic cascade. PMID:27767185

  7. Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes.

    Science.gov (United States)

    Mohamed, Tarek Mostafa; Ghaffar, Hamdy M Abdel; El Husseiny, Rabee M R

    2015-12-01

    The present study is an unsubstantiated qualitative assessment of the abused drugs-tramadol and clonazepam. The aim of this study is to evaluate whether the effects of tramadol, clonazepam, and their combination on mitochondrial electron transport chain (ETC) complexes were influential at therapeutic or at progressively increasing doses. The study comprised of a total of 70 healthy male rats, aged 3 months. According to the drug intake regimen, animals were divided into seven groups: control, tramadol therapeutic, clonazepam therapeutic, combination therapeutic, tramadol abuse, clonazepam abuse, and combination abuse group. At the end of the experiment, brain mitochondrial ETC complexes (I, II, III, and IV) were evaluated. Histopathological examinations were also performed on brain tissues. The results showed that groups that received tramadol (therapeutic and abuse) suffered from weight loss. Tramadol abuse group and combination abuse group showed significant decrease in the activities of I, III, and IV complexes but not in the activity of complex II. In conclusion, tramadol but not clonazepam has been found to partially inhibit the activities of respiratory chain complexes I, III, and IV but not the activity of complex II and such inhibition occurred only at doses that exceeded the maximum recommended adult human daily therapeutic doses. This result explains the clinical and histopathological effects of tramadol, such as seizures and red neurons (marker for apoptosis), respectively. PMID:23843224

  8. Combined interstitial and percutaneous radiotherapy for localized prostate cancer

    International Nuclear Information System (INIS)

    Objectives: To test the feasibility and effectiveness of a combined interstitial and percutaneous radiotherapy approach for localized prostate cancer a prospective phase II trial was carried out. Methods: Between 10/92 and 12/94 89 evaluable patients (pts.) were treated. All of the patients were pathologically proven node negative by laparoscopic node dissection of the fossa obturatoria region. T1c-3 tumours according to the classification system of 1992 were one, 24 and 64, respectively. During the first and second week 9Gy each (10/92-12/93: 10Gy each) were given interstitial with high-dose-rate 192Iridium brachytherapy to the prostate and tumour extension beyond the capsule. After this a percutaneous 4 field box irradiation was given to the prostate to a dose of 45Gy/25 fractions (10/92-12/93: 40Gy/20 fx). Results: A PSA value above 3 ng/ml before starting treatment was found in 85% (74/87) with a median PSA of 15 ng/ml. Median PSA three and 12 months (mos.) after completion of therapy was 1.17 and 0.85 ng/ml, respectively. A PSA relapse was found in 18.6% (13/70). 31 of 45 pts. (69%) had negative punch biopsies 12 months after therapy, 8 of 10 pts. had negative biopsies after 24 mos. A positive biopsy combined with a PSA value above 3 ng/ml were scheduled as local failure and were observed in 15.6% (7/45). Acute side effects were as follows: no grade 3 or 4 cystitis/diarrhoea, bladder tamponade (completely healed after rinsing) 2.2% (2/89), proctitis grade 1 13.7% (10/73) and grade 2 1.4% (1/73) and no grade 3 or 4 reaction. Late side effects: no cystitis nor urethral stricture, proctitis (12 mos. after treatment) grade 1 13.6% (9/66), no grade 2 or 3. Severe side effects were observed in two pts. with additionally risk factors (colitis ulcerosa; diabetes mellitus): they were temporary lost in follow-up and have biopsies of the anterior rectal wall elsewhere for late proctitis and developed a rectourethral fistula requiring colostomy both, but not in the high

  9. Multi-study integration of brain cancer transcriptomes reveals organ-level molecular signatures.

    Directory of Open Access Journals (Sweden)

    Jaeyun Sung

    Full Text Available We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone. These signatures were based on a new method reported herein--Identification of Structured Signatures and Classifiers (ISSAC--that resulted in a brain cancer marker panel of 44 unique genes. Many of these genes have established relevance to the brain cancers examined herein, with others having known roles in cancer biology. Analyses on large-scale data from multiple sources must deal with significant challenges associated with heterogeneity between different published studies, for it was observed that the variation among individual studies often had a larger effect on the transcriptome than did phenotype differences, as is typical. For this reason, we restricted ourselves to studying only cases where we had at least two independent studies performed for each phenotype, and also reprocessed all the raw data from the studies using a unified pre-processing pipeline. We found that learning signatures across multiple datasets greatly enhanced reproducibility and accuracy in predictive performance on truly independent validation sets, even when keeping the size of the training set the same. This was most likely due to the meta-signature encompassing more of the heterogeneity across different sources and conditions, while amplifying signal from the repeated global characteristics of the phenotype. When molecular signatures of brain cancers were constructed from all currently available microarray data, 90% phenotype prediction accuracy, or the accuracy of identifying a particular brain cancer from the background of all phenotypes, was found. Looking forward, we discuss our approach in the context of the eventual development of organ-specific molecular signatures from peripheral fluids such as the blood.

  10. The effect of combined hormonal contraceptives use on brain reactivity during response inhibition.

    Science.gov (United States)

    Gingnell, Malin; Bannbers, Elin; Engman, Jonas; Frick, Andreas; Moby, Lena; Wikström, Johan; Sundström-Poromaa, Inger

    2016-04-01

    Objectives Cognitive control, which can be described as the ability to moderate impulses, has not previously been investigated in users of combined hormonal contraception (CHC). Given the suggested modulatory role of ovarian steroids in prefrontal dopaminergic function, which in turn taps into cognitive control, this randomised, double-blinded, placebo-controlled oral contraceptive trial set out to investigate the brain activity pattern during response inhibition in CHC users. Methods Thirty-four women were randomised to one treatment cycle with a levonorgestrel-containing CHC or placebo. The women performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging (fMRI) prior to and during the CHC/placebo treatment cycle. Results No differences between CHC and placebo users in number of correct inhibitions were found during treatment, but only women on CHC significantly improved their performance between the baseline and treatment assessments. During the treatment cycle CHC users displayed decreased activity in the right middle frontal gyrus in comparison with placebo users. No other significant activations were evident between treatment groups or within groups. Conclusion Overall, CHC use had marginal effects on brain activity during response inhibition. If anything, the findings of the study may suggest reduced effort or increased efficiency in maintaining orbitofrontal cortex inhibitory cognitive control when using a combined oral contraceptive. PMID:26291330

  11. Comparative analysis of survival, treatment, cost and resource use among patients newly diagnosed with brain metastasis by initial primary cancer.

    Science.gov (United States)

    Ray, Saurabh; Dacosta-Byfield, Stacey; Ganguli, Arijit; Bonthapally, Vijayveer; Teitelbaum, April

    2013-08-01

    Brain metastases are a frequent complication of many systemic cancers and portend a poor prognosis. This retrospective analysis of health claims data compared survival, treatment and health care utilization and costs in patients with brain metastasis by primary tumor site. Adult commercial and Medicare Advantage enrollees newly diagnosed with brain metastasis in 01 Jan 2004 through 30 Apr 2010 were identified. Inclusion required at least 2 claims that identified the same primary cancer site prior to diagnosis of brain metastasis and no evidence of primary brain tumors. Health care utilization rates and costs were calculated at the patient level for each month of follow-up. Differences among primary cancer site cohorts were assessed by ANOVA (continuous variables), Chi square test (proportions) and the Poisson distribution (utilization rates). The primary cancer cohorts comprised 1,031 lung cancer, 93 melanoma and 395 female breast cancer patients. During the 6 months prior to brain metastasis diagnosis, 59 % of lung cancer patients had no evidence of lymph node involvement or other metastatic disease compared to 55 and 42 % of melanoma and breast cancer patients (P < 0.001). Survival after brain metastasis diagnosis was less than 3 months for 52, 43 and 39 % for lung cancer, breast cancer and melanoma, respectively (P < 0.001). Melanoma patients had the highest rate of inpatient stays and outpatient visits (P ≤ 0.003). Total monthly all-cause costs were: melanoma, $23,426; breast cancer $19,708; lung cancer, $17,007 (P = 0.003). Health care utilization and costs after brain metastasis diagnosis were substantial and differed by primary tumor site.

  12. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2016-03-15

    Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

  13. Survival following gamma knife radiosurgery for brain metastasis from breast cancer

    International Nuclear Information System (INIS)

    Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes. A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis. Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant (p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival. The MST for patients of age <65 years was 14.5 months, compared to age ≥65 which was 7.7 months (p = 0.06) and remained a significant prognostic factor for overall survival on multivariate analysis. The MST for patients with a single lesion was 16.9 months, not significantly different than the MST of 14.5 months for patients with 2–3 lesions

  14. Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.

    Science.gov (United States)

    Weitzel, Douglas H; Tovmasyan, Artak; Ashcraft, Kathleen A; Boico, Alina; Birer, Samuel R; Roy Choudhury, Kingshuk; Herndon, James; Rodriguiz, Ramona M; Wetsel, William C; Peters, Katherine B; Spasojevic, Ivan; Batinic-Haberle, Ines; Dewhirst, Mark W

    2016-06-01

    Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have recently shown that MnTnBuOE-2-PyP(5+) (Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium -2-yl)porphyrin) rescued RT-induced white matter damage in cranially-irradiated mice. Radiotherapy is not used in isolation for treatment of brain tumors; temozolomide is the standard-of-care for adult glioblastoma, whereas cisplatin is often used for treatment of pediatric brain tumors. Therefore, we evaluated the brain radiation mitigation ability of MnTnBuOE-2-PyP(5+) after either temozolomide or cisplatin was used singly or in combination with 10 Gy RT. MnTnBuOE-2-PyP(5+) accumulated in brains at low nanomolar levels. Histological and neurobehavioral testing showed a drastic decrease (1) of axon density in the corpus callosum and (2) rotorod and running wheel performance in the RT only treatment group, respectively. MnTnBuOE-2-PyP(5+) completely rescued this phenotype in irradiated animals. In the temozolomide groups, temozolomide/ RT treatment resulted in further decreased rotorod responses over RT alone. Again, MnTnBuOE-2-PyP(5+) treatment rescued the negative effects of both temozolomide ± RT on rotorod performance. While the cisplatin-treated groups did not give similar results as the temozolomide groups, inclusion of MnTnBuOE-2-PyP(5+) did not negatively affect rotorod performance. Additionally, MnTnBuOE-2-PyP(5+) sensitized glioblastomas to either RT ± temozolomide in flank tumor models. Mice treated with both MnTnBuOE-2-PyP(5+) and radio-/chemo-therapy herein demonstrated brain radiation mitigation. MnTnBuOE-2-PyP(5+) may well serve as a normal tissue radio-/chemo-mitigator adjuvant therapy to standard brain cancer treatment regimens. Environ. Mol. Mutagen. 57:372-381, 2016. © 2016 Wiley Periodicals, Inc

  15. Efficacy of XELOX plus Bevacizumab in Brain Metastasis from Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Yoichiro Yoshida

    2014-02-01

    Full Text Available Brain metastasis (BM is rare in colorectal cancer (CRC patients. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. The prognosis of patients with BM from CRC was associated with the curability of the therapy for BM and the number of metastatic organs. Metastatic brain tumors are generally treated with radiotherapy because many anticancer drugs cannot cross the blood-brain barrier. Here, we present a case treated with XELOX (capecitabine and oxaliplatin plus bevacizumab for BM from rectal cancer. To our knowledge, this is the first report of a patient who was successfully treated for BM from CRC without radiotherapy. The findings could lead to a paradigm shift in the use of chemotherapy for BM from CRC.

  16. Some Brain Cancer Patients Have Radiation Options: Study

    Science.gov (United States)

    ... The report was published July 26 in the Journal of the American Medical Association . In the past, whole brain radiation was ... New Hyde Park, N.Y.; July 26, 2016, Journal of the American Medical Association HealthDay Copyright (c) 2016 HealthDay . All rights ...

  17. Analysis of radiation therapy in a model of triple-negative breast cancer brain metastasis.

    Science.gov (United States)

    Smart, DeeDee; Garcia-Glaessner, Alejandra; Palmieri, Diane; Wong-Goodrich, Sarah J; Kramp, Tamalee; Gril, Brunilde; Shukla, Sudhanshu; Lyle, Tiffany; Hua, Emily; Cameron, Heather A; Camphausen, Kevin; Steeg, Patricia S

    2015-10-01

    Most cancer patients with brain metastases are treated with radiation therapy, yet this modality has not yet been meaningfully incorporated into preclinical experimental brain metastasis models. We applied two forms of whole brain radiation therapy (WBRT) to the brain-tropic 231-BR experimental brain metastasis model of triple-negative breast cancer. When compared to sham controls, WBRT as 3 Gy × 10 fractions (3 × 10) reduced the number of micrometastases and large metastases by 87.7 and 54.5 %, respectively (both p radiation dose of 15 Gy × 1 (15 × 1) was less effective, reducing metastases by 58.4 % (p radiation regimens. The nature of radiation resistance was investigated by ex vivo culture of tumor cells that survived initial WBRT ("Surviving" cultures). The Surviving cultures surprisingly demonstrated increased radiosensitivity ex vivo. In contrast, re-injection of Surviving cultures and re-treatment with a 3 × 10 WBRT regimen significantly reduced the number of large and micrometastases that developed in vivo, suggesting a role for the microenvironment. Micrometastases derived from tumor cells surviving initial 3 × 10 WBRT demonstrated a trend toward radioresistance upon repeat treatment (p = 0.09). The data confirm the potency of a fractionated 3 × 10 WBRT regimen and identify the brain microenvironment as a potential determinant of radiation efficacy. The data also nominate the Surviving cultures as a potential new translational model for radiotherapy.

  18. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury

    Science.gov (United States)

    Tu, Yue; Miao, Xiao-mei; Yi, Tai-long; Chen, Xu-yi; Sun, Hong-tao; Cheng, Shi-xiang; Zhang, Sai

    2016-01-01

    Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.

  19. Neuroprotective effects of bloodletting atJing points combined with mild induced hypothermia in acute severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Yue Tu; Xiao-mei Miao; Tai-long Yi; Xu-yi Chen; Hong-tao Sun; Shi-xiang Cheng; Sai Zhang

    2016-01-01

    Bloodletting atJing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting atJing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe trau-matic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inlfammatory response were lessened. These ifndings suggest that the combined effects of bloodletting atJing points (20 µL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.

  20. Improved survival with combined modality treatment for Stage IV breast cancer

    International Nuclear Information System (INIS)

    Between 1974 and 1977, 85 patients with breast cancer at first postmastectomy relapse were irradiated (Radiation 3500 to 6000 rad--3/5 weeks) to all clinically evident lesions. Radiation fields were properly shaped to include a maximum 40% active bone marrow. After 3 to 4 weeks rest, chemotherapy was started as adjuvant therapy for residual or subclinical disease (ADR 30 mg/M2 Day 1 and 8, 5-FU 400 mg/M2 Day 1 and 8, CY 100 mg/M2 Day 1 through 14: repeated after 14 days). ADR was discontinued at 500/M2 and substituted by MTX 30 mg/M2 Day 1 and 8 for a total of 2 years. Irradiated sites were chest wall in 35, supraclavicular and internal mammary nodes in 22, bone in 56, single lung lesions in 12, brain in 24. Controls were 52 comparable but non-randomized patients treated with chemotherapy only. Forty days after x-irradiation 68 patients (80%) were free of disease (NED) while in 17 cases (20%) some residual was still present (RED). In 28 of 68 cases (41%) NED after x-irradiation and 13 of 17 (76%) in RED group developed second relapse after a median interval of 26 and 20 mos., respectively. Four of 52 patients (8%) in the control group had complete regression with a median interval to second relapse of 7 mos. Median survival was 30 mos., 24 mos., and 13 mos., respectively, for NED, RED and chemotherapy only. Eighteen patients (26%) are free of disease after 36 to 48 mos. in the combined modality group; none in the chemotherapy group. Combined treatment cases did not show untolerable myelodepression. In 10 long-surviving patients a marked subcutaneous and skin fibrosis developed because of drug additive effect. Stage IV breast cancers rendered clinically free of disease with x-irradiation and subsequently treated with chemotherapy survive significantly longer than with chemotherapy alone

  1. Combined Hyperthermia and Radiotherapy for the Treatment of Cancer

    International Nuclear Information System (INIS)

    Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an integral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, cardiac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threatening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic

  2. Combined Hyperthermia and Radiotherapy for the Treatment of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Punit [Department of Pathology, Scott & White Hospital and the Texas A& M Health Science Center, College of Medicine, Temple, TX 76504 (United States); Hurwitz, Mark D. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center and Harvard Medical School, Boston, MA 02115 (United States); Krishnan, Sunil [Department of Radiation Oncology, The University of Texas MD Anderson Medical Center, Houston, TX 77030 (United States); Asea, Alexzander, E-mail: asea@medicine.tamhsc.edu [Department of Pathology, Scott & White Hospital and the Texas A& M Health Science Center, College of Medicine, Temple, TX 76504 (United States)

    2011-09-30

    Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an integral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, cardiac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threatening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic

  3. Quantification of transient increase of the blood–brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles

    Directory of Open Access Journals (Sweden)

    Shi L

    2014-09-01

    Full Text Available Lingyan Shi,1 Paolo Palacio-Mancheno,1 Joseph Badami,2 Da Wi Shin,1 Min Zeng,1 Luis Cardoso,1 Raymond Tu,2 Bingmei M Fu11Department of Biomedical Engineering, 2Department of Chemical Engineering, The City College of the City University of New York, New York, NY, USAAbstract: Radioimmunotherapy using a radiolabeled monoclonal antibody that targets tumor cells has been shown to be efficient for the treatment of many malignant cancers, with reduced side effects. However, the blood–brain barrier (BBB inhibits the transport of intravenous antibodies to tumors in the brain. Recent studies have demonstrated that focused ultrasound (FUS combined with microbubbles (MBs is a promising method to transiently disrupt the BBB for the drug delivery to the central nervous system. To find the optimal FUS and MBs that can induce reversible increase in the BBB permeability, we employed minimally invasive multiphoton microscopy to quantify the BBB permeability to dextran-155 kDa with similar molecular weight to an antibody by applying different doses of FUS in the presence of MBs with an optimal size and concentration. The cerebral microcirculation was observed through a section of frontoparietal bone thinned with a micro-grinder. About 5 minutes after applying the FUS on the thinned skull in the presence of MBs for 1 minute, TRITC (tetramethylrhodamine isothiocyanate-dextran-155 kDa in 1% bovine serum albumin in mammalian Ringer’s solution was injected into the cerebral circulation via the ipsilateral carotid artery by a syringe pump. Simultaneously, the temporal images were collected from the brain parenchyma ~100–200 µm below the pia mater. Permeability was determined from the rate of tissue solute accumulation around individual microvessels. After several trials, we found the optimal dose of FUS. At the optimal dose, permeability increased by ~14-fold after 5 minutes post-FUS, and permeability returned to the control level after 25 minutes. FUS without

  4. Combined effects of smoking and HPV16 in oropharyngeal cancer

    DEFF Research Database (Denmark)

    Anantharaman, Devasena; Muller, David C; Lagiou, Pagona;

    2016-01-01

    BACKGROUND: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer...... is not understood. METHODS: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible...... intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression. RESULTS: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association...

  5. [Whole Brain Irradiation and Hypo-fractionation Radiotherapy for the Metastases in Non-small Cell Lung Cancer].

    Science.gov (United States)

    Gu, Xingting; Zhao, Yaqin; Xu, Feng

    2016-04-20

    Up to 40% non-small cell lung cancer patients developed brain metastasis during progression. Multiple brain metastases are common in non-small cell lung cancer. The prognosis of brain metastasis is poor with median survival of less than 1 year. Radio therapy for brain metastases has gradually developed from whole brain radiotherapy (WBRT) to various radiation strategies. WBRT, surgery+WBRT, stereotactic radiotherapy+WBRT or WBRT with simultaneous integrated boost (SIB), etc. have better overall survival than those untreated patients. The damage of the cognitive function from WBRT has been realized recently, however, options of radiation strategies for long expected survival patients remain controversial. This paper will discuss different WBRT strategies and treatment side effects of non-small cell lung cancer with brain metastases. PMID:27118651

  6. Prognostic predictors for non-small cell lung cancer patients with brain metastasis after radiotherapy

    Directory of Open Access Journals (Sweden)

    Qiuhong FAN

    2008-06-01

    Full Text Available Background and objective Brain metastasis (BM is often found in the patients with lung cancer. Radiotherapy is regular and effective means of therapy and it aims at palliating symptoms and prolonging survival time. However, now there are different viewpoints on protocols of radiotherapy and prognostic factors. A retrospective analysis is used to evaluate the results of treatment for 82 cases with brain metastasis from non-small cell lung cancer (NSCLC and explore the prognostic factors to establish a prognostic index (PI model. Methods From Feb.1995 to Oct. 2006, 82 patients irradiated for BM from NSCLC, with both complete medical charts and follow-up data available, were eligible for this retrospective analysis. A number of potential factors which might affect prognosis after irradiation were evaluated. The significance of prognostic variables in the survival resulted from both univariate analysis by Kaplan-Meier combining with log-rank test and multivariate Cox regression model. The prognostic index (PI was established based on Cox regression analysis and subgrouping values. Results The follow-up time was 1-120 months. For the entire cohort, the median survival from the start of radiation for BM was 10.5 months, and the actuarial overall survival rate was 50.8%, 23.7% and 5.1% at 0.5, 1 and 2 years respectively. Univariate analysis showed KPS, control of primary tumor, interval from the beginning of diagnostic to BM, extracranial systemic metastasis, counts of lymphocyte and solitary BM were predictors of prognosis. However, in the Cox multivariate analysis, only KPS, control of primary tumor, interval from the beginning of diagnostic to BM and solitary BM were significant prognostic factors. The prognostic index was established based on Cox regression analysis and 82 patients were stratified good, intermediate and poor prognostic sub-groups. The difference of survival rate among 3 subgroups is significant (P<0.001. Conclusion Radiotherapy is

  7. Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

    International Nuclear Information System (INIS)

    This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

  8. Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

    1999-03-01

    This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

  9. Resting state brain dynamics and its transients: a combined TMS-EEG study.

    Science.gov (United States)

    Bonnard, Mireille; Chen, Sophie; Gaychet, Jérôme; Carrere, Marcel; Woodman, Marmaduke; Giusiano, Bernard; Jirsa, Viktor

    2016-01-01

    The brain at rest exhibits a spatio-temporally rich dynamics which adheres to systematic behaviours that persist in task paradigms but appear altered in disease. Despite this hypothesis, many rest state paradigms do not act directly upon the rest state and therefore cannot confirm hypotheses about its mechanisms. To address this challenge, we combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to study brain's relaxation toward rest following a transient perturbation. Specifically, TMS targeted either the medial prefrontal cortex (MPFC), i.e. part of the Default Mode Network (DMN) or the superior parietal lobule (SPL), involved in the Dorsal Attention Network. TMS was triggered by a given brain state, namely an increase in occipital alpha rhythm power. Following the initial TMS-Evoked Potential, TMS at MPFC enhances the induced occipital alpha rhythm, called Event Related Synchronisation, with a longer transient lifetime than TMS at SPL, and a higher amplitude. Our findings show a strong coupling between MPFC and the occipital alpha power. Although the rest state is organized around a core of resting state networks, the DMN functionally takes a special role among these resting state networks. PMID:27488504

  10. Resting state brain dynamics and its transients: a combined TMS-EEG study.

    Science.gov (United States)

    Bonnard, Mireille; Chen, Sophie; Gaychet, Jérôme; Carrere, Marcel; Woodman, Marmaduke; Giusiano, Bernard; Jirsa, Viktor

    2016-08-04

    The brain at rest exhibits a spatio-temporally rich dynamics which adheres to systematic behaviours that persist in task paradigms but appear altered in disease. Despite this hypothesis, many rest state paradigms do not act directly upon the rest state and therefore cannot confirm hypotheses about its mechanisms. To address this challenge, we combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to study brain's relaxation toward rest following a transient perturbation. Specifically, TMS targeted either the medial prefrontal cortex (MPFC), i.e. part of the Default Mode Network (DMN) or the superior parietal lobule (SPL), involved in the Dorsal Attention Network. TMS was triggered by a given brain state, namely an increase in occipital alpha rhythm power. Following the initial TMS-Evoked Potential, TMS at MPFC enhances the induced occipital alpha rhythm, called Event Related Synchronisation, with a longer transient lifetime than TMS at SPL, and a higher amplitude. Our findings show a strong coupling between MPFC and the occipital alpha power. Although the rest state is organized around a core of resting state networks, the DMN functionally takes a special role among these resting state networks.

  11. Combined MRI and MRS improves pre-therapeutic diagnoses of pediatric brain tumors over MRI alone

    Energy Technology Data Exchange (ETDEWEB)

    Shiroishi, Mark S.; Nelson, Marvin D. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Pediatric Radiology, Pittsburgh, PA (United States); Moore, Kevin R. [Primary Children' s Medical Center, Department of Radiology, Salt Lake City, UT (United States); Gilles, Floyd H. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Pathology, Los Angeles, CA (United States); Gonzalez-Gomez, Ignacio [All Children' s Hospital, Department of Pathology, St. Petersburg, FL (United States); Blueml, Stefan [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States)

    2015-09-15

    The specific goal of this study was to determine whether the inclusion of MRS had a measureable and positive impact on the accuracy of pre-surgical MR examinations of untreated pediatric brain tumors over that of MRI alone in clinical practice. Final imaging reports of 120 pediatric patients with newly detected brain tumors who underwent combined MRI/MRS examinations were retrospectively reviewed. Final pathology was available in all cases. Group A comprised 60 subjects studied between June 2001 and January 2005, when MRS was considered exploratory and radiologists utilized only conventional MRI to arrive at a diagnosis. For group B, comprising 60 subjects studied between January 2005 and March 2008, the radiologists utilized information from both MRI and MRS. Furthermore, radiologists revisited group A (blind review, time lapse >4 years) to determine whether the additional information from MRS would have altered their interpretation. Sixty-three percent of patients in group A were diagnosed correctly, whereas in 10 % the report was partially correct with the final tumor type mentioned (but not mentioned as most likely tumor), while in 27 % of cases the reports were wrong. For group B, the diagnoses were correct in 87 %, partially correct in 5 %, and incorrect in 8 % of the cases, which is a significant improvement (p < 0.005). Re-review of combined MRI and MRS of group A resulted 87 % correct, 7 % partially correct, and 7 % incorrect diagnoses, which is a significant improvement over the original diagnoses (p < 0.05). Adding MRS to conventional MRI significantly improved diagnostic accuracy in preoperative pediatric patients with untreated brain tumors. (orig.)

  12. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  13. Engineering a Brain Cancer Chip for High-throughput Drug Screening

    Science.gov (United States)

    Fan, Yantao; Nguyen, Duong Thanh; Akay, Yasemin; Xu, Feng; Akay, Metin

    2016-01-01

    Glioblastoma multiforme (GBM) is the most common and malignant of all human primary brain cancers, in which drug treatment is still one of the most effective treatments. However, existing drug discovery and development methods rely on the use of conventional two-dimensional (2D) cell cultures, which have been proven to be poor representatives of native physiology. Here, we developed a novel three-dimensional (3D) brain cancer chip composed of photo-polymerizable poly(ethylene) glycol diacrylate (PEGDA) hydrogel for drug screening. This chip can be produced after a few seconds of photolithography and requires no silicon wafer, replica molding, and plasma bonding like microfluidic devices made of poly(dimethylsiloxane) (PDMS). We then cultured glioblastoma cells (U87), which formed 3D brain cancer tissues on the chip, and used the GBM chip to perform combinatorial treatment of Pitavastatin and Irinotecan. The results indicate that this chip is capable of high-throughput GBM cancer spheroids formation, multiple-simultaneous drug administration, and a massive parallel testing of drug response. Our approach is easily reproducible, and this chip has the potential to be a powerful platform in cases such as high-throughput drug screening and prolonged drug release. The chip is also commercially promising for other clinical applications, including 3D cell culture and micro-scale tissue engineering. PMID:27151082

  14. Engineering a Brain Cancer Chip for High-throughput Drug Screening.

    Science.gov (United States)

    Fan, Yantao; Nguyen, Duong Thanh; Akay, Yasemin; Xu, Feng; Akay, Metin

    2016-05-06

    Glioblastoma multiforme (GBM) is the most common and malignant of all human primary brain cancers, in which drug treatment is still one of the most effective treatments. However, existing drug discovery and development methods rely on the use of conventional two-dimensional (2D) cell cultures, which have been proven to be poor representatives of native physiology. Here, we developed a novel three-dimensional (3D) brain cancer chip composed of photo-polymerizable poly(ethylene) glycol diacrylate (PEGDA) hydrogel for drug screening. This chip can be produced after a few seconds of photolithography and requires no silicon wafer, replica molding, and plasma bonding like microfluidic devices made of poly(dimethylsiloxane) (PDMS). We then cultured glioblastoma cells (U87), which formed 3D brain cancer tissues on the chip, and used the GBM chip to perform combinatorial treatment of Pitavastatin and Irinotecan. The results indicate that this chip is capable of high-throughput GBM cancer spheroids formation, multiple-simultaneous drug administration, and a massive parallel testing of drug response. Our approach is easily reproducible, and this chip has the potential to be a powerful platform in cases such as high-throughput drug screening and prolonged drug release. The chip is also commercially promising for other clinical applications, including 3D cell culture and micro-scale tissue engineering.

  15. Brain cancer and pesticide relationship in orchard farmers of Kashmir

    Directory of Open Access Journals (Sweden)

    Bhat Abdul

    2010-01-01

    Full Text Available Background: The increasing trend in the incidence of primary malignant brain tumors in orchard farmers and their families in Kashmir. Aim: To determine the relationship between the patients of primary malignant brain tumors and their occupation. Materials and Methods: Retrospectively, case files along with death certificates of 432 patients of primary malignant brain tumors and 457 controls (non-tumor neurologic diseases, admitted for treatment simultaneously over a period of 4 years from January 2005 to December 2008, to the Neurosurgery, Sher-i-Kashmir Institute of Medical Sciences (SKIMS, Kashmir, were studied. Follow-up and family interaction was established. Results: Analysis revealed that 90.04% (389 out of 432 patients were orchard farm workers, orchard residents and orchard playing children exposed to the high levels of multiple types of neurotoxic and carcinogenic (chlorpyriphos, dimethoate, mancozeb and captan chemicals for more than 10 years [relative risk (RR = 10.6; odds ratio (OR = >10; 95% confidence interval (CI = >25-40]. The 9.96% (43 out of 432 patients were not exposed to pesticides. On the other hand, only 19 patients out of 457 controls had recorded history of pesticide exposure and 438 were unrelated to pesticides. Out of 389 patients, 71.7% (279 out of 389 were males and 28.3% (110 out of 389, including six members of three families, were females (one male child. Conclusion: All orchard-related 389 patients had high-grade tumors as compared to the non-pesticide tumors. Mortality in pesticide-exposed tumors was 12%. The higher or upper-normal levels of serum cholinesterase (AChE were observed in 54.7% (213 out of 389 patients and decreased levels were found in only 45.3% (176 out of 389 orchard-related patients (RR = 19.4; OR = >5; 95% CI = >1-10. Although serum AChE levels were a routine investigation in malignant brain tumors, this was not a routine in other neurological conditions (hospitalized controls. The familial

  16. Surgery Versus Stereotactic Radiosurgery for Single Synchronous Brain Metastasis from Non-Small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Hui LI; Sheng-cai HOU; Bin HU; Tong LI; Yang Wang; Jin-bai Miao; Bin You; Yi-li Fu

    2009-01-01

    Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer.Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32(85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS.Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (N0), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P>0.05). In lymph node negative patients (N0), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1(2). The difference was significant (P0.05).Conclusion: Although the overall survival rate for

  17. Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients

    Science.gov (United States)

    Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival.

  18. 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.

  19. CLINICAL USE OF COMBINED DETECTION WITH TUMOR MARKERS FOR PANCREATIC CANCER

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To explore the value of clinical use of combined detection with tumor markers for pancreatic cancer. Methods Tumor markers CA242,CA19-9 and CA50 in serum of 32 patinets with pancreatic cancer;26 patients with non-pancreatic digestive tract cancers and 24 patietns with benign pancreatic or biliary tract diseases were measured by immunoradiometric assay (IRMA). Results The levels of three markers in serum and positive rates of patients with pancreatic cancer were higher than those of other patients. The effect of measurement combining CA242 with CA19-9 was the best. The sensitivity ,specificity and accuracy of diagnosis for pancreatic cancer were 92.6%, 73.8% and 81.2% respectively. The levels of CA242 and CA19-9 were positively relative to burden of pancreatic cancer, and serum levels of these two markers of patients with resectable pancreatic cancer were lower than those with unresectable, but on difference was observed for CA50. Conclusion Combined detection of serum CA242 and CA19-9 could prove the effectual indicator for finding the patients with pancreatic cancer in high risk population or for resectable pancreatic cancer. Pre-operative measurement of serum levels of CA242 and CA19-9 is helpful to evaluate the burden of the tumors and possiblity of resect for pancreatic cancers.

  20. Combining EEG Microstates with fMRI Structural Features for Modeling Brain Activity.

    Science.gov (United States)

    Michalopoulos, Kostas; Bourbakis, Nikolaos

    2015-12-01

    Combining information from Electroencephalography (EEG) and Functional Magnetic Resonance Imaging (fMRI) has been a topic of increased interest recently. The main advantage of the EEG is its high temporal resolution, in the scale of milliseconds, while the main advantage of fMRI is the detection of functional activity with good spatial resolution. The advantages of each modality seem to complement each other, providing better insight in the neuronal activity of the brain. The main goal of combining information from both modalities is to increase the spatial and the temporal localization of the underlying neuronal activity captured by each modality. This paper presents a novel technique based on the combination of these two modalities (EEG, fMRI) that allow a better representation and understanding of brain activities in time. EEG is modeled as a sequence of topographies, based on the notion of microstates. Hidden Markov Models (HMMs) were used to model the temporal evolution of the topography of the average Event Related Potential (ERP). For each model the Fisher score of the sequence is calculated by taking the gradient of the trained model parameters. The Fisher score describes how this sequence deviates from the learned HMM. Canonical Partial Least Squares (CPLS) were used to decompose the two datasets and fuse the EEG and fMRI features. In order to test the effectiveness of this method, the results of this methodology were compared with the results of CPLS using the average ERP signal of a single channel. The presented methodology was able to derive components that co-vary between EEG and fMRI and present significant differences between the two tasks.

  1. Whole brain radiotherapy plus concurrent chemotherapy in non-small cell lung cancer patients with brain metastases: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hong Qin

    Full Text Available The aim of the present meta-analysis is to evaluate the response rate, median survival time (MST and toxicity in patients with brain metastases (BM originating from non-small cell lung cancer (NSCLC and who were treated using either whole brain radiotherapy (WBRT plus concurrent chemotherapy or WBRT alone.PubMed, EMBASE, Web of Science, The Cochrane Library, clinical trials and current controlled trials were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using Stata11.0 software.In total, six randomized controlled trials (RCT involving 910 participants were included in the meta-analysis. The results of the analysis indicate that WBRT plus concurrent chemotherapy was more effective at improving response rate (RR = 2.06, 95% CI [1.13, 3.77]; P = 0.019 than WBRT alone. However, WBRT plus concurrent chemotherapy did not improve median survival time (MST (HR = 1.09, 95%CI [0.94, 1.26]; P = 0.233 or time of neurological progression (CNS-TTP (HR = 0.93, 95%CI [0.75, 1.16]; P = 0.543, and increased adverse events (Grade≥3 (RR = 2.59, 95% CI [1.88, 3.58]; P = 0.000. There were no significant differences in Grade 3-5 neurological or hematological toxicity between two patient groups (RR = 1.08, 95%CI [0.23, 5.1]; P = 0.92.The combination of chemotherapy plus WBRT in patients with BM originating from NSCLC may increase treatment response rates of brain metastases with limited toxicity. Although the therapy schedule did not prolong MST or CNS-TTP, further assessment is warranted.

  2. Exploring combinations of auditory and visual stimuli for gaze-independent brain-computer interfaces.

    Directory of Open Access Journals (Sweden)

    Xingwei An

    Full Text Available For Brain-Computer Interface (BCI systems that are designed for users with severe impairments of the oculomotor system, an appropriate mode of presenting stimuli to the user is crucial. To investigate whether multi-sensory integration can be exploited in the gaze-independent event-related potentials (ERP speller and to enhance BCI performance, we designed a visual-auditory speller. We investigate the possibility to enhance stimulus presentation by combining visual and auditory stimuli within gaze-independent spellers. In this study with N = 15 healthy users, two different ways of combining the two sensory modalities are proposed: simultaneous redundant streams (Combined-Speller and interleaved independent streams (Parallel-Speller. Unimodal stimuli were applied as control conditions. The workload, ERP components, classification accuracy and resulting spelling speed were analyzed for each condition. The Combined-speller showed a lower workload than uni-modal paradigms, without the sacrifice of spelling performance. Besides, shorter latencies, lower amplitudes, as well as a shift of the temporal and spatial distribution of discriminative information were observed for Combined-speller. These results are important and are inspirations for future studies to search the reason for these differences. For the more innovative and demanding Parallel-Speller, where the auditory and visual domains are independent from each other, a proof of concept was obtained: fifteen users could spell online with a mean accuracy of 87.7% (chance level <3% showing a competitive average speed of 1.65 symbols per minute. The fact that it requires only one selection period per symbol makes it a good candidate for a fast communication channel. It brings a new insight into the true multisensory stimuli paradigms. Novel approaches for combining two sensory modalities were designed here, which are valuable for the development of ERP-based BCI paradigms.

  3. Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Hai-xiao Zhou; Zhi-gang Liu; Xiao-jiao Liu; Qian-xue Chen

    2016-01-01

    Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO) treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized lfuid (2.5–3.0 atm impact force). The injured rats were then administered UC-MSC transplantationvia the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function signiifcantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and signiifcantly promotes recovery of neurological functions.

  4. Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hai-xiao Zhou

    2016-01-01

    Full Text Available Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5-3.0 atm impact force. The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions.

  5. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

    Directory of Open Access Journals (Sweden)

    Zhou Weihua

    2007-02-01

    Full Text Available Abstract Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal®, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A and a human malignant glioma (U87-MG. Methods Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal® was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal® on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet. Results KetoCal® administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal® diet reduced plasma glucose levels while elevating plasma ketone body (β-hydroxybutyrate levels. Tumor microvessel density was less in the calorically restricted KetoCal® groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, β-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid Co

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

    Directory of Open Access Journals (Sweden)

    Yun-feng Lou

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

  7. Prediction of Clinical Outcomes by Chemokine and Cytokine Profiling In CSF from Radiation Treated Breast Cancer Primary with Brain Metastases

    Science.gov (United States)

    Lok, Edwin

    Whole brain radiation is the standard treatment for patients with brain metastasis but unfortunately tumors can recover from radiation-induced damage with the help of the immune system. The hypothesis that differences in immunokines in the cerebrospinal fluid (CSF) pre- and post-irradiation could reveal tumor biology and correlate with outcome of patients with metastatic breast cancer to the brain is tested. Collected CSF samples were analyzed using Luminex's multiplexing assays to survey global immunokine levels while Enzyme-Linked Immunosorbent Assays were used to quantify each individual immunokines. Cluster analysis was performed to segregate patients based on their common immunokine profile and each cluster was correlated with survival and other clinical parameters. Breast cancer brain metastasis was found to have altered immunokine profiles in the CSF, and that Interleukin-1α expression was elevated after irradiation. Therefore, immunokine profiling in the CSF could enable cancer physicians to monitor the status of brain metastases.

  8. Brain metastasis from differentiated thyroid cancer in patients treated with radioiodine for bone and lung lesions

    International Nuclear Information System (INIS)

    Brain metastasis of differentiated thyroid cancer (DTC) often is detected during treatment of other remote lesions. We examined the prevalence, risk factors and treatment outcome of this disease encountered during nuclear medicine practice. Of the 167 patients with metastasis to lung or bone treated 1-14 times with radioactive iodine (RAI), 9 (5.4%) also had lesions in the brain. Five were males and 4 females, aged 49-84, out of the original population of 49 males and 118 females aged 10-84 (mean 54.7) years. Three of them underwent removal of their brain tumors, 5 received conventional external beam irradiation, and 2 had stereotactic radiosurgery with supervoltage X-ray. None of the brain lesions showed significant uptake of RAI despite demonstrable accumulation in most extracerebral lesions. Seven patients died 4-23 (mean 9.4) months after the discovery of cerebral metastasis, brain damage being the primary or at least a contributing cause. The 8th and 9th patients remained relatively well for more than 42 and 3 months, respectively, without any evidence of intracranial recurrence. Our results confirmed that the brain is a major site of secondary metastasis from DTC. No statistically significant demographic risk factor was detected. Any suspicious neurological symptoms in the course of RAI treatment warrant cerebral computed tomography. As for therapy, from out initial experience, radiosurgery seemed promising as an effective and less invasive alternative to surgical removal. (author)

  9. Selective induction of oxidative stress in cancer cells via synergistic combinations of agents targeting redox homeostasis.

    Science.gov (United States)

    Akladios, Fady N; Andrew, Scott D; Parkinson, Christopher J

    2015-07-01

    Cancer cell resistance to chemotherapy is still a heavy burden that impairs the response of many cancer patients to conventional chemotherapy. Using drug combinations is one therapeutic approach to overcome the developing resistance to any one drug. Oxidative stress is now a generally regarded hallmark of cancer that can be one approach to selectively target cancer cells while sparing normal cells. With the aim of increasing oxidative stress in cancer cells to a lethal set point, we have generated and combined several series of redox active compounds that act at different points of the cellular oxidative cascade. The premise of such combinations is to deplete of endogenous antioxidant defence proteins (e.g., Glutathione) while concomitantly increasing the generation of ROS via metal redox recycling and Fenton chemistry which eventually leads to the disruption of cellular redox homeostasis and induction of cell death. Through this approach, we have identified highly synergistic combinations of two distinctive classes of compounds (Azines and Copper(II) complexes of 2-pyridyl ketone thiosemicarbazones) which are capable of eliminating cancer cells without concomitant increase in toxicity toward normal cells. In one of our most potent combinations, a combination index (CI) value of 0.056 was observed, representing a 17 fold enhancement in activity beyond additive effects. Such new combination regimen of redox active compounds can be one step closer to potentially safer low dose chemotherapy. PMID:26022081

  10. The contribution of drug resistant cancer stem cells to paediatric brain tumours

    OpenAIRE

    Punjaruk, Wiyada

    2010-01-01

    Introduction: Recent studies have revealed that cancer stem cells (CSCs) exist in malignant disease. Additionally, it is proposed that these cells may survive following chemotherapy, and hence contribute to tumour relapse. A significant mechanism of drug resistance in CSCs is believed to be the expression of ATP-binding cassette (ABC) transporters that efflux cytotoxic agents out of cells. The objective of this study was to study the existence of CSCs in a panel of primary paediatric brain tu...

  11. Advances in Treatment of Brain Metastases 
from Primary Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Gen LIN

    2014-12-01

    Full Text Available Metastatic tumors involving the brain are an important complication in the overall management of non-small cell lung cancers. Surgery and radiation remain the cornerstones of the therapy, however, the burgeoning knowledge of tumor biology has facilitated the entry of systemically administered therapies into the clinic. This review mainly summarizes the current applications of these data to surgery, radiation therapy, chemotherapy and targeted therapy.

  12. Combining Brain-Computer Interfaces and Assistive Technologies: State-of-the-Art and Challenges

    Directory of Open Access Journals (Sweden)

    José del R. Millán

    2010-09-01

    Full Text Available In recent years, new research has brought the field of EEG-based Brain-Computer Interfacing (BCI out of its infancy and into a phase of relative maturity through many demonstrated prototypes such as brain-controlled wheelchairs, keyboards, and computer games. With this proof-of-concept phase in the past, the time is now ripe to focus on the development of practical BCI technologies that can be brought out of the lab and into real-world applications. In particular, we focus on the prospect of improving the lives of countless disabled individuals through a combination of BCI technology with existing assistive technologies (AT. In pursuit of more practical BCIs for use outside of the lab, in this paper, we identify four application areas where disabled individuals could greatly benefit from advancements in BCI technology, namely,“Communication & Control”, “Motor Substitution”, “Entertainment”, and “Motor Recovery”. We review the current state of the art and possible future developments, while discussing the main research issues in these four areas. In particular, we expect the most progress in the development of technologies such as hybrid BCI architectures, user-machine adaptation algorithms, the exploitation of users’ mental states for BCI reliability and confidence measures, the incorporation of principles in human-computer interaction (HCI to improve BCI usability, and the development of novel BCI technology including better EEG devices.

  13. Resting state brain dynamics and its transients: a combined TMS-EEG study

    Science.gov (United States)

    Bonnard, Mireille; Chen, Sophie; Gaychet, Jérôme; Carrere, Marcel; Woodman, Marmaduke; Giusiano, Bernard; Jirsa, Viktor

    2016-01-01

    The brain at rest exhibits a spatio-temporally rich dynamics which adheres to systematic behaviours that persist in task paradigms but appear altered in disease. Despite this hypothesis, many rest state paradigms do not act directly upon the rest state and therefore cannot confirm hypotheses about its mechanisms. To address this challenge, we combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to study brain’s relaxation toward rest following a transient perturbation. Specifically, TMS targeted either the medial prefrontal cortex (MPFC), i.e. part of the Default Mode Network (DMN) or the superior parietal lobule (SPL), involved in the Dorsal Attention Network. TMS was triggered by a given brain state, namely an increase in occipital alpha rhythm power. Following the initial TMS-Evoked Potential, TMS at MPFC enhances the induced occipital alpha rhythm, called Event Related Synchronisation, with a longer transient lifetime than TMS at SPL, and a higher amplitude. Our findings show a strong coupling between MPFC and the occipital alpha power. Although the rest state is organized around a core of resting state networks, the DMN functionally takes a special role among these resting state networks. PMID:27488504

  14. Subject combination and electrode selection in cooperative brain-computer interface based on event related potentials.

    Science.gov (United States)

    Cecotti, Hubert; Rivet, Bertrand

    2014-01-01

    New paradigms are required in Brain-Computer Interface (BCI) systems for the needs and expectations of healthy people. To solve this issue, we explore the emerging field of cooperative BCIs, which involves several users in a single BCI system. Contrary to classical BCIs that are dependent on the unique subject's will, cooperative BCIs are used for problem solving tasks where several people shall be engaged by sharing a common goal. Similarly as combining trials over time improves performance, combining trials across subjects can significantly improve performance compared with when only a single user is involved. Yet, cooperative BCIs may only be used in particular settings, and new paradigms must be proposed to efficiently use this approach. The possible benefits of using several subjects are addressed, and compared with current single-subject BCI paradigms. To show the advantages of a cooperative BCI, we evaluate the performance of combining decisions across subjects with data from an event-related potentials (ERP) based experiment where each subject observed the same sequence of visual stimuli. Furthermore, we show that it is possible to achieve a mean AUC superior to 0.95 with 10 subjects and 3 electrodes on each subject, or with 4 subjects and 6 electrodes on each subject. Several emerging challenges and possible applications are proposed to highlight how cooperative BCIs could be efficiently used with current technologies and leverage BCI applications. PMID:24961765

  15. Subject Combination and Electrode Selection in Cooperative Brain-Computer Interface Based on Event Related Potentials

    Directory of Open Access Journals (Sweden)

    Hubert Cecotti

    2014-04-01

    Full Text Available New paradigms are required in Brain-Computer Interface (BCI systems for the needs and expectations of healthy people. To solve this issue, we explore the emerging field of cooperative BCIs, which involves several users in a single BCI system. Contrary to classical BCIs that are dependent on the unique subject’s will, cooperative BCIs are used for problem solving tasks where several people shall be engaged by sharing a common goal. Similarly as combining trials over time improves performance, combining trials across subjects can significantly improve performance compared with when only a single user is involved. Yet, cooperative BCIs may only be used in particular settings, and new paradigms must be proposed to efficiently use this approach. The possible benefits of using several subjects are addressed, and compared with current single-subject BCI paradigms. To show the advantages of a cooperative BCI, we evaluate the performance of combining decisions across subjects with data from an event-related potentials (ERP based experiment where each subject observed the same sequence of visual stimuli. Furthermore, we show that it is possible to achieve a mean AUC superior to 0.95 with 10 subjects and 3 electrodes on each subject, or with 4 subjects and 6 electrodes on each subject. Several emerging challenges and possible applications are proposed to highlight how cooperative BCIs could be efficiently used with current technologies and leverage BCI applications.

  16. Effect of Combined Treatment Using Wilfortrine and Paclitaxel in Liver Cancer and Related Mechanism

    Science.gov (United States)

    Li, Shuzhen; Zheng, Lei

    2016-01-01

    Background Liver cancer is a common malignant tumor with high mortality. Currently, effective medicines against liver cancer are still lacking. Paclitaxel is a wide-spectrum anti-tumor agent, while wilfortrine has been shown to have an inhibitory effect on the proliferation of liver cancer cells. This study thus investigated the potential effect of paclitaxel combined with wilfortrine on cultured liver cancer cells and related mechanisms, in order to provide evidence for pathogenesis and treatment of liver cancer. Material/Methods Liver cancer cell line HpeG2 was divided into control, paclitaxel, wilfortrine, and combined treatment groups. Cell proliferation was tested by MTT, while invasion was detected in Transwell chamber assay. Apoptotic protein Bcl-2 and Bax expression levels were further quantified using real-time PCR and Western blotting. Results Both of those 2 drugs can effectively inhibit cancer cell proliferation, depress invasion ability, increase Bcl-2 expression, and elevate Bax expression levels (p<0.05 in all cases). The combined therapy had better treatment efficacy compared to either of those drugs alone (p<0.05). Conclusions The combined treatment using wilfortrine and paclitaxel can inhibit proliferation and invasion of liver cancer cells via down-regulating Bcl-2 and up-regulating Bax, with better efficacy than single use of either drug. PMID:27043783

  17. The activity of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) in the sera of patients with brain cancer.

    Science.gov (United States)

    Jelski, Wojciech; Laniewska-Dunaj, Magdalena; Orywal, Karolina; Kochanowicz, Jan; Rutkowski, Robert; Szmitkowski, Maciej

    2014-12-01

    Human brain tissue contains various alcohol dehydrogenase (ADH) isoenzymes and possess also aldehyde dehydrogenase (ALDH) activity. In our last experiments we have shown that ADH and ALDH are present also in the brain tumour cells. Moreover the activities of total ADH and class I isoenzymes were significantly higher in cancer tissue than healthy cells. It can suggests that these changes may be reflected by enzyme activity in the serum of patients with brain cancer. Serum samples were taken for routine biochemical investigation from 62 patients suffering from brain cancer (36 glioblastoma, 26 meningioma). For the measurement of the activity of class I and II ADH isoenzymes and ALDH activity, the fluorometric methods were used. The total ADH activity and activity of class III and IV isoenzymes were measured by the photometric method. A statistically significant increase of class I alcohol dehydrogenase isoenzymes was found in the sera of patients with brain cancer. The median activity of this class isoenzyme in the patients group increased about 24 % in the comparison to the control level. The total alcohol dehydrogenase activity was also significantly higher (26 %) among patients with brain tumour than healthy ones. The activities of other tested ADH isoenzymes and total ALDH were unchanged. The increase of the activity of total ADH and class I alcohol dehydrogenase isoenzyme in the sera of patients with brain cancer seems to be caused by the release of this isoenzyme from tumour's cells.

  18. Enhancement of Combined Umami and Salty Taste by Glutathione in the Human Tongue and Brain.

    Science.gov (United States)

    Goto, Tazuko K; Yeung, Andy Wai Kan; Tanabe, Hiroki C; Ito, Yuki; Jung, Han-Sung; Ninomiya, Yuzo

    2016-09-01

    Glutathione, a natural substance, acts on calcium receptors on the tongue and is known to enhance basic taste sensations. However, the effects of glutathione on brain activity associated with taste sensation on the tongue have not been determined under standardized taste delivery conditions. In this study, we investigated the sensory effect of glutathione on taste with no effect of the smell when glutathione added to a combined umami and salty taste stimulus. Twenty-six volunteers (12 women and 14 men; age 19-27 years) performed a sensory evaluation of taste of a solution of monosodium L-glutamate and sodium chloride, with and without glutathione. The addition of glutathione changed taste qualities and significantly increased taste intensity ratings under standardized taste delivery conditions (P tasting an umami and salty mixture. PMID:27353260

  19. Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

    Science.gov (United States)

    Thomas, Frédéric; Lafferty, Kevin D.; Brodeur, Jacques; Elguero, Eric; Gauthier-Clerc, Michel; Missé, Dorothée

    2012-01-01

    We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product because wealth probably increases the ability to detect cancer. We also included gender, cell phone use and latitude as variables in our initial models. Prevalence of T. gondii explained 19 per cent of the residual variance in brain cancer incidence after controlling for the positive effects of gross domestic product and latitude among nations. Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4–67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.

  20. Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells.

    Science.gov (United States)

    Wang, Yunshan; Wei, Junmin; Li, Li; Fan, Cong; Sun, Ying

    2014-01-01

    Everolimus inhibits mammalian target of rapamycin (mTOR) and leads to decreased protein synthesis and decreased cancer cell proliferation in many experimental systems. Adenosine 5'-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR. Histopathological and biochemical studies of breast cancer show frequent dysregulation of the AMPK and the mTOR pathway. Therefore, we investigated the efficacy of the mTOR inhibitor everolimus and metformin in the treatment of breast cancer cells. This study evaluated the in vitro and in vivo effects of everolimus alone or in combination with metformin on breast cancer cells. MTT assay was used to quantify the inhibitory effect of the drugs on breast cancer cells in vitro. SCID mice injected with HCC1428 cells followed by different treatments were used to assess the in vivo efficacy of different agents. Data showed that the combination of everolimus and metformin exerted synergistic inhibitory effects on the growth of breast cancer cells both in culture and in a mouse xenograft model. Further, this combination abrogated S6 and 4EBP1phosphorylation. Collectively, we suggest that the combination of everolimus and metformin may be an effective regimen for treatment of breast cancer, hence warranting further evaluation of the combination in the clinic. PMID:26351208

  1. A combination strategy based brain-computer interface for two-dimensional movement control

    Science.gov (United States)

    Xia, Bin; Maysam, Oladazimi; Veser, Sandra; Cao, Lei; Li, Jie; Jia, Jie; Xie, Hong; Birbaumer, Niels

    2015-08-01

    Objective. Two-dimensional (2D) movement control is an important issue in brain-computer interfaces (BCIs) research because being able to move, for example, a cursor with the brain will enable patients with motor disabilities to control their environment. However, it is still a challenge to continuously control 2D movement with a non-invasive BCI system. In this paper, we developed a 2D cursor control with motor imagery BCI tasks allowing users to move a cursor to any position by using a combination strategy. With this strategy, a user can combine multiple motor imagery tasks, alternatively or simultaneously, to control 2D movements. Approach. After a training session, six participants took part in the first control strategy experiment (the center-out experiment) to verify the effectiveness of the cursor control. Three of the six participants performed an additional experiment, in which they were required to move the cursor to hit five targets in a given sequence. Main results. The average hit rate was more than 95.6% and the trajectories were close to the shortest path. The average hit rate was more than 95.6% and the trajectories were close to the shortest path in the center-out experiment. In the additional experiment, three participants achieved a 100% hit rate with a short trajectory. Significance. The results demonstrated that users were able to effectively control the 2D movement using the proposed strategy. The present system may be used as a tool to interact with the external world.

  2. Clinical Observation on Combined Tuina and Medicated Bath for Early Intervention of Neonatal Brain Injuries

    Institute of Scientific and Technical Information of China (English)

    刘振寰; 丁建英; 韩丑萍

    2010-01-01

    目的:观察推拿、药浴等中医疗法早期干预对婴儿脑损伤的临床疗效.方法:对60例中重度脑损伤婴儿进行小儿健脑推拿及中药浴式水疗,同时配合中医传统五行音乐聆听及运动疗法等治疗.分别于治疗前、治疗3个月后采用Gesell测查法进行发育商(Development Quotient,DQ)评估,并在治疗1年半后进行远期随访.结果:治疗前、治疗3个月及一年半后发育商分别为(34.98±28.94),(66.17±14.91)和(75.40±14.69),与治疗前比较,治疗3个月及一年半后发育商各指标均有显著提高(P=0.000).结论:对脑损伤婴儿进行推拿中医早期干预可促进大脑发育,修复神经损伤,促进运动、认知的发育,有效预防神经系统后遗症的发生.%Objective: To observe the clinical effect of early intervention of combined tuina with medicated bath for neonatal brain injuries.Methods: Brain-benefiting tuina manipulations,medicated bath and music plus exercise therapies were employed in 60 infants with medium or severe brain injuries.The Gesell measurement methods were adopted prior to and 3 months after treatment to evaluate the development quotient(DQ).In addition,the long-term follow-up was made after one and a half years.Result: The scores of DQ prior to treatment,3 month after treatment and 1.5 years after treatment were(34.98±28.94),(66.17±14.91)and(75.40±14.69)respectively,showing a marked improvement after 3months and 1.5 years of treatment(P=0.000).Conclusion: Early intervention using tuina manipulations could enhance the brain development,repair the nerve injury,improve the motion and cognitive ability and prevent the sequela of the nervous system.

  3. Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population

    DEFF Research Database (Denmark)

    Kjaer-Frifeldt, Sanne; Fredslund, Rikke; Lindebjerg, Jan;

    2012-01-01

    To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients.......To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients....

  4. The clinical-immunological analysis of a specific and combined immunotherapy of patients with cervical cancer

    OpenAIRE

    D. K. Kenbayeva; A. F. Lazarev

    2012-01-01

    Research objective is the comparative assessment of efficiency of two various ways of an immunotherapy of patients with cervical cancer. 57 patients with cervical cancer, the III stages, distributed on 3 groups – combined radiotherapy, a combination of a radiotherapy and specific immunotherapy, and also a radiotherapy, specific and adaptive immunotherapy are surveyed. Clinical efficiency of treatment was estimated by means of primary tumor regression and 3-year survival rate. The scheme of co...

  5. Combined endobronchial and oesophageal endosonography for the diagnosis and staging of lung cancer

    DEFF Research Database (Denmark)

    Vilmann, Peter; Clementsen, Paul Frost; Colella, Sara;

    2015-01-01

    New guidelines for combined endobronchial and oesophageal mediastinal nodal staging of lung cancer. This is an official guideline of the European Society of Gastrointestinal Endoscopy (ESGE), produced in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic...... Surgeons (ESTS). It addresses the benefit and burden associated with combined endobronchial and oesophageal mediastinal nodal staging of lung cancer. The Scottish Intercollegiate Guidelines Network (SIGN) approach was adopted to define the strength of recommendations and the quality of evidence....

  6. Combination of the transurethral resection and prostate HIFU ablation at treatment of the localized cancer

    OpenAIRE

    Popkov V.M.; Fomkin R.N.; Blyumberg B.l.; Shatylko T.V.; Sedova L.N.; Abramova E.P.

    2014-01-01

    Research objective: to estimate results of treatment of patients with the localized form of a cancer of a prostate at a combination of a transurethral resection (TURP) and HIFU of an ablation. Objects and research methods: From February, 2009 to February, 2014 of 100 patients with the localized form of a cancer of a prostate were selected for research: 26 patients were included into HIFU and 74 group in group of the combined treatment (TURP+HIFU). Selection criteria for HIFU ablation were ...

  7. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  8. Brain radiation - discharge

    Science.gov (United States)

    Radiation - brain - discharge; Cancer-brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  9. Toward a rational design of combination therapy in cancer

    Science.gov (United States)

    Doucey, Marie-Agnès; Xenarios, Ioannis

    2015-01-01

    By merging computational systems modeling and experimental approaches, we have uncovered treatments reprogramming pro-angiogenic monocytes present in breast tumor into immunologically potent cells capable of mediating an anti-tumor immune response. The unraveled pathways and ligands which underlie monocyte pro-angiogenic activity have a strong predictive value for breast cancer patient relapse – free survival. PMID:26451320

  10. Impact of Triple-Negative Phenotype on Prognosis of Patients With Breast Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Xu Zhiyuan [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Schlesinger, David [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Toulmin, Sushila [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Rich, Tyvin [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Sheehan, Jason, E-mail: jps2f@virginia.edu [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States)

    2012-11-01

    Purpose: To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). Methods and Materials: A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. Results: The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. Conclusion: The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor.

  11. The role of MMP-1 in breast cancer growth and metastasis to the brain in a xenograft model

    Directory of Open Access Journals (Sweden)

    Liu Hui

    2012-12-01

    Full Text Available Abstract Background Brain metastasis is an increasingly common complication for breast cancer patients; approximately 15– 30% of breast cancer patients develop brain metastasis. However, relatively little is known about how these metastases form, and what phenotypes are characteristic of cells with brain metastasizing potential. In this study, we show that the targeted knockdown of MMP-1 in breast cancer cells with enhanced brain metastatic ability not only reduced primary tumor growth, but also significantly inhibited brain metastasis. Methods Two variants of the MDA-MB-231 human breast cancer cell line selected for enhanced ability to form brain metastases in nude mice (231-BR and 231-BR3 cells were found to express high levels of matrix metalloproteinase-1 (MMP-1. Short hairpin RNA-mediated stable knockdown of MMP-1 in 231-BR and 231-BR3 cells were established to analyze tumorigenic ability and metastatic ability. Results Short hairpin RNA-mediated stable knockdown of MMP-1 inhibited the invasive ability of MDA-MB 231 variant cells in vitro, and inhibited breast cancer growth when the cells were injected into the mammary fat pad of nude mice. Reduction of MMP-1 expression significantly attenuated brain metastasis and lung metastasis formation following injection of cells into the left ventricle of the heart and tail vein, respectively. There were significantly fewer proliferating cells in brain metastases of cells with reduced MMP-1 expression. Furthermore, reduced MMP-1 expression was associated with decreased TGFα release and phospho-EGFR expression in 231-BR and BR3 cells. Conclusions Our results show that elevated expression of MMP-1 can promote the local growth and the formation of brain metastases by breast cancer cells.

  12. Pediatric Cancers and Brain Tumors in Adolescents and Young Adults.

    Science.gov (United States)

    McCabe, Martin G; Valteau-Couanet, Dominique

    2016-01-01

    Embryonal tumors classically occur in young children, some principally within the first year of life. Prospective national and international clinical trials during recent decades have brought about progressive improvements in survival, and associated biological studies have advanced our understanding of tumor biology, in some cases allowing biological tumor characteristics to be harnessed for therapeutic benefit. Embryonal tumors continue to occur, albeit less commonly, during childhood, adolescence and throughout adulthood. These tumors are less well understood, usually not managed according to standardized protocols and rarely included in clinical trials. Survival outcomes are generally poorer than their childhood equivalents. We present here a summary of the published literature on embryonal tumors that present ectopically during adolescence and adulthood. We show that for some tumors protocol-driven treatment, supported by accurate and complete diagnostics and staging, can result in equivalent outcomes to those seen during childhood. We make the case that clinical trial eligibility criteria should be disease-based rather than age-based, and support improvements in dialogue between children's and adults' cancer clinicians to improve outcomes for these rare tumors. PMID:27595358

  13. Vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective Systemic chemotherapy for metastatic pancreatic cancer is still a difficult problem in clinical practice.The standard chemotherapy of pancreatic cancer has been gemcitabine,but the response rate is low.Therefore,it is in urgent need to explore an effective clinical therapy for this cancer.This paper,a case report,is aimed at discussing the effectiveness of vinorelbine and cisplatin combined with endostatin as the first-line therapy for metastatic pancreatic cancer.Methods A 52-year-old female pati...

  14. A WKYMVm-containing combination elicits potent anti-tumor activity in heterotopic cancer animal model.

    Directory of Open Access Journals (Sweden)

    Sang Doo Kim

    Full Text Available The development of efficient anti-cancer therapy has been a topic of intense interest for several decades. Combined administration of certain molecules and immune cells has been shown to be an effective form of anti-cancer therapy. Here, we examined the effects of administering an immune stimulating peptide (WKYMVm, 5-fluoro-uracil (5-FU, and mature dendritic cells (mDCs against heterotopic cancer animal model. Administration of the triple combination strongly reduced tumor volume in CT-26-inoculated heterotopic cancer animal model. The induced anti-tumor activity was well correlated with FAS expression, caspase-3 activation, and cancer cell apoptosis. The triple combination treatment caused recruitment of CD8 T lymphocytes and natural killer (NK cells into the tumor. The production of two cytokines, IFN-γ and IL-12, were strongly stimulated by administration of the triple combination. Depletion of CD8 T lymphocytes or NK cells by administration of anti-CD8 or anti-asialoGM1 antibody inhibited the anti-tumor activity and cytokine production of the triple combination. The triple combination strongly inhibited metastasis of colon cancer cells in a heterotopic cancer animal model as well as in a metastatic cancer animal model, and enhanced the survival rate of the mice model. Adoptive transfer of CD8 T lymphocytes and NK cells further increased the survival rate. Taken together, we suggest that the use of triple combination therapy of WKYMVm, 5-FU, and mDCs may have implications in solid tumor and metastasis treatment.

  15. Pancreatic cancer screening employing noncontrast magnetic resonance imaging combined with ultrasonography

    International Nuclear Information System (INIS)

    We have conducted an initial evaluation on the potential of combining noncontrast magnetic resonance imaging (MRI) and ultrasonography (US) to screen for pancreatic cancer. An independent ethics committee approved this study. A total of 2511 patients who underwent US were enrolled. Among them, noncontrast MRI was performed in patients in whom the entire pancreas was difficult to depict or in those with US-suspected pancreatic lesions. In total, using 1.5-T MRI, T1- and T2-weighted imaging, magnetic resonance cholangiopancreatography, and diffusion-weighted imaging, we acquired a variety of images. The efficacy of US and MRI in screening for pancreatic lesions, including pancreatic cancer, was evaluated. Of 2511 patients, 184 underwent MRI, and the pancreas was demonstrated in all of them. Among the 2511, five pancreatic cancers were detected by MRI combined with US (detection rate 0.20%). Of the five pancreatic cancers, three were detected by US (detection rate 0.12%) and two by MRI. Four of the five pancreatic cancers were resectable. By combining noncontrast MRI with US, pancreatic cancer can be detected with high accuracy. Other pancreatic lesions that require follow-up, including intraductal papillary mucinous neoplasms, can also be detected. Thus, pancreatic cancer screening with a combination of US and MRI is suggested. (author)

  16. Profound prevention of experimental brain metastases of breast cancer by temozolomide in an MGMT-dependent manner

    Science.gov (United States)

    Palmieri, Diane; Duchnowska, Renata; Woditschka, Stephan; Hua, Emily; Qian, Yongzhen; Biernat, Wojciech; Sosińska-Mielcarek, Katarzyna; Gril, Brunilde; Stark, Andreas; Hewitt, Stephen; Liewehr, David J; Steinberg, Seth M; Jassem, Jacek; Steeg, Patricia S

    2014-01-01

    Purpose Brain metastases of breast cancer cause neurocognitive damage and are incurable. We evaluated a role for temozolomide in the prevention of brain metastases of breast cancer in experimental brain metastasis models. Experimental Design Temozolomide was administered in mice following earlier injection of brain-tropic human epidermal growth factor receptor 2 (HER2)-positive Jimt1-BR3 and triple negative 231-BR-EGFP sublines, the latter with and without expression of 06-methylguanine-DNA methyltransferase (MGMT). Additionally, the percentage of MGMT-positive tumor cells in 62 patient-matched sets of breast cancer primary tumors and resected brain metastases was determined immunohistochemically. Results Temozolomide, when dosed at 50, 25, 10 or 5 mg/kg, 5 days/week, beginning 3 days after inoculation, completely prevented the formation of experimental brain metastases from MGMT-negative 231-BR-EGFP cells. At a 1 mg/kg dose, temozolomide prevented 68% of large brain metastases, and was ineffective at a dose of 0.5 mg/kg. When the 50 mg/kg dose was administered beginning on days 18 or 24, temozolomide efficacy was reduced or absent. Temozolomide was ineffective at preventing brain metastases in MGMT-transduced 231-BR-EGFP and MGMT-expressing Jimt-1-BR3 sublines. In 62 patient-matched sets of primary breast tumors and resected brain metastases, 43.5% of the specimens had concordant low MGMT expression, while in another 14.5% of sets high MGMT staining in the primary tumor corresponded with low staining in the brain metastasis. Conclusions Temozolomide profoundly prevented the outgrowth of experimental brain metastases of breast cancer in an MGMT-dependent manner. These data provide compelling rationale for investigating the preventive efficacy of temozolomide in a clinical setting. PMID:24634373

  17. Music-induced emotions can be predicted from a combination of brain activity and acoustic features.

    Science.gov (United States)

    Daly, Ian; Williams, Duncan; Hallowell, James; Hwang, Faustina; Kirke, Alexis; Malik, Asad; Weaver, James; Miranda, Eduardo; Nasuto, Slawomir J

    2015-12-01

    It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music-induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music-induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,pmusic induced emotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01). PMID:26544602

  18. MAP training: combining meditation and aerobic exercise reduces depression and rumination while enhancing synchronized brain activity.

    Science.gov (United States)

    Alderman, B L; Olson, R L; Brush, C J; Shors, T J

    2016-01-01

    Mental and physical (MAP) training is a novel clinical intervention that combines mental training through meditation and physical training through aerobic exercise. The intervention was translated from neuroscientific studies indicating that MAP training increases neurogenesis in the adult brain. Each session consisted of 30 min of focused-attention (FA) meditation and 30 min of moderate-intensity aerobic exercise. Fifty-two participants completed the 8-week intervention, which consisted of two sessions per week. Following the intervention, individuals with major depressive disorder (MDD; n=22) reported significantly less depressive symptoms and ruminative thoughts. Typical healthy individuals (n=30) also reported less depressive symptoms at follow-up. Behavioral and event-related potential indices of cognitive control were collected at baseline and follow-up during a modified flanker task. Following MAP training, N2 and P3 component amplitudes increased relative to baseline, especially among individuals with MDD. These data indicate enhanced neural responses during the detection and resolution of conflicting stimuli. Although previous research has supported the individual beneficial effects of aerobic exercise and meditation for depression, these findings indicate that a combination of the two may be particularly effective in increasing cognitive control processes and decreasing ruminative thought patterns. PMID:26836414

  19. Music-induced emotions can be predicted from a combination of brain activity and acoustic features.

    Science.gov (United States)

    Daly, Ian; Williams, Duncan; Hallowell, James; Hwang, Faustina; Kirke, Alexis; Malik, Asad; Weaver, James; Miranda, Eduardo; Nasuto, Slawomir J

    2015-12-01

    It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music-induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music-induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,pmusic induced emotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01).

  20. Results of combination treatment for triple-negative breast cancer

    OpenAIRE

    M. A. Sekundova; V.I. Borisov; A. M. Sdvizhkov

    2014-01-01

    The authors give the results of treatment in 128 patients with operable triple-negative breast cancer (BC). All the patients underwent surgical intervention, the volume of which depended on the stage of the disease. The efficiency of adjuvant and neoadjuvant chemotherapy, as well as pre- and postoperative radiotherapy was evaluated. The side effects of different treatment options were analyzed. Five-year relapse-free and overall survival rates were traced in this patient group. It is conclude...

  1. Combined modality therapy for stage ⅠB cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Yang Qiuan; Qian Shao; Yang Xingsheng

    2009-01-01

    Objective:To evaluate the current approaches for multimodality therapy for stage ⅠB cervical cancer. Methods:The relevant literature has served as a source for identified high or intermediate risks and management of stage ⅠB cervical cancer. Result:The high risks include pelvic lymph node metastasis (PLNM), positive resection margin (PRM), and the in-volvement of parametrium (IPM). The intermediate risks include deep stromal invasion (DSI), bulky tumor size ( BTS), lymphovascular space invasion (LVSI). Adeno-carcinomatous histo-type is the new risk feature relevant to poor prognoses. Both radical hysterectomy plus bilateral pelvic lymph node dissection(PLND) and radical radiotherapy have proven to be equally effec-tive. Surgery is more performed for stage ⅠB1 disease;radiotherapy or chemoradiotherapy is preferable for stage ⅠB2 disease. For patients with one high risk or two of intermediate risks, radical hysterectomy plus PLND followed by concurrent chemoradiotherapy can improve overall survival(OS) and disease-free survival (DFS). Conclusion:The management should be indi-vidualized for stage ⅠB cervical cancer. The optimized multidisciplinary therapy can benefit pa-tients with the best cure and minimum morbidity and complications.

  2. Metformin and phenethyl isothiocyanate combined treatment in vitro is cytotoxic to ovarian cancer cultures

    Directory of Open Access Journals (Sweden)

    Chan Daniel K

    2012-07-01

    Full Text Available Abstract Background High mortality rates in ovarian cancer are largely a result of resistance to currently used chemotherapies. Expanding therapies with a variety of drugs has the potential to reduce this high mortality rate. Metformin and phenethyl isothiocyanate (PEITC are both potentially useful in ovarian cancer, and they are particularly attractive because of their safety. Methods Cell proliferation of each drug and drug combination was evaluated by hemacytometry with Trypan blue exclusion or Sytox green staining for cell death. Levels of total and cleaved PARP were measured by Western blot. General cellular and mitochondrial reactive oxygen species were measured by flow cytometry and live cell confocal microscopy with the fluorescent dyes dihydroethidine and MitoSOX. Results Individually, metformin and PEITC each show inhibition of cell growth in multiple ovarian cancer cell lines. Alone, PEITC was also able to induce apoptosis, whereas metformin was primarily growth inhibitory. Both total cellular and mitochondrial reactive oxygen species were increased when treated with either metformin or PEITC. The growth inhibitory effects of metformin were reversed by methyl succinate supplementation, suggesting complex I plays a role in metformin's anti-cancer mechanism. PEITC's anti-cancer effect was reversed by N-acetyl-cysteine supplementation, suggesting PEITC relies on reactive oxygen species generation to induce apoptosis. Metformin and PEITC together showed a synergistic effect on ovarian cancer cell lines, including the cisplatin resistant A2780cis. Conclusions Here we show that when used in combination, these drugs are effective in both slowing cancer cell growth and killing ovarian cancer cells in vitro. Furthermore, the combination of these drugs remains effective in cisplatin resistant cell lines. Novel combinations such as metformin and PEITC show promise in expanding ovarian cancer therapies and overcoming the high incidence of

  3. Effects of combined octreotide and aspirin on the growth of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    唐承薇; 王春晖; 汤丽平

    2003-01-01

    Objective To investigate the effects of the combination of octreotide and aspirin on the growth of gastric cancer. Methods Proliferation of gastric cancer cell lines treated with octreotide or aspirin was determined by 3 H-thymidine incorporation. After xenografts of human gastric cancer were implanted orthotropically in the stomach of nude mice, they were administered octreotide plus aspirin for 8 weeks. The mRNA of somatostatin receptor in the tissues of gastric carcinoma was detected by reverse transcription polymerase chain reaction (RT-PCR). Cyclooxygenase-2 in gastric cancer tissues was measured by immuno~histochemistry. Results Both octreotide and aspirin significantly reduced the 3 H-thymidine incorporation of gastric cancer cells. Xenografts in situ were found in all stomachs of nude mice except for two in the combination group. Either size or weight of tumors treated by octreotide, aspirin or in combination was significantly reduced as compared with that of controls. The inhibition rate for tumor was 60.6% (octreotide), 39.3% (aspirin), and 85.6% (in combination) respectively. No severe side effects were observed in any treated groups. Somatostatin receptor-2 and -3 were expressed in the transplanted gastric adenocarcinomas. Aspirin could down-regulate the strong expression of cyclooxygenase-2 in the tissue of gastric adenocarcinomas of nude mice.Conclusion A combination of octreotide and aspirin significantly inhibited proliferation of gastric cancer through mediation of somatosatin receptors and suppression of cyclooxygenase-2.

  4. Synthesis and iodine-125 labelling of glucuronide compounds for combined chemo- and radiotherapy of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Unak, T.; Ongun, B. [Ege Univ., Izmir (Turkey). Dept. of Chemistry; Unak, P. [Ege Univ., Izmir (Turkey). Inst. of Nuclear Sciences; Duman, Y. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Medicine

    1997-06-01

    Some types of cancer cells have high levels of beta-glucuronidase activity. This enzyme is able to deglucuronidate a variety of glucuronie derivatives on the cell membrane. Either O- or N-glucuronides can be selectively incorporated into the cancer cells. If the aglycone is cytotoxic, the glucuronide can potentially be used as a selective anti-cancer drug in cancers with high levels of beta-glucuronidase activity. Nevertheless, in vitro studies carried out by various investigators have shown that the cytotoxicities of several glucuronides in cancer cells are not sufficiently high for their use as effective anti-cancer drugs. For this reason, we have synthesized glucuronide compounds radiolabelled with iodine-125 combining the radiotoxicity of this Auger electron emitter with the chemotoxicity of the aglycone portion of the glucuronide. (author).

  5. The Analysis of Erlotinib on Brain Metastases in Patients with Non-small-cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Baohui HAN

    2009-12-01

    Full Text Available Background and objective Brain metastases are common in non-small-cell lung cancer (NSCLC and the prognosis is poor. Erlotinib is a specific inhibitor of the epidermal growth factor receptor-associated tyrosine kinase (EGFRTKI, which has been gradually used in the treatment for advanced NSCLC. The aim of this study is to evaluate the antitumor efficacy and its relevant factors of erlotinib in NSCLC patients with brain metastases. Methods The clinical data of 30 NSCLC patients with brain metastases were reviewed retrospectively. All of them were treated with erlotinib, given orally 150mg daily. These patients discontinued administration of erlotinib until disease progression, death or intolerable side effects. Results In terms of intracranial lesions, partial response (PR was observed in 2 patients (6.7%, with stable disease (SD in 17 patients (56.7%, for overall disease control rate (DCR of 63.4%. As for systemic disease, PR was observed in 2 patients (6.7%, with SD in 5 patients (16.7%, for overall DCR of 23.4%. There was no statistical difference in DCR among different subtypes of age, gender, smoking history, histology, PS score, the number of brain metastases, the onset of brain metastases, chemotherapy, brain radiotherapy and side effects. The median time to disease progression (MTTP and median survival time (MST was 2.4 months and 7.7 months respectively. The 1 and 2 year survival rate was 38.4% and 15.2%. The univariate analysis showed that the survival time was related to the patients’ PS score, smoking history, brain radiotherapy and chemotherapy. The multivariate analysis indicated that brain radiotherapy was the independent prognostic factor and the relationship between the survival time and smoking history was near to statistical significance. Conclusion The patients receiving brain radiotherapy may have better survival benefit. Non-smokers have a trend to survive longer than smokers. Erlotinib may be effective on brain metastases

  6. Toward a brain-computer interface for Alzheimer's disease patients by combining classical conditioning and brain state classification.

    Science.gov (United States)

    Liberati, Giulia; Dalboni da Rocha, Josué Luiz; van der Heiden, Linda; Raffone, Antonino; Birbaumer, Niels; Olivetti Belardinelli, Marta; Sitaram, Ranganatha

    2012-01-01

    Brain-computer interfaces (BCIs) provide alternative methods for communicating and acting on the world, since messages or commands are conveyed from the brain to an external device without using the normal output pathways of peripheral nerves and muscles. Alzheimer's disease (AD) patients in the most advanced stages, who have lost the ability to communicate verbally, could benefit from a BCI that may allow them to convey basic thoughts (e.g., "yes" and "no") and emotions. There is currently no report of such research, mostly because the cognitive deficits in AD patients pose serious limitations to the use of traditional BCIs, which are normally based on instrumental learning and require users to self-regulate their brain activation. Recent studies suggest that not only self-regulated brain signals, but also involuntary signals, for instance related to emotional states, may provide useful information about the user, opening up the path for so-called "affective BCIs". These interfaces do not necessarily require users to actively perform a cognitive task, and may therefore be used with patients who are cognitively challenged. In the present hypothesis paper, we propose a paradigm shift from instrumental learning to classical conditioning, with the aim of discriminating "yes" and "no" thoughts after associating them to positive and negative emotional stimuli respectively. This would represent a first step in the development of a BCI that could be used by AD patients, lending a new direction not only for communication, but also for rehabilitation and diagnosis.

  7. Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs

    Science.gov (United States)

    Gunn, Roger N; Summerfield, Scott G; Salinas, Cristian A; Read, Kevin D; Guo, Qi; Searle, Graham E; Parker, Christine A; Jeffrey, Phil; Laruelle, Marc

    2012-01-01

    The passage of drugs in and out of the brain is controlled by the blood–brain barrier (BBB), typically, using either passive diffusion across a concentration gradient or active transport via a protein carrier. In-vitro and preclinical measurements of BBB penetration do not always accurately predict the in-vivo situation in humans. Thus, the ability to assay the concentration of novel drug candidates in the human brain in vivo provides valuable information for derisking of candidate molecules early in drug development. Here, positron emission tomography (PET) measurements are combined with in-vitro equilibrium dialysis assays to enable assessment of transport and estimation of the free brain concentration in vivo. The PET and equilibrium dialysis data were obtained for 36 compounds in the pig. Predicted P-glycoprotein (P-gp) status of the compounds was consistent with the PET/equilibrium dialysis results. In particular, Loperamide, a well-known P-gp substrate, exhibited a significant concentration gradient consistent with active efflux and after inhibition of the P-gp process the gradient was removed. The ability to measure the free brain concentration and assess transport of novel compounds in the human brain with combined PET and equilibrium dialysis assays can be a useful tool in central nervous system (CNS) drug development. PMID:22274741

  8. Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wairagu, Peninah M. [Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Park, Kwang Hwa [Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Kim, Jihye [Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Choi, Jong-Whan; Kim, Hyun-Won; Yeh, Byung-Il [Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Jung, Soon-Hee [Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Yong, Suk-Joong [Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Jeong, Yangsik, E-mail: yjeong@yonsei.ac.kr [Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of); Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of)

    2014-05-09

    Highlights: • The 48 NR genes and 48 biological anti-cancer targets are profiled in paired-cells. • Growth inhibition by NR ligands or TKIs is target receptor level-dependent. • T0901317 with gefitinib/PHA665752 shows additive growth inhibition in lung cells. - Abstract: Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs.

  9. Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer

    International Nuclear Information System (INIS)

    Highlights: • The 48 NR genes and 48 biological anti-cancer targets are profiled in paired-cells. • Growth inhibition by NR ligands or TKIs is target receptor level-dependent. • T0901317 with gefitinib/PHA665752 shows additive growth inhibition in lung cells. - Abstract: Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. The combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs

  10. DOXIL when combined with Withaferin A (WFA) targets ALDH1 positive cancer stem cells in ovarian cancer

    Science.gov (United States)

    Kakar, Sham S.; Worth, Christopher A.; Wang, Zhenglong; Carter, Kelsey; Ratajczak, Mariusz; Gunjal, Pranesh

    2016-01-01

    Ovarian cancer is a highly aggressive and deadly disease. Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly cisplatin or carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately, after few months of initial treatment, tumor relapse occurs due to platinum-resistance. DOXIL (liposomal preparation of doxorubicin) is a choice of drug for recurrent ovarian cancer. However, its response rate is very low and is accompanied by myocardial toxicity. Resistance to chemotherapy and recurrence of cancer is primarily attributed to the presence of cancer stem cells (CSCs), a small population of cells present in cancer. Effect of DOXIL and withaferin A (WFA), both alone and in combination, was investigated on cell proliferation of ovarian cancer cell line A2780 and tumor growth in SCID mice bearing i.p. ovarian tumors. ALDH1 cells were isolated from A2780 using cell sorter, and effect of DOXIL and WFA both alone and in combination on tumorigenic function of ALDH1 was studied using spheroids formation assays in vitro. Western blots were performed to examine the expression of ALDH1 and Notch 1 genes. In our studies, we showed, for the first time, that DOXIL when combined with withaferin A (WFA) elicits synergistic effect on inhibition of cell proliferation of ovarian cancer cells and inhibits the expression of ALDH1 protein, a marker for ALDH1 positive cancer stem cells (CSCs), and Notch1, a signaling pathway gene required for self-renewal of CSCs. Inhibition of expression of both ALDH1 and Notch1 genes by WFA was found to be dose dependent, whereas DOXIL (200 nM) was found to be ineffective. SCID mice, bearing i.p. ovarian tumors, were treated with a small dose of DOXIL (2 mg/kg) in combination with a sub-optimal dose of WFA (2 mg/kg) which resulted in a highly significant (60% to 70%) reduction in tumor growth, and complete inhibition of metastasis

  11. The clinical-immunological analysis of a specific and combined immunotherapy of patients with cervical cancer

    Directory of Open Access Journals (Sweden)

    D. K. Kenbayeva

    2012-01-01

    Full Text Available Research objective is the comparative assessment of efficiency of two various ways of an immunotherapy of patients with cervical cancer. 57 patients with cervical cancer, the III stages, distributed on 3 groups – combined radiotherapy, a combination of a radiotherapy and specific immunotherapy, and also a radiotherapy, specific and adaptive immunotherapy are surveyed. Clinical efficiency of treatment was estimated by means of primary tumor regression and 3-year survival rate. The scheme of combined immunotherapy was shown to possess the most clinical efficiency. Positive dynamics of cell immunity indicators was accompanied to clinical efficiency of treatment.

  12. Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ding Xiao

    2012-07-01

    Full Text Available Abstract Background Brain metastases (BM is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2 NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset. Methods Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM. Results Fifty-three (24.4 % patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001 and the ratio of metastatic to examined nodes or lymph node ratio (LNR ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000 were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %. Conclusions In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.

  13. Combination Treatment of Tamoxifen with Risperidone in Breast Cancer

    OpenAIRE

    Wei-Lan Yeh; Hui-Yi Lin; Hung-Ming Wu; Dar-Ren Chen

    2014-01-01

    Tamoxifen has long been used and still is the most commonly used endocrine therapy for treatment of both early and advanced estrogen receptor-positive breast cancer in pre- and post-menopause women. Tamoxifen exerts its cytotoxic effect primarily through cytostasis which is associated with the accumulation of cells in the G0/G1 phase of the cell cycle. Apoptotic activity can also be exerted by tamoxifen which involves cleavage of caspase 9, caspase 7, caspase 3, and poly-ADP-ribose polymerase...

  14. Breast cancer brain metastases responding to lapatinib plus capecitabine as second-line primary systemic therapy.

    Science.gov (United States)

    Bergen, Elisabeth S; Berghoff, Anna S; Rudas, Margaretha; Preusser, Matthias; Bartsch, Rupert

    2015-06-01

    Brain metastases (BM) are diagnosed in up to 40% of HER2-positive breast cancer patients. Standard treatment includes local approaches such as whole-brain radiotherapy (WBRT), radiosurgery, and neurosurgery. The landscape trial established primary systemic therapy as an effective and safe alternative to WBRT in selected patients with Her2-positive BM. We aim to further focus on the role of systemic therapy in oligosymptomatic patients by presenting this case report. We report on a 50-year-old patient diagnosed with multiple BM 5 years after early breast cancer diagnosis. As the patient was asymptomatic and had a favorable diagnosis-specific GPA score, she received primary systemic treatment with T-DM1. She achieved partial remission within the brain for eight treatment cycles and then progressed despite stable extracranial disease. As the patient remained asymptomatic and refused WBRT, we decided upon trastuzumab, lapatinib plus capecitabine as second-line therapy. Another partial remission of BM was observed; to date, she has received 11 treatment cycles without any sign of disease progression. In this case, WBRT was delayed by at least 14 months, again indicating the activity of systemic treatment in BM. Apparently, in selected patients, BM can be controlled with multiple lines of systemic therapy similar to extracranial disease. Further investigation of systemic treatment approaches is therefore warranted.

  15. Labeling and biodistribution of therapeutic radiopharmaceutical for brain cancer 125I-Nimotuzumab in normal mice

    International Nuclear Information System (INIS)

    Nimotuzumab is a monoclonal antibody which known giving contribution in anti proliferation, pro apoptosis and antiangionik effect on the therapy of brain cancer (glioma). The labeling of monoclonal antibody nimotuzumab with 125I which radiate auger electrons has been done with idogen method. The best result of radiochemical purity (97%) was shown in fraction 6 with the mol ratio of nimotuzumab towards potassium iodide and iodogen was 1 : 2 : 1200. Radiochemical purity was examined by paper chromatography with whatman paper no. 1 as the stationary phase and ethano!-butanol-ammonium hydroxide with a ratio of 3 : 2 : 1 as the mobile phase. Rf Values for 125I-nimotuzumab is 0.0, while Rf value of 125I .is 0.9. The biodistribution result on normal mice for 72 hours showed that 125I-nimotuzumab not only has a long half-life time but also has high accumulation in liver (1.97 + 1.18%), kidney (0.82 + 0.28%) and muscle (0.61+ 0.98%). The highest accumulation in brain on normal mice (0.128 + 0.06 %) occurred 24 hours after injection. Based on the therapeutic effects and organ accumulation on normal mice, 125I-nimotuzumab could be potentially used for brain cancer therapy. (author)

  16. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs.

  17. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs. PMID:26454049

  18. 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.

  19. A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Larsen, Pia Bükmann; Kümler, Iben; Nielsen, Dorte Lisbet

    2013-01-01

    Patients with HER2-positive breast cancer are living still longer and increasingly experiencing brain metastases. Current HER2-targeted therapies have limited potential to cross the blood-brain-barrier. We performed a systematic review to investigate data on HER2-targeting therapies...... in the treatment of brain metastases in breast cancer. We searched PUBMED for all human studies published 1998-2012 using the following search terms: breast neoplasm/cancer, human epidermal growth factor receptor 2/HER2, ErbB2, trastuzumab, lapatinib, brain/cerebral neoplasm/metastases and blood-brain barrier. We...

  20. Synergistic inhibition of cancer cell proliferation with a combination of δ-tocotrienol and ferulic acid

    Energy Technology Data Exchange (ETDEWEB)

    Eitsuka, Takahiro, E-mail: eitsuka@nupals.ac.jp [Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603 (Japan); Tatewaki, Naoto; Nishida, Hiroshi; Kurata, Tadao [Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603 (Japan); Nakagawa, Kiyotaka; Miyazawa, Teruo [Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan)

    2014-10-24

    Highlights: • δ-Tocotrienol (δ-T3) and ferulic acid (FA) synergistically inhibit cancer cell growth. • The combination of δ-T3 and FA induces G1 arrest by up-regulating p21. • The synergy is attributed to an increase in the cellular concentration of δ-T3 by FA. - Abstract: Rice bran consists of many functional compounds and thus much attention has been focused on the health benefits of its components. Here, we investigated the synergistic inhibitory effects of its components, particularly δ-tocotrienol (δ-T3) and ferulic acid (FA), against the proliferation of an array of cancer cells, including DU-145 (prostate cancer), MCF-7 (breast cancer), and PANC-1 (pancreatic cancer) cells. The combination of δ-T3 and FA markedly reduced cell proliferation relative to δ-T3 alone, and FA had no effect when used alone. Although δ-T3 induced G1 arrest by up-regulating p21 in PANC-1 cells, more cells accumulated in G1 phase with the combination of δ-T3 and FA. This synergistic effect was attributed to an increase in the cellular concentration of δ-T3 by FA. Our results suggest that the combination of δ-T3 and FA may present a new strategy for cancer prevention and therapy.

  1. The application of prodrug-based nano-drug delivery strategy in cancer combination therapy.

    Science.gov (United States)

    Ge, Yanxiu; Ma, Yakun; Li, Lingbing

    2016-10-01

    Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N-DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. PMID:27400243

  2. Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

    Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

  3. Intra-arterial and intra-venous chemotherapy combined with radiation in the treatment of brain tumours

    International Nuclear Information System (INIS)

    The present investigations were undertaken to study the effect of combining different modalities of chemotherapy with radiation in post-operative treatment of brain tumours. The conclusions and clinical implication of the investigations are as follows: The combination of combined intra-arterial chemotherapy followed by radiation leads to an increased median survival with more long term survivors in patients with anaplastic astrocytomas and in patients older than 40 years with astrocytomas. In patients with glioblastoma multiforme, this modality of treatment do not improve median survival, but an increased number of long-term survivors may be seen. Patients younger than 40 years with astrocytomas do not benefit from this modality of treatment. A parallelism exists between sensitivity to chemotherapy and response to radiotherapy. Patients who will benefit from the treatment may be selected early, normally two months after treatment start. Combining intra-arterial chemotherapy and radiation does not lead to an increased incidence of adverse CNS reactions. Specific transient abnormalities in the brain may occur during the first year after treatment and may be misinterpreted as tumour recurrence. EEG may be valuable in predicting adverse CNS reactions following treatment. Nuclear brain scan may be of valuable in selecting the patients who are in danger of developing adverse CNS reactions. Intra-arterial chemotherapy does have an effect in patients with brain tumours who have recurrent tumour after radiation. The most important prognostic factors are age, corticosteroid dependency at treatment start, performance status, histology and frontal lobe location. 103 refs., 2 tabs

  4. In vivo evaluation of P-glycoprotein and breast cancer resistance protein modulation in the brain using [{sup 11}C]gefitinib

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Kazunori [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: kawamur@nirs.go.jp; Yamasaki, Tomoteru; Yui, Joji; Hatori, Akiko; Konno, Fujiko; Kumata, Katsushi; Irie, Toshiaki; Fukumura, Toshimitsu; Suzuki, Kazutoshi; Kanno, Iwao; Zhang Mingrong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2009-04-15

    Gefitinib (Iressa) is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. Recent studies confirmed that gefitinib interacted with the breast cancer resistance protein (BCRP) at submicromolar concentrations, whereas other multidrug transporters, including P-glycoprotein (P-gp), showed much lower reactivity toward gefitinib. Recently, many tracers for positron emission tomography (PET) have been prepared to study P-gp function in vivo; however, PET tracers had not been evaluated for both P-gp and BCRP modulation in the brain. Therefore, we evaluated in vivo brain penetration-mediated P-gp and BCRP in mice using [{sup 11}C]gefitinib. Co-injection with gefitinib (over 50 mg/kg), a nonspecific P-gp modulator cyclosporin A (50 mg/kg), and the dual P-gp and BCRP modulator GF120918 (over 5 mg/kg) induced an increase in the brain uptake of [{sup 11}C]gefitinib in mice 30 min after injection. In the PET study of mice, the radioactivity level in the brain with co-injection of GF120918 (5 mg/kg) was three- to fourfold higher than that in control after initial uptake. The radioactivity level in the brain in P-gp and Bcrp knockout mice was approximately eightfold higher than that in wild-type mice 60 min after injection. In conclusion, [{sup 11}C]gefitinib is a promising PET tracer to evaluate the penetration of gefitinib into the brain by combined therapy with P-gp or BCRP modulators, and into brain tumors. Furthermore, PET study with GF120918 is a promising approach for evaluating brain penetration-mediated P-gp and BCRP.

  5. Use of estetrol with other steroids for attenuation of neonatal hypoxic-Ischemic brain injury: to combine or not to combine?

    Science.gov (United States)

    Tskitishvili, Ekaterine; Pequeux, Christel; Munaut, Carine; Viellevoye, Renaud; Nisolle, Michelle; Noël, Agnes; Foidart, Jean-Michel

    2016-01-01

    Estetrol (E4), estradiol (E2) and progesterone (P4) have important antioxidative and neuroprotective effects in neuronal system. We aimed to study the consequence of combined steroid therapy in neonatal hypoxic-ischemic encephalopathy (HIE). In vitro the effect of E4 combined with other steroids on oxidative stress and the cell viability in primary hippocampal cultures was evaluated by lactate dehydrogenase and cell survival assays. In vivo neuroprotective and therapeutic efficacy of E4 combined with other steroids was studied in HIE model of immature rats. The rat pups rectal temperature, body and brain weights were evaluated. The hippocampus and the cortex were investigated by histo/immunohistochemistry: intact cell number counting, expressions of markers for early gray matter lose, neuro- and angiogenesis were studied. Glial fibrillary acidic protein was evaluated by ELISA in blood samples. In vitro E4 and combinations of high doses of E4 with P4 and/or E2 significantly diminished the LDH activity and upregulated the cell survival.In vivopretreatment or treatment by different combinations of E4 with other steroids had unalike effects on body and brain weight, neuro- and angiogenesis, and GFAP expression in blood. The combined use of E4 with other steroids has no benefit over the single use of E4. PMID:27231853

  6. Use of estetrol with other steroids for attenuation of neonatal hypoxic-ischemic brain injury: to combine or not to combine?

    Science.gov (United States)

    Tskitishvili, Ekaterine; Pequeux, Christel; Munaut, Carine; Viellevoye, Renaud; Nisolle, Michelle; Noël, Agnes; Foidart, Jean-Michel

    2016-06-01

    Estetrol (E4), estradiol (E2) and progesterone (P4) have important antioxidative and neuroprotective effects in neuronal system. We aimed to study the consequence of combined steroid therapy in neonatal hypoxic-ischemic encephalopathy (HIE). In vitro the effect of E4 combined with other steroids on oxidative stress and the cell viability in primary hippocampal cultures was evaluated by lactate dehydrogenase and cell survival assays. In vivo neuroprotective and therapeutic efficacy of E4 combined with other steroids was studied in HIE model of immature rats. The rat pups rectal temperature, body and brain weights were evaluated.The hippocampus and the cortex were investigated by histo/immunohistochemistry: intact cell number counting, expressions of markers for early gray matter lose, neuro- and angiogenesis were studied. Glial fibrillary acidic protein was evaluated by ELISA in blood samples. In vitro E4 and combinations of high doses of E4 with P4 and/or E2 significantly diminished the LDH activity and upregulated the cell survival.In vivopretreatment or treatment by different combinations of E4 with other steroids had unalike effects on body and brain weight, neuro- and angiogenesis, and GFAP expression in blood. The combined use of E4 with other steroids has no benefit over the single use of E4. PMID:27231853

  7. SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Qianxia Li

    Full Text Available PURPOSE: Brain metastasis (BM from non-small cell lung cancer (NSCLC is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of brain metastasis. PATIENTS AND METHODS: We genotyped 33 SNPs from 13 genes in the TGF-β signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC. Kaplan-Meier analysis was used to assess brain metastasis risk; Cox hazard analyses were used to evaluate the effects of various patient and disease characteristics on the risk of brain metastasis. RESULTS: The median age of the 116 men and 45 women in the study was 58 years; 62 (39% had stage IIIB or IV disease. Within 24 months after initial diagnosis of lung cancer, brain metastasis was found in 60 patients (37%. Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain metastasis at 24 months follow-up (hazard ratio [HR] 2.540, 95% confidence interval [CI] 1.204-5.359, P = 0.014; and HR 1.885, 95% CI 1.086-3.273, P = 0.024, compared with the GA or CT/CC genotypes, respectively. When we analyzed combined subgroups, these rates showed higher for those having both the GG genotype of SMAD6: rs12913975 and the TT genotype of INHBC: rs4760259 (HR 2.353, 95% CI 1.390-3.985, P = 0.001. CONCLUSIONS: We found the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with risk of brain metastasis in patients with NSCLC. This finding, if confirmed, can help to identify patients at high risk of brain metastasis.

  8. Combined doxorubicin and paclitaxel in advanced breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T;

    1996-01-01

    -550). The main toxicities were neutropenia, parestesia, nausea/vomiting, alopecia, myalgia and cardiotoxicity. Fifteen patients (50%) had reductions of left ventricular ejection fraction of below normal levels and 6 of these patients (20%) developed congestive heart failure. CONCLUSION: The combination...

  9. Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models

    Energy Technology Data Exchange (ETDEWEB)

    Marino, Ana-Maria [Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden); Sofiadis, Anastasios [Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Department of Oncology-Pathology, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden); Baryawno, Ninib; Johnsen, John Inge [Department of Women' s and Children' s Health, Karolinska Institutet, Stockholm (Sweden); Larsson, Catharina [Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden); Vukojevic, Vladana [Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden); Ekstroem, Tomas J., E-mail: tomas.ekstrom@ki.se [Department of Clinical Neuroscience, Karolinska Institutet, Stockholm (Sweden); Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm (Sweden)

    2011-07-22

    Highlights: {yields} The histone deacetylase inhibitor 4-phenylbutyrate substantially enhance efficacy of the receptor tyrosine kinase inhibitors gefitinib or vandetanib in glioma and medulloblastoma cell lines. {yields} Cell death increases and clonogenic survival is reduced in the combination treatments, over mono-therapy. {yields} Combination treatments with these drugs may improve clinical outcome for cancer therapy. -- Abstract: We have investigated in vitro effects of anticancer therapy with the histone deacetylase inhibitor (HDACi) 4-phenylbutyrate (4-PB) combined with receptor tyrosine kinase inhibitors (RTKi) gefitinib or vandetanib on the survival of glioblastoma (U343MGa) and medulloblastoma (D324Med) cells. In comparison with individual effects of these drugs, combined treatment with gefitinib/4-PB or vandetanib/4-PB resulted in enhanced cell killing and reduced clonogenic survival in both cell lines. Our results suggest that combined treatment using HDACi and RTKi may beneficially affect the outcome of cancer therapy.

  10. Treatment of brain metastases of lung cancer in the era of precision medicine.

    Science.gov (United States)

    Haughton, Michael E; Chan, Michael D; Watabe, Kounosuke; Bonomi, Marcelo; Debinski, Waldemar; Lesser, Glenn J; Ruiz, Jimmy

    2016-01-01

    Common and deadly complications of non-small cell lung cancer (NSCLC) are brain metastases (BM). BM portends a poorer prognosis with limited effective treatment options and current management strategies present several challenges from iatrogenic complications of supportive medications, optimal delivery of drug across the blood-brain barrier, and preservation of neurocognitive function. Long term side effects and survivorship issues have become more evident in the era of targeted therapy where a systemic disease is much better controlled. Targeted therapies and immunotherapy are beginning to provide improvements in responses and survival rates. With further advancements and experience, our knowledge in this era of precision medicine will likely lead to strides in improving the quality of life and overall survival of patients with BM from NSCLC. In this review, we present the most recent updates in treatment of BM in NSCLC in regards to targeted and immunotherapy. PMID:26709658

  11. Next Generation Sequencing As an Aid to Diagnosis and Treatment of an Unusual Pediatric Brain Cancer

    Directory of Open Access Journals (Sweden)

    John Glod

    2014-07-01

    Full Text Available Classification of pediatric brain tumors with unusual histologic and clinical features may be a diagnostic challenge to the pathologist. We present a case of a 12-year-old girl with a primary intracranial tumor. The tumor classification was not certain initially, and the site of origin and clinical behavior were unusual. Genomic characterization of the tumor using a Clinical Laboratory Improvement Amendment (CLIA-certified next-generation sequencing assay assisted in the diagnosis and translated into patient benefit, albeit transient. Our case argues that next generation sequencing may play a role in the pathological classification of pediatric brain cancers and guiding targeted therapy, supporting additional studies of genetically targeted therapeutics.

  12. Frontiers of X-ray spectromicroscopy in biology and medicine: Gadolinium in brain cancer

    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.

    2000-02-01

    We present the first feasibility test of spectromicroscopy on the microlocalization of gadolinium in brain cancer tissue. A gadolinium compound was injected to the patients before the brain tumor was extracted with surgery, and we looked for Gd in the tumor tissue. The goal of the experiment was to understand if Gd Neutron Capture Therapy (GdNCT) is viable for clinical tests, i.e. if there is enough Gd, and it is localized near the nuclei of tumor cells. The experiments were performed using the MEPHISTO X-ray PhotoElectron Emission Microscope (X-PEEM) at the Wisconsin Synchrotron Radiation Center. The present results demonstrate the feasibility of the experiment, and suggest how to improve the sample preparation and data acquisition to achieve the goal.

  13. Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment.

    Science.gov (United States)

    Niwińska, Anna

    2016-10-01

    The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.

  14. Combination of external irradiation and androgen suppression for prostate cancer: Facts and questions

    International Nuclear Information System (INIS)

    The combination of radiotherapy and androgen suppression with luteinizing hormone releasing hormone agonist is mainly devoted to locally advanced prostate cancer and intermediate or poor risk localized prostate cancer. They are based on phase III randomized trials which have shown that for locally advanced prostate cancer, a four-month complete androgen blockade initiated two months prior radiotherapy and stopped at the completion of radiotherapy increased overall survival in patients with Gleason scores 2-6, meanwhile, an adjuvant long-term androgen suppression (2.5 to three years) improved significantly the overall survival. Complete androgen blockade with a four to six months duration, combined with external irradiation, enhanced the overall survival in patients with intermediate or poor risk localized prostate cancer. (authors)

  15. The importance of combining MRI and large-scale digital histology in neuroimaging studies of brain connectivity and disease.

    Directory of Open Access Journals (Sweden)

    Jacopo eAnnese

    2012-04-01

    Full Text Available One of the major issues hindering a comprehensive connectivity model for the human brain is the difficulty in linking Magnetic Resonance Imaging (MRI to anatomical evidence produced by histological methods. Non-invasive and postmortem neuroimaging methodologies are still largely incompatible in terms of sample size, scale, and resolution. To help bridge the hiatus between different approaches we established a program that characterizes the brain of individual subjects, combining in vivo MRI with postmortem neuroanatomy. The direct correlation of MRI and histological features is possible, because registered images from different modalities represent the same regions in the same brain. Our comparisons are also facilitated by large-scale, digital microscopy techniques that afford images of the whole-brain sections at cellular resolution. The goal is to create a neuroimaging catalogue representative of discrete age groups and specific neurological conditions. Individually, the datasets allow for investigating the relationship between different modalities; combined, they provide sufficient predictive power to inform analyses and interpretations made in the context of exclusively non-invasive studies of brain connectivity and disease.

  16. Quality of Life Patients with Breast Cancer Therapy Combination Fluorouracil, Doxorubicin, and Cyclofosfamide

    OpenAIRE

    Dewi D. Agustini; Emma Surahman; Rizky Abdulah

    2015-01-01

    Treatment of breast cancer with combination chemotherapy Florouracil, doxorubicin, and Cyclofosfamide (FAC) lead to differences in the quality of life of patients is important to know because it can support the effectiveness of patient treatment. The aim of the study was to measure the difference and know the dimensions that affect the quality of life of breast cancer patients from each cycle of chemotherapy in Hasan Sadikin Hospital. This research is an observational analytic cross sectio...

  17. Morphological aspects of efficiency of the combined treatment of distal gastric cancer with preoperative irradiation

    OpenAIRE

    Dumanskiy Y.V.; Balashova O.I.; Vlasenko D.L.; Teteryadchenko T.E.; Velichko I.N.

    2009-01-01

    The cancer of stomach continues to occupy one of leading places in the structure of oncologic pathology in Ukraine and in the world. The general goal of our research was an estimation of efficiency and comparison of results of the combined and surgical treatment of distal gastric cancer, and also investigation of dependence of the got results from the morphological features of tumor. From January, 1995 for December, 2002 in the Dnepropetrovsk regional clinical oncologic dispensary got treatme...

  18. Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration

    Science.gov (United States)

    Gibbs, Holly C.; Dodson, Colin R.; Bai, Yuqiang; Lekven, Arne C.; Yeh, Alvin T.

    2014-12-01

    During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

  19. Cancer risk by combined levels of YKL-40 and C-reactive protein in the general population

    DEFF Research Database (Denmark)

    Allin, Kristine Højgaard; Bojesen, S E; Johansen, J S;

    2012-01-01

    YKL-40 and C-reactive protein (CRP) are biomarkers that may reflect cancer-related subclinical inflammation. We assessed elevated YKL-40 and CRP levels as combined risk predictors for cancer.......YKL-40 and C-reactive protein (CRP) are biomarkers that may reflect cancer-related subclinical inflammation. We assessed elevated YKL-40 and CRP levels as combined risk predictors for cancer....

  20. Intraoperative radiotherapy combined with resection for pancreatic cancer. Analysis of survival rates and prognostic factors

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the efficiency of intraoperative radiotherapy (IORT) combined with surgical resection. Subjects were consecutive 69 patients with pancreatic cancer treated with surgery alone (n=31) or surgical resection combined with IORT (n=38) in a 13 year period between 1991 and 2003. We evaluated the effects of IORT against local recurrence of cancer and patients' survival, retrospectively. Furthermore, clinicopathological factors affecting the 5-year survival rate in the two groups were comparatively investigated. The IORT group showed a significantly lower local recurrence rate of cancer than that in the surgery alone group (7.8% and 22.6%, respectively; p<0.05). The 5-year survival probability in the IORT group was significantly higher than that in the surgery alone group (29.9% and 3.4%, respectively; p<0.05). According to the Japanese classification of pancreatic cancer, cancers located in the pancreas body or tail, no local residual cancer post operative procedure (R0), low grade local cancer progression (t1, 2), and low grade intrapancreatic neural invasion (ne0, 1) were significantly better prognostic factors in the IORT group than those in the surgery alone group. There were no significant differences between the both groups in the 5-year survival rate in terms of the sex of the patients, cancer of the pancreas head, histological type, more than R1, the presence of lymph node involvement, ne2-3, and clinical stages. IORT is a useful intraoperative adjuvant therapy for pancreatic cancer, when the curative resection is achieved. Our data have suggested that IORT suppresses the local recurrence of cancer and provides the significant survival benefit for those patients. (author)

  1. Duodenal Hemorrhage from Pancreatic Cancer Infiltration Controlled through Combination Therapy with Gemcitabine and S-1

    Directory of Open Access Journals (Sweden)

    Ryoji Takada

    2014-06-01

    Full Text Available 2.6% of pancreatic cancer patients have the primary manifestation of gastrointestinal bleeding. It is not feasible to stop the duodenal hemorrhage caused by the pancreatic cancer infiltration. A 43-year-old woman who was diagnosed as having pancreatic cancer with multiple hepatic metastases and duodenal infiltration was administered gemcitabine and S-1 combination therapy. During the chemotherapy, initially, bleeding occurred due to duodenal infiltration. However, we continued the chemotherapy and duodenal infiltration was markedly reduced in size and did not rebleed. Aggressive chemotherapy contributed to maintenance of performance status as well as improvement of quality of life for the patient.

  2. Cryotherapy and radiotherapy combination in extensive and recurrent types of head and neck skin cancer treatment

    International Nuclear Information System (INIS)

    The method of infiltrative skin cancer treatment based on different variants of radiotherapy and cryotherapy combination is described. During the period of 1988-2006 the Department of head and neck neoplasms of N. N. Blohin Russian Cancer Research Center provided radiation and cryogenic treatment of 94 patients with locally advanced head and neck epidermoid and basal cell cancer. For this purpose before every radiotherapy session the tumor was exposed to cryo cooling till freezing temperature (-5 degrees C). The total involution of tumors was observed at 91 patients. Residual tumors were removed surgically. The follow-up showed good functional and aesthetic results, retention of local tissues.

  3. Combined HSP90 and kinase inhibitor therapy: Insights from The Cancer Genome Atlas.

    Science.gov (United States)

    Schwartz, Harvey; Scroggins, Brad; Zuehlke, Abbey; Kijima, Toshiki; Beebe, Kristin; Mishra, Alok; Neckers, Len; Prince, Thomas

    2015-09-01

    The merging of knowledge from genomics, cellular signal transduction and molecular evolution is producing new paradigms of cancer analysis. Protein kinases have long been understood to initiate and promote malignant cell growth and targeting kinases to fight cancer has been a major strategy within the pharmaceutical industry for over two decades. Despite the initial success of kinase inhibitors (KIs), the ability of cancer to evolve resistance and reprogram oncogenic signaling networks has reduced the efficacy of kinase targeting. The molecular chaperone HSP90 physically supports global kinase function while also acting as an evolutionary capacitor. The Cancer Genome Atlas (TCGA) has compiled a trove of data indicating that a large percentage of tumors overexpress or possess mutant kinases that depend on the HSP90 molecular chaperone complex. Moreover, the overexpression or mutation of parallel activators of kinase activity (PAKA) increases the number of components that promote malignancy and indirectly associate with HSP90. Therefore, targeting HSP90 is predicted to complement kinase inhibitors by inhibiting oncogenic reprogramming and cancer evolution. Based on this hypothesis, consideration should be given by both the research and clinical communities towards combining kinase inhibitors and HSP90 inhibitors (H90Ins) in combating cancer. The purpose of this perspective is to reflect on the current understanding of HSP90 and kinase biology as well as promote the exploration of potential synergistic molecular therapy combinations through the utilization of The Cancer Genome Atlas. PMID:26070366

  4. Long-term outcome of gamma knife radiosurgery for metastatic brain tumors  originating from lung cancer

    Directory of Open Access Journals (Sweden)

    Shyamal C Bir

    2014-01-01

    Full Text Available Background: Gamma knife radiosurgery (GKRS has emerged as an important treatment option for metastasis brain tumors (MBTs. However, the long-term outcome of GKRS on MBTs originating from lung carcinoma is not well understood. The treatment of MBTs derived from lung cancer with GKRS at our institution is reviewed. Methods: We performed a retrospective review (2000-2013 of 173 patients with MBTs from lung cancer who received GKRS. Out of 173 patients, 38 patients had recurrent tumors after microsurgical resection and whole brain radiotherapy (WBT. Results: GKRS in MBTs metastasized from lung carcinoma showed significant variations in tumor growth control (decreased in 79 [45.7%] patients, arrested growth in 54 [31.2%] patients, and increased tumor size in 40 [23.1%] patients. The median survival in the study population was 14 months. Overall survival after 3 years was 25%, whereas progression-free survival after 3 years was 45%. The predictive factors for improving survival in the patients with MBTs were recursive partitioning analysis (RPA class I (P = 0.005, absence of hydrocephalus (P = 0.001, Karnofsky performance scale (KPS >70 (P = 0.007, age ≤65 (P = 0.041, tumor size ≤3 cm (P = 0.023, controlled primary tumor (P = 0.049, and single number of MBTS (P = 0.044. Conclusion: Long-term follow-up revealed that GKRS offers a high rate of tumor control and good overall survival period in both new and recurrent patients with MBTs originating from lung carcinoma. Thus, GKRS is an effective treatment option for new patients with MBTs from lung cancer, as well as an adjuvant therapy in patients with recurrent MBTs derived from lung cancer.

  5. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy.

    Science.gov (United States)

    Leone, José Pablo; Lee, Adrian V; Brufsky, Adam M

    2015-07-01

    Brain metastasis (BM) in patients with breast cancer is a catastrophic event that results in poor prognosis. Identification of prognostic factors associated with breast cancer brain metastases (BCBM) could help to identify patients at risk. The aim of this study was to assess clinical characteristics, prognostic factors, and survival of patients with BCBM who had craniotomy and resection in a series of patients treated with modern multimodality therapy. We analyzed 42 patients with BCBM who underwent resection. Patients were diagnosed with breast cancer between April 1994 and May 2010. Cox proportional hazards regression was selected to describe factors associated with time to BM, survival from the date of first recurrence, and overall survival (OS). Median age was 51 years (range 24-74). Median follow-up was 4.2 years (range 0.6-18.5). The proportion of the biological subtypes of breast cancer was ER+/HER2- 25%, ER+/HER2+ 15%, ER-/HER2+ 30%, and ER-/HER2- 30%. Median OS from the date of primary diagnosis was 5.74 years. Median survival after diagnosis of BM was 1.33 years. In multivariate Cox regression analyses, stage was the only factor associated with shorter time to the development of BM (P = 0.033), whereas age was the only factor associated with survival from the date of recurrence (P = 0.027) and with OS (P = 0.037). Stage at primary diagnosis correlated with shorter time to the development of BM, while age at diagnosis was associated with shorter survival in BCBM. None of the other clinical factors had influence on survival.

  6. Initial experience with combined BRAF and MEK inhibition with stereotactic radiosurgery for BRAF mutant melanoma brain metastases.

    Science.gov (United States)

    Patel, Bindiya G; Ahmed, Kamran A; Johnstone, Peter A S; Yu, Hsiang-Hsuan Michael; Etame, Arnold B

    2016-08-01

    The combined use of the BRAF inhibitor dabrafenib and MEK inhibitor trametinib has been found to improve survival over dabrafenib alone. The management of melanoma brain metastases continues to present challenges. In this study, we report our initial experience in the management of melanoma brain metastases with stereotactic radiosurgery (SRS) with the use of BRAF and MEK inhibitors. We identified six patients treated with SRS for 17 brain metastases within 3 months of BRAF and MEK inhibitor administration. The median planning target volume was 0.42 cm (range: 0.078-2.08 cm). The median treatment dose was 21 Gy (range 18-24 Gy). The median follow-up of all lesions from SRS was 10.6 months (range 5.8-28.5 months). One lesion was found to undergo local failure 21.7 months following SRS treatment. The median overall survival was 20.0 months (range 6.1-31.8 months) from the time of SRS treatment and 23.1 months (range: 12.1-30.9 months) from the date of BRAFi and MEKi administration. There was no evidence of increased nor unexpected toxicity with the two modalities combined. In this initial experience of melanoma brain metastases treated with BRAF and MEK inhibition with SRS, we find the two modalities can be combined safely. These outcomes should be assessed further in prospective evaluations. PMID:26926151

  7. Safety Study of MGA271 in Combination With Ipilimumab in Refractory Cancer

    Science.gov (United States)

    2016-05-03

    Melanoma; Head and Neck Cancer; Non Small Cell Lung Cancer; Mesothelioma; Urothelial Carcinoma; Clear Cell Renal Cell Carcinoma; Ovarian Cancer; Thyroid Cancer; Triple Negative Breast Cancer; Pancreatic Cancer; Colon Cancer; Soft Tissue Sarcoma; Prostate Cancer

  8. Safety Study of MGA271 in Combination With Pembrolizumab in Refractory Cancer

    Science.gov (United States)

    2016-05-03

    Melanoma; Head and Neck Cancer; Non Small Cell Lung Cancer; Mesothelioma; Urethelial Carcinoma; Clear Cell Renal Cell Carcinoma; Ovarian Cancer; Thyroid Cancer; Triple Negative Breast Cancer; Pancreatic Cancer; Colon Cancer; Soft Tissue Sarcoma; Prostate Cancer

  9. Drug Combinations in Preoperative Chemoradiation for Rectal Cancer.

    Science.gov (United States)

    Glynne-Jones, Rob; Carvalho, Carlos

    2016-07-01

    Preoperative radiotherapy has an accepted role in reducing the risk of local recurrence in locally advanced resectable rectal cancer, particularly when the circumferential resection margin is breached or threatened, according to magnetic resonance imaging. Fluoropyrimidine-based chemoradiation can obtain a significant down-sizing response and a curative resection can then be achieved. Approximately, 20% of the patients can also obtain a pathological complete response, which is associated with less local recurrences and increased survival. Patients who achieve a sustained complete clinical response may also avoid radical surgery. In unresectable or borderline resectable tumors, around 20% of the patients still fail to achieve a sufficient down-staging response with the current chemoradiation schedules. Hence, investigators have aspired to increase pathological complete response rates, aiming to improve curative resection rates, enhance survival, and potentially avoid mutilating surgery. However, adding additional cytotoxic or biological agents have not produced dramatic improvements in outcome and often led to excess surgical morbidity and higher levels of acute toxicity, which effects on compliance and in the global efficacy of chemoradiation. PMID:27238473

  10. Dynamic infrared imaging in identification of breast cancer tissue with combined image processing and frequency analysis.

    Science.gov (United States)

    Joro, R; Lääperi, A-L; Soimakallio, S; Järvenpää, R; Kuukasjärvi, T; Toivonen, T; Saaristo, R; Dastidar, P

    2008-01-01

    Five combinations of image-processing algorithms were applied to dynamic infrared (IR) images of six breast cancer patients preoperatively to establish optimal enhancement of cancer tissue before frequency analysis. mid-wave photovoltaic (PV) IR cameras with 320x254 and 640x512 pixels were used. The signal-to-noise ratio and the specificity for breast cancer were evaluated with the image-processing combinations from the image series of each patient. Before image processing and frequency analysis the effect of patient movement was minimized with a stabilization program developed and tested in the study by stabilizing image slices using surface markers set as measurement points on the skin of the imaged breast. A mathematical equation for superiority value was developed for comparison of the key ratios of the image-processing combinations. The ability of each combination to locate the mammography finding of breast cancer in each patient was compared. Our results show that data collected with a 640x512-pixel mid-wave PV camera applying image-processing methods optimizing signal-to-noise ratio, morphological image processing and linear image restoration before frequency analysis possess the greatest superiority value, showing the cancer area most clearly also in the match centre of the mammography estimation. PMID:18666012

  11. Evaluating the prognosis and degree of brain injury by combined S-100 protein and neuron specific enolase determination

    Institute of Scientific and Technical Information of China (English)

    Xihua Wang; Xinding Zhang

    2006-01-01

    Background:S-100 and neuron specific enolase(NSE)possess the characteristics of specific distribution in brain and relative stable content.Some studies suggest that combined detection of the both is of very importance for evaluating the degree of brain injury.OBJECTIVE: To observe the changes of S-100 protein and NSE levels at different time points after acute brain injury,and evaluate the values of combined detection detection of the both for different injury degrees,pathological changes and prognosis.DESIGN: Case-control observation SETTING: Department of Neurosurgery,Second Affiliated Hospital,Lanzhou University.PARTICIPANTS:Thirty-four inpatients with brain injury,19 males and 15 females,aged 15 to 73 years.who received treatment between September 2005 and May 2006 in the Department of Neurosurgery. Second Affiliated Hospital,Lanzhou University,were recruited.The patients were admitted to hospital at 24 hours after brain injury.After admission,skull CT confirmed that they suffered from brain injury.Following Glasgow coma score(GCS)on admission,the patients were assigned into 3 groups:severe group(GCS 3 to 8 points,n=15).moderate group(GCS 9 to 12 points,n=8)and mild group(GCS 13 to 15 points,n=11).Following Glasgow outcome scale(GOS)at 3 months after brain injury,the patients were assigned into good outcome group (GOS 4 to 5 points,good recovery and moderate disability included,n=19)and poor outcome group(GOS 1 to 3 points,severe disability,vegetative state and death,n=15).Ten subjects who received health examination concurrently were chosen as normal control group,including 6 males and 4 females,aged(45.4±14.3)years.In our laboratory,the normal level of NSE was≤15.2 ng/L,and that of S100 was≤0.105 μg/L.METHODS:①Blood samples of control group were collected when the subjects received health examination Blood samples of patients with brain injury were collected at 24 hours,3,7 and 14 days after injury.According to the instructions of NSE and S-100 kits

  12. Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

    Directory of Open Access Journals (Sweden)

    M. Suzuki

    2014-01-01

    Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

  13. Vojta and Bobath combined treatment for high risk infants with brain damage at early period

    Institute of Scientific and Technical Information of China (English)

    Chunyan Wu; Xiaohui Peng; Xuesong Li; Qingling Niu; Hong Guo; Huitao Huang

    2007-01-01

    BACKGROUND: In the process of early screening and interventions to high risk infants with brain damage,the occasion and choosing methods of interventions and the combined application of different interventions are still at the exploratory phase.OBJECTIVE: To observe the efficacy of early intervention using Vojta and Bobath combined treatment in high risk infants with brain damage, and investigate the effect of early rehabilitation on the prognosis.DESIGN: A randomized controlled comparative observation.SETTING: Daqing Oil Field General Hospital of Heilongjiang Province.PARTICIPANTS: Eighty-four high risk infants younger than 1 year were selected from the Department of Pediatrics, Daqing Oil Field General Hospital of Heilongjiang Province from October 2005 to October 2006,including 52 boys (62%) and 32 girls (38%). The treatment started at the age of 0 - 3 months in 11 cases (13%), 4 - 6 months in 28 cases (33%), 7 - 9 months in 35 cases (42%), and 10 - 12 months in 10 cases (12%). Infants with at least two of the followings were enrolled, including 7 Vojta abnormal postural reflexes,slow or disorder of motor development, increase of muscular tension, postural abnormality, primary reflection residual and CT/MRI abnormalities. Informed consents were obtained from their guardians. The 84 infants were randomly divided into treatment group (n =42) and control group (n =42).METHODS: All the children were intravenously injected with cerebroprotein hydrolysate injection or cattle encephalon glycoside and ignotin injection, 10 times as a course for 2 - 5 courses; Besides, the infants in the treatment group also received early rehabilitative training of Vojta and Bobath combined treatment, once a day, 40 minutes per time, 5 times a week followed by a 2-day rest, 1 month as a course, and totally 2 - 5 courses. The Vojta method was to facilitate the automatic regulation by reflexlocomotion. Bobath method was to inhibit abnormal posture but facilitate the normal one, thus it is

  14. ST6GALNAC5 Expression Decreases the Interactions between Breast Cancer Cells and the Human Blood-Brain Barrier

    Science.gov (United States)

    Drolez, Aurore; Vandenhaute, Elodie; Delannoy, Clément Philippe; Dewald, Justine Hélène; Gosselet, Fabien; Cecchelli, Romeo; Julien, Sylvain; Dehouck, Marie-Pierre; Delannoy, Philippe; Mysiorek, Caroline

    2016-01-01

    The ST6GALNAC5 gene that encodes an α2,6-sialyltransferase involved in the biosynthesis of α-series gangliosides, was previously identified as one of the genes that mediate breast cancer metastasis to the brain. We have shown that the expression of ST6GALNAC5 in MDA-MB-231 breast cancer cells resulted in the expression of GD1α ganglioside at the cell surface. By using a human blood-brain barrier in vitro model recently developed, consisting in CD34+ derived endothelial cells co-cultivated with pericytes, we show that ST6GALNAC5 expression decreased the interactions between the breast cancer cells and the human blood-brain barrier. PMID:27529215

  15. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2012-01-01

    Full Text Available We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient’s headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer.

  16. Efficacy of Radiofrequency Hyperthermia Combined with Chemotherapy 
in Treatment of Malignant Pericardial Effusion Caused by Lung Cancer

    OpenAIRE

    Luo, Pengfei; Cao, Peiguo; Zhiping YAO

    2011-01-01

    Background and objective Malignant pericardial effusion is one of the serious complications of lung cancer and lack effective treatment methods. The aim of this study is to evaluate the efficacy and safety of radiofrequency hyperthermia combined with chemotherapy for patients with malignant pericardial effusion caused by lung cancer. Methods Fifty-five patients with malignant pericardial effusion caused by lung cancer were divided into hyperthermia combined with chemotherapy group (combined t...

  17. THE USE OF ORGANOSPARING OPERATIONS IN COMBINED THERAPY FOR PATIENTS WITH INVASIVE SQUAMOUSE PENILE CANCER

    Directory of Open Access Journals (Sweden)

    E. A. Belova

    2012-01-01

    Full Text Available Background. Penis cancer is rare malignant tumor with morbidity 0,1−0,9 on 100 000 male in year. Most patients come to a doctor late, when performance of organosparing treatment is impossible. Organosparing operations associate with high frequency of development of local reccurence as compared with penectomy. Combined method is optimal treatment for patients with invasive penile cancer and provides good long-term results and preservation organ's function.Objectives. to increase of cure effectiveness by performance of organosparing operations into combined treatment.Subjects and methods. The investigation was included 72 patients with invasive squamouse penile cancer. Patients were divided into two groups subject to kind of treatment: I (42 — organosparing operations, II (30 — combined method. Surgical treatment was performing whole of 72 patients: 51 — resection, 12 — circumcision, 3 — local excision. Beam therapy was carrying out to 30 patients.Results. The frequency of relapse in I group was 52,4 %, in II — 13,2 % (p < 0,01. Duration of period without relapse was four times higher in group of combined method — 71,3 ± 13,4 monthes as compared with group of surgical treatment — 17 ± 5,7.Conclusion. The combined method of cure for patients with invasive squamous penile cancer provides good long-term results and preservation of organ's function.

  18. THE USE OF ORGANOSPARING OPERATIONS IN COMBINED THERAPY FOR PATIENTS WITH INVASIVE SQUAMOUSE PENILE CANCER

    Directory of Open Access Journals (Sweden)

    E. A. Belova

    2014-08-01

    Full Text Available Background. Penis cancer is rare malignant tumor with morbidity 0,1−0,9 on 100 000 male in year. Most patients come to a doctor late, when performance of organosparing treatment is impossible. Organosparing operations associate with high frequency of development of local reccurence as compared with penectomy. Combined method is optimal treatment for patients with invasive penile cancer and provides good long-term results and preservation organ's function.Objectives. to increase of cure effectiveness by performance of organosparing operations into combined treatment.Subjects and methods. The investigation was included 72 patients with invasive squamouse penile cancer. Patients were divided into two groups subject to kind of treatment: I (42 — organosparing operations, II (30 — combined method. Surgical treatment was performing whole of 72 patients: 51 — resection, 12 — circumcision, 3 — local excision. Beam therapy was carrying out to 30 patients.Results. The frequency of relapse in I group was 52,4 %, in II — 13,2 % (p < 0,01. Duration of period without relapse was four times higher in group of combined method — 71,3 ± 13,4 monthes as compared with group of surgical treatment — 17 ± 5,7.Conclusion. The combined method of cure for patients with invasive squamous penile cancer provides good long-term results and preservation of organ's function.

  19. Gender, Race, and Survival: A Study in Non-Small-Cell Lung Cancer Brain Metastases Patients Utilizing the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification

    International Nuclear Information System (INIS)

    Purpose: To explore whether gender and race influence survival in non-small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. Methods and materials: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. Results: Median follow-up was 5.4 months (range, 0-122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. Conclusions: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.

  20. Effect of volume replacement during combined experimental hemorrhagic shock and traumatic brain injury in prostanoids, brain pathology and pupil status

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    Fernando Campos Gomes Pinto

    2015-06-01

    Full Text Available Traumatic brain injury (TBI is the main cause of trauma-related deaths. Systemic hypotension and intracranial hypertension causes cerebral ischemia by altering metabolism of prostanoids. We describe prostanoid, pupilar and pathological response during resuscitation with hypertonic saline solution (HSS in TBI.Method Fifteen dogs were randomized in three groups according to resuscitation after TBI (control group; lactated Ringer’s (LR group and HSS group, with measurement of thromboxane, prostaglandin, macroscopic and microscopic pathological evaluation and pupil evaluation.Result Concentration of prostaglandin is greater in the cerebral venous blood than in plasma and the opposite happens with concentration of thromboxane. Pathology revealed edema in groups with the exception of group treated with HSS.Discussion and conclusion There is a balance between the concentrations of prostaglandin and thromboxane. HSS prevented the formation of cerebral edema macroscopically detectable. Pupillary reversal occurred earlier in HSS group than in LR group.

  1. Effect of volume replacement during combined experimental hemorrhagic shock and traumatic brain injury in prostanoids, brain pathology and pupil status.

    Science.gov (United States)

    Pinto, Fernando Campos Gomes; Oliveira, Matheus Fernandes de; Prist, Ricardo; Silva, Maurício Rocha E; Silva, Luiz Fernando Ferraz da; Capone Neto, Antonio

    2015-06-01

    Traumatic brain injury (TBI) is the main cause of trauma-related deaths. Systemic hypotension and intracranial hypertension causes cerebral ischemia by altering metabolism of prostanoids. We describe prostanoid, pupilar and pathological response during resuscitation with hypertonic saline solution (HSS) in TBI. Method Fifteen dogs were randomized in three groups according to resuscitation after TBI (control group; lactated Ringer's (LR) group and HSS group), with measurement of thromboxane, prostaglandin, macroscopic and microscopic pathological evaluation and pupil evaluation.Result Concentration of prostaglandin is greater in the cerebral venous blood than in plasma and the opposite happens with concentration of thromboxane. Pathology revealed edema in groups with the exception of group treated with HSS.Discussion and conclusion There is a balance between the concentrations of prostaglandin and thromboxane. HSS prevented the formation of cerebral edema macroscopically detectable. Pupillary reversal occurred earlier in HSS group than in LR group. PMID:26083885

  2. The Vitamin D Receptor (VDR Gene Polymorphisms in Turkish Brain Cancer Patients

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    Bahar Toptaş

    2013-01-01

    Full Text Available Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR gene polymorphisms and the risk of glioma and meningioma. Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP. Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9% compared with controls (2.5%, and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles. Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma.

  3. Correlation of neurocognitive function and brain parenchyma volumes in children surviving cancer

    Science.gov (United States)

    Reddick, Wilburn E.; White, Holly A.; Glass, John O.; Mulhern, Raymond K.

    2002-04-01

    This research builds on our hypothesis that white matter damage and associated neurocognitive symptoms, in children treated for cancer with cranial spinal irradiation, spans a continuum of severity that can be reliably probed using non-invasive MR technology. Quantitative volumetric assessments of MR imaging and psychological assessments were obtained in 40 long-term survivors of malignant brain tumors treated with cranial irradiation. Neurocognitive assessments included a test of intellect (Wechsler Intelligence Test for Children, Wechsler Adult Intelligence Scale), attention (Conner's Continuous Performance Test), and memory (California Verbal Learning Test). One-sample t-tests were conducted to evaluate test performance of survivors against age-adjusted scores from the test norms; these analyses revealed significant impairments in all apriori selected measures of intelligence, attention, and memory. Partial correlation analyses were performed to assess the relationships between brain tissues volumes (normal appearing white matter (NAWM), gray matter, and CSF) and neurocognitive function. Global intelligence (r = 0.32, p = 0.05) and global attentional (r = 0.49, p cancer treated with cranial irradiation reveal that loss of NAWM is associated with decreased intellectual and attentional deficits, whereas overall parenchyma loss, as reflected by increased CSF and decreased white matter, is associated with memory-related deficits.

  4. A study of an effective sunitinib–chemotherapeutic combination regimen for bladder cancer treatment using a mouse model

    Directory of Open Access Journals (Sweden)

    Dah-Shyong Yu

    2014-06-01

    Conclusion: Combination of the tyrosine kinase receptor inhibitor sunitinib with gemcitabine chemotherapy synergistically enhances tumor cytotoxicity and may provide a new treatment modality for advanced bladder cancer.

  5. Population-based outcomes after brain radiotherapy in patients with brain metastases from breast cancer in the Pre-Trastuzumab and Trastuzumab eras

    International Nuclear Information System (INIS)

    To evaluate the survival of patients with human epidermal growth factor receptor 2 (HER2) positive and negative metastatic breast cancer irradiated for brain metastases before and after the availability of trastuzumab (T). Women diagnosed with brain metastasis from breast cancer in two eras between 2000 and 2007 (T-era, n = 441) and 1986 to 1992 (PreT-era, n = 307), treated with whole brain radiotherapy (RT) were identified. In the T-era, HER2 testing was part of routine clinical practice, and in the preT-era 128/307 (42%) cases had HER2 testing performed retrospectively on tissue microarrays. Overall survival (OS) was estimated using the Kaplan-Meier method and comparisons between eras used log-rank tests. In the preT- and T-era cohorts, the rate of HER2 positivity was 40% (176/441) and 26% (33/128) (p < 0.001). The median time from diagnosis to brain RT was longer in the preT-era (3.3 years versus 2.3 years, p < 0.001). Survival after brain RT was improved in the T-era compared to the preT-era (1-year OS 26% versus 12%, p < 0.001). The 1-year OS rate for HER2 negative patients was 20% in both eras (p = 0.97). Among HER2 positive patients, the 1-year OS in the preT-era was 5% compared to 40% in the T-era (p < 0.001). Distinct from patients with HER2 negative disease in whom no difference in survival after brain RT was observed over time, patients with HER2 positive brain metastases experienced significantly improved survival subsequent to the availability of trastuzumab

  6. A combined MR and CT study for precise quantitative analysis of the avian brain

    Science.gov (United States)

    Jirak, Daniel; Janacek, Jiri; Kear, Benjamin P.

    2015-10-01

    Brain size is widely used as a measure of behavioural complexity and sensory-locomotive capacity in avians but has largely relied upon laborious dissections, endoneurocranial tissue displacement, and physical measurement to derive comparative volumes. As an alternative, we present a new precise calculation method based upon coupled magnetic resonance (MR) imaging and computed tomography (CT). Our approach utilizes a novel interactive Fakir probe cross-referenced with an automated CT protocol to efficiently generate total volumes and surface areas of the brain tissue and endoneurocranial space, as well as the discrete cephalic compartments. We also complemented our procedures by using sodium polytungstate (SPT) as a contrast agent. This greatly enhanced CT applications but did not degrade MR quality and is therefore practical for virtual brain tissue reconstructions employing multiple imaging modalities. To demonstrate our technique, we visualized sex-based brain size differentiation in a sample set of Ring-necked pheasants (Phasianus colchicus). This revealed no significant variance in relative volume or surface areas of the primary brain regions. Rather, a trend towards isometric enlargement of the total brain and endoneurocranial space was evidenced in males versus females, thus advocating a non-differential sexually dimorphic pattern of brain size increase amongst these facultatively flying birds.

  7. Pemetrexed/cisplatin as first-line chemotherapy for advanced lung cancer with brain metastases

    Science.gov (United States)

    He, Guangzhao; Xiao, Xiaoguang; Zou, Man; Zhang, Chengliang; Xia, Shu

    2016-01-01

    Abstract Background: Brain metastases (BMs) are a common and serious complication of non-small cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT), surgery, and molecular targeted therapy are usually used to treat NSCLC with BM. Chemotherapeutic options for BM are limited by tumor resistance, ineffective agents, and the blood–brain barrier. Pemetrexed/cisplatin is the preferred chemotherapy in nonsquamous NSCLC, but the efficacy of this treatment for nonsquamous NSCLC with BM is uncertain. Methods: We present a case of nonsquamous NSCLC with asymptomatic BM presenting with irritating cough and right shoulder back pain (unknown sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase). Results: He benefited from administration of first-line chemotherapy of pemetrexed/cisplatin. Partial remission was achieved in the primary lesion of the lungs and BM lesion. He was further given 3 cycles of pemetrexed monotherapy and WBRT. Complete remission was further achieved in BM lesion. Conclusion: The findings of clinical trials and theoretical studies about the current pemetrexed/cisplatin in the treatment of nonsquamous NSCLC with BM are also summarized to provide a reference for the application of pemetrexed/cisplatin in nonsquamous NSCLC with BM. Whether or not pemetrexed/cisplatin is definitely effective in nonsquamous NSCLC with BM must be proven by subsequent phase III clinical trials. PMID:27512852

  8. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    Directory of Open Access Journals (Sweden)

    Faris Shweikeh

    2014-01-01

    Full Text Available Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing’s sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma, some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma, and a few after 36 months (chondrosarcoma and liposarcoma. Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing’s sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas. Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.

  9. MRI findings of radiation encephalopathy of brain stem after radiotherapy for nasopharyngeal cancer

    International Nuclear Information System (INIS)

    Purpose: To study MRI findings and clinical manifestation of radiation encephalopathy (RE) of brain stem. Methods: MRI findings and clinical symptoms in 51 patients with RE of brain stem after radiotherapy for nasopharyngeal cancer were reviewed. Results: Clinical symptoms included number weakness or paralysis in the limbs and symptoms of damaged cranial nerves. All lesions appeared hypo- or iso-intense on spin echo(SE) T1-weighted images and inhomogeneous and mixed hyper- and iso-intense on Turbo spin echo (TSE) T2-weighted images. The lesions were located in mesencephalon, pons, medulla, basilar part of pons, basilar part of pons and medulla oblongata in 2,7,3,9 and 30 patients respectively. The enhancement patterns included irregular rings in 39 patients, spotty in 3 and no enhancement in 9 patients. Mass effect was minimal in all patients. On follow-up MRI, the lesions disappeared in 4 patients, did not change in size and shape in 8 patients and enlarged in 2 patients. Conclusion: MRI could demonstrate the characteristic findings of RE of brain stem. MRI findings sometimes are not consistent with the clinical symptoms

  10. Potential of anti-cancer therapy based on anti-miR-155 oligonucleotides in glioma and brain tumours.

    Science.gov (United States)

    Poltronieri, Palmiro; D'Urso, Pietro I; Mezzolla, Valeria; D'Urso, Oscar F

    2013-01-01

    MicroRNAs are aberrantly expressed in many cancers and can exert tumour-suppressive or oncogenic functions. As oncomirs promote growth of cancer cells and support survival during chemotherapy, thus microRNA-silencing therapies could be a valuable approach to be associated with anticancer drugs and chemotherapy treatments. miR-155 microRNA was found overexpressed in different types of cancer, such as leukaemias (PML, B-cell lymphomas), lung cancer and glioblastoma. GABA-A receptor downregulation was found correlated with glioma grading, with decreasing levels associated with higher grade of malignancies. A relationship between knock-down of miR-155 and re-expression of GABRA 1 protein in vivo was recently individuated. This finding has implication on the effectiveness of RNA-silencing approaches against miR-155 with the scope to control proliferation and signalling pathways regulated by GABA-A receptor. Applying microRNAs for treatment of brain tumours poses several problems, and fields to be solved are mainly the passage of the brain-blood barrier and the targeted delivery to specific cell types. Glioblastoma multiforme cells bud off microvesicles that deliver cytoplasmic contents to nearby cells. Thus, the exploitation of these mechanisms to deliver antagomir therapeutics targeting microvescicles in the brain could take the lead in the near future in the treatment for brain cancers in substitution of invasive surgical intervention. PMID:22834637

  11. Cinnamon intake alleviates the combined effects of dietary-induced insulin resistance and acute stress on brain mitochondria.

    Science.gov (United States)

    Couturier, Karine; Hininger, Isabelle; Poulet, Laurent; Anderson, Richard A; Roussel, Anne-Marie; Canini, Frédéric; Batandier, Cécile

    2016-02-01

    Insulin resistance (IR), which is a leading cause of the metabolic syndrome, results in early brain function alterations which may alter brain mitochondrial functioning. Previously, we demonstrated that rats fed a control diet and submitted to an acute restraint stress exhibited a delayed mitochondrial permeability transition pore (mPTP) opening. In this study, we evaluated the combined effects of dietary and emotional stressors as found in western way of life. We studied, in rats submitted or not to an acute stress, the effects of diet-induced IR on brain mitochondria, using a high fat/high fructose diet (HF(2)), as an IR inducer, with addition or not of cinnamon as an insulin sensitizer. We measured Ca(2+) retention capacity, respiration, ROS production, enzymatic activities and cell signaling activation. Under stress, HF(2) diet dramatically decreased the amount of Ca(2+) required to open the mPTP (13%) suggesting an adverse effect on mitochondrial survival. Cinnamon added to the diet corrected this negative effect and resulted in a partial recovery (30%). The effects related to cinnamon addition to the diet could be due to its antioxidant properties or to the observed modulation of PI3K-AKT-GSK3β and MAPK-P38 pathways or to a combination of both. These data suggest a protective effect of cinnamon on brain mitochondria against the negative impact of an HF(2) diet. Cinnamon could be beneficial to counteract deleterious dietary effects in stressed conditions. PMID:26878796

  12. Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer.

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    Nikita Pozdeyev

    Full Text Available NF-κB signaling plays an important role in tumor cell proliferation, cell survival, angiogenesis, invasion, metastasis and drug/radiation resistance. Combination therapy involving NF-κB pathway inhibition is an attractive strategy for the treatment of advanced forms of thyroid cancer. This study was designed to test the efficacy of NF-κB pathway inhibition in combination with cytotoxic chemotherapy, using docetaxel and ionizing radiation in in vitro models of thyroid cancer. We found that while both docetaxel and ionizing radiation activated NF-κB signaling in thyroid cancer cells, there was no synergistic effect on cell proliferation and/or programmed cell death with either genetic (transduction of a dominant negative mutant form of IκBα or pharmacologic (proteasome inhibitor bortezomib and IKKβ inhibitor GO-Y030 inhibition of the NF-κB pathway in thyroid cancer cell lines BCPAP, 8505C, THJ16T and SW1736. Docetaxel plus bortezomib synergistically decreased in vitro invasion of 8505C cells, but not in the other cell lines. Screening of a panel of clinically relevant targeted therapies for synergy with genetic NF-κB inhibition in a proliferation/cytotoxicity assay identified the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA as a potential candidate. However, the synergistic effect was confirmed only in the BCPAP cells. These results indicate that NF-κB inhibitors are unlikely to be beneficial as combination therapy with taxane cytotoxic chemotherapy, external radiation therapy or radioiodine therapy. There may be unique circumstances where NF-κB inhibitors may be considered in combination with docetaxel to reduce tumor invasion or in combination with HDAC inhibitors to reduce tumor growth, but this does not appear to be a combination therapy that could be broadly applied to patients with advanced thyroid cancer. Further research may identify which subsets of patients/tumors may respond to this therapeutic

  13. Tumor grade evaluation after patients with peripheral lung cancer received microwave ablation combined with radiochemotherapy

    Institute of Scientific and Technical Information of China (English)

    Yin Zhang

    2016-01-01

    Objective:To study the effect of microwave ablation combined with radiochemotherapy on tumor grade of patients with peripheral lung cancer.Methods:A total of84 cases of patients diagnosed with III stage peripheral non-small cell lung cancer in our hospital from May 2010 to October 2014 were selected for study and randomly divided into two groups, combination group received microwave ablation combined with radiochemotherapy, control group received radiochemotherapy, and then serum tumor marker contents as well as mRNA contents of pro-apoptotic molecules, anti-apoptotic molecules, protease molecules, EMT marker molecules and autophagy marker molecules in tumor tissue were detected.Results:2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks and 12 weeks after chemotherapy, serum CEA and CYFRA21-1 contents of combination group were significantly lower than those of control group; 12 weeks after chemotherapy, mRNA contents of Caspase-8, Fas, FasL, E-cadherin, cytokeratin, pULK, Benlin-1, PI3KC3, Atg-1, Atg-13, Atg-17, Atg-21 and Atg-24 in tumor tissue of combination group were significantly higher than those of control group; mRNA contents of c-myc, Survivin, MMP-2, MMP-9, MMP-13, N-cadherin and vimentin were significantly lower than those of control group.Conclusion:Microwave ablation combined with radiochemotherapy can more effectively kill lung cancer cells, induce cell apoptosis and autophagy, and inhibit MMPs expression and EMT process.

  14. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer

    OpenAIRE

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G. William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand–receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma.

  15. RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer.

    Science.gov (United States)

    Thanasupawat, Thatchawan; Glogowska, Aleksandra; Burg, Maxwell; Wong, G William; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine; Klonisch, Thomas

    2015-01-01

    The relaxin-like RXFP1 ligand-receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer. Here, we review the role of CTRP members in cancers cells with particular emphasis on CTRP8 in glioblastoma. PMID:26322020

  16. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    OpenAIRE

    Moch Holger; Miller Kurt; Johannsen Manfred; Lein Michael; Jung Monika; Tölle Angelika; Jung Klaus; Kristiansen Glen

    2009-01-01

    Abstract Background Renal cell carcinoma (RCC) is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP) are involved in the intracellular transport of fatty acids (FA). We examined the level of brain-type (B) and liver-type (L) FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Methods Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative...

  17. Exploiting Synergy: Immune-Based Combinations in the Treatment of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Mauricio eBurotto

    2014-12-01

    Full Text Available Cancer treatment is being revolutionized by the emergence of immunotherapies such as immune check point inhibitors and therapeutic cancer vaccines. Prostate cancer has is amenable to such therapeutic approaches. The improved understanding of the relationship between the immune system and tumors has allowed therapeutic targeting of immune checkpoints and tumor associated antigens to be developed. Furthermore, interventions used in prostate cancer are capable of impacting the immune system. As demonstrated by preclinical data and emerging clinical data, radiation therapy, anti-androgen therapy and chemotherapy can be used with immunotherapies to obtain synergistic results. Current and future clinical trials will further investigate these principals as immunotherapeutics are combined with each other and standard therapies for optimal clinical utility.

  18. Diverticular Bleeding of the Colon during Combination Chemotherapy with Bevacizumab and Paclitaxel for Recurrent Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yoshie Nakayama

    2013-01-01

    Full Text Available Background: Bevacizumab has been increasingly used in combination chemotherapy with paclitaxel for treatment of metastatic or recurrent breast cancer. The aim of this report is to underline possible risks associated with the new combination chemotherapy. Case Presentation: A 39-year-old woman with recurrent breast cancer was treated with bevacizumab and paclitaxel. Positron emission tomography revealed breast cancer metastasis to the left supraclavicular lymph nodes and right axillary lymph nodes, with no distant metastasis. Results: After the third cycle of bevacizumab and paclitaxel, the patient developed a bloody bowel discharge. Emergent colonoscopy demonstrated diverticular bleeding on one of the multiple diverticula in the ascending colon. The bleeding point was successfully clipped colonoscopically. Conclusion: The factors for diverticular bleeding are believed to be non-steroidal anti-inflammatory drugs, constipation, and bevacizumab. We recommend reviewing anamneses for diverticulitis, multiple prior abdominal surgeries, peritoneal carcinomatosis, and regular use of certain drugs.

  19. Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer

    International Nuclear Information System (INIS)

    Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer. (author)

  20. Saliva analysis combining membrane protein purification with surface-enhanced Raman spectroscopy for nasopharyngeal cancer detection

    Science.gov (United States)

    Feng, Shangyuan; Lin, Duo; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Li, Yongzeng; Huang, Shaohua; Zhao, Jianhua; Chen, Rong; Zeng, Haishan

    2014-02-01

    A method for saliva analysis combining membrane protein purification with silver nanoparticle-based surface-enhanced Raman spectroscopy (SERS) for non-invasive nasopharyngeal cancer detection was present in this paper. In this method, cellulose acetate membrane was used to obtain purified whole proteins from human saliva while removing other native saliva constituents and exogenous substances. The purified proteins were mixed with silver nanoparticle for SERS analysis. A diagnostic accuracy of 90.2% can be achieved by principal components analysis combined with linear discriminate analysis, for saliva samples obtained from patients with nasopharyngeal cancer (n = 62) and healthy volunteers (n = 30). This exploratory study demonstrated the potential for developing non-invasive, rapid saliva SERS analysis for nasopharyngeal cancer detection.

  1. DNA damage in peripheral blood lymphocytes in patients during combined chemotherapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Suarez, Patricia [Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, Col. Doctores, 06725 Mexico, D.F. (Mexico); Ostrosky-Wegman, Patricia [Biomedical Research Institute, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico); Gallegos-Hernandez, Francisco [Department of Clinical Oncology, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City (Mexico); Penarroja-Flores, Rubicelia; Toledo-Garcia, Jorge [Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, Col. Doctores, 06725 Mexico, D.F. (Mexico); Bravo, Jose Luis [Atmospheric Sciences Institute, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico); Rojas del Castillo, Emilio [Biomedical Research Institute, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico); Benitez-Bribiesca, Luis [Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, Col. Doctores, 06725 Mexico, D.F. (Mexico)], E-mail: luisbenbri@mexis.com

    2008-04-02

    Combined chemotherapy is used for the treatment of a number of malignancies such as breast cancer. The target of these antineoplastic agents is nuclear DNA, although it is not restricted to malignant cells. The aim of the present study was to assess DNA damage in peripheral blood lymphocytes (PBLs) of breast cancer patients subjected to combined adjuvant chemotherapy (5-fluorouracil, epirubicin and cyclophosphamide, FEC), using a modified comet assay to detect DNA single-strand breaks (SSB) and double-strand breaks (DSB). Forty-one female patients with advanced breast cancer before and after chemotherapy and 60 healthy females participated in the study. Alkaline and neutral comet assays were performed in PBLs according to a standard protocol, and DNA tail moment was measured by a computer-based image analysis system. Breast cancer patients before treatment had higher increased background levels of SSB and DSB as compared to healthy women. During treatment, a significant increase in DNA damage was observed after the 2nd cycle, which persisted until the end of treatment. Eighty days after the end of treatment the percentage of PBLs with SSB and DSB remained elevated, but the magnitude of DNA damage (tail moment) returned to baseline levels. There was no correlation between PBL DNA damage and response to chemotherapy. DNA-SSB and DSB in PBLs are present in cancer patients before treatment and increase significantly after combined chemotherapy. No correlation with response to adjuvant chemotherapy was found. Biomonitoring DNA damage in PBLs of cancer patients could help prevent secondary effects and the potential risks of developing secondary cancers.

  2. A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption

    Directory of Open Access Journals (Sweden)

    Sharabi Shirley

    2016-03-01

    Full Text Available Electroporation-based therapies such as electrochemotherapy (ECT and irreversible electroporation (IRE are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This model can be used for individual treatment planning.

  3. A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption

    OpenAIRE

    Sharabi Shirley; Kos Bor; Last David; Guez David; Daniels Dianne; Harnof Sagi; Mardor Yael; Miklavcic Damijan

    2016-01-01

    Background Electroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This m...

  4. Combined age- and trauma-related proteomic changes in rat neocortex: a basis for brain vulnerability

    OpenAIRE

    Mehan, Neal D.; Strauss, Kenneth I

    2011-01-01

    This proteomic study investigates the widely observed clinical phenomenon, that after comparable brain injuries, geriatric patients fare worse and recover less cognitive and neurologic function than younger victims. Utilizing a rat traumatic brain injury model, sham surgery or a neocortical contusion was induced in 3 age groups. Geriatric (21 months) rats performed worse on behavioral measures than young adults (12–16 weeks) and juveniles (5– 6 weeks). Motor coordination and certain cognitive...

  5. Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost

    DEFF Research Database (Denmark)

    Jakobsen, Anders; Mortensen, John P; Bisgaard, Claus;

    2006-01-01

    PURPOSE: To investigate the effect and feasibility of concurrent radiation and chemotherapy combined with endorectal brachytherapy in T3 rectal cancer with complete pathologic remission as end point. METHODS AND MATERIALS: The study included 50 patients with rectal adenocarcinoma. All patients had...

  6. Combined effect of ionizing radiation and other risk factors on the incidence of breast cancer

    International Nuclear Information System (INIS)

    A study was made on combined effect of ionizing radiation (the number of roentgenoscopies and integral absorbed dose) and other risk factors (age, observation period etc) on the incidence of breast cancer (BC). It is shown that the relative BC risk, related with radiation, is affected by woman age during exposure

  7. Ultrasmall Biocompatible WO3- x Nanodots for Multi-Modality Imaging and Combined Therapy of Cancers.

    Science.gov (United States)

    Wen, Ling; Chen, Ling; Zheng, Shimin; Zeng, Jianfeng; Duan, Guangxin; Wang, Yong; Wang, Guanglin; Chai, Zhifang; Li, Zhen; Gao, Mingyuan

    2016-07-01

    Ultrasmall biocompatible WO3 - x nanodots with an outstanding X-ray radiation sensitization effect are prepared, and demonstrated to be applicable for multi-modality tumor imaging through computed tomography and photoacoustic imaging (PAI), and effective cancer treatment combining both photothermal therapy and radiation therapy.

  8. Recent Advances in Upconversion Nanoparticles-Based Multifunctional Nanocomposites for Combined Cancer Therapy.

    Science.gov (United States)

    Tian, Gan; Zhang, Xiao; Gu, Zhanjun; Zhao, Yuliang

    2015-12-16

    Lanthanide-doped upconversion nanoparticles (UCNPs) have the ability to generate ultraviolet or visible emissions under continuous-wave near-infrared (NIR) excitation. Utilizing this special luminescence property, UCNPs are approved as a new generation of contrast agents in optical imaging with deep tissue-penetration ability and high signal-to-noise ratio. The integration of UCNPs with other functional moieties can endow them with highly enriched functionalities for imaging-guided cancer therapy, which makes composites based on UCNPs emerge as a new class of theranostic agents in biomedicine. Here, recent progress in combined cancer therapy using functional nanocomposites based on UCNPs is reviewed. Combined therapy referring to the co-delivery of two or more therapeutic agents or a combination of different treatments is becoming more popular in clinical treatment of cancer because it generates synergistic anti-cancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. Here, the recent advances of combined therapy contributed by UCNPs-based nanocomposites on two main branches are reviewed: i) photodynamic therapy and ii) chemotherapy, which are the two most widely adopted therapies of UCNPs-based composites. The future prospects and challenges in this emerging field will be also discussed. PMID:26505885

  9. Effects of pre- and postnatal combined exposure to Pb and Mn on brain development in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, S.V.; Murthy, R.C.; Saxena, D.K.; Lal, B.

    1983-01-01

    The effect of maternally administered lead (Pb 5.0 mg/kg) and/or manganese (Mn 6 mg/kg) on the brain growth and some biochemicals was investigated in 21 day old pups exposed during gestation and/or lactation. The pups continuously exposed to the mixture of Pb and Mn during pre- and postnatal life presented with significant alterations in the body, brain weights, contents of DNA, RNA, protein and accumulation of both the metals in the brain, the magnitude of these changes was greater in pups exposed to the mixture of Pb and Mn during gestation + lactation than observed in pups identically exposed during gestation only. Pups subjected to any regime of metal exposure during lactation were least affected as indicated by no changes in the brain growth and biochemical parameters. Accumulation of Pb in the brain increased several folds in the animals exposed to the mixture of Pb and Mn in comparison to that observed after exposure to Pb alone. These data suggest that exposure to the two metal ions during prenatal and early postnatal life is more injurious to the brain growth than the identical exposure during the lactation alone.

  10. Gemcitabine Based Combination Regimens for Treatment of Refractory Advanced Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    CHE Li; DI Li-jun; SONG Guo-hong; JIA Jun; YU Jing; WANG Xiao-li; ZHU Yu-lin; JIANG Han-fang; LIANG Xu

    2008-01-01

    Objective:Anthracycline and taxane are the standard agents in combined chemotherapy of advanced breast cancer.However,when these agents based chemotherapy is failure,the selection of salvage regimen is still of problem.Gemcitabine,an active agent in both lung cancer and pancreas cancer,is demonstrated effective in breast caner.But there have been relatively less data of gemcitabine in anthracycline and/or taxane-resistant breast cancer.Therefore we employe this study to explore the efficacy and safety of gemcitabine based combination regimen in this population.Methods:From May 2002 to March 2006,28 patients with measurable lesion of advanced metastatic breast cancer who were resistant to prior anthracycline and taxane based chemotherapy were enrolled.Patients were treated with gemcitabine based combination chemotherapy with a median cycles of 3(range 2-6).Results:The overall response rate was 28.6%(8/28),with 1 CR(Complete response 3.5%)and 7 PRs(Partial response 25%).Stable disease was seen in 8 patients(28.6%)while disease progressed in 12 patiens(42.8%).The median time to progression was 4.5 m(range,2-23 m).The main toxicity included bone marrow depression,alopecia,mucositis and peripheral neurotoxicity.The grade 3 to 4 clinical adverse effect was leukopenia in 5 cases(17.9%)and thrombocytopenia in 8 cases(30%).Conclusion:Gemcitabine based combination regimens is feasible in anthracycline and taxane-resistant advanced breast cancer.The clinical response and TTP is acceptable with limited toxicity pattern.

  11. The Chemopreventive Effect of Tamoxifen Combined with Celecoxib on DMBA chemically-Induced Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoxu Liu; Huafeng Kang; Xijing Wang; Zhijun Dai; Fengjie Xue; Xinghuan Xue

    2007-01-01

    Objective: To investigate the chemopreventive effect of tamoxifen combined with a COX-2 selective inhibitor, celecoxib, on breast cancer in rats chemically induced by 7,12-dimethylben (a)anthracene (DMBA). Methods:DMBA was irrigated into the stomaches of SD female rats to build breast cancer model. A total of 120 rats were divided into four groups: control group, tamoxifen group, celecoxib group and combined group. The incidence rate, latent period, number and volume of breast cancer were detected and analyzed. Results:The tumor incidence rate of tamoxifen group (48.15%, 13/27) and celecoxib group (50.00%,14/28) were lower than that of control group (85.71%, 24/28), but higher than that of combined group (21.43%, 6/28). The tumor's latent period of tamoxifen group (97.54±1.85 d) and celecoxib group (96.79±2.89 d) were longer than that of control group (89.50±5.99 d), but shorter than that of combined group (103.67±3.39 d). The average tumor number of tamoxifen group (1.77±0.73) and celecoxib group (1.71±0.61) were less than that of control group (3.50±1.62), but more than that of combined group ( 1.17±0.42 ). The average tumor volume of tamoxifen group (1.78±0.71 cm3) and celecoxib group (2.05±1.04 cm3) were smaller than that of control group (6.42±3.96 cm3), but bigger than that of combined group (0.71±0.96 cm3) (P < 0.05 respectively).Conclusion:Celecoxib and tamoxifen are effective drugs in preventing the occurrence of rat breast cancer chemically induced by DMBA. Furthermore, combination of them has better chemopreventive effect.

  12. Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    XU Tian-min; XIN Ying; CUI Man-hua; JIANG Xin; GU Li-ping

    2007-01-01

    Background Ginsenoside Rg3, the main component isolated from ginseng, inhibits some kinds of tumour growth and angiogenesis. The combination of low dose chemotherapy and antiangiogenesis inhibitors suppresses growth of experimental tumours more effectively than conventional therapy. The effect of this combination on ovarian cancer remains to be evaluated. Therefore, we investigated the synergism of ginsenoside Rg3 and cyclophosphamide (CTX) on growth and angiogenesis of human ovarian cancer.Methods Twenty-eight female athymic mice were divided randomly into 4 groups of 7: ginsenoside Rg3, CTX,ginsenoside Rg3 and CTX combination and control, after being transplanted with ovarian cancer cells (SKOV-3). The mice were given intraperitoneal injection of ginsenoside Rg3 and CTX for the 10 days following inoculation of SKOV-3cells. The life quality and number of living days of mice were recorded. The size of tumour, tumour inhibitive rate, life elongation rate, proliferating cell nuclear antigen labelling index (PCNALI), expression of vascular endothelial cell growth factor (VEGF) and microvessel density (MVD) of the tumour tissues were estimated.Results Life quality of mice in ginsenoside Rg3 and combined treatment groups were better and number of living days longer than control. Average tumour weights of each treated group were less than control and there was no significant difference among the treated groups. PCNALI of treated groups was lower than control. The MVD value and VEGF expression in treated groups were significantly lower than control and the MVD values of ginsenoside Rg3 and combined treatment groups were lower than that of CTX group.Conclusions Ginsenoside Rg3 significantly inhibited growth and angiogenesis of ovarian cancer when used alone or combined with CTX. Ginsenoside Rg3 and CTX combination reinforced the antitumour effect each other and improved the living quality and survival time of mice with tumour.

  13. Combined image interpretation of computed tomography and hybrid PET in head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zimny, M.; Cremerius, U.; Nowak, B.; Buell, U. [Technische Hochschule Aachen (Germany). Klinik fuer Nuklearmedizin; Wildberger, J.E. [Dept. of Diagnostic Radiology, Univ. of Technology, Aachen (Germany); DiMartino, E. [Dept. of Otorhinolaryngology, Univ. of Technology, Aachen (Germany); Jaenicke, S. [Dept. of Maxillofacial and Facial Plastic Surgery, Univ. of Technology, Aachen (Germany)

    2002-02-01

    Aim: Evaluation of potential synergistic effects of combined image interpretation of FDG PET using a gamma camera modified for coincidence detection (hybrid PET) and computed tomography (CT) and comparison of the diagnostic accuracy of hybrid PET and dedicated PET in patients with head and neck cancer. Methods: Forty-two patient with suspected primary or recurrent cancer were included. Twenty-four patients underwent dedicated PET in addition to attenuation-corrected hybrid PET using a one-day protocol. Results: Sensitivity, specificity and accuracy for detection of primary or recurrent head and neck cancer were 74, 73, and 74% for hybrid PET, 52, 82, and 60% for CT and 77, 82, and 79% for combined reading. With the combination of CT and hybrid PET all cases of recurrent disease were detected. The largest tumour not detected was 1.7 cm in diameter. Sensitivity, specificity and accuracy for the detection of neck sides with lymph node metastases were 69, 88, and 85% for hybrid PET, 62, 88, and 84% for CT, 69, 99, and 94% for combined image interpretation. With combined interpretation four involved neck sides were missed including two cases of microscopic metastases. Hybrid PET revealed concordant results to dedicated PET in all patients with respect to the detection of primary or recurrent tumour and in 45 of 48 neck sides (94%) with the same number of false negative findings. Conclusion: The combination of functional information of hybrid PET and morphological information of CT by the simple approach of combined image interpretation improves the sensitivity for the detection of primary/recurrent head and neck cancer and increases the specificity of lymph node staging compared to CT alone. The accuracy of hybrid PET and dedicated PET was almost identical. (orig.)

  14. Antiangiogenic agents combined with chemotherapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shanshan Chen; Shun Lu 

    2015-01-01

    As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-smal cel lung cancer (NSCLC) and has proven ef ective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in com-bination with first-line chemotherapy for non-squamous NSCLC. Smal-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not al other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.

  15. In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

    Science.gov (United States)

    Heyn, Chris; Ronald, John A; Ramadan, Soha S; Snir, Jonatan A; Barry, Andrea M; MacKenzie, Lisa T; Mikulis, David J; Palmieri, Diane; Bronder, Julie L; Steeg, Patricia S; Yoneda, Toshiyuki; MacDonald, Ian C; Chambers, Ann F; Rutt, Brian K; Foster, Paula J

    2006-11-01

    Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease. PMID:17029229

  16. Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment

    Science.gov (United States)

    Quinto, Christopher A.; Mohindra, Priya; Tong, Sheng; Bao, Gang

    2015-07-01

    Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy.Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could

  17. Workshop on immunotherapy combinations. Society for immunotherapy of cancer annual meeting Bethesda, November 3, 2011

    Directory of Open Access Journals (Sweden)

    Forero Ivan

    2012-05-01

    Full Text Available Abstract Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination immunotherapy to discuss: 1 the most promising combinations found in the laboratory; 2 early success of combination immunotherapy in clinical trials; 3 industry perspectives on combination approaches, and 4 relevant regulatory issues. The integrated theme was how to accelerate the implementation of efficacious combined immunotherapies for cancer patients. Rodent animal models are providing many examples of synergistic combinations that typically include more than two agents. However, mouse and human immunology differ in a significant number of mechanisms and hence we might be missing opportunities peculiar to humans. Nonetheless, incisive animal experimentation with deep mechanistic insight remains the best compass that we can use to guide our paths in combinatorial immunotherapy. Combination immunotherapy clinical trials are already in progress and preliminary results are extremely promising. As a key to translate promising combinations into clinic, real and “perceived” business and regulatory hurdles were debated. A formidable step forward would be to be able to test combinations of investigational agents prior to individual approval. Taking together the FDA and the industrial perspective on combinatorial immunotherapy, the audience was left with the clear message that this is by no means an impossible task. The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer

  18. Workshop on immunotherapy combinations. Society for Immunotherapy of Cancer annual meeting Bethesda, November 3, 2011.

    Science.gov (United States)

    Martinez Forero, Ivan; Okada, Hideho; Topalian, Suzanne L; Gajewski, Thomas F; Korman, Alan J; Melero, Ignacio

    2012-01-01

    Although recent FDA approvals on ipilimumab and sipuleucel-T represent major milestones, the ultimate success of immunotherapy approaches will likely benefit from appropriate combinations with other immunotherapeutic and/or non-immunotherapeutic approaches. However, implementation of ideal combinations in the clinic may still face formidable challenges in regulatory, drug-availability and intellectual property aspects. The 2011 SITC annual meeting hosted a workshop on combination immunotherapy to discuss: 1) the most promising combinations found in the laboratory; 2) early success of combination immunotherapy in clinical trials; 3) industry perspectives on combination approaches, and 4) relevant regulatory issues. The integrated theme was how to accelerate the implementation of efficacious combined immunotherapies for cancer patients. Rodent animal models are providing many examples of synergistic combinations that typically include more than two agents. However, mouse and human immunology differ in a significant number of mechanisms and hence we might be missing opportunities peculiar to humans. Nonetheless, incisive animal experimentation with deep mechanistic insight remains the best compass that we can use to guide our paths in combinatorial immunotherapy. Combination immunotherapy clinical trials are already in progress and preliminary results are extremely promising. As a key to translate promising combinations into clinic, real and "perceived" business and regulatory hurdles were debated. A formidable step forward would be to be able to test combinations of investigational agents prior to individual approval. Taking together the FDA and the industrial perspective on combinatorial immunotherapy, the audience was left with the clear message that this is by no means an impossible task. The general perception is that the road ahead of us is full of combination clinical trials which hopefully will bring clinical benefit to our cancer patients at a fast pace. PMID

  19. Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton.

    Science.gov (United States)

    Grimm, Florian; Walter, Armin; Spüler, Martin; Naros, Georgios; Rosenstiel, Wolfgang; Gharabaghi, Alireza

    2016-01-01

    Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation

  20. Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton.

    Science.gov (United States)

    Grimm, Florian; Walter, Armin; Spüler, Martin; Naros, Georgios; Rosenstiel, Wolfgang; Gharabaghi, Alireza

    2016-01-01

    Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation

  1. Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

    Science.gov (United States)

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

  2. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

    Directory of Open Access Journals (Sweden)

    Piotr Milecki

    2010-10-01

    Full Text Available Piotr Milecki1,2, Piotr Martenka1, Andrzej Antczak3, Zbigniew Kwias31Department of Radiotherapy, Greater Poland Cancer Center, Poznan, Poland; 2Department of Electroradiology, Medical University, Poznan, Poland; 3Chair of Urology, Medical University, Poznan, PolandAbstract: Androgen-deprivation therapy (ADT is used routinely in combination with definitive external beam radiation therapy (EBRT in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT–EBRT also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.Keywords: prostate cancer, radiotherapy, androgen deprivation, combined treatment

  3. Anemia in patients on combined androgen block therapy for prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Li-XinQian; Li-XinHua; Hong-FeiWu; Yuan-GengSui; Shuang-GuanCheng; WeiZhang,JieLi; Xin-RuWang

    2004-01-01

    Aim: To study the effect of combined androgen block therapy on hemoglobin and hematocrit values in patients with prostate cancer. Methods: One hundred and thirty-six patients with adenocarcinoma of prostate were treated with combined androgen block (orchiectomy and flutamide 250 mg, tid). Complete blood counts were determined before and after 1,2,3,6,9 and 12 months of therapy. Results: The hemoglobin and hematocrit levels declined significantly in all patients and at all the time points after treatment (P<0.05). Conclusion: Prostate cancer patients treated with combined androgen block would develop obvious anemia. Recombinant human erythropoietin can be used to treat patients with severe anemia. (Asian J Androl 2004 Dec;6: 383-384)

  4. Combined glutamate and glutamine levels in pain-processing brain regions are associated with individual pain sensitivity.

    Science.gov (United States)

    Zunhammer, Matthias; Schweizer, Lauren M; Witte, Vanessa; Harris, Richard E; Bingel, Ulrike; Schmidt-Wilcke, Tobias

    2016-10-01

    The relationship between glutamate and γ-aminobutyric acid (GABA) levels in the living human brain and pain sensitivity is unknown. Combined glutamine/glutamate (Glx), as well as GABA levels can be measured in vivo with single-voxel proton magnetic resonance spectroscopy. In this cross-sectional study, we aimed at determining whether Glx and/or GABA levels in pain-related brain regions are associated with individual differences in pain sensitivity. Experimental heat, cold, and mechanical pain thresholds were obtained from 39 healthy, drug-free individuals (25 men) according to the quantitative sensory testing protocol and summarized into 1 composite measure of pain sensitivity. The Glx levels were measured using point-resolved spectroscopy at 3 T, within a network of pain-associated brain regions comprising the insula, the anterior cingulate cortex, the mid-cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus. GABA levels were measured using GABA-edited spectroscopy (Mescher-Garwood point-resolved spectroscopy) within the insula, the anterior cingulate cortex, and the mid-cingulate cortex. Glx and/or GABA levels correlated positively across all brain regions. Gender, weekly alcohol consumption, and depressive symptoms were significantly associated with Glx and/or GABA levels. A linear regression analysis including all these factors indicated that Glx levels pooled across pain-related brain regions were positively associated with pain sensitivity, whereas no appreciable relationship with GABA was found. In sum, we show that the levels of the excitatory neurotransmitter glutamate and its precursor glutamine across pain-related brain regions are positively correlated with individual pain sensitivity. Future studies will have to determine whether our findings also apply to clinical populations. PMID:27649042

  5. Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients.

    Science.gov (United States)

    Qin, Fengxia; Zhang, Huikun; Ma, Li; Liu, Xiaoli; Dai, Kun; Li, Wenliang; Gu, Feng; Fu, Li; Ma, Yongjie

    2015-09-24

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast cancer brain metastasis for the first time. Our results demonstrated that (1) Invasive ductal carcinoma patients with low expression of Slit2 or Robo1 exhibited worse prognosis and brain-specific metastasis, but not liver, bone or lung. (2) Lower expression of Slit2 and Robo1 were observed in patients with brain metastasis, especially in their brain metastasis tumors, compared with patients without brain metastasis. (3) The interval from diagnosis of breast cancer to brain metastasis and brain metastasis to death were both much shorter in patients with low expression of Slit2 or Robo1 compared with the high expression group. Overall, our findings indicated that Slit2/Robo1 axis possibly be regarded as a significant clinical parameter for predicting brain metastasis in breast cancer patients.

  6. Combined strategies of apomorphine diester prodrugs and nanostructured lipid carriers for efficient brain targeting

    Science.gov (United States)

    Liu, Kuo-Sheng; Wen, Chih-Jen; Yen, Tzu-Chen; Sung, K. C.; Ku, Ming-Chuan; Wang, Jhi-Joung; Fang, Jia-You

    2012-03-01

    Our aim is to develop nanostructured lipid carriers (NLCs) for loading the apomorphine diester prodrugs, diacetyl apomorphine (DAA) and diisobutyryl apomorphine (DIA), into the brain. NLCs were prepared using sesame oil/cetyl palmitate as the lipid matrices. Experiments were performed with the objective of evaluating the physicochemical characteristics, drug release, safety and brain-targeting efficacy of the NLCs. The size of regular NLCs (N-NLCs) was 214 nm. The addition of Forestall (FE) and polyethylene glycol (PEG) to the NLCs (P-NLCs) increased the particle diameter to 250 nm. The zeta potentials of N-NLCs and P-NLCs were respectively shown to be - 21 and 48 mV. Diester prodrugs were more lipophilic and more chemically stable than the parent apomorphine. The hydrolysis study indicated that the prodrugs underwent bioconversion in plasma and brain extract, with DAA exhibiting faster degradation than DIA. Sustained release was achieved through the synergistic effect of integrating strategies of prodrugs and NLCs, with the longer carbon chain showing the slower release (DIA brain. The distribution duration of the fluorescent dye in the brain region was also prolonged by the nanocarriers.

  7. MEG inversion using spherical head model combined with brain-shaped head model

    Institute of Scientific and Technical Information of China (English)

    LI Jun

    2001-01-01

    The spherical head model has been widely used in magnetoen cephalography (MEG) as a simple forward model for calculating the external mag netic field producing by neural currents in a human brain. But this model may lead to an inaccurate result, even if the computation speed is fast. For more precise computation, realistic brain-shaped head model is used with the boundary element method (BME), but at greatly increased computational cost. When solving MEG inverse problem by using optimization methods, the forward problem must often be solved for thousands of possible source configurations. So if the brain-shaped head model is used in all iterative steps of optimization, it may be computationally infeasible for practical application. In this paper, we present a method about using compound head model in MEG inverse solution. In this method, first spherical head model is used for a rough estimation, then brain-shaped head model is adopted for more precise solution. Numerical simulation indicates that under the condition of same accuracy, the computation speed for the present method is about three times faster than a method using the brain-shaped head model at all iterations.

  8. Combination of cold atmospheric plasma and iron nanoparticles in breast cancer: gene expression and apoptosis study

    Directory of Open Access Journals (Sweden)

    Jalili A

    2016-09-01

    Full Text Available Azam Jalili,1 Shiva Irani,1 Reza Mirfakhraie2 1Department of Biology, Science and Research Branch, Islamic Azad University, 2Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran Background: Current cancer treatments have unexpected side effects of which the death of normal cells is one. In some cancers, iron nanoparticles (NPs can be subjected to diagnosis and passive targeting treatment. Cold atmospheric plasma (CAP has a proven induction of selective cell death ability. In this study, we have attempted to analyze the synergy between CAP and iron NPs in human breast adenocarcinoma cells (MCF-7.Materials and methods: In vitro cytotoxicity of CAP treatment and NPs in cells measured by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and cell death was shown by 4',6-diamidino-2-phenylindole and annexin V staining. Fluctuations in BAX and BCL-2 gene expression were investigated by means of real-time polymerase chain reaction.Results: MTT assay results showed that combination of plasma and iron NPs decreased the viability of cancer cells significantly (P<0.05. Real-time analysis showed that the combination therapy induced shifting the BAX/BCL-2 ratio in favor of apoptosis.Conclusion: Our data indicate that synergy between CAP and iron NPs can be applied in breast cancer treatment selectively. Keywords: breast cancer, cold atmospheric plasma, iron nanoparticles, BAX, BCL-2

  9. Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report

    OpenAIRE

    Morinaga, Nobuhiro; Tanaka, Naritaka; Shitara, Yoshinori; Ishizaki, Masatoshi; Yoshida, Takatomo; Kouga, Hideaki; Wakabayashi, Kazuki; Fukuchi, Minoru; Tsunoda, Yoshiyuki; Kuwano, Hiroyuki

    2016-01-01

    Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. De...

  10. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

    International Nuclear Information System (INIS)

    Cancer of the brain and central nervous system (CNS) is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN) can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared to passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis

  11. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Freund, Derek; Zhang, Rui, E-mail: rzhang@marybird.com [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States); Sanders, Mary [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Newhauser, Wayne [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States)

    2015-04-13

    Cancer of the brain and central nervous system (CNS) is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN) can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared to passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

  12. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

    Directory of Open Access Journals (Sweden)

    Derek Freund

    2015-04-01

    Full Text Available Cancer of the brain and central nervous system (CNS is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT compared to passively scattered proton therapy (PSPT and intensity modulated proton therapy (IMPT. Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

  13. Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xu Zhiyuan [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Marko, Nicholas F. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Chao, Sam T. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Angelov, Lilyana; Vogelbaum, Michael A. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States); Suh, John H. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH (United States); Barnett, Gene H. [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Weil, Robert J., E-mail: weilr@ccf.org [Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH (United States); Department of Neurosurgery, Cleveland Clinic, Cleveland, OH (United States)

    2012-04-01

    Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2- breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2- lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2- and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

  14. Relationship Between HER2 Status and Prognosis in Women With Brain Metastases From Breast Cancer

    International Nuclear Information System (INIS)

    Purpose: To analyze factors affecting outcomes in breast cancer patients with brain metastases (BM) and characterize the role of HER2 status. Methods and Materials: We identified 264 breast cancer patients treated between 1999 and 2008 for BM. HER2 status was known definitively for 172 patients and was used to define cohorts in which survival and risk factors were analyzed. Results: Kaplan-Meier survival analysis demonstrated improved mean overall survival (105.7 vs. 74.3 months, p < 0.02), survival after diagnosis of BM (neurologic survival, NS) (32.2 vs. 18.9 months, p < 0.01), and survival after treatment with stereotactic radiosurgery (RS) (31.3 vs. 14.1, p < 0.01) in HER2+ patients relative to those with HER2− breast cancer. HER2+ status was an independent, positive prognostic factor for survival on univariate and multivariate hazard analysis (hazard ratio: overall survival = 0.66, 0.18; NS = 0.50, 0.34). Additionally, subgroup analysis suggests that stereotactic radiosurgery may be of particular benefit in patients with HER2+ tumors. Conclusions: Overall survival, NS, and RS are improved in patients with HER2+ tumors, relative to those with HER2− lesions, and HER2 amplification is independently associated with increased survival in patients with BM from breast cancer. Our findings suggest that the prognosis of HER2+ patients may be better than that of otherwise similar patients who are HER2− and that stereotactic radiosurgery may be beneficial for some patients with HER2+ lesions.

  15. Using the 60Co source to assess the dose received by risky organs during a cancer brain treatment

    International Nuclear Information System (INIS)

    Summary of an investigation of exposures associated with brain cancer treatment for a child in order to determine the level of doses received by the different organs at risk during the treatment. Measurements have been performed at the vicinity of a cobalto therapy apparatus. Then, cumulative doses in each organ have been compared to admitted doses with respect to the organ

  16. Effects of Physical Exercise Combined with Nutritional Supplements on Aging Brain Related Structures and Functions: A Systematic Review.

    Science.gov (United States)

    Schättin, Alexandra; Baur, Kilian; Stutz, Jan; Wolf, Peter; de Bruin, Eling D

    2016-01-01

    Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: "Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?" Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods with

  17. Can global variation of nasopharynx cancer be retrieved from the combined analyses of IARC Cancer Information (CIN databases?

    Directory of Open Access Journals (Sweden)

    Xin Sun

    Full Text Available BACKGROUND: The international nasopharynx cancer (NPC burdens are masked due to the lack of integrated studies that examine epidemiological data based on up-to-date international disease databases such as the Cancer Information (CIN databases provided by the International Agency for Research on Cancer (IARC. METHODS: By analyzing the most recently updated NPC epidemiological data available from IARC, we tried to retrieve the worldwide NPC burden and patterns from combined analysis with GLOBOCAN2008 and the Cancer Incidence in Five Continents (CI5 databases. We provide age-standardized rates (ASR for NPC mortality in 20 highest cancer registries from GLOBOCAN2008 and the World Health Organization (WHO mortality databases, respectively. However, NPC incidence data can not be retrieved since it is not individually listed in CI5 database. The trend of NPC mortality was investigated with Joinpoint analysis in the selected countries/regions with high ASR. RESULTS: GLOBOCAN 2008 revealed that the highest NPC incidence rates in 2008 were in registries from South-Eastern Asia, Micronesia and Southern Africa with Malaysia, Indonesia and Singapore ranking the top 3. WHO mortality database analysis revealed that China Hong Kong, Singapore and Malta ranks the top 3 regions with the highest 5-year mortality rates. CONCLUSIONS: NPC mortality rate is about 2-3 times higher in male than that in female, and shows decrease tendency in those selected countries/regions during the analyzed periods. However, the integrated analyses of the current IARC CIN databases may not be suitable to retrieve epidemiological data of NPC. Much effort is required to improve the local cancer entry and regional death-reporting systems so as to aid similar studies.

  18. Influence of TACE combined with radioactive seed radiotherapy on primary liver cancer patients’ malignant biological indicators

    Institute of Scientific and Technical Information of China (English)

    Yao Liu; Yu Wang; Guang-Yan Lei; Xiao-Hong Yan; Qiao Yang; Hai-Ping Zhu; Yi Geng

    2016-01-01

    Objective:To analyze the influence of TACE combined with radioactive seed radiotherapy on primary liver cancer patients’ malignant biological indicators.Methods:A total of 112 cases of primary liver cancer patients who received treatment in our hospital, Xijing Hospital and Tumor Hospital of Shaanxi Province were chosen as research subjects and divided into control group (TACE therapy alone) with 63 cases in it and observation group (TACE combined with radioactive seed radiotherapy) with 49 cases according to different treatment, and then the levels of malignant biological indicators after 2 months of treatment were compared between two groups.Results:Serum VEGF, FGF and MMP levels of observation group after treatment were significantly lower than those of control group; serum AFP-L3, GP73, Sb7-H3, AFU and CatS levels were significantly lower than those of control group; serum ICAM-1, ESM-1 and uPA levels were lower than those of control group.Conclusion: TACE combined with radioactive seed radiotherapy can effectively reduce primary liver cancer patients’ serum malignant biological indicator levels, decrease the degree of malignancy of cancer cells and slow disease progression, and is an ideal treatment.

  19. nab-Paclitaxel in combination with biologically targeted agents for early and metastatic breast cancer.

    Science.gov (United States)

    Megerdichian, Christine; Olimpiadi, Yuliya; Hurvitz, Sara A

    2014-06-01

    Taxanes are highly active chemotherapeutic agents used in the treatment of early-stage and metastatic breast cancer. Novel formulations have been developed to improve efficacy and decrease toxicity associated with these cytotoxic agents. nab-Paclitaxel is a biologically interactive, solvent-free, 130-nm-sized albumin-bound paclitaxel, developed to avoid the Cremophor vehicle used in solvent-based paclitaxel. Based on a pivotal phase 3 study, nab-paclitaxel was shown to be safely infused at a significantly higher dose of paclitaxel than the doses used with standard paclitaxel therapy, and had a shorter infusion time, no premedication, and higher response rates. It is now approved in the United States for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant therapy, and has demonstrated promising efficacy and favorable tolerability. Recently, several phase 2 and 3 studies have suggested a role for nab-paclitaxel in combination with biologically targeted agents for the treatment of early- and late-stage breast cancer. This review will discuss the findings of clinical trials evaluating nab-paclitaxel in combination with biologically targeted therapeutic agents for breast cancer in the neoadjuvant, adjuvant, and metastatic settings. PMID:24560997

  20. Effect of large decompressive craniectomy combined with vascular reconstruction on cerebral perfusion in patients with severe brain injury

    Directory of Open Access Journals (Sweden)

    Liang-zhen HUANG

    2015-11-01

    Full Text Available Objective To compare the efficacies of large decompressive craniectomy combined with vascular reconstruction and traditional decompressive craniectomy in treatment of severe brain injury. Methods Forty-eight patients with severe brain injury, which was dominated by brain contusion to the frontoparietal lobes, admitted to our hospital from March 2012 to March 2014 were divided equally into experimental group and control group. The patients in the experimental group underwent large decompressive craniectomy combined with vascular reconstruction, and the patients in the control group received traditional decompressive craniectomy. The hemodynamic changes including cerebral blood flow (CBF, cerebral blood volume (CBV, mean transit time (MTT, time to peak (TTP and the ratios of these values (rCBF, rCBV, rMTT and rTTP on two sides were observed by CT perfusion imaging, and the Glasgow outcome score (GOS was analyzed 6 months after operation. Results The CBF and CBV scores in experimental group were higher than those in the control group at 1 week and 1 month after the operation (P0.05. The rate of satisfactory recovery (including good recovery and moderate disability was higher in the experimental group than in the control group, while the rate of poor recovery (including severe disability, vegetative state and death was lower in the experimental group than in the control group (P<0.05. Conclusion The large decompressive craniectomy combined with vascular reconstruction can not only decrease the intracranial pressure, but also recover the blood supply of brain, thus deserving the clinical application and popularization. DOI: 10.11855/j.issn.0577-7402.2015.11.15

  1. Clinical Study of Endostar Combined with DP Protocol in Treatment of Advanced Esophageal Cancer

    Directory of Open Access Journals (Sweden)

    Wen-ying DENG

    2015-09-01

    Full Text Available Objective: To observe the clinical outcomes of Endostar combined with DP regimen for treating advanced esophageal cancer.Methods: A total of 62 patients with advanced esophageal cancer admitted from May, 2011 to May, 2013 were enrolled for a prospective, randomized controlled trial and 2 cases were excluded from the study because of Ⅳ degree of digestive tract reaction and myelosuppression. Therefore, 60 cases could be evaluated, and then divided into combined group (given Endostar+DP plan and single chemotherapy group, 30 cases in each group. The level of VEGF, tumor size and CT perfusion (CTP parameters, including blood flow (BF, blood volume (BV, mean transit time (MTT, and permeability surface (PS before and after treatment were determined for comparison. Kaplan-Merier method was used to analyze the overall survival (OS of 2 groups.Results: The efficacy of combined group was superior to single chemotherapy group. The level of vascular endothelial growth factor (VEGF in combined group was obviously lower than that in single chemotherapy group after treatment (P<0.01. Compared with treatment before in combined group, BF, BV and PS decreased while MTT increased after treatment (P<0.05. However, there were no significant differences in single chemotherapygroup before and after treatment (P>0.05. The median OS was 30 months (95%CI: 20.935-39.065 for combined group and 21 months (95%CI: 15.109-26.591 for single chemotherapy group, respectively (P=0.048. The 1-, 2- and 3-year survival rates were 86.2%, 59.3% and 36.6% in combined group, and 70.8%, 32.1% and 17.8% in single chemotherapy group, respectively.Conclusion: Endostar can down-regulate the expression of VEGF, improve the state of hypertransfusion and high permeability of tumor vessels, has better curative effect without slighter adverse reactions, and prolong the survival time of patients with advanced esophageal cancer when combined with chemotherapy.

  2. Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Jelveh, Salomeh [Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, ON (Canada); Department of Radiation Physics, Princess Margaret Hospital, Toronto, ON (Canada); Chithrani, Devika B., E-mail: devika.chithrani@rmp.uhn.on.ca [Department of Radiation Physics, Princess Margaret Hospital, Toronto, ON (Canada); STTARR Innovation Centre, Toronto Medical Discovery Tower, Toronto, ON (Canada)

    2011-03-04

    The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research.

  3. Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Salomeh Jelveh

    2011-03-01

    Full Text Available The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs, gold nanorods (GNRs, gold nanoshells (GNSs and gold nanocages (GNCs in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research.

  4. Radiotherapy combined with aclarubicin and neocarzinostatin for cancer of the gallbladder

    Energy Technology Data Exchange (ETDEWEB)

    Okuyama, Shin-ichi; Mishina, Hitoshi; Funaki, Ken-ichi; Mori, Toshihiko (Tohoku Rosai Hospital, Sendai (Japan))

    1991-03-01

    Cancer of the gallbladder is radioresistant. When it was found inoperable, she was subjected to radiotherapy combined with aclarubicin and neocarzinostatin. Therapeutic effectiveness was confirmed at autopsy as she later succumbed to uterine cervical cancer. Thus, the present radiochemotherapeutic regimen would probably provide a means of overcoming those radioresistant inoperable malignancies. Intravenous administrations of appropriate antibiotics such as azthreonam and reniran may probably be helpful in the prevention and treatment of septic peritonitis possible during the course of reinforced radiotherapy of the abdomen. (author).

  5. Intraoperative radiofrequency ablation combined with ~(125)iodine seed implantation for unresectable pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To evaluate the feasibility, efficacy and safety of intraoperative radiofrequency ablation (RFA) combined with 125 iodine seed implantation for unresectable pancreatic cancer. METHODS: Thirty-two patients (21 males and 11 females) at the age of 68 years (range 48-90 years) with unresectable locally advanced pancreatic cancer admitted to our hospital from January 2006 to May 2008 were enrolled in this study. The tumor, 4-12 cm in diameter, located in pancreatic head of 23 patients and in pancreatic body...

  6. Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

    OpenAIRE

    Okita Yoshihiro; Hirakawa Toshiki; Shinto Osamu; Tamura Tatsuro; Nakao Shigetomi; Amano Ryosuke; Nakata Bunzo; Yamada Nobuya; Hirakawa Kosei

    2010-01-01

    Abstract Background The combination of gemcitabine (GEM) and S-1, an oral 5-fluorouracil (5-FU) derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer. Methods Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK) study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1...

  7. A meta-analysis of bevacizumab combined with chemotherapy in the treatment of ovarian cancer

    Directory of Open Access Journals (Sweden)

    T S Wang

    2014-01-01

    Full Text Available Introduction: Angiogenesis plays an important role in the biology of ovarian cancer. The clinical efficacy and side effects of bevacizumab, the vascular endothelial growth factor inhibitor, on survival and toxicity in women with this ovarian cancer, was not conclusive. We performed this systematic review and meta-analysis in order to clarify the efficacy of bevacizumab combined with chemotherapy in the treatment of ovarian cancer. Materials and Methods: We searched the electronic database of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CNKI for clinical controlled trials of comparing bevacizumab combined with chemotherapy and chemotherapy alone in the treatment of ovarian cancer. The primary outcomes of eligible studies included median progression-free survival (PFS, overall survival (OS, and toxicities such as enterobrosis, hypertension, albuminuria, congestive heart failure (CHF, neutrophils, thrombosis, and bleeding. The Hazard ratio (HR and relative risk were used for the meta-analysis and were expressed with 95% confidence intervals (CIs. All the statistical analyses were carried out by  Stata 11.0 software (http://www.stata.com; Stata Corporation, College Station, TX, USA. Results: We included 5 studies with 1798 cases in the bevacizumab combined with the chemotherapy group and 1810 subjects in the chemotherapy alone group. The pooled results showed that bevacizumab + chemotherapy compared with chemotherapy alone can significant prolong the median PFS (HR, 0.64; 95% CI, 0.46-0.82; P 0.05; the toxicity analysis showed that the enterobrosis, hypertension, albuminuria, neutrophils, thrombosis, and bleeding were significantly increased in the bevacizumab + chemotherapy group compared with chemotherapy alone (Pall 0.05. Conclusion: Bevacizumab combined with chemotherapy prolonged the median PFS in patients with ovarian cancer but also increase the risk of developing enterobrosis, hypertension, albuminuria, neutrophils

  8. Metastatic brain cancer: prediction of response to whole-brain helical tomotherapy with simultaneous intralesional boost for metastatic disease using quantitative MR imaging features

    Science.gov (United States)

    Sharma, Harish; Bauman, Glenn; Rodrigues, George; Bartha, Robert; Ward, Aaron

    2014-03-01

    The sequential application of whole brain radiotherapy (WBRT) and more targeted stereotactic radiosurgery (SRS) is frequently used to treat metastatic brain tumors. However, SRS has side effects related to necrosis and edema, and requires separate and relatively invasive localization procedures. Helical tomotherapy (HT) allows for a SRS-type simultaneous infield boost (SIB) of multiple brain metastases, synchronously with WBRT and without separate stereotactic procedures. However, some patients' tumors may not respond to HT+SIB, and would be more appropriately treated with radiosurgery or conventional surgery despite the additional risks and side effects. As a first step toward a broader objective of developing a means for response prediction to HT+SIB, the goal of this study was to investigate whether quantitative measurements of tumor size and appearance (including first- and second-order texture features) on a magnetic resonance imaging (MRI) scan acquired prior to treatment could be used to differentiate responder and nonresponder patient groups after HT+SIB treatment of metastatic disease of the brain. Our results demonstrated that smaller lesions may respond better to this form of therapy; measures of appearance provided limited added value over measures of size for response prediction. With further validation on a larger data set, this approach may lead to a means for prediction of individual patient response based on pre-treatment MRI, supporting appropriate therapy selection for patients with metastatic brain cancer.

  9. Radiolabeled cetuximab plus whole-brain irradiation (WBI) for the treatment of brain metastases from non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Background and Purpose: The addition of systemic drugs to whole-brain irradiation has not improved the survival of patients with multiple brain metastases, most likely because the agents did not readily cross the blood-brain barrier (BBB). Radiolabeling of cetuximab was performed to investigate whether this antibody crosses the BBB. Case Report: A patient with multiple brain lesions from non-small cell lung cancer was investigated. The largest metastasis (40 x 33 x 27 mm) was selected the reference lesion. On day 1, 200 mg/m2 cetuximab (0.25% hot and 99.75% cold antibody) were given. On day 3, 200 mg/m2 cetuximab (cold antibody) were given. Weekly doses of 250 mg/m2 cetuximab were administered for 3 months. Results: The reference lesion showed enhancement of radiolabeled cetuximab (123I-Erbi) on scintigraphy; 123I-Erbi crossed the BBB and accumulated in the lesion. The reference lesion measured 31 x 22 x 21 mm at 4 months. Enhancement of contrast medium was less pronounced. Conclusion: This is the first demonstration of cetuximab crossing the BBB and accumulating in brain metastasis. (orig.)

  10. Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review

    Directory of Open Access Journals (Sweden)

    Shihong Chen

    2014-01-01

    Full Text Available Ginseng, a well-known herb, is often used in combination with anticancer drugs to enhance chemotherapy. Its wide usage as well as many documentations are often cited to support its clinical benefit of such combination therapy. However the literature based on objective evidence to make such recommendation is still lacking. The present review critically evaluated relevant studies reported in English and Chinese literature on such combination. Based on our review, we found good evidence from in vitro and in vivo animal studies showing enhanced antitumor effect when ginseng is used in combination with some anticancer drugs. However, there is insufficient clinical evidence of such benefit as very few clinical studies are available. Future research should focus on clinically relevant studies of such combination to validate the utility of ginseng in cancer.

  11. A Novel Electrochemical Microfluidic Chip Combined with Multiple Biomarkers for Early Diagnosis of Gastric Cancer

    Science.gov (United States)

    Xie, Yao; Zhi, Xiao; Su, Haichuan; Wang, Kan; Yan, Zhen; He, Nongyue; Zhang, Jingpu; Chen, Di; Cui, Daxiang

    2015-12-01

    Early diagnosis is very important to improve the survival rate of patients with gastric cancer and to understand the biology of cancer. In order to meet the clinical demands for early diagnosis of gastric cancer, we developed a disposable easy-to-use electrochemical microfluidic chip combined with multiple antibodies against six kinds of biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), Helicobacter pylori CagA protein (H.P.), P53oncoprotein (P53), pepsinogen I (PG I), and PG-II). The six kinds of biomarkers related to gastric cancer can be detected sensitively and synchronously in a short time. The specially designed three electrodes system enables cross-contamination to be avoided effectively. The linear ranges of detection of the electrochemical microfluidic chip were as follows: 0.37-90 ng mL-1 for CEA, 10.75-172 U mL-1 for CA19-9, 10-160 U L-1 for H.P., 35-560 ng mL-1 for P53, 37.5-600 ng mL-1 for PG I, and 2.5-80 ng mL-1for PG II. This method owns better sensitivity compared with enzyme-linked immunosorbent assay (ELISA) results of 394 specimens of gastric cancer sera. Furthermore, we established a multi-index prediction model based on the six kinds of biomarkers for predicting risk of gastric cancer. In conclusion, the electrochemical microfluidic chip for detecting multiple biomarkers has great potential in applications such as early screening of gastric cancer patients, and therapeutic evaluation, and real-time dynamic monitoring the progress of gastric cancer in near future.

  12. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer.

    Science.gov (United States)

    Wu, Sheng-Kai; Chiang, Chi-Feng; Hsu, Yu-Hone; Lin, Tzu-Hung; Liou, Houng-Chi; Fu, Wen-Mei; Lin, Win-Li

    2014-01-01

    The blood-brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. PMID:25278753

  13. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Science.gov (United States)

    Wu, Sheng-Kai; Chiang, Chi-Feng; Hsu, Yu-Hone; Lin, Tzu-Hung; Liou, Houng-Chi; Fu, Wen-Mei; Lin, Win-Li

    2014-01-01

    The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. PMID:25278753

  14. Heparanase mediates a novel mechanism in lapatinib-resistant brain metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Lixin Zhang

    2015-01-01

    Full Text Available Heparanase (HPSE is the dominant mammalian endoglycosidase and important tumorigenic, angiogenic, and pro-metastatic molecule. Highest levels of HPSE activity have been consistently detected in cells possessing highest propensities to colonize the brain, emphasizing the therapeutic potential for targeting HPSE in brain metastatic breast cancer (BMBC. Lapatinib (Tykerb is a small-molecule and dual inhibitor of human epidermal growth factor receptor1 and 2 (EGFR and HER2, respectively which are both high-risk predictors of BMBC. It was approved by the US Food and Drug Administration for treatment of patients with advanced or metastatic breast cancer. However, its role is limited in BMBC whose response rates to lapatinib are significantly lower than those for extracranial metastasis. Because HPSE can affect EGFR phosphorylation, we examined Roneparstat, a non-anticoagulant heparin with potent anti-HPSE activity, to inhibit EGFR signaling pathways and BMBC onset using lapatinib-resistant clones generated from HER2-transfected, EGFR-expressing MDA-MB-231BR cells. Cell growth, EGFR pathways, and HPSE targets were assessed among selected clones in the absence or presence of Roneparstat and/or lapatinib. Roneparstat overcame lapatinib resistance by inhibiting pathways associated with EGFR tyrosine residues that are not targeted by lapatinib. Roneparstat inhibited the growth and BMBC abilities of lapatinib-resistant clones. A molecular mechanism was identified by which HPSE mediates an alternative survival pathway in lapatinib-resistant clones and is modulated by Roneparstat. These results demonstrate that the inhibition of HPSE-mediated signaling plays important roles in lapatinib resistance, and provide mechanistic insights to validate the use of Roneparstat for novel BMBC therapeutic strategies.

  15. Brain-computer interface game applications for combined neurofeedback and biofeedback treatment for children on the autism spectrum

    Directory of Open Access Journals (Sweden)

    Elisabeth V C Friedrich

    2014-07-01

    Full Text Available Individuals with Autism Spectrum Disorder (ASD show deficits in social and communicative skills, including imitation, empathy, and shared attention, as well as restricted interests and repetitive patterns of behaviors. Evidence for and against the idea that dysfunctions in the mirror neuron system are involved in imitation and could be one underlying cause for ASD is discussed in this review. Neurofeedback interventions have reduced symptoms in children with ASD by self-regulation of brain rhythms. However, cortical deficiencies are not the only cause of these symptoms. Peripheral physiological activity, such as the heart rate, is closely linked to neurophysiological signals and associated with social engagement. Therefore, a combined approach targeting the interplay between brain, body and behavior could be more effective. Brain-computer interface applications for combined neurofeedback and biofeedback treatment for children with ASD are currently nonexistent. To facilitate their use, we have designed an innovative game that includes social interactions and provides neural- and body-based feedback that corresponds directly to the underlying significance of the trained signals as well as to the behavior that is reinforced.

  16. Target inhibition networks: predicting selective combinations of druggable targets to block cancer survival pathways.

    Directory of Open Access Journals (Sweden)

    Jing Tang

    Full Text Available A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks. Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and synthetic lethal interactions. However, due to the exponentially increasing number of potential drug and target combinations, systematic approaches are needed for prioritizing the most potent multi-target alternatives on a global network level. We took a functional systems pharmacology approach toward the identification of selective target combinations for specific cancer cells by combining large-scale screening data on drug treatment efficacies and drug-target binding affinities. Our model-based prediction approach, named TIMMA, takes advantage of the polypharmacological effects of drugs and infers combinatorial drug efficacies through system-level target inhibition networks. Case studies in MCF-7 and MDA-MB-231 breast cancer and BxPC-3 pancreatic cancer cells demonstrated how the target inhibition modeling allows systematic exploration of functional interactions between drugs and their targets to maximally inhibit multiple survival pathways in a given cancer type. The TIMMA prediction results were experimentally validated by means of systematic siRNA-mediated silencing of the selected targets and their pairwise combinations, showing increased ability to identify not only such druggable kinase targets that are essential for cancer survival either individually or in combination, but also synergistic interactions indicative of non-additive drug efficacies. These system-level analyses were enabled by a novel model construction method utilizing maximization and minimization rules, as well as a model selection algorithm based on sequential forward floating search. Compared with an existing computational solution, TIMMA showed both enhanced

  17. Effect of Endostar Combined with Gemcitabine on the Mouse Model of Human Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    林清风

    2007-01-01

    Objective To investigate the effects of recombinant human endostatin,that is,endostar combined with gemcitabine on the mouse model of human pancreatic cancer.Methods We use the cell line PANC-1 and the severe combined immune deficient mice to set up the mouse model of human pancreatic cancer,then devide them into three groups,treat them with gemcitabine,gemcitabine combined with endostar,and 0.9% saline water respectively.We observe the change of the tumor volumn,use ELISA method to detect the serum VEGF level,stain the micro vessel in the tumor tissue with immunohistochemistry method,and compare the data among the different groups respectively.Results On the twenty-eighth day,the tumor volume of the control group,the monotherapy group and the combination group,averaged 1 700 mm3,19.2 mm3,10.4 mm3,serum VEGF level 88.6 L,35.5,26.3 pg/mL and MVD 43.9,30.3,19.2 respectively,which had significant difference.Conclusion Endostar can strengthen the lethal effect of gemcitabine on the mouse model of human pancreatic cancer.

  18. Superoxide Enhances the Antitumor Combination of AdMnSOD Plus BCNU in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Joseph J. Cullen

    2010-02-01

    Full Text Available Overexpression of manganese superoxide dismutase (MnSOD can sensitize a variety of cancer cell lines to many anticancer drugs. Recent work has shown that cancer cells can be sensitized to cell killing by raising peroxide levels through increased manganese superoxide dismutase (MnSOD when combined with inhibition of peroxide removal. Here we utilize the mechanistic property of one such anticancer drug, BCNU, which inhibits glutathione reductase (GR, compromising the glutathione peroxidase system thereby inhibiting peroxide removal. The purpose of this study was to determine if anticancer modalities known to produce superoxide radicals can increase the antitumor effect of MnSOD overexpression when combined with BCNU. To enhance MnSOD, an adenoviral construct containing the cDNA for MnSOD (AdMnSOD was introduced into human breast cancer cell line, ZR-75-1. AdMnSOD infection alone did not alter cell killing, however when GR was inhibited with either BCNU or siRNA, cytotoxicity increased. Futhermore, when the AdMnSOD + BCNU treatment was combined with agents that enhance steady-state levels of superoxide (TNF-α, antimycin, adriamycin, photosensitizers, and ionizing radiation, both cell cytotoxicity and intracellular peroxide levels increased. These results suggest that the anticancer effect of AdMnSOD combined with BCNU can be enhanced by agents that increase generation of superoxide.

  19. Optimal multitrial prediction combination and subject-specific adaptation for minimal training brain switch designs

    NARCIS (Netherlands)

    Spyrou, L.; Blokland, Y.M.; Farquhar, J.D.R.; Bruhn, J.

    2016-01-01

    Brain-Computer Interface systems are traditionally designed by taking into account user-specific data to enable practical use. More recently, subject independent (SI) classification algorithms have been developed which bypass the subject specific adaptation and enable rapid use of the system. A brai

  20. New potential chemotherapy for ovarian cancer - Combined therapy with WP 631 and epothilone B.

    Science.gov (United States)

    Bukowska, Barbara; Rogalska, Aneta; Marczak, Agnieszka

    2016-04-15

    Despite more modern therapeutics approaches and the use of new drugs for chemotherapy, patients with ovarian cancer still have poor prognosis and therefore, new strategies for its cure are highly needed. One of the promising ways is combined therapy, which has many advantages as minimizing drug resistance, enhancing efficacy of treatment, and reducing toxicity. Combined therapy has rich and successful history in the field of ovarian cancer treatment. Currently use therapy is usually based on platinum-containing agent (carboplatin or cisplatin) and a member of taxanes (paclitaxel or docetaxel). In the mid-2000s this standard regimen has been expanded with bevacizumab, monoclonal antibody directed to Vascular Endothelial Growth Factor (VEGF). Another drug combination with promising perspectives is WP 631 given together with epothilone B (Epo B). WP 631 is a bisanthracycline composed of two molecules of daunorubicin linked with a p-xylenyl linker. Epo B is a 16-membered macrolide manifesting similar mechanism of action to taxanes. Their effectiveness against ovarian cancer as single agents is well established. However, the combination of WP 631 and Epo B appeared to act synergistically, meaning that it is much more potent than the single drugs. The mechanism lying under its efficacy includes disturbing essential cell cycle-regulating proteins leading to mitotic slippage and following apoptosis, as well as affecting EpCAM and HMGB1 expression. In this article, we summarized the current state of knowledge regarding combined therapy based on WP 631 and Epo B as a potential way of ovarian cancer treatment. PMID:26944437

  1. The anti-cancer effects of carotenoids and other phytonutrients resides in their combined activity.

    Science.gov (United States)

    Linnewiel-Hermoni, Karin; Khanin, Marina; Danilenko, Michael; Zango, Gabriel; Amosi, Yaara; Levy, Joseph; Sharoni, Yoav

    2015-04-15

    Epidemiological studies have consistently shown that regular consumption of fruits and vegetables is strongly associated with reduced risk of developing chronic diseases, such as cancer. It is now accepted that the actions of any specific phytonutrient alone do not explain the observed health benefits of diets rich in fruits and vegetables as nutrients that were taken alone in clinical trials did not show consistent preventive effects. The considerable cost and complexity of such clinical trials requires prudent selection of combinations of ingredients rather than single compounds. Indeed, synergistic inhibition of prostate and mammary cancer cell growth was evident when using combinations of low concentrations of various carotenoids or carotenoids with retinoic acid and the active metabolite of vitamin-D. In this study we aimed to develop simple and sensitive in vitro methods which provide information on potent combinations suitable for inclusion in clinical studies for cancer prevention. We, thus, used reporter gene assays of the transcriptional activity of the androgen receptor in hormone-dependent prostate cancer cells and of the electrophile/antioxidant response element (EpRE/ARE) transcription system. We found that combinations of several carotenoids (e.g., lycopene, phytoene and phytofluene), or carotenoids and polyphenols (e.g., carnosic acid and curcumin) and/or other compounds (e.g., vitamin E) synergistically inhibit the androgen receptor activity and activate the EpRE/ARE system. The activation of EpRE/ARE was up to four fold higher than the sum of the activities of the single ingredients, a robust hallmark of synergy. Such combinations can further be tested in the more complex in vivo models and human studies.

  2. Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac

    Institute of Scientific and Technical Information of China (English)

    Li Ma; Yong-Le Xie; Yi Yu; Qiu-Ning Zhang

    2005-01-01

    AIM: To investigate the effects of mitomycin (MMC)combined with sulindac on cell viability, apoptotic induction and expression of apoptosis-related gene Bcl-2 and cyclooxygenase-2 (COX-2)in gastric cancer SGC-7901cells.METHODS: Human gastric cancer SGC-7901 cells were divided into three treatment groups,namely sulindac treatment group, MMC treatment group and combined sulindac with MMC treatment group. After being treated with drugs, cell viability was examined by MTr assay.Flow cytometry was used to evaluate the cell cycle distribution and apoptotic rates. Morphology of the cells was observed under light microscope and interactive laser microscope. Expression of COX-2 and Bcl-2 was determined by immunocytochemical method.RESULTS: After exposure for 12 h to three kinds of drugs,gastric cancer SGC-7901 cells presented some morphological features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apoptotic bodies. Growth inhibition was more obvious in combined sulindac with MMC treatment group and sulindac treatment group than in MMC treatment group. The apoptotic rates in co-treated cells and MMC-treated cells 24 h after treatment were 12.0% and 7.2%, respectively.After exposure for 24 h to MMC, the expression of COX-2and Bcl-2 protein was up-regulated, COX-2 levels were down-regulated but Bcl-2 gene expression was not changed significantly in combined treatment group.CONCLUSION: MMC-induced apoptosis is reduced by up-regulating the expression of COX-2 and Bcl-2 genes.MMC combined with sulindac can suppress the growth of gastric cancer cells through induction of apoptosis mediated by down-regulation of apoptosis-related Bcl-2and COX-2 gene.

  3. Clinical Study of Endostar Combined with DP Protocol in Treatment of Advanced Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    DENG Wen-ying; LI Ning; LUO Su-xia

    2015-01-01

    Objective: To observe the clinical outcomes of Endostar combined with DP regimen for treating advanced esophageal cancer. Methods: A total of 62 patients with advanced esophageal cancer admitted from May, 2011 to May, 2013 were enrolled for a prospective, randomized controlled trial and 2 cases were excluded from the study because ofⅣ degree of digestive tract reaction and myelosuppression. Therefore, 60 cases could be evaluated, and then divided into combined group (given Endostar+DP plan) and single chemotherapy group, 30 cases in each group. The level of VEGF, tumor size and CT perfusion (CTP) parameters, including blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS) before and after treatment were determined for comparison. Kaplan-Merier method was used to analyze the overall survival (OS) of 2 groups. Results:The efifcacy of combined group was superior to single chemotherapy group. The level of vascular endothelial growth factor (VEGF) in combined group was obviously lower than that in single chemotherapy group after treatment (P0.05). The median OS was 30 months (95%CI: 20.935-39.065) for combined group and 21 months (95%CI: 15.109-26.591) for single chemotherapy group, respectively (P=0.048). The 1-, 2- and 3-year survival rates were 86.2%, 59.3% and 36.6% in combined group, and 70.8%, 32.1% and 17.8% in single chemotherapy group, respectively. Conclusion: Endostar can down-regulate the expression of VEGF, improve the state of hypertransfusion and high permeability of tumor vessels, has better curative effect without slighter adverse reactions, and prolong the survival time of patients with advanced esophageal cancer when combined with chemotherapy.

  4. PHASE Ⅱ STUDY OF GEMCITABINE COMBINED WITH PLATINUM CHEMOTHERAPY FOR RECURRENT EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer.Methods Phase Ⅱ study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50. 5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractor. All patients received gemcitabine combined with carboplatin or oxaliplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated.Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36.4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10. 0 months (95% CI: 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy.There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P = 0. 061 ). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8 % of patients. Grade Ⅱ/Ⅲ anemia (54.5%) and grade Ⅲ/Ⅳ neutropenia (54.5%) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia,and 8 (36. 4% ) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death.Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.

  5. 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

  6. Patients with brain metastases from gastrointestinal tract cancer treated with whole brain radiation therapy:Prognostic factors and survival

    Institute of Scientific and Technical Information of China (English)

    Susanne Bartelt; Felix Momm; Christian Weissenberger; Johannes Lutterbach

    2004-01-01

    AIM: To identify the prognostic factors with regard to survival for patients with brain metastasis from primary tumors of the gastrointestinal tract.METHODS: Nine hundred and sixteen patients with brain metastases, treated with whole brain radiation therapy (WBRT) between January 1985 and December 2000 at the Department of Radiation Oncology, University Hospital Freiburg, were analyzed retrospectively.RESULTS: Fifty-seven patients presented with a primary tumor of the gastrointestinal tract (esophagus: n = 0, stomach:n = 10, colorectal: n = 47). Twenty-six patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 25 patients.WBRTwas applied with daily fractions of 2 Gray (Gy) or 3 Gy to a total dose of 50 Gy or 30 Gy, respectively. The interval between diagnoses of the primary tumors and brain metastases was 22.6 mo vs8.0 mo for patients with primary tumors of the colon/rectum vs other primary tumors,respectively (P<0.01, log-rank). Median overall survival for all patients with brain metastases (n = 916) was 3.4 mo and 3.2 mo for patients with gastrointestinal neoplasms.Patients with gastrointestinal primary tumors presented significantly more often with a solitary brain metastasis than patients with other primary tumors (P<0.05, log-rank). In patients with gastrointestinal neoplasms (n = 57), the median overall survival was 5.8 mo for patients with solitary brain metastasis vs 2.7 mo for patients with multiple brain metastases (P<0.01, log-rank). The median overall survival for patients with a Karnofsky performance status (KPS) ≥70was 5.5 mo vs2.1 mo for patients with KPS <70 (P<0.01,log-rank). At multivariate analysis (Cox Model) the performance status and the number of brain metastases were identified as independent prognostic factors for overall survival.CONCLUSION: Brain metastases occur late in the course of gastrointestinal tumors. Pretherapeutic variables like KPS and the

  7. Epidemiological features of brain tumors

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2013-01-01

    Full Text Available Brain tumors account for 1.4% of all cancers and 2.4% of all cancer-related deaths. The incidence of brain tumors varies and it is higher in developed countries of Western Europe, North America, Australia and New Zealand. In Serbia, according to data from 2009, malignant brain tumors account for 2. 2 of all tumors, and from all cancer­related deaths, 3.2% is caused by malignant brain tumors. According to recent statistical reports, an overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 persons/year. The most common benign brain tumor in adults is meningioma, which is most present in women, and the most common malignant tumor is glioblastoma, which is most present in adult men. Due to high mortality, especially in patients diagnosed with glioblastoma and significant brain tumor morbidity, there is a constant interest in understanding its etiology in order to possibly prevent tumor occurrence in future and enable more efficient treatment strategies for this fatal brain disease. Despite the continuously growing number of epidemiological studies on possible factors of tumor incidence, the etiology remains unclear. The only established environmental risk factor of gliomas is ionizing radiation exposure. Exposure to radiofrequency electromagnetic fields via cell phone use has gained a lot of attention as a potential risk factor of brain tumor development. However, studies have been inconsistent and inconclusive, so more definite results are still expected.

  8. Kanglaite combined Gemcitabine inhibits growth of nude mouse subcutaneous transplantation tumor of human PC-3 pancreatic cancer cell

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; JIN Jian-guang; QIN Zhao-yin

    2005-01-01

    Objective:To study the mechanisms of pancreatic cancer treatment with Kanglaite combined Gemcitabine by investigating the relationship between the apoptosis and the expression of bcl-2, Bax and VEGF in pancreatic cancer cells.Methods:Nude mouse subcutaneous transplantation tumor model of Human PC-3 pancreatic cancer was established; the expressions of bcl-2, Bax and VEGF of transplantation tumor cell were determined; the earlier apoptosis rate of pancreatic cancer cell and the gross tumor volume were determined. Results:Kanglaite combined Gemcitabine remarkably decreased the protein expression of bcl-2,raised the expression of Bax,increased the apoptosis rate of the pancreatic cancer and contract the gross tumor volume. Kanglaite greatly decreased the protein expression of VEGF of the tumor cell. Conclusion:Therapeutic efficacy of Kanglaite combined Gemcitabine is far better than separate use of the two medicines in the pancreatic cancer transplantation tumor treatment.

  9. Synergistic effects of fresh frozen plasma and valproic acid treatment in a combined model of traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Imam, Ayesha M; Jin, Guang; Duggan, Michael;

    2013-01-01

    Traumatic brain injury (TBI) and hemorrhagic shock (HS) are major causes of trauma-related deaths and are especially lethal as a combined insult. Previously, we showed that early administration of fresh frozen plasma (FFP) decreased the size of the brain lesion and associated swelling in a swine ...

  10. A mathematical model of combined therapies against cancer using viruses and inhibitors

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This paper deals with a procedure for combined therapies against cancer using oncolytic viruses and inhibitors. Replicating genetically modified adenoviruses infect cancer cells, reproduce inside them and eventually cause their death (lysis). As infected cells die, the viruses inside them are released and then proceed to infect other tumor cells. The successful entry of virus into cancer cells is related to the presence of the coxsackie-adenovirus receptor (CAR). Mitogen-activated protein kinase kinase (known as MEK) inhibitors can promote CAR expression, resulting in enhanced adenovirus entry into cancer cells. However, MEK inhibitors can also cause G1 cell-cycle arrest, inhibiting reproduction of the virus. To design an effective synergistic therapy, the promotion of virus infection must be optimally balanced with inhibition of virus production. We introduce a mathematical model to describe the effects of MEK inhibitors and viruses on tumor cells, and use it to explore the reduction of the tumor size that can be achieved by the combined therapies. Furthermore, we find an optimal dose of inhibitor: Poptimal = 1 - μ/δ for a certain initial density of cells (where μ is the removal rate of the dead cells and δ is the death rate of the infected cells). The optimal timing of MEK inhibitors is also numerically studied.

  11. Anticoagulation in combination with antiangiogenesis and chemotherapy for cancer patients: evidence and hypothesis.

    Science.gov (United States)

    Wang, Ji; Zhu, Chengchu

    2016-01-01

    Hypercoagulable state and disorganized angiogenesis are two conspicuous characteristics during tumor progression. There are a considerable number of clinical trials focusing on the effects of anticoagulant and antiangiogenic drugs on the survival of cancer patients. Favorable outcomes have been observed. Excessive blood coagulation not only causes cancer-associated thrombosis, which is a common complication and is the second leading cause of death in patients, but also decreases intratumoral perfusion rates and drug delivery by reducing the effective cross-sectional area of blood vessels. Meanwhile, structural and functional abnormalities of the tumor microvasculature also compromise convective drug transport and create a hypoxic and acidic microenvironment. Vascular normalization strategy can temporarily recover the abnormal state of tumor vasculature by improving blood density, dilation, and leakiness, resulting in enhanced penetration of chemotherapies and oxygen within a short time window. In this article, we first review the evidence to support the opinion that anticoagulant and antiangiogenic therapy can improve cancer survival through several underlying mechanisms. Next, we speculate on the feasibility and value of the combined strategy and discuss whether such a combination has a synergistic antineoplastic effect in cancer patients by way of increasing blood vessel perfusion and drug distribution. PMID:27536135

  12. A mathematical model of combined therapies against cancer using viruses and inhibitors

    Institute of Scientific and Technical Information of China (English)

    TAO YouShan; GUO Qian

    2008-01-01

    This paper deals with a procedure for combined therapies against cancer using oncolytic viruses and inhibitors. Replicating genetically modified adenoviruses infect cancer cells, reproduce inside them and eventually cause their death (lysis). As infected cells die, the viruses inside them are released and then proceed to infect other tumor cells. The successful entry of virus into cancer cells is related to the presence of the coxsackie-adenovirus receptor (CAR). Mitogen-activated protein kinase kinase (known as MEK) inhibitors can promote CAR expression, resulting in enhanced adenovirus entry into cancer cells. However, MEK inhibitors can also cause G1 cell-cycle arrest, inhibiting reproduction of the virus. To design an effective synergistic therapy, the promotion of virus infection must be optimally balanced with inhibition of virus production. We introduce a mathematical model to describe the effects of MEK inhibitors and viruses on tumor cells, and use it to explore the reduction of the tumor size that can be achieved by the combined therapies. Furthermore, we find an optimal dose of inhibitor: Poptimal = I - μ/δ for a certain initial density of cells (where μ is the removal rate of the dead cells and δ is the death rate of the infected cells). The optimal timing of MEK inhibitors is also numerically studied.

  13. Anticoagulation in combination with antiangiogenesis and chemotherapy for cancer patients: evidence and hypothesis

    Directory of Open Access Journals (Sweden)

    Wang J

    2016-07-01

    Full Text Available Ji Wang, Chengchu Zhu Department of Cardiothoracic Surgery, Taizhou Hospital, Wenzhou Medical University, Linhai, Zhejiang, People’s Republic of China Abstract: Hypercoagulable state and disorganized angiogenesis are two conspicuous characteristics during tumor progression. There are a considerable number of clinical trials focusing on the effects of anticoagulant and antiangiogenic drugs on the survival of cancer patients. Favorable outcomes have been observed. Excessive blood coagulation not only causes cancer-associated thrombosis, which is a common complication and is the second leading cause of death in patients, but also decreases intratumoral perfusion rates and drug delivery by reducing the effective cross-sectional area of blood vessels. Meanwhile, structural and functional abnormalities of the tumor microvasculature also compromise convective drug transport and create a hypoxic and acidic microenvironment. Vascular normalization strategy can temporarily recover the abnormal state of tumor vasculature by improving blood density, dilation, and leakiness, resulting in enhanced penetration of chemotherapies and oxygen within a short time window. In this article, we first review the evidence to support the opinion that anticoagulant and antiangiogenic therapy can improve cancer survival through several underlying mechanisms. Next, we speculate on the feasibility and value of the combined strategy and discuss whether such a combination has a synergistic antineoplastic effect in cancer patients by way of increasing blood vessel perfusion and drug distribution. Keywords: tumor microenvironment, anticoagulation, antiangiogenesis, vascular normalization, tumor perfusion

  14. Pharmacologic inhibition of MLK3 kinase activity blocks the in vitro migratory capacity of breast cancer cells but has no effect on breast cancer brain metastasis in a mouse xenograft model.

    Directory of Open Access Journals (Sweden)

    Kun Hyoe Rhoo

    Full Text Available Brain metastasis of breast cancer is an important clinical problem, with few therapeutic options and a poor prognosis. Recent data have implicated mixed lineage kinase 3 (MLK3 in controlling the in vitro migratory capacity of breast cancer cells, as well as the metastasis of MDA-MB-231 breast cancer cells from the mammary fat pad to distant lymph nodes in a mouse xenograft model. We therefore set out to test whether MLK3 plays a role in brain metastasis of breast cancer cells. To address this question, we used a novel, brain penetrant, MLK3 inhibitor, URMC099. URMC099 efficiently inhibited the migration of breast cancer cells in an in vitro cell monolayer wounding assay, and an in vitro transwell migration assay, but had no effect on in vitro cell growth. We also tested the effect of URMC099 on tumor formation in a mouse xenograft model of breast cancer brain metastasis. This analysis showed that URMC099 had no effect on the either the frequency or size of breast cancer brain metastases. We conclude that pharmacologic inhibition of MLK3 by URMC099 can reduce the in vitro migratory capacity of breast cancer cells, but that it has no effect on either the frequency or size of breast cancer brain metastases, in a mouse xenograft model.

  15. Synergistic chemoprotective mechanisms of dietary phytoestrogens in a select combination against prostate cancer.

    Science.gov (United States)

    Kumar, Rajeev; Verma, Vikas; Jain, Ashish; Jain, Rajeev K; Maikhuri, Jagdamba P; Gupta, Gopal

    2011-08-01

    Combination of dietary phytoestrogens with diverse molecular mechanisms may enhance their anticancer efficacy at physiological concentrations, as evidenced in epidemiological studies. A select combination of three dietary phytoestrogens containing 8.33 μM each of genistein (G), quercetin (Q) and biochanin A (B) was found to be more potent in inhibiting the growth of androgen-responsive prostate cancer cells (LNCaP) as well as DU-145 and PC-3 prostate cancer cells in vitro than either 25 μM of G, B or Q or 12.5+12.5 μM of G+Q, Q+B or G+B. Subsequent mechanistic studies in PC-3 cells indicated that the action of phytoestrogens was mediated both through estrogen receptor (ER)-dependent and ER-independent pathways as potent estrogen antagonist ICI-182780 (ICI, 5 μM) could not completely mask the synergistic anticancer effects, which were sustained appreciably in presence of ICI. G+Q+B combination was significantly more effective than individual compounds or their double combinations in increasing ER-β, bax (mRNA expression); phospho-JNK, bax (protein levels); and in decreasing bcl-2, cyclin E, c-myc (mRNA expression); phospho-AKT, phospho-ERK, bcl-2, proliferating cell nuclear antigen (protein levels) in PC-3 cells. Phytoestrogens also synergistically stimulated caspase-3 activity. Our findings suggest that selectively combining anticancer phytoestrogens could significantly increase the efficacy of individual components resulting in improved efficacy at physiologically achievable concentrations. The combination mechanism of multiple anticancer phytochemicals may be indicative of the potential of some vegetarian diet components to elicit chemopreventive effects against prostate cancer at their physiologically achievable concentrations, in vivo. PMID:21062672

  16. Time-Frequency Analysis of Peptide Microarray Data: Application to Brain Cancer Immunosignatures.

    Science.gov (United States)

    O'Donnell, Brian; Maurer, Alexander; Papandreou-Suppappola, Antonia; Stafford, Phillip

    2015-01-01

    One of the gravest dangers facing cancer patients is an extended symptom-free lull between tumor initiation and the first diagnosis. Detection of tumors is critical for effective intervention. Using the body's immune system to detect and amplify tumor-specific signals may enable detection of cancer using an inexpensive immunoassay. Immunosignatures are one such assay: they provide a map of antibody interactions with random-sequence peptides. They enable detection of disease-specific patterns using classic train/test methods. However, to date, very little effort has gone into extracting information from the sequence of peptides that interact with disease-specific antibodies. Because it is difficult to represent all possible antigen peptides in a microarray format, we chose to synthesize only 330,000 peptides on a single immunosignature microarray. The 330,000 random-sequence peptides on the microarray represent 83% of all tetramers and 27% of all pentamers, creating an unbiased but substantial gap in the coverage of total sequence space. We therefore chose to examine many relatively short motifs from these random-sequence peptides. Time-variant analysis of recurrent subsequences provided a means to dissect amino acid sequences from the peptides while simultaneously retaining the antibody-peptide binding intensities. We first used a simple experiment in which monoclonal antibodies with known linear epitopes were exposed to these random-sequence peptides, and their binding intensities were used to create our algorithm. We then demonstrated the performance of the proposed algorithm by examining immunosignatures from patients with Glioblastoma multiformae (GBM), an aggressive form of brain cancer. Eight different frameshift targets were identified from the random-sequence peptides using this technique. If immune-reactive antigens can be identified using a relatively simple immune assay, it might enable a diagnostic test with sufficient sensitivity to detect tumors in a

  17. [Strategy of combined treatment in patient with cancer of paranasal sinuses].

    Science.gov (United States)

    Kiprian, Dorota

    2007-01-01

    Cancers of pranasal sinuses are rare neoplasms in humans. In 2003, in Poland there were 132 new patients diagnosed for this disease. Squamous cell cancer is the most frequent one in this region. Other types of cancer in this region are adenocarcinoma (about 30%), carcinoma adenoides cysticum or neoplasms such as rhabdosarcoma, chondrosarcoma, lymphoma or melanoma malignum. There is a very rare neoplasm as a olfactory neuroblastoma in this localization. Cancer of the paranasal sinuses infiltrates only locoregionally. Metastases to the lymph nodes are seldom--below 30%; this is why elective lymphangiectomy or irradiation are not obligatory treatment in this case. The most important is histopathological verification performed by biopsy. For clinical staging it is obligatory to perform endoscopy, CT or MR examination. The treatment of cancers of paranasal sinuses is always surgery with adjuvant irradiation. The modern radiotherapy techniques provide the possibility to spare healthy tissues and organs at risk. The organs at risk in this localization are optical nerves and chiasm, and parotid glands. The conformal radiotherapy is used most frequently. In case of the tumour being of complex shape and located in the vicinity of the organs at risk the IMRT technique is used. The radiation treatment combined with chemotherapy is applied in cases of not radical surgery in the region of ethmoides sinuses.

  18. Gene expression profiling of gastric cancer by microarray combined with laser capture microdissection

    Institute of Scientific and Technical Information of China (English)

    Ming-Shiang Wu; Yi-Shing Lin; Yu-Ting Chang; Chia-Tung Shun; Ming-Tsan Lin; Jaw-Town Lin

    2005-01-01

    AIM: To examine the gene expression profile of gastric cancer (GC) by combination of laser capture microdissection (LCM) and microarray and to correlate the profiling with histological subtypes. METHODS: Using LCM, pure cancer cells were procured from 45 cancerous tissues. After procurement of about 5 000 cells, total RNA was extracted and the quality of RNA was determined before further amplification and hybridization. One microgram of amplified RNA was converted to cDNA and hybridized to cDNA microarray. RESULTS: Among 45 cases, only 21 were qualified for their RNAs. A total of 62 arrays were performed. These included 42 arrays for cancer (21 cases with dyeswab duplication) and 20 arrays for non-tumorous cells (10 cases with dye-swab duplication) with universal reference. Analyzed data showed 504 genes were differentially expressed and could distinguish cancerous and non-cancerous groups with more than 99% accuracy. Of the 504 genes, trefoil factors 1, 2, and 3 were in the list and their expression patterns were consistent with previous reports. Immunohistochemical staining of trefoil factor 1 was also consistent with the array data. Analyses of the tumor group with these 504 genes showed that there were 3 subgroups of GC that did not correspond to any current classification system, including Lauren's classification. CONCLUSION: By using LCM, linear amplification of RNA, and cDNA microarray, we have identified a panel of genes that have the power to discriminate between GC and non-cancer groups. The new molecular classification and the identified novel genes in gastric carcinogenesis deserve further investigations to elucidate their dinicopathological significance.

  19. Longitudinal MRI evaluation of intracranial development and vascular characteristics of breast cancer brain metastases in a mouse model.

    Directory of Open Access Journals (Sweden)

    Heling Zhou

    Full Text Available Longitudinal MRI was applied to monitor intracranial initiation and development of brain metastases and assess tumor vascular volume and permeability in a mouse model of breast cancer brain metastases. Using a 9.4T system, high resolution anatomic MRI and dynamic susceptibility contrast (DSC perfusion MRI were acquired at different time points after an intracardiac injection of brain-tropic breast cancer MDA-MB231BR-EGFP cells. Three weeks post injection, multifocal brain metastases were first observed with hyperintensity on T2-weighted images, but isointensity on T1-weighted post contrast images, indicating that blood-tumor-barrier (BTB at early stage of brain metastases was impermeable. Follow-up MRI revealed intracranial tumor growth and increased number of metastases that distributed throughout the whole brain. At the last scan on week 5, T1-weighted post contrast images detected BTB disruption in 160 (34% of a total of 464 brain metastases. Enhancement in some of the metastases was only seen in partial regions of the tumor, suggesting intratumoral heterogeneity of BTB disruption. DSC MRI measurements of relative cerebral blood volume (rCBV showed that rCBV of brain metastases was significantly lower (mean= 0.89±0.03 than that of contralateral normal brain (mean= 1.00±0.03; p<0.005. Intriguingly, longitudinal measurements revealed that rCBV of individual metastases at early stage was similar to, but became significantly lower than that of contralateral normal brain with tumor growth (p<0.05. The rCBV data were concordant with histological analysis of microvascular density (MVD. Moreover, comprehensive analysis suggested no significant correlation among tumor size, rCBV and BTB permeability. In conclusion, longitudinal MRI provides non-invasive in vivo assessments of spatial and temporal development of brain metastases and their vascular volume and permeability. The characteristic rCBV of brain metastases may have a diagnostic value.

  20. Heat shock proteins 27, 40, and 70 as combinational and dual therapeutic cancer targets

    OpenAIRE

    McConnell, Jeanette R.; McAlpine, Shelli R.

    2013-01-01

    The heat shock proteins are essential players in the development of cancer and they are prime therapeutic targets. Targeting multiple hsps in dual therapies decreases the likelihood of drug resistance compared to utilizing mono-therapies. Further, employing an hsp inhibitor in combination with another therapy has proven clinically successful. Examples of efficacious strategies include the inhibition of hsp27, which prevents protein aggregation, controlling hsp40’s role as an ATPase modulator,...

  1. Combination of internal radiation therapy and hyperthermia to treat liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Grady, E.D.; McLaren, J.; Auda, S.P.; McGinley, P.H.

    1983-09-01

    Sixteen patients were treated for liver cancer (primary and metastatic) by a combination of internal radiation therapy with intra-arterial yttrium 90 microspheres and regional hyperthermia with electromagnetic radiation. Four patients have their liver disease apparently controlled; two had a partial regression of more than 50%; and two had a partial regression of less than 50%. The complications consisted of one case of radiation hepatitis and one of peptic ulcer.

  2. Effects of Celecoxib and Ly117018 Combination on Human Breast Cancer Cells in Vitro

    Directory of Open Access Journals (Sweden)

    Klaus H. Baumann

    2009-01-01

    Full Text Available Activation and signalling of estrogen receptor (ER and COX-2 represent two important pathways in breast cancer cell regulation. Activation of either pathway is associated with breast cancer cell proliferation and eventually malignant progression. Raloxifene analogue, Ly117018, a selective estrogen receptor modulator and celecoxib, a specific COX- 2 inhibitor have been shown to inhibit breast cancer cell proliferation when used alone in vitro and in vivo. In this study, the combined drug effects on hormone-dependent MCF-7 and hormone-independent MDA-MB-435 cells in vitro were evaluated. Cell proliferation assays excluded drug antagonism and revealed a moderate synergistic growth inhibitory activity of Ly117018 and celecoxib on both cell lines when combined in specific concentrations. Growth inhibition of either compound was not associated with cell cycle arrest. In MCF-7 cells, western blot analysis revealed a decreased phosphorylation of the AKT protein by either agent alone or in combination. In MDA-MB-435 cells, celecoxib alone induced an increase in AKT phosphorylation relative to total AKT protein; this effect was decreased in the presence of Ly117018. These results indicate that these two drugs are non-antagonistic; and when combined in specific concentrations, moderate synergistic antiproliferative activity of celecoxib and Ly117018 were observed in hormone-dependent MCF-7 and hormone- independent MDA-MB-435 cells associated with changes in cell cycle distribution and regulation of AKT protein and phosphorylation. These findings further support a central role of the ER- and COX-2 pathways in human breast cancer cells.

  3. Clinical observation of raltitrexed/bevacizumab combined with irinotecan or oxaliplation for advanced colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Jianwei Yang; Wei Gao; Jinyuan Lin; Yan Meng; Shuzhen Zhang; Tong Wang

    2014-01-01

    Objective: The aim of the study was to investigate the ef icacy and safety of raltitrexed/bevacizumab in combina-tion with irinotecan or oxaliplation for advanced colorectal cancer as the second-line and second-line above treatments. Meth-ods: Fifteen cases of advanced colorectal cancer were enrol ed to receive regimens including raltitrexed/bevacizumab com-bined with irinotecan or oxaliplation. Two cases were treated with raltitrexed + bavacizumab regimen, 9 cases with raltitrexed+ bavacizumab + irinotecan regimen, and 4 cases with raltitrexed + bevacizumab + oxaliplation regimen. The doses of the drugs were as fol ows: bevacizumab 5 mg/kg ivgtt, d1; raltitrexed 2.0 mg/m2 ivgtt 15 min, d2; irinotecan 180 mg/m2 ivgtt 1 h, d2; and oxaliplatin 85 mg/m2 ivgtt 2 h, d2. Two weeks was a cycle for each regimen. Results: The ef icacy of the 15 patients could be evaluated. Two cases were in PR ,10 cases in SD, 3 cases in PD, the response rate was 13.3%, and the disease control rate was 80.0%. The median progress-free survival was 5.1 months (95% CI: 3.404-6.813 months), and the median overal survival was 11.5 months (95% CI: 8.985-13.930 months). The adverse ef ects included anorexia, nausea/vomit-ing, fatigue, leucopenia, thrombocytopenia, etc, and the main 3-4 grades adverse ef ects were anorexia, nausea/vomiting, fatigue, and thrombocytopenia. Conclusion: Raltitrexed/bevacizumab combined with irinotecan or oxaliplatin as the second-line and second-line above treatments for advanced colorectal cancer has high disease control rates, and the adverse ef ect is wel tolerated. The combined regimen can be recommended as a phase III clinical research and second-line and second-lines above treatments for advanced colorectal cancer.

  4. A combined neuropsychological and brain imaging study of obstructive sleep apnea.

    OpenAIRE

    Yaouhi, Khalid; Bertran, Françoise; Clochon, Patrice; Mézenge, Florence; Denise, Pierre; Foret, Jean; Eustache, Francis; Desgranges, Béatrice

    2009-01-01

    Patients with obstructive sleep apnea (OSA) show neuropsychological impairments ranging from vigilance decrements, attentional lapses and memory gaps to decreased motor coordination, but their cognitive profile, and the origin of the impairments, remain unclear. We sought to establish the neuropsychological profile of 16 newly diagnosed apneics and to highlight both their morphological and functional brain abnormalities. We used an extensive neuropsychological test battery to investigate atte...

  5. The ways of improvement of combination therapy results in patients with local cervical cancer

    International Nuclear Information System (INIS)

    A new solutions of a scientific task of modern oncogynecology, improvement of the efficacy of treatment for local cervical cancer on the account of expansion of the indications to operative treatment is presented on the clinical material (275 patients with stage II-III CC). The use of the developed technique of multimodality therapy based on the split course of combination radiation therapy against a background of neoadjuvant chemotherapy allowed to convert in 49.6% of cases of immobile tumor process to an operable stage followed by uterus and adnexae removal while at the traditional combination radiotherapy the resectability index was 6.9%.

  6. Combination of omega-3 Fatty acids, lithium, and aripiprazole reduces oxidative stress in brain of mice with mania.

    Science.gov (United States)

    Arunagiri, Pandiyan; Rajeshwaran, Krishnamoorthy; Shanthakumar, Janakiraman; Tamilselvan, Thangavel; Balamurugan, Elumalai

    2014-09-01

    Manic episode in bipolar disorder (BD) was evaluated in the present study with supplementation of omega-3 fatty acids in combination with aripiprazole and lithium on methylphenidate (MPD)-induced manic mice model. Administration of MPD 5 mg/kg bw intraperitoneally (i.p.) caused increase in oxidative stress in mice brain. To retract this effect, supplementation of omega-3 fatty acids 1.5 ml/kg (p.o.), aripiprazole 1.5 mg/kg bw (i.p.), and lithium 50 mg/kg bw (p.o) were given to mice. Omega-3 fatty acids alone and in combination with aripiprazole- and lithium-treated groups significantly reduced the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation products (thiobarbituric acid reactive substances) in the brain. MPD treatment significantly decreased the reduced glutathione (GSH) level and glutathione peroxidase (GPx) activity, and they were restored by supplementation of omega-3 fatty acids with aripiprazole and lithium. There is no remarkable difference in the effect of creatine kinase (CK) activity between MPD-induced manic model and the treatment groups. Therefore, our results demonstrate that oxidative stress imbalance and mild insignificant CK alterations induced by administration of MPD can be restored back to normal physiological levels through omega-3 fatty acids combined with lithium and aripiprazole that attributes to effective prevention against mania in adult male Swiss albino mice.

  7. Fueling the engine and releasing the break:combinational therapy of cancer vaccines and immune checkpoint inhibitors

    Institute of Scientific and Technical Information of China (English)

    Jennifer Kleponis; Richard Skelton; Lei Zheng

    2015-01-01

    Immune checkpoint inhibitors are increasingly drawing much attention in the therapeutic development for cancer treatment. However, many cancer patients do not respond to treatments with immune checkpoint inhibitors, partly because of the lack of tumor-inifltrating effector T cells. Cancer vaccines may prime patients for treatments with immune checkpoint inhibitors by inducing effector T-cell infiltration into the tumors and immune checkpoint signals. The combination of cancer vaccine and an immune checkpoint inhibitor may function synergistically to induce more effective antitumor immune responses, and clinical trials to test the combination are currently ongoing.

  8. Effects of recombinant epidermal growth factor receptor antisense adenovirus combined with irradiation on breast cancer cells

    International Nuclear Information System (INIS)

    Objective: To investigate the effects of a recombinant antisense adenovirus for epidermal growth factor receptor (EGFR) combined with irradiation on breast cancer cells. Methods: Human EGFR cDNA fragment was subcloned in the opposite orientation to the cytomegaloviral promoter and inserted into a E1/E3-deleted type 5 adenoviral vector to obtain AdE5 construct which expresses EGFR antisense RNA. Combined with γ-ray irradiation, its effects on clonogenicity and cell cycle phase distribution were studied in a human breast cancer line MDA-MB-23. Results: EGFR protein expression was dramatically inhibited in MDA-MB-231 cells after AdE5 infection. The post-irradiation clonogenicity was reduced by AdE5 in a viral and irradiation dose-dependent manner. Further cytometric analysis showed that AdE5 infection at a MOI of 300 pfu/cell induced a cell cycle progression from radio-resistant G0 + G1 phases to radiosensitive G2 + M phases, resulting in a synergistic effect after combination of these two treatments. Conclusions: The transduction of EGFR antisense RNA by adenoviral vector is effective for antisense strategy targeting EGFR, and increases the cell-killing effect of ionizing radiation on breast cancer cells.(authors)

  9. Comparative dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for brain tumors

    OpenAIRE

    Samia de Freitas Brandao; Tarcisio Passos Ribeiro de Campos

    2013-01-01

    Objective Comparative analysis of dosimetry in intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT for treatment of brain tumors. Materials and Methods Simulations of intracavitary balloon catheter brachytherapy with I-125 and in Cf-252 brachytherapy combined with BNCT were performed with the MCNP5 code, modeling the treatment of a brain tumor on a voxel computational phantom representing a human head. Absorbed dose rates were converted int...

  10. Importance of Extracranial Disease Status and Tumor Subtype for Patients Undergoing Radiosurgery for Breast Cancer Brain Metastases

    International Nuclear Information System (INIS)

    Purpose: In this retrospective study, we report on outcomes and prognostic factors for patients treated with stereotactic radiosurgery (SRS) for breast cancer brain metastases. Methods and Materials: We identified 132 consecutive patients with breast cancer who were treated with SRS for brain metastases from January 2000 through June 2010. We retrospectively reviewed records of the 51 patients with adequate follow-up data who received SRS as part of the initial management of their brain metastases. Overall survival (OS) and time to central nervous system (CNS) progression from the date of SRS were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: Triple negative subtype was associated with CNS progression on univariate analysis (hazard ratio [HR] = 5.0, p = 0.008). On multivariate analysis, triple negative subtype (HR = 8.6, p = 0.001), Luminal B subtype (HR = 4.3, p = 0.03), and omission of whole-brain radiation therapy (HR = 3.7, p = 0.02) were associated with CNS progression. With respect to OS, Karnofsky Performance Status (KPS) ≤ 80% (HR = 2.0, p = 0.04) and progressive extracranial disease (HR = 3.1, p = 0.002) were significant on univariate analysis; KPS ≤ 80% (HR = 4.1, p = 0.0004), progressive extracranial disease (HR = 6.4, p < 0.0001), and triple negative subtype (HR = 2.9, p = 0.04) were significant on multivariate analysis. Although median survival times were consistent with those predicted by the breast cancer-specific Graded Prognostic Assessment (Breast-GPA) score, the addition of extracranial disease status further separated patient outcomes. Conclusions: Tumor subtype is associated with risk of CNS progression after SRS for breast cancer brain metastases. In addition to tumor subtype and KPS, which are incorporated into the Breast-GPA, progressive extracranial disease may be an important prognostic factor for OS.

  11. Importance of Extracranial Disease Status and Tumor Subtype for Patients Undergoing Radiosurgery for Breast Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Dyer, Michael A.; Kelly, Paul J. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (United States); Pinnell, Nancy E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Claus, Elizabeth B. [Harvard Medical School, Boston, MA (United States); Department of Neurosurgery, Brigham and Women' s Hospital, Boston, MA (United States); Yale University School of Medicine, New Haven, CT (United States); Lee, Eudocia Q. [Harvard Medical School, Boston, MA (United States); Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Center, Boston, MA (United States); Weiss, Stephanie E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Arvold, Nils D. [Harvard Radiation Oncology Program, Boston, MA (United States); Lin, Nancy U. [Harvard Medical School, Boston, MA (United States); Department of Medical Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

    2012-07-15

    Purpose: In this retrospective study, we report on outcomes and prognostic factors for patients treated with stereotactic radiosurgery (SRS) for breast cancer brain metastases. Methods and Materials: We identified 132 consecutive patients with breast cancer who were treated with SRS for brain metastases from January 2000 through June 2010. We retrospectively reviewed records of the 51 patients with adequate follow-up data who received SRS as part of the initial management of their brain metastases. Overall survival (OS) and time to central nervous system (CNS) progression from the date of SRS were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: Triple negative subtype was associated with CNS progression on univariate analysis (hazard ratio [HR] = 5.0, p = 0.008). On multivariate analysis, triple negative subtype (HR = 8.6, p = 0.001), Luminal B subtype (HR = 4.3, p = 0.03), and omission of whole-brain radiation therapy (HR = 3.7, p = 0.02) were associated with CNS progression. With respect to OS, Karnofsky Performance Status (KPS) {<=} 80% (HR = 2.0, p = 0.04) and progressive extracranial disease (HR = 3.1, p = 0.002) were significant on univariate analysis; KPS {<=} 80% (HR = 4.1, p = 0.0004), progressive extracranial disease (HR = 6.4, p < 0.0001), and triple negative subtype (HR = 2.9, p = 0.04) were significant on multivariate analysis. Although median survival times were consistent with those predicted by the breast cancer-specific Graded Prognostic Assessment (Breast-GPA) score, the addition of extracranial disease status further separated patient outcomes. Conclusions: Tumor subtype is associated with risk of CNS progression after SRS for breast cancer brain metastases. In addition to tumor subtype and KPS, which are incorporated into the Breast-GPA, progressive extracranial disease may be an important prognostic factor for OS.

  12. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Directory of Open Access Journals (Sweden)

    Wu SK

    2014-09-01

    Full Text Available Sheng-Kai Wu,1 Chi-Feng Chiang,1 Yu-Hone Hsu,1,4 Tzu-Hung Lin,2 Houng-Chi Liou,2 Wen-Mei Fu,2 Win-Li Lin1,3 1Institute of Biomedical Engineering, College of Medicine and College of Engineering, 2Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; 4Department of Neurosurgery, Cheng-Hsin General Hospital, Taipei, Taiwan Abstract: The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The

  13. Nimotuzumab combined with radiotherapy for esophageal cancer: preliminary study of a Phase II clinical trial

    Directory of Open Access Journals (Sweden)

    Liang J

    2013-11-01

    Full Text Available Jun Liang,1 Mingyan E,2 Gang Wu,3 Lujun Zhao,4 Xia Li,5 Xia Xiu,6 Ning Li,1 Bo Chen,1 Zhouguang Hui,1 Jima Lv,1 Hui Fang,1 Yu Tang,1 Nan Bi,1 Wenqing Wang,1 Yirui Zhai,1 Tao Li,1 Dongfu Chen,1 Shuangmei Zou,7 Ning Lu,7 Rolando Perez-Rodríguez,8 Junqi Zheng,9 Luhua Wang11Department of Radiotherapy, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China; 2Department of Radiotherapy, Cancer Hospital of Harbin Medical University, Harbin, People's Republic of China; 3Department of Radiotherapy, Tongji Cancer Center Hospital, Wuhan, People's Republic of China; 4Department of Radiotherapy, Cancer Hospital of Tianjin Medical University, Tianjin, People's Republic of China; 5Department of Radiotherapy, LiaoNing Province Cancer Hospital, Shenyang, People's Republic of China; 6Department of Radiotherapy, Beijing Hospital, Beijing, People's Republic of China; 7Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, People's Republic of China; 8Center of Molecular Immunology, Havana, Cuba; 9School of Medicine, Tongji University, Shanghai, People's Republic of ChinaObjective: To determine the safety and therapeutic effects of nimotuzumab (h-R3 combined with radiotherapy in esophageal cancer.Methods: This Phase II clinical trial involved 42 patients with stage II (inoperable or refused surgery to stage IV (supraclavicular lymph node metastasis only esophageal cancers treated between November 2008 and July 2010. All patients had squamous cell carcinomas, and all received three-dimensional conformal radiotherapy and 200 mg nimotuzumab per week during radiotherapy.Results: There were 9, 25, and 8 patients with stage II, III and IV disease, respectively. All except two patients received 50–70 Gy radiation; 37 patients (88.1% received more than five nimotuzumab doses. Grade III toxicities (21.4% of all adverse events included esophagitis and gastrointestinal, dermatological and hematological

  14. Enhanced Brain Disposition and Effects of Δ9-Tetrahydrocannabinol in P-Glycoprotein and Breast Cancer Resistance Protein Knockout Mice

    OpenAIRE

    Spiro, Adena S.; Alexander Wong; Boucher, Aurélie A.; Arnold, Jonathon C.

    2012-01-01

    The ABC transporters P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (Bcrp, Abcg2) regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9)-tetrahydrocannabinol (THC) has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to ca...

  15. Real time analysis of brain tissue by direct combination of ultrasonic surgical aspiration and sonic spray mass spectrometry.

    Science.gov (United States)

    Schäfer, Karl-Christian; Balog, Júlia; Szaniszló, Tamás; Szalay, Dániel; Mezey, Géza; Dénes, Júlia; Bognár, László; Oertel, Matthias; Takáts, Zoltán

    2011-10-15

    Direct combination of cavitron ultrasonic surgical aspirator (CUSA) and sonic spray ionization mass spectrometry is presented. A commercially available ultrasonic surgical device was coupled to a Venturi easy ambient sonic-spray ionization (V-EASI) source by directly introducing liquified tissue debris into the Venturi air jet pump. The Venturi air jet pump was found to efficiently nebulize the suspended tissue material for gas phase ion production. The ionization mechanism involving solely pneumatic spraying was associated with that of sonic spray ionization. Positive and negative ionization spectra were obtained from brain and liver samples reflecting the primary application areas of the surgical device. Mass spectra were found to feature predominantly complex lipid-type constituents of tissues in both ion polarity modes. Multiply charged peptide anions were also detected. The influence of instrumental settings was characterized in detail. Venturi pump geometry and flow parameters were found to be critically important in ionization efficiency. Standard solutions of phospholipids and peptides were analyzed in order to test the dynamic range, sensitivity, and suppression effects. The spectra of the intact tissue specimens were found to be highly specific to the histological tissue type. The principal component analysis (PCA) and linear discriminant analysis (LDA) based data analysis method was developed for real-time tissue identification in a surgical environment. The method has been successfully tested on post-mortem and ex vivo human samples including astrocytomas, meningeomas, metastatic brain tumors, and healthy brain tissue.

  16. The importance of combining of ultrasound and mammography in breast cancer diagnosis

    Directory of Open Access Journals (Sweden)

    Svjetlana Mujagić

    2011-05-01

    Full Text Available Objective. The aim of this study was to analyse individual and combined sensitivity and specificity of ultrasound and mammography in breast cancer diagnosis and emphasize the importance of combining breast imaging modalities. Patients and methods. By means of a cross-sectional study, ultrasound and mammographic examinations of 148 women (mean age 51.6 ± 10.8 years with breast symptoms were analysed. All women underwent surgery and all lesions were examined by histopathology analysis which revealed the presence of 63 breast cancers, and 85 benign lesions. In relation to age, the women were separated in to a group under 50 years and a group 50 years and older. Ultrasound and mammographic findings were classified on the BI-RADS categorical scale of 1-5. Categories 1, 2 and 3 were considered negative, while categories 4 and 5 were positive for cancer. For statistical data processing the McNemar chi-square test for paired proportions was used. The differences on the level of p<0.05 were considered statistically significant. Results. In the group under 50 years, the ultrasound sensitivity was significantly higher than the mammographic sensitivity (p=0.045, c2=4, without a statistically significant difference in specificity (p=0.24, c2=1.39. In the women over 50, a significant difference between sensitivity of ultrasound and mammography was not proved (p=0.68, c2=0.17, nor any difference in the specificities (p=0.15, c2=2.08. In the group consisting of all patients, the sensitivity of ultrasound was statistically significantly higher in comparison with the sensitivity of mammography (p=0.04, c2=4.27 with higher specificity (p=0.04, c2=4. By combining the two methods in all patients sensitivity of 96.8% was achieved, in patients up to 50 sensitivity was 90.47% and in patients over 50, sensitivity was 100%. When the two methods were combined in all patients, a decrease in specificity was noted. Conclusion. The combination of ultrasound and mammography

  17. Hybrid neuroprosthesis for the upper limb: combining brain-controlled neuromuscular stimulation with a multi-joint arm exoskeleton

    Directory of Open Access Journals (Sweden)

    Florian Grimm

    2016-08-01

    Full Text Available Brain-machine interface-controlled (BMI neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related range of motion and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. Neuromuscular electrical stimulation was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD and electromyography (EMG activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e. induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p=0.028 or EMG (p=0.021 modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related range of motion (p=0.009 and the movement-related brain modulation (p=0

  18. Brain Correlates of Self-Evaluation Deficits in Schizophrenia: A Combined Functional and Structural MRI Study.

    Directory of Open Access Journals (Sweden)

    Shuping Tan

    Full Text Available Self-evaluation plays an important role in adaptive functioning and is a process that is typically impaired in patients with schizophrenia. Underlying neural mechanisms for this dysfunction may be associated with manifested psychosis. However, the brain substrates underlying this deficit are not well known. The present study used brain blood oxygen level dependent (BOLD functional magnetic resonance imaging (fMRI and gray matter voxel-based morphometry to explore the functional and structural brain correlates of self-evaluation deficits in schizophrenia. Eighteen patients with schizophrenia and 17 healthy controls were recruited and asked to judge whether a set of personality-trait adjectives were appropriate for describing themselves, a familiar other, or whether the adjectives were of positive or negative valence. Patients had slower response times for negative trait attributions than controls did; responses to positive trait attributions were faster than those for negative traits among the patient group, while no differences were observed in the control group. Control subjects showed greater activation within the dorsal medial prefrontal cortex (dMPFC and the anterior cingulate cortex (ACC than the patient group during the self-evaluation > semantic positivity-evaluation contrast. Patients showed greater activation mainly within the posterior cingulate gyrus (PCC as compared to controls for the other-evaluation > semantic positivity-evaluation contrast. Furthermore, gray matter volume was reduced in the MPFC, temporal lobe, cuneus, and the dorsal lateral prefrontal cortex (DLPFC among the patient group when compared to controls. The present study adds to previous findings regarding self- and other-referential processing in schizophrenia, providing support for neurobiological models of self-reflection impairment.

  19. Efficacy and nursing of stereotactic radiotherapy in lung cancer patients with brain metastases%立体定向放射治疗肺癌脑转移的疗效观察及护理

    Institute of Scientific and Technical Information of China (English)

    Xiaoxia Zhang; Wenrong Yin; Yueqin Liu

    2008-01-01

    Objective:To observe the efficacy of stereotactic radiotherapy (SRT) in lung cancer patients with brain metastases and explore the nursing for those patients.Methods:From June 2002 to December 2006,43 patients of lung cancer with brain metastases were treated with SRT,8 of them were treated with the association of whole-brain radiotherapy (WBRT) and 6 of them were treated with combination of chemotherapy.During the period of SRT,the patients were applied with active psychological nursing and diet nursing.We also tried to prevent patients from epicranium injury,and meanwhile,patients were asked to took active convalesce exercise.Results:All patients finished SRT without serious reaction and complication.Local control rate was 81.4%,nervous system symptoms relief rate was 76.7% and KPS score was raised significantly.Survival time ranged from 2 to 34 months,median survival time was 8.5 months,and 6-month,1-and 2-year survival rates were 58.9%,26.2%,and 6.0% respectively.Conclusion:SRT was one of the effective palliation treatments for the lung cancer patients with brain metastases,and with the assistance of effective nursing,which would prolong their survival time and improved quality of life.

  20. Combination chemotherapy of cancer using the inhibitor of DNA methylation 5-aza-2'-deoxycytidine (decitabine

    Directory of Open Access Journals (Sweden)

    Stephan L

    2015-06-01

    Full Text Available The epigenetic alterations marked by DNA methylation contribute to the malignant transformation of cells by silencing critical genes responsible for the regulation of growth. The potent DNA methylation inhibitor 5-aza-2’-deoxycytidine (decitabine; DAC has shown effectiveness in patients with myeloid malignancies. However, the responses are of short duration. The effectiveness of the DAC therapy may be limited by its incapacity to reactivate enough tumor suppressor genes. Other epigenetic mechanisms, such as the histone modification of target genes, may also hinder gene reactivation by DAC. The dose limiting toxicity of DAC is myelosuppression, which limits the duration of this therapy for clinical use. The clinical effectiveness of DAC may be enhanced by its use in combination with other agents that have diverse mechanisms of action. In this literature review, we summarize the results of preclinical and recent clinical trials of DAC used in combination with other agents to treat cancer. This review was conducted by searching online databases to analyze the available evidence regarding this area of interest. We looked at the combination of DAC with other epigenetic agents, cytotoxic agents, tyrosine kinase inhibitors, biochemical modulators and non-toxic agents. The data compiled suggests that combination epigenetic therapy is feasible, moderately toxic and has promising clinical potential. Preclinical studies showed that some combinations of DAC have additive to synergistic antineoplastic action as compared to DAC alone. The data indicate that combination chemotherapy with DAC merits further investigation. This review may be helpful for the future design of clinical trials using DAC in combination for cancer therapy.

  1. Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iwasawa, Toshihisa; Matsumoto, Hidetsugu [Social Health Insurance Medical Center, Tokyo (Japan)

    1996-11-01

    To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier`s method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier`s method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

  2. Modulating cancer multidrug resistance by sertraline in combination with a nanomedicine.

    Science.gov (United States)

    Drinberg, Velthe; Bitcover, Rivka; Rajchenbach, Wolf; Peer, Dan

    2014-11-28

    Inherent and acquired multiple drug resistance (MDR) to chemotherapeutic drugs is a major obstacle in cancer treatment. The ATP Binding Cassettes (ABC) transporter super family that act as extrusion pumps such as P-glycoprotein and multidrug-resistance-associated-proteins have prominent roles in cancer MDR. One of the most efficient strategies to modulate this active drug efflux from the cells is to physically block the pump proteins and thus change the balance between drug influx and efflux toward an accumulation of drug inside the cell, which eventually cumulates into cell death. MDR modulators (also known as chemosensitizers) were found among drugs approved for non-cancer indications. Yet, toxicity, adverse effects, and poor solubility at doses required for MDR reversal prevent their clinical application. Previous reports have shown that drugs belonging to the selective serotonin reuptake inhibitors (SSRI) family, which are clinically used as antidepressants, can act as effective chemosensitizers both in vitro and in vivo in tumor bearing mouse models. Here, we set out to explore whether sertraline (Zoloft®), a molecule belonging to the SSRI family, can be used as an MDR modulator. Combining sertraline with another FDA approved drug, Doxil® (pegylated liposomal doxorubicin), is expected to enhance the effect of chemotherapy while potentially reducing adverse effects. Our findings reveal that sertraline acts as a pump modulator in cellular models of MDR. In addition, in an aggressive and highly resistant human ovarian xenograft mouse model the use of sertraline in combination with Doxil® generated substantial reduction in tumor progression, with extension of the median survival of tumor-bearing mice. Taken together, our results show that sertraline could act as a clinically relevant cancer MDR inhibitor. Moreover, combining two FDA approved drugs, DOXIL®, which favor the influx of chemotherapy inside the malignant cell with sertraline, which blocks the

  3. Combination therapy with hormonal, radiation and chemotherapy for stage C prostate cancer

    International Nuclear Information System (INIS)

    To improve the effectiveness of treatment for patients with stage C prostate cancer, therapy in combination with hormonal, radiation and chemotherapy was given for the initial period, and there after, hormonal therapy was continuously administered to 18 patients with chemotherapy and three patients without it. At the Social Health Insurance Medical Center, between May 1988 and August 1991, 21 patients were diagnosed to have stage C histologically confirmed adenocarcinoma of the prostate. The average age of the patients was 69.0 years. The tumor was well, moderate and poorly differentiated in 5, 6 and 10 patients, respectively. As hormonal therapy, orchiectomy was performed on 19 of the 21 patients. Furthermore, 11 patients were administered estramustine phosphate, 9 chlormadinone acetate, and one diethylstilbesterol diphosphate. As, radiation therapy, all patients were treated with AP-PA parallel opposing technique to small pelvis with a 12 cm x 12 cm treatment field (44-45 Gy) combined with conformation radiotherapy to prostate (20-26 Gy). Chemotherapy was performed using either one or a combination of the following; cis-diamminedichloroplatinum, adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate and etoposide. The observation period was 54.5 months on the average. Recurrence was observed in 3 patients, for all of which the sites were at bone. The 5-year non-recurrence rate was 90.4% by Kaplan-Meier's method. There were 4 deaths, three were due to prostate cancer and one to gastric cancer. The 5-year cumulative survival rate by Kaplan-Meier's method was 90.5%. In conclusion, this treatment was effective for stage C cases of prostate cancer. (author)

  4. Clinical outcomes of HER2-positive metastatic breast cancer patients with brain metastasis treated with lapatinib and capecitabine: an open-label expanded access study in Korea

    Directory of Open Access Journals (Sweden)

    Ro Jungsil

    2012-07-01

    Full Text Available Abstract Background To evaluate efficacy in patients with brain metastasis (BM on entry into the lapatinib expanded access program (LEAP. Methods LEAP is a worldwide, single-arm, open-label study. HER2-positive, locally-advanced or metastatic breast cancer patients with progression after an anthracycline, taxane, and trastuzumab were eligible. Patients received capecitabine 2000 mg/m2 daily in two divided doses, days 1–14, every 21 days and lapatinib 1250 mg once daily. Results Among 186 patients enrolled in 6 Korean centers, 58 had BM. Progression-free survival (PFS was 18.7 weeks in patients with BM and 19.4 weeks without BM (P = 0.88. In patients with BM, brain response was synchronized with systemic responses (P = 0.0001. Overall survival (OS was 48.9 weeks in patients with BM and 64.6 weeks without BM (P = 0.23. Multivariable analysis found hormone receptor positivity (P = 0.003 and clinical benefit rate (CBR of combined systemic and brain disease (P  Conclusion Lapatinib plus capecitabine is equally effective in patients with or without BM. Trial registration ClinicalTrials.gov (NCT00338247

  5. 鸦胆子油乳联合放疗对肺癌脑转移患者生活质量及认知水平的影响%THE AFFECT OF BRUCEOLIC OIL EMULSION COMBINED WITH RADIOTHERAPY ON THE LIFE QUALITY AND COGNITIVE LEVEL OF PATIENTS WITH BRAIN METASTASIS OF LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    郑国红; 杨俊泉; 王晓红; 李义慧; 王静怡; 肖磊

    2015-01-01

    目的 观察鸦胆子油乳注射剂联合放疗对肺癌脑转移患者临床疗效及生活质量、认知水平的影响.方法 收集该院2012年1月-2014年6月收治的肺癌脑转移患者90例的临床及随访资料,分为治疗组48例、对照组42例,对照组采用单纯放疗,治疗组采用放疗+鸦胆子油乳,1次/d,每次30ml,30d为1个疗程.观察比较二组患者治疗效果、1年生存率,并采用欧洲癌症研究和治疗组织(European Organization for Research and Treatment of Cancer,EORTC)简体中文版的生活质量调查核心问卷QLQ-C30对患者进行评价,应用简易智能量表(mini-mental state examination,MMSE)评价患者智能、记忆的水平.结果 治疗组总有效率77.1%,对照组总有效率57.1%,组间差异具有统计学意义(P<0.05);1年生存率二组间无显著差别;治疗组胃肠道不良反应发生比例显著低于对照组(P<0.05);二组治疗前后生活质量、认知功能评分的比较均有显著差别,治疗后好于治疗前,治疗后组间比较有显著差别,治疗组好于对照组.结论 与单纯放疗相比,鸦胆子油联合放疗治疗肺癌脑转移临床疗效良好,并可降低并发症发生比例、提高患者生活质量和认知程度.

  6. Methionine-dependence and combination chemotherapy on human gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Wei-Xin Cao; Jing-Min Ou; Xu-Feng Fei; Zheng-Gang Zhu; Hao-Ran Yin; Min Yan; Yan-Zhen Lin

    2002-01-01

    AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial calls in vitro can grow normally in a rnethionine (Met) depleted environment, i.e.Met-dependence, and whether Met-depleting status can enhance the killing effect of chemotherapy on gastric cancer cells.lMETHODS: Fresh human gastric cancer and mucosal tissueswere managed to form monocellular suspensions, whichwere then cultured in the Met-free but homocysteine-containing ( MetHcy+ ) medium, with differentchemotherapeutic drugs. The proliferation of the cells wasexamined by cell counter, flow cytometry (FCM) andmicrocytotoxicity assay (MTT).RESULTS: The growth of human primary gastric cancer cellsin Met Hcy+ was suppressed, manifested by the decrease oftotal cell counts [1.46±0.42 ( x 109@L-1) in Met-Hcy+ vs .64±0.44 ( x l09@L-1) in Met+ Hcy, P<0.01], the decline inthe percentage of G0G1 phase cells (0.69±0.24 in Met-Hey+vs 0.80±0.18 in Met+ Hcy, P<0.01) and the increase of Scells(0.24±0.20inMet-Hcy+ vs 0.17 ± 0.16 in Met+ Hcy-, P< 0.01); however, gastric mucusal cells grew normally. IfMet-Hcy+ medium was used in combination withchemotherapeutic drugs, the number of surviving gastriccancer cells dropped significantly.CONCLUSION: Human primary gastric cancer cells in vitroare Met-dependent; however, gastric mucosal cells have notshown the same characteristica. Met- Hcy+ environment maystrengthen the killing effect of chemotherapy on humanprimary gastric cancer cells.

  7. The Combined Operation The Cancer Of The Rectum With Germination In Genital Organs

    Directory of Open Access Journals (Sweden)

    H Bobokulov

    2010-04-01

    Full Text Available  The Purpose of the study: define the indications and contraindications to, combined operation in locally invasive tumor of the rectum.The Material and methods of the study: we have analysed results combined operation in cancer of the rectum with germination in genital organs, performed in department of coloproctology in National Oncological Scientific centre during 2005-2009 years.Under observation were 118 women at age from 21 to 68 years.      This before 45 years - 26 patients, from 46 to 59 years - 54 patients, 60 and above years.The Results and their discussion: Postoperative complications suppurative-inflammatory character appeared beside 36 patients (30,5%, most of all after abdomeno - perineal extirpation of rectum (35,5% and abdominoanal resection of the rectum (33,3%. In lesser extend after front resection of the rectum and after operation Hartman (28,5% and 22,7%.The General lethality has formed 3,4%, have died after combined operation 4 patients from 118 operated patients.The Conclusion: thereby, brought data evident that such important factors, as frequency of the origin relapse (28%, 5-year probability of survival (37,1%, under combined interference and operation of the standard volume in the cancer of the rectum practically the same.

  8. Combination of the transurethral resection and prostate HIFU ablation at treatment of the localized cancer

    Directory of Open Access Journals (Sweden)

    Popkov V.M.

    2014-09-01

    26 patients were included into HIFU and 74 group in group of the combined treatment (TURP+HIFU. Selection criteria for HIFU ablation were the localized cancer of a prostate concerning which earlier it wasn't carried out treatments, and level of a PSA at the time of statement of the diagnosis 15 ng/ml. All patients corresponding to these by criteria, were considered as candidates for treatment and inclusion in the analysis. The nadir and stability of PSA, the histologic conclusion, IPSS, quality of life and complication were estimated at time of postoperative supervision. Results: Statistically significant influence of a combination TURP+HIFU for the term of transurethral drainage of a bladder (a median of 40 days against 7 days, incontience frequency (15.4% against 6.9%, infections of urinary ways (47.9% against 11.4% and IPSS change during the postoperative period (on the average 8.91 against 3.37 is noted. During the short period of supervision it wasn't observed considerable changes in relation to efficiency: in HIFU group the frequency of repeated sessions made 25%, in TUR/HIFU group 4%. Conclusion: HIFU therapy is modern, minimum invasive method of a cancer therapy of a prostate. The combination of a transurethral resection and HIFU ablation significantly reduces the frequency of the complications connected with treatment. Maintaining the patient after combined TURP and HIFU ablation is comparable with maintaining the patient after usual TURP.

  9. Plasma pro-brain natriuretic peptide and electrocardiographic changes in combination improve risk prediction in persons without known heart disease

    DEFF Research Database (Denmark)

    Jørgensen, Peter G; Jensen, Jan S; Appleyard, Merete;

    2015-01-01

    cohort study. Median follow-up was 10.4 years. High pro-BNP was defined as above 90th percentile of age and sex adjusted levels. The end-points were all-cause mortality and the combination of admission with ischemic heart disease, heart failure or CVD death. RESULTS: ECG changes were present in 907......BACKGROUND: Though the electrocardiogram(ECG) and plasma pro-brain-natriuretic-peptide (pro-BNP) are widely used markers of subclinical cardiac injury and can be used to predict future cardiovascular disease(CVD), they could merely be markers of the same underlying pathology. We aimed to determine...... if ECG changes and pro-BNP are independent predictors of CVD and if the combination improves risk prediction in persons without known heart disease. METHODS: Pro-BNP and ECG were obtained on 5454 persons without known heart disease from the 4th round of the Copenhagen City Heart Study, a prospective...

  10. Combined transperineal radiofrequency (RF) interstitial hyperthermia and brachytherapy for localized prostate cancer (PC)

    Energy Technology Data Exchange (ETDEWEB)

    Urakami, Shinji; Gonda, Nobuko; Kikuno, Nobuyuki [Shimane Medical Univ., Izumo (Japan)] (and others)

    2001-05-01

    Hyperthermia has been used effectively as a radiation sensitizer. Interstitial hyperthermoradiotherapy has been therefore utilized as a minimal invasive therapy in attempts to improve local tumor control for various cancers, but not for urological cancer. The purpose of this study was to investigate the safety and feasibility of transperineal hyperthermoradiotherapy for localized PC. Based on our basic study of hyperthermoradiotherapy, we devised the procedure of combined transperineal RF interstitial hyperthermia and brachytherapy for localized prostate cancer. Two patients with localized PC underwent transperineal RF interstitial hyperthermia combined with brachytherapy operation the 192-Ir remote after-loading system (RALS). Under transrectal ultrasound guidance, a total number of 12-18 stainless steel needles for 192-Ir RALS were implanted into the prostatic gland and seminal vesicles (SV) in an optimized pattern. Eight of the needles were used as electrodes for hyperthermia, and were electrically insultated using the vinyl catheter along the length of the subdermal fatty tissue to protect from overheating. Three other needles were utilized for continuous temperature mapping in the prostate. Rectal temperature was also monitored. Total radiation doses of 70 Gy to the prostate and SV were planned as a combination of brachytherapy (24 Gy/4 fraction) and external irradiation using a four-field box technique (46 Gy/23 fraction). Hyperthermic treatment (goal of 42 to 43 deg C for 60 minutes) was performed twice following the 1st and 4th brachytherapy at an interval of more than 48 hours for the recovery of cancer cells from thermotolerance. Both patients reached the treatment goal of all intraprostatic temperatures >43.0 deg C, which was considered favorable for hyperthermia, and the rectal temperatures of both patients remained <38 deg C during hyperthermia. In serial PSA measurements of both patients, serum PSA was less than 1.0 ng/ml within 3 months and has since

  11. Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy

    Science.gov (United States)

    Xiao, Bo; Han, Moon Kwon; Viennois, Emilie; Wang, Lixin; Zhang, Mingzhen; Si, Xiaoying; Merlin, Didier

    2015-10-01

    Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1 : 1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy.Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments

  12. Prognostic indices in stereotactic radiotherapy of brain metastases of non-small cell lung cancer

    International Nuclear Information System (INIS)

    Our purpose was to analyze the long-term clinical outcome and to identify prognostic factors after Linac-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) on patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). We performed a retrospective analysis of survival on 90 patients who underwent SRS or FSRT of intracranial NSCLC metastases between 04/2004 and 05/2014 that had not undergone prior surgery or whole brain radiotherapy (WBRT) for BM. Follow-up data was analyzed until May 2015. Potential prognostic factors were examined in univariable and multivariable analyses. The Golden Grading System (GGS), the disease-specific graded prognostic assessment (DS-GPA), the RADES II prognostic index as well as the NSCLC-specific index proposed by Rades et al. in 2013 (NSCLC-RADES) were calculated and their predictive values were tested in univariable analysis. The median follow-up time of the surviving patients was 14 months. The overall survival (OS) rate was 51 % after 6 months and 29.9 % after 12 months. Statistically significant factors of better OS after univariable analysis were lower International Union Against Cancer (UICC) stage at first diagnosis, histology of adenocarcinoma, prior surgery of the primary tumor and lower total BM volume. After multivariable analysis adenocarcinoma histology remained a significant factor; higher Karnofsky Performance Score (KPS) and the presence of extracranial metastases (ECM) were also significant. The RADES II and the NSCLC-RADES indices were significant predictors of OS. However, the NSCLC-RADES failed to differentiate between intermediate- and low-risk patients. The DS-GPA and GGS were not statistically significant predictors of survival in univariable analysis. The ideal prognostic index has not been defined yet. We believe that more specific indices will be developed in the future. Our results indicate that the histologic subtype of NSCLC could add to the prognostic

  13. Enhanced brain disposition and effects of Δ9-tetrahydrocannabinol in P-glycoprotein and breast cancer resistance protein knockout mice.

    Directory of Open Access Journals (Sweden)

    Adena S Spiro

    Full Text Available The ABC transporters P-glycoprotein (P-gp, Abcb1 and breast cancer resistance protein (Bcrp, Abcg2 regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9-tetrahydrocannabinol (THC has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT mice. Abcb1a/b (-/-, Abcg2 (-/- and wild-type (WT mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (-/- and Abcg2 (-/- mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (-/- mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis.

  14. Quality of Life Patients with Breast Cancer Therapy Combination Fluorouracil, Doxorubicin, and Cyclofosfamide

    Directory of Open Access Journals (Sweden)

    Dewi D. Agustini

    2015-09-01

    Full Text Available Treatment of breast cancer with combination chemotherapy Florouracil, doxorubicin, and Cyclofosfamide (FAC lead to differences in the quality of life of patients is important to know because it can support the effectiveness of patient treatment. The aim of the study was to measure the difference and know the dimensions that affect the quality of life of breast cancer patients from each cycle of chemotherapy in Hasan Sadikin Hospital. This research is an observational analytic cross sectional approach. A sample of 200 breast cancer patients who were selected purposively and separated based on cycles of therapy. Assessment of quality of life of patients is done using a multidimensional instrument EORTC QLQ (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and BR23. Data analysis was calculated using independent t test and linear regression. The results showed that there are differences in quality of life is very significant between QLQ-C30 functioning scale baseline with treatment 5, the QLQ-C30 symptom scale baseline therapy 5th, QLQ-BR23 function scale baseline with therapy 1st, 2nd, 3rd, 4th, and 5th, QLQ-BR23 symptoms scale baseline with therapy 4th, then a significant difference between scale symptoms of QLQ-BR23 baseline therapy with the 1st, 3rd, and 5th. Dimensions have a significant effect on quality of life is a social function, nausea and vomiting, dyspnea, sleep disorders and financial difficulties.

  15. An overview of the effective combination therapies for the treatment of breast cancer.

    Science.gov (United States)

    Núñez, Cristina; Capelo, José Luis; Igrejas, Gilberto; Alfonso, Amparo; Botana, Luis M; Lodeiro, Carlos

    2016-08-01

    Breast cancer (BC) is generally classified based on the receptors overexpressed on the cell nucleus, which include hormone receptors such as progesterone (PR) and estrogen (ER), and HER2. Triple-negative breast cancer (TNBC) is a type of cancer that lacks any of these three types of receptor proteins (ER/PR/HER2). Tumor cells exhibit drug resistant phenotypes that decrease the efficacy of chemotherapeutic treatments. Generally, drug resistance has a genetic basis that is caused by an abnormal gene expression, nevertheless, there are several types of drug resistance: efflux pumps reducing the cellular concentration of the drug, alterations in membrane lipids that reduce cellular uptake, increased or altered drug targets, metabolic alteration of the drug, inhibition of apoptosis, repair of the damaged DNA, and alteration of the cell cycle checkpoints. The use of "combination therapy" is recognized as an efficient solution to treat human diseases, in particular, breast cancer. In this review, we give examples of different nanocarriers used to co-deliver multiple therapeutics (chemotherapeutic agent and nucleic acid) to drug-resistant tumor cells, and lastly, we give our recommendations for the future directions for the co-delivery treatments.

  16. COMBINED DETECTION OF CYCLIN D1, P27 AND DNA CONTENT IN ESOPHAGEAL CANCER

    Institute of Scientific and Technical Information of China (English)

    MA Ping; YIN Yuan-qin; WANG Xiao-hua

    2006-01-01

    Objective: To investigate the expressions of cyclin D1 and p27 and DNA content in esophageal cancer and adjacent normal tissues, and to discuss the relationship between them. Methods: The cyclinD1 and p27 were detected by immunohistochemical staining; DNA content was measured by flow cytometry. Results: The positive expression rates of cyclinD1 and p27 in cancer were 45.8% and 33.3% respectively, the DNA content in the positive group of cyclinD1 was higher than that in the negative group of cyclinD1(1.54(0.21 versus 1.08(0.43, P<0.05), while the DNA content and SPF (S-phase fraction) in the positive group of p27 were lower than those in the negative group (1.10(0.19 and 5.56%(5.18% versus 1.66(0.28 and 19.78%(6.12%, P<0.05). Conclusion: The data show that the expression of cyclinD1 and p27 are related to the ontogenesis and progression of esophageal cancer. The combined detection of cyclinD1, p27 and DNA content may be indicators of diagnosis and assessment of esophageal cancer.

  17. Cytotoxic Effect of Erythroxylum suberosum Combined with Radiotherapy in Head and Neck Cancer Cell Lines.

    Science.gov (United States)

    Macedo, Taysa B C; Elias, Silvia T; Torres, Hianne M; Yamamoto-Silva, Fernanda Paula; Silveira, Dâmaris; Magalhães, Pérola O; Lofrano-Porto, Adriana; Guerra, Eliete N S; Silva, Maria Alves G

    2016-01-01

    The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas. PMID:27007356

  18. An overview of the effective combination therapies for the treatment of breast cancer.

    Science.gov (United States)

    Núñez, Cristina; Capelo, José Luis; Igrejas, Gilberto; Alfonso, Amparo; Botana, Luis M; Lodeiro, Carlos

    2016-08-01

    Breast cancer (BC) is generally classified based on the receptors overexpressed on the cell nucleus, which include hormone receptors such as progesterone (PR) and estrogen (ER), and HER2. Triple-negative breast cancer (TNBC) is a type of cancer that lacks any of these three types of receptor proteins (ER/PR/HER2). Tumor cells exhibit drug resistant phenotypes that decrease the efficacy of chemotherapeutic treatments. Generally, drug resistance has a genetic basis that is caused by an abnormal gene expression, nevertheless, there are several types of drug resistance: efflux pumps reducing the cellular concentration of the drug, alterations in membrane lipids that reduce cellular uptake, increased or altered drug targets, metabolic alteration of the drug, inhibition of apoptosis, repair of the damaged DNA, and alteration of the cell cycle checkpoints. The use of "combination therapy" is recognized as an efficient solution to treat human diseases, in particular, breast cancer. In this review, we give examples of different nanocarriers used to co-deliver multiple therapeutics (chemotherapeutic agent and nucleic acid) to drug-resistant tumor cells, and lastly, we give our recommendations for the future directions for the co-delivery treatments. PMID:27162073

  19. Combinations of FUT2 gene polymorphisms and environmental factors are associated with oral cancer risk.

    Science.gov (United States)

    Su, Kuo-Jung; Ho, Chuan-Chen; Lin, Chiao-Wen; Chen, Mu-Kuan; Su, Shih-Chi; Yu, Yung-Luen; Yang, Shun-Fa

    2016-05-01

    In humans, fucosyltransferase-2 (FUT2) plays an important role in α1,2- linkage of fucose and participates in complex cellular processes such as fertilization, embryogenesis, and immune responses. However, little information is available concerning the FUT2 expression in tumorigenesis. The aim of this work was to investigate the combined effect of FUT2 gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinic pathological characteristics of oral cancer. Four SNPs of the FUT2 gene (rs281377, rs1047781, rs601338, and rs602662) from 1200 non-cancer controls and 700 oral squamous cell carcinoma (OSCC) patients were analyzed by real-time polymerase chain reaction (PCR). The samples were further analyzed to clarify the associations between these gene polymorphisms and the risk of OSCC, and the impact of these SNPs on the susceptibility and clinic pathological characteristics of OSCC. After adjusting for other covariant, we observed that betel quid chewing among 1255 smokers who carrying at least one C genotype (TC and CC) at rs281377 and least one T genotype (TA and TT) at rs1047781 were exhibited synergistic effects of environmental factors (betel quid and cigarette use) on the susceptibility of oral cancer. Taken together, our results support gene-environment interactions of FUT2 polymorphisms with smoking and betel quid chewing habits possibly altering oral cancer susceptibility. Furthermore, to our knowledge, this is the first study of association between FUT2 gene variants and OSCC risk. PMID:26646561

  20. Cytotoxic effect of Erythroxylum suberosum combined with radiotherapy in head and neck cancer cell lines

    International Nuclear Information System (INIS)

    The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as 'cabelo-de-negro'. The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas. (author)

  1. Combination Therapy of PPAR Ligands and Inhibitors of Arachidonic Acid in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jordi Tauler

    2008-01-01

    Full Text Available Lung cancer is the leading cause of cancer death in the United States and five-year survival remains low. Numerous studies have shown that chronic inflammation may lead to progression of carcinogenesis. As a result of inflammatory stimulation, arachidonic acid (AA metabolism produces proliferation mediators through complex and dynamic interactions of the products of the LOX/COX enzymes. One important mediator in the activation of the AA pathways is the nuclear protein PPAR. Targeting LOX/COX enzymes and inducing activation of PPAR have resulted in significant reduction of cell growth in lung cancer cell lines. However, specific COX-inhibitors have been correlated with an increased cardiovascular risk. Clinical applications are still being explored with a novel generation of dual LOX/COX inhibitors. PPAR activation through synthetic ligands (TZDs has revealed a great mechanistic complexity since effects are produced through PPAR-dependent and -independent mechanisms. Furthermore, PPAR could also be involved in regulation of COX-2. Overexpression of PPAR has reported to play a role in control of invasion and differentiation. Exploring the function of PPAR, in this new context, may provide a better mechanistic model of its role in cancer and give an opportunity to design a more efficient therapeutic approach in combination with LOX/COX inhibitors.

  2. Cytotoxic effect of Erythroxylum suberosum combined with radiotherapy in head and neck cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Macedo, Taysa B.C.; Torres, Hianne M.; Yamamoto-Silva, Fernanda Paula; Silva, Maria Alves G. [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Escola de Odontologia; Elias, Silvia T.; Silveira, Damaris; Magalhaes, Perola O.; Lofrano-Porto, Adriana; Guerra, Eliete N.S., E-mail: elieteneves@unb.br [Universidade de Brasilia (UnB), Brasilia, DF (Brazil). Faculdade de Ciencias da Saude

    2016-01-15

    The mouth and oropharynx cancer is the 6{sup th} most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as 'cabelo-de-negro'. The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas. (author)

  3. Effects of Rh-endostar in Combination with Radiotherapy on Rats with Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ximin XU

    2010-04-01

    Full Text Available Background and objective Radiation sensitivity is closely related to tissue oxygen, and rh-endostatin can induce the high level of oxygen content in tumor by "normalizing" tumor angiogenesis which is associated with radiotherapy sensitivity. The aim of this study is to observe the effect of combination of radiotherapy with rh-endostatin in the rats with lung cancer. Methods Immediate lewis cancerous ascetic injection method was used to make rats tumors bearing model, then the rats was divided into four groups randomly: group A was treated with saline; group B was treated with rh-endostatin; group C was treated with irradiation and group D was treated with rh-endostatin and irradiation. After all rats were treated, inhibition rates and the tumor growth curve were calculated. Immunohistochemisty was adopted to check the expressions of vascular endothelial growth factor (VEGF and microvessel density (MVD. Results Compared with group A, the growth rates of the tumors in the other group were obviously slower, and the tumor weights were significantly different form group A (P<0.05. Compared with the other groups, the tumor weights of group D were obviously reduced (P<0.05. Compared with group A, VEGF and MVD of other three groups were reduced (P<0.05, and group D were significantly cut down. Conclusion Combination with radiotherapy and rh-endostatin could inhibit the lung cancer significantly in rats. The possible mechanisms are to decrease the expression of VEGF and inhibit the production of angiogenesis.

  4. Survey of the Role of Combined Screening Method with Ultrasonography in the Diagnosis of Breast Cancer

    Directory of Open Access Journals (Sweden)

    F. Gharekhanloo

    2011-01-01

    Full Text Available Introduction & Objective: The breast cancer is the most common malignancy in women and in recent years it is seen in younger ages. Because of dense breast tissue in these ages, the mammography sensitivity for breast cancer detection is reduced, so high quality ultrasonography (US as a combined screening method is effective. The aim of this study is the evaluation of the mammographic finding with the positive finding of ultrasonogarphy.Materials & Methods: In this cross-sectional study 300 cases were referred to the Mehr Medical Imaging Center for breast US and sonography of breast and axilla was performed. Mammography before or after US was also performed by another radiologist. All suspicious patients were referred for biopsy or surgery.Results: Mean age of patients was 46 y/o with the range of 32-76 y/o. Pathologic specimens approved malignancy in 21 patients and abscess in 1 patient. The most frequent symptom was palpable breast mass with mean diameter of 29 mm. Mean diameter of lymph nodes was 17.3 mm. Positive mammographic findings were seen in 85.7%and negative findings or only an asymmetric density in 14.3%.Conclusion: According to dense breast tissue especially in young women sensitivity of single screening by mammography is reduced in breast cancer detection, so combined screening with sonography and mammography especially in younger women improves the detection rate of breast carcinoma. (Sci J Hamadan Univ Med Sci 2011;17(4:57-60

  5. A Combined Shotgun and Targeted Mass Spectrometry Strategy for Breast Cancer Biomarker Discovery.

    Science.gov (United States)

    Sjöström, Martin; Ossola, Reto; Breslin, Thomas; Rinner, Oliver; Malmström, Lars; Schmidt, Alexander; Aebersold, Ruedi; Malmström, Johan; Niméus, Emma

    2015-07-01

    It is of highest importance to find proteins responsible for breast cancer dissemination, for use as biomarkers or treatment targets. We established and performed a combined nontargeted LC-MS/MS and a targeted LC-SRM workflow for discovery and validation of protein biomarkers. Eighty breast tumors, stratified for estrogen receptor status and development of distant recurrence (DR ± ), were collected. After enrichment of N-glycosylated peptides, label-free LC-MS/MS was performed on each individual tumor in triplicate. In total, 1515 glycopeptides from 778 proteins were identified and used to create a map of the breast cancer N-glycosylated proteome. Based on this specific proteome map, we constructed a 92-plex targeted label-free LC-SRM panel. These proteins were quantified across samples by LC-SRM, resulting in 10 proteins consistently differentially regulated between DR+/DR- tumors. Five proteins were further validated in a separate cohort as prognostic biomarkers at the gene expression level. We also compared the LC-SRM results to clinically reported HER2 status, demonstrating its clinical accuracy. In conclusion, we demonstrate a combined mass spectrometry strategy, at large scale on clinical samples, leading to the identification and validation of five proteins as potential biomarkers for breast cancer recurrence. All MS data are available via ProteomeXchange and PASSEL with identifiers PXD001685 and PASS00643. PMID:25944384

  6. Clinical outcome of hyperthermo-radio-chemotherapy combined with surgery for patients with advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Kokuriki; Fujimoto, Shigeru; Takahashi, Makoto; Nemoto, Kazuhisa; Mutou, Takaaki; Toyosawa, Tadashi [Social Insurance Funabashi Central Hospital, Chiba (Japan)

    2001-09-01

    For the patients with breast cancer that are locally advanced or metastatic, treatment to control not only local disease but also distant metastasis is desirable. Hyperthermo-radio-chemotherapy (HRC) combined with surgery was performed for 16 patients with stage III or stage IV breast cancer and the clinical outcomes of this multimodal treatment were analyzed. The size of the primary tumor was significantly reduced after preoperative HRC with the CR rate of 18.8% (3/16) and PR rate of 81.3% (13/16). Three- and 5-year overall survival rates for the stage III patients were 100% and 87.5%, respectively; their 3- and 5- year disease free rates were 78.8% and 52.5%, respectively. One- and 3-year survival rates for the stage IV patients were 80.0% and 20.0%, respectively. No loco-regional recurrence was observed. HRC combined with surgery for advanced breast cancer patients was effective for down-staging of the primary tumor and maintaining local control. (author)

  7. The criteria for further examination in breast cancer screening using combined mammography and ultrasonography

    International Nuclear Information System (INIS)

    We studied the favorable criteria in breast cancer screening using mammography (MMG) and ultrasonography (US). We examined 1,542 females who had never undergone combined screening, and evaluated the following criteria: Need to recall due to category 3 in either MMG or US. To evaluate MMG and US films together. To estimate the next time recall rate. We identified the benefit of combined screening, which is able to rule out benign lesions in category 3 of MMG. So, it is important to evaluate MMG and US films together. It is also necessary to interpret results in comparison with previous films. Our results showed that the recall rate was 8% in the first screening, and it was 4-5% in the repeat screening. Therefore, the target recall rate on combined screening would be less than 5%. (author)

  8. Adoptive immunotherapy combined chemoradiotherapy for non-small-cell lung cancer: a meta-analysis.

    Science.gov (United States)

    Qian, Haili; Wang, Haijuan; Guan, Xiuwen; Yi, Zongbi; Ma, Fei

    2016-06-01

    The aim of this study was to compare the efficacies between adoptive immunotherapy combined chemoradiotherapy and chemoradiotherapy alone in patients with non-small-cell lung cancer (NSCLC). The databases PubMed, EMBASE, and Cochrane database were searched to identify eligible clinical trials. Data analyses were carried out using a comprehensive meta-analysis program, version 2 software. A total of seven articles were finally included in the analysis. Meta-analyses showed that compared with chemoradiotherapy alone, adoptive immunotherapy combined with chemoradiotherapy could improve the 2-year overall survival [odds ratio (OR)=2.45, 95% confidence interval (CI): 1.60-3.75, Pshiver, nausea, fatigue, etc. and severe toxicities were not observed. Adoptive immunotherapy combined with chemoradiotherapy can delay the recurrence of NSCLC and improve survival in patients, where the benefits are even more significant in patients with early-stage NSCLC. PMID:26872311

  9. Combination of genistein with ionizing radiation on andro-gen-independent prostate cancer cells

    Institute of Scientific and Technical Information of China (English)

    Sen-XiangYan; YasuoEjima; RyoheiSasaki; Shu-SenZheng; YusukeDemizu; ToshinoriSoejima; KazuroSugimura

    2004-01-01

    Aim: To study the effect of the combined use of genistein and ionizing radiation (IR) on prostate DUI45 cancer cells. Methods: DU145, an androgen-independent human prostate cancer cell line, was used in the experiment.Clonogenic assay was used to compare the survival of DU145 cells after treatments with genistein alone and in combination with graded IR. Apoptosis was assayed by DNA ladder and TUNEL stain. Cell cycle alterations were observed by flow cytometry and related protein expressions by immunoblotting. Results: Clonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU 145 cells. Twenty four hours after treatment with IR and/or genistein, apoptosis was mainly seen with genistein at high concentrations and was minimally related to IR. At 72 h, apoptosis also occurred in treatment with lower concentration of genistein,especially when combined with IR. While both IR and genistein led to G2/M cell cycle arrest, combination of them further increased the DUI45 cells at G2/M phase. This G2/M arrest was largely maintained at 72 h, accompanied by increasing apoptosis and hyperdiploid cell population. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B 1 and less dramatically cdc-2, but stably elevated p21cip1 levels with increasing genistein concentrations.Conclusion: Genistein enhanced the radiosensitivity of DUI45 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair. (Asian J Androl 2004 Dec; 6: 285-290)

  10. Effectiveness of immune therapy combined with chemotherapy on the immune function and recurrence rate of cervical cancer

    OpenAIRE

    Chen, Bin; Liu, Lifen; Xu, Haiyan; YANG, YIJIN; Zhang, Ling; Zhang, Fengchun

    2015-01-01

    The aim of this study was to compare the immune function of patients with cervical cancer and the cancer recurrence rate in patients treated with biological immune therapy combined with chemotherapy or with chemotherapy only. A total of 79 postoperative patients with cervical cancer participated in the present study. They were randomly divided into a control group and an experimental group. Patients in the control group were treated with cisplatin chemotherapy. Patients in the experimental gr...

  11. Outcome of surgical resection for brain metastases and radical treatment of the primary tumor in Chinese non–small-cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Li Z

    2015-04-01

    Full Text Available Zhenye Li,1,3,* Xiangheng Zhang,1,* Xiaobing Jiang,1 Chengcheng Guo,1 Ke Sai,1 Qunying Yang,1 Zhenqiang He,1 Yang Wang,1 Zhongping Chen,1 Wei Li,2 Yonggao Mou1 1Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Anesthesiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 3Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China *These authors have contributed equally to this work Purpose: Brain metastasis is the most common complication of brain cancer; nevertheless, primary lung cancer accounts for approximately 20%–40% of brain metastases cases. Surgical resection is the preferred treatment for brain metastases. However, no studies have reported the outcome of surgical resection of brain metastases from non–small-cell lung cancer (NSCLC in the People’s Republic of China. Moreover, the optimal treatment for primary NSCLC in patients with synchronous brain metastases is hitherto controversial. Patients and methods: We retrospectively analyzed the cases of NSCLC patients with brain metastases who underwent neurosurgical resection at the Sun Yat-sen University Cancer Center, and assessed the efficacy of surgical resection and the necessity of aggressive treatment for primary NSCLC in synchronous brain metastases patients. Results: A total of 62 patients, including 47 men and 15 women, with brain metastases from NSCLC were enrolled in the study. The median age at the time of craniotomy was 54 years (range 29–76 years. At the final follow-up evaluation, 50 patients had died. The median OS time was 15.1 months, and the survival rates were 70% and 37% at 1 and 2 years, respectively. The median OS

  12. 5-Fluorocytosine combined with Fcy-hEGF fusion protein targets EGFR-expressing cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lan, Keng-Hsueh [Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei 100, Taiwan (China); Shih, Yi-Sheng [Cancer Center, Taipei Veterans General Hospital, Taipei 112, Taiwan (China); Chang, Cheng Allen [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); School of Biomedical Science and Engineering, National Yang-Ming University, Taipei 112, Taiwan (China); Yen, Sang-Hue [Cancer Center, Taipei Veterans General Hospital, Taipei 112, Taiwan (China); Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Lan, Keng-Li, E-mail: kllan@vghtpe.gov.tw [Cancer Center, Taipei Veterans General Hospital, Taipei 112, Taiwan (China); Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer EGFR-expressing epithelial cancers account for significant portion of cancer deaths. Black-Right-Pointing-Pointer EGF-EGFR signaling pathway is validated as an important anticancer drug target. Black-Right-Pointing-Pointer EGF and Fcy fusion protein (Fcy-hEGF) can bind to EGFR and convert 5-FC to 5-FU. Black-Right-Pointing-Pointer Fcy-hEGF combined with 5-FC preferentially inhibits EGFR-expressing cells viability. -- Abstract: Human epithelial cancers account for approximately 50% of all cancer deaths. This type of cancer is characterized by excessive activation and expression of the epidermal growth factor receptor (EGFR). The EGFR pathway is critical for cancer cell proliferation, survival, metastasis and angiogenesis. The EGF-EGFR signaling pathway has been validated as an important anticancer drug target. Increasing numbers of targeted therapies against this pathway have been either approved or are currently under development. Here, we adopted a prodrug system that uses 5-fluorocytosine (5-FC) and human EGF (hEGF) fused with yeast cytosine deaminase (Fcy) to target EGFR-overexpressing cancer cells and to convert 5-FC to a significantly more toxic chemotherapeutic, 5-fluorouracil (5-FU). We cloned and purified the Fcy-hEGF fusion protein from Pichia pastoris yeast. This fusion protein specifically binds to EGFR with a similar affinity as hEGF, approximately 10 nM. Fcy-hEGF binds tightly to A431 and MDA-MB-468 cells, which overexpress EGFR, but it binds with a lower affinity to MDA-MB-231 and MCF-7, which express lower levels of EGFR. Similarly, the viability of EGFR-expressing cells was suppressed by Fcy-hEGF in the presence of increasing concentrations of 5-FC, and the IC{sub 50} values for A431 and MDA-MB-468 were approximately 10-fold lower than those of MDA-MB-231 and MCF-7. This novel prodrug system, Fcy-hEGF/5-FC, might represent a promising addition to the available class of inhibitors that specifically target EGFR

  13. 5-Fluorocytosine combined with Fcy–hEGF fusion protein targets EGFR-expressing cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► EGFR-expressing epithelial cancers account for significant portion of cancer deaths. ► EGF–EGFR signaling pathway is validated as an important anticancer drug target. ► EGF and Fcy fusion protein (Fcy–hEGF) can bind to EGFR and convert 5-FC to 5-FU. ► Fcy–hEGF combined with 5-FC preferentially inhibits EGFR-expressing cells viability. -- Abstract: Human epithelial cancers account for approximately 50% of all cancer deaths. This type of cancer is characterized by excessive activation and expression of the epidermal growth factor receptor (EGFR). The EGFR pathway is critical for cancer cell proliferation, survival, metastasis and angiogenesis. The EGF–EGFR signaling pathway has been validated as an important anticancer drug target. Increasing numbers of targeted therapies against this pathway have been either approved or are currently under development. Here, we adopted a prodrug system that uses 5-fluorocytosine (5-FC) and human EGF (hEGF) fused with yeast cytosine deaminase (Fcy) to target EGFR-overexpressing cancer cells and to convert 5-FC to a significantly more toxic chemotherapeutic, 5-fluorouracil (5-FU). We cloned and purified the Fcy–hEGF fusion protein from Pichia pastoris yeast. This fusion protein specifically binds to EGFR with a similar affinity as hEGF, approximately 10 nM. Fcy–hEGF binds tightly to A431 and MDA-MB-468 cells, which overexpress EGFR, but it binds with a lower affinity to MDA-MB-231 and MCF-7, which express lower levels of EGFR. Similarly, the viability of EGFR-expressing cells was suppressed by Fcy–hEGF in the presence of increasing concentrations of 5-FC, and the IC50 values for A431 and MDA-MB-468 were approximately 10-fold lower than those of MDA-MB-231 and MCF-7. This novel prodrug system, Fcy–hEGF/5-FC, might represent a promising addition to the available class of inhibitors that specifically target EGFR-expressing cancers.

  14. Treatment of Breast Cancer Cells by IGF1R Tyrosine Kinase Inhibitor Combined with Conventional Systemic Drugs

    NARCIS (Netherlands)

    Hartog, H.; Van der Graaf, W. T. A.; Boezen, H. M.; Wesseling, J.

    2012-01-01

    Aim: Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase receptor mediating cell growth and survival of cancer cells. We studied responses to IGF1R tyrosine kinase inhibitor NVP-AEW541 combined with conventional systemic drugs in breast cancer cell lines of different clinical subtype.

  15. Treatment of breast cancer cells by IGF1R tyrosine kinase inhibitor combined with conventional systemic drugs.

    NARCIS (Netherlands)

    Hartog, H.; Graaf, W.T.A. van der; Boezen, H.M.; Wesseling, J.

    2012-01-01

    AIM: Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase receptor mediating cell growth and survival of cancer cells. We studied responses to IGF1R tyrosine kinase inhibitor NVP-AEW541 combined with conventional systemic drugs in breast cancer cell lines of different clinical subtype.

  16. Combined effect of genetic polymorphisms in phase I and II biotransformation enzymes on head and neck cancer risk

    NARCIS (Netherlands)

    Lacko, M.; Voogd, A.C.; Roelofs, H.M.J.; Morsche, R.H.M. te; Ophuis, M.B.; Peters, W.H.M.; Manni, J.J.

    2013-01-01

    BACKGROUND: Combinations of genetic polymorphisms in biotransformation enzymes might modify the individual risk for head and neck cancer. METHODS: Blood from 432 patients with head and neck cancer and 437 controls was investigated for genetic polymorphisms in 9 different phase I and II biotransforma

  17. Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D L; Nørgaard, H; Weber Vestermark, Lene;

    2012-01-01

    The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease....

  18. A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer

    OpenAIRE

    Chen, Bang-Bin; Lu, Yen-Shen; Lin, Ching-Hung; Chen, Wei-Wu; Wu, Pei-Fang; Hsu, Chao-Yu; Yu, Chih-Wei; Wei, Shwu-Yuan; Cheng, Ann-Lii; Shih, Tiffany Ting-Fang

    2016-01-01

    Background To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. Methods Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that e...

  19. Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer

    OpenAIRE

    H Billur Engin; Emre Guney; Ozlem Keskin; Baldo Oliva; Attila Gursoy

    2013-01-01

    Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer H. Billur Engin1, Emre Guney2, Ozlem Keskin1, Baldo Oliva2, Attila Gursoy1* 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Istanbul, Turkey, 2 Structural Bioinformatics Group (GRIB), Universitat Pompeu Fabra Abstract Blocking specific protein interactions can lead to human diseases. Accordingly, protein i...

  20. A naringenin–tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hatkevich, Talia; Ramos, Joseph; Santos-Sanchez, Idalys; Patel, Yashomati M., E-mail: ympatel@uncg.edu

    2014-10-01

    Since over 60% of breast cancers are estrogen receptor positive (ER+), many therapies have targeted the ER. The ER is activated by both estrogen binding and phosphorylation. While anti-estrogen therapies, such as tamoxifen (Tam) have been successful they do not target the growth factor promoting phosphorylation of the ER. Other proliferation pathways such as the phosphatidylinositol-3 kinase, (PI3K) and the mitogen-activated protein kinase (MAPK) pathways are activated in breast cancer cells and are associated with poor prognosis. Thus targeting multiple cellular proliferation and survival pathways at the onset of treatment is critical for the development of more effective therapies. The grapefruit flavanone naringenin (Nar) is an inhibitor of both the PI3K and MAPK pathways. Previous studies examining either Nar or Tam used charcoal-stripped serum which removed estrogen as well as other factors. We wanted to use serum containing medium in order to retain all the potential inducers of cell proliferation so as not to exclude any targets of Nar. Here we show that a Nar–Tam combination is more effective than either Tam alone or Nar alone in MCF-7 breast cancer cells. We demonstrate that a Nar–Tam combination impaired cellular proliferation and viability to a greater extent than either component alone in MCF-7 cells. Furthermore, the use of a Nar–Tam combination requires lower concentrations of both compounds to achieve the same effects on proliferation and viability. Nar may function by inhibiting both PI3K and MAPK pathways as well as localizing ERα to the cytoplasm in MCF-7 cells. Our results demonstrate that a Nar–Tam combination induces apoptosis and impairs proliferation signaling to a greater extent than either compound alone. These studies provide critical information for understanding the molecular mechanisms involved in cell proliferation and apoptosis in breast cancer cells. - Highlights: • Nar–Tam impairs cell viability more effectively than

  1. Increased nephrotoxicity of combination taxol and cisplatin chemotherapy in gynecologic cancers as compared to cisplatin alone.

    Science.gov (United States)

    Merouani, A; Davidson, S A; Schrier, R W

    1997-01-01

    To investigate the increased nephrotoxicity of taxol and cisplatin combination chemotherapy in gynecologic cancers as compared to cisplatin alone, the medical records of 25 patients with gynecological cancers were reviewed for evaluation of nephrotoxicity after chemotherapy treatment. The data included age, serum creatinine, calculated creatinine clearance, initial and cumulative dose of cisplatin and taxol, primary site of the cancer, renal ultrasound and hydration protocols. Renal function was evaluated before, during and 6 months after chemotherapy. Renal dysfunction was defined as a greater than 25% decrease in creatinine clearance. Comparing 11 patients treated with taxol and cisplatin versus 14 treated with cisplatin alone, there was a significant difference in effect on renal function. Nine of 11 patients (81%) treated with the combination chemotherapy had a greater than 25% decrease in creatinine clearance while only 4 of the 14 patients (29%) treated with cisplatin alone had such a decrease in creatinine clearance (p < 0.004). The patients treated with the combination chemotherapy, however, received a higher dose of cisplatin (80.4 vs. 66.4 mg/m2, p < 0.02) and were treated longer (6.7 vs. 4.3 months, p < 0.002). Nevertheless, when the patients were matched for age, initial dose and cumulative dose of cisplatin, a higher f