WorldWideScience

Sample records for cancer combination therapies

  1. 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.

  2. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignanci......ART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.......PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer...

  3. Small RNA combination therapy for lung cancer

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    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

  4. COMBINATION THERAPY FOR PROSTATE CANCER: CLINICAL OBSERVATIONS

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2014-08-01

    Full Text Available Prostate cancer (PC is one of the urgent problems of modern urological oncology. The incidence of this pathology is steadily growing worldwide. Despite the fact that PSA diagnosis is extensively used and programs for the early detection of this disease are introduced, the rate of dia gnosis of advanced PC forms remains high. Furthermore, a number of aspects of therapy for this disease remain controversial so far. The 7 th Congress of the Russian Society of Urological Oncologists, which dealt with some issues of combination therapy for locally advanced PC, was held in Moscow in October 3 to 5, 2012. The paper covers a number of controversial issues in the management of patients with PC in different clinical situations.

  5. Combination immunotherapy and photodynamic therapy for cancer

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    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.

  6. 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....

  7. 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...... 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....... 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...

  8. Precision medicine and personalized breast cancer: combination pertuzumab therapy

    Directory of Open Access Journals (Sweden)

    Reynolds K

    2014-03-01

    Full Text Available Kerry Reynolds, Sasmit Sarangi, Aditya Bardia, Don S Dizon Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA Abstract: Trastuzumab (Herceptin, a monoclonal antibody directed against the human epidermal growth-factor receptor 2 (HER2, is the poster child for antibody-based targeted therapy in breast cancer. Pertuzumab, another humanized monoclonal antibody, binds to a different domain of HER2 and prevents the formation of HER2:HER3 dimers, which is the most potent heterodimer in the HER family. The combination of trastuzumab and pertuzumab has synergistic activity, and is associated with improved clinical outcomes. The US Food and Drug Administration (FDA approved pertuzumab in combination with trastuzumab-based chemotherapy originally as first-line therapy for metastatic HER2-positive breast cancer in 2012, and more recently as neoadjuvant therapy for localized disease in 2013. Pertuzumab is the first neoadjuvant drug to receive accelerated approval by the FDA based on pathological complete response as the primary end point. In this article, we review the mechanism of action, pharmacokinetics, clinical efficacy, safety, and current role of pertuzumab in the management of breast cancer, as well as ongoing clinical trials and future directions regarding the utility of pertuzumab as a personalized therapeutic option for HER2-positive breast cancer. In the coming years, we anticipate increased utilization of neoadjuvant trials for drug development, biomarker discovery, and validation, and envision conduct of personalized breast cancer clinics in which therapies will be routinely selected based on genetic alterations in the tumor. Regardless of the targeted therapy combinations employed based on tumor genomic profile, trastuzumab and pertuzumab will likely continue to form the backbone of the personalized regimen for HER2-positive breast cancer. Keywords: pertuzumab, HER2 breast cancer, personalized therapy

  9. Epigenetic therapy in gastrointestinal cancer: the right combination

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    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

  10. Cancer nanomedicine: from targeted delivery to combination therapy.

    Science.gov (United States)

    Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

    2015-04-01

    The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of various diseases, including cancer. The unique properties of nanoparticles (NPs), such as large surface-to-volume ratio, small size, the ability to encapsulate various drugs, and tunable surface chemistry, give them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make NPs a mode of treatment potentially superior to conventional cancer therapies. This review highlights the most recent developments in cancer treatment using NPs as drug delivery vehicles, including promising opportunities in targeted and combination therapy.

  11. 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.

  12. 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.

  13. Combined modality preoperative therapy for unresectable rectal cancer.

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    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.

  14. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

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    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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    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......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...... on the surface of cancer cells, have been characterized. To this end, recent years research has focussed on characterization of antigens that play an important role for the growth and survival of cancer cells. Anti-apoptotic molecules like survivin that enhance the survival of cancer cells and facilitate...

  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. Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

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    Swart, Maarten; Verbrugge, Inge; Beltman, Joost B.

    2016-01-01

    In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing. PMID:27847783

  18. Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy.

    Science.gov (United States)

    Swart, Maarten; Verbrugge, Inge; Beltman, Joost B

    2016-01-01

    In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing.

  19. Calreticulin as cancer treatment adjuvant: combination with photodynamic therapy and photodynamic therapy-generated vaccines

    Directory of Open Access Journals (Sweden)

    Mladen eKorbelik

    2015-02-01

    Full Text Available Calreticulin is recognized as one of pivotal damage-associated molecular pattern (DAMP molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT. The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure-rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4 mg/mouse was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor responses elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.

  20. 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.

  1. Combination Adriamycin and radiation therapy in gynecologic cancers

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    Watring, W.G.; Byfield, J.E.; Lagasse, L.D.; Lee, Y.D.; Juillard, G.; Jacobs, M.; Smith, M.L.

    1974-12-01

    Anthracyclic antibiotics, of which adriamycin is representative, have the ability to bind to cellular DNA and thereby interfere with the X ray repair process. When radiation survival curves of tissue cultures were studied, increased cell-killing was noted in those cultures with adriamycin over those without the drug. The mechanism by which this occurs may be related to a reduced rate of DNA strand break rejoining, as demonstrated by use of alkaline sucrose gradient techniques. A preliminary clinical Phase I study, in which patients with advanced gynecologic malignancy were treated by simultaneous adriamycin and X radiation, suggests that combined therapy is well-tolerated, and that such combinations may prove useful in selected patients.

  2. Combined preoperative therapy for oral cancer with nedaplatin and radiation

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    Adachi, Masatoshi; Shibata, Akihiko; Hayashi, Munehiro [Nippon Dental Univ., Tokyo (Japan). Hospital] (and others)

    2002-03-01

    We performed preoperative combined therapy using nedaplatin (CDGP) and radiation in 12 patients with squamous cell carcinoma originating from the oral cavity and maxillary sinus, and examined for any adverse events that may have occurred during this therapeutic regimen. Regarding the irradiation, external irradiation utilizing a 6 MV linac (linear accelerator) at a dose of 2.0 Gy/day was performed 5 times a week, with the target total radiation dose set at 40 Gy. In addition, CDGP was intravenously administered 30 minutes before irradiation at a dose of 5 mg/m{sup 2}/day. Mucositis was observed in all 12 subjects, however, the severity was observed to be grade 1-2 with no major differences in comparison to the patients given standard radiation monotherapy. Two subjects developed grade 3 leucopenia and were thus given granulocyte colony stimulating factor (G-CSF). In addition, grade 2 and grade 3 thrombocytopenia were both observed in one subject each. The subject with grade 3 thrombocytopenia required a platelet transfusion during surgery. No marked changes in serum creatinine levels were noted. These findings are therefore considered to provide evidence supporting the safety of this combination therapy. (author)

  3. 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.

  4. 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...

  5. Optimization of combined radiation therapy of the cervix cancer

    Directory of Open Access Journals (Sweden)

    Vladimir Philippenko

    2010-04-01

    Full Text Available Use of a new combination of known medical products - inhibitorsenzyme of cyclooxigenase-2 (diclofenac, ketoprofen with smalldoses cytostatics (methotrexate, 5-fluorouracil as“nonconventional” radiosensibilizators for optimization of combinedradial treatment of cervical cancer is offered. One hundred andtwenty patients with cervix cancer were involved into research(average age - 52.5±3.3, mainly II stage of process (50.8±4.6%,morphologically - nonkeratinizing squamous cell carcinoma(65.0±4.4%. Frequency of full regress of a tumor in the basicgroups has reached in 77.5±6.6% (1-basic group and 82.5±6.0% (2-basic group in comparison with a control group 70.0±7.2%(р<0.05. By results of the cytological research in cells thepathomorphosis of IV degree was recorded in 1-basic group - 60.0%(superficial smears and 57.5% (a puncture biopsy, in 2-basic group- 85.0% (superficial smears and 82.5% (a puncture biopsy incomparison with the control - 55.0% (superficial smears and apuncture biopsy, р<0.05.

  6. 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.

  7. 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

  8. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    Science.gov (United States)

    2013-03-01

    critical determinants of physiological processes (i.e., absorption, metabolism, excretion and tissue solubility phenomena ) [16]. Accordingly, PBPK models... Balis FM, Dedrick RL (1994) A pharmacokinetic model of topotecan clearance from plasma and cerebrospinal fluid. Cancer Res 54(19):5118–5122 38. Bradshaw

  9. Targeting Metabolic Survival Pathways in Lung Cancer via Combination Therapy

    Science.gov (United States)

    2014-06-01

    13C metabolic flux analysis studies in LKB1 proficient or deficient NSCLC cells under nutrient complete or metabolic stress conditions (e.g. hypoxia... metabolic flux analysis . Subsequent studies in Year 2 of this grant will aim to design combinatorial treatments that simultaneously induce these...growth control in tumour suppression. Nat Rev Cancer, 2009. 9(8): p. 563-75. 4. Zamboni, N., (13)C metabolic flux analysis in complex systems. Curr

  10. 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.

  11. Gold nanostructures as a platform for combinational therapy in future cancer therapeutics.

    Science.gov (United States)

    Jelveh, Salomeh; Chithrani, Devika B

    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.

  12. 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.

  13. Expanding the therapeutic index of radiation therapy by combining in situ gene therapy in the treatment of prostate cancer.

    Science.gov (United States)

    Tetzlaff, Michael T; Teh, Bin S; Timme, Terry L; Fujita, Tetsuo; Satoh, Takefumi; Tabata, Ken-Ichi; Mai, Wei-Yuan; Vlachaki, Maria T; Amato, Robert J; Kadmon, Dov; Miles, Brian J; Ayala, Gustavo; Wheeler, Thomas M; Aguilar-Cordova, Estuardo; Thompson, Timothy C; Butler, E Brian

    2006-02-01

    The advances in radiotherapy (3D-CRT, IMRT) have enabled high doses of radiation to be delivered with the least possible associated toxicity. However, the persistence of cancer (local recurrence after radiotherapy) despite these increased doses as well as distant failure suggesting the existence of micro-metastases, especially in the case of higher risk disease, have underscored the need for continued improvement in treatment strategies to manage local and micro-metastatic disease as definitively as possible. This has prompted the idea that an increase in the therapeutic index of radiotherapy might be achieved by combining it with in situ gene therapy. The goal of these combinatorial therapies is to maximize the selective pressure against cancer cell growth while minimizing treatment-associated toxicity. Major efforts utilizing different gene therapy strategies have been employed in conjunction with radiotherapy. We reviewed our and other published clinical trials utilizing this combined radio-genetherapy approach including their associated pre-clinical in vitro and in vivo models. The use of in situ gene therapy as an adjuvant to radiation therapy dramatically reduced cell viability in vitro and tumor growth in vivo. No significant worsening of the toxicities normally observed in single-modality approaches were identified in Phase I/II clinical studies. Enhancement of both local and systemic T-cell activation was noted with this combined approach suggesting anti-tumor immunity. Early clinical outcome including biochemical and biopsy data was very promising. These results demonstrate the increased therapeutic efficacy achieved by combining in situ gene therapy with radiotherapy in the management of local prostate cancer. The combined approach maximizes tumor control, both local-regional and systemic through radio-genetherapy induced cytotoxicity and anti-tumor immunity.

  14. Combination approaches with immune checkpoint blockade in cancer therapy

    Directory of Open Access Journals (Sweden)

    Maarten Swart

    2016-11-01

    Full Text Available In healthy individuals, immune checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune checkpoint blockade of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 (PD-1 emerged as promising strategies to activate anti-tumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune checkpoint blockade, aimed at increasing response-rates to the single treatments.

  15. 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)

  16. Combined systemic therapy and radiotherapy for bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, C.; Weiss, C. [Dept. of Radiotherapy and Oncology, Univ. of Frankfurt (Germany); Sauer, R. [Dept. of Radiotherapy, Univ. of Erlangen (Germany)

    2007-12-15

    The standard of care for transitional-cell carcinoma of the bladder with invasion to the muscularis propria is radical cystectomy. Sophisticated techniques for urinary diversion have been developed to improve patients' quality of life. Even the construction of a neobladder with continent urinary diversion, however, cannot substitute for the patient's original bladder. Attempts to obtain organ preservation are only justified when they have a high likelihood of achieving local cure with no compromise in survival rates. Adequate local control cannot be achieved with transurethral resection of the bladder tumor (TURBT), chemotherapy, or radiotherapy, when used alone. Several groups have reported the value of combining all three modalities, with salvage cystectomy being reserved for patients with incomplete response or local relapse. (orig.)

  17. 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

  18. Pleiotropic Role of Dietary Phytochemicals in Cancer: Emerging Perspectives for Combinational Therapy.

    Science.gov (United States)

    Banudevi, Sivanantham; Swaminathan, Sethuraman; Maheswari, Krishnan Uma

    2015-01-01

    Cancer is considered a complicated health issue worldwide. The mean cancer survival through standard therapeutic strategies has not been significantly improved over the past few decades. Hence, alternate remedies are needed to treat or prevent this dreadful disease being explored. Currently, it has been recognized that repeated treatment with chemotherapeutic agents has been largely ineffective due to multidrug resistance and further conventional treatment possesses limited drug accessibility to cancerous tissues, which in turn necessitates a higher dose resulting in increased cytotoxicity. Drug combinations have been practiced to address the problems associated with conventional single drug treatment. Recently, natural dietary agents have attracted much attention in cancer therapy because of their synergistic effects with anticancer drugs against different types of cancer. Natural phytochemicals may execute their anticancer activity through targeting diverse cancer cell signaling pathways, promoting cell cycle arrest and apoptosis, regulating antioxidant status and detoxification. This review focuses mainly on the anticancer efficacy of dietary phytochemicals in combination with standard therapeutic drugs reported from various in vitro and in vivo experimental studies apart from clinical trials. This review adds knowledge to the field of intervention studies using combinational modalities that opens a new window for cancer treatment/chemoprevention.

  19. 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.

  20. 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.

  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. Combined intraarterial cisplatin infusion and radiation therapy for invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mizoguchi, Hiroaki; Nomura, Yoshio; Terada, Katsuhiko; Nakagawa, Masayuki; Ogata, Jiro [Oita Medical Univ., Hasama (Japan)

    1995-03-01

    Twenty-three patients with invasive bladder cancer (T2 in 17, T3 in 6) were treated initially with combined intraarterial cisplatin infusion and radiation therapy. Cisplatin (50 mg) was infused into the internal iliac artery through a subcutaneous reservoir twice a week over three weeks while concurrent radiation therapy with 30 Gy, delivered in 15 fractions, was given. In 23 patients, 6 received additional cisplatin infusion and the other 17 had transurethral resection of bladder tumor (TURBT). Two of the patients undergoing total cystectomy exhibited a complete response (CR). Thus overall response rate was 87% (CR in 13 and partial response in 7). CR was achieved in 53% for T2 patients and 67% for T3 patients. CR was slightly higher in patients with non-papillary cancer than those with papillary one. Toxic reaction included a decrease in bladder capacity in 2 patients and severe diarrhea due to methicillin-resistant Staphylococcus aureus colitis in one. The other toxicities, including nausea, vomiting, neurotoxicity and myelosuppression, were tolerable. All except for one are alive. Seven patients had a local recurrence of bladder cancer. One patient developed invasive bladder cancer reaching the prostatic urethra. One other patient had recurrence at the same site as the previous tumor. Five others had superficial bladder cancer and were managed by TURBT. Bladder function was preserved in 65% at a mean follow-up of 29 months. In conclusion, the combined intraarterial cisplatin infusion and radiation therapy is useful for the initial treatment of invasive bladder cancer. (N.K.).

  3. Inhibitors of DNA Methylation, Histone Deacetylation, and Histone Demethylation: A Perfect Combination for Cancer Therapy.

    Science.gov (United States)

    Zahnow, C A; Topper, M; Stone, M; Murray-Stewart, T; Li, H; Baylin, S B; Casero, R A

    2016-01-01

    Epigenetic silencing and inappropriate activation of gene expression are frequent events during the initiation and progression of cancer. These events involve a complex interplay between the hypermethylation of CpG dinucleotides within gene promoter and enhancer regions, the recruitment of transcriptional corepressors and the deacetylation and/or methylation of histone tails. These epigenetic regulators act in concert to block transcription or interfere with the maintenance of chromatin boundary regions. However, DNA/histone methylation and histone acetylation states are reversible, enzyme-mediated processes and as such, have emerged as promising targets for cancer therapy. This review will focus on the potential benefits and synergistic/additive effects of combining DNA-demethylating agents and histone deacetylase inhibitors or lysine-specific demethylase inhibitors together in epigenetic therapy for solid tumors and will highlight what is known regarding the mechanisms of action that contribute to the antitumor response.

  4. [Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

    Science.gov (United States)

    Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

    2016-07-01

    We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

  5. Synergistic Enhancement of Cancer Therapy Using a Combination of Ceramide and Docetaxel

    Directory of Open Access Journals (Sweden)

    Li-Xia Feng

    2014-03-01

    Full Text Available Ceramide (CE-based combination therapy (CE combination as a novel therapeutic strategy has attracted great attention in the field of anti-cancer therapy. The principal purposes of this study were to investigate the synergistic effect of CE in combination with docetaxel (DTX (CE + DTX and to explore the synergy mechanisms of CE + DTX. The 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT and combination index (CI assay showed that simultaneous administration of CE and DTX with a molar ratio of 0.5:1 could generate the optimal synergistic effect on murine malignant melanoma cell (B16, CI = 0.31 and human breast carcinoma cell (MCF-7, CI = 0.48. The apoptosis, cell cycle, and cytoskeleton destruction study demonstrated that CE could target and destruct the microfilament actin, subsequently activate Caspase-3 and induce apoptosis. Meanwhile, DTX could target and disrupt the microtubules cytoskeleton, leading to a high proportion of cancer cells in G2/M-phase arrest. Moreover, CE plus DTX could cause a synergistic destruction of cytoskeleton, which resulted in a significantly higher apoptosis and a significantly higher arrest in G2/M arrest comparing with either agent alone (p < 0.01. The in vivo antitumor study evaluated in B16 tumor-bearing mice also validated the synergistic effects. All these results suggested that CE could enhance the antitumor activity of DTX in a synergistic manner, which suggest promising application prospects of CE + DTX combination treatment.

  6. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art.

    Science.gov (United States)

    Milecki, Piotr; Martenka, Piotr; Antczak, Andrzej; Kwias, Zbigniew

    2010-10-11

    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.

  7. 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

  8. Enhanced Radiosensitization of Gold Nanospikes via Hyperthermia in Combined Cancer Radiation and Photothermal Therapy.

    Science.gov (United States)

    Ma, Ningning; Jiang, Yao-Wen; Zhang, Xiaodong; Wu, Hao; Myers, John N; Liu, Peidang; Jin, Haizhen; Gu, Ning; He, Nongyue; Wu, Fu-Gen; Chen, Zhan

    2016-10-14

    Metallic nanostructures as excellent candidates for nanosensitizers have shown enormous potentials in cancer radiotherapy and photothermal therapy. Clinically, a relatively low and safe radiation dose is highly desired to avoid damage to normal tissues. Therefore, the synergistic effect of the low-dosed X-ray radiation and other therapeutic approaches (or so-called "combined therapeutic strategy") is needed. Herein, we have synthesized hollow and spike-like gold nanostructures by a facile galvanic replacement reaction. Such gold nanospikes (GNSs) with low cytotoxicity exhibited high photothermal conversion efficiency (η = 50.3%) and had excellent photostability under cyclic near-infrared (NIR) laser irradiations. We have demonstrated that these GNSs can be successfully used for in vitro and in vivo X-ray radiation therapy and NIR photothermal therapy. For the in vitro study, colony formation assay clearly demonstrated that GNS-mediated photothermal therapy and X-ray radiotherapy reduced the cell survival fraction to 89% and 51%, respectively. In contrast, the cell survival fraction of the combined radio- and photothermal treatment decreased to 33%. The synergistic cancer treatment performance was attributable to the effect of hyperthermia, which efficiently enhanced the radiosensitizing effect of hypoxic cancer cells that were resistant to ionizing radiation. The sensitization enhancement ratio (SER) of GNSs alone was calculated to be about 1.38, which increased to 1.63 when the GNS treatment was combined with the NIR irradiation, confirming that GNSs are effective radiation sensitizers to enhance X-ray radiation effect through hyperpyrexia. In vivo tumor growth study indicated that the tumor growth inhibition (TGI) in the synergistically treated group reached 92.2%, which was much higher than that of the group treated with the GNS-enhanced X-ray radiation (TGI = 29.8%) or the group treated with the GNS-mediated photothermal therapy (TGI = 70.5%). This research

  9. Spatiotemporally synchronized cancer combination therapy using photo-activated nanoparticle drug delivery systems (Conference Presentation)

    Science.gov (United States)

    Hasan, Tayyaba

    2016-03-01

    This talk will introduce a new nanotechnology platform for cancer combination therapy that utilizes near infrared light activation not only for photodynamic damage but also as an extrinsic mechanism to initiate release of complimentary drugs to suppress dynamic bursts in molecular signaling networks that promote tumor cell survival and treatment escape. The goal is to achieve co-delivery with concomitant activity of photodynamic, molecular inhibitor and chemotherapeutic agents, selectively within the tumor. This approach overcomes challenges in achieving synergistic interactions using sequential drug delivery. Conventional drug delivery is compromised by the differential pharmacokinetics of individual agents and potentially antagonistic effects—such as vascular shutdown by one agent that limits delivery of the second. Here, photodynamic damage—which efficiently kills drug-resistant cells via damage of common proteins involved in drug-resistance (such as anti-apoptosis factors and drug-efflux transporters)—is synchronized spatially and temporally with the photo-initiated release of complimentary agents—to enable full interaction amongst the individual therapies. This spatiotemporal synchronization offers new prospects for exploiting time-sensitive synergistic interactions. Specific implementations of these concepts will be presented in preclinical models of cancer. Strategies to enable molecular-targeting of cancer cells via site-specific attachment of targeting moieties to the outer lipid shell of these nanovehicles will also be discussed. If successful in humans, this new paradigm for synchronized, tumor-focused combination therapy will ultimately supersede the present use of chronic drug injection by increasing efficacy per cycle whilst reducing systemic exposure to toxic drugs.

  10. Trials of combined radiation and hyperthermia with various heating modalities in cancer therapy.

    Science.gov (United States)

    Egawa, S; Ishioka, K; Kawada, Y

    1984-01-01

    A microwave heating apparatus with a frequency of 2,450 MHz and an inductive radio-frequency heating apparatus were developed for hyperthermia for cancer therapy, and clinical trials of combined radiation and hyperthermia were conducted. During the same period, a capacitive type radiofrequency unit was used. The tumors included superficial tumors, cancer of the uterine cervix, recurrent tumors at the stump of the cervix, and some deep-seated tumors. Cases showing complete response were as follows: 5 out of 13 cases treated with 2,450 MHz heating for superficial tumors, 8 out of 17 cases treated with 2,450 MHz intracavitary heating, and 2 out of 15 cases treated with radiofrequency heating. A feasibility study of various heating modalities was performed.

  11. Combination therapy of murine liver cancer with IL-12 gene and HSV-TK gene

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the synergistic anti-tumor effects of murine IL-12 gene and HSV-TK gene therapy in mice bearing liver cancer. Methods: Mouse liver cancer MM45T. Li (H-2d) cells were transfected with retroviral vector containing IL-12 gene or HSV-TK gene insert. Gene-modified liver cancer cells, MM45T. Li/IL-12 and MM45T. Li/TK, with stable expression of IL-12 and TK were obtained. Balb/c mice were inoculated subcutaneously with 2′ 105 MM45T. Li cells. When the tumor reached a size of 0.5-1.0 cm, a mixture of MM45T.Li/TK cells and 60Co-irradiated MM45T. Li/IL-12 cell were injected intratumoraly. Ganciclovir (GCV) was injected ip (40 mg.kg-1.d-1) for 10 days. Intratumoral injection of 60Co-irradiated MM45T. Li/IL-12 cells was repeated twice in one week apart. Mice with distant tumors were treated according to the same protocol. CTL activity of spleen cells was measured by 51Cr-release assay and phenotype of tumor infiltrating lymphocytes by immunohistochemical staining. Results: In mice treated with MM45T. Li/IL-12 or MM45T. Li/TK+GCV individually led to moderate reduction in tumor growth, but neither could eradicate the tumor completely, while in 60% of mice treated with a mixture of MM45T. Li/IL-12 and MM45T. Li/TK cells plus GCV, complete tumor regression was observed, with no tumor recurrence for two months. The growth of distant tumor was also inhibited significantly in mice similarly treated. Most of the mice received combined gene therapy plus GCV had abundant CD4+, CD8+T lymphocyte infiltration. Their CTL activity was significantly higher than in mice received single gene therapy. Conclusion Combination therapy with IL-12 gene and HSV-TK gene plus GCV is effective for mouse liver cancer.

  12. 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.

  13. Pemetrexed and cyclophosphamide combination therapy for the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Li, Dong; He, Song

    2015-01-01

    Lung cancer is the leading cause of cancer-related mortality. This study was undertaken to investigate the efficacy and safety of adding regulatory T cell inhibitor cyclophosphamide to pemetrexed therapy for the second-line treatment of NSCLC with wild-type epidermal growth factor receptor (EGFR). A total of 70 patients were screened between March 2011 and December 2013, out of which 62 patients were enrolled in the study. Patients were randomized to receive 500 mg/m(2) pemetrexed in combination with 20 mg/kg cyclophosphamide in a 21 day cycle (n=30) or 500 mg/m(2) pemetrexed (n=32), and followed up for 30 months. Disease progression was observed in 23 patients in the pemetrexed plus cyclophosphamide arm and 27 patients in the pemetrexed monotherapy arm. Median progression-free survival was 3.6 months (95% confidence interval [CI], 1.3 to 5.9 months) in the pemetrexed plus cyclophosphamide arm and 2.2 months (95% CI, 1.3 to 3.1 months) in the pemetrexed monotherapy arm. The 6-month PFS rates were 22% (95% CI, 10 to 34) and 14.5% (95% CI, 6 to 23) in the pemetrexed plus cyclophosphamide arm and pemetrexed monotherapy arm, respectively. Median overall survival was 9.8 months for the pemetrexed combination therapy arm and 8.8 months for the pemetrexed arm, and the 1-year survival rates were 46% and 33%, respectively. The present study showed that pemetrexed in combination with low-dose cyclophosphamide may be a better treatment approach than pemetrexed monotherapy when considering second-line treatment for wild-type EGFR NSCLC.

  14. Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model

    Science.gov (United States)

    Conde, João; Oliva, Nuria; Zhang, Yi; Artzi, Natalie

    2016-10-01

    Conventional cancer therapies involve the systemic delivery of anticancer agents that neither discriminate between cancer and normal cells nor eliminate the risk of cancer recurrence. Here, we demonstrate that the combination of gene, drug and phototherapy delivered through a prophylactic hydrogel patch leads, in a colon cancer mouse model, to complete tumour remission when applied to non-resected tumours and to the absence of tumour recurrence when applied following tumour resection. The adhesive hydrogel patch enhanced the stability and provided local delivery of embedded nanoparticles. Spherical gold nanoparticles were used as a first wave of treatment to deliver siRNAs against Kras, a key oncogene driver, and rod-shaped gold nanoparticles mediated the conversion of near-infrared radiation into heat, causing the release of a chemotherapeutic as well as thermally induced cell damage. This local, triple-combination therapy can be adapted to other cancer cell types and to molecular targets associated with disease progression.

  15. Effect of chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy on patients’ prognosis

    Institute of Scientific and Technical Information of China (English)

    Xin-Cheng Shu; Ping Gao; Xin-Jua Zuo

    2016-01-01

    Objective:To study the effect of chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy on patients' prognosis.Methods:A total of78 cases of patients with colon cancer who received radical surgery of colon cancer assisted by postoperative chemotherapy in our hospital from May 2012 to December 2014 were selected for treatment and randomly divided into two groups, combined treatment group received chemotherapy combined with cascade primed immune cell therapy, simple chemotherapy group received FOLFOX chemotherapy, and then serum tumor marker contents and angiogenesis molecule contents as well as red blood cell immune function indicators in peripheral blood were detected.Results:Serum tumor markers CCSA-2, CCSA-3, CCSA-4, PTN, NGAL and sMICA as well as angiogenesis molecules VEGF, FGF10, sICAM-1, sVCAM-1, Musashi1 and Dkk1 contents of combined treatment group were lower than those of conventional chemotherapy group; the proportion of CR1, CR3, CD58 and CD59 as well as the rosette formation rates of red blood cell C3b receptor and immune complex in peripheral blood of combined treatment group were significantly higher than those of conventional chemotherapy group.Conclusions:Chemotherapy after radical surgery of colon cancer combined with cascade primed immune cell therapy helps to kill tumor cells and inhibit angiogenesis while enhance red blood cell immune function, and it can improve the prognosis of radical surgery of colon cancer.

  16. Acceptable Safety of Bevacizumab Therapy in Combination with Chemotherapy in Patients with Advanced Lung Cancer

    Directory of Open Access Journals (Sweden)

    Wei WU

    2009-03-01

    Full Text Available Background and objective Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that selectively binds to and neutralizes the biologic activity of human vascular endothelial growth factor (VEGF. Bevacizumab was approved by the U.S. Food and Drug Administration (FDA in October 2006 for use in combination withcarboplatin and paclitaxel for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic,nonsquamous, non-small cell lung cancer (NSCLC. The aim of this study is to observe the safety of bevacizumab therapy in combination with chemotherapy in Chinese patients with NSCLC. Methods Patients with advanced non-squamous NSCLC were treated with Bevacizumab 15 mg/kg, d1, repeated every 21 days until PD; Plus paclitaxel 175 mg/m2, on dl and carboplatin AUC=6 on dl. The cycle was repeated every 21 days. Results One grade 3 epistaxis was observed in onepatient. One grade 4 thrombosis was observed in one patient. 3/4-grade epistaxis and thrombosis was the most significant adverse events. Other adverse effects, such as hemoptysis, hypertension and proteinuria, were not severe and could be well tolerated. Conclusion Most chemotherapy-naive patients with advanced non-squamous NSCLC treated with bevacizumab in combination with paclitaxel and carboplatin have little adverse effects that can be well tolerated.

  17. Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist.

    Science.gov (United States)

    Frew, Ailsa J; Lindemann, Ralph K; Martin, Ben P; Clarke, Christopher J P; Sharkey, Janelle; Anthony, Desiree A; Banks, Kellie-Marie; Haynes, Nicole M; Gangatirkar, Pradnya; Stanley, Kym; Bolden, Jessica E; Takeda, Kazuyoshi; Yagita, Hideo; Secrist, J Paul; Smyth, Mark J; Johnstone, Ricky W

    2008-08-12

    Histone deacetylase inhibitors (HDACi) and agents such as recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic anti-TRAIL receptor (TRAIL-R) antibodies are anticancer agents that have shown promise in preclinical settings and in early phase clinical trials as monotherapies. Although HDACi and activators of the TRAIL pathway have different molecular targets and mechanisms of action, they share the ability to induce tumor cell-selective apoptosis. The ability of HDACi to induce expression of TRAIL-R death receptors 4 and 5 (DR4/DR5), and induce tumor cell death via the intrinsic apoptotic pathway provides a molecular rationale to combine these agents with activators of the TRAIL pathway that activate the alternative (death receptor) apoptotic pathway. Herein, we demonstrate that the HDACi vorinostat synergizes with the mouse DR5-specific monoclonal antibody MD5-1 to induce rapid and robust tumor cell apoptosis in vitro and in vivo. Importantly, using a preclinical mouse breast cancer model, we show that the combination of vorinostat and MD5-1 is safe and induces regression of established tumors, whereas single agent treatment had little or no effect. Functional analyses revealed that rather than mediating enhanced tumor cell apoptosis via the simultaneous activation of the intrinsic and extrinsic apoptotic pathways, vorinostat augmented MD5-1-induced apoptosis concomitant with down-regulation of the intracellular apoptosis inhibitor cellular-FLIP (c-FLIP). These data demonstrate that combination therapies involving HDACi and activators of the TRAIL pathway can be efficacious for the treatment of cancer in experimental mouse models.

  18. 重视胰腺癌的综合治疗%Attach importance to combined therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    孙诚谊; 陈自力

    2009-01-01

    Pancreatic cancer is a common malignancy of gastrointestinal system, with features of early metastasis, easy invasion to adjacent tissues and organs and neural metastasis. Therapies include surgery, chemotherapy, radiotherapy, physi-cal and biological therapy and so on. Surgical management, including radical resection and palliative operation, is a major approach. Radiotherapy and chemotherapy could improve the resectional rate and decrease the tumor dissemination. Physical and biological therapies are widely recommended, and there is a rapid progress in zoopery. However, the efficacy of all the thera-pies is far from satisfactory. Recently, the therapy consisting of surgical resection, radiotherapy, chemotherapy, physical and biological therapy in increasing the long-term survival rate and improving the life quality of patients, along with combined thera-py has attracted the attention of surgeons.

  19. Combination of Aprepitant, Azasetron, and Dexamethasone as Antiemetic Prophylaxis in Women with Gynecologic Cancers Receiving Paclitaxel/Carboplatin Therapy

    Science.gov (United States)

    Koshiyama, Masafumi; Matsumura, Noriomi; Imai, Saeko; Yamanoi, Koji; Abiko, Kaoru; Yoshioka, Yumiko; Yamaguchi, Ken; Hamanishi, Junzo; Baba, Tsukasa; Konishi, Ikuo

    2017-01-01

    Background The aim of this study was to evaluate the antiemetic effect of aprepitant and to determine how to provide triple combination therapy (aprepitant/azasetron/dexamethasone) to women receiving paclitaxel/carboplatin moderately emetogenic chemotherapy (MEC). Material/Methods The current study was a prospective study of 163 women with gynecologic cancers. We compared the digestive symptoms scores (nausea, vomiting, appetite loss, and dietary intake) of 37 women with ovarian cancers before and after aprepitant administration. We also compared these symptoms in women who underwent 193 cycles of triple combination therapy with symptoms of women who underwent 226 cycles of double combination therapy. For triple combination therapy, azasetron, dexamethasone (reduced dose: 40% of 20 mg), and aprepitant (125 mg) were administered on Day 1, followed by only aprepitant (80 mg) administration on Days 2 and Day 3. Results In 37 women with ovarian cancer, three symptoms, nausea, appetite loss, and dietary intake, were significantly improved by primarily adding aprepitant to double combination therapy in the delayed phase of MEC. Upon comparing their digestive symptoms in all cycles, however, these three symptoms were not significantly different in the delayed phase. Furthermore, all four symptoms in all cycles were worse following triple combination therapy than following double combination therapy in the acute phase (p<0.02). The control of digestive symptoms was generally insufficient without the administration of dexamethasone. Conclusions Primary aprepitant as an addition to MEC demonstrated efficacy in improving digestive symptoms in the delayed phase. However, its effect may decrease with repeated use. To improve the antiemetic effect, the dose reduction of dexamethasone should be restricted on Day 1 and dexamethasone should be used throughout the delayed phase as well. PMID:28198358

  20. Combined magnetic nanoparticle-based microRNA and hyperthermia therapy to enhance apoptosis in brain cancer cells.

    Science.gov (United States)

    Yin, Perry T; Shah, Birju P; Lee, Ki-Bum

    2014-10-29

    A novel therapy is demonstrated utilizing magnetic nanoparticles for the dual purpose of delivering microRNA and inducing magnetic hyperthermia. In particular, the combination of lethal-7a microRNA (let-7a), which targets a number of the survival pathways that typically limit the effectiveness of hyperthermia, with magnetic hyperthermia greatly enhances apoptosis in brain cancer cells.

  1. Radiation therapy with or without chemotherapy and hyperthermia for recurrent rectal cancer. Efficacy and disadvantage of combined therapy

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Takashi; Fujii, Ikuzo; Yoshino, Masanari; Nagata, Kenji; Imamura, Masahiro; Uda, Mitsunobu; Yamamoto, Keizo; Tanaka, Yoshimasa [Kansai Medical Univ., Moriguchi, Osaka (Japan)

    1997-03-01

    Forty-seven patients with intrapelvic recurrent rectal cancer were prescribed radiation alone (17 cases), radiation and chemotherapy (18 cases) or radiation with hyperthermia (12 cases) from 1989 to 1995. To discuss efficacies and disadvantages of these combined therapies, tumor response rate, pain control rate, duration of tumor control and pain control, and influence on patients` survival were evaluated. Radiation was delivered to the whole pelvis. Mean total dose was 45.5 Gy (1.5-2 Gy/fraction). Chemotherapy consisted 5-FU or CDDP and ADM. Hyperthermia were added 3-6 times concomitantly to the radiation. In all patients receiving more than 30 Gy radiation, tumor response rate was 56.8%. Tumor response rates were 35.3%, 43.7% and 41.7% in the radiation alone group, radiation and chemotherapy group and radiation with hyperthermia group respectively. Radiation combined chemotherapy was more effective for the tumor less than 5 cm diameter than radiation alone. In cases receiving over 50 Gy radiation, combined treatments were more effective than radiation alone. Pain relief was obtained in 75.9% of patients and there were no difference between three treatment groups. Tumor control was significantly prolonged in combined groups. Median survival periods were 6, 10 and 7 months for radiation alone, radiation and chemotherapy, and radiation with hyperthermia respectively. In PR cases and for tumors under 5 cm in diameter, there were no difference between three groups. In cases receiving over 50 Gy radiation, survival period was prolonged in radiation with hyperthermia. Fourteen patients developed acute toxicity (Leucopenia) and late complication due to bowel obstruction. The incidence of bowel complication was 27.8% for radiation and chemotherapy and 33.3% for radio-hyperthermia, while 17.6%, significantly low percentage, for radiation alone. Bowel obstruction may occur positively correlated with postsurgical adhesions and infections at initial surgery. (K.H.)

  2. Potential benefits of combining cytosine deaminase/5-fluorocytosine gene therapy and irradiation for prostate cancer. Experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hiroaki; Koshida, Kiyoshi; Yokoyama, Kunihiko; Mizokami, Atsushi; Namiki, Mikio [Kanazawa Univ. (Japan). School of Medicine

    2002-10-01

    The purpose of this study was to investigate the potential of combining cytosine deaminase/5-fluorocytosine (CD/5-FC) gene therapy and radiation therapy (either external beam radiation or radioimmunotherapy [RIT]), for the treatment of prostate cancer. Tumor xenografts of CD-transduced LNCaP cells grown in the testes of severe combined immunodeficiency (SCID) mice were used to evaluate antitumor effect. The mice were injected intraperitoneally with 500 mg/kg of 5-FC, or with 5, 15 or 30 mg/kg of 5-fluorouracil (5-FU), for 9 days. The tumors were treated with fractionated radiation at a dose of 1 or 3 Gy/day for 3 days, or I-131 labelled anti-prostate specific antigen (anti-PSA) monoclonal antibody (mAb) administration at a subtherapeutic dose of 20 or 80 {mu}Ci. Intratumoral and serum concentrations of 5-FU were measured using high performance liquid chromatography. Mice treated with CD/5-FC gene therapy presented a significant tumor growth inhibition comparable to that obtained with 15 mg/kg, 5-FU systemic administration without marked weight loss. Treatment with CD/5-FC gene therapy resulted in higher tumor but lower serum concentrations of 5-FU than treatment with systemic 5-FU chemotherapy. An additive antitumor effect was obtained when CD/5-FC therapy was combined with 1 Gy irradiation, which by itself did not produce a significant antitumor effect. However, the efficacy of CD/5-FC therapy was not enhanced when combined with RIT, probably due to poor accumulation of the mAb as the tumor/blood ratio never exceeded 1. These findings indicate that CD/5-FC gene therapy for prostate cancer may function with enhanced antitumor effect when combined with external beam radiation. However, combining CD/5-FC gene therapy and RIT using an anti-PSA mAb may not be effective because of insufficient accumulation of the mAb at the target tumors. (author)

  3. Risk of Breast Cancer in Relation to Combined Effects of Hormone Therapy, Body Mass Index, and Alcohol Use, by Hormone-receptor Status

    DEFF Research Database (Denmark)

    Hvidtfeldt, Ulla Arthur; Tjonneland, Anne; Keiding, Niels;

    2015-01-01

    BACKGROUND: Alcohol consumption, increased body mass index (BMI), and hormone therapy are risk factors for postmenopausal breast cancer, but their combined effects are not well understood. Because hormone therapy is effective for the relief of menopausal symptoms, the identification of "high...... therapy users across all BMI strata (P for interaction = 0.003). A markedly higher risk of breast cancer was also observed for alcohol combined with hormone therapy use compared with abstinent nonusers (P for interaction = 0.02). These effects were primarily restricted to ER-positive cases. Combined...... effects of hormone therapy/high BMI and hormone therapy/alcohol on serum estradiol and testosterone supported the hypothesis of a hormonal pathway linking these exposures to breast cancer. CONCLUSION: These analyses suggest an increased risk of breast cancer associated with hormone therapy use-a risk...

  4. Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.

    Science.gov (United States)

    Dhillon, Sohita

    2013-08-01

    Bevacizumab (Avastin®) is a recombinant, humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody that neutralizes the biological activity of VEGF and inhibits tumor angiogenesis. In the EU, in adult patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, bevacizumab (in combination with carboplatin and paclitaxel) is approved for the first-line treatment of advanced disease and (in combination with carboplatin and gemcitabine) is approved for the treatment of patients with first recurrence of platinum-sensitive disease who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. This article summarizes the pharmacology of bevacizumab and reviews the efficacy and tolerability of bevacizumab combination therapy in well-designed clinical studies in these indications. The addition of bevacizumab to first-line carboplatin plus paclitaxel, followed by bevacizumab maintenance therapy significantly prolonged progression-free survival in women with newly-diagnosed advanced disease (GOG-0218 and ICON7 studies). Progression-free survival was also significantly prolonged after second-line treatment with bevacizumab in combination with carboplatin and gemcitabine, followed by maintenance treatment with bevacizumab alone in women with recurrence (≥ 6 months after front-line platinum-based therapy) of platinum-sensitive disease (OCEANS study). Bevacizumab combination therapy had a generally acceptable tolerability profile in these studies, with the nature of adverse events generally similar to that observed in previous clinical trials in patients with other solid tumors. Although several unanswered questions remain, such as the optimal dosage and duration of treatment, current evidence suggests that bevacizumab combination therapy extends the treatment options available for patients with ovarian cancer.

  5. Photodynamic Therapy for Cancer

    Science.gov (United States)

    ... References Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nature Reviews Cancer 2003; 3(5):380–387. [PubMed Abstract] Wilson BC. Photodynamic therapy for cancer: principles. Canadian Journal of Gastroenterology 2002; ...

  6. 胰腺癌综合治疗的现状%Current status of the combined therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    倪泉兴; 李骥

    2009-01-01

    Pancreatic cancer is one of the worst digestive malignancies characterized by non-specific symptoms, rapid progression and high mortality. Despite great efforts that have been made in basic and clinical research, the prognosis remains poor with an overall 5-year survival rate of less than 5%. Complete surgical resection is the only curative treatment option, but the curative resectabillty is still about 15% in China. Pancreatic surgery is considered one of the most techni-cally demanding and challenging procedures. The development of pancreatic surgery in China depends not only on the progress in surgical techniques, but also the specialization on pancreatic surgery. There has been advancement in combined therapy with a modern interdisciplinary approach including chemotherapy,radiotherapy, biotherapy and thermotherapy. The research pro-gress of gene therapy on pancreatic cancer showed us some hopes for the future. The outcome of pancreatic cancer treated by Chinese medicine with herbal drugs is encouraging, but still needs the support of more solid evidences from randomized con-trolled trials. It is suggested that the combined therapy should play an important role in the treatment of pancreatic cancer, and the fallow-up should be paid more attention.

  7. Preliminary clinical evaluation of continuous infusion of 5-FU and low dose cisplatin (LFP) combined with radiation therapy for the treatment of advanced or recurrent esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Satoshi; Morita, Soujiro; Hisa, Nobuaki; Tsuji, Akihito; Takamatsu, Masahiro; Takasaki, Motohiro; Horimi, Tadashi [Kochi Municipal Central Hospital (Japan)

    2000-11-01

    We evaluated the LFP combined with radiation therapy for the treatment of advanced or recurrent esophageal cancer. The patients consisted of 4 inoperable cases, 4 cases in combination with operation, and 5 cases with recurrent tumor. The response rate was 80% (CR2, PR6, NC1 and PD1). We conclude that the LFP combined with radiation therapy was effective and useful for the treatment of advanced or recurrent esophageal cancer. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Kinuya, Seigo; Yokoyama, Kunihiko; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa [Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa (Japan); Koshida, Kiyoshi [Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa (Japan); Mori, Hirofumi; Shiba, Kazuhiro [Radioisotope Center, Kanazawa University, Kanazawa, Ishikawa (Japan); Watanabe, Naoto [Department of Radiology, Toyama Medical and Pharmaceutical University, Toyama (Japan); Shuke, Noriyuki [Department of Radiology, Asahikawa Medical College, Asahikawa, Hokkaido (Japan)

    2004-07-01

    We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of {sup 131}I-A7, an IgG1 anti-colorectal monoclonal antibody, or {sup 131}I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation (n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice (n=8) (P<0.05). {sup 131}I-A7 RIT displayed a marked therapeutic effect (n=8) (P<0.001); however, all animals eventually died due to metastases by 99 days. The combined regimen of {sup 131}I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy (n=10) (P<0.05); three mice survived the entire 160-day observation period. The combination of antiangiogenic therapy and {sup 131}I-HPMS-1 RIT failed to provide an appreciable benefit (n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases. (orig.)

  9. Rapid tumor necrosis and massive hemorrhage induced by bevacizumab and paclitaxel combination therapy in a case of advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Ono M

    2013-10-01

    Full Text Available Mayu Ono, Tokiko Ito, Toshiharu Kanai, Koichi Murayama, Hiroshi Koyama, Kazuma Maeno, Yasuhiro Mochizuki, Asumi Iesato, Toru Hanamura, Toshihiro Okada, Takayuki Watanabe, Ken-ichi ItoDivision of Breast and Endocrine Surgery, Department of Surgery (II, Shinshu University School of Medicine, Matsumoto, JapanAbstract: Bevacizumab when combined with chemotherapy exerts significant activity against many solid tumors through tumor angiogenesis inhibition; however, it can induce severe side effects. We report the rare case of a 27-year-old premenopausal woman with locally advanced breast cancer that was marked by rapid tumor necrosis followed by massive hemorrhage shortly after bevacizumab and paclitaxel administration. On the basis of histopathological examination of a biopsy specimen and computed tomography findings, she was diagnosed with stage IV estrogen and progesterone receptor-negative and human epidermal growth factor receptor type 2-positive breast cancer with multiple organ metastases when she had entered gestational week 24. Cyclophosphamide, Adriamycin®, fluorouracil therapy was initiated, but multiple liver metastases continued to progress. A healthy fetus was delivered by induced delivery and trastuzumab-based treatment was initiated. Although the multiple liver metastases were controlled successfully by trastuzumab combined with paclitaxel, the primary tumor continued to expand even after subsequent administration of three other treatment regimens including anti-human epidermal growth factor receptor type 2 agents and cytotoxic drugs. To inhibit primary tumor growth, a combination therapy with paclitaxel and bevacizumab was subsequently initiated. Following therapy initiation, however, the large tumor occupying the patient's entire left breast became necrotic and ulcerated rapidly. Furthermore, massive hemorrhage from the tumor occurred 5 weeks after bevacizumab-based therapy initiation. Although hemostasis was achieved by manual

  10. [Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose Cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer].

    Science.gov (United States)

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi

    2002-02-01

    We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m2/day) was continuously infused over 24 hours, and CDDP (3-7 mg/m2/day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer.

  11. Preliminary clinical evaluation of continuous infusion of 5-FU and low-dose cisplatin (LFP) therapy alone and combined with radiation therapy for treatment of advanced or recurrent esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Satoshi; Morita, Sojiro; Ohnishi, Takenao; Tsuji, Akihito; Takamatsu, Masahiro; Horimi, Tadashi [Kochi Municipal Central Hospital, Nankoku (Japan). Cancer Research Center

    2002-02-01

    We evaluated the clinical effect of 5-FU and low-dose Cisplatin (LFP) therapy alone and LFP therapy combined with radiation therapy in patients with advanced or recurrent esophageal cancer. From March 1995 to September 2000, 11 patients with inoperable esophageal cancer, 8 patients with adjuvant chemotherapy post operation, and 14 patients with recurrent esophageal cancer were treated with LFP therapy. 5-FU (160 mg/m{sup 2}/day) was continuously infused over 24 hours, and CDDP (3-7 mg/m{sup 2}/day) was infused for 30 minutes. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest, each for four weeks. We combined radiation therapy for the patients with all lesions that could be included in the radiation field. Of 30 patients with measurable lesions the response rates of LFP therapy alone and LFP therapy combined with radiation therapy were 33% and 60%, respectively. Toxicity over grade 3 appeared in 3 of 15 patients with LFP therapy combined with radiation therapy. There was no significant difference between LFP therapy alone and LFP therapy combined with radiation therapy with regard to survival rate of inoperable and recurrent esophageal cancer. In conclusion, LFP therapy alone may be effective for esophageal cancer. (author)

  12. New design of nucleotide excision repair (NER) inhibitors for combination cancer therapy.

    Science.gov (United States)

    Gentile, Francesco; Tuszynski, Jack A; Barakat, Khaled H

    2016-04-01

    Many cancer chemotherapy agents act by targeting the DNA of cancer cells, causing substantial damage within their genome and causing them to undergo apoptosis. An effective DNA repair pathway in cancer cells can act in a reverse way by removing these drug-induced DNA lesions, allowing cancer cells to survive, grow and proliferate. In this context, DNA repair inhibitors opened a new avenue in cancer treatment, by blocking the DNA repair mechanisms from removing the chemotherapy-mediated DNA damage. In particular, the nucleotide excision repair (NER) involves more than thirty protein-protein interactions and removes DNA adducts caused by platinum-based chemotherapy. The excision repair cross-complementation group 1 (ERCC1)-xeroderma pigmentosum, complementation group A (XPA) protein (XPA-ERCC1) complex seems to be one of the most promising targets in this pathway. ERCC1 is over expressed in cancer cells and the only known cellular function so far for XPA is to recruit ERCC1 to the damaged point. Here, we build upon our recent advances in identifying inhibitors for this interaction and continue our efforts to rationally design more effective and potent regulators for the NER pathway. We employed in silico drug design techniques to: (1) identify compounds similar to the recently discovered inhibitors, but more effective at inhibiting the XPA-ERCC1 interactions, and (2) identify different scaffolds to develop novel lead compounds. Two known inhibitor structures have been used as starting points for two ligand/structure-hybrid virtual screening approaches. The findings described here form a milestone in discovering novel inhibitors for the NER pathway aiming at improving the efficacy of current platinum-based therapy, by modulating the XPA-ERCC1 interaction.

  13. Photothermal and biodegradable polyaniline/porous silicon hybrid nanocomposites as drug carriers for combined chemo-photothermal therapy of cancer.

    Science.gov (United States)

    Xia, Bing; Wang, Bin; Shi, Jisen; Zhang, Yu; Zhang, Qi; Chen, Zhenyu; Li, Jiachen

    2017-03-15

    To develop photothermal and biodegradable nanocarriers for combined chemo-photothermal therapy of cancer, polyaniline/porous silicon hybrid nanocomposites had been successfully fabricated via surface initiated polymerization of aniline onto porous silicon nanoparticles in our experiments. As-prepared polyaniline/porous silicon nanocomposites could be well dispersed in aqueous solution without any extra hydrophilic surface coatings, and showed a robust photothermal effect under near-infrared (NIR) laser irradiation. Especially, after an intravenous injection into mice, these biodegradable porous silicon-based nanocomposites as non-toxic agents could be completely cleared in body. Moreover, these polyaniline/porous silicon nanocomposites as drug carriers also exhibited an efficient loading and dual pH/NIR light-triggered release of doxorubicin hydrochloride (DOX, a model anticancer drug). Most importantly, assisted with NIR laser irradiation, polyaniline/PSiNPs nanocomposites with loading DOX showed a remarkable synergistic anticancer effect combining chemotherapy with photothermal therapy, whether in vitro or in vivo. Therefore, based on biodegradable PSiNPs-based nanocomposites, this combination approach of chemo-photothermal therapy would have enormous potential on clinical cancer treatments in the future.

  14. Effect of Kushen injection in combined with continuing nursing on the patients with instillation therapy after bladder cancer surgery

    Institute of Scientific and Technical Information of China (English)

    Rui-Xia Han; Rui-Min Han; Li-Kun Chen; Ming-Juan Liu; Hai-Ming Du; Zhi-Qian Tang; Lian-Xia Geng

    2016-01-01

    Objective: To observe the effect of Kushen injection in combined with continuing nursing on the patients with instillation therapy after bladder cancer surgery. Methods:A total of 60 patients with bladder cancer who were admitted in our hospital from January, 2013 to January, 2015 for instillation therapy were included in the study and were randomized into the observation group and the control group. The patients in the two groups were given routine THP instillation therapy. On this basis, the patients in the observation group were given additional Kushen injection in combined with continuing nursing. The occurrence rate of adverse reactions during the chemotherapy period and the improvement of immunological indicators in the two groups were compared. SF-36 health survey scale was used to evaluate the living qualities. Results:After treatment, CD4+and NK cell level in the observation group were significantly elevated, but CD8+level was significantly reduced when compared with before treatment. CD4+, CD8+, and NK cell levels after treatment in the control group were not significantly different from those before treatment. The bladder irritation symptoms during the chemotherapy period in the observation group were significantly lighter than those in the control group. The occurrence rate of main adverse reactions during the chemotherapy period in the observation group was significantly lower than that in the control group. The living quality scores in the observation group were significantly higher than those in the control group. Conclusions:Kushen injection in combined with continuing nursing can effectively regulate the immunological function in patients with instillation therapy after bladder cancer surgery, reduce the occurrence rate of adverse reactions, and enhance the living qualities.

  15. The Rationale for Optimal Combination Therapy With Sipuleucel-T for Patients With Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Mouraviev, Vladimir; Mariados, Neil; Albala, David; Concepcion, Raoul S; Shore, Neal D; Sims, Robert B; Emberton, Mark; Pieczonka, Christopher M

    2014-01-01

    Immunotherapy encourages the recipient's own immune response to destroy cancer cells, and current evidence suggests that immunotherapies may be most beneficial in early metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T is the first therapeutic cancer vaccine to be approved by both the US Food and Drug Administration and European Medicines Agency for the treatment of asymptomatic or minimally symptomatic mCRPC. Combining immunotherapy with other treatments may have potent anticancer effects; cytoreductive therapies can release tumor antigens and promote a proinflammatory environment that could augment immunotherapies. However, some cytoreductive agents or coadministered drugs may be immunosuppressive. Understanding these interactions between different mCRPC treatment modalities may offer further potential to improve patient outcomes.

  16. Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy

    Directory of Open Access Journals (Sweden)

    Zhang XF

    2016-08-01

    Full Text Available Xi-Feng Zhang,1 Sangiliyandi Gurunathan2 1College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, People’s Republic of China; 2Department of Stem Cell and Regenerative Biology, Konkuk University, Seoul, South Korea Abstract: Ovarian cancer is one of the most important malignancies, and the origin, detection, and pathogenesis of epithelial ovarian cancer remain elusive. Although many cancer drugs have been developed to dramatically reduce the size of tumors, most cancers eventually relapse, posing a critical problem to overcome. Hence, it is necessary to identify possible alternative therapeutic approaches to reduce the mortality rate of this devastating disease. To identify alternative approaches, we first synthesized silver nanoparticles (AgNPs using a novel bacterium called Bacillus clausii. The synthesized AgNPs were homogenous and spherical in shape, with an average size of 16–20 nm, which are known to cause cytotoxicity in various types of human cancer cells, whereas salinomycin (Sal is able to kill cancer stem cells. Therefore, we selected both Sal and AgNPs to study their combined effect on apoptosis and autophagy in ovarian cancer cells. The cells treated with either Sal or AgNPs showed a dose-dependent effect with inhibitory concentration (IC-50 values of 6.0 µM and 8 µg/mL for Sal and AgNPs, respectively. To determine the combination effect, we measured the IC25 values of both Sal and AgNPs (3.0 µM and 4 µg/mL, which showed a more dramatic inhibitory effect on cell viability and cell morphology than either Sal or AgNPs alone. The combination of Sal and AgNPs had more pronounced effect on cytotoxicity and expression of apoptotic genes and also significantly induced the accumulation of autophagolysosomes, which was associated with mitochondrial dysfunction and loss of cell viability. Our data show a strong synergistic interaction between Sal and AgNPs in tested cancer cells. The combination

  17. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

    Energy Technology Data Exchange (ETDEWEB)

    Kordes, Sil, E-mail: s.kordes@amc.uva.nl [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Berge Henegouwen, Mark I. van [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Hulshof, Maarten C. [Department of Radiotherapy, Academic Medical Center, Amsterdam (Netherlands); Bergman, Jacques J.G.H.M. [Department of Gastroenterology, Academic Medical Center, Amsterdam (Netherlands); Vliet, Hans J. van der [Department of Medical Oncology, Vrije Universiteit Medical Center, Amsterdam (Netherlands); Kapiteijn, Ellen [Department of Medical Oncology, Leiden University Medical Center, Leiden (Netherlands); Laarhoven, Hanneke W.M. van; Richel, Dick J. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands); Klinkenbijl, Jean H.G. [Department of Surgery, Academic Medical Center, Amsterdam (Netherlands); Meijer, Sybren L. [Department of Pathology, Academic Medical Center, Amsterdam (Netherlands); Wilmink, Johanna W. [Department of Medical Oncology, Academic Medical Center, Amsterdam (Netherlands)

    2014-09-01

    Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m{sup 2}) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%.

  18. High-Throughput Testing of Novel-Novel Combination Therapies for Cancer: An Idea Whose Time Has Come.

    Science.gov (United States)

    Scarlett, Uciane K; Chang, Dennis C; Murtagh, Thomas J; Flaherty, Keith T

    2016-09-01

    Combination therapies are essential to address the genetic complexity, plasticity, and heterogeneity of tumors and to overcome resistance mechanisms that confound single-agent approaches, and are a paradigm that became well established in the era of conventional cytotoxic chemotherapies. Today, we are well equipped to address many of the scientific, clinical, and collaboration challenges that have existed historically; however, the pace of testing rational combinations is modest. Our analysis shows that the volume of clinical trials testing multiple investigational pipeline agents ("novel-novel" combinations) is dismally low, as out of approximately 1,500 phase I to III investigational combination trials initiated in 2014-2015, only 80 were for novel-novel combinations, and only 9 of those involved more than one company. The Collaborative Novel-Novel Combination Therapies (CoNNCT) initiative aims to alleviate this bottleneck by developing a new, faster paradigm for early investigation of scientifically informed, novel-novel drug combinations. The initiative kicked off on March 7, 2016, when representatives from top academic centers, biopharma, nonprofits, the FDA, and other groups gathered to define an actionable path forward. Cancer Discov; 6(9); 956-62. ©2016 AACR.

  19. Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy.

    Science.gov (United States)

    Zhang, Xi-Feng; Gurunathan, Sangiliyandi

    2016-01-01

    Ovarian cancer is one of the most important malignancies, and the origin, detection, and pathogenesis of epithelial ovarian cancer remain elusive. Although many cancer drugs have been developed to dramatically reduce the size of tumors, most cancers eventually relapse, posing a critical problem to overcome. Hence, it is necessary to identify possible alternative therapeutic approaches to reduce the mortality rate of this devastating disease. To identify alternative approaches, we first synthesized silver nanoparticles (AgNPs) using a novel bacterium called Bacillus clausii. The synthesized AgNPs were homogenous and spherical in shape, with an average size of 16-20 nm, which are known to cause cytotoxicity in various types of human cancer cells, whereas salinomycin (Sal) is able to kill cancer stem cells. Therefore, we selected both Sal and AgNPs to study their combined effect on apoptosis and autophagy in ovarian cancer cells. The cells treated with either Sal or AgNPs showed a dose-dependent effect with inhibitory concentration (IC)-50 values of 6.0 µM and 8 µg/mL for Sal and AgNPs, respectively. To determine the combination effect, we measured the IC25 values of both Sal and AgNPs (3.0 µM and 4 µg/mL), which showed a more dramatic inhibitory effect on cell viability and cell morphology than either Sal or AgNPs alone. The combination of Sal and AgNPs had more pronounced effect on cytotoxicity and expression of apoptotic genes and also significantly induced the accumulation of autophagolysosomes, which was associated with mitochondrial dysfunction and loss of cell viability. Our data show a strong synergistic interaction between Sal and AgNPs in tested cancer cells. The combination treatment increased the therapeutic potential and demonstrated the relevant targeted therapy for the treatment of ovarian cancer. Furthermore, we provide, for the first time, a mode of action for Sal and AgNPs in ovarian cancer cells: enhanced apoptosis and autophagy.

  20. Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy

    Science.gov (United States)

    He, Chunbai; Duan, Xiaopin; Guo, Nining; Chan, Christina; Poon, Christopher; Weichselbaum, Ralph R.; Lin, Wenbin

    2016-08-01

    Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response.

  1. Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy.

    Science.gov (United States)

    He, Chunbai; Duan, Xiaopin; Guo, Nining; Chan, Christina; Poon, Christopher; Weichselbaum, Ralph R; Lin, Wenbin

    2016-08-17

    Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response.

  2. Laser therapy for cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...

  3. Progestagen component in combined hormone replacement therapy in postmenopausal women and breast cancer risk: a debated clinical issue.

    Science.gov (United States)

    Gadducci, Angiolo; Biglia, Nicoletta; Cosio, Stefania; Sismondi, Piero; Genazzani, Andrea Riccardo

    2009-12-01

    The relevance of the progestagen component in combined hormone replacement therapy (HRT) for breast cancer risk has been long debated. In vitro studies have shown that progestins exert both genomic transcriptional and non-genomic effects that can enhance the proliferation, invasiveness and spread of breast cancer cells. According to a novel hypothesis, progestins can still activate cancer stem cells in patients with pre-existing, clinically undetected breast cancer. However, some experimental and clinical data suggest that different progestins may have a different impact on the pathophysiology of malignant breast cells. In vitro studies on estrogen receptor (ER)+ breast cancer cells have shown that the addition of medroxyprogesterone acetate (MPA) to estradiol (E(2)) produces a significantly higher increase of the mRNA levels and activities of estrogen-activating enzymes aromatase, 17beta hydroxysteroid dehydrogenase type-1 and sulfatase when compared with progesterone plus E(2). In randomised trial performed on ovariectomised adult female monkeys, oral E(2) plus MPA have resulted in a significantly greater proliferation of breast lobular and ductal epithelium when compared with placebo, whereas E(2) plus micronised progesterone have not. In the same experimental model, oral E(2) plus MPA have been found to induce the expression of genes encoding epidermal growth factor receptor (EGFR) ligands and downstream targets, whereas E(2) alone or E(2) plus micronised progesterone had no or modest effects on EGFR-related genes. In last years, some clinical studies on HRT users have shown that androgenic progestin- or MPA-based formulations are associated with an increased breast cancer incidence, whereas micronised progesterone- or dydrogesterone-based formulations are not. Further basic and clinical investigations on this topic are strongly warranted to elucidate whether the choice of the progestagen component in combined HRT could be of clinical relevance as for breast

  4. Biologic Therapy (Immunotherapy) for Kidney Cancer

    Science.gov (United States)

    ... Stage for Kidney Cancer Kidney Cancer Treating Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer The goal of biologic therapy ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  5. Effect of dendritic cell/cytokine-induced killer cell immunobiological cancer therapy combined with adjuvant chemotherapy in patients with triple-negative breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ranran Zhang; Dongchu Ma; Xiaodong Xie; Wanqing Xie Co-first author; Tao Han; Yongye Liu; Zhaozhe Liu; Fang Guo; Yaling Han; Zhenyu Ding; Yinghui Sun

    2015-01-01

    Objective The aim of the present study was to investigate the ef ect of dendritic cel (DC)/cytokine-in-duced kil er cel (CIK) immunobiological cancer therapy in patients with triple-negative breast cancer (TNBC) who underwent adjuvant chemotherapy. Methods From January 2010 to October 2013, 120 patients with postoperative TNBC were recruited and included in the study. Patients were enrol ed in one of two groups according to whether they accepted DC/CIK immunobiological cancer therapy during adjuvant chemotherapy; the patients in the DC/CIK group underwent adjuvant chemotherapy combined with DC/CIK immunobiological cancer therapy, and the control group underwent adjuvant chemotherapy alone. When six cycles of adjuvant chemotherapy and six cycles of DC/CIK immunobiological cancer therapy had been completed, dif erences between the two groups with regard to quality of life (QoL), immunological indicators (CD3, CD4, CD8, and NK cel levels), disease-free survival (DFS), and side ef ects of chemotherapy and DC/CIK treatment were evaluated. Results In the DC/CIK group, the proportion of NK cel s and CD3+ and CD4+ T-cel subgroups significantly increased, and the proportion of CD8+ cel s decreased when they were compared before and after DC/CIK therapy (P Conclusion The DC/CIK treatment had potential benefits for patients with TNBC compared with the con-trol group, and was not associated with any obvious side ef ects. Therefore, DC/CIK therapy is a safe and ef ective method for the treatment of TNBC.

  6. Massage therapy alone and in combination with meditation for breast cancer patients undergoing autologous tissue reconstruction: A randomized pilot study.

    Science.gov (United States)

    Dion, Liza J; Engen, Deborah J; Lemaine, Valerie; Lawson, Donna K; Brock, Charise G; Thomley, Barbara S; Cha, Stephen S; Sood, Amit; Bauer, Brent A; Wahner-Roedler, Dietlind L

    2016-05-01

    This study explored whether massage combined with meditation is more helpful than massage alone for women recovering from autologous tissue reconstruction after mastectomy for breast cancer. Forty patients were randomly assigned to either massage therapy or massage plus meditation on postoperative days 1 through 3. Outcome measures were 1) visual analog scale (VAS) scores for stress, anxiety, relaxation, insomnia, alertness, fatigue, tension, pain, mood, and energy, and 2) Perceived Stress Scale-14 scores. Nineteen patients in each group finished the study. Preintervention and postintervention mean total VAS scores improved significantly in both groups (P < .001), but no significant difference occurred between groups.

  7. Radiation Therapy for Testicular Cancer

    Science.gov (United States)

    ... Testicular Cancer Treating Testicular Cancer Radiation Therapy for Testicular Cancer Radiation therapy uses a beam of high-energy ... Testicular Cancer, by Type and Stage More In Testicular Cancer About Testicular Cancer Causes, Risk Factors, and Prevention ...

  8. 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.

  9. Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.

    Science.gov (United States)

    Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios

    2016-08-01

    Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.

  10. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy

    OpenAIRE

    2015-01-01

    The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT) and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mic...

  11. Palbociclib in Combination With Tamoxifen as First Line Therapy for Metastatic Hormone Receptor Positive Breast Cancer

    Science.gov (United States)

    2016-10-04

    Hormone Receptor Positive Malignant Neoplasm of Breast; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Metastatic Breast Cancer

  12. Lefunomide in combination therapy

    NARCIS (Netherlands)

    Kalden, J.R.; Smolen, J.S.; Emery, P.; Riel, P.L.C.M. van; Dougados, M.; Strand, C.V.; Breedveld, F.C.

    2004-01-01

    In most studies of disease modifying antirheumatic drug therapy, in combination with either leflunomide or biological agents, patients are given an additional agent after they have failed treatment with methotrexate (MTX). This review of clinical studies shows that leflunomide is clinically efficaci

  13. Locally advanced prostate cancer: combination of high-dose high-precision radiotherapy and androgen deprivation therapy%Locally advanced prostate cancer:combination of high-dose high-precision radiotherapy and androgen deprivation therapy

    Institute of Scientific and Technical Information of China (English)

    Michel Bolla; René-Olivier Mirimanoff

    2014-01-01

    Locally advanced prostate cancer entails a risk of local,regional and systemic relapse requiring the combination of a Ioco-regional treatment,namely external beam radiotherapy(EBRT) to control the pelvic-confined disease,combined with a systemic therapy,namely androgen-deprivation therapy(ADT),to potentiate irradiation and to destroy the infra-clinical androgen-dependant disease outside the irradiated volume.Many phases Ⅲ randomized trials have paved the way in establishing the indications of this combined approach,which requires a long term ADT(≥2 years) with LHRH agonists.The duration of ADT may be reduced to 6 months should there be a significant comorbidity,a reluctance from the patient or a poor tolerance.A multidisciplinary approach will enable physicians to tailor the treatment strategy and a close cooperation between the specialists and the general practitioners will be set up to prevent as much as possible the side-effects of ADT.

  14. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Alan eDal Pra

    2016-02-01

    Full Text Available Radiation therapy (RT is one of the mainstay treatments for prostate cancer (PCa. The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: I. androgen signaling pathway; II. hypoxic tumor cells and regions; III. DNA damage response (DDR pathway; and IV. abnormal extra/intra-cell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa.

  15. Meta-analysis on inoperable pancreatic cancer: A comparison between gemcitabine-based combination therapy and gemcitabine alone

    Institute of Scientific and Technical Information of China (English)

    De-Rong Xie; Han-Lin Liang; Yu Wang; Shuan-Shuan Guo; Qiong Yang

    2006-01-01

    AIM: To compare gemcitabine-based combination therapy and gemcitabine (GEM) alone in patients with advanced pancreatic cancer (APCa) through metaanalysis.METHODS: MEDLINE and EMBASE searches were supplemented by information from trial registers of randomized controlled trials (RCTs) for GEM-based combination therapy and GEM alone for APCa. A quantitative meta-analysis was carried out by two reviewers based on the inclusion criteria from all available RCTs. The meta-analysis involved overall survival (OS), objective remission rate (ORR), clinical benefit rate (CBR), time to progress/progress free survival (TTP/PFS) and toxicity.RESULTS: The meta-analysis included 22 RCTs. There was significant improvement in the GEM combination group with regard to the 6-mo survival rate (RD = 0.04,95% CI 0.01-0.06, P = 0.008), 1-year survival rate (RD = 0.03, 95% CI 0.01-0.05, P = 0.01), ORR (RD =0.04, 95% CT 0.01-0.07, P = 0.02), CBR (RD = 0.10,95% CI 0.02-0.17, P = 0.01) and 6-mo TTP/PFS (RD =0.07, 95% CI 0.04-0.10, P < 0.00001). However, the Grade 3-4 toxicity set by WHO was higher for the GEM combination group for neutropenia (RD = 0.05, 95%CI 0.01-0.10, P = 0.02), thrombocytopenia (RD = 0.05,95% CI 0.02-0.08, P = 0.002) and vomiting/nausea (RD= 0.03, 95% CI 0.00-0.05, P = 0.02).CONCLUSION: GEM-based combination therapy may improve the overall survival and palliation in optimal patients with APCa as compared with GEM alone.

  16. Evaluation of Outcome and Tolerability of Combination Chemotherapy with Capecitabine and Oxaliplatin as First Line Therapy in Advanced Gastric Cancer

    Science.gov (United States)

    Mashhadi, Mohammad Ali; Sepehri, Zahra; Bakhshipour, Ali Reza; Zivari, Ali; Danesh, Hossein Ali; Metanat, Hasan Ali; Karimkoshteh, Azra; Hashemi, Seyed Mehdi; Rahimi, Hossein; Kiani, Zohre

    2016-01-01

    Background: Combination chemotherapy is accepted as a high efficacy treatment for gastric cancer, whereas choice of standard treatment is unclear. Multiple chemotherapeutic regimens have been used to achieve higher efficacy and lower toxicity. This study was designed to evaluate the treatment results of advanced gastric cancer with Capecitabine and Oxaliplatin regimen. Subjects and Methods : All cases with documented gastric adenocarcinoma and advanced disease were candidates for receiving Xelox regimen (Capecitabine – 750 mg/m2/twice daily/ 1-14 days and Oxaliplatin 125 mg/m2 in 1st day). Results: Twenty five cases with advanced gastric cancer entered in study while 24 cases continued treatment protocol and were evaluated. Mean age was 59.5 ± 12.1 years (range: 20-75), male and female cases were 66.7% and 33.3%, respectively. All cases received at least four cycles of Xelox regimen. Overall response rate was 74.99% with 29.16% complete response. Overall survival rate was 13 ± 0.53 months and DFS (disease-free survival) was 6 ± 1.09 months. Extremities neuropathy (62.5%), headache (45.8%) and muscle cramps (29.2%) were the most common complains. Haematological changes were rare and 16.7% of cases had mild cytopenia. Treatment related death was not observed. Conclusion: Xelox regimen is a safe and highly effective first line treatment for gastric cancer; however, considering it as first line therapy needs larger studies. PMID:27928475

  17. Effective gene-viral therapy for telomerase-positive cancers by selective replicative-competent adenovirus combining with endostatin gene

    Institute of Scientific and Technical Information of China (English)

    Zhang Q; Liu C; Jiang M; Fang G; Liu X; Wu M; Qian Q; Nie M; Sham J; Su C; Xue H; Chua D; Wang W; Cui Z; Liu Y

    2005-01-01

    Gene-viral therapy, which uses replication-selective transgene-expressing viruses to manage tumors, can exploit the virtues of gene therapy and virotherapy and overcome the limitations of conventional gene therapy. Using a human telomerase reverse transcriptase-targeted replicative adenovirus as an antiangiogenic gene transfer vector to target new angiogenesis and making use of its unrestrained proliferation are completely new concepts in tumor management. CNHK300-mE is a selective replication transgene-expressing adenovirus constructed to carry mouse endostatin gene therapeutically. Infection with CNHK300-mE was associated with selective replication of the adenovirus and production of mouse endostatin in telomerase-positive cancer cells. Endostatin secreted from a human gastric cell line, SGC-7901, infected with CNHK300-mE was significantly higher than that infected with nonreplicative adenovirus Ad-mE in vitro (800±94.7 ng/ml versus 132.9±9.9 ng/ml) and in vivo (610±42 ng/ml versus 126 +/- 13 ng/ml). Embryonic chorioallantoic membrane assay showed that the mouse endostatin secreted by CNHK300-mE inhibited angiogenesis efficiently and also induced distortion of pre-existing vasculature. CNHK300-mE exhibited a superior suppression of xenografts in nude mice compared with CNHK300 and Ad-mE. In summary, we provided a more efficient gene-viral therapy strategy by combining oncolysis with antiangiogenesis.

  18. Benefits of combined radioimmunotherapy and anti-angiogenic therapy in a liver metastasis model of human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiao-Feng; Kinuya, Seigo; Yokoyama, Kunihiko; Michigishi, Takatoshi; Tonami, Norihisa [Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640 (Japan); Koshida, Kiyoshi [Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa (Japan); Mori, Hirofumi; Shiba, Kazuhiro [Radioiosotope Center, Kanazawa University, Kanazawa (Japan); Watanabe, Naoto [Department of Radiology, Toyama Medical and Pharmaceutical University, Toyama (Japan); Shuke, Noriyuki [Department of Radiology, Asahikawa Medical College, Asahikawa (Japan)

    2002-12-01

    The combined use of anti-angiogenic therapy (AT) and radioimmunotherapy (RIT) may improve the therapeutic outcome in patients with cancer lesions. This hypothesis is based on the ability of AT to suppress tumour endothelial compartments and the direct action of RIT against tumour cells. We previously confirmed this hypothesis in an established subcutaneous xenograft model of colon cancer. The purpose of the current investigation was to determine the benefit of this combination within a liver metastasis model, which mimics treatment of minimal disease in an adjuvant setting. Liver metastases were established in nude mice by intrasplenic inoculation of LS180 colon cancer cells; following such inoculation, metastases of <1 mm in diameter can be observed at 1 week and these lesions can attain a size of several millimetres at 2 weeks. Daily AT with 2-methoxyoestradiol (2-ME), 75 mg/kg, was initiated at 1 week. RIT with 7 MBq of {sup 131}I-A7, an IgG1 anti-colorectal monoclonal antibody, was conducted at 2 weeks. RIT employing an irrelevant IgG1, {sup 131}I-HPMS-1, was implemented for comparison. The weight of liver metastases was measured 4 weeks after cell inoculation. The effect of AT on {sup 131}I-A7 accumulation in metastases was also observed. Toxicity of treatment was monitored by blood cell counts. Monotherapy with 2-ME AT or {sup 131}I-A7 RIT significantly suppressed metastasis growth (P<0.0001): metastasis weight was 5.96{+-}0.87 g in non-treated controls, 2.67{+-}1.89 g in cases receiving AT and 0.85{+-}0.68 g in those receiving {sup 131}I-A7 RIT. Combination of AT and {sup 131}I-A7 RIT more effectively suppressed the growth to 0.28{+-}0.32 g (P<0.05 vs RIT alone). The effect of {sup 131}I-HPMS-1 RIT, which suppressed metastasis growth to 2.25{+-}0.88 g, was significant in comparison with the control (P<0.0001); however, the combination of AT and {sup 131}I-HPMS-1 RIT (which suppressed growth to 1.41{+-}0.68 g) was far less effective than the combination of AT

  19. Effect of nimotuzumab targeted therapy combined with conventional chemotherapy in treatment of advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Hai-Ping Xu; Hui-Juan Wu; Shang-Shuang Shi

    2016-01-01

    Objective:To study the clinical efficacy of nimotuzumab targeted therapy combined with conventional chemotherapy in treatment of advanced non-small cell lung cancer.Methods:Patients with non-small cell lung cancer were selected for study and randomly divided into targeted group and conventional group, efficacy of two groups after 2 and 4 treatment cycles was evaluated, tumor tissue was collected and activation of PI3K/AKT pathway, MAPK/ERK pathway and JAK2/STAT3 pathway was detected.Results:After 2 and 4 chemotherapy cycles, CR case number, PR case number and SD case number of targeted group were significantly more than those of conventional group (P<0.05); PD case number was significantly less than that of conventional group (P<0.05). Expression levels of PI3K, AKT, MAPK, ERK1, ERK2, JAK2 andSTAT3 in tumor tissue of targeted group were significantly lower than those of conventional group (P<0.05). Expression levels of FasL and Bim in tumor tissue of targeted group were significantly higher than those of conventional group (P<0.05), and expression levels ofBcl-2, Survivin, VEGF, HIF-1α andEPO were significantly lower than those of conventional group (P<0.05).Conclusions:Nimotuzumab targeted therapy combined with conventional chemotherapy can achieve more precise short-term efficacy and inhibit the activation of PI3K/AKT pathway, MAPK/ERK pathway and JAK2/STAT3 pathway, and it is a more ideal solution for treatment of advanced non-small cell lung cancer.

  20. Advances in Cancer Therapy

    OpenAIRE

    Jordan BF, Sonveaux P

    2011-01-01

    The book "Advances in Cancer Therapy" is a new addition to the Intech collection of books and aims at providing scientists and clinicians with a comprehensive overview of the state of current knowledge and latest research findings in the area of cancer therapy. For this purpose research articles, clinical investigations and review papers that are thought to improve the readers' understanding of cancer therapy developments and/or to keep them up to date with the most recent advances in this fi...

  1. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.

    Directory of Open Access Journals (Sweden)

    A M Poff

    Full Text Available The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control, low glucose (LG, ketone supplementation (βHB, hyperbaric oxygen (HBOT, or combination therapy (LG+βHB+HBOT on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers.

  2. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.

    Science.gov (United States)

    Poff, A M; Ward, N; Seyfried, T N; Arnold, P; D'Agostino, D P

    2015-01-01

    The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT) and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control), low glucose (LG), ketone supplementation (βHB), hyperbaric oxygen (HBOT), or combination therapy (LG+βHB+HBOT) on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers.

  3. Nanomedicine and cancer therapies

    CERN Document Server

    Sebastian, Mathew; Elias, Eldho

    2012-01-01

    Introduction Nanotechnological-Based Systems for CancerIn vivo Spectroscopy for Detection and Treatment of GBM with NPt® ImplantationNanobiotechnology for Antibacterial Therapy and DiagnosisChitosan NanoparticlesSynthesis and Biomedical Application of Silver NanoparticlesRecent Advances in Cancer Therapy Using PhytochemicalsMitochondrial Dysfunction and Cancer: Modulation by Palladium-Lipoic Acid ComplexUnity of Mind and Body: The Concept of Life Purpose DominantThuja Occidentalis and Breast Cancer ChemopreventionAntioxidants and Com

  4. Future directions in combined modality therapy for rectal cancer: reevaluating the role of total mesorectal excision after chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Solanki AA

    2013-08-01

    Full Text Available Abhishek A Solanki,1 Daniel T Chang,2 Stanley L Liauw11Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA; 2Department of Radiation Oncology, Stanford University, Stanford, CA, USAAbstract: Most patients who develop rectal cancer present with locoregionally advanced (T3 or node-positive disease. The standard management of locoregionally advanced rectal cancer is neoadjuvant concurrent chemoradiotherapy (nCRT, followed by radical resection (low-anterior resection or abdominoperineal resection with total mesorectal excision. Approximately 15% of patients can have a pathologic complete response (pCR at the time of surgery, indicating that some patients can have no detectable residual disease after nCRT. The actual benefit of surgery in this group of patients is unclear. It is possible that omission of surgery in these patients, termed selective nonoperative management, can limit the toxicities associated with standard, multimodal combined modality therapy without compromising disease control. In this review, we discuss the clinical experiences to date using selective nonoperative management and various attempts at escalation of nCRT to improve the number of patients who have a pCR. We also explore several clinical, laboratory, imaging, histopathologic, and genetic biomarkers that have been tested as tools to predict which patients are most likely to have a pCR after nCRT.Keywords: rectal cancer, chemoradiotherapy, total mesorectal excision, nonoperative management, organ preservation

  5. Neuroleptic malignant syndrome induced by combination therapy with tetrabenazine and tiapride in a Japanese patient with Huntington's disease at the terminal stage of recurrent breast cancer.

    Science.gov (United States)

    Nozaki, Ichiro; Furukawa, Yutaka; Kato-Motozaki, Yuko; Ikeda, Tokuhei; Tagami, Atsuro; Takahashi, Kazuya; Ishida, Chiho; Komai, Kiyonobu

    2014-01-01

    We herein describe the case of an 81-year-old Japanese woman with neuroleptic malignant syndrome that occurred 36 days after the initiation of combination therapy with tiapride (75 mg/day) and tetrabenazine (12.5 mg/day) for Huntington's disease. The patient had been treated with tiapride or tetrabenazine alone without any adverse effects before the administration of the combination therapy. She also had advanced breast cancer when the combination therapy was initiated. To the best of our knowledge, the occurrence of neuroleptic malignant syndrome due to combination therapy with tetrabenazine and tiapride has not been previously reported. Tetrabenazine should be administered very carefully in combination with other neuroleptic drugs, particularly in patients with a worsening general condition.

  6. Combination therapy of potential gene to enhance oral cancer therapeutic effect

    Science.gov (United States)

    Yeh, Chia-Hsien; Hsu, Yih-Chih

    2015-03-01

    The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

  7. Unproven (questionable) cancer therapies.

    OpenAIRE

    Brigden, M.L.

    1995-01-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects...

  8. Statin as a Combined Therapy for Advanced-Stage Ovarian Cancer: A Propensity Score Matched Analysis

    Directory of Open Access Journals (Sweden)

    Hong-Yu Chen

    2016-01-01

    Full Text Available Background. Despite the great achievements in the treatment of advanced-stage ovarian cancer, it is still a severe condition with an unfavorable 5-year survival rate. Statins have been suggested to reduce the risk of several cancers beyond their cholesterol-lowing effects. However, the prognostic significance of statins in patients with advanced-stage ovarian cancer remains controversial. Methods. A retrospective study was performed to evaluate the association between statin intake and overall survival (OS among patients with advanced-stage ovarian cancer. Patients who underwent cytoreductive surgery followed by courses of intravenous chemotherapy were matched through a propensity score analysis. Results. A total of 60 propensity-matched patients were included. Women in statin group showed a similar OS than the nonstatin counterparts (P=0.966, whereas residual tumor was significantly associated with better OS (P=0.013 and was an independent factor that associated with OS (P=0.002, hazard ratio = 5.460, and 95% confidence interval: 1.894 to 15.742 in multivariable analysis. Conclusions. Our results suggested that statin usage was not associated with improved OS in patients with advanced-stage ovarian cancer undergoing surgery and chemotherapy. Considering the retrospective nature and the relative small sample size of the study, further prospective studies and random control trials are needed.

  9. The importance of combined radiation and endocrine therapy in locally advanced prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Phillip J Gray; William U Shipley

    2012-01-01

    The management of all stages of prostate cancer has become an increasingly complex task as new treatment paradigms are tested and the results of large randomized studies become available.Despite these advances,prostate cancer remains the second leading cause of eancer death and the seventh overall cause of death in men in the United States.1 The advent of prostate-specific antigen (PSA) testing in the 1980s resulted in a significant downward stage migration such that many men now present with the earliest and most curable form of the disease.2,3 Despite this fact,high-risk locally advanced prostate cancer remains a common and complex problem facing clinicians across the world.

  10. A Combination Therapy of JO-I and Chemotherapy in Ovarian Cancer Models

    Science.gov (United States)

    2013-10-01

    Cancer PreINDMeetingInformationPackage Reference:IND117820 14 ***Obtaintissueblockfromadiagnostic surgery orprocedure.If...process causing infectious complications , or a bed ridden state or hospitalization;Offstudy. SampleSizeConsiderations Theanticipated...laboratory equipment also includes two BioRad BioPlex machines, a Perkin Elmer Janus robot for automated plate handling, a Biomek fluorescent plate reader

  11. Development of a Combination Therapy for Prostate Cancer by Targeting Stat3 and HIF-1alpha

    Science.gov (United States)

    2013-07-01

    USA. Although localized disease is often curable, advanced disease is generally not, especially when the cancer becomes castration resistant (mCRPC...for 4h. Cooling the mixture to Fig.B1. NDT extracted from Z.nitidum Fig.B2a. TEL03 is a derivative of perylence, which is origenal derived from

  12. Reduction of PSA values by combination pharmacological therapy in patients with chronic prostatitis: implications for prostate cancer detection.

    Science.gov (United States)

    Magri, Vittorio; Trinchieri, Alberto; Montanari, Emanuele; Del Nero, Alberto; Mangiarotti, Barbara; Zirpoli, Pasquale; de Eguileor, Magda; Marras, Emanuela; Ceriani, Isabella; Vral, Anne; Perletti, Gianpaolo

    2007-06-01

    We identified from our clinical database a total of 471 patients affected by cat. II chronic bacterial prostatitis (CBP), cat. III (IIIa and IIIb) chronic pelvic pain syndrome (CP/CPPS), or cat. IV asymptomatic inflammatory prostatitis (AIP), according to NIH criteria. 132 intent-to-treat patients, showing levels of PSA > or =4 ng/mL, were subjected to a 6-week course of combination pharmacological therapy with 500 mg/day ciprofloxacin, 500 mg/day azithromycin (3 days/week), 10 mg/day alfuzosin and 320 mg b.i.d. Serenoa repens extract. At the end of treatment, 111 per-protocol patients belonging to all categories of prostatitis showed a total 32.5% reduction of PSA levels. In the same group, 66 patients (59.4%) showed "normalization" of PSA values under the 4 ng/mL limit. Patients affected by cat. IIIb CP/CPPS showed the highest PSA reduction and normalization rates (40% and 68.4%, respectively). Follow-up data show that, after a marked, significant reduction at completion of therapy, PSA levels, urine peak flow rates and NIH-CPSI symptom scores remained constant or decreased throughout a period of 18 months in patients showing normalization of PSA values. Prostatic biopsy was proposed to 45 patients showing persistently high PSA values (> or = 4 ng/mL) at the end of treatment. Fourteen patients rejected biopsy; of the remaining 31, 10 were diagnosed with prostate cancer. Four months after a first biopsy, a second biopsy was proposed to the 21 patients with a negative first diagnosis and persistently elevated PSA levels. Three patients rejected the procedure; of the remaining 18, four were diagnosed with prostatic carcinoma. In summary, combination pharmacological therapy decreased the number of patients undergoing prostatic biopsy from 111 to 45. Normalization of PSA values in 59.4% of patients--not subjected to biopsy--increased the prostate cancer detection rate from 12.6% (14/111) to 31.1% (14/45). The reduction of PSA after a 6-week course of therapy was

  13. Gene Therapy of Cancerous Diseases

    OpenAIRE

    Valenčáková, A.; Dziaková, A.; Hatalová, E.

    2015-01-01

    Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purp...

  14. Unproven (questionable) cancer therapies.

    Science.gov (United States)

    Brigden, M L

    1995-11-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects of questionable therapies that make these treatments attractive to patients and that may be perceived as being deficient in the practice of conventional health care professionals. Physicians with patients with cancer should always make sure that unproven therapies are discussed early in the therapeutic relationship. They should also attempt to be aware of alternative therapies that are in vogue in their particular geographic area.

  15. 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.

  16. A Novel Combination of Thermal Ablation and Heat-Inducible Gene therapy for Breast Cancer Treatment

    Science.gov (United States)

    2009-04-01

    11. Khokhlova, V.A., et al., Effects of nonlinear propagation, cavitation , and boiling in lesion formation by high intensity focused ultrasound in...intensity focused ultrasound (HIFU) has been developed as an emerging non-invasive strategy for cancer treatment by thermal ablation of tumor tissue. The...Concepts, Seattle, WA) operating at its fundamental frequency (1.1 MHz) or its third harmonics (3.3 MHz). The ultrasound imaging system was a 5/7

  17. Targeted Cancer Therapies

    Science.gov (United States)

    ... targeted therapies are directed against HER-2, including trastuzumab (Herceptin®), which is approved to treat certain breast and ... traditional chemotherapy drugs. For example, the targeted therapy trastuzumab (Herceptin®) has been used in combination with docetaxel , ...

  18. Effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Jia-Lun Zhu; Zhi-Yong Deng; Chuan-Zhou Yang

    2016-01-01

    Objective:To find the effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis.Methods: A total of 102 lung cancer patients with bone metastases were included in the study and randomly divided into observation group and control group (n=51) according to different treatment they received. Control group received zoledronic acid injection therapy alone, observation group received zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy, and then differences in the growth of lung cancer bone metastasis, bone metabolism, tumor markers and alkaline phosphatase, pain score and pain-related mediator levels,etc. were compared between two groups.Results: Number of metastases of observation group after treatment was less than that of control group, and serum bone metabolism indexes OPG, BSP, TRACP-5b, ICTP and BAP levels, serum tumor markers CYFRA21-1, CEA, NSE, CA125 and BALP levels as well as serum pain-related mediators PGE2, ET-1 and TNF-α levels were lower than those of control group (P<0.05).Conclusions:Zoledronic acid injection combined with radiopharmaceutical89SrCI2 therapy can contain the growth of lung cancer bone metastasis, optimize bone metabolism state while alleviate patients’ perception of pain.

  19. Targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Neal Rosen; Carlos Arteaga

    2011-01-01

    With unprecedented understanding of molecular events underlying human cancer in this genomic era, a large number of drugs specifically targeting hypothesized oncogenic drivers to which tumors are potentially addicted to have been developed and continue to be developed. These targeted cancer therapies are being actively tested in clinical trials with mixed successes. This editorial provides an overview on successful targeted cancer drugs on the market and those drugs that are in late clinical development stages. Importantly, the article lays out main challenges in developing molecular targeted therapies and potential path forward to overcome these challenges, as well as opportunities for China in this new era of targeted agents. The editorial serves as an introduction to the Targeted Cancer Therapies serias that will review in depth of major pathways and drugs targeting these pathways to be published in the coming issues of the Chinese Journal of Cancer.

  20. EFFECTS OF p53 GENE THERAPY COMBINED WITH CYCLOOXYGENASE-2 INHIBITOR ON CYCLOOXYGENASE-2 GENE EXPRESSION AND GROWTH INHIBITION OF HUMAN LUNG CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    WANG Zhao-Xia; LU Bin-Bin; WANG Teng; YIN Yong-Mei; DE Wei; SHU Yong-Qian

    2007-01-01

    Background Gene therapy by adenovirus-mediated wild-type p53 gene transfer has been shown to inhibit lung cancer growth in vitro, in animal models, and in human clinical trials. The antitumor effect of selective cyclooxygenase (COX)-2 inhibitors has been demonstrated in preclinical studies. However, no information is available on the effects of p53 gene therapy combined with selective COX-2 inhibitor on COX-2 gene expression and growth inhibition of human lung cancer cells. Methods We evaluated the effects of recombinant adenovirus-p53 (Ad-p53) gene therapy combined with selective COX-2 inhibitor on the proliferation, apoptosis, cell cycle arrest of human lung adenocarcinoma A549 cell line, and the effects of tumor suppressor exogenous wild type p53 on COX-2 gene expression. Results Ad-p53 gene therapy combined with selective COX-2 inhibitor celecoxib shows significant synergistic inhibition effects on the growth of human lung adenocarcinoma A549 cell line. Exogenous p53 gene can suppress COX-2 gene expression. Conclusions Significant synergistic inhibition effects of A549 cell line by the combined Ad-p53 and selective COX-2 inhibitor celecoxib may be achieved by enhancement of growth inhibition, apoptosis induction and suppression of COX-2 gene expression. This study provides first evidence that the administration of p53 gene therapy in combination with COX-2 inhibitors might be a new clinical strategy for the treatment or prevention of NSCLC.

  1. Combined therapy using suicide gef gene and paclitaxel enhances growth inhibition of multicellular tumour spheroids of A-549 human lung cancer cells.

    Science.gov (United States)

    Prados, Jose; Melguizo, Consolacion; Rama, Ana; Ortiz, Raul; Boulaiz, Houria; Rodriguez-Serrano, Fernando; Caba, Octavio; Rodriguez-Herva, Jose Juan; Ramos, Juan Luis; Aranega, Antonia

    2008-07-01

    The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. The potential use of combined gene therapy is under intensive study. One approach uses the expression of genes encoding cytotoxic proteins that affect cellular viability. The gef gene from E. coli, identified as a member of a gene family encoding homologous cell-killing functions, encodes for a membrane protein with a toxic domain which leads to a decrease in the rate of tumour cell growth. To improve the antitumoral effect of the paclitaxel in lung cancer cells, we investigated a combined suicide gene therapy using this drug and gef gene in vitro, using A-549 lung cancer cells in culture and forming multicellular tumour spheroids (MTS). Our results showed that gef expression in A-549 cells led to an ultrastructural changes, including dilated mitochondria with clear matrices and disrupted cristae and cell surface alterations such as reduction in length and number of microvilli and cytoplasmic membrane evaginations. The use of paclitaxel in A-549 lung cancer cells transfected with gef gene enhanced the chemotherapeutic effect of this drug. Volume analyses showed an 87.4% decrease in the A-549 MTS growth after 96 h in comparison with control MTS. This inhibition was greater than that obtained using the gene therapy or chemotherapy alone. In conclusion, gef gene has a cytotoxic effect in lung cancer cells and enhances cell growth inhibition when used with paclitaxel. These results indicate that this combined therapy may be of potential therapeutic value in lung cancer.

  2. 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....

  3. Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer.

    Science.gov (United States)

    Misra, Santosh K; Ghoshal, Goutam; Gartia, Manas R; Wu, Zhe; De, Arun K; Ye, Mao; Bromfield, Corinne R; Williams, Emery M; Singh, Kuldeep; Tangella, Krishnarao V; Rund, Laurie; Schulten, Klaus; Schook, Lawrence B; Ray, Partha S; Burdette, Everette C; Pan, Dipanjan

    2015-11-24

    Repurposing of existing cancer drugs to overcome their physical limitations, such as insolubility, represents an attractive strategy to achieve enhanced therapeutic efficacy and broaden the range of clinical applications. Such an approach also promises to offer substantial cost savings in drug development efforts. Here we repurposed FDA-approved topical agent bexarotene (Targretin), currently in limited use for cutaneous manifestations of T-cell lymphomas, and re-engineer it for use in solid tumor applications by forming self-assembling nanobubbles. Physico-chemical characterization studies of the novel prodrug nanobubbles demonstrated their stability, enhanced target cell internalization capability, and highly controlled release profile in response to application of focused ultrasound energy. Using an in vitro model of hepatocellular carcinoma and an in vivo large animal model of liver ablation, we demonstrate the effectiveness of bexarotene prodrug nanobubbles when used in conjunction with catheter-based ultrasound, thereby highlighting the therapeutic promise of this trimodal approach.

  4. A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials

    Directory of Open Access Journals (Sweden)

    Xu L

    2016-07-01

    Full Text Available Liang Xu,1,2,* Xiaobo Wu,3,* Chun Hu,1,2 Zhiying Zhang,4 Le Zhang,1,2 Shujing Liang,1,2 Yingchun Xu,5 Fengchun Zhang1,2 1Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, 2Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 3Prevention and Cure Center of Breast Disease, Third Hospital of Nanchang, Nanchang, 4Graduate School, Xuzhou Medical College, Xuzhou, 5Department of Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Nowadays, the philosophy of treating metastatic breast cancer (MBC is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015 comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS, and the secondary end points were the progression-free survival (PFS, overall response rate (ORR, and grade 3 or 4 toxicities. The pooled hazard ratio (HR and pooled risk ratio (RR were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84–0.96, P=0.002, PFS (HR 0.81, 95% CI 0.76–0.88, P<0.001, and ORR (RR 1.72, 95% CI 1.34–2.21, P<0.001. Notably, subgroup analysis

  5. Antiproton Cancer Therapy

    DEFF Research Database (Denmark)

    Bassler, Niels

    An essential part in cancer radiotherapy, is to direct a sufficiently high dose towards the tumour, without damaging the surrounding tissue. Different techniques such as intensity modulated radiation therapy and proton therapy have been developed, in order to reduce the dose to the normal tissue...

  6. Receptor-Mediated Surface Charge Inversion Platform Based on Porous Silicon Nanoparticles for Efficient Cancer Cell Recognition and Combination Therapy.

    Science.gov (United States)

    Zhang, Feng; Correia, Alexandra; Mäkilä, Ermei; Li, Wei; Salonen, Jarno; Hirvonen, Jouni J; Zhang, Hongbo; Santos, Hélder A

    2017-03-22

    Negatively charged surface-modified drug delivery systems are promising for in vivo applications as they have more tendency to accumulate in tumor tissues. However, the inefficient cell uptake of these systems restricts their final therapeutic performance. Here, we have fabricated a receptor-mediated surface charge inversion nanoparticle made of undecylenic acid modified, thermally hydrocarbonized porous silicon (UnTHCPSi) nanoparticles core and sequentially modified with polyethylenimine (PEI), methotrexate (MTX), and DNA aptamer AS1411 (herein termed as UnTHCPSi-PEI-MTX@AS1411) for enhancing the cell uptake of nucleolin-positive cells. The efficient interaction of AS1411 and the relevant receptor nucleolin caused the disintegration of the negative-charged AS1411 surface. The subsequent surface charge inversion and exposure of the active targeting ligand, MTX, enhanced the cell uptake of the nanoparticles. On the basis of this synergistic effect, the UnTHCPSi-PEI-MTX@AS1411 (hydrodynamic diameter is 242 nm) were efficiently internalized by nucleolin-positive MDA-MB-231 breast cancer cells, with an efficiency around 5.8 times higher than that of nucleolin-negative cells (NIH 3T3 fibroblasts). The receptor competition assay demonstrated that the major mechanism (more than one-half) of the internalized nanoparticles in MDA-MB-231 cells was due to the receptor-mediated surface charge inversion process. Finally, after loading of sorafenib, the nanosystem showed efficient performance for combination therapy with an inhibition ratio of 35.6%.

  7. Overall survival benefits for combining targeted therapy as second-line treatment for advanced non-small-cell-lung cancer: a meta-analysis of published data.

    Directory of Open Access Journals (Sweden)

    Wei-Xiang Qi

    Full Text Available BACKGROUND: Combining targeted therapy has been extensively investigated in previously treated advanced non-small-cell lung cancer (NSCLC, but it is still unclear whether combining targeted therapy might offer any benefits against standard monotherapy with erlotinib. We thus performed a meta-analysis of randomized controlled trials to compare the efficacy and safety of combining targeted therapy versus erlotinib alone as second-line treatment for advanced NSCLC. METHODS: Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS, progression-free survival (PFS, overall response rate (ORR and grade 3 or 4 adverse event (AEs. The pooled hazard ratio (HR or odds ratio (OR, and 95% confidence intervals (CI were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: Eight eligible trials involved 2417 patients were ultimately identified. The intention to treatment (ITT analysis demonstrated that combining targeted therapy significantly improved OS (HR 0.90, 95% CI: 0.82-0.99, p = 0.024, PFS (HR 0.83, 95% CI: 0.72-0.97, p = 0.018, and ORR (OR 1.35, 95% CI 1.01-1.80, P = 0.04. Sub-group analysis based on phases of trials, EGFR-status and KRAS status also showed that there was a tendency to improve PFS and OS in combining targeted therapy, except that PFS for patients with EGFR-mutation or wild type KRAS favored erlotinib monotherapy. Additionally, more incidence of grade 3 or 4 rash, fatigue and hypertension were observed in combining targeted therapy. CONCLUSIONS: With the available evidence, combining targeted therapy seems superior over erlotinib monotherapy as second-line treatment for advanced NSCLC. More studies are still needed to identify patients who will most likely benefit from the appropriate combining targeted therapy.

  8. Androgen-deprivation therapy alone versus combined with radiation therapy or chemotherapy for nonlocalized prostate cancer: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Jun-Hao Lei

    2016-01-01

    Full Text Available In this paper, we reviewed the long-term survival outcomes, safety, and quality-of-life of androgen-deprivation therapy (ADT alone versus combined with radiation therapy (RT or chemotherapy for locally advanced and metastatic prostate cancer (PCa. A literature search was performed using OvidSP. Randomized controlled trials (RCTs that met the following criteria were included: including locally advanced or metastatic PCa, comparing ADT alone versus combined with any treatment method and reporting quantitative data of disease control or survival outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three compared ADT versus ADT plus RT (n = 2344 and one compared ADT versus ADT plus docetaxel-estramustine (n = 413 in locally advanced PCa; two compared ADT versus ADT plus docetaxel (n = 1175 and two compared ADT versus ADT plus estramustine (n = 114 in metastatic PCa. For locally advanced PCa, the addition of RT to long-term ADT can improve the outcomes of survival and tumor control with fully acceptable adverse effects. Specially, the pooled odds ratio (OR of overall survival (OS was 1.43 (95% confidence interval 1.20-1.71 when compared ADT plus RT with ADT alone (P < 0.0001. For metastatic hormonally sensitive PCa, the concurrent use of docetaxel plus ADT was effective and safe (pooled OR of OS: 1.29 [1.01-1.65]: P = 0.04. In all, long-term ADT plus RT and long-term ADT plus docetaxel should be considered as proper treatment option in locally advanced and metastatic hormonally sensitive PCa, respectively. The major limitation for the paper was that only eight RCTs were available.

  9. Curcumin–Piperine/Curcumin–Quercetin/Curcumin–Silibinin dual Drug-loaded Nanoparticulate Combination Therapy: A Novel Approach to Target and Treat Multidrug-resistant Cancers

    Directory of Open Access Journals (Sweden)

    C. Moorthi

    2013-01-01

    Full Text Available Curcumin is a functional food, which provides a wide range of health benefits including anti-cancer activity and considered as a suitable alternative for chemotherapeutic agents. However, cancer cells exhibit resistance to most chemotherapeutic agents including curcumin due to overexpression of adenosine triphosphate (ATP-binding cassette transporter proteins in the cancer cell membrane, which decrease the intracellular concentration of chemotherapeutic agents. Similarly, most chemotherapeutic agents including curcumin experience lack of cancer cell targeting, lack of aqueous solubility, rapid systemic clearance, intestinal metabolism and hepatic metabolism. These limitations hinder the clinical usefulness of curcumin in the treatment of multidrug-resistant cancers. In this article, we propose curcumin–piperine, or curcumin–quercetin or curcumin–silibinin dual drug-loaded nanoparticulate combination therapy to target and treat multidrug-resistant cancers. The proposed dual drug-loaded nanoparticulate combination is expected to reverse the multidrug resistance, prevent the rapid systemic clearance, prevent the intestinal and the hepatic metabolism, increase the aqueous solubility, enhance the bioavailability, target the cancer cells, produce a synergistic anti-cancer effect and enhance the efficacy of curcumin in the treatment of multidrug-resistant cancers.

  10. Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy

    Directory of Open Access Journals (Sweden)

    Jeyamohan P

    2013-07-01

    Full Text Available Prashanti Jeyamohan, Takashi Hasumura, Yutaka Nagaoka, Yasuhiko Yoshida, Toru Maekawa, D Sakthi Kumar Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Japan Abstract: The photothermal effect of single-walled carbon nanotubes (SWCNTs in combination with the anticancer drug doxorubicin (DOX for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX binds at physiological pH (pH 7.4 and is released only at a lower pH, ie, lysosomal pH (pH 4.0, which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light–heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy. Keywords: cancer, nanotherapy, SWCNTs, targeted drug delivery

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

    Directory of Open Access Journals (Sweden)

    Lu Han

    2013-04-01

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

  12. Factors contributing to risk for cancer among HIV-infected individuals, and evidence that earlier combination antiretroviral therapy will alter this risk

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Dubrow, Robert; Silverberg, Michael J

    2014-01-01

    PURPOSE OF REVIEW: To critically appraise recent published literature about factors associated with cancer risk likely to be influenced by combination antiretroviral therapy (cART) in HIV-infected individuals, and the potential of earlier cART initiation to reduce this risk. RECENT FINDINGS...... and epidemiological data have been reported as to whether (and how) cART affects NADM risk. Furthermore, secondary analyses of randomized controlled trials comparing early versus delayed cART initiation were inconclusive. SUMMARY: Continuous epidemiological surveillance is warranted to monitor trends in cancer...... incidence among HIV-infected individuals and to better understand the impact of earlier cART on NADM risk. The role of adjuvant anti-inflammatory or antithrombotic therapies to reduce cancer risk deserves further investigation....

  13. Doxorubicin in combination with a small TGFbeta inhibitor: a potential novel therapy for metastatic breast cancer in mouse models.

    Directory of Open Access Journals (Sweden)

    Abhik Bandyopadhyay

    Full Text Available BACKGROUND: Recent studies suggested that induction of epithelial-mesenchymal transition (EMT might confer both metastatic and self-renewal properties to breast tumor cells resulting in drug resistance and tumor recurrence. TGFbeta is a potent inducer of EMT and has been shown to promote tumor progression in various breast cancer cell and animal models. PRINCIPAL FINDINGS: We report that chemotherapeutic drug doxorubicin activates TGFbeta signaling in human and murine breast cancer cells. Doxorubicin induced EMT, promoted invasion and enhanced generation of cells with stem cell phenotype in murine 4T1 breast cancer cells in vitro, which were significantly inhibited by a TGFbeta type I receptor kinase inhibitor (TbetaRI-KI. We investigated the potential synergistic anti-tumor activity of TbetaR1-KI in combination with doxorubicin in animal models of metastatic breast cancer. Combination of Doxorubicin and TbetaRI-KI enhanced the efficacy of doxorubicin in reducing tumor growth and lung metastasis in the 4T1 orthotopic xenograft model in comparison to single treatments. Doxorubicin treatment alone enhanced metastasis to lung in the human breast cancer MDA-MB-231 orthotopic xenograft model and metastasis to bone in the 4T1 orthotopic xenograft model, which was significantly blocked when TbetaR1-KI was administered in combination with doxorubicin. CONCLUSIONS: These observations suggest that the adverse activation of TGFbeta pathway by chemotherapeutics in the cancer cells together with elevated TGFbeta levels in tumor microenvironment may lead to EMT and generation of cancer stem cells resulting in the resistance to the chemotherapy. Our results indicate that the combination treatment of doxorubicin with a TGFbeta inhibitor has the potential to reduce the dose and consequently the toxic side-effects of doxorubicin, and improve its efficacy in the inhibition of breast cancer growth and metastasis.

  14. The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

    Institute of Scientific and Technical Information of China (English)

    Rui-Yi Wu; Guo-Min Wang; Lei Xu; Bo-Heng Zhang; Ye-Qing Xu; Zhao-Chong Zeng; Bing Chen

    2011-01-01

    The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound (HIFU) combined with (+) low-dose external beam radiotherapy (LRT) as supplemental therapy for advanced prostate cancer (PCa) following hormonal therapy (HT). Our definition of HIFU+LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy (CRT). We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU+LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU+LRT treatment. There were significant differences among four groups with regard to overall survival (OS) and disease-specific survival (DSS) curves (P=0.018 and 0.015). Further comparison between each pair of groups suggested that the long-term DSS of the HIFU+LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU+LRT group and the CRT group. Multivariable Cox's proportional hazard model showed that both HIFU+LRT and CRT were independently associated with DSS (P=0.001 and 0.035) and had protective effects with regard to the risk of death. Compared with CRT, HIFU+LRT significantly decreased incidences of radiation-related late gastrointestinal (GI) and genitourinary (GU) toxicity grade ≥II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and regional lymph node metastases after HT. As an alternative to CRT, HIFU+LRT showed good efficacy and better safety.

  15. Engineering of lipid prodrug-based, hyaluronic acid-decorated nanostructured lipid carriers platform for 5-fluorouracil and cisplatin combination gastric cancer therapy

    Directory of Open Access Journals (Sweden)

    Qu CY

    2015-06-01

    Full Text Available Chun-Ying Qu,1,* Min Zhou,1,* Ying-wei Chen,2 Mei-mei Chen,3 Feng Shen,1 Lei-Ming Xu11Digestive Endoscopic Diagnosis and Treatment Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, People’s Republic of China; 3Digestive Department, Xinhua Hospital, School of medicine, Shanghai Jiaotong University, Shanghai, People’s Republic of China*These authors contributed equally to this workPurpose: The first-line chemotherapy treatment protocol for gastric cancer is combination chemotherapy of 5-fluorouracil (5-FU and cisplatin (CDDP. The aim of this study was to engineer prodrug-based nanostructured lipid carriers (NLC platform for codelivery of 5-FU and CDDP to enhance therapy and decrease toxicity.Methods: First, 5-FU-stearic acid lipid conjugate was synthesized by two steps. Second, 5-FU-stearic acid prodrug and CDDP were loaded in NLC. Finally, hyaluronic acid (HA was coated onto NLC surface. Average size, zeta potential, and drug loading capacity of NLC were evaluated. Human gastric cancer cell line BGC823 (BGC823 cells was used for the testing of in vitro cytotoxicity assays. In vivo antitumor activity of NLC was evaluated in mice bearing BGC823 cells model.Results: HA-coated 5-FU-stearic acid prodrug and CDDP-loaded NLC (HA-FU/C-NLC showed a synergistic effect in combination therapy and displayed the greatest antitumor activity than all of the free drugs or uncoated NLC in vitro and in vivo.Conclusion: This work reveals that HA-coated NLC could be used as a novel carrier to codeliver 5-FU and CDDP for gastric cancer therapy. HA-FU/C-NLC could be a promising targeted and combinational therapy in nanomedicine.Keywords: gastric cancer, nanostructured lipid carriers, hyaluronic acid, combination chemotherapy, lipid prodrug

  16. Gold nanoshelled liquid perfluorocarbon nanocapsules for combined dual modal ultrasound/CT imaging and photothermal therapy of cancer.

    Science.gov (United States)

    Ke, Hengte; Yue, Xiuli; Wang, Jinrui; Xing, Sen; Zhang, Qian; Dai, Zhifei; Tian, Jie; Wang, Shumin; Jin, Yushen

    2014-03-26

    The integration of multimodal contrast-enhanced diagnostic imaging and therapeutic capabilities could utilize imaging guided therapy to plan the treatment strategy based on the diagnostic results and to guide/monitor the therapeutic procedures. Herein, gold nanoshelled perfluorooctylbromide (PFOB) nanocapsules with PEGylation (PGsP NCs) are constructed by oil-in-water emulsion method to form polymeric PFOB nanocapsules, followed by the formation of PEGylated gold nanoshell on the surface. PGsP NCs could not only provide excellent contrast enhancement for dual modal ultrasound and CT imaging in vitro and in vivo, but also serve as efficient photoabsorbers for photothermal ablation of tumors on xenografted nude mouse model. To our best knowledge, this is the first report of gold nanoshell serving as both CT contrast agents and photoabsorbers for photothermal therapy. The novel multifunctional nanomedicine would be of great value to offer more comprehensive diagnostic information to guide more accurate and effective cancer therapy.

  17. Radiation Therapy for Lung Cancer

    Science.gov (United States)

    ... of the lung cancer and your overall health. Radiation Therapy Radiation is a high-energy X-ray that can ... surgery, chemotherapy or both depending upon the circumstances. Radiation therapy works within cancer cells by damaging their ...

  18. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor\\'s vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  19. Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer

    NARCIS (Netherlands)

    Piccart-Gebhart, Martine J.; Burzykowski, Tomasz; Buyse, Marc; Sledge, George; Carmichael, James; Lueck, Hans-Joachim; Mackey, John R.; Nabholtz, Jean-Marc; Paridaens, Robert; Biganzoli, Laura; Jassem, Jacek; Bontenbal, Marijke; Bonneterre, Jacques; Chan, Stephen; Basaran, Gul Atalay; Therasse, Patrick

    2008-01-01

    Purpose Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, prog

  20. Combined therapy with {sup 131}I and retinoic acid in Korean patients with radioiodine-refractory papillary thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oh, So Won [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University Boramae Medical Center, Department of Nuclear Medicine, Seoul (Korea, Republic of); Moon, Seung-hwan; Chung, June-Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Park, Do Joon; Cho, Bo Youn [Seoul National University College of Medicine, Department of Internal Medicine, Seoul (Korea, Republic of); Jung, Kyeong Cheon [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Lee, Dong Soo [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Seoul National University WCU Graduate School of Convergence Science and Technology, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul (Korea, Republic of)

    2011-10-15

    The aim of this study was to assess the clinical outcome of redifferentiation therapy using retinoic acid (RA) in combination with {sup 131}I therapy, and to identify biological parameters that predict therapeutic response in Korean patients with radioiodine-refractory papillary thyroid carcinoma (PTC). A total of 47 patients (13 men, 34 women; age 54.2 {+-} 13.6 years) with radioiodine-refractory PTC underwent therapy consisting of consecutive treatment with {sup 131}I and RA. Each {sup 131}I/RA treatment cycle involved the administration of oral isotretinoin for 6 weeks at 1-1.5 mg/kg daily followed by a single oral dose of {sup 131}I (range 5.5-16.7 GBq). Therapeutic responses were determined using serum thyroglobulin (Tg) levels and the change in tumour size 6 months after completing the {sup 131}I/RA therapy. Biological parameters and pathological parameters before and after combined therapy were compared. After completing {sup 131}I/RA therapy, 1 patient showed a complete response, 9 partial response, 9 stable disease, and 28 progressive disease, representing an overall response rate of 21.3%. Univariate analysis revealed that an age of <45 years and a persistently high serum Tg level were related to a good response. No clinical response was achieved when metastases showing no iodine uptake were present. Multivariate regression analysis showed that an age of <45 years was significantly associated with a good response. Of the 24 patients with well-differentiated carcinoma, 5 (20.8%) responded to {sup 131}I/RA therapy, whereas all 6 patients with poorly differentiated carcinoma failed to respond. {sup 131}I/RA therapy was found to elicit a response rate of 21.3% among patients with radioiodine-refractory PTC, and an age of <45 years was found to be significantly associated with a good response. (orig.)

  1. Accelerators for Cancer Therapy

    Science.gov (United States)

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  2. Nano-assemblies of J-aggregates based on a NIR dye as a multifunctional drug carrier for combination cancer therapy.

    Science.gov (United States)

    Song, Xuejiao; Zhang, Rui; Liang, Chao; Chen, Qian; Gong, Hua; Liu, Zhuang

    2015-07-01

    The combination of chemotherapy with photothermal therapy, which may lead to improved therapeutic efficacies and reduced side effects of conventional chemotherapy, would require safe drug delivery systems (DDSs) with strong near-infrared (NIR) absorbance, efficient drug loading, and effective tumor homing ability. Herein, we fabricate nano-assemblies containing J-aggregates of a NIR dye, IR825, for drug delivery and combined photothermal & chemotherapy of cancer. It is found that IR825 could be complexed with a low-molecular-weight cationic polymer polyethylenimine (PEI), forming IR825@PEI J-aggregates with greatly enhanced NIR absorbance red-shifted to 915 nm. Those nano-assemblies of J-aggregates are further modified with polyethylene glycol (PEG), obtaining IR825@PEI-PEG nano-complex which exhibits great dispersity in physiological solutions, excellent photostability, and is able to efficiently load chemotherapeutic drug doxorubicin (DOX) via a unique strategy different from drug loading in conventional amphiphilic polymer-based DDSs. In vivo animal experiments uncover that IR825@PEI-PEG/DOX upon intravenous injection into tumor-bearing mice shows rather high tumor uptake as illustrated by photoacoustic imaging. In vivo combined photothermal & chemotherapy is then carried out, demonstrating great synergistic anti-tumor therapeutic effect remarkably superior to those achieved by the respective mono-therapies. Hence, we present a novel type of nanoscale DDSs based on nano-assemblies of small molecules without involving amphiphilic polymers, promising for imaging-guided combination cancer therapy.

  3. Self-immolative nanoparticles for simultaneous delivery of microRNA and targeting of polyamine metabolism in combination cancer therapy.

    Science.gov (United States)

    Xie, Ying; Murray-Stewart, Tracy; Wang, Yazhe; Yu, Fei; Li, Jing; Marton, Laurence J; Casero, Robert A; Oupický, David

    2017-01-28

    Combination of anticancer drugs with therapeutic microRNA (miRNA) has emerged as a promising anticancer strategy. However, the promise is hampered by a lack of desirable delivery systems. We report on the development of self-immolative nanoparticles capable of simultaneously delivering miR-34a mimic and targeting dysregulated polyamine metabolism in cancer. The nanoparticles were prepared from a biodegradable polycationic prodrug, named DSS-BEN, which was synthesized from a polyamine analog N(1),N(11)-bisethylnorspermine (BENSpm). The nanoparticles were selectively disassembled in the cytoplasm where they released miRNA. Glutathione (GSH)-induced degradation of self-immolative linkers released BENSpm from the DSS-BEN polymers. MiR-34a mimic was effectively delivered to cancer cells as evidenced by upregulation of intracellular miR-34a and downregulation of Bcl-2 as one of the downstream targets of miR-34a. Intracellular BENSpm generated from the degraded nanoparticles induced the expression of rate-limiting enzymes in polyamine catabolism (SMOX, SSAT) and depleted cellular natural polyamines. Simultaneous regulation of polyamine metabolism and miR-34a expression by DSS-BEN/miR-34a not only enhanced cancer cell killing in cultured human colon cancer cells, but also improved antitumor activity in vivo. The reported findings validate the self-immolative nanoparticles as delivery vectors of therapeutic miRNA capable of simultaneously targeting dysregulated polyamine metabolism in cancer, thereby providing an elegant and efficient approach to combination nanomedicines.

  4. Unmet Medical Needs in Non-Small-Cell Lung Cancer Treatment: How to Design Pre-Emptive Combination Therapies

    Directory of Open Access Journals (Sweden)

    Niki Karachaliou

    2014-11-01

    Full Text Available The rapidly expanding catalogue of human oncogenic mutations, coupled with difficulties in identifying the cellular targets of active compounds in phenotypic screens, has refocused drug discovery efforts on inhibitors of specific cellular proteins. This new ‘target-based’ approach has enjoyed some spectacular successes in several types of tumours, including non-small-cell lung cancer (NSCLC. Epidermal growth factor receptor (EGFR mutations occur in 17% of NSCLC patients, with notable response to single agent therapy. Unfortunately, all patients eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs, while complete remission rate to EGFR TKIs monotherapy is low. Priming BIM, a proapoptotic signalling BH3-only protein, induces sensitivity to erlotinib [Tarceva®] in EGFR-mutant cell lines. Synthetic lethal approaches and pre-emptive therapies based on the initial expression of BIM may significantly improve treatment outcomes. EGFR mutations result in transient pro-death imbalance of survival and apoptotic signalling in response to EGFR inhibition. Src homology 2 domain-containing phosphatase 2 is essential to the balance between extracellular signal-regulated kinase, phosphoinositide- 3-kinase/protein kinase B and signal transducer and activator of transcription 3 activity. Furthermore, stromal hepatocyte growth factor confers EGFR TKI resistance and induces inter-receptor crosstalk with Ephrin Type-A receptor 2, CDCP1, AXL, and JAK1. A better understanding of the complex cancer molecular biology of EGFR mutant lung cancer is crucial for development of effective treatment and design of successful future clinical studies.

  5. Fertility and cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Maguire, L.C.

    1979-05-01

    With increased survival of increasing numbers of cancer patients as a result of therapy, the consequences, early and late, of the therapies must be realized. It is the treating physician's duty to preserve as much reproductive potential as possible for patients, consistent with adequate care. With radiotherapy this means shielding the gonads as much as possible, optimal but not excessive doses and fields, oophoropexy, or sperm collection and storage prior to irradiation. With chemotherapy it means the shortest exposure to drugs consistent with best treatment and prior to therapy the collection and storage of sperm where facilities are available. At present this is still an experimental procedure. Artificial insemination for a couple when the male has received cancer therapy is another alternative. Finally, it is the responsibility of physicians caring for patients with neoplasms to be knowledgeable about these and all other effects of therapy so that patients may be counseled appropriately and understand the implications of therapy for their life.

  6. 3D dosimetry in patients with early breast cancer undergoing Intraoperative Avidination for Radionuclide Therapy (IART {sup registered}) combined with external beam radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferrari, Mahila E.; Cremonesi, Marta; Di Dia, Amalia; Botta, Francesca; Pedroli, Guido [European Institute of Oncology, Division of Medical Physics, Milan (Italy); De Cicco, Concetta; Calabrese, Michele; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Sarnelli, Anna [IRCCS Istituto Romagnolo per lo Studio e la Cura dei Tumori, Medical Physics Unit, Meldola, FC (Italy); Pedicini, Piernicola [Centro Regionale Oncologico Basilicata (IRCCS-CROB), Department of Radiation Oncology, Rionero in Vulture, PZ (Italy); Orecchia, Roberto [European Institute of Oncology, Division of Radiotherapy, Milan (Italy)

    2012-11-15

    Intraoperative Avidination for Radionuclide Therapy (IART {sup registered}) is a novel targeted radionuclide therapy recently used in patients with early breast cancer. It is a radionuclide approach with {sup 90}Y-biotin combined with external beam radiotherapy (EBRT) to release a boost of radiation in the tumour bed. Two previous clinical trials using dosimetry based on the calculation of mean absorbed dose values with the hypothesis of uniform activity distribution (MIRD 16 method) assessed the feasibility and safety of IART {sup registered}. In the present retrospective study, a voxel dosimetry analysis was performed to investigate heterogeneity in distribution of the absorbed dose. The aim of this work was to compare dosimetric and radiobiological evaluations derived from average absorbed dose vs. voxel absorbed dose approaches. We evaluated 14 patients who were injected with avidin into the tumour bed after conservative surgery and 1 day later received an intravenous injection of 3.7 GBq of {sup 90}Y-biotin (together with 185 MBq {sup 111}In-biotin for imaging). Sequential images were used to estimate the absorbed dose in the target region according to the standard dosimetry method (SDM) and the voxel dosimetry method (VDM). The biologically effective dose (BED) distribution was also evaluated. Dose/volume and BED volume histograms were generated to derive equivalent uniform BED (EUBED) and equivalent uniform dose (EUD) values. No ''cold spots'' were highlighted by voxel dosimetry. The median absorbed-dose in the target region was 20 Gy (range 15-27 Gy) by SDM, and the median EUD was 20.4 Gy (range 16.5-29.4 Gy) by the VDM; SDM and VDM estimates differed by about 6 %. The EUD/mean voxel absorbed dose ratio was >0.9 in all patients, indicative of acceptable uniformity in the target. The median BED and EUBED values were 21.8 Gy (range 15.9-29.3 Gy) and 22.8 Gy (range 17.3-31.8 Gy), respectively. VDM highlighted the absence of significant

  7. Doxorubicin/gold-loaded core/shell nanoparticles for combination therapy to treat cancer through the enhanced tumor targeting.

    Science.gov (United States)

    Kim, Kyungim; Oh, Keun Sang; Park, Dal Yong; Lee, Jae Young; Lee, Beom Suk; Kim, In San; Kim, Kwangmeyung; Kwon, Ick Chan; Sang, Yoon Kim; Yuk, Soon Hong

    2016-04-28

    A combination therapy consisting of radiotherapy and chemotherapy is performed using the core/shell nanoparticles (NPs) containing gold NPs and doxorubicin (DOX). Gold NPs in the core/shell NPs were utilized as a radiosensitizer. To examine the morphology and size distribution of the core/shell NPs, transmittance electron microscopy and dynamic light scattering were used. The in vitro release behavior, cellular uptake and toxicity were also observed to verify the functionality of the core/shell NPs as a nanocarrier. To demonstrate the advantage of the core/shell NPs over traditional gold NPs reported in the combination therapy, we evaluated the accumulation behavior of the core/shell NPs at the tumor site using the biodistribution. Antitumor efficacy was observed with and without radiation to evaluate the role of gold NPs as a radiosensitizer.

  8. Boron neutron capture therapy: Moving toward targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Hamid Reza Mirzaei

    2016-01-01

    Full Text Available Boron neutron capture therapy (BNCT occurs when a stable isotope, boton-10, is irradiated with low-energy thermal neutrons to yield stripped down helium-4 nuclei and lithium-7 nuclei. It is a binary therapy in the treatment of cancer in which a cytotoxic event is triggered when an atom placed in a cancer cell. Here, we provide an overview on the application of BNCT in cancer therapy as well as current preclinical and clinical evidence on the efficacy of BNCT in the treatment of melanoma, brain tumors, head and neck cancer, and thyroid cancer. Several studies have shown that BNCT is effective in patients who had been treated with a full dose of conventional radiotherapy, because of its selectivity. In addition, BNCT is dependent on the normal/tumor tissue ratio of boron distribution. Increasing evidence has shown that BNCT can be combined with different drug delivery systems to enhance the delivery of boron to cancer cells. The flexibility of BNCT to be used in combination with different tumor-targeting approaches has made this strategy a promising option for cancer therapy. This review aims to provide a state-of-the-art overview of the recent advances in the use of BNCT for targeted therapy of cancer.

  9. Inhibition of the Akt, cyclooxygenase-2, and matrix metalloproteinase-9 pathways in combination with androgen deprivation therapy: potential therapeutic approaches for prostate cancer.

    Science.gov (United States)

    Miyamoto, Hiroshi; Altuwaijri, Saleh; Cai, Yi; Messing, Edward M; Chang, Chawnshang

    2005-09-01

    Prostate cancer cells are generally dependent on androgen stimulation mediated by the androgen receptor (AR) for growth and survival, and, therefore, hormonal manipulation, such as castration and/or the use of AR antagonists, results in a regression of the cancer. However, this treatment very rarely leads to the "cure" of advanced disease, and cancers eventually become androgen-independent. A number of genes/pathways have been reported to be activated in prostate cancer, most of which are possibly associated with disease progression. In this article, among them, we focus on Akt (also known as protein kinase B), cyclooxygenase (COX)-2, and matrix metalloproteinase (MMP)-9, whose activities or expressions have been found to be regulated by androgens/AR. Previous studies by us and others, with androgen-sensitive prostate cancer cell lines, have demonstrated that androgen deprivation results in activation/overexpression of Akt, COX-2, and MMP-9 in cells. This suggests that androgen deprivation in clinical settings activates the Akt, COX-2, and MMP-9 pathways in prostate cancer, which may increase cell growth and in turn promote the transition to the androgen-independent state. We hypothesize that androgen deprivation, in combination with inhibition of the Akt, COX-2, and MMP-9 pathways, delays the androgen-independent transition and has more beneficial effects than hormonal therapy alone.

  10. Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    LIANG Xiao-bo; HOU Sheng-huai; Li Yao-ping; WANG Li-chun; ZHANG Xin; YANG Jun

    2010-01-01

    Background To compare clinical efficacy and toxicity of irinotecan combined with 5-fluorouracil and leucovorin with those of oxaliplatin combined with 5-fiuorouracil and leucovorin as first-line therapy for advanced colorectal cancer.Methods Literature search was performed by keywords "irinotecan", "oxaliplatin" and "colorectal cancer" on all randomized controlled trails reported on irinotecan versus oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer in MEDLINE, OVID, Springer, Cochrane Controlled Trials Register (CCTR) and CBMdisc (Chinese Biology and Medicine disc) before January 2010. Two authors drew the details of trial design, characteristics of patients, outcomes, and toxicity from the studies included. Data analysis was performed by RevMan 4.2.Results According to the screening criteria, 7 clinical studies with 2095 participants of advanced colorectal cancer were included in this meta analysis. The baseline characteristics of irinotecan group were similar to those of oxaliplatin group.The response rate of oxaliplatin group was higher than that of irinotecan group (relative risk (RR)=0.82, 95% confidence interval (95%CI) (0.70, 0.96), P=0.01), and the median overall survival of oxaliplatin group was longer by 2.04 months than that of irinotecan group (95%CI (-3.54, -0.54), P=0.008). In the comparison of grade 3-4 toxicity between the two groups, the incidences of nausea, emesis, diarrhoea and alopecia in irinotecan group were higher than those in oxaliplatin group (RR=1.94, 95%CI(1.22, 3.09), P=0.005; 1.71, 95%CI (1.34, 2.18), P <0.001; 14.56, 95%CI (4.11,51.66), P <0.0001), respectively. However, the incidence of neurotoxicity, neutropenia and thrombocytopenia in irinotecan group were lower than those in oxaliplatin group (RR=0.06, 95%CI(0.03, 0.14), P <0.00001; 0.70, 95%CI(0.55, 0.91), P=0.006; 0.18, 95%CI(0.05, 0.61), P=0.006), respectively.Conclusions Both irinotecan and oxaliplatin combined

  11. Killing effect of EGFR-TKI combined with 125I seed implantation therapy onⅢB-Ⅳ stage lung cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Ai-Sheng Xiang

    2016-01-01

    Objective:To analyze the killing effect of EGFR-TKI combined with 125I seed implantation therapy onⅢB-Ⅳ stage lung cancer tissue.Methods:A total of 78 patients withⅢB-Ⅳ stage lung cancer were randomly divided into observation group and control group (n=39), control group received EGFR-TKI treatment and observation group received EGFR-TKI combined with 125I seed implantation therapy. Differences in apoptosis gene, invasion gene and autophagy gene expression in lung tissue were compared between two groups after 1 month of treatment.Results:Apoptosis genesPDCD5, bax andbcl-xSmRNA expression levels in lung tissue of observation group after 1 month of treatment were higher than those of control group whileBag-1, survivin andbcl-xL mRNA expression levels were lower than those of control group; invasion genesCD147, EGFRandDDX17 mRNA expression levels were lower than those of control group while Bin1, E-cadherin andOvol2mRNA expression levels were higher than those of control group; autophagy genes ARHI, Beclin1, Atg5, LC3B, pULK andPI3KC3 mRNA expression levels were higher than those of control group.Conclusions: EGFR-TKI combined with 125I seed implantation therapy can enhance the tumor killing effect on patients withⅢB-Ⅳ stage lung cancer, and contribute to the optimization of overall condition and the extension of survival time.

  12. Building immunity to cancer with radiation therapy.

    Science.gov (United States)

    Haikerwal, Suresh J; Hagekyriakou, Jim; MacManus, Michael; Martin, Olga A; Haynes, Nicole M

    2015-11-28

    Over the last decade there has been a dramatic shift in the focus of cancer research toward understanding how the body's immune defenses can be harnessed to promote the effectiveness of cytotoxic anti-cancer therapies. The ability of ionizing radiation to elicit anti-cancer immune responses capable of controlling tumor growth has led to the emergence of promising combination-based radio-immunotherapeutic strategies for the treatment of cancer. Herein we review the immunoadjuvant properties of localized radiation therapy and discuss how technological advances in radio-oncology and developments in the field of tumor-immunotherapy have started to revolutionize the therapeutic application of radiotherapy.

  13. Synergistic enhancement of cancer therapy using a combination of docetaxel and photothermal ablation induced by single-walled carbon nanotubes

    Directory of Open Access Journals (Sweden)

    Zhang ZZ

    2011-10-01

    Full Text Available Lei Wang1, Mingyue Zhang1, Nan Zhang1, Jinjin Shi1, Hongling Zhang1, Min Li1, Chao Lu2, Zhenzhong Zhang1 1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2University of Maryland, College Park, MD, USA Background: Single-walled carbon nanotubes (SWNT are poorly soluble in water, so their applications are limited. Therefore, aqueous solutions of SWNT, designed by noncovalent functionalization and without toxicity, are required for biomedical applications. Methods: In this study, we conjugated docetaxel with SWNT via p-p accumulation and used a surfactant to functionalize SWNT noncovalently. The SWNT were then conjugated with docetaxel (DTX-SWNT and linked with NGR (Asn-Gly-Arg peptide, which targets tumor angiogenesis, to obtain a water-soluble and tumor-targeting SWNT-NGR-DTX drug delivery system. Results: SWNT-NGR-DTX showed higher efficacy than docetaxel in suppressing tumor growth in a cultured PC3 cell line in vitro and in a murine S180 cancer model. Tumor volumes in the S180 mouse model decreased considerably under near-infrared radiation compared with the control group. Conclusion: The SWNT-NGR-DTX drug delivery system may be promising for high treatment efficacy with minimal side effects in future cancer therapy. Keywords: single-walled carbon nanotubes, docetaxel, NGR peptide, tumor-targeting, near-infrared radiation

  14. Targeted therapies in gastroesophageal cancer.

    Science.gov (United States)

    Kasper, Stefan; Schuler, Martin

    2014-05-01

    Gastroesophageal cancers comprising gastric cancer (GC), and cancers of the distal oesophagus and gastroesophageal junction (GEJ) are a global health threat. In Western populations the incidence of GC is declining which has been attributed to effective strategies of eradicating Helicobacter pylori infection. To the contrary, GEJ cancers are on the rise, with obesity and reflux disease being viewed as major risk factors. During the past decade perioperative chemotherapy, pre- or postoperative radio-chemotherapy, and, in Asian populations, adjuvant chemotherapy have been shown to improve the outcome of patients with advanced GC and GEJ cancers suited for surgery. Less progress has been made in the treatment of metastatic disease. The introduction of trastuzumab in combination with platinum/fluoropyrimidine-based chemotherapy for patients with HER2-positive disease has marked a turning point. Recently, several novel agents targeting growth factor receptors, angiogenic pathways, adhesion molecules and mediators of intracellular signal transduction have been clinically explored. Here we summarise the current status and future developments of molecularly targeted therapies in GC and GEJ cancer.

  15. Application and possible mechanisms of combining LLLT (low level laser therapy), infrared hyperthermia and ionizing radiation in the treatment of cancer

    Science.gov (United States)

    Abraham, Edward H.; Woo, Van H.; Harlin-Jones, Cheryl; Heselich, Anja; Frohns, Florian

    2014-02-01

    Benefit of concomitant infrared hyperthermia and low level laser therapy and ionizing radiation is evaluated in this study. The purpose/objectives: presentation with locally advanced bulky superficial tumors is clinically challenging. To enhance the efficacy of chemotherapy and IMRT (intensity-modulated radiation therapy) and/or electron beam therapy we have developed an inexpensive and clinically effective infrared hyperthermia approach that combines black-body infrared radiation with halogen spectrum radiation and discrete wave length infrared clinical lasers LLLT. The goal is to produce a composite spectrum extending from the far infrared to near infrared and portions of the visible spectrum with discrete penetrating wavelengths generated by the clinical infrared lasers with frequencies of 810 nm and/or 830 nm. The composite spectrum from these sources is applied before and after radiation therapy. We monitor the surface and in some cases deeper temperatures with thermal probes, but use an array of surface probes as the limiting safe thermal constraint in patient treatment while at the same time maximizing infrared entry to deeper tissue layers. Fever-grade infrared hyperthermia is produced in the first centimeters while non-thermal infrared effects act at deeper tissue layers. The combination of these effects with ionizing radiation leads to improved tumor control in many cancers.

  16. Combined 2-deoxy glucose and metformin improves therapeutic efficacy of sodium-iodide symporter-mediated targeted radioiodine therapy in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Chatterjee S

    2015-08-01

    Full Text Available Sushmita Chatterjee, Nirmal Thaker, Abhijit DeMolecular Functional Imaging Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, IndiaAbstract: Radiosensitization using either metformin or 2-deoxy-d-glucose (2-DG in various cancer cells has been reported. The present study reveals novel information on combining these drugs to enhance radiosensitization effect in breast cancer (BC cells. Responses to low-dose Cobalt60 radiation, as well as a newly emerged radioiodine therapy target for BC, that is, sodium-iodide symporter (NIS or SLC5A5 protein, are tested. As therapeutic potential of NIS in BC is often limited due to low uptake and fast efflux rate of iodine, the scope of these two radiosensitizers to further improve NIS-mediated 131I therapeutic efficacy is explored. Two BC cell lines, MCF-7, and MDA MB231 are tested to optimize minimal drug doses required for radiosensitization. A combination of 2 mM metformin and 20 mM 2-DG with 2 grey (Gy Cobalt60 radiation shows significant radiosensitization effect (P=0.0002. In cells treated with the combination therapy, increased γH2A.X foci formation was noted. Further, MCF-7 BC cells overexpressing NIS (MCF-7 NIS was established, and using the optimized drug concentrations, significant radiosensitization (P=0.0019 by 50 µ Ci 131I usage was found to be the case as well. Apoptosis data corroborates with the result of clonogenic assay showing significant increase in apoptotic population upon dual drug-mediated radiosensitization. In case of metformin treatment, lowered adenosine triphosphate (ATP content of the cell has been observed. The encouraging radiosensitization effect observed using combined 2-DG and metformin may aid in reducing Cobalt60 radiation exposure or for targeted radioiodine therapy in BC cells with NIS expression. This study indicates high potential of this drug combination in sensitizing BC cells for NIS

  17. Combined therapy of p53-wt and drug in an orthotopic multidrug-resistant human lung cancer model

    Institute of Scientific and Technical Information of China (English)

    高振强; 高志萍; 张涛

    1997-01-01

    Balb/c nu/nu mice were inoculated intratracheally with multidrug-resistant human lung cancer cells GLK containing p53 mutation at codon 245 and treated with intratracheal instillation of p53-wt retroviral vector (pDOR53W) to increase cell chemosensitivity, and then with intraperitoneal injection of doxorubicin. 30 d after tumor cell inoculation, 75% of the control mice showed macroscopic tumors in the lung. Sole pDOR53W suppressed GLK tumor formation in 68 % of mice; sole doxorubicin 33. 3 % , but the combination of pDOR53W and doxorubicin 88.9%. The exogenous p53 sequence was detected and confirmed in the tumor that grew after treatment with pDOR53W retroviral vector by PCR and Southern blot hybridization with p53 cDNA. These results suggested that di-rect administration of a retroviral vector expressing p53-wt combined with treatment of anticancer agent was an effec-tive therapeutic method for multidrug-resistant human lung cancer.

  18. Targeted therapies for cancer

    Science.gov (United States)

    ... types of these cancers: Leukemia and lymphoma Breast cancer Colon cancer Skin cancer Lung cancer Prostate Other cancers ... ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 44. Review Date 9/13/2015 Updated by: Todd Gersten, ...

  19. The effect of TACE combined with tumor interstitial therapy on immune globulin, complement and T lymphocyte subsets in patients with liver cancer

    Institute of Scientific and Technical Information of China (English)

    Bu-Tian Li; Sheng-Ping Zhang

    2016-01-01

    Objective:To explore the effect of TACE combined with interstitial therapy on immune globulin, complement and T lymphocyte subsets in patients with liver cancer.Methods:A total of 95 patients with liver cancer from March 2013 to April 2015 in the hospital were selected, and they were randomly divided into group A (n = 47) and group B (n=48), patients in group A were given simple TACE treatment, while patients in group B underwent TACE + tumor interstitial therapy (percutaneous liver tumor injection of lipiodol chemotherapy). Immune globulin, complement and T lymphocyte subsets in peripheral blood preoperative 1w and postoperative 4w were observed.Results: After treatment, the lipiodol deposition rate, local control rate and tumor reduction rate of group B were significantly higher than that in group A, which had statistically significant difference between the two groups. Compared with that before treatment, CD3+, CD4+, CD4+/CD8+ were significantly increased, CD8+ was significantly decreased after treatment. There were significantly differences in CD3+, CD4+, CD4+/CD8+, CD8+ between the two groups after treatment. The immune globulin and complement levels increased in group A after treatment, but had no significant difference. Immunoglobulin and complement levels increased significantly in group B, there were significantly differences in immunoglobulin and complement levels in the two groups after treatment.Conclusions:The results showed that single TACE treatment in patients with liver cancer could enhance immune function, which had little effect on the humoral immunity. TACE combined with interstitial therapy could improve patients' cellular immunity and humoral immunity, which was benefit for prognosis.

  20. The marriage of conventional cancer treatments and alternative cancer therapies.

    Science.gov (United States)

    Decker, Georgia M

    2008-06-01

    The terms "alternative" or "unconventional" have been used to describe any therapy used instead of conventional approaches. Conventional approaches, known as "standard" or "traditional" or "biomedical" approaches, have had broad application in Western medicine. Complementary and alternative medicine has been referred to as "integrative," "integrated," or "complementary" when therapies are combined with conventional approaches, such as those for cancer.

  1. Gene therapy of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ruben Hernandez-Alcoceba; Bruno Sangro; Jesus Prieto

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/prodrug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition,gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy.These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer.

  2. Re: Final Report of the Intergroup Randomized Study of Combined AndrogenDeprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Malcolm D. Mason

    2015-06-01

    Full Text Available No certain treatment recommendations were given for locally advanced or high-risk prostate cancer in the European Association of Urology (EAU guidelines (1. In the guidelines, studies supporting surgery or radiotherapy (RT were listed, and the readers were left alone to make their own decisions. In the present study, Mason et al. reported the impact of adding RT to androgen deprivation therapy (ADT. One thousand two hundred and five patients with T3- 4, N0/Nx, M0 prostate cancer or T1-2 disease with either PSA more than 40 μg/L or PSA 20 to 40 μg/L plus Gleason score of 8 to 10 were randomized to ADT alone (n=602 or to ADT+RT (n=603. A lower dose radiation 64 to 69 Gy was used for RT. Overall survival (OS risk reduction was 30% for ADT+RT group (P<0.001 at a median follow-up of 8 years. Cancer-specific survival (CSS was significantly improved by the addition of RT to ADT (HR: 0.46, 95% CI: 0.34 to 0.61; p<0.001. Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity. However, reported frequency of ADT-related toxicities (impotence, hot flushes, urinary frequency, ischemia, and hypertension were similar for both arms. The present study provided results of high-risk patients in a longer median follow-up time than SPCG-7 study (2. Because the study took place between 1995 and 2005, less than 70 Gy was used for RT. Even at lower radiation doses, the authors confirmed that adding RT to ADT improved both OS and cancer-specific survival (CSS with minimal general toxicity. In the modern era, improved RT techniques may help achieve better outcomes with much higher radiation doses without increased morbidity in this group of patients

  3. Effect of herceptin combined with second-line therapy paclitaxel + S-1 on malignant degree and angiogenesis in patients with HER-2-positive gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Lei-Fan Li; Xiu-Yun Wang; Hui-Qiong Xu; Xia Liu

    2016-01-01

    Objective:To analyze the effect of herceptin combined with second-line therapy paclitaxel + S-1 on the malignant degree and angiogenesis in patients with HER-2-positive gastric cancer.Methods: A total of 90 patients with HER-2-positive gastric cancer were randomly divided into observation group and control group (n=45), control group received paclitaxel + S-1 chemotherapy, observation group received herceptin combined with paclitaxel + S-1 chemotherapy, and differences in the content of tumor markers and angiogenesis indexes in serum as well as mRNA expression levels of apoptosis and invasion genes in tumor biopsy specimens were compared between two groups of patients after 4 cycles of treatment.Results:CA19-9, CEA, CA242, CA724 and AFP content in serum of observation group were lower than those of control group; VEGF, bFGF, Ang-2 and IGF-Ⅱ content in serum were lower than those of control group while PEDF and ES content were higher than those of control group; apoptosis genesNorrin andp-Bad mRNA expression levels were lower than those of control group while BadandCaspase-3 mRNA expression levels were higher than those of control group; invasion genesEaf2 andE-cadherin mRNA expression levels were higher than those of control group while eIF4E, CD44, UHRF1 and Vav3mRNA expression levels were lower than those of control group.Conclusions:Herceptin combined with second-line therapy paclitaxel + S-1 can effectively inhibit the disease progression in patients with HER-2-positive gastric cancer, and is advantageous in reducing the malignant degree of tumor and prolonging patients’ survival time.

  4. Hypofractionated Intensity Modulated Radiation Therapy in Combined Modality Treatment for Bladder Preservation in Elderly Patients With Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Turgeon, Guy-Anne [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Souhami, Luis, E-mail: luis.souhami@muhc.mcgill.ca [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Cury, Fabio L.; Faria, Sergio L.; Duclos, Marie [Department of Oncology, Division of Radiation Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Sturgeon, Jeremy [Department of Medical Oncology, McGill University Health Centre, Montreal, Quebec (Canada); Kassouf, Wassim [Department of Urology, McGill University Health Centre, Montreal, Quebec (Canada)

    2014-02-01

    Purpose/Objective(s): To review our experience with bladder-preserving trimodality treatment (TMT) using hypofractionated intensity modulated radiation therapy (IMRT) for the treatment of elderly patients with muscle-invasive bladder cancer. Methods and Materials: Retrospective study of elderly patients treated with TMT using hypofractionated IMRT (50 Gy in 20 fractions) with concomitant weekly radiosensitizing chemotherapy. Eligibility criteria were as follows: age ≥70 years, a proven diagnosis of muscle-invasive transitional cell bladder carcinoma, stage T2-T3N0M0 disease, and receipt of TMT with curative intent. Response rate was assessed by cystoscopic evaluation and bladder biopsy. Results: 24 patients with a median age of 79 years were eligible. A complete response was confirmed in 83% of the patients. Of the remaining patients, 1 of them underwent salvage cystectomy, and no disease was found in the bladder on histopathologic assessment. After a median follow-up time of 28 months, of the patients with a complete response, 2 patients had muscle-invasive recurrence, 1 experienced locoregional failure, and 3 experienced distant metastasis. The overall and cancer-specific survival rates at 3 years were 61% and 71%, respectively. Of the surviving patients, 75% have a disease-free and functioning bladder. All patients completed hypofractionated IMRT, and 19 patients tolerated all 4 cycles of chemotherapy. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in only 4% of the patients, and acute grade 3 or 4 hematologic toxicities, liver toxicities, or both were experienced by 17% of the cohort. No patient experienced grade 4 gastrointestinal or genitourinary toxicity. Conclusions: Hypofractionated IMRT with concurrent radiosensitizing chemotherapy appears to be an effective and well-tolerated curative treatment strategy in the elderly population and should be considered for patients who are not candidates for cystectomy or who wish to avoid

  5. Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy

    DEFF Research Database (Denmark)

    Bruyand, Mathias; Ryom, Lene; Shepherd, Leah;

    2015-01-01

    -AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma). RESULTS: A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were...

  6. Estimated radiation pneumonitis risk after photon versus proton therapy alone or combined with chemotherapy for lung cancer

    DEFF Research Database (Denmark)

    Vogelius, Ivan R.; Westerly, David C; Aznar, Marianne Camille

    2011-01-01

    of clinical G3RP at zero CERD is 5% for tomotherapy (range: 1-18 %) and 14% for 3D-CRT (range 2-49%). When the CERD exceeds 9 Gy, however, the risk of RP with the tomotherapy plans become higher than the 3D-CRT plans. The IMPT plans are less toxic both at zero CERD (mean 2%, range 1-5%) and at CERD = 10 Gy...... treatment plans are compared in 18 non-small cell lung cancer patients previously treated with helical tomotherapy; the tomotherapy plan, an intensity modulated proton therapy plan (IMPT) and a three dimensional conformal radiotherapy (3D-CRT) plan. All plans are optimized without consideration...... of the chemotherapy effect. The effect of chemotherapy is modeled as an independent cell killing process using a uniform chemotherapy equivalent radiation dose (CERD) added to the entire organ at risk. We estimate the risk of grade 3 or higher RP (G3RP) using the critical volume model. Results. The mean risk...

  7. Accelerated split-course (Type B) thoracic radiation therapy plus vinorelbine/carboplatin combination chemotherapy in Stage III inoperable non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iaffaioli, R.V.; Tortoriello, A.; Facchini, G.; Maccauro, M.; Dimitri, P. [Cagliari Univ. (Italy). Ist. Medicina Interna; Caponigro, F. [Istituto Medico Legale, Milan (Italy); Ravo, V.; Muto, P. [Naples Univ. (Italy). Ist. Scienze Radiologiche; Crovella, F. [Ospedale Oliveto, Citra (Italy). Div. Chirurgia Generale

    1996-10-01

    43 patients with stage III NSCLC (non-small cell lung cancer) entered a phase II study aimed at evaluating the toxicity and the activity of a combined modality programme including an accelerated split-course schedule (type B) of thoracic radiation therapy and a combination chemotherapy with vinorelbine and carboplatin. An objective response was achieved in 18/42 evaluable patients (5 complete and 13 partial responses), for an overall response rate of 43% (95% confidence interval, 28-58%). Four complete responses had a duration which exceeded 16 months. Treatment was well tolerated; grade III myelotoxicity occurred in only 14% of patients and treatment was delayed in only 2 cases because of grade 3 oesophagitis. Both tolerability and efficacy data suggest that this regimen holds promise for the treatment of patients with stage III NSCLC. (author).

  8. Clinical nursing of oxaliplatin combined chemotherapy for colorectal cancer therapy%奥沙利铂联合化疗治疗大肠癌临床护理

    Institute of Scientific and Technical Information of China (English)

    徐崇立

    2014-01-01

    Objective To explore the measures of adverse reactions of oxaliplatin combined with chemotherapy in the treatment of colorectal cancer and its clinical nursing.MethodsA retrospective analysis of 40 cases of colorectal cancer with oxaliplatin combined chemotherapy.Results 40 patients completed 4 cycles of therapy,the treatment process were insensitive,finger(toe) numbness,gastrointestinal reaction,bone marrow inhibition of different degrees of adverse reactions,no severe adverse reaction occurred.ConclusionPsychological nursing,diet nursing during the chemotherapy for colorectal cancer,chemotherapy,nursing before,after,can make the successful completion of therapy in patients,improve the quality of life.%目的:探讨奥沙利铂联合化疗治疗大肠癌的不良反应及其临床护理措施。方法:回顾性分析40例大肠癌应用奥沙利铂联合化疗的临床资料。结果:40例患者均完成了4个周期的治疗,治疗过程中均出现感觉迟钝、手指(趾)麻木、胃肠道反应、骨髓抑制不同程度的不良反应,未发生严重的不良反应。结论:对大肠癌化疗期间做好饮食护理、心理护理,化疗前、中、后的护理,可使患者顺利完成化疗,提高生活质量。

  9. Biofield therapies and cancer pain.

    Science.gov (United States)

    Anderson, Joel G; Taylor, Ann Gill

    2012-02-01

    The public and healthcare professionals have become increasingly aware and accepting of the benefit in physical, psychological, social, and spiritual support for patients with cancer. Patients with cancer often seek nonpharmacologic interventions to complement conventional care and decrease the pain associated with cancer and its treatment. Most often referred to as complementary and alternative medicine (CAM), these supportive therapies consist of a heterogeneous group of modalities used as adjuncts to allopathic health care. Biofield therapies are CAM modalities that involve the direction of healing energy through the hands to facilitate well-being by modifying the energy field of the body. This critical review of studies of biofield therapies emphasizes research using these modalities to decrease pain in patients with cancer. Although the therapies have demonstrated clinical efficacy, additional research is warranted. Oncology nurses should familiarize themselves with biofield therapies so they can offer informed recommendations to patients with cancer experiencing pain.

  10. Enhanced vesicular stomatitis virus (VSVΔ51 targeting of head and neck cancer in combination with radiation therapy or ZD6126 vascular disrupting agent

    Directory of Open Access Journals (Sweden)

    Alajez Nehad M

    2012-06-01

    Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC is the 5th most common cancer worldwide. Locally advanced HNSCC are treated with either radiation or chemo-radiotherapy, but still associated with high mortality rate, underscoring the need to develop novel therapies. Oncolytic viruses have been garnering increasing interest as anti-cancer agents due to their preferential killing of transformed cells. In this study, we evaluated the therapeutic potential of mutant vesicular stomatitis virus (VSVΔ51 against the human hypopharyngeal FaDu tumour model in vitro and in vivo. Results Our data demonstrated high toxicity of the virus against FaDu cells in vitro, which was associated with induction of apoptosis. In vivo, systemic injection of 1 × 109 pfu had minimal effect on tumour growth; however, when combined with two doses of ionizing radiation (IR; 5 Gy each or a single injection of the vascular disrupting agent (ZD6126, the virus exhibited profound suppression of tumour growth, which translated to a prolonged survival in the treated mice. Concordantly, VSVΔ51 combined with ZD6126 led to a significant increase in viral replication in these tumours. Conclusions Our data suggest that the combinations of VSVΔ51 with either IR or ZD6126 are potentially novel therapeutic opportunities for HNSCC.

  11. Interval to Biochemical Failure Predicts Clinical Outcomes in Patients With High-Risk Prostate Cancer Treated by Combined-Modality Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Shilkrut, Mark; McLaughlin, P. William [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan (United States); Merrick, Gregory S. [Schiffler Cancer Center, Wheeling Jesuit University, Wheeling, West Virginia (United States); Vainshtein, Jeffrey M.; Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan (United States); Hamstra, Daniel A., E-mail: dhamm@med.umich.edu [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan (United States)

    2013-07-15

    Purpose: To validate the prognostic value of interval to biochemical failure (IBF) in patients with high-risk prostate cancer (HiRPCa) treated with combined-modality radiation therapy (CMRT) with or without androgen deprivation therapy (ADT). Methods and Materials: We conducted a retrospective review of HiRPCa (prostate-specific antigen >20 ng/mL, Gleason score [GS] 8-10, or clinical T stage T3-T4) treated with either dose-escalated external beam radiation therapy (EBRT) or CMRT. Interval to biochemical failure was classified as ≤18 or >18 months from the end of all therapy to the date of biochemical failure (BF). Kaplan-Meier methods and Cox proportional hazards regression were used to evaluate the prognostic value of IBF ≤18 months for distant metastasis (DM) and prostate cancer-specific mortality (PCSM). Results: Of 958 patients with a median follow-up of 63.2 months, 175 patients experienced BF. In those with BF, there were no differences in pretreatment clinical characteristics between the EBRT and CMRT groups, except for a higher proportion of patients with GS 8-10 in the CMRT group (70% vs 52%, P=.02). Median IBF after all therapy was 24.0 months (interquartile range 9.6-46.0) in the EBRT group and 18.9 months (interquartile range 9.2-34.5) in the CMRT group (P=.055). On univariate analysis, IBF ≤18 months was associated with increased risk of DM and PCSM in the entire cohort and the individual EBRT and CMRT groups. On multivariate analysis, only GS 9-10 and IBF ≤18 months, but not the radiation therapy regimen or ADT use, predicted DM (hazard ratio [HR] 3.7, P<.01, 95% confidence interval [CI] 1.4-10.3 for GS 9-10; HR 3.9, P<.0001, 95% CI 2.4-6.5 for IBF ≤18 months) and PCSM (HR 14.8, P<.009, 95% CI 2.0-110 for GS 9-10; HR 4.4, P<.0001, 95% CI 2.4-8.1 for IBF ≤18 months). Conclusions: Short IBF was highly prognostic for higher DM and PCSM in patients with HiRPCa. The prognostic value of IBF for DM and PCSM was not affected by the radiation

  12. Neutron therapy for salivary and thyroid gland cancer

    Science.gov (United States)

    Gribova, O. V.; Musabaeva, L. I.; Choynzonov, E. L.; Lisin, V. A.; Novikov, V. A.

    2016-08-01

    The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

  13. Ganetespib radiosensitization for liver cancer therapy

    Science.gov (United States)

    Chettiar, Sivarajan T.; Malek, Reem; Annadanam, Anvesh; Nugent, Katriana M.; Kato, Yoshinori; Wang, Hailun; Cades, Jessica A.; Taparra, Kekoa; Belcaid, Zineb; Ballew, Matthew; Manmiller, Sarah; Proia, David; Lim, Michael; Anders, Robert A.; Herman, Joseph M.; Tran, Phuoc T.

    2016-01-01

    ABSTRACT Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on 3 liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33–1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies. PMID:26980196

  14. Biologic therapies for advanced pancreatic cancer.

    Science.gov (United States)

    He, Aiwu Ruth; Lindenberg, Andreas Peter; Marshall, John Lindsay

    2008-08-01

    Patients with metastatic pancreatic cancer have poor prognosis and short survival due to lack of effective therapy and aggressiveness of the disease. Pancreatic cancer has widespread chromosomal instability, including a high rate of translocations and deletions. Upregulated EGF signaling and mutation of K-RAS are found in most pancreatic cancers. Therefore, inhibitors that target EGF receptor, K-RAS, RAF, MEK, mTOR, VEGF and PDGF, for example, have been evaluated in patients with pancreatic cancer. Although significant activities of these inhibitors have not been observed in the majority of pancreatic cancer patients, an enormous amount of experience and knowledge has been obtained from recent clinical trials. With a better inhibitor or combination of inhibitors, and improvement in the selection of patients for available inhibitors, better therapy for pancreatic cancer is on the horizon.

  15. Combined targeted therapies of non-small cell lung cancer%非小细胞肺癌联合靶向治疗的研究现状

    Institute of Scientific and Technical Information of China (English)

    李明; 陈小东

    2008-01-01

    Non-small cell lung cancer(NSCLC) is a common malignant tumor. Majority of NSCLC patients can not be cured by traditional therapies, such as chemotherapy, radiotherapy or operations. Because most of them are in advanced stage when diagnosed. After a series of phase Ⅲ clinical trials,single targeted drugs have already been approbated to be used for patients. However, the effect can not meet expectation.With the study of pathogenesis of lung cancer and targeted drugs, combined targeted therapies would be a new choice.%非小细胞肺癌是常见的恶性肿瘤,大多数患者发现时已处于晚期,化疗、放疗和手术等传统治疗效果不佳.经过多个Ⅲ期临床试验,已经有单靶点药物被批准用于临床,但是效果亦不能令人满意.近年来,随着肺癌发病机制和靶向药物研究的深入,联合靶向治疗成为新的选择.

  16. Rehabilitation in cancer: Training and talking? Effects of physical training versus physical training combined with cognitive-behavioural therapy

    NARCIS (Netherlands)

    May-de Groot, A.M.

    2008-01-01

    Objective. As a result of recent advances in diagnosis and treatment, the number of people surviving cancer is increasing. A subgroup of cancer survivors report long-lasting physical and psychological complaints including decreased cardiorespiratory capacity, decreased physical functioning, and decr

  17. 自杀基因联合细胞因子的癌症治疗%Combined therapy of suicide gene and cytokine gene for cancer

    Institute of Scientific and Technical Information of China (English)

    王红孝; 袁家英; 张建华; 潘伯荣

    2004-01-01

    @@ INTRODUCTION The transfer of suicide genes into tumor cells is currently being used in a variety of clinical gene therapy trials for the treatment of cancer, and suicide gene therapy is the transduction of a gene that transforms a non-toxic into a toxic substance[1].

  18. Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

    DEFF Research Database (Denmark)

    Michaelsen, Signe R; Christensen, Camilla L; Sehested, Maxwell

    2012-01-01

    Transcriptional targeted suicide gene (SG) therapy driven by the insulinoma-associated 1 (INSM1) promoter makes it possible to target suicide toxin production and cytotoxicity exclusively to small cell lung cancer (SCLC) cells and tumors. It remains to be determined whether acquired chemoresistance......, as observed in the majority of SCLC patients, desensitizes SCLC cells to INSM1 promoter-driven SG therapy....

  19. Efficacy radiotherapy combined with immune therapy for head and neck cancer%放疗联合免疫治疗头颈癌的疗效观察

    Institute of Scientific and Technical Information of China (English)

    崔榕; 范敏; 袁洛花; 罗智莘

    2012-01-01

      目的研究分析放疗联合免疫治疗头颈癌的效果,总结优势和不足,以更好的指导临床治疗。方法随机选择我院2009年8月~2011年8月头颈癌患者56名,分成A、B两组,A组23名患者为对照组,给予单纯放疗方法医治;B组33名患者为治疗组,给予放疗联合免疫治疗方法。将A、B组患者治疗后缓解率,有效率,细胞免疫水平等进行对比分析,并加以总结。结果经治疗,B组治疗组患者缓解率明显高于A组对照组患者,治疗有效率高于A组,患者细胞免疫水平高于A组患者。结论放疗联合免疫治疗头颈癌,患者缓解率较高,有效率较高,细胞免疫水平得到较好提升,具有较高临床使用和推广价值。%  Objective The study of combined effect of radiotherapy and immune therapy in head and neck cancers, summarizing the advantages and disadvantages, to guide clinical treatment better. Methods 56 patients with head and neck cancers in our hospital from August 2009 to August 2011 were randomized into two groups. A group composed of 23 patients as the control group were given radiotherapy while; the othert 33 patients were,given radiotherapy combined with immunotherapy as treatment group, B. We analyzed the remission rate, effect rate and cel immunity levels of each group, to compare the advantage of these two therapeutic processes Results the complete remission rate, effect rate and levels of cel immunity of the patients in group B were significantly higher than those of the patients ijn group A. Conclusion Radiotherapy combined with immune therapy for head and neck cancers, which shows higher response rate and effect rate than traditional radiotherapy, and enhance celular immunity, is useful and promote the value of higher clinical outcome

  20. Cancer-Related Fatigue and Rehabilitation : A Randomized Controlled Multicenter Trial Comparing Physical Training Combined With Cognitive-Behavioral Therapy With Physical Training Only and With No Intervention

    NARCIS (Netherlands)

    van Weert, E.; May, A.M.; Korstjens, I.; Post, W.J.; van der Schans, C.P.; van den Borne, B.; Mesters, I.; Ros, W.J.G.; Hoekstra-Weebers, J.E.H.M.

    2010-01-01

    Background. Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial. Objective. This randomized controlled trial compared the effect on cancer-related fatigue of physical training combined with cogniti

  1. Use of Combination Thermal Therapy and Radiation in Breast-Conserving Treatment of Extensive Intraductal Breast Cancer

    Science.gov (United States)

    1997-07-01

    heart size/Per- effusion/Constrictive heart failure wave inversion and ST sistent abnormality T peric~arditis/Maderato Sever. coastric- R changes... Sociedad Venezolana de Mastologia Major Committee Assignments: 1993- Medical Records Committee, Dana-Farber Cancer Institute 1996- Drug Use...1993 Invited speaker, The University of New Mexico ,"Treatment of Breast Cancer: Mastectormy vs Less" and "Sterotactic Core Needle Biopsy", Albuquerque

  2. Adjuvant therapies for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced (stage Ⅲ and selected stage Ⅱ) colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage Ⅱ disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.

  3. Gene therapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Xu Chang-tai; Guo Xue-gang; Pan Bo-rong

    2003-01-01

    @@ 1 Introduction We have reviewed the gene therapy in gastrointestinal diseases[1]. Gastric cancer is common in China[2~20] ,and its early diagnosis andtreatment are still difficult up to now[13~36]. The expression of anexogenous gene introduced by gene therapy into patients with gliomascan be monitored non- invasively by positron- emission tomography[4]. In recent years, gene study in cancer is a hotspot, and great progress hasbeen achieved[33~41].

  4. Enhancing Hormonal Therapy for Breast Cancer by Combination with a Well-Known Approved Pharmaceutical with Little Toxicity

    Science.gov (United States)

    2008-07-01

    enhancing the efficacy of tamoxifen in inhibiting breast tumors. Acknowledgments We would particularly like to thank Dr. Fred Schaufele for the careful ...cells. Anticancer Res 22(2A):1007–1009 9. Osborne CK, Kitten L, Arteaga CL (1989) Antagonism of chemotherapy-induced cytotoxicity for human breast cancer

  5. Development of a label-free LC-MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy.

    LENUS (Irish Health Repository)

    Morrissey, Brian

    2013-06-01

    Combined hormone and radiation therapy (CHRT) is one of the principle curative regimes for localised prostate cancer (PCa). Following treatment, many patients subsequently experience disease recurrence however; current diagnostics tests fail to predict the onset of disease recurrence. Biomarkers that address this issue would be of significant advantage.

  6. Cancer Alternative Therapies

    Science.gov (United States)

    You have many choices to make about your cancer treatment. One choice you might be thinking about ... are acupuncture, chiropractic, and herbal medicines. People with cancer may use CAM to Help cope with the ...

  7. Combination therapies in iron chelation

    Directory of Open Access Journals (Sweden)

    Raffaella Origa

    2014-12-01

    Full Text Available The availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have significantly improved the life expectancy and quality of life of patients with b thalassemia major. However, monotherapy is not effective in all patients for a variety of reasons. We analyzed the most relevant reports recently published on alternating or combined chelation therapies in thalassemia major with special attention to safety aspects and to their effects in terms of reduction of iron overload in different organs, improvement of complications, and survival. When adverse effects, such as gastrointestinal upset with deferasirox or infusional site reactions with deferoxamine are not tolerable and organ iron is in an acceptable range, alternating use of two chelators (drugs taken sequentially on different days, but not taken on the same day together may be a winning choice. The association deferiprone and deferoxamine should be the first choice in case of heart failure and when dangerously high levels of cardiac iron exist. Further research regarding the safety and efficacy of the most appealing combination treatment, deferiprone and deferasirox, is needed before recommendations for routine clinical practice can be made.

  8. Risk-optimized proton therapy to minimize radiogenic second cancers

    DEFF Research Database (Denmark)

    Rechner, Laura A; Eley, John G; Howell, Rebecca M

    2015-01-01

    Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were...... to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment...

  9. Combination Therapy of Gefitinib and Korean Herbal Medicines Could be a Beneficial Option for Patients with Non-Small-Cell Lung Cancer

    OpenAIRE

    2016-01-01

    Abstract Abstract Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in...

  10. Cancer-related fatigue and rehabilitation: A randomized controlled multicenter trial comparing physical training combined with cognitive-behavioral therapy with physical training only and with no intervention

    NARCIS (Netherlands)

    E. van Weert (Ellen); A.M. May (Anne); I. Korstjens (Irene); W.J. Post (Wendy); C.P. van der Schans (Cees); B. van den Borne (Bart); I. Mesters (Ilse); W.J.G. Ros (Wynand); J.E.H.M. Hoekstra-Weebers (Josette)

    2010-01-01

    textabstractBackground. Research suggests that cancer rehabilitation reduces fatigue in survivors of cancer. To date, it is unclear what type of rehabilitation is most beneficial. Objective. This randomized controlled trial compared the effect on cancerrelated fatigue of physical training combined w

  11. Biological Therapies for Cancer

    Science.gov (United States)

    ... Medicine 2009;7:11. [PubMed Abstract] Pardoll D. Cancer immunology. In: Abeloff M, Armitage J, Niederhuber J, Kastan ... 363(5):411-422. [PubMed Abstract] Finn OJ. Cancer immunology. New England Journal of Medicine 2008;358(25): ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-01

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

  13. Combination therapy: the next opportunity and challenge of medicine

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-07-01

    Full Text Available Abstract From an historical point of view, combination therapy was the basis for the care of important diseases like infection diseases or cancer. Today the "cocktail drug" of the Highly Active Anti Retroviral Therapy (HAART has reduced the death for HIV infection changing the outcome of such disease. Moreover, the combination of different strategies changed the course of transplants (both in haematology and surgical transplant. Different diseases with high social impact including cardiovascular, metabolic (obesity, hypercholesterolaemia and diabetes and autoimmune diseases, have better results with combinations of different drug classes of drugs. After recent successes in the immunotherapy field (Sepuleucel-T, ipilimumab and the new promising small molecule therapies, cancer should be the next challenge for combination strategies.

  14. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  15. Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer

    DEFF Research Database (Denmark)

    Joensuu, H; Holli, K; Heikkinen, M;

    1998-01-01

    (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2...

  16. Art therapy in cancer fight

    Directory of Open Access Journals (Sweden)

    Érica Rodrigues D'Alencar

    2014-01-01

    Full Text Available Art therapy is the therapeutic use of artistic activity in the context of the professional relationship with people affected by disease, injury or by seeking personal development. This study aims to report the experience of art therapy activities with a group of patients and their caregivers in a university hospital. This is an experience report, in Fortaleza - CE, during September 2010 to February 2011. In the meetings, participated 49 people, who performed activities, using the methods of art therapy, like painting, cutting, drawing, collage, creative visualization and color therapy. In the assessments, after the groups, the participants demonstrated the effects of art therapy, which described that the intervention allowed speak from the process of facing life to cancer fight. It is concluded that the techniques of art therapy provided self-knowledge, self-esteem and redemption sense of well-being with relaxation, and promote happiness and reduce stress.

  17. Vitamin D for combination photodynamic therapy of skin cancer in individuals with vitamin D deficiency: Insights from a preclinical study in a mouse model of squamous cell carcinoma

    Science.gov (United States)

    Anand, Sanjay; Thomas, Erik; Hasan, Tayyaba; Maytin, Edward V.

    2016-03-01

    Combination photodynamic therapy (cPDT) in which vitamin D (VD) is given prior to aminolevulinate, a precursor (pro-drug) for protoporphyrin IX (PpIX), is an approach developed in our laboratory. We previously showed that 1α,25- dihydroxyvitamin D3 (calcitriol), given prior to PDT, enhances accumulation of PpIX and improves cell death post-PDT in a mouse skin cancer model. However, since calcitriol poses a risk for hypercalcemia, we replaced systemic calcitriol with oral cholecalciferol (D3), administered as a high (tenfold, "10K") diet over a ten-day period. Here, we ask whether VD deficiency might alter the response to cPDT. Nude mice were fed a VD-deficient diet for at least 4 weeks ("deficient"); controls were fed a normal 1,000 IU/kg diet ("1K"). Human A431 cells were implanted subcutaneously and mice were switched to the 10K diet or continued on their baseline diets (controls). In other experiments, mice received a human equivalent dose of 50,000 IU D3 by oral gavage, to simulate administration of a single, high-dose VD pill. At various times, tumors were harvested and serum was collected to measure levels of VD metabolic intermediates. A significant increase in PpIX levels and in the expression of differentiation and proliferation markers in tumor tissue was observed after VD supplementation of both the deficient and 1K mice. Further results describing mechanistic details of PpIX enhancement through alteration of heme- and VD-metabolic enzyme levels will be presented. Based on these results, a clinical study using oral vitamin D prior to PDT for human skin cancer should be performed.

  18. Combined inhibition of EZH2 and histone deacetylases as a potential epigenetic therapy for non-small-cell lung cancer cells.

    Science.gov (United States)

    Takashina, Taichi; Kinoshita, Ichiro; Kikuchi, Junko; Shimizu, Yasushi; Sakakibara-Konishi, Jun; Oizumi, Satoshi; Nishimura, Masaharu; Dosaka-Akita, Hirotoshi

    2016-07-01

    Recent discoveries have revealed that human cancer involves aberrant epigenetic alterations. We and others have previously shown that the histone methyltransferase EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), is frequently overexpressed in non-small-cell lung cancer (NSCLC) and that an EZH2 inhibitor, 3-deazaneplanocin A, inhibits the proliferation of NSCLC cells. Transcriptional silencing by EZH2 was recently shown to be required for the activity of histone deacetylases (HDACs) that interact with another PRC2 protein, EED. To develop a more effective epigenetic therapy for NSCLC, we determined the effects of co-treatment with 3-deazaneplanocin A and the HDAC inhibitor vorinostat (SAHA) in NSCLC cells. The co-treatment synergistically suppressed the proliferation of all tested NSCLC cell lines, regardless of their epidermal growth factor receptor (EGFR) status. The synergistic effect was associated with slightly decreased histone H3 lysine 27 trimethylation, modestly increased histone acetylation, and the depletion of EZH2 and other PRC2 proteins. The co-treatment resulted in an accumulation of p27Kip1, decrease in cyclin A, and increased apoptotic fraction in an additive/synergistic manner. Interestingly, the co-treatment strongly suppressed EGFR signaling, not only in EGFR-wild-type NSCLC cells, but also in EGFR-mutant cells, mainly through dephosphorylation of EGFR. Furthermore, the co-treatment suppressed the in vivo tumor growth of EGFR-mutant, EGFR-tyrosine kinase-resistant H1975 cells more effectively than did each agent alone, without visible toxicity. These results suggest that the combined pharmacological targeting of EZH2 and HDACs may provide more effective epigenetic therapeutics for NSCLC.

  19. Sonoporation: Applications for Cancer Therapy.

    Science.gov (United States)

    Qin, Jiale; Wang, Tzu-Yin; Willmann, Jürgen K

    2016-01-01

    Therapeutic efficacy of both traditional chemotherapy and gene therapy in cancer is highly dependent on the ability to deliver drugs across natural barriers, such as the vessel wall or tumor cell membranes. In this regard, sonoporation induced by ultrasound-guided microbubble (USMB) destruction has been widely investigated in the enhancement of therapeutic drug delivery given it can help overcome these natural barriers, thereby increasing drug delivery into cancer. In this chapter we discuss challenges in current cancer therapy and how some of these challenges could be overcome using USMB-mediated drug delivery. We particularly focus on recent advances in delivery approaches that have been developed to further improve therapeutic efficiency and specificity of various cancer treatments. An example of clinical translation of USMB-mediated drug delivery is also shown.

  20. Antiangiogenic therapies in ovarian cancer

    OpenAIRE

    Reinthaller, Alexander

    2016-01-01

    Summary Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the formation and progression of ovarian cancer. Several well-designed phase II and III trials studied the efficacy of antiangiogenic agents in advanced ovarian cancer. The results of these trials demonstrated significantly prolonged progression-free survival when antiangiogenic agents were used as a maintenance therapy. To date, no effect on overall survival could be ascertained. The most widely studied anti...

  1. Selected Secondary Plant Metabolites for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2015-01-01

    Full Text Available Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases. As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics, either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in oncology. Two major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid, artesunate, dicentrine and camptothecin derivatives.

  2. Adaptive Upregulation of EGFR Limits Attenuation of Tumor Growth by Neutralizing IL6 Antibodies, with Implications for Combined Therapy in Ovarian Cancer.

    Science.gov (United States)

    Milagre, Carla S; Gopinathan, Ganga; Everitt, Gemma; Thompson, Richard G; Kulbe, Hagen; Zhong, Haihong; Hollingsworth, Robert E; Grose, Richard; Bowtell, David D L; Hochhauser, Daniel; Balkwill, Frances R

    2015-04-01

    Excess production of the proinflammatory IL6 has both local and systemic tumor-promoting activity in many cancers, including ovarian cancer. However, treatment of advanced ovarian cancer patients with a neutralizing IL6 antibody yielded little efficacy in a previous phase II clinical trial. Here, we report results that may explain this outcome, based on the finding that neutralizing antibodies to IL6 and STAT3 inhibition are sufficient to upregulate the EGFR pathway in high-grade serous and other ovarian cancer cells. Cell treatment with the EGFR inhibitor gefitinib abolished upregulation of the EGFR pathway. Combining neutralizing IL6 antibodies and gefitinib inhibited malignant cell growth in 2D and 3D culture. We found that ErbB-1 was localized predominantly in the nucleus of ovarian cancer cells examined, contrasting with plasma membrane localization in lung cancer cells. Treatment with anti-IL6, gefitinib, or their combination all led to partial restoration of ErbB-1 on the plasma membrane. In vivo experiments confirmed the effects of IL6 inhibition on the EGFR pathway and the enhanced activity of a combination of anti-IL6 antibodies and gefitinib on malignant cell growth. Taken together, our results offer a preclinical rationale to combine anti-IL6 and gefitinib to treat patients with advanced stage ovarian cancer.

  3. Targeted Therapies in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Selen Dogan

    2014-04-01

    Full Text Available Endometrial cancer is the most common genital cancer in developed world. It is generally diagnosed in early stage and it has a favorable prognosis. However, advanced staged disease and recurrences are difficult to manage. There are some common genetic alterations related to endometrial carcinogenesis in similar fashion to other cancers. Personalized medicine, which means selection of best suited treatment for an individual, has gain attention in clinical care of patients in recent years. Targeted therapies were developed as a part of personalized or %u201Ctailored%u201D medicine and specifically acts on a target or biologic pathway. There are quite a number of molecular alteration points in endometrial cancer such as PTEN tumor suppressor genes, DNA mismatch repair genes, PI3K/AKT/mTOR pathway and p53 oncogene which all might be potential candidates for tailored targeted therapy. In recent years targeted therapies has clinical application in ovarian cancer patients and in near future with the advent of new agents these %u201Ctailored%u201D drugs will be in market for routine clinical practice in endometrial cancer patients, in primary disease and recurrences as well.

  4. Enhancing Immune Responses for Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Shao-An Xue; Hans J Stauss

    2007-01-01

    Although the immune system possesses the means to respond to cancer, it often fails to control the spread of malignancy. Nonetheless, equipping endogenous immunity to release a strong antitumor response has significant advantages over conventional therapies. This review explores some of the options available to accomplish this,focusing first on vaccinations with tumor antigens to stimulate the immune system and empower stronger antitumor responses. We then compare and contrast the so-far limited clinical success of vaccination with the well-documented curative potential of adoptive therapy using T lymphocytes transfer. Finally, we highlight novel approaches using T cell receptor (TCR) gene transfer strategy to exploit allogeneic T cell repertoires in conjunction with receptors selected in vitro for defined MHC/peptide combinations, as a basis for antigen-specific gene therapy of cancers.

  5. [Genetic basis of head and neck cancers and gene therapy].

    Science.gov (United States)

    Özel, Halil Erdem; Özkırış, Mahmut; Gencer, Zeliha Kapusuz; Saydam, Levent

    2013-01-01

    Surgery and combinations of traditional treatments are not successful enough particularly for advanced stage head and neck cancer. The major disadvantages of chemotherapy and radiation therapy are the lack of specificity for the target tissue and toxicity to the patient. As a result, gene therapy may offer a more specific approach. The aim of gene therapy is to present therapeutic genes into cancer cells which selectively eliminate malignant cells with no systemic toxicity to the patient. This article reviews the genetic basis of head and neck cancers and important concepts in cancer gene therapy: (i) inhibition of oncogenes; (ii) tumor suppressor gene replacement; (iii) regulation of immune response against malignant cells; (iv) genetic prodrug activation; and (v) antiangiogenic gene therapy. Currently, gene therapy is not sufficient to replace the traditional treatments of head and neck cancers, however there is no doubt that it will have an important role in the near future.

  6. Transcriptional Selectivity of Epigenetic Therapy in Cancer.

    Science.gov (United States)

    Sato, Takahiro; Cesaroni, Matteo; Chung, Woonbok; Panjarian, Shoghag; Tran, Anthony; Madzo, Jozef; Okamoto, Yasuyuki; Zhang, Hanghang; Chen, Xiaowei; Jelinek, Jaroslav; Issa, Jean-Pierre J

    2017-01-15

    A central challenge in the development of epigenetic cancer therapy is the ability to direct selectivity in modulating gene expression for disease-selective efficacy. To address this issue, we characterized by RNA-seq, DNA methylation, and ChIP-seq analyses the epigenetic response of a set of colon, breast, and leukemia cancer cell lines to small-molecule inhibitors against DNA methyltransferases (DAC), histone deacetylases (Depsi), histone demethylases (KDM1A inhibitor S2101), and histone methylases (EHMT2 inhibitor UNC0638 and EZH2 inhibitor GSK343). We also characterized the effects of DAC as combined with the other compounds. Averaged over the cancer cell models used, we found that DAC affected 8.6% of the transcriptome and that 95.4% of the genes affected were upregulated. DAC preferentially regulated genes that were silenced in cancer and that were methylated at their promoters. In contrast, Depsi affected the expression of 30.4% of the transcriptome but showed little selectivity for gene upregulation or silenced genes. S2101, UNC0638, and GSK343 affected only 2% of the transcriptome, with UNC0638 and GSK343 preferentially targeting genes marked with H3K9me2 or H3K27me3, respectively. When combined with histone methylase inhibitors, the extent of gene upregulation by DAC was extended while still maintaining selectivity for DNA-methylated genes and silenced genes. However, the genes upregulated by combination treatment exhibited limited overlap, indicating the possibility of targeting distinct sets of genes based on different epigenetic therapy combinations. Overall, our results demonstrated that DNA methyltransferase inhibitors preferentially target cancer-relevant genes and can be combined with inhibitors targeting histone methylation for synergistic effects while still maintaining selectivity. Cancer Res; 77(2); 470-81. ©2016 AACR.

  7. Combined Limb-Sparing Surgery and Radiation Therapy to Treat Sarcomas of the Hands and Feet: Long-Term Cancer Outcomes and Morbidity

    Energy Technology Data Exchange (ETDEWEB)

    Bishop, Andrew J.; Zagars, Gunar K. [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Moon, Bryan S.; Lin, Patrick P.; Lewis, Valerae O. [Department of Orthopedic Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Guadagnolo, B. Ashleigh, E-mail: aguadagn@mdanderson.org [Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (United States); Department of Health Services Research, MD Anderson Cancer Center, Houston, Texas (United States)

    2015-08-01

    Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with limb-sparing surgery and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet. Methods and Materials: We reviewed the medical records of 85 consecutive patients treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and 2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven patients (79%) received postoperative RT after resection of their tumor (median dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with preoperative RT followed by tumor resection (median dose, 50 Gy; range, 50-64 Gy). Results: Median follow-up was 140 months (range, 24-442 months). Five-year local control, overall survival, and disease-specific survival rates were 86%, 89%, and 89%, respectively. Positive or uncertain surgical margin status was the only factor adversely associated with local recurrence (19% vs 6% for negative margins, P=.046) but this lost significance on multivariate analysis when adjusting for RT dose ≥64 Gy. Of the 12 patients who had local relapses, 6 (50%) were salvaged, and only 2 of those required salvage amputation. Five patients had grade ≥3 late RT sequelae, with 2 patients (2%) having moderate limitations of limb function and 3 patients (4%) having severe limitations requiring procedures for skin ulceration. Conclusions: Limb-sparing surgery combined with RT provides excellent local control outcomes for sarcomas arising in the hands or feet. In patients who have local recurrence, salvage without amputation is possible. The excellent cancer control outcomes observed, considering the minimal impact on limb function, support use of combined modality, limb-sparing local therapy for STS arising in the hands or feet.

  8. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D.L.; Andersson, M.; Andersen, Jon Alexander Lykkegaard;

    2010-01-01

    tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria...

  9. Gene therapy for gastric cancer: A review

    Institute of Scientific and Technical Information of China (English)

    Chao Zhang; Zhan-Kui Liu

    2003-01-01

    Gastric cancer is common in China, and its early diagnosis and treatment are difficult. In recent years great progress has been achieved in gene therapy, and a wide array of gene therapy systems for gastric cancer has been investigated. The present article deals with the general principles of gene therapy and then focuses on how these principles may be applied to gastric cancer.

  10. Heterogeneity of liver cancer and personalized therapy.

    Science.gov (United States)

    Li, Liang; Wang, Hongyang

    2016-09-01

    Liver cancer is an extraordinarily heterogeneous malignant disease among the tumors that have so far been identified. Hepatocellular carcinoma (HCC) arises most frequently in the setting of chronic liver inflammation and fibrosis, and takes a variety of course in individual patients to process to tumor. The risk factors such as HBV and/or HCV infections, aflatoxin infection, abuse alcohol intake, metabolic syndrome, obesity and diabetes are closely related to the environmental and genetic susceptibilities to HCC. The consequent resulting genomic instability, molecular and signal transduction network disorders and microenvironmental discrepancies are characterized by the extraordinary heterogeneity of liver cancer. The histology-based definition of the morphological heterogeneity of liver cancer has been modified and refined to treat patients with targeted therapies, but this still cannot solve all the problems. Lack of consistent outcome for anticancer agents and conventional therapies in liver cancer treatment calls for assessing the benefits of new molecularly targeted drugs and combined therapy, under the heterogeneity condition of tumor. The present review article will provide the complex mechanism and phenotype of liver cancer heterogeneity, and help us to execute precision medicine in a really personalized manner.

  11. Targeted therapy: tailoring cancer treatment

    Institute of Scientific and Technical Information of China (English)

    Min Yan; Quentin Qiang Liu

    2013-01-01

    Targeted therapies include small-molecule inhibitors and monoclonal antibodies,have made treatment more tumor-specific and less toxic,and have opened new possibilities for tailoring cancer treatment.Nevertheless,there remain several challenges to targeted therapies,including molecular identification,drug resistance,and exploring reliable biomarkers.Here,we present several selected signaling pathways and molecular targets involved in human cancers including Aurora kinases,PI3K/mTOR signaling,FOXO-FOXM1 axis,and MDM2/MDM4-p53 interaction.Understanding the molecular mechanisms for tumorigenesis and development of drug resistance will provide new insights into drug discovery and design of therapeutic strategies for targeted therapies.

  12. Combined Pharmacologic Therapy in Postmenopausal Osteoporosis.

    Science.gov (United States)

    Shen, Yang; Gray, Dona L; Martinez, Dorothy S

    2017-03-01

    Antiresorptive agents for treating postmenopausal osteoporosis include selective estrogen receptor modulator (SERM), bisphosphonates and denoumab. Teriparatide is the only Food and Drug Administration-approved anabolic agent. Synergistic effects of combining teriparatide with an antiresorptive agent have been proposed and studied. This article reviews the trial designs and the outcomes of combination therapies. Results of the combination therapy for teriparatide and bisphosphonates were mixed; while small increases of bone density were observed in the combination therapy of teriparatide and estrogen/SERM and that of teriparatide and denosumab. Those clinical studies were limited by small sample sizes and lack of fracture outcomes.

  13. Noxa and cancer therapy

    OpenAIRE

    2014-01-01

    Biochemical analyses have characterized the BH3-only protein family member Noxa as a “sensitizer” with weak pro-apoptotic activity. Investigations into cancer cell responses to chemotherapeutic agents have identified Noxa as a pivotal factor mediating the cytotoxic effect of a plethora of anticancer treatments independent of its own pro-apoptotic activity. Accumulating evidence now suggests that tumor cells exert a number of strategies to counteract Noxa function by exploiting diverse cellula...

  14. Alternative cancer therapies.

    Science.gov (United States)

    Cronsberry, T

    1996-04-01

    Conventional treatments for cancer are designed to cure the disease or slow its destructive effects, but they do little to establish a feeling of control in the patient. Because of the nature of the disease, patients often consent to treatment with the frightening knowledge that a cure cannot be promised. In addition, the side effects of surgery, chemotherapy and radiotherapy can make patients very ill, both physically and psychologically.

  15. Targeting in Cancer Therapies

    Directory of Open Access Journals (Sweden)

    Ramon Mangues

    2016-03-01

    Full Text Available Drug developers recruit and combine principles, procedures and strategies from chemistry, pharmacology, nanotechnology and biotechnology, focusing on the generation of functional vehicles as nano-carriers of drugs for improved stability and enhanced intracellular delivery.[...

  16. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D.L.; Andersson, M.; Andersen, Jon Alexander Lykkegaard

    2010-01-01

    and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF...... tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria......ABSTRACT: Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development...

  17. Carboplatin and Paclitaxel in Combination With Either Vorinostat or Placebo for First-Line Therapy of Advanced Non–Small-Cell Lung Cancer

    Science.gov (United States)

    Ramalingam, Suresh S.; Maitland, Michael L.; Frankel, Paul; Argiris, Athanassios E.; Koczywas, Marianna; Gitlitz, Barbara; Thomas, Sachdev; Espinoza-Delgado, Igor; Vokes, Everett E.; Gandara, David R.; Belani, Chandra P.

    2010-01-01

    Purpose Vorinostat, a histone deacetylase inhibitor, exerts anticancer effects by both histone and nonhistone–mediated mechanisms. It also enhances the anticancer effects of platinum compounds and taxanes in non–small-cell lung cancer (NSCLC) cell lines. This phase II randomized, double-blinded, placebo-controlled study evaluated the efficacy of vorinostat in combination with carboplatin and paclitaxel in patients with advanced-stage NSCLC. Patients and Methods Patients with previously untreated stage IIIB (ie, wet) or IV NSCLC were randomly assigned (2:1) to carboplatin (area under the curve, 6 mg/mL × min) and paclitaxel (200 mg/m2 day 3) with either vorinostat (400 mg by mouth daily) or placebo. Vorinostat or placebo was given on days 1 through 14 of each 3-week cycle to a maximum of six cycles. The primary end point was comparison of the response rate. Results Ninety-four patients initiated protocol therapy. Baseline patient characteristics were similar between the two arms. The median number of cycles was four for both treatment arms. The confirmed response rate was 34% with vorinostat versus 12.5% with placebo (P = .02). There was a trend toward improvement in median progression-free survival (6.0 months v 4.1 months; P = .48) and overall survival (13.0 months v 9.7 months; P = .17) in the vorinostat arm. Grade 4 platelet toxicity was more common with vorinostat (18% v 3%; P < .05). Nausea, emesis, fatigue, dehydration, and hyponatremia also were more frequent with vorinostat. Conclusion Vorinostat enhances the efficacy of carboplatin and paclitaxel in patients with advanced NSCLC. HDAC inhibition is a promising therapeutic strategy for treatment of NSCLC. PMID:19933908

  18. Results of treatment of patients with advanced stomach cancer treated by combination of low-level laser therapy (LLLT) and other methods: ten-year experience

    Science.gov (United States)

    Mikhailov, V. A.

    2000-06-01

    In 1988 we started our investigation on the influence of low-level laser on oncologic patient. Now we have an experience of application of LLLT on more than 700 patients with the confirmed diagnosis of cancer at different stage. We used LLLT on 112 with stomach cancer 4th stage before and after operation and on patients without operating interference. LLLT investigations, with a wavelength of 890 nm, have shown that the laser therapy before operation is most effective. Laser therapy activates the immune system by increasing T-active rosette-formed cells and T-helpers and by decreasing T-suppressor cells. Application of LLLT decreases postoperative complications by 11.86 percent after palliative operations; by 9.63 percent after non-radical operations. It also promotes more rapid restorations of the motility and improves general status of patients by 58.69 percent. Investigations of low-level radiation have shown that the life-span of patients with 4th stage stomach cancer who were treated by laser therapy before surgery was increased by 2.03 percent; for those who were treated by LLLT after surgery it was increased by 1.81 times and by 3.03 times in those who took LLLT without surgery.

  19. Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay

    2016-03-01

    In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

  20. Gene Therapy of Cancer: Induction of Anti-Tumor Immunity

    Institute of Scientific and Technical Information of China (English)

    Cheng Qian; Jesus Prieto

    2004-01-01

    Many malignancies lack satisfactory treatment and new therapeutic options are urgently needed. Gene therapy is a new modality to treat both inherited and acquired diseases based on the transfer of genetic material to the tissues. Different gene therapy strategies against cancers have been developed. A considerable number of preclinical studies indicate that a great variety of cancers are amenable to gene therapy. Among these strategies,induction of anti-tumorimmunity is the most promising approach. Gene therapy with cytokines has reached unprecedented success in preclinical models of cancer. Synergistic rather than additive effects have beendemonstrated by combination of gene transfer of cytokines/chemokines, costimulatory molecules or adoptive cell therapy. Recent progress in vector technology and in imaging techniques allowing in vivo assessment of gene expression will facilitate the development of clinical applications of gene therapy, a procedure which may have a notorious impact in the management of cancers lacking effective treatment.

  1. NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu [Massachusetts General Hospital, Boston, Massachusetts (United States); Moughan, Jennifer [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Garofalo, Michael C. [University of Maryland School of Medicine, Baltimore, Maryland (United States); Bendell, Johanna [Sarah Cannon Research Institute, Nashville, Tennessee (United States); Berger, Adam C. [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Oldenburg, Nicklas B.E. [North Main Radiation Oncology, Providence, Rhode Island (United States); Anne, Pramila Rani [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Perera, Francisco [London Regional Cancer Program/Western Ontario, London, Ontario (Canada); Lee, R. Jeffrey [Intermountain Medical Center, Salt Lake City, Utah (United States); Jabbour, Salma K. [Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Nowlan, Adam [Piedmont Hospital, Atlanta, Georgia (United States); DeNittis, Albert [Main Line Community Clinical Oncology Program, Wynnewood, Pennsylvania (United States); Crane, Christopher [University of Texas-MD Anderson Cancer Center, Houston, Texas (United States)

    2015-09-01

    Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint of the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

  2. Engineering antibodies for cancer therapy.

    Science.gov (United States)

    Boder, Eric T; Jiang, Wei

    2011-01-01

    The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.

  3. Death receptors: Targets for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mahmood, Zafar [Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001 (India); Shukla, Yogeshwer, E-mail: yogeshwer_shukla@hotmail.com [Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001 (India)

    2010-04-01

    Apoptosis is the cell's intrinsic program to death, which plays an important role in physiologic growth control and homeostasis. Apoptosis can be triggered by death receptors (DRs), without any adverse effects. DRs are the members of tumor necrosis factor (TNF) receptor superfamily, known to be involved in apoptosis signaling, independent of p53 tumor-supressor gene. Selective triggering of DR-mediated apoptosis in cancer cells is a novel approach in cancer therapy. So far, the best characterized DRs are CD95 (Fas/Apo1), TNF-related apoptosis-inducing ligand receptor (TRAILR) and tumor necrosis factor receptor (TNFR). Among these, TRAILR is emerging as most promising agent for cancer therapy, because it induces apoptosis in a variety of tumor and transformed cells without any toxicity to normal cells. TRAIL treatment in combination with chemotherapy or radiotherapy enhances TRAIL sensitivity or reverses TRAIL resistance by regulating downstream effectors. This review covers the current knowledge about the DRs, summarizes main signaling in DRs and also summarizes the preclinical approaches of these DRs in cancer therapy.

  4. [Gastrointestinal surgeons should master the adjuvant therapy of colorectal cancer].

    Science.gov (United States)

    Gu, Jin; Chen, Pengju

    2015-10-01

    The diagnosis and treatment of colorectal cancer is one of the main diseases of gastrointestinal surgeons. It is very important to master the adjuvant chemotherapy of colorectal cancer for gastrointestinal surgeons. In recent years, with the development of a number of clinical trials and the appearance of new drugs, fluorouracil combined with oxaliplatin had been established as the standard regimen of adjuvant chemotherapy for colorectal cancer. In the current guidelines, stage III( colon cancer is the indication for adjuvant chemotherapy, while stage II( colon cancer should receive adjuvant chemotherapy is uncertain. Unlike colon cancer, adjuvant therapy of rectal cancer is not evidence-based. Especially, the indication and duration of adjuvant chemotherapy for rectal cancer after neoadjuvant chemoradiotherapy remain controversial. Adjuvant therapy of colorectal cancer still needs further investigation.

  5. Antiangiogenic Steroids in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Richard J. Pietras

    2005-01-01

    Full Text Available Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na+/H+ exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell–cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies

  6. Antiangiogenic Steroids in Human Cancer Therapy.

    Science.gov (United States)

    Pietras, Richard J; Weinberg, Olga K

    2005-03-01

    Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na(+)/H(+) exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell-cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies, including ovarian, non

  7. Immunotoxins and Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    ZhengLi; TaoYu; PingZhao; JieMa

    2005-01-01

    In the past decade, an increased amount of clinically-oriented research involving immunotoxins has been published. Immunotoxins are a group of artificially-made cytotoxic molecules targeting cancer cells. These molecules composed of a targeting moiety, such as a ligand or an antibody, linked to toxin moiety, which is a toxin with either truncated or deleted cell-binding domain that prevents it from binding to normal cells. Immunotoxins can be divided into two categories: chemically conjugated immunotoxins and recombinant ones. The immunotoxins of the first category have shown limited efficacy in clinical trials in patients with hematologic malignancies and solid tumors. Within the last few years, single-chain immunotoxins provide enhanced therapeutic efficacy over conjugated forms and result in improved antitumor activity. In this review, we briefly illustrate the design of the immunotoxins and their applications in clinical trials. Cellular & Molecular Immunology. 2005;2(2):106-112.

  8. Immunotoxins and Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Zheng Li; Tao Yu; Ping Zhao; Jie Ma

    2005-01-01

    In the past decade, an increased amount of clinically-oriented research involving immunotoxins has been published.Immunotoxins are a group of artificially-made cytotoxic molecules targeting cancer cells. These molecules composed of a targeting moiety, such as a ligand or an antibody, linked to toxin moiety, which is a toxin with either truncated or deleted cell-binding domain that prevents it from binding to normal cells. Immunotoxins can be divided into two categories: chemically conjugated immunotoxins and recombinant ones. The immunotoxins of the first category have shown limited efficacy in clinical trials in patients with hematologic malignancies and solid tumors. Within the last few years, single-chain immunotoxins provide enhanced therapeutic efficacy over conjugated forms and result in improved antitumor activity. In this review, we briefly illustrate the design of the immunotoxins and their applications in clinical trials. Cellular & Molecular Immunology. 2005;2(2):106-112.

  9. VEGF Inhibitors for Cancer Therapy

    OpenAIRE

    Prakash S. Sukhramani; Maulik P. Suthar

    2010-01-01

    Despite significant advances in systemic therapies, radiation oncology, and surgical techniques, many patients with cancer are still incurable. A novel therapeutic approach has been to target the vascular endothelial growth factors (VEGFs) which are often mutated and/or over-expressed in many tumors. The ligands and receptors of VEGF family are well established as key regulators of angiogenesis and vasculogenesis processes. VEGF is a homodimeric, basic, 45 kDa glycoprotein specific for vascul...

  10. New targeted therapies in pancreatic cancer.

    Science.gov (United States)

    Seicean, Andrada; Petrusel, Livia; Seicean, Radu

    2015-05-28

    Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

  11. Oncolytic virus therapy for cancer

    Directory of Open Access Journals (Sweden)

    Goldufsky J

    2013-09-01

    Full Text Available Joe Goldufsky,1 Shanthi Sivendran,3 Sara Harcharik,4 Michael Pan,4 Sebastian Bernardo,4 Richard H Stern,5 Philip Friedlander,4 Carl E Ruby,1,2 Yvonne Saenger,4 Howard L Kaufman1,2 Departments of 1Immunology & Microbiology and 2Surgery, Rush University Medical Center, Chicago IL, USA 3Hematology/Oncology Medical Specialists, Lancaster General Health, Lancaster, PA, USA, and Departments of 4Medical Oncology and 5Radiology, Tisch Cancer Institute, The Mount Sinai School of Medicine, New York, NY, USA Abstract: The use of oncolytic viruses to treat cancer is based on the selection of tropic tumor viruses or the generation of replication selective vectors that can either directly kill infected tumor cells or increase their susceptibility to cell death and apoptosis through additional exposure to radiation or chemotherapy. In addition, viral vectors can be modified to promote more potent tumor cell death, improve the toxicity profile, and/or generate host antitumor immunity. A variety of viruses have been developed as oncolytic therapeutics, including adenovirus, vaccinia virus, herpesvirus, coxsackie A virus, Newcastle disease virus, and reovirus. The clinical development of oncolytic viral therapy has accelerated in the last few years, with several vectors entering clinical trials for a variety of cancers. In this review, current strategies to optimize the therapeutic effectiveness and safety of the major oncolytic viruses are discussed, and a summary of current clinical trials is provided. Further investigation is needed to characterize better the clinical impact of oncolytic viruses, but there are increasing data demonstrating the potential promise of this approach for the treatment of human and animal cancers. Keywords: cancer, gene therapy, oncolytic therapy, virus, treatment

  12. [Hormonal therapy for prostatic cancer--state of the art].

    Science.gov (United States)

    Miyakita, Hideshi

    2005-02-01

    Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high dose estrogen. Labrie et al introduced combined use of a LHRH agonist and an androgen antagonist for prostatic cancer. Various reports demonstrated a beneficial effect for combined androgen blockade using nonsteroidal antiandrogens for advanced prostatic cancer through meta-analysis of published randomized control trials. In Japanese status, a combined androgen blockade is popular for advanced prostatic cancer as well as local cancer by J-Cap survey. There is a lot of controversy about adjuvant hormonal therapy for prostatic cancer including intermittent hormonal therapy, but the results are not gotten yet.

  13. Photodynamic therapy of gastric cancer

    Science.gov (United States)

    Kharnas, Sergey S.; Kuzin, N. M.; Zavodnov, Victor Y.; Sclyanskaya, Olga A.; Linkov, Kirill G.; Loschenov, Victor B.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Stratonnikov, Alexander A.; Steiner, Rudolf W.

    1996-01-01

    Photodynamic therapy (PDT) with the use of laser endoscopic spectrum analyzer (LESA-5), the spectral-analyzing video-imaging system, Kr laser and various types of catheters for different tumor localizations, and Phthalocyanine aluminum photosensitizers in patients with gastric cancer was discussed. PDT was carried out in fifteen patients with gastric cancer. There were the following indications for PDT: early gastric cancer (3 patients), malignant stenosis of the cardia or pyloric portion of the stomach (4 patients), cancer of gastric stump with stenosis of gastrojejunal anastomosis (1 patient), preoperative treatment of patients with large but probably resectable gastric tumor size (7 patients). Usually we used 3 - 4 seances of laser treatment 10 - 30 minutes long. Concentration of photosensitizer in normal and malignant tissue was controlled by LESA-5. Treatment was monitored by spectral-analyzing video- imaging system in fluorescent light. The results show high efficiency of PDT especially in patients with early gastric cancer (necrosis of all tumor mass, i.e. complete regression of tumor). For all other patients we obtained partial regression of gastric cancer.

  14. High-dose-rate interstitial brachytherapy in combination with androgen deprivation therapy for prostate cancer. Are high-risk patients good candidates

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ken; Narumi, Yoshifumi [Osaka Medical College, Department of Radiology, Takatsuki, Osaka (Japan); Yamazaki, Hideya; Masui, Koji [Kyoto Prefectural University of Medicine, Department of Radiology, Kyoto (Japan); Takenaka, Tadashi [National Hospital Organization Osaka National Hospital, Department of Radiology, Osaka city, Osaka (Japan); Kotsuma, Tadayuki; Yoshida, Mineo; Tanaka, Eiichi [National Hospital Organization Osaka National Hospital, Department of Radiation Oncology, Osaka city, Osaka (Japan); Yoshioka, Yasuo [Osaka University Graduate School of Medicine, Department of Radiation Oncology, Suita, Osaka (Japan); Oka, Toshitsugu [National Hospital Organization Osaka National Hospital, Department of Urology, Osaka city, Osaka (Japan)

    2014-11-15

    To evaluate the effectiveness of high-dose-rate interstitial brachytherapy (HDR-ISBT) as the only form of radiotherapy for high-risk prostate cancer patients. Between July 2003 and June 2008, we retrospectively evaluated the outcomes of 48 high-risk patients who had undergone HDR-ISBT at the National Hospital Organization Osaka National Hospital. Risk group classification was according to the criteria described in the National Comprehensive Cancer Network (NCCN) guidelines. Median follow-up was 73 months (range 12-109 months). Neoadjuvant androgen deprivation therapy (ADT) was administered to all 48 patients; 12 patients also received adjuvant ADT. Maximal androgen blockade was performed in 37 patients. Median total treatment duration was 8 months (range 3-45 months). The planned prescribed dose was 54 Gy in 9 fractions over 5 days for the first 13 patients and 49 Gy in 7 fractions over 4 days for 34 patients. Only one patient who was over 80 years old received 38 Gy in 4 fractions over 3 days. The clinical target volume (CTV) was calculated for the prostate gland and the medial side of the seminal vesicles. A 10-mm cranial margin was added to the CTV to create the planning target volume (PTV). The 5-year overall survival and biochemical control rates were 98 and 87 %, respectively. Grade 3 late genitourinary and gastrointestinal complications occurred in 2 patients (4 %) and 1 patient (2 %), respectively; grade 2 late genitourinary and gastrointestinal complications occurred in 5 patients (10 %) and 1 patient (2 %), respectively. Even for high-risk patients, HDR-ISBT as the only form of radiotherapy combined with ADT achieved promising biochemical control results, with acceptable late genitourinary and gastrointestinal complication rates. (orig.) [German] Beurteilung der Wirksamkeit von interstitieller Brachytherapie mit Hochdosisraten (''high-dose-rate interstitial brachytherapy'', HDR-ISBT) als einzige Form der Radiotherapie fuer Hochrisiko

  15. Systemic cancer multistep therapy; Systemische Krebs-Mehrschritt-Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Weigang-Koehler, K. [Medizinische Klinik 5, Arbeitsgruppe Biologische Krebstherapie, Staedtisches Klinikum Nuernberg (Germany); Kaiser, G. [Medizinische Klinik 5, Arbeitsgruppe Biologische Krebstherapie, Staedtisches Klinikum Nuernberg (Germany); Gallmeier, W.M. [Medizinische Klinik 5, Arbeitsgruppe Biologische Krebstherapie, Staedtisches Klinikum Nuernberg (Germany)

    1997-04-11

    To get an insight into the claimed efficacy of `systemic cancer multistep therapy` (sKMT) with hyperglycemia, whole-body hyperthermia and hyperoxemia, we conducted a best case analysis with 20 patients who had received sKMT alone (9 patients) or in combination with chemo- or radiotherapy (11 patients). There was no complete remission or an unquestionable partial remission when sKMT was used alone. When sKMT was combined with classical effective therapies like chemo- and radiotherapy, 1 patient had questionable complete remission and 3 patients had partial remission. In these three patients sKMT had been combined with a newly applied chemotherapy: Therefore, it remains unclear which method was effective in causing the remission. (orig.) [Deutsch] Um eine Ueberblick ueber die behauptete Wirksamkeit der systemischen Krebs-Mehrschritt-Therapie (sKMT) nach von Ardenne zu erlangen, fuehrten wir eine Best-case-Analyse bei 20 Patienten durch, die die sKMT ohne Chemotherapie (9 Patienten) und in Kombination mit Chemo- bzw. Strahlentherapie (11 Patienten) erhalten hatten. sKMT allein hatte zu keiner kompletten Remission oder sicheren partiellen Remission gefuehrt. Bei der Kombination von sKMT mit klassischen Therapieverfahren wie Chemotherapie und Bestrahlung trat bei einem Patienten eine fragliche komplette Remission ein sowie bei 3 Patienten eine partielle Remission. Im letzteren Fall war jeweils eine fuer den Patienten neue Chemotherapie mit der sKMT kombiniert worden, so dass unklar bleibt, was die Verbesserung herbeifuehrte. (orig.)

  16. MR-Guided Pulsed High-Intensity Focused Ultrasound Enhancement of Gene Therapy Combined With Androgen Deprivation and Radiotherapy for Prostate Cancer Treatment

    Science.gov (United States)

    2009-09-01

    ultrasound . J. Acoust. Soc.Am. 72 1926-1932, (1982) (7) Neppiras E A. Acoustic cavitation . Physics reports 61(3): 159-251, (1980) (8) ter Haar G R, Daniels...Guided Pulsed High-Intensity Focused Ultrasound Enhancement of 5b. GRANT NUMBER W81XWH-08-1-0469 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...failing to This work is aimed to study MR guided high intensity focused ultrasound (MRgHIFU) enhancement of gene therapy for Prostate Cancer. The

  17. Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Pollom, Erqi L.; Deng, Lei [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Pai, Reetesh K. [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Brown, J. Martin; Giaccia, Amato; Loo, Billy W.; Shultz, David B.; Le, Quynh Thu; Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Chang, Daniel T., E-mail: dtchang@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2015-07-01

    Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action of toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.

  18. Assessment of quality of life and changes in body composition in men with localized prostate cancer on hormone therapy combined with radiotherapy prostate cancer, quality of life, body composition

    Energy Technology Data Exchange (ETDEWEB)

    Pires, Daniele de Campos; Salvajoli, Joao Victor; Gagliardi, Joao Fernando; Evangelista, Alexandre Lopes; Lopes, Charles Ricardo; Cruz, Ticiane

    2014-07-01

    Objective: the aim of this study was to evaluate the quality of life and changes in body composition in adult men (71.3 ± 6.9 years) with prostate cancer on hormone therapy combined with radiotherapy. Methodology: to assess the quality of life of individuals, we used the 36-Item Short Form Health Survey (SF-36), which is a tool developed to survey health status in the Medical Outcomes Study. This questionnaire was applied at the beginning and six months after the start of the study. Weight was measured and the percentage of fat was estimated from an anthropometric equation from Jackson and Pollock (1978). The period of assessments and reassessments was September 2009 to October 2010. Radiotherapy was performed in other hospitals (information contained in participant's data form), as the management of patients was conducted at the oncology pharmacy of Varzea do Carmo Specialties Clinic. Results: of the eight domains of the SF-36 questionnaire, five were worse with significant differences from the first to the second assessment. They are: overall health status (p <0.01), vitality (p <0.01), functional capacity (p <0.01), social functioning (p <0.01) and pain (p <0, 01). Body weight ranged statistically significant (p <0.01) between the first evaluation (75.3 ± 12.5kg) and the second evaluation (77.4 ± 12.5kg). The same occurred with the percentage of fat, where the initial values (25.1 ± 3.8%) and final (25.8 ± 3.5%) experienced statistically significant difference (p <0.01). Conclusion: the results of this study showed that hormone therapy combined with radiotherapy led to a gain of weight and body fat percentage in the men evaluated, as well as deterioration in the quality of life of these patients. Therefore, it is necessary to continue researching this topic in order to develop strategies that mitigate the side effects of hormone therapy. The risks of hormone therapy should be evaluated and compared with gains in order to define the length of treatment

  19. Minimally invasive local therapies for liver cancer

    Institute of Scientific and Technical Information of China (English)

    David Li; Josephine Kang; Benjamin J Golas; Vincent W Yeung; David C Madoff

    2014-01-01

    Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have iflled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed.

  20. Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy

    Directory of Open Access Journals (Sweden)

    Jaleh Barar

    2013-02-01

    Full Text Available It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called “tumor microenvironment (TME”, in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.

  1. Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy.

    Science.gov (United States)

    Barar, Jaleh; Omidi, Yadollah

    2013-01-01

    It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called "tumor microenvironment (TME)", in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs) that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF) functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.

  2. Up-regulation of insulin-like growth factor-binding protein 3 by 5-fluorouracil (5-FU) leads to the potent anti-proliferative effect of androgen deprivation therapy combined with 5-FU in human prostate cancer cell lines.

    Science.gov (United States)

    Kawabata, Rumi; Oie, Shinji; Takahashi, Masayuki; Kanayama, Hiroomi; Oka, Toshinori; Itoh, Kohji

    2011-06-01

    In this study, we investigated the synergistic mechanism of anti-androgen and 5-fluorouracil (5-FU) combination therapy against castration-resistant prostate cancer (CRPC). Four prostate cancer cell lines, LNCaP, 22Rv1, DU145 and PC3, were examined for their growth dependency on androgens and the insulin-like growth factor 1 (IGF1). We assessed the expression changes of certain growth factor receptors and regulating proteins when treated with 5-FU, and found that 5-FU increased the expression of the IGF-binding protein 3 (IGFBP3). Furthermore, 5-FU inhibited the phosphorylation of Akt and p70 S6K, while the knockdown of IGFBP3 reduced the levels of poly (ADP-ribose) polymerase cleaved by 5-FU in PC3 cells. Therefore, the up-regulation of IGFBP3 by 5-FU not only inhibits cell growth by reducing the IGF1 signal but also induces apoptosis in PC3 cells. The synergistic effect of bicalutamide and 5-FU on 22Rv1 cells was reduced by IGFBP3 gene silencing using small-interfering RNA. These results suggest that the up-regulation of IGFBP3 induced by 5-FU plays an important role in the potent anti-tumor effect of 5-FU combined with anti-androgens on CRPC. Androgen-deprivation therapy combined with 5-FU could therefore be an appropriate therapy for CRPC patients.

  3. The influence of hormone therapies on colon and rectal cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels;

    2016-01-01

    followed 1995-2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression...... analyses with 5-year age bands included hormone exposures as time-dependent covariates. Use of estrogen-only therapy and combined therapy were associated with decreased risks of colon cancer (adjusted incidence rate ratio 0.77, 95 % confidence interval 0.68-0.86 and 0.88, 0.80-0.96) and rectal cancer (0......Exogenous sex hormones seem to play a role in colorectal carcinogenesis. Little is known about the influence of different types or durations of postmenopausal hormone therapy (HT) on colorectal cancer risk. A nationwide cohort of women 50-79 years old without previous cancer (n = 1,006,219) were...

  4. Magnetic nanoparticle-based cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Yu Jing; Huang Dong-Yan; Muhammad Zubair Yousaf; Hou Yang-Long; Gao Song

    2013-01-01

    Nanoparticles (NPs) with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles (MNPs) that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging (MRI) monitoring cancer therapy and magnetic tissue engineering are also addressed.

  5. 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

  6. Modulating autophagy: a strategy for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Jun-Lin Li; Shao-Liang Han; Xia Fan

    2011-01-01

    Autophagy is a process in which long-lived proteins,damaged cell organelles,and other cellular particles are sequestered and degraded.This process is important for maintaining the cellular microenvironment when the cell is under stress.Many studies have shown that autophagy plays a complex role in human diseases,especially in cancer,where it is known to have paradoxical effects.Namely,autophagy provides the energy for metabolism and tumor growth and leads to cell death that promotes tumor suppression.The link between autophagy and cancer is also evident in that some of the genes that regulate carcinogenesis,oncogenes and tumor suppressor genes,participate in or impact the autophagy process.Therefore,modulating autophagy will be a valuable topic for cancer therapy.Many studies have shown that autophagy can inhibit the tumor growth when autophagy modulators are combined with radiotherapy and/or chemotherapy.These findings suggest that autophagy may be a potent target for cancer therapy.

  7. MR Guided Pulsed High Intensity Focused Ultrasound Enhancement of Gene Therapy Combined with Androgen Deprivation and Radiotherapy for Prostate Cancer Treatment

    Science.gov (United States)

    2012-09-01

    the observed enhancement are not well understood. It is thought mainly due to the nonthermal effects of ultrasound —mechanical streaming and cavitation ...AD ________________ Award Number: W81XWH-08-1-0469 TITLE: MR Guided Pulsed High Intensity Focused Ultrasound Enhancement of (Enter title of award...Intensity Focused Ultrasound Enhancement of 5b. GRANT NUMBER Gene Therapy Combined with Androgen Deprivation and Radiotherapy W81XWH-08-1-0469 for Prostate

  8. A New Era for Cancer Target Therapies: Applying Systems Biology and Computer-Aided Drug Design to Cancer Therapies.

    Science.gov (United States)

    Wong, Yung-Hao; Chiu, Chia-Chiun; Lin, Chih-Lung; Chen, Ting-Shou; Jheng, Bo-Ren; Lee, Yu-Ching; Chen, Jeremy; Chen, Bor-Sen

    In recent years, many systems biology approaches have been used with various cancers. The materials described here can be used to build bases to discover novel cancer therapy targets in connection with computer-aided drug design (CADD). A deeper understanding of the mechanisms of cancer will provide more choices and correct strategies in the development of multiple target drug therapies, which is quite different from the traditional cancer single target therapy. Targeted therapy is one of the most powerful strategies against cancer and can also be applied to other diseases. Due to the large amount of progress in computer hardware and the theories of computational chemistry and physics, CADD has been the main strategy for developing novel drugs for cancer therapy. In contrast to traditional single target therapies, in this review we will emphasize the future direction of the field, i.e., multiple target therapies. Structure-based and ligand-based drug designs are the two main topics of CADD. The former needs both 3D protein structures and ligand structures, while the latter only needs ligand structures. Ordinarily it is estimated to take more than 14 years and 800 million dollars to develop a new drug. Many new CADD software programs and techniques have been developed in recent decades. We conclude with an example where we combined and applied systems biology and CADD to the core networks of four cancers and successfully developed a novel cocktail for drug therapy that treats multiple targets.

  9. Targeted therapies in upper gastrointestinal cancer

    NARCIS (Netherlands)

    Kordes, S.

    2016-01-01

    Upper gastrointestinal (GI) cancers, as esophageal, gastric and pancreatic cancer, are still highly lethal diseases, in spite of advances in surgery, radiotherapy, chemotherapy and specific targeted therapy. Especially when patients are diagnosed with locally advanced or metastasized disease, upper

  10. Types of Cancer Treatment: Hormone Therapy

    Science.gov (United States)

    Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.

  11. Targeted alpha therapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Rizvi, Syed [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Li Yong [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Tsui, Wendy [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Zhang, David [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Song, Emma [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Qu, C F [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Kearsley, John [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Graham, Peter [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Thompson, John [Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown 2050 NSW (Australia)

    2004-08-21

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The {sup 213}Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 {mu

  12. Stereotactic radiosurgery: a "targeted" therapy for cancer

    Institute of Scientific and Technical Information of China (English)

    Ming Zeng; Liang-Fu Han

    2012-01-01

    The developments of medicine always follow innovations in science and technology.In the past decade,such innovations have made cancer-related targeted therapies possible.In general,the term "targeted therapy" has been used in reference to cellular and molecular level oriented therapies.However,improvements in the delivery and planning of traditional radiation therapy have also provided cancer patients more options for "targeted" treatment,notably stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT).In this review,the progress and controversies of SRS and SBRT are discussed to show the role of stereotactic radiation therapy in the ever evolving multidisciplinary care of cancer patients.

  13. Emerging therapies in gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    Jyoti Nautiyal; Arun K Rishi; Adhip PN Majumdar

    2006-01-01

    Members of the receptor tyrosine kinase family, that include EGFR, ErbB-2/HER-2, ErbB-3/HER-3 and ErbB-4/HER-4, are frequently implicated in experimental models of epithelial cell neoplasia as well as in human cancers.Therefore, interference with the activation of these growth factor receptors represents a promising strategy for development of novel and selective anticancer therapies.Indeed, a number of inhibitors that target either EGFR or HER-2, with the exception of a few that target both;have been developed for treatment of epithelial cancers.Since most solid tumors express different ErbB receptors and/or their ligands, identification of inhibitor(s), targeting multiple EGFR family members may provide a therapeutic benefit to a broader patient population. Here we describe the significance of an ErbB family of receptors in epithelial cancers, and summarize different available therapeutics targeting these receptors. It also emphasizes the need to develop pan-ErbB inhibitors and discusses EGF-Receptor Related Protein, a recently isolated negative regulator of EGFR as a potential pan-ErbB therapeutic for a wide variety of epithelial cancers.

  14. Combined 5-FU and ChoKα inhibitors as a new alternative therapy of colorectal cancer: evidence in human tumor-derived cell lines and mouse xenografts.

    Directory of Open Access Journals (Sweden)

    Ana de la Cueva

    Full Text Available BACKGROUND: Colorectal cancer (CRC is the third major cause of cancer related deaths in the world. 5-fluorouracil (5-FU is widely used for the treatment of colorectal cancer but as a single-agent renders low response rates. Choline kinase alpha (ChoKα, an enzyme that plays a role in cell proliferation and transformation, has been reported overexpressed in many different tumors, including colorectal tumors. ChoKα inhibitors have recently entered clinical trials as a novel antitumor strategy. METHODOLOGY/PRINCIPAL FINDINGS: ChoKα specific inhibitors, MN58b and TCD-717, have demonstrated a potent antitumoral activity both in vitro and in vivo against several tumor-derived cell line xenografts including CRC-derived cell lines. The effect of ChoKα inhibitors in combination with 5-FU as a new alternative for the treatment of colon tumors has been investigated both in vitro in CRC-tumour derived cell lines, and in vivo in mouse xenografts models. The effects on thymidilate synthase (TS and thymidine kinase (TK1 levels, two enzymes known to play an essential role in the mechanism of action of 5-FU, were analyzed by western blotting and quantitative PCR analysis. The combination of 5-FU with ChoKα inhibitors resulted in a synergistic effect in vitro in three different human colon cancer cell lines, and in vivo against human colon xenografts in nude mice. ChoKα inhibitors modulate the expression levels of TS and TK1 through inhibition of E2F production, providing a rational for its mechanism of action. CONCLUSION/SIGNIFICANCE: Our data suggest that both drugs in combination display a synergistic antitumoral effect due to ChoKα inhibitors-driven modulation of the metabolization of 5-FU. The clinical relevance of these findings is strongly supported since TCD-717 has recently entered Phase I clinical trials against solid tumors.

  15. Combined interventional therapies of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun Qian; Gan-Sheng Feng; Thomas Vogl

    2003-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonmalignancies in the world, responsible for an estimated one million deaths annually. It has a poor prognosis due to its rapid infiltrating growth and complicating liver cirrhosis.Surgical resection, liver transplantation and cryosurgery are considered the best curative options, achieving a high rate of complete response, especially in patients with small HCC and good residual liver function. In nonsurgery, regional interventional therapies have led to a major breakthrough in the management of unresectable HCC, which include transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave coagulation therapy (MCT), laser-induced thermotherapy (LITT), etc. As a result of the technical development of locoregional approaches for HCC during the recent decades,the range of combined interventional therapies has been continuously extended. Most combined multimodal interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone,and play more important roles in treating unresectable HCC.

  16. Cancer immunology - development of novel anti-cancer therapies.

    Science.gov (United States)

    Rothschild, Sacha I; Thommen, Daniela S; Moersig, Wolfgang; Müller, Philipp; Zippelius, Alfred

    2015-01-01

    The vast majority of tumours are characterised by high frequencies of genetic and epigenetic alterations resulting in tumour-specific antigens, which may, in principle, be recognised by cytotoxic T cells. Though early clinical immunotherapy trials have yielded mixed results with ambiguous clinical benefit, cancer immunotherapy is now attracting increasing attention as a viable therapeutic option, mainly in melanoma and lung cancer, but increasingly also in other malignancies. In particular, recent therapeutic efforts targeting inhibitory receptors on T cells to overcome tumour-induced immune dysfunction have the potential to reshape current treatment standards in oncology. The clinical development has been pioneered by the antibody ipilimumab, which blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and has demonstrated survival benefit in two randomised landmark trials in melanoma. Capitalising on this success, the research on the clinical implication of T cell checkpoint inhibition has been boosted. Early clinical trials have demonstrated meaningful response rates, sustained clinical benefits with encouraging survival rates and good tolerability of next-generation checkpoint inhibitors, including programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors, across multiple cancer types. Attractive perspectives include the concurrent blockade of immunological (non-redundant) checkpoints, which has recently been demonstrated using combinations of immune checkpoint modulators themselves or with other therapies, such as chemotherapy, targeted therapy or radiotherapy. This article summarises the mechanism of action and subsequent clinical studies of immune checkpoint antibodies in oncology with a particular focus on melanoma and lung cancer.

  17. Discodermolide analogues as the chemical component of combination bacteriolytic therapy.

    Science.gov (United States)

    Smith, Amos B; Freeze, B Scott; LaMarche, Matthew J; Sager, Jason; Kinzler, Kenneth W; Vogelstein, Bert

    2005-08-01

    The marine natural product (+)-discodermolide (1) and several simplified analogues of this microtubule-stabilizing agent have proven to be potent in vitro cell growth inhibitory agents in several human cancer cell lines. Here, we demonstrate the in vivo efficacy of discodermolide and several simplified congeners, both as stand-alone anti-tumor agents and, in the case of (+)-2,3-anhydrodiscodermolide (3), as a chemical component of the combination bacteriolytic therapy. A single intravenous injection of (+)-3 plus genetically modified Clostridium novyi-NT spores caused rapid and complete regressions of tumors in mice bearing HCT116 colorectal cancer xenografts.

  18. Impact of Pretreatment Combined {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging on Radiation Therapy Treatment Decisions in Locally Advanced Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Sweet Ping, E-mail: sweet.ng@petermac.org [Peter MacCallum Cancer Centre, Melbourne (Australia); David, Steven [Peter MacCallum Cancer Centre, Melbourne (Australia); Alamgeer, Muhammad; Ganju, Vinod [Monash Cancer Centre, Melbourne (Australia)

    2015-09-01

    Purpose: To assess the diagnostic performance of pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC). Methods and Materials: Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body {sup 18}F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings. Results: A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2. Conclusions: Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary

  19. Peptide Vaccine Therapy in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shi-Yu Yang

    2012-08-01

    Full Text Available Colorectal cancer is the third most common cause of cancer-related deaths and the second most prevalent (after breast cancer in the western world. High metastatic relapse rates and severe side effects associated with the adjuvant treatment have urged oncologists and clinicians to find a novel, less toxic therapeutic strategy. Considering the limited success of the past clinical trials involving peptide vaccine therapy to treat colorectal cancer, it is necessary to revise our knowledge of the immune system and its potential use in tackling cancer. This review presents the efforts of the scientific community in the development of peptide vaccine therapy for colorectal cancer. We review recent clinical trials and the strategies for immunologic monitoring of responses to peptide vaccine therapy. We also discuss the mechanisms underlying the therapy and potential molecular targets in colon cancer.

  20. Bacterial proteins and peptides in cancer therapy

    Science.gov (United States)

    Chakrabarty, Ananda M; Bernardes, Nuno; Fialho, Arsenio M

    2014-01-01

    Cancer is one of the most deadly diseases worldwide. In the last three decades many efforts have been made focused on understanding how cancer grows and responds to drugs. The dominant drug-development paradigm has been the “one drug, one target.” Based on that, the two main targeted therapies developed to combat cancer include the use of tyrosine kinase inhibitors and monoclonal antibodies. Development of drug resistance and side effects represent the major limiting factors for their use in cancer treatment. Nowadays, a new paradigm for cancer drug discovery is emerging wherein multi-targeted approaches gain ground in cancer therapy. Therefore, to overcome resistance to therapy, it is clear that a new generation of drugs is urgently needed. Here, regarding the concept of multi-targeted therapy, we discuss the challenges of using bacterial proteins and peptides as a new generation of effective anti-cancer drugs. PMID:24875003

  1. Synergistic nanomedicine by combined gene and photothermal therapy.

    Science.gov (United States)

    Kim, Jinhwan; Kim, Jihoon; Jeong, Cherlhyun; Kim, Won Jong

    2016-03-01

    To date, various nanomaterials with the ability for gene delivery or photothermal effect have been developed in the field of biomedicine. The therapeutic potential of these nanomaterials has raised considerable interests in their use in potential next-generation strategies for effective anticancer therapy. In particular, the advancement of novel nanomedicines utilizing both therapeutic strategies of gene delivery and photothermal effect has generated much optimism regarding the imminent development of effective and successful cancer treatments. In this review, we discuss current research progress with regard to combined gene and photothermal therapy. This review focuses on synergistic therapeutic systems combining gene regulation and photothermal ablation as well as logically designed nano-carriers aimed at enhancing the delivery efficiency of therapeutic genes using the photothermal effect. The examples detailed in this review provide insight to further our understanding of combinatorial gene and photothermal therapy, thus paving the way for the design of promising nanomedicines.

  2. PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE

    Science.gov (United States)

    Agostinis, Patrizia; Berg, Kristian; Cengel, Keith A.; Foster, Thomas H.; Girotti, Albert W.; Gollnick, Sandra O.; Hahn, Stephen M.; Hamblin, Michael R.; Juzeniene, Asta; Kessel, David; Korbelik, Mladen; Moan, Johan; Mroz, Pawel; Nowis, Dominika; Piette, Jacques; Wilson, Brian C.; Golab, Jakub

    2011-01-01

    Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. PMID:21617154

  3. Approach of combined cancer gene therapy and radiation: response of promoters to ionizing radiation; Approche de therapie genique anti-cancereuse combinee a l'irradiation: etude de la reponse de promoteurs aux radiations ionisantes

    Energy Technology Data Exchange (ETDEWEB)

    Anstett, A

    2005-09-15

    Gene therapy is an emerging cancer treatment modality. We are interested in developing a radiation-inducible gene therapy system to sensitize the tumor vasculature to the effects of ionizing radiation (IR) treatment. An expression system based on irradiation-inducible promoters will drive the expression of anti-tumor genes in the tumor vasculature. Solid tumors are dependent on angio genesis, a process in which new blood vessels are formed from the pre-existing vasculature. Vascular endothelial cells are un transformed and genetically stable, thus avoiding the problem of resistance to the treatments. Vascular endothelial cells may therefore represent a suitable target for this therapeutic gene therapy strategy.The identification of IR-inducible promoters native to endothelial cells was performed by gene expression profiling using cDNA micro array technology. We describe the genes modified by clinically relevant doses of IR. The extension to high doses aimed at studying the effects of total radiation delivery to the tumor. The radio-inductiveness of the genes selected for promoter study was confirmed by RT-PCR. Analysis of the activity of promoters in response to IR was also assessed in a reporter plasmid. We found that authentic promoters cloned onto a plasmid are not suitable for cancer gene therapy due to their low induction after IR. In contrast, synthetic promoters containing repeated sequence-specific binding sites for IR-activated transcription factors such as NF-{kappa}B are potential candidates for gene therapy. The activity of five tandemly repeated TGGGGACTTTCCGC elements for NF-{kappa}B binding in a luciferase reporter was increased in a dose-dependent manner. Interestingly, the response to fractionated low doses was improved in comparison to the total single dose. Thus, we put present evidence that a synthetic promoter for NF-{kappa}B specific binding may have application in the radio-therapeutic treatment of cancer. (author)

  4. Novel therapy for advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yue; Zhang; Shenhong; Wu

    2015-01-01

    Gastric cancer(GC) is a common lethal malignancy.Gastroesophageal junction and gastric cardia tumors are the fastest rising malignancies due to increasing prevalence of obesity and acid reflex in the United States.Traditional chemotherapy remains the main treatment with trastuzumab targeting human epidermal growth factor receptor 2 positive disease.The median overall survival(OS) is less than one year for advanced GC patients; thus,there is an urgent unmet need to develop novel therapy for GC.Although multiple targeted agents were studied,only the vascular endothelial growth factor receptor inhibitor ramucirumab was approved recently by the United States Food and Drug Administration because of its 1.4 mo OS benefit(5.2 mo vs 3.8 mo,P = 0.047) as a single agent; 2.2 mo improvement of survival(9.6 mo vs 7.4 mo,P = 0.017) when combined with paclitaxel in previously treated advanced GC patients.It is the first single agent approved for previously treated GC and the second biologic agent after trastuzumab.Even with limited success,targeted therapy may be improved by developing new biomarkers.Immune therapy is changing the paradigm of cancer treatment and is presently under active investigation for GC in clinical trials.More evidence supports GC stem cells existence and early stage studies are looking for its potential therapeutic possibilities.

  5. Personalized Radiation Therapy (PRT) for Lung Cancer.

    Science.gov (United States)

    Jin, Jian-Yue; Kong, Feng-Ming Spring

    2016-01-01

    This chapter reviews and discusses approaches and strategies of personalized radiation therapy (PRT) for lung cancers at four different levels: (1) clinically established PRT based on a patient's histology, stage, tumor volume and tumor locations; (2) personalized adaptive radiation therapy (RT) based on image response during treatment; (3) PRT based on biomarkers; (4) personalized fractionation schedule. The current RT practice for lung cancer is partially individualized according to tumor histology, stage, size/location, and combination with use of systemic therapy. During-RT PET-CT image guided adaptive treatment is being tested in a multicenter trial. Treatment response detected by the during-RT images may also provide a strategy to further personalize the remaining treatment. Research on biomarker-guided PRT is ongoing. The biomarkers include genomics, proteomics, microRNA, cytokines, metabolomics from tumor and blood samples, and radiomics from PET, CT, SPECT images. Finally, RT fractionation schedule may also be personalized to each individual patient to maximize therapeutic gain. Future PRT should be based on comprehensive considerations of knowledge acquired from all these levels, as well as consideration of the societal value such as cost and effectiveness.

  6. Oncolytic virus therapy for cancer.

    Science.gov (United States)

    Goldufsky, Joe; Sivendran, Shanthi; Harcharik, Sara; Pan, Michael; Bernardo, Sebastian; Stern, Richard H; Friedlander, Philip; Ruby, Carl E; Saenger, Yvonne; Kaufman, Howard L

    2013-01-01

    The use of oncolytic viruses to treat cancer is based on the selection of tropic tumor viruses or the generation of replication selective vectors that can either directly kill infected tumor cells or increase their susceptibility to cell death and apoptosis through additional exposure to radiation or chemotherapy. In addition, viral vectors can be modified to promote more potent tumor cell death, improve the toxicity profile, and/or generate host antitumor immunity. A variety of viruses have been developed as oncolytic therapeutics, including adenovirus, vaccinia virus, herpesvirus, coxsackie A virus, Newcastle disease virus, and reovirus. The clinical development of oncolytic viral therapy has accelerated in the last few years, with several vectors entering clinical trials for a variety of cancers. In this review, current strategies to optimize the therapeutic effectiveness and safety of the major oncolytic viruses are discussed, and a summary of current clinical trials is provided. Further investigation is needed to characterize better the clinical impact of oncolytic viruses, but there are increasing data demonstrating the potential promise of this approach for the treatment of human and animal cancers.

  7. Nanoshells for photothermal cancer therapy.

    Science.gov (United States)

    Morton, Jennifer G; Day, Emily S; Halas, Naomi J; West, Jennifer L

    2010-01-01

    Cancer is a leading cause of death in the United States and contributes to yearly rising health care costs. Current methods of treating cancer involve surgical removal of easily accessible tumors, radiation therapy, and chemotherapy. These methods do not always result in full treatment of the cancer and can in many cases damage healthy cells both surrounding the tissue area and systemically. Nanoshells are optically tunable core/shell nanoparticles that can be fabricated to strongly absorb in the near-infrared (NIR) region where light transmits deeply into tissue. When injected systemically, these particles have been shown to accumulate in the tumor due to the enhanced permeability and retention (EPR) effect and induce photothermal ablation of the tumor when irradiated with an NIR laser. Tumor specificity can be increased via functionalizing the nanoshell surface with tumor-targeting moieties. Nanoshells can also be made to strongly scatter light and therefore can be used in various imaging modalities such as dark-field microscopy and optical coherence tomography (OCT).

  8. Gene Therapy In Oral Cancer : An Overview

    OpenAIRE

    2010-01-01

    The treatment and prevention of oral cancer is one of the major hurdles in the field ofcancer. Gene therapy is one of the recent advances in this field to tackle this hurdle with promisingprospects. This overview introduces the reader into the basic idea of gene therapy, types of genetherapy and the various modes of introduction of therapeutic gene into the cancer affected cell.

  9. Multifunctional Theranostic Agent of Cu2(OH)PO4 Quantum Dots for Photoacoustic Image-Guided Photothermal/Photodynamic Combination Cancer Therapy.

    Science.gov (United States)

    Guo, Wei; Qiu, Zhenyu; Guo, Chongshen; Ding, Dandan; Li, Tianchan; Wang, Fei; Sun, Jianzhe; Zheng, Nannan; Liu, Shaoqin

    2017-03-22

    Image-guided phototherapy is considered to be a prospective technique for cancer treatment because it can provide both oncotherapy and bioimaging, thus achieving an optimized therapeutic efficacy and higher treatment accuracy. Compared to complicated systems with multiple components, using a single material for this multifunctional purpose is preferable. In this work, we strategically fabricated poly(acrylic acid)- (PAA-) coated Cu2(OH)PO4 quantum dots [denoted as Cu2(OH)PO4@PAA QDs], which exhibit a strong near-infrared photoabsorption ability. As a result, an excellent photothermal conversion ability and the photoactivated formation of reactive oxygen species could be realized upon NIR irradiation, concurrently meeting the basic requirements for photothermal and photodynamic therapies. Moreover, phototherapeutic investigations on both cervical cancer cells in vitro and solid tumors of an in vivo mice model illustrated the effective antitumor effects of Cu2(OH)PO4@PAA upon 1064-nm laser irradiation, with no detectable lesions in major organs during treatment. Meanwhile, Cu2(OH)PO4@PAA is also an exogenous contrast for photoacoustic tomography (PAT) imaging to depict tumors under NIR irradiation. In brief, the Cu2(OH)PO4@PAA QDs prepared in this work are expected to serve as a multifunctional theranostic platform.

  10. Combination goserelin and tamoxifen therapy in premenopausal advanced breast cancer: a multicentre study by the ITMO group. Italian Trials in Medical Oncology.

    Science.gov (United States)

    Buzzoni, R.; Biganzoli, L.; Bajetta, E.; Celio, L.; Fornasiero, A.; Mariani, L.; Zilembo, N.; Di Bartolomeo, M.; Di Leo, A.; Arcangeli, G.

    1995-01-01

    It has been suggested that tamoxifen may improve the efficacy of medical castration with luteinising hormone-releasing hormone analogues, but very few data have so far been published concerning the clinical and endocrinological activity of this therapeutic modality. In this phase II multicentre trial conducted by the Italian Trials in Medical Oncology group (ITMO), 64 premenopausal patients with hormone receptor-positive or unknown breast cancer were treated with monthly s.c. injections of goserelin 3.6 mg, in association with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced disease. All of the patients were evaluable for efficacy and there was an overall response rate of 41% (95% confidence interval 28-52%), with 7 of the 26 responders achieving complete remission. The median time to response was 4 months (range 2-17), and the median response duration was 13 months (range 6-37 +). Better responses were observed in soft tissues (51%); the response in visceral and bone metastases was respectively 19% and 37%. Serum concentrations of gonadotrophins and oestradiol were significantly decreased by the treatment, oestrogen levels being constantly suppressed to within the range observed in post-menopausal women. No significant change was detected in serum testosterone levels. In our experience, although it was not associated with any increased clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a feasible approach in the management of premenopausal advanced breast cancer. PMID:7734310

  11. Potential risk and benefit of the combination of trastuzumab to chemotherapy and radiation therapy in non-metastatic breast cancer; Benefice et risques potentiels de l'association du trastuzumab a la chimiotherapie et a la radiotherapie dans le cancer du sein non metastatique

    Energy Technology Data Exchange (ETDEWEB)

    Belkacemi, Y. [CLCC Oscar-Lambret, Universite de Lille-2, Dept. d' Oncologie-Radiotherapie, 59 - Lille (France); Laharie-Mineur, H. [CLCC, institut Bergonie, 33 - Bordeaux (France); Gligorov, J. [APHP, Hopital Tenon, Cancer-Est, 75 - Paris (France); Azria, D. [CLCC Val d' Aurelle-Paul-Lamarque, Inserm, EMI 0227, 34 - Montpellier (France)

    2007-09-15

    Trastuzumab (Herceptin) is the first humanized monoclonal antibody targeting the HER2 antigen in breast cancer. HER2 receptor has been individualised 20 years ago. During the past 10 years, trastuzumab administration has radically modified the prognosis of the patients that are treated for HER2 positive breast cancer. Its efficacy has been demonstrated in the metastatic and adjuvant settings. While, trastuzumab based-regimens became the standard of care in the treatment of HER2/neu positive breast cancer, the optimal combination (concurrently or sequentially) to chemotherapy and radiation therapy is still unknown. Indeed, while the concurrent administration of trastuzumab and anthracyclines is not recommended because of a high risk of cardiac toxicity, there is no published data on the best sequence of trastuzumab and radiation therapy administration, particularly when internal mammary chain is involved. The benefit/risk ratio of the concurrent and sequential administration of trastuzumab with chemotherapy and radiation therapy will be discussed in this review. (authors)

  12. Targeted therapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shou-Ching Tang

    2004-01-01

    @@ 1 Introduction Recent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes,giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human lung cancer. In addition, many signal transduction pathways have been discovered that play important roles in lung cancer. Novel strategy of anti-cancer drug development now involves the identification and development of targeted therapy that interrupts one or more than one pathways or cross-talk among different signal transduction pathways. In addition, efforts are underway that combine the traditional cytotoxic (non-targeted) agents with the biological (targeted) therapy to increase the response rate and survival in patients with lung cancer, especially advanced non-small cell lung cancer (NSCLC).

  13. Antiangiogenic Steroids in Human Cancer Therapy

    OpenAIRE

    2005-01-01

    Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of ...

  14. Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Tobias Engel Ayer Botrel

    Full Text Available Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA and Western Europe. Androgen-deprivation therapy alone (ADT remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel for metastatic hormone-naive prostate cancer (mHNPC.Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR or risk ratio (RR with their corresponding 95% confidence intervals (95% CI.The final analysis included 3 trials comprising 2,264 patients (mHNPC. Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001, and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%. The biochemical progression-free survival (bPFS also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001, also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%. Finally, the combination of ADT with docetaxel showed a superior overall survival (OS compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001, with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%. A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002. In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003. Regarding adverse events and severe toxicity (grade ≥3, the group receiving the combined therapy

  15. Nanomaterials in Targeting Cancer Stem Cells for Cancer Therapy

    Science.gov (United States)

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

    2017-01-01

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

  16. Targeting DNA Replication Stress for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-08-01

    Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.

  17. Targeting DNA Replication Stress for Cancer Therapy

    Science.gov (United States)

    Zhang, Jun; Dai, Qun; Park, Dongkyoo; Deng, Xingming

    2016-01-01

    The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR) mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress. PMID:27548226

  18. Proton therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Romaine; C; Nichols; Soon; Huh; Zuofeng; Li; Michael; Rutenberg

    2015-01-01

    Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy.

  19. Nanoparticle-based Combination Therapies for Cancer Treatment%纳米给药系统的抗肿瘤药物联合治疗策略∗

    Institute of Scientific and Technical Information of China (English)

    叶鹏; 张文典; 杨坦; 盖永康; 项光亚

    2016-01-01

    Combination chemotherapy and nanoparticle drug delivery are two promising strategies in cancer treatment. The use of multiple therapeutic agents in combination provides synergistic effects among different drugs against cancer cells and suppresses drug resistance through distinct mechanisms of action.Nanocarriers can improve anti-tumor effects of drugs and reduce systemic toxicity through delivering drugs into the tumor tissue specially. Recently, many studies are aiming to encapsulate multiple agents into nanocarriers to optimize the anti-tumor effects. In the present review, the recent advances of nanoparticle platforms applied with co-delivering two or more drugs were summarized and the various combination strategies based on nanoparticles in oncology were discussed.%药物联合治疗和纳米给药系统的应用在肿瘤药物治疗领域均展现出广阔的前景。多种治疗药物联用能够同时作用于多个靶点,发挥药物间的协同作用,提高疗效并对抗肿瘤细胞的耐药性。纳米给药系统能够实现药物对肿瘤细胞的靶向传递,提高抗肿瘤效果,降低不良反应,改善患者预后。上述两项治疗策略的融合有望进一步提升药物化学治疗和药物联用的效果。该文介绍近年来纳米给药系统在抗肿瘤药物联合治疗方面的应用情况,并对各种药物联用策略进行分类阐述。

  20. Adjuvant therapy in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Paula Ghaneh; John Slavin; Robert Sutton; Mark Hartley; John P Neoptolemos

    2001-01-01

    The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic csncer, leading to a drsmatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone.The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

  1. Cancer incidence and novel therapies developed in Japan.

    Science.gov (United States)

    Iwasaki, M

    2012-01-01

    -injected into the body to exert their action against the cancer. There are different kinds of Immuno-cell therapies being practised in more than 25 private and public institutions in Japan using Natural Killer (NK) cells, Cytotoxic T lymphocytes (CTLs), Tumour Infiltrating Lymphocytes (TIL), Lymphokine activated Killer (LAK) cells, Dendritic cells and Gamma Delta T (γδ T) cells.([7]) Importantly most of the innovations in cell based therapies in the world have been made in Japan because immunotherapy is a part of the Japanese Health care system and routine therapies for cancer in Japan. There have been randomized clinical trials on Immuno-cell therapy for liver cancer, lung cancer, gastric cancer, ovarian cancer with the results suggesting statistically significant increase in survival rate and increase in disease free survival rate. ([8, 9, 10, 11]) There are more than 25 institutions in Japan performing such cell based immunotherapies. A comprehensive review by Egawa et al on 1401 patients showed that when Immuno-cell therapy was combined with the conventional therapies, the efficacy increased upto 20-30%. ([7]) Immuno-cell is the least toxic of all therapies and can be administered even to terminally ill cancer patients. ([12]) Contrast to drugs, as autologous cell based Immuno-therapies are from the patient's own blood and as they are custom tailored to each patient, though expensive, the adverse effects are minimal. To conclude, cancer-Immunocell therapies are the future of cancer therapies and further research is needed to enhance its efficacy and validate the results.

  2. New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

    Directory of Open Access Journals (Sweden)

    Stroncek David F

    2012-03-01

    Full Text Available Abstract A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL, are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs, chimeric antibody-T cell receptors (CARs and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies.

  3. Long-term outcomes for surgical treatment in patients with locally advanced and disseminated gastric cancer combined with intraoperative photodynamic therapy

    Directory of Open Access Journals (Sweden)

    L. A. Vashakmadze

    2013-01-01

    Full Text Available This article represents the study of safety and efficiency of intraoperative photodynamic peritoneal therapy (IOPDT developed in P.A. Herzen Moscow Cancer Research Institute. IPPDT was performed in 84 patients with locally advanced and disseminated gastric cancer. The control group included 100 patients with surgical treatment only. All patients underwent subradical or palliative subtotal distal gastroectomy or total gastrectomy with D2, D3 lymph node dissection. For IOPDT group Photohem was administrated intravenously in dose 2,5 mg/kg 48 h prior to operation, the session of peritoneal irradiation was performed after completion of the surgery (with laser device LFT-630-01 «Biospec», wavelength 630nm, light dose 6 J/cm2. IOPDT of peritoneum was associated with good tolerance, did not increase the rate and severity of post-operative complications. The efficiency of IOPDT was assessed with adjusted survival rates in study and control groups by Kaplan-Meier analysis. IOPDT significantly improved the prognosis in patients with subradical treatment, with metastasis in less then 15 lymph nodes. The use of IOPDT after surgery in this group of patients contributed to increase of median survival rate from 29.3 up to 43.6 months, annual survival rates from 80.0±5.7% to 93.7±4.2%, 3-year survival rates from 45.5±7.6% to 82.1±7.1%. Accordingly, IOPDT did not improved outcomes for palliative surgery R1–R2 and in patients with more than 15 involved lymph nodes. 

  4. Silicon nanostructures for cancer diagnosis and therapy.

    Science.gov (United States)

    Peng, Fei; Cao, Zhaohui; Ji, Xiaoyuan; Chu, Binbin; Su, Yuanyuan; He, Yao

    2015-01-01

    The emergence of nanotechnology suggests new and exciting opportunities for early diagnosis and therapy of cancer. During the recent years, silicon-based nanomaterials featuring unique properties have received great attention, showing high promise for myriad biological and biomedical applications. In this review, we will particularly summarize latest representative achievements on the development of silicon nanostructures as a powerful platform for cancer early diagnosis and therapy. First, we introduce the silicon nanomaterial-based biosensors for detecting cancer markers (e.g., proteins, tumor-suppressor genes and telomerase activity, among others) with high sensitivity and selectivity under molecular level. Then, we summarize in vitro and in vivo applications of silicon nanostructures as efficient nanoagents for cancer therapy. Finally, we discuss the future perspective of silicon nanostructures for cancer diagnosis and therapy.

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

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

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

  6. Music therapy in supportive cancer care.

    Science.gov (United States)

    Stanczyk, Malgorzata Monika

    2011-06-08

    The purpose of this paper is to show some aspects of music therapy application in cancer care and to present the integration of music therapy program into a continuous supportive cancer care for inpatients. A cancer diagnosis is one of the most feared and serious life events that causes stress in individuals and families. Cancer disrupts social, physical and emotional well-being and results in a range of emotions, including anger, fear, sadness, guilt, embarrassment and shame. Music therapy is a part of a complementary medicine program in supportive cancer care which accompanies medical treatment. There are many benefits of music therapy for cancer patients-interactive music therapy techniques (instrumental improvisation, singing) as well as receptive music therapy techniques (listening to recorded or live music, music and imaginary) can be used to improve mood, decrease stress, pain, anxiety level and enhance relaxation. Music therapy is an effective form of supporting cancer care for patients during the treatment process. It may be also basic for planning effective programs of rehabilitation to promote wellness, improve physical and emotional well-being and the quality of life.

  7. Translational Approaches towards Cancer Gene Therapy: Hurdles and Hopes

    Directory of Open Access Journals (Sweden)

    Yadollah Omidi

    2012-09-01

    Full Text Available Introduction: Of the cancer gene therapy approaches, gene silencing, suicide/apoptosis inducing gene therapy, immunogene therapy and targeted gene therapy are deemed to sub­stantially control the biological consequences of genomic changes in cancerous cells. Thus, a large number of clinical trials have been conducted against various malignancies. In this review, we will discuss recent translational progresses of gene and cell therapy of cancer. Methods: Essential information on gene therapy of cancer were reviewed and discussed towards their clinical translations. Results: Gene transfer has been rigorously studied in vitro and in vivo, in which some of these gene therapy endeavours have been carried on towards translational investigations and clinical applications. About 65% of gene therapy trials are related to cancer therapy. Some of these trials have been combined with cell therapy to produce personalized medicines such as Sipuleucel-T (Provenge®, marketed by Dendreon, USA for the treatment of asymptomatic/minimally symptomatic metastatic hormone-refractory prostate cancer. Conclusion: Translational approach links two diverse boundaries of basic and clinical researches. For successful translation of geno­medicines into clinical applications, it is essential 1 to have the guidelines and standard operating procedures for development and application of the genomedicines specific to clinically relevant biomarker(s; 2 to conduct necessary animal experimental studies to show the “proof of concept” for the proposed genomedicines; 3 to perform an initial clinical investigation; and 4 to initiate extensive clinical trials to address all necessary requirements. In short, translational researches need to be refined to accelerate the geno­medicine development and clinical applications.

  8. Microtubule-Targeting Therapy for Prostate Cancer

    Science.gov (United States)

    2007-02-01

    Cancer1828 Mol Cancer Ther 2005;4(12). December 2005 22. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning : a laboratory manual. 2nd ed. Cold Spring...Harbor (NY): Cold Spring Harbor Laboratory; 1989. 23. Zhu XX, Kozarsky K, Strahler JR, et al. Molecular cloning of a novel human leukemia-associated...of Cancer Research, Abstract #4940, 2005. 3. Mistry, SJ, Atweh, GF. Microtubule targeting therapy: Anti-stathmin based molecular cancer

  9. CERN launches new cancer therapy initiative

    CERN Multimedia

    2002-01-01

    "The first meeting of a new European network for research in cancer therapy was held at CERN, in February 2002. ENLIGHT, the European Network for Research in Light Ion Therapy aims to coordinate the development of a variety of projects at European facilities for "light ion therapy" - a form of radiation therapy that uses beams of the nuclei of lightweight atoms" (1/2 page).

  10. Cancer incidence and novel therapies developed in Japan

    Directory of Open Access Journals (Sweden)

    Masaru Iwasaki

    2012-01-01

    -injected into the body to exert their action against the cancer. There are different kinds of Immuno-cell therapies being practised in more than 25 private and public institutions in Japan using Natural Killer (NK cells, Cytotoxic T lymphocytes (CTLs, Tumour Infiltrating Lymphocytes (TIL, Lymphokine activated Killer (LAK cells, Dendritic cells and Gamma Delta T (γδ T cells. [7] Importantly most of the innovations in cell based therapies in the world have been made in Japan because immunotherapy is a part of the Japanese Health care system and routine therapies for cancer in Japan. There have been randomized clinical trials on Immuno-cell therapy for liver cancer, lung cancer, gastric cancer, ovarian cancer with the results suggesting statistically significant increase in survival rate and increase in disease free survival rate. [8, 9, 10, 11] There are more than 25 institutions in Japan performing such cell based immunotherapies. A comprehensive review by Egawa et al on 1401 patients showed that when Immuno-cell therapy was combined with the conventional therapies, the efficacy increased upto 20-30%. [7] Immuno-cell is the least toxic of all therapies and can be administered even to terminally ill cancer patients. [12] Contrast to drugs, as autologous cell based Immuno-therapies are from the patient’s own blood and as they are custom tailored to each patient, though expensive, the adverse effects are minimal. To conclude, cancer-Immunocell therapies are the future of cancer therapies and further research is needed to enhance its efficacy and validate the results. References: 1.Cancer Statistics in Japan 2011. http://ganjoho.jp/data/public/statistics/backnumber/2011/files/cancer_statistics_2011.pdf2.Japan Cancer Society. Statistics on dynamic trends in Population compiled by the Ministry of Health, Labour and welfare. http://www.jcancer.jp/english/cancerinjapan/3.Maehara Y. Current Status of Cancer Treatment in Japan, and Future Prospects for the Japan Society of Clinical

  11. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers......, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women...

  12. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    , including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women......Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers...

  13. Targeting the EGFR pathway for cancer therapy

    DEFF Research Database (Denmark)

    Johnston, JB; Navaratnam, S; Pitz, MW

    2006-01-01

    provided the rationale for the targeting of the components of the EGFR signaling pathways for cancer therapy. Below we discuss various aspects of EGFR-targeted therapies mainly in hematologic malignancies, lung cancer and breast cancer. Beside novel therapeutic approaches, we also discuss specific side......Clinical studies have shown that HER-2/Neu is over-expressed in up to one-third of patients with a variety of cancers, including B-cell acute lymphoblastic leukemia (B-ALL), breast cancer and lung cancer, and that these patients are frequently resistant to conventional chemo-therapies. Additionally...... effects associated with the therapeutic inhibition of components of the EGFR-pathways. Alongside small inhibitors, such as Lapatinib (Tykerb, GW572016), Gefitinib (Iressa, ZD1839), and Erlotinib (Tarceva, OSI-774), a significant part of the review is also dedicated to therapeutic antibodies (e...

  14. 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.

  15. Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer

    Science.gov (United States)

    2014-04-21

    Recurrent Cervical Cancer; Recurrent Vaginal Cancer; Stage IB Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Vaginal Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Therapy-related Toxicity

  16. Clinical study on intensity modulated radiation therapy combined with thermotherapy in treating advanced rectum cancer%IMRT联合热疗治疗中晚期直肠癌临床研究

    Institute of Scientific and Technical Information of China (English)

    王园园; 王义善; 杨柯; 胡蓉蓉; 杨桂青

    2012-01-01

    目的 观察适形调强放射治疗(IMRT)联合热疗治疗中晚期直肠癌的临床疗效.方法 将60例中晚期直肠癌患者随机分为单纯IMRT组及IMRT联合热疗组,分别给予相应治疗,比较2组患者治疗后临床疗效.结果 IMRT联合热疗组的治疗有效率87%,单纯IMRT组63%,2组有效率比较有显著性差异(P<0.05);在ZPS评分改善方面,IMRT联合热疗组也优于单纯IMRT组,且差异具有统计学意义.结论 IMRT联合热疗能够更有效地控制中晚期直肠癌,值得临床推广应用.%Objective It is to observe the clinical effect of intensity-modulated radiation therapy ( IMRT ) combined with thermotherapy in the treatment for advanced rectum cancer. Methods Sixty patients with advanced rectum cancer were randomly divided into IMRT group and IMRT combined with thermotherapy group. After treatment, the differences of clinical effect between these two groups were evaluated. Results The therapeutic effect was 87% in IMRT combined with thermotherapy group, and that was 63% in IMRT group, there was significant difference between both groups ( P <0.05 ). In the aspect of the improvement of ZPS scores, IMRT combined with thermotherapy group was also better than IMRT group only, there was significant difference between both groups ( P <0.05 ). Conclusion IMRT combined with thermotherapy can control advanced rectum cancer better, and thus, it deserves popularize clinical application.

  17. Photodynamic therapy in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Kamil H Nelke

    2014-02-01

    Full Text Available Photodynamic therapy (PDT is a special type of treatment involving the use of a photosensitizer or a photosensitizing agent along with a special type of light, which, combined together, induces production of a form of oxygen that is used to kill surrounding cells in different areas of the human body. Specification of the head and neck region requires different approaches due to the surrounding of vital structures. PDT can also be used to treat cells invaded with infections such as fungi, bacteria and viruses. The light beam placed in tumor sites activates locally applied drugs and kills the cancer cells. Many studies are taking place in order to invent better photosensitizers, working on a larger scale and to treat deeply placed and larger tumors. It seems that PDT could be used as an alternative surgical treatment in some tumor types; however, all clinicians should be aware that the surgical approach is still the treatment of choice. PDT is a very accurate and effective therapy, especially in early stages of head and neck squamous cell carcinomas (HNSCC, and can greatly affect surgical outcomes in cancerous patients. We present a detailed review about photosensitizers, their use, and therapeutic advantages and disadvantages.

  18. Pneumonia in immunocompetent patients: combination antibiotic therapy.

    Science.gov (United States)

    Salva, S; Borgatta, B; Rello, J

    2014-04-01

    Pneumonia's burden is still important worldwide not only because of its high incidence and mortality, but also for the elevated costs related to it. Despite the concerted efforts to reduce the incidence of sepsis-related complications, they continue to represent a major human and economic burden. The cornerstone of sepsis management is early appropriate empiric broad spectrum antibiotics, resuscitation, and source control. The association between inappropriate use of antibiotics and increased mortality is the rationale for the use of empiric antibiotic combination therapy in critically ill patients. The aim of this manuscript was to discuss recent literature regarding the management of severe pneumonia, both community-acquired and hospital-acquired/ventilator-associated, in critically ill patients. Use of combination therapy is warranted in severe infections with shock; considerations should be made on the importance of optimal antibiotic administration and adverse reactions, thus providing guidance for a rational use of antibiotics.

  19. Combination therapy of renal cell carcinoma or breast cancer patients with dendritic cell vaccine and IL-2: results from a phase I/II trial

    Directory of Open Access Journals (Sweden)

    Kim YongMan

    2011-10-01

    Full Text Available Abstract Background Ten cancer patients (Six renal cell carcinoma and four breast cancer patients were treated in a phase I/II study with a vaccine composed of autologous dendritic cells (DCs and IL-2 to evaluate the DC vaccine-related toxicity and antigen-specific immune alteration. Methods Cancer patients were treated twice with autologous CD34+ hematopoietic stem cell-derived, GM-CSF/IFN-γ-differentiated DCs pulsed with autologous tumor lysate and KLH, by 4-week interval. Following each subcutaneous injection of therapeutic DCs, low-dose (200 MIU IL-2 was introduced for 14 consecutive days as an immune adjuvant. To determine the DC vaccine-induced immunological alterations, the KLH-specific lymphocyte proliferation, number of IFN-γ secreting T cells (ELISPOT assay, NK activity and the cytokine modulation were measured. Results Cultured-DCs expressing HLA-DR, CD11c, CD83, and B7.1/B7.2 produced IL-12p70. After vaccination, the patients tolerated it. Clinical response was observed in one RCC patient as stable disease. However DC-vaccine related antigen-specific immune responses including peripheral blood lymphocyte proliferation and the number of IFN-r secreting cells were induced in six patients without clear correlation with clinical responses. Also NK activity was induced significantly in six patients after vaccination. DC vaccine-related decrease of TGF-β level or increase of IL-12p70 level and decline of CD4+CD25+ T cells were observed in three patients. However only in the RCC patient whose disease stabilized, combination of stimulatory as well as inhibitory immune alterations including induction of IFN-γ secreting T cell with reduction of CD4+ CD25+ T cell were correlated with clinical responses. Conclusion Data indicated that DC vaccine combined with IL-2 is well tolerated without major side effects. DC vaccine induced the specific immunity against introduced antigen. Combinatorial alterations of immunological parameters indicating

  20. [Combination therapy of chronic bacterial prostatitis].

    Science.gov (United States)

    Khryanin, A A; Reshetnikov, O V

    2016-08-01

    The article discusses the possible etiological factors in the development of chronic bacterial prostatitis. The authors presented a comparative long-term analysis of morbidity from non-viral sexually transmitted infections (STIs) in Russia. Against the background of general decline in STIs incidence, a significant percentage of them is made up by urogenital trichomoniasis. The findings substantiated the advantages of combination therapy (ornidazole and ofloxacin) for bacterial urinary tract infections.

  1. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    of cancer treatments. In the search for more effective cancer treatments, nanoparticle- based drug delivery systems, such as liposomes, that are capable of delivering their drug payload selectively to cancer cells are among the most promising approaches. Areas covered in this review: This review provides...... of new liposomal drug delivery systems that better exploit tumor characteristic features is likely to result in more efficacious cancer treatments....... an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What...

  2. Amodiaquine and Ciprofloxacin Combination in Plasmodiasis Therapy

    Directory of Open Access Journals (Sweden)

    Peace Mayen Edwin Ubulom

    2015-01-01

    Full Text Available Objective. The study was designed to determine the efficacy of combined Amodiaquine and Ciprofloxacin in plasmodiasis therapy. Method. The in vivo antiplasmodial effect of different dosage levels of Amodiaquine, Ciprofloxacin, and their combinations against Plasmodium berghei berghei was evaluated using Swiss albino mice. Results. Amodiaquine (a known antiplasmodial agent had a fairly significant antiplasmodial effect reducing the parasites for every 100 red blood cells (RBC from 66 to 16 (75.75% at the tolerable dosage level of 7.5 mg/kg body weight while Ciprofloxacin (an antibiotic known to have antimalarial effect showed an insignificant antiplasmodial effect reducing the parasites for every 100 RBC from 65 to 64 (1.53% at the tolerable dosage level of 10.7 mg/kg body weight. Conversely, the combination therapy of Amodiaquine and Ciprofloxacin had a significant antiplasmodial effect at all the doses administered. The combination of 7.5 mg/kg of Amodiaquine and 12.8 mg/kg of Ciprofloxacin, however, showed the most significant antiplasmodial effect of the doses used reducing the number of parasites per 100 RBC from 60 to 10 (83.33%. Conclusions. Appropriate Amodiaquine and Ciprofloxacin combination will be effective for the treatment of malaria and better than either Amodiaquine or Ciprofloxacin singly at their recommended dosage levels.

  3. Amodiaquine and Ciprofloxacin Combination in Plasmodiasis Therapy.

    Science.gov (United States)

    Ubulom, Peace Mayen Edwin; Udobi, Chinweizu Ejikeme; Madu, Mark Iheukwumere

    2015-01-01

    Objective. The study was designed to determine the efficacy of combined Amodiaquine and Ciprofloxacin in plasmodiasis therapy. Method. The in vivo antiplasmodial effect of different dosage levels of Amodiaquine, Ciprofloxacin, and their combinations against Plasmodium berghei berghei was evaluated using Swiss albino mice. Results. Amodiaquine (a known antiplasmodial agent) had a fairly significant antiplasmodial effect reducing the parasites for every 100 red blood cells (RBC) from 66 to 16 (75.75%) at the tolerable dosage level of 7.5 mg/kg body weight while Ciprofloxacin (an antibiotic known to have antimalarial effect) showed an insignificant antiplasmodial effect reducing the parasites for every 100 RBC from 65 to 64 (1.53%) at the tolerable dosage level of 10.7 mg/kg body weight. Conversely, the combination therapy of Amodiaquine and Ciprofloxacin had a significant antiplasmodial effect at all the doses administered. The combination of 7.5 mg/kg of Amodiaquine and 12.8 mg/kg of Ciprofloxacin, however, showed the most significant antiplasmodial effect of the doses used reducing the number of parasites per 100 RBC from 60 to 10 (83.33%). Conclusions. Appropriate Amodiaquine and Ciprofloxacin combination will be effective for the treatment of malaria and better than either Amodiaquine or Ciprofloxacin singly at their recommended dosage levels.

  4. Hormone Replacement Therapy After Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mueck AO

    2008-01-01

    Full Text Available So far, patient samples in all studies investigating hormone replacement therapy (HRT after breast cancer have been small.Therefore, HRT should only be used if alternatives such as specifically not contraindicated phytopreparations or selective sero-tonin reuptake inhibitors (SSRIs are not effective. This is primarily due to forensic reasons since clinical data on the risk ofalternatives (based on present evidence are even more sparse. Regarding HRT, four prospective randomized studies and at least15 observational studies after breast cancer are available. Only the HABITS study shows an increased risk of relapse. The authorssuggest that this is probably associated with the relatively high number of patients with HRT treatment after ER-positive cancersas well as due to the preferred use of estrogen/progestin-combined preparations. Based on the results of the randomized pla-cebo-controlled study Women’s Health Initiative (WHI as well as of at least 12 observational studies, the progestin componentseems to be mainly responsible for the probability of increased diagnosis frequency of primary breast cancer. However, no dataare available on the impact of progestin on the use of combined HRT after breast cancer. However, also with estrogen only anincreased risk of relapse must be expected and patients should be informed about it. This has to be concluded due to biologicalplausibility and observational studies although the estrogen-only arm in WHI did not show any increased primary risk. Thus, anyform of HRT should only be performed in exceptional cases, and treatment duration should be as short as possible with thelowest effective dose.

  5. Radiation Therapy for Lung Cancer

    Science.gov (United States)

    ... are available to help. HELPFUL WEB SITES ON LUNG CANCER American Lung Association www.lung.org Lungcancer.org www.lungcancer.org Lung Cancer Alliance www.lungcanceralliance.org Lung Cancer Online www. ...

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

    Science.gov (United States)

    2016-09-07

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

  7. Combination Drug Delivery Approaches in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jun H. Lee

    2012-01-01

    Full Text Available Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms.

  8. Pegvisomant and cabergoline combination therapy in acromegaly.

    Science.gov (United States)

    Bernabeu, I; Alvarez-Escolá, C; Paniagua, A E; Lucas, T; Pavón, I; Cabezas-Agrícola, J M; Casanueva, F F; Marazuela, M

    2013-03-01

    Combination with cabergoline may offer additional benefits to acromegalic patients on pegvisomant monotherapy. We evaluated the safety and efficacy profile of this combination and investigated the determinants of response. An observational, retrospective, cross-sectional study. Fourteen acromegalic patients (9 females), who were partially resistant to somatostatin analogs and on pegvisomant monotherapy. Cabergoline was added because of the presence of persistent mildly increased IGF-I. The mean follow-up time was 18.3 ± 10.4 months. The efficacy and safety profile was assessed. The influence of clinical and biochemical characteristics on treatment efficacy was studied. IGF-I levels returned to normal in 4 patients (28%) at the end of the study. In addition, some decline in IGF-I levels was observed in a further 5 patients. The % IGF-I decreased from 158 ± 64% to 124 ± 44% (p = 0.001). The average change in IGF-I was -18 ± 27% (range -67 to +24%). Lower baseline IGF-I (p = 0.007), female gender (p = 0.013), lower body weight (p = 0.031), and higher prolactin (PRL) levels (p = 0.007) were associated with a better response to combination therapy. There were no significant severe adverse events. Significant tumour shrinkage was observed in 1 patient. Combination therapy with pegvisomant and cabergoline could provide better control of IGF-I in some patients with acromegaly. Baseline IGF-I levels, female gender, body weight, and PRL levels affect the response to this combination therapy.

  9. Targeting tumor suppressor genes for cancer therapy.

    Science.gov (United States)

    Liu, Yunhua; Hu, Xiaoxiao; Han, Cecil; Wang, Liana; Zhang, Xinna; He, Xiaoming; Lu, Xiongbin

    2015-12-01

    Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.

  10. Clinical Opportunities in Combining Immunotherapy with Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Steven Eric Finkelstein

    2012-11-01

    Full Text Available Preclinical work in murine models suggests that local radiotherapy plus intratumoral syngeneic DC injection can mediate immunologic tumor eradication. Radiotherapy affects the immune response to cancer, besides the direct impact on the tumor cells, and other ways to coordinate immune modulation with radiotherapy have been explored. We review here the potential for immune mediated anticancer activity of radiation on tumors. This is mediated by antigen acquisition and presentation by dendritic cells, and through changes of lymphocytes’ activity. Recent work has implemented the combination of external beam radiation (EBRT with intratumoral injection of dendritic cells (DC. This included a pilot study of coordinated intraprostatic, autologous DC injection together with radiation therapy with five HLA-A2(+ subjects with high-risk, localized prostate cancer; the protocol used androgen suppression, external beam radiation therapy (25 fractions, 45 Gy, DC injections after fractions 5, 15, and 25, and then interstitial radioactive implant. Another was a phase II trial using neo-adjuvant cell death-inducing EBRT plus intra-tumoral DC in soft tissue sarcoma, to test if this would increase immune activity toward soft tissue sarcoma associated antigens. Clinical experience using radiation therapies combined with other systemic immune treatments are additionally surveyed, including use of investigational recombinant vaccinia and fowlpox, interleukin-2, toll like receptor 9 (TLR9 agonists and lymphocyte checkpoint inhibitors directed at PD1 and at CTLA4.

  11. A Model to Estimate the Risk of Breast Cancer-Related Lymphedema: Combinations of Treatment-Related Factors of the Number of Dissected Axillary Nodes, Adjuvant Chemotherapy, and Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Myungsoo; Kim, Seok Won; Lee, Sung Uk; Lee, Nam Kwon; Jung, So-Youn; Kim, Tae Hyun; Lee, Eun Sook; Kang, Han-Sung [Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Shin, Kyung Hwan, E-mail: shin.kyunghwan@gmail.com [Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2013-07-01

    Purpose: The development of breast cancer-related lymphedema (LE) is closely related to the number of dissected axillary lymph nodes (N-ALNs), chemotherapy, and radiation therapy. In this study, we attempted to estimate the risk of LE based on combinations of these treatment-related factors. Methods and Materials: A total of 772 patients with breast cancer, who underwent primary surgery with axillary lymph node dissection from 2004 to 2009, were retrospectively analyzed. Adjuvant chemotherapy (ACT) was performed in 677 patients (88%). Among patients who received radiation therapy (n=675), 274 (35%) received supraclavicular radiation therapy (SCRT). Results: At a median follow-up of 5.1 years (range, 3.0-8.3 years), 127 patients had developed LE. The overall 5-year cumulative incidence of LE was 17%. Among the 127 affected patients, LE occurred within 2 years after surgery in 97 (76%) and within 3 years in 115 (91%) patients. Multivariate analysis showed that N-ALN (hazard ratio [HR], 2.81; P<.001), ACT (HR, 4.14; P=.048), and SCRT (HR, 3.24; P<.001) were independent risk factors for LE. The total number of risk factors correlated well with the incidence of LE. Patients with no risk or 1 risk factor showed a significantly lower 5-year probability of LE (3%) than patients with 2 (19%) or 3 risk factors (38%) (P<.001). Conclusions: The risk factors associated with LE were N-ALN, ACT, and SCRT. A simple model using combinations of these factors may help clinicians predict the risk of LE.

  12. [Development of ultrasonic cancer therapy using ultrasound sensitive liposome].

    Science.gov (United States)

    Suzuki, Ryo; Oda, Yusuke; Utoguchi, Naoki; Maruyama, Kazuo

    2010-12-01

    Ultrasound (US) has been utilized as a useful tool for diagnosis and therapy. US mediated drug and gene delivery is paid to attention as a non-invasive system. The combination of US and microbubbles generated microjet stream by inducing disruption of bubbles and resulted in enhancing permeability of cell membrane. This phenomenon has been utilized as driving force for drug and gene delivery. Recently, we developed ultrasound sensitive liposome [Bubble liposome (BL)] containing perfluoropropane gas. US combined with BL could effectively transfer gene in vivo compared to conventional cationic liposomes. Using this method, we succeeded to obtain a therapeutic effect in cancer gene therapy with Interleukin-12 corded plasmid DNA. Therefore, it is expected that US combined with BL might be a useful non-viral vector system. From this result, the fusion of liposomal and ultrasound technologies would be important for establishment of advanced cancer therapy.

  13. Safety and efficacy of first-line bevacizumab combined with taxane therapy in Chinese patients with HER2-negative locally recurrent or metastatic breast cancer: findings from the ATHENA study

    Institute of Scientific and Technical Information of China (English)

    XU Bing-he; TONG Zhong-sheng; QIN Shu-kui; LUO Yi; YAO Min; WANG Li-wei; HE Jing; JIANG Ze-fei; SHEN Zhen-zhou; GUAN Zhong-zhen; CHEN Zheng-dong; CHENG Ying; ZHENG Hong; JIANG Jun; WANG Xiao-jia

    2012-01-01

    Background Three randomised trials have demonstrated that combining bevacizumab with first-line chemotherapy significantly improves progression-free survival versus chemotherapy alone in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC).However,data from Chinese populations are limited and possible differences between ethnic and geographic populations are unknown.This study was conducted to determine whether there are differences in safety and efficacy in patients with HER2-negative LR/mRC between Chinese and Western populations after they receive first-line bevacizumab combined with taxane-based therapy.Methods In the single-arm,open-label,Avastin Therapy for Advanced Breast Cancer (ATHENA) study (NCT00448591),patients with H ER2-negative LR/mBC received first-line bevacizumab (investigator's choice of 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) combined with taxane-based therapy.The primary endpoint was safety profile and the secondary is time to progression (TTP).A subpopulation analysis was conducted to assess safety and efficacy in Chinese patients.Results Of 2264 patients treated in ATHENA,202 were enrolled in China.Bevacizumab was combined with docetaxel in 90% of Chinese patients and paclitaxel in 10%.The most common grade 3/4 adverse events were diarrhoea (in 5.0% of patients) and hypertension (in 2.5% of patients).Grade 3/4 proteinuria occurred in 0.5%.After median follow-up of 17.6 months and events in 56% of patients,median TTP was 9.0 months (95%C/,8.4-11.1).Overall survival data were immature.Conclusions We found no evidence of increased bevacizumab-related toxicity or reduced efficacy in Chinese LR/mBC patients receiving first-line bevacizumab-taxane therapy compared with predominantly Western populations.The safety profile was generally similar to previously reported LR/mBC trials.Subtle differences may be attributable to different lifestyle and cardiovascular risk factors in Chinese patients compared with the

  14. Anaplastic thyroid cancer, tumorigenesis and therapy.

    LENUS (Irish Health Repository)

    O'Neill, J P

    2010-03-01

    Anaplastic thyroid cancer (ATC) is a fatal endocrine malignancy. Current therapy fails to significantly improve survival. Recent insights into thyroid tumorigenesis, post-malignant dedifferentiation and mode of metastatic activity offer new therapeutic strategies.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  16. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    Cappello P

    2015-12-01

    Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

  17. Gene Therapy In Oral Cancer : An Overview

    Directory of Open Access Journals (Sweden)

    Kanaram Choudhary

    2010-07-01

    Full Text Available The treatment and prevention of oral cancer is one of the major hurdles in the field ofcancer. Gene therapy is one of the recent advances in this field to tackle this hurdle with promisingprospects. This overview introduces the reader into the basic idea of gene therapy, types of genetherapy and the various modes of introduction of therapeutic gene into the cancer affected cell.

  18. Radiation Therapy for Early Stage Lung Cancer

    OpenAIRE

    Parashar, Bhupesh; Arora, Shruthi; Wernicke, A. Gabriella

    2013-01-01

    Radiation therapy for early stage lung cancer is a promising modality. It has been traditionally used in patients not considered candidates for standard surgical resection. However, its role has been changing rapidly since the introduction of new and advanced technology, especially in tumor tracking, image guidance, and radiation delivery. Stereotactic radiation therapy is one such advancement that has shown excellent local control rates and promising survival in early stage lung cancer. In a...

  19. PET-Adjusted Intensity Modulated Radiation Therapy and Combination Chemotherapy in Treating Patients With Stage II-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2017-01-23

    Metastatic Malignant Neoplasm in the Brain; Recurrent Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  20. Optimal combination of antiangiogenic therapy forhepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The success of sorafenib in prolonging survival of patientswith hepatocellular carcinoma (HCC) makes therapeuticinhibition of angiogenesis a component of treatmentfor HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination ofantiangiogenic agents with chemotherapy,radiotherapyor other targeted agents were evaluated. Nevertheless,the use of antiangiogenic therapy remains suboptimalregarding dosage, schedule and duration of therapy.The issue is further complicated by combinationantiangiogenesis to other cytotoxic or biologic agents.There is no way to determine which patients are mostlikely respond to a given form of antiangiogenic therapy.Activation of alternative pathways associated with diseaseprogression in patients undergoing antiangiogenictherapy has also been recognized. There is increasingimportance in identifying, validating and standardizingpotential response biomarkers for antiangiogenesistherapy for HCC patients. In this review, biomarkers forantiangiogenesis therapy including systemic, circulating,tissue and imaging ones are summarized. The strengthand deficit of circulating and imaging biomarkerswere further demonstrated by a series of studies inHCC patients receiving radiotherapy with or withoutthalidomide.

  1. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics.

    Science.gov (United States)

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping

    2016-01-01

    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment of cancer metastasis. Numerous types of photothermal nanotherapeutics (PTN) have been developed with encouraging therapeutic efficacy on metastatic cancer in many preclinical animal experiments. We summarize the design and performance of various PTN in PTT alone and their combinational therapy. We also point out the lacking area and the most promising approaches in this challenging field. In conclusion, PTT or their combinational therapy can provide an essential promising therapeutic modality against cancer metastasis.

  2. Combination of photodynamic therapy and immunotherapy - evolving role in dermatology

    Science.gov (United States)

    Wang, Xiu-Li; Wang, Hong-Wei; Huang, Zheng

    2008-02-01

    Photodynamic therapy (PDT) is a promising treatment modality. It offers alternative options in the treatment of cancer and vascular diseases. In cancer treatment, PDT has been used primarily for localized superficial or endoluminal malignant and premalignant conditions. More recently, its application has also been expanded to solid tumors. However, its antitumor efficacy remains debatable and its acceptance still variable. Pre-clinical studies demonstrate that, in addition to the primary local cytotoxicity, PDT might induce secondary host immune responses, which may further enhance PDT's therapeutic effects on primary tumor as well as metastasis. Therefore, PDT-induced local and systemic antitumor immune response might play an important role in successful control of malignant diseases. Furthermore, PDT's antitumor efficacy might also be enhanced through an effective immunoadjuvant or immunomodulator. Our recent clinical data also indicate that improved clinical outcomes can be obtained by a combination of PDT and immunomodulation therapy for the treatment of pre-malignant skin diseases. For instance, the combination of topical ALA-PDT and Imiquimod is effective for the treatment of genital bowenoid papulosis. This presentation will also report our preliminary data in developing combination approaches of PDT and immunotherapy for actinic keratosis (AK), basal cell carcinomas (BCCs) and Bowen's disease.

  3. Combination therapy in hypertension: An update

    Directory of Open Access Journals (Sweden)

    Kalra Sanjay

    2010-06-01

    Full Text Available Abstract Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females.

  4. Combined therapy for diabetic macular edema

    Directory of Open Access Journals (Sweden)

    Saba Al Rashaed

    2013-01-01

    Full Text Available Diabetic macular edema (DME is the main cause of visual impairment in diabetic patients. Macular edema within 1 disk diameter of the fovea is present in 9% of the diabetic population. The management of DME is complex and often multiple treatment approaches are needed. This review demonstrates the benefits of intravitreal triamcinolone, bevacizumab and ranibizumab as adjunctive therapy to macular laser treatment in DME. The published results indicate that intravitreal injections of these agents may have a beneficial effect on macular thickness and visual acuity, independent of the type of macular edema that is present. Therefore, pharmacotherapy could complement focal/grid laser photocoagulation in the management of DME. For this review, we performed a literature search and summarized recent findings regarding combined therapy for DME.

  5. Combination therapy for pain in musculoskeletal diseases

    Directory of Open Access Journals (Sweden)

    Andrei Evgenyevich Karateev

    2012-01-01

    Full Text Available When managing patients with locomotor pathology, serious attention is paid to symptomatic therapy aimed at eliminating the unpleasant manifestations of the disease. At the same time, rational analgesia is of the greatest importance. If acute pain should be arrested, parenteral or tableted formulations of fast-acting analgesics are used for days. Longer analgesic therapy especially for clinically relevant inflammation is based on the use of nonsteroidal anti-inflammatory drugs (NSAID having analgesic and anti-inflammatory effectiveness and good tolerance. The level of analgesia may be increased, by combining NSAID with tramadol and paracetamol. When clinical muscular spasm is implicated in the pathogenesis of chronic pain, it is expedient to prescribe myorelaxants that have an analgesic potential and are able to potentiate the analgesic effect of NSAID.

  6. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Gundgaard, M.G.; Ehrnrooth, E.; Sørensen, Jens Benn

    2008-01-01

    , panitumumab. As a result, third-line treatment is now a necessary step in the optimal treatment of patients with metastatic colorectal cancer (MCRC). MATERIALS AND METHODS: We conducted a literature review of English language publications on third-line therapy for MCRC from January 2000 to April 2007. Data......OS of 16 months. With irinotecan and 5-FU, mOS around 8 months were reported and with cetuximab combined with irinotecan, the highest mOS was 9.8 months. CONCLUSION: Third-line therapy in advanced colorectal cancer may improve mOS for patients with MCRC. Therefore, randomized studies should be conducted...

  7. Pharmacogenomics: Biomarker-Directed Therapy for Bladder Cancer.

    Science.gov (United States)

    Jones, Robert T; Felsenstein, Kenneth M; Theodorescu, Dan

    2016-02-01

    The clinical management of bladder cancer has seen little change over the last three decades and there is pressing need to identify more effective treatments for advanced disease. Low clinical use of neoadjuvant therapies stems from historical limitations in the ability to predict patients most likely to respond to combination chemotherapies. This article focuses on recent molecular and genetic studies, highlighting promising clinical trials and retrospective studies, and discusses emerging trials that use predictive biomarkers to match patients with therapies to which they are most likely to respond. The implementation of predictive genomic and molecular biomarkers will revolutionize urologic oncology and the clinical management of bladder cancer.

  8. Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Ji-Jie Huang; Shu-Xiang Ma; Xue Hou; Zhao Wang; Yin-Duo Zeng; Tao Qin; Xiao-Xiao Dinglin; Li-Kun Chen

    2015-01-01

    Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinical y characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

  9. Palliative Endoscopic Therapy of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    H.Schaefer; A.H.Hoelscher

    2004-01-01

    Patients with locally unresectable esophageal cancer or distant metastasis are usually treated with definite radiotherapy or radiochemotherapy. Dysphagia of these patients should further be treated by endoscopic therapy in order to maintain swallowing and oral food intake as long as possible. The same situation is present in patients with local recurrence of esophageal cancer after surgery or radiochemotherapy.

  10. Therapy for bone metastasis from different cancers

    Institute of Scientific and Technical Information of China (English)

    Zheng Zhang; Peng Tan; Baoguo Mi; Chao Song; Yi Deng; Hanfeng Guan

    2016-01-01

    The bone is the most common target organ of cancer metastasis. Bone metastasis leads to considerable morbidity due to skeletal-related events (SREs). These include bone pain, hypercalcemia, pathologic frac-tures, and compression of the spinal cord. Cancers such as those of the lung, breast, prostate, and kidney are more likely to cause SREs than other cancer types. Additionaly, some blood cancers, including multiple myeloma and lymphoma, frequently cause SREs. In this article, we review the conventional therapies for metastatic bone disease, including drug therapy, radiotherapy, and surgery. Among osteoclast-targeting agents, bisphosphonates and nuclear factor kappa-B ligand inhibitors are the most widely used agents to prevent cancer-related bone loss. Unsealed radioisotopes are also considered promising in cancer therapy. Currently, iodine-131, strontium-89, and radium-223 are available for the treatment of bone metastasis. However, the treatments for blood cancers with SREs are diferent from those of other cancers. In those cases, new classes of agents including proteasome inhibitors, immunomodulatory drugs, monoclonal anti-bodies, and histone deacetylase inhibitors have shown remarkable eficacy. We also discuss the potential development of new therapies for these diseases.

  11. [Interdisciplinary and individualized therapy of prostate cancer : International prostate cancer symposium Bonn 2013 - challenges and targets].

    Science.gov (United States)

    Schwardt, M; Debus, J; Feick, G; Hadaschik, B; Hohenfellner, M; Schüle, R; Zacharias, J-P; Combs, S E

    2015-11-01

    Multimodal treatment of prostate cancer is based on specific staging via imaging, clinical parameters, tumor markers and histopathological grading. Risk-adapted therapy encompasses wait and see, active surveillance, surgical intervention, radiotherapy and hormone therapy. Some patients also need a combination of these treatment options. Even though clinical parameters guide the treatment plan, patient wishes and preferences are incorporated. Against this background leading basic research scientists, urologists, radiotherapists, epidemiologists and members of other associated disciplines discussed state of the art treatment concepts, innovative trial designs and translational research projects at the international meeting "Challenges and Chances in Prostate Cancer Research" organized by the German Cancer Aid (Deutsche Krebshilfe).

  12. Non-invasive Photodynamic Therapy in Brain Cancer by Use of Tb3+-Doped LaF3 Nanoparticles in Combination with Photosensitizer Through X-ray Irradiation: A Proof-of-Concept Study

    Science.gov (United States)

    Chen, Min-Hua; Jenh, Yi-Jhen; Wu, Sheng-Kai; Chen, Yo-Shen; Hanagata, Nobutaka; Lin, Feng-Huei

    2017-01-01

    The use of photodynamic therapy (PDT) in the treatment of brain cancer has produced exciting results in clinical trials over the past decade. PDT is based on the concept that a photosensitizer exposed to a specific light wavelength produces the predominant cytotoxic agent, to destroy tumor cells. However, delivering an efficient light source to the brain tumor site is still a challenge. The light source should be delivered by placing external optical fibers into the brain at the time of surgical debulking of the tumor. Consequently, there exists the need for a minimally invasive treatment for brain cancer PDT. In this study, we investigated an attractive non-invasive option on glioma cell line by using Tb3+-doped LaF3 scintillating nanoparticles (LaF3:Tb) in combination with photosensitizer, meso-tetra(4-carboxyphenyl)porphyrin (MTCP), followed by activation with soft X-ray (80 kVp). Scintillating LaF3:Tb nanoparticles, with sizes of approximately 25 nm, were fabricated. The particles have a good dispersibility in aqueous solution and possess high biocompatibility. However, significant cytotoxicity was observed in the glioma cells while the LaF3:Tb nanoparticles with MTCP were exposed under X-ray irradiation. The study has demonstrated a proof of concept as a non-invasive way to treat brain cancer in the future.

  13. Infliximab, azathioprine, or combination therapy for Crohn's disease

    DEFF Research Database (Denmark)

    Colombel, Jean Frédéric; Sandborn, William J; Reinisch, Walter

    2010-01-01

    The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.......The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown....

  14. Future Directions in Pancreatic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    David Orchard-Webb

    2015-05-01

    Full Text Available Pancreatic cancer is a major disease burden that is essentially incurable at present. However significant understanding of the molecular basis of pancreatic cancer has been achieved through sequencing. This is allowing the rational design of therapeutics. The purpose of this review is to introduce the molecular basis of pancreatic cancer, explain the current state of molecular therapy and provide examples of the ongoing developments. These include improvements in chemotherapy, small molecule inhibitors, vaccines, immune checkpoint antibodies, and oncolytics.

  15. Network systems biology for targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Zhou

    2012-01-01

    The era of targeted cancer therapies has arrived.However,due to the complexity of biological systems,the current progress is far from enough.From biological network modeling to structural/dynamic network analysis,network systems biology provides unique insight into the potential mechanisms underlying the growth and progression of cancer cells.It has also introduced great changes into the research paradigm of cancer-associated drug discovery and drug resistance.

  16. Targeted Radiation Therapy for Cancer Initiative

    Science.gov (United States)

    2015-09-01

    and whether this difference changed the outcome for palliative patients, 6) use of the Calypso system, and other advanced radiation therapy equipment...use of advanced technology radiation therapy techniques, such as IMRT and VMAT, in treating palliative patients. The main obstacle to overcome in...treating low-to-intermediate risk prostate cancer with intensity modulated radiation therapy (IMRT) using an electromagnetic localization system. IMRT

  17. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics

    OpenAIRE

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping

    2016-01-01

    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment...

  18. Dance as a therapy for cancer prevention.

    Science.gov (United States)

    Aktas, Gurbuz; Ogce, Filiz

    2005-01-01

    Even though the field of medicine has developed tremendously, the wide variety of cancer is still among chronic and life threatening disease today. Therefore, the specialists constantly research and try every possible way to find cure or preventive ways to stop its further development. For this reason, studies concerning the chronic disease such as cancer have been spread to many different fields. In this regard, many other alternative ways besides medicine, are used in prevention of cancer. Nutritional therapy, herbal therapy, sportive activities, art therapy, music therapy, dance therapy, imagery, yoga and acupuncture can be given as examples. Among these, dance/movement therapy which deals with individuals physical, emotional, cognitive as well as social integration is widely used as a popular form of physical activity. The physical benefits of dance therapy as exercise are well documented. Studies have shown that physical activity is known to increase special neurotransmitter substances in the brain (endorphins), which create a state of well-being. And total body movement such as dance enhances the functions of other body systems, such as circulatory, respiratory, skeletal, and muscular systems. Regarding its unique connection to the field of medicine, many researches have been undertaken on the effects of dance/movement therapy in special settings with physical problems such as amputations, traumatic brain injury, and stroke, chronic illnesses such as anorexia, bulimia, cancer, Alzheimer's disease, cystic fibrosis, heart disease, diabetes, asthma, AIDS, and arthritis. Today dance/movement therapy is a well recognized form of complementary therapy used in hospitals as well as at the comprehensive clinical cancer centres.

  19. New cancer-treatment model of photodynamic therapy combined with a type I topoisomerase inhibitor, CPT-11, against HeLa cell tumors in nude mice used by OPO parametric tunable laser

    Science.gov (United States)

    Yoshida, Takato O.; Matsuzawa, Eiji; Matsuo, Tetsumichi; Koide, Yukio; Terakawa, Susumu; Yokokura, Teruo; Hirano, Toru

    1995-03-01

    A new cancer-treatment model, photodynamic therapy (PDT) combined with a type I topoisomerase inhibitor, camptothecin derivative (CPT-11), against HeLa cell tumors in BALB/c nude mice has been developed using a wide-band tunable coherent light source operated on optical parametric oscillation (OPO parametric tunable laser). The Photosan-3 PDT and CPT-11 combined therapy was remarkably effective, that is the inhibition rate (I.R.) 40 - 80%, as compared to PDT only in vivo. The analysis of HpD (Photosan-3) and CPT-11 effects on cultured HeLa cells in vitro has been studied by a video-enhanced contrast differential interference contrast microscope (VEC-DIC). Photosan-3 with 600 nm light killed cells by mitochondrial damage within 50 min, but not with 700 nm light. CPT-11 with 700 - 400 nm light killed cells within 50 min after nucleolus damage appeared after around 30 min. The localization of CPT-11 in cells was observed as fluorescence images in the nucleus, particularly the nucleoral area produced clear images using an Argus 100.

  20. Menopausal Hormone Therapy and Cancer

    Science.gov (United States)

    ... type Progress Annual Report to the Nation Cancer Portfolio Snapshots Milestones in Cancer Research & Discovery Stories of ... woman’s body? Where does evidence about risks and benefits of MHT come from? What are the benefits ...

  1. Hormone Therapy for Prostate Cancer

    Science.gov (United States)

    ... Galvão DA, Taaffe DR, Spry N, Newton RU. Exercise can prevent and even reverse adverse effects of androgen suppression treatment in men with prostate cancer. Prostate Cancer and Prostatic Diseases 2007; 10(4): ...

  2. Combination bacteriolytic therapy for the treatment of experimental tumors.

    Science.gov (United States)

    Dang, L H; Bettegowda, C; Huso, D L; Kinzler, K W; Vogelstein, B

    2001-12-18

    Current chemotherapeutic approaches for cancer are in part limited by the inability of drugs to destroy neoplastic cells within poorly vascularized compartments of tumors. We have here systematically assessed anaerobic bacteria for their capacity to grow expansively within avascular compartments of transplanted tumors. Among 26 different strains tested, one (Clostridium novyi) appeared particularly promising. We created a strain of C. novyi devoid of its lethal toxin (C. novyi-NT) and showed that intravenously injected C. novyi-NT spores germinated within the avascular regions of tumors in mice and destroyed surrounding viable tumor cells. When C. novyi-NT spores were administered together with conventional chemotherapeutic drugs, extensive hemorrhagic necrosis of tumors often developed within 24 h, resulting in significant and prolonged antitumor effects. This strategy, called combination bacteriolytic therapy (COBALT), has the potential to add a new dimension to the treatment of cancer.

  3. Functionalized nanobodies for cancer therapy

    NARCIS (Netherlands)

    van Vught, R.W.M.

    2014-01-01

    Cancer treatment is complicated by the high similarity between cancerous and healthy tissue. New anti-cancer drugs, the monoclonal antibodies, act on one specific molecule/process and thereby minimize side effects. Despite that these monoclonal antibodies are highly specific and harbor multiple mode

  4. Oncolytic adenovirus-mediated therapy for prostate cancer

    Science.gov (United States)

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy) prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen–androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting local-ized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support future systemic delivery of oncolytic adenoviruses. PMID:27579296

  5. Cancer and electromagnetic radiation therapy: Quo Vadis?

    CERN Document Server

    Makropoulou, Mersini

    2016-01-01

    In oncology, treating cancer with a beam of photons is a well established therapeutic technique, developed over 100 years, and today over 50% of cancer patients will undergo traditional X-ray radiotherapy. However, ionizing radiation therapy is not the only option, as the high-energy photons delivering their cell-killing radiation energy into cancerous tumor can lead to significant damage to healthy tissues surrounding the tumor, located throughout the beam's path. Therefore, in nowadays, advances in ionizing radiation therapy are competitive to non-ionizing ones, as for example the laser light based therapy, resulting in a synergism that has revolutionized medicine. The use of non-invasive or minimally invasive (e.g. through flexible endoscopes) therapeutic procedures in the management of patients represents a very interesting treatment option. Moreover, as the major breakthrough in cancer management is the individualized patient treatment, new biophotonic techniques, e.g. photo-activated drug carriers, help...

  6. Cognitive Behavioral Therapy in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Cem Soylu

    2014-09-01

    Full Text Available Cognitive behavioral therapy is one of the structured but flexible psychosocial interventions that could be applied to patients with cancer. In many studies the positive effects of cognitive behavioral therapy in reducing psychological morbidity and improving the quality of life of cancer patients have been shown. In this article, the contents and techniques of adapted cognitive behavioral therapy for patients with cancer and its effectiveness in commonly seen psychiatric disorders have been reviewed. The aim of this article is to contribute positively to physicians and nurses in Turkey for early detection of psychological distress and referral to the therapist that would clearly increase the quality of life of cancer patients. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 257-270

  7. Exercise therapy across the lung cancer continuum.

    Science.gov (United States)

    Jones, Lee W; Eves, Neil D; Waner, Emily; Joy, Anil A

    2009-07-01

    A lung cancer diagnosis and associated therapeutic management are associated with unique and varying degrees of adverse physical/functional impairments that dramatically reduce patients' ability to tolerate exercise. Poor exercise capacity predisposes to increased susceptibility to other common age-related diseases, poor quality of life, and likely premature death. This article reviews the literature investigating the role of exercise as an adjunct therapy across the lung cancer continuum (ie, prevention to palliation). The current evidence suggests that exercise training is a safe and feasible adjunct therapy for patients with operable lung cancer both before and after pulmonary resection. Among patients with inoperable disease, feasibility and safety studies of carefully prescribed exercise training are warranted. Preliminary evidence in this area suggests that exercise therapy may be an important consideration in multidisciplinary management of patients diagnosed with lung cancer.

  8. Optimizing systemic therapy for bladder cancer.

    Science.gov (United States)

    Pal, Sumanta K; Milowsky, Matthew I; Plimack, Elizabeth R

    2013-07-01

    Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.

  9. Feasibility Study of EndoTAG-1, a Tumor Endothelial Targeting Agent, in Combination with Paclitaxel followed by FEC as Induction Therapy in HER2-Negative Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Michail Ignatiadis

    Full Text Available EndoTAG-1, a tumor endothelial targeting agent has shown activity in metastatic triple-negative breast cancer (BC in combination with paclitaxel.HER2-negative BC patients candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weekly EndoTAG-1 22mg/m2 plus paclitaxel 70mg/m2 followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 every 3 weeks followed by surgery. Primary endpoint was percent (% reduction in Magnetic Resonance Imaging (MRI estimated Gadolinium (Gd enhancing tumor volume at the end of EndoTAG-1 plus paclitaxel administration as compared to baseline. Safety, pathological complete response (pCR defined as no residual tumor in breast and axillary nodes at surgery and correlation between % reduction in MRI estimated tumor volume and pCR were also evaluated.Fifteen out of 20 scheduled patients were included: Six patients with estrogen receptor (ER-negative/HER2-negative and 9 with ER-positive/HER2-negative BC. Nine patients completed treatment as per protocol. Despite premedication and slow infusion rates, grade 3 hypersensitivity reactions to EndoTAG-1 were observed during the 1st, 2nd, 3rd and 6th weekly infusion in 4 patients, respectively, and required permanent discontinuation of the EndoTAG-1. Moreover, two additional patients stopped EndoTAG-1 plus paclitaxel after 8 and 9 weeks due to clinical disease progression. Two patients had grade 3 increases in transaminases and 1 patient grade 4 neutropenia. pCR was achieved in 5 of the 6 ER-/HER2- and in none of the 9 ER+/HER2- BC patients. The mean % reduction in MRI estimated tumor volume at the end of EndoTAG-1 plus paclitaxel treatment was 81% (95% CI, 66% to 96%, p<0.001 for the 15 patients that underwent surgery; 96% for patients with pCR and 73% for patients with no pCR (p = 0.04.The EndoTAG-1 and paclitaxel combination showed promising preliminary activity as preoperative treatment, especially in ER-/HER2

  10. Clinical benefit of bone-targeted radiometabolic therapy with {sup 153}Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ricci, Sergio; Pastina, Ilaria; Cianci, Claudia; Orlandini, Cinzia; Chioni, Aldo; Di Donato, Samantha [Hospital, Nuclear Medicine Service-PET Center, Rovigo (Italy); Boni, Giuseppe; Genovesi, Dario; Grosso, Mariano; AlSharif, Abedallatif; Mariani, Giuliano [Univ. of Pisa (Italy). Regional Center of Nuclear Medicine; Chiacchio, Serena [Univ. of Pisa (Italy). Regional Center of Nuclear Medicine; CNR Inst. of Clinical Physiology, Pisa (Italy); Francesca, Francesco [University Hospital, Pisa (Italy). Div. of Urology; Selli, Cesare [Univ. of Pisa (Italy). Section Urology; Rubello, Domenico [Nuclear Medicine Service-PET, Rovigo (Italy)

    2007-07-15

    Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). {sup 153}Sm-ethylenediaminetetramethylene phosphonate ({sup 153}Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of {sup 153}Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy. Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was {<=}10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with {sup 153}Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after {sup 153}Sm-EDTMP (14 patients, group B) or within 1 month after {sup 153}Sm-EDTMP (16 patients, group C). Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either {sup 153}Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both {sup 153}Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by {sup 153}Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A (p = 0.0235). Overall median survival from the time of administration of {sup 153}Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008). The results of this study confirm that

  11. Cancer research and therapy: Where are we today?

    Directory of Open Access Journals (Sweden)

    Sampada Sawant

    2014-12-01

    Full Text Available Till date scientists are struggling to understand the complete mechanism of carcinogenesis. In future, the real time detection of cancer may help scientists to identify some of the complicated biological mechanisms. Certain special features of cancer cells enable researchers to deliver the drug or to develop the right drug therapy. These cell properties include over expression or over activity in uptake of certain nutrients e.g. folic acid and increased permeability. Listed properties might vary depending upon the type of cancer and can be fully exploited by using nanoparticles either to detect the site of cancer or to direct the drug at the affected site. Product approach like drug conjugates, complexes serves as a good platform to solve issues like solubility, toxicity, poor penetration and stability related to cancer drugs. Beside this, several drug delivery platforms are under development by researchers in academia as well as in industry to deliver therapeutic molecules and new chemical entities to the targeted site in body. Amongst them, nanotechnology both at molecular and supramolecular level is a leading platform and can help to image, detect and treat cancer. Surface modification of nanoparticles by coating or anchoring their surface with special markers, materials, peptide, proteins, antibodies or antigens add extra feature and thereby can enhance the effectiveness. These treatments can be used individually or in combined form. In this review, advances on nanotechnological platform are discussed together with some assisting techniques like magnetic field, photo or light field, sonic rays are touched upon. New biological therapies that are advancing in this direction include the antisense therapy, cell therapy, gene therapy, radiation therapy and SiRNA interfaces which are discussed in brief in this article. This article gives short overview on use of complementary and alternative medicine for treatment of cancer such as traditional

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

    Science.gov (United States)

    2011-07-14

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

  13. Assessment of the Evolution of Cancer Treatment Therapies

    Directory of Open Access Journals (Sweden)

    Mónica Valladares

    2011-08-01

    Full Text Available Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.. In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine. We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

  14. Assessment of the Evolution of Cancer Treatment Therapies

    Energy Technology Data Exchange (ETDEWEB)

    Arruebo, Manuel [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Vilaboa, Nuria [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, Madrid 28046 (Spain); Sáez-Gutierrez, Berta; Lambea, Julio; Tres, Alejandro [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); Servicio de Oncología Médica, Hospital Clínico Universitario Lozano Blesa, Avda. San Juan Bosco 50009, Zaragoza (Spain); Instituto Aragonés de Ciencias de la Salud (I-CS), Avda. Gómez Laguna, 25, Zaragoza 50009 (Spain); Valladares, Mónica [Lonza Biologics Porriño, A relva s/n, Porriño (Pontevedra) 36410 (Spain); González-Fernández, África, E-mail: africa@uvigo.es [Immunology Department, Biomedical Research Center (CINBIO), University of Vigo, Campus Lagoas Marcosende, Vigo (Pontevedra) 36310 (Spain)

    2011-08-12

    Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

  15. Cancer Stem Cells: Targeting the Roots of Cancer, Seeds of Metastasis, and Sources of Therapy Resistance

    Science.gov (United States)

    Adorno-Cruz, Valery; Kibria, Golam; Liu, Xia; Doherty, Mary; Junk, Damian J.; Guan, Dongyin; Hubert, Chris; Venere, Monica; Mulkearns-Hubert, Erin; Sinyuk, Maksim; Alvarado, Alvaro; Caplan, Arnold I.; Rich, Jeremy; Gerson, Stanton L.; Lathia, Justin; Liu, Huiping

    2015-01-01

    With the goal to remove the roots of cancer, eliminate metastatic seeds, and overcome therapy resistance, the 2014 inaugural International Cancer Stem Cell (CSC) Conference at Cleveland, OH, convened together over 320 investigators, including 55 invited world-class speakers, 25 short oral presenters, and 100 poster presenters, to gain an in-depth understanding of CSCs and explore therapeutic opportunities targeting CSCs. The meeting enabled intriguing discussions on several topics including: genetics and epigenetics; cancer origin and evolution; microenvironment and exosomes; metabolism and inflammation; metastasis and therapy resistance; single cell and heterogeneity; plasticity and reprogramming; as well as other new concepts. Reports of clinical trials targeting CSCs emphasized the urgent need for strategically designing combinational CSC-targeting therapies against cancer. PMID:25604264

  16. Complementary therapies for cancer pain.

    Science.gov (United States)

    Cassileth, Barrie; Trevisan, Carrie; Gubili, Jyothirmai

    2007-08-01

    Pharmacologic treatment of pain does not always meet patients' needs and may produce difficult side effects. Complementary therapies, which are safe, noninvasive, and generally considered to be relatively free of toxicity, may be used adjunctively with standard pain management techniques to improve outcome and reduce the need for prescription medication. Approaches such as acupuncture, massage therapy, mind-body interventions, and music therapy effectively reduce pain, enhance quality of life, and provide patients with the opportunity to participate in their own care. Such therapies have an important role in modern pain management.

  17. Evaluating localized prostate cancer and identifying candidates for focal therapy.

    Science.gov (United States)

    Sartor, A Oliver; Hricak, Hedvig; Wheeler, Thomas M; Coleman, Jonathan; Penson, David F; Carroll, Peter R; Rubin, Mark A; Scardino, Peter T

    2008-12-01

    accurate staging, grading, and tumor localization needed for a focal therapy program. Nevertheless, for men with minimal cancer who are amenable to active surveillance or focal therapy, consensus about the most accurate biopsy strategy has not yet been reached. Imaging, particularly magnetic resonance imaging and magnetic resonance spectroscopic imaging, has been used to assess men with early-stage prostate cancer. Large-volume cancers can be seen reasonably well, but small lesions have been difficult to detect reliably or measure accurately. Factors such as voxel resolution, organ movement, biopsy artifact, and benign changes have limited the consistent estimation of the quantitative tumor volume. Nevertheless, magnetic resonance imaging and magnetic resonance spectroscopic imaging can aid in evaluating patients with prostate cancer being considered for focal therapy by providing additional evidence that the patient does not harbor an otherwise undetected high-risk, aggressive cancer. In some cases, imaging can usefully identify the location of even a limited-sized index cancer. When imaging findings are substantiated by mapping biopsy results, confidence in the accurate characterization of the cancer is enhanced. Correlating the imaging results with tissue changes during and after treatment can be of use in monitoring the ablative effects in the prostate and in assessing for tumor recurrence. More work is necessary before staging studies can uniformly characterize a prostate cancer before therapy, much less reliably identify and locate small-volume cancer within the prostate. However, exploring the role of focal ablation as a therapeutic option for selected men with low-risk, clinically localized, prostate cancer need not await the emergence of perfectly accurate staging studies, any more than the application of radical surgery or radiotherapy have. Modern biopsy strategies, combined with optimal imaging and nomograms to estimate the pathologic stage and risk, taken

  18. Advances in early diagnosis and therapy of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Qiang Xu; Tai-Ping Zhang; Yu-Pei Zhao

    2011-01-01

    BACKGROUND: Pancreatic cancer remains a devastating disease with a 5-year survival rate of less than 5%. Recent advances in diagnostic methods and therapeutic approaches have increased the possibility of improving the existing poor prognosis. DATA  SOURCES: English-language articles reporting early diagnosis and therapy of pancreatic cancer were searched from the MEDLINE and PubMed databases, Chinese-language articleswerefromCHKD(ChinaHospitalKnowledgeDatabase). RESULT: The current literature about pancreatic cancer was reviewed from three aspects: statistics, screening and early detection, and therapy. CONCLUSIONS: Early detection and screening of pancreatic cancer currently should be limited to high risk patients. Surgical resection is the only curative approach available, with some recent improvement in outcomes. Gemcitabine has been a standard treatment during the last decade. Gemcitabine-based combination treatment, especially combined with newer molecular targeted agents, is promising. The rationale for radiotherapy is controversial, but with the recent development of modern radiation delivery techniques, radiotherapy should be intensified. Patients with borderline pancreatic cancer could benefit from neoadjuvant therapy but more evidence is needed and the best neoadjuvant regimen is still to be determined.

  19. Epigenetic Therapy in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Stephen V Liu

    2013-05-01

    Full Text Available Epigenetic dysregulation of gene function has been strongly implicated in carcinogenesis and is one of the mechanisms contributing to the development of lung cancer. The inherent reversibility of epigenetic alterations makes them viable therapeutic targets. Here, we review the therapeutic implications of epigenetic changes in lung cancer, and recent advances in therapeutic strategies targeting DNA methylation and histone acetylation.

  20. New possibilities for cancer therapy with advances in cancer immunology.

    Science.gov (United States)

    MacLean, G D; Longenecker, B M

    1994-04-01

    There has been progress over the last decade in addressing three questions: Are there cancer-associated antigens that could be targets for immunotherapy? Can the human immune system recognize cancer-associated antigens? Can an anti-cancer immune response affect cancer cells and lead to increased survival? Results from animal model studies have been interpreted by optimists as encouraging, and by pessimists as being irrelevant to human cancer. Earlier studies on "cancer vaccines" utilized heterogeneous cell extracts of cell components. Monoclonal antibodies have enabled identification of relevant cancer-associated antigens or epitopes, such as the ganglioside GM2, the carbohydrates TF and STn, and the peptide sequences of MUC-1. In parallel with research on immune adjuvants and measures designed to inhibit suppressor activity, these epitopes are being tested for their potential in the immunotherapy of solid tumors. It is clear that some of these cancer-associated epitopes are immunogenic in humans. Mixed responses may relate to cancer heterogeneity and may indicate the importance of multi-epitopic vaccines. Responses are encouraging, but are they relevant? Prolonged disease stability challenges us to re-think the goals of cancer therapy. Recent advances in the knowledge of the effect of cytokines on tumor antigen expression and the regulation of the immune response, coupled with advances in active specific immunotherapy, provide hope that biomodulation may become an important part of the therapy of solid tumors in the next century.

  1. Future of Bacterial Therapy of Cancer.

    Science.gov (United States)

    Hoffman, Robert M

    2016-01-01

    Bacterial therapy of cancer has a centuries-long history and was first-line therapy at the hospital in New York City that would become Memorial Sloan-Kettering Cancer Center, under Dr. William B. Coley. However, after Coley's death in 1936, bacterial therapy of cancer ceased in the clinic until the present century. Clinical trials have been recently carried out for strains of the obligate anaerobe Clostridium novyi with the toxin gene deleted, and on an attenuated strain of Salmonella typhimurium (S. typhimurium), which is a facultative anaerobe that can grow in viable, as well as necrotic, areas of tumors, unlike Clostridium, which can only grow in the hypoxic areas. Our laboratory has developed the novel strain S. typhimurium A1-R that is effective against all tumor types in clinically-relevant mouse models, including patient-derived orthotopic xenograft (PDOX) mouse models. This chapter suggests future clinical applications for S. typhimurium A1-R.

  2. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  3. Breast cancer and possible mechanisms of therapy resistance

    Directory of Open Access Journals (Sweden)

    Ana-Maria Florea

    2013-03-01

    Full Text Available Breast cancer represents one of the most common cancers in women and is a major life threatening illness found all over the world. Therapy approaches include irradiation and surgery, with chemotherapy considered an important strategy to treat breast cancer. Platinum based anticancer drugs, such as cisplatin (cis-di-amino-dichloride-platin, CDDP, carboplatin, orthoplatin, etc., have been successfully used in breast cancer therapy because they activate multiple mechanisms to induce apoptosis in tumor cells. Nevertheless, during chemotherapy, drug resistance frequently develops; this impairs the successful treatment of breast cancer and often leads to patients’ decease. While combinations of anticancer drugs used in chemotherapy regimens reduced the occurrence of drug resistance (e.g. doxorubicin + docetaxel, doxorubicin + cyclophosphamide, docetaxel + herceptin + carboplatin the molecular mechanism of those effects are not completely understood. Here we review possible mechanisms related to breast cancer treatment and resistance to current therapies as well as possible new therapeutic targets (e.g. calcium signaling which could be used in the future.

  4. Clinical Study of Autoimmune Cells Therapy combined with Chemotherapy for Colorectal Cancer%自体免疫细胞治疗联合化疗治疗大肠癌的临床研究

    Institute of Scientific and Technical Information of China (English)

    朱卫; 李佳丽; 张利红; 牛静秀; 尹晓东; 杨雪晶; 李敬; 庞雁

    2016-01-01

    目的:探讨结直肠恶性肿瘤术后化疗与树突状细胞(dendritic cells,DCs)细胞因子诱导的杀伤细胞(cytokine-induced killer,CIK)联合治疗临床应用价值.方法:选择结直肠癌术后化疗联合DC-CIK治疗的病人242例作为联合治疗组,将同期术后只进行化疗的病人463例作为单纯化疗组,分析联合治疗组的免疫功能激活状况以及生存质量,比较两组病人生存率差异.结果:在细胞治疗结束后一周对联合治疗组患者进行迟发性变态反应皮肤试验,结果显示57.85%患者免疫反应被激活,单纯治疗组在治疗过程中体力、食欲、睡眠和体重的变化情况,至少有2项生存质量指标改善的患者有185例(76.45%).联合治疗组和单纯化疗组病人进行为期18个月的生存率对比,联合治疗组生存率为95.04%,单纯化疗组生存率为89.63%,差异显著(P=0.016).结论:结直肠癌术后化疗联合DC-CIK治疗可以激活患者的免疫功能,改善患者的生活质量,提高生存率.%Objective: To investigate clinical application value of dendritic cells combined with cyto?kine-induced killer (DC-CIK) in the treatment of colorectal cancer. Methods Two hundred and forty-two cas?es of postoperative patients of colorectal cancer treated with chemotherapy combined with DC-CIK in Tianjin People's Hospital were selected as combined treatment group, and 463 cases of colorectal cancer treated with chemotherapy were selected as control group. The type hypersensitivity delayed (DTH) skin test was performed at the end of cell therapy. The changes of physical activity, appetite and sleep were recorded. Results In 57.85% of the patients in combined treatment group, DTH was activated. In the same group,there are 185 cases (76.45%) with at least 2 indexes of quality of life being improved. The combined treatment group and control group were compared in 18 months of survival. The survival rate of combined treatment group was 95.04%, and that of the

  5. Immune-Mediated Therapies for Liver Cancer

    Science.gov (United States)

    Aravalli, Rajagopal N.; Steer, Clifford J.

    2017-01-01

    In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer. Preclinical and clinical studies with immune-mediated therapies have shown potential benefits in patients with liver cancer. In this review, we summarize current knowledge and recent developments in tumor immunology by focusing on two main primary liver cancers: hepatocellular carcinoma and cholangiocarcinoma. PMID:28218682

  6. Clinical adenoviral gene therapy for prostate cancer.

    Science.gov (United States)

    Schenk, Ellen; Essand, Magnus; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Danielsson, Angelika; Dautzenberg, Iris J C; Dzojic, Helena; Erbacher, Patrick; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Hoeben, Rob; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Lindholm, Leif; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nilsson, Berith; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schooten, Erik; Seymour, Len; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; Veldhoven-Zweistra, Joke L M; de Vrij, Jeroen; van Weerden, Wytske; Wagner, Ernst; Willemsen, Ralph

    2010-07-01

    Prostate cancer is at present the most common malignancy in men in the Western world. When localized to the prostate, this disease can be treated by curative therapy such as surgery and radiotherapy. However, a substantial number of patients experience a recurrence, resulting in spreading of tumor cells to other parts of the body. In this advanced stage of the disease only palliative treatment is available. Therefore, there is a clear clinical need for new treatment modalities that can, on the one hand, enhance the cure rate of primary therapy for localized prostate cancer and, on the other hand, improve the treatment of metastasized disease. Gene therapy is now being explored in the clinic as a treatment option for the various stages of prostate cancer. Current clinical experiences are based predominantly on trials with adenoviral vectors. As the first of a trilogy of reviews on the state of the art and future prospects of gene therapy in prostate cancer, this review focuses on the clinical experiences and progress of adenovirus-mediated gene therapy for this disease.

  7. Combined cannabinoid therapy via an oromucosal spray.

    Science.gov (United States)

    Perez, Jordi

    2006-08-01

    Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.

  8. HIFU as a Neoadjuvant Therapy in Cancer Treatment

    Science.gov (United States)

    Zhong, P.; Xing, F.; Huang, X.; Zhu, H.; Lo, H. W.; Zhong, X.; Pruitt, S.; Robertson, C.

    2011-09-01

    To broaden the application spectrum of HIFU in cancer therapy, we performed a pilot experiment to evaluate the potential of using HIFU as a neoadjuvant therapy prior to surgery. Mice bearing wild-type B16F10 melanoma inoculated subcutaneously were either untreated (control) or treated by HIFU, CPA-7 or HIFU+CPA-7 before surgical resection of the primary tumor two days after HIFU treatment. The animals were then followed for four weeks or up to the humane endpoint to determine local recurrence, distant metastasis, and survival rate. The results demonstrate that animals treated by HIFU+CPA-7 (which is a small molecule that suppresses STAT3 activity) had a significantly lower recurrence rate, and slower growth of the recurrent tumor, with concomitantly higher survival rate, followed by those treated with CPA-7 and HIFU, respectively. Immunological assays revealed that CPA-7 treatment could significantly lower STAT3, and subsequently, Treg activities. In particular, the combination of HIFU and CPA-7 can induce a much stronger anti-tumor immune response than HIFU or surgery alone, as assessed by CTL and IFN-γ secretion. Overall, our results suggest that HIFU in combination with immunotherapy strategies has the potential to be used as a neoadjuvant therapy to prime the host with a strong anti-tumor immune response before surgical resection of the primary tumor. This multimodality, combinational therapy has the potential to greatly broaden the range of HIFU applications in cancer therapy with lower tumor recurrence and improved survival rate.

  9. Radiation Therapy for Skin Cancer

    Science.gov (United States)

    ... make sure they are safe to use during radiation therapy. • Eat a balanced diet. If food tastes ... your fluid intake. • Treat the skin exposed to radiation with special care. Stay out of the sun, ...

  10. Cardiovascular disease after cancer therapy

    Directory of Open Access Journals (Sweden)

    Berthe M.P. Aleman

    2014-06-01

    Better knowledge of these cardiac effects will contribute to both primary and secondary prevention of late complications where exposure to cardiotoxic treatment is unavoidable. Also surrogate markers would help to identify patients at increased risk of cardiotoxicity. Evidence-based screening guidelines for CVD following cancer are also needed. Finally, risk prediction models should be developed to guide primary treatment choice and appropriate follow up after cancer treatment.

  11. The autophagic paradox in cancer therapy.

    Science.gov (United States)

    Wu, W K K; Coffelt, S B; Cho, C H; Wang, X J; Lee, C W; Chan, F K L; Yu, J; Sung, J J Y

    2012-02-23

    Autophagy, hallmarked by the formation of double-membrane bound organelles known as autophagosomes, is a lysosome-dependent pathway for protein degradation. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in early-stage carcinogenesis, autophagy inhibits inflammation and promotes genomic stability. Moreover, disruption of autophagy-related genes accelerates tumorigenesis in animals. However, autophagy may also act as a pro-survival mechanism to protect cancer cells from various forms of cellular stress. In cancer therapy, adaptive autophagy in cancer cells sustains tumor growth and survival in face of the toxicity of cancer therapy. To this end, inhibition of autophagy may sensitize cancer cells to chemotherapeutic agents and ionizing radiation. Nevertheless, in certain circumstances, autophagy mediates the therapeutic effects of some anticancer agents. Data from recent studies are beginning to unveil the apparently paradoxical nature of autophagy as a cell-fate decision machinery. Taken together, modulation of autophagy is a novel approach for enhancing the efficacy of existing cancer therapy, but its Janus-faced nature may complicate the clinical development of autophagy modulators as anticancer therapeutics.

  12. Targeting the TGFβ pathway for cancer therapy.

    Science.gov (United States)

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

    2015-03-01

    The TGFβ signaling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, motility and invasion, extracellular matrix production, angiogenesis, and immune response. TGFβ signaling deregulation is frequent in tumors and has crucial roles in tumor initiation, development and metastasis. TGFβ signaling inhibition is an emerging strategy for cancer therapy. The role of the TGFβ pathway as a tumor-promoter or suppressor at the cancer cell level is still a matter of debate, due to its differential effects at the early and late stages of carcinogenesis. In contrast, at the microenvironment level, the TGFβ pathway contributes to generate a favorable microenvironment for tumor growth and metastasis throughout all the steps of carcinogenesis. Then, targeting the TGFβ pathway in cancer may be considered primarily as a microenvironment-targeted strategy. In this review, we focus on the TGFβ pathway as a target for cancer therapy. In the first part, we provide a comprehensive overview of the roles played by this pathway and its deregulation in cancer, at the cancer cell and microenvironment levels. We go on to describe the preclinical and clinical results of pharmacological strategies to target the TGFβ pathway, with a highlight on the effects on tumor microenvironment. We then explore the perspectives to optimize TGFβ inhibition therapy in different tumor settings.

  13. Breast-conserving surgery and combined therapy for women breast cancer:a report of 216 cases%216例女性乳腺癌保乳手术及综合治疗的临床分析

    Institute of Scientific and Technical Information of China (English)

    Xianju Qin; Junxue Chen; Hongwei Zhang; Dafang Zhao; Hua Zhang; Wenjie Luo; Qian Huang; Shixian Lian; Hanxing Tong

    2007-01-01

    Objective:To explore the therapeutic effect and associated techniques of breast-conserving therapy on patients with clinical stage Ⅰand stage Ⅱ breasl cancer.Methods:216 female patients with breast cancer underwent breast-conserving therapy from December 1993 to October 2004.Their data were analyzed retrospectively.The breast-conserving therapy consisted of lumpectomy or quadrant removal of the breast,postoperative radiotherapy.chemotherapy and endocrine therapy.of them.209 patients underwent axillary lymph node dissection.Results:There were no operative complications.216patients were followed-up 3 to 147 months.the medial follow-up time was 78 months.The local recurrence rate was 1.85%.Two patients died and one of them was not related with breast cancer.Presence or absence of fibrosis,shape of breast,asymmetry,pigmentation and handle were taken into consideration for cosmetic evaluation by the patients and experienced breast surgeon.Breasts were scored cosmetically asexcellent and good in 199 patients.the rate of satisfactory was92.13%.Conclusion:Breast-conserving therapy for early breast cancer is a safe and effective therapy.It has less trauma and less complications and can also raise the quality of life in the patients.But we must obey the strict indications and reasonable techniques.

  14. Enhancing Cold Atmospheric Plasma Treatment Efficiency for Cancer Therapy

    Science.gov (United States)

    Cheng, Xiaoqian

    To improve efficiency and safety of anti-cancer therapies the researchers and clinicians alike are prompted to develop targeted combined therapies that especially minimize damage to healthy tissues while eradicating the body of cancerous tissues. Previous research in cold atmospheric plasma (CAP) and cancer cell interaction has repeatedly proven that cold plasma induced cell death. In this study, we seek to integrate the medical application of CAP. We proposed and implemented 3 novel ideas to enhance efficacy and selectivity of cancer therapy. It is postulated that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a major role in the CAP cancer therapy. We determined a mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of the composition of CAP, including output voltage, treatment time, and gas flow-rate. We varied the characteristics of the cold plasma in order to obtain different major species (such as O, OH, N2+, and N2 lines). "plasma dosage" D ~ Q * V * t. is defined, where D is the entire "plasma dosage"; Q is the flow rate of feeding gas; V is output voltage; t is treatment time. The proper CAP dosage caused 3-fold cell death in the U87 cells compared to the normal human astrocytes E6/E7 cells. We demonstrated there is a synergy between AuNPS and CAP in cancer therapy. Specifically, the concentration of AuNPs plays an important role on plasma therapy. At an optimal concentration, gold nanoparticles can significantly induce U87 cell death up to a 30% overall increase compared to the control group with the same plasma dosage but no AuNPs applied. The ROS intensity of the corresponding conditions has a reversed trend compared to cell viability. This matches with the theory that intracellular ROS accumulation results in oxidative stress, which further changes the intracellular pathways, causing damage to the proteins, lipids and DNA. Our results show that this synergy has great potential in improving the

  15. 联用依维莫司治疗乳腺癌疗效与安全性的Meta分析%Efficacy and safety of adjuvant therapy combined with everolimus in treatment of breast cancer:a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    李刚; 陈岷

    2016-01-01

    Objective To evaluate the efficacy and safety of adjuvant therapy combined with everolimus in theatment of breast cancer. Methods The related data-bases were searched. The RCTs in neoadjuvant therapy or adjunctive therapy for breast cancer in combination with everolimus( experimental group)or placebo( control group)were collected. The RCTs were Meta-analyzed using RevMan 5. 3 software. The efficacy and safety of the two groups were compared. The results were shown by relative risk ( RR),hazard ratio( HR)and 95%GI. Results Eight RCTs and 2 877 patients were enrolled into the Meta-analysis,including 1 679 patients in the experimental group and 1198 patients in the control group. Two RCTs applied neoadjuvant therapy and 6 RCTs applied adjunctive therapy. The results of quality evaluation of 8 reports showed 2 of low risk and 6 of unknown risk. Meta-analysis show the following results. The effective rate of the experimental group and the control group applying neoadjuvant therapy were 92. 6%(150/162)and 88. 7%(141/159),the difference was not statistically significant( RR=1. 04,95%GI:0. 97-1. 12,P = 0. 23 ). The effective rate of the experimental group and the control group applying adjunctive therapy were 83. 0%(1 081/1 303)and 76. 0%(623/820),the difference was not statistically significant(RR=1. 12,95%GI:0. 96-1. 29,P=0. 14). The progression-free survival of the patients in the experimental group applying adjunctive therapy were longer than that in the control group,the difference was statistically significant(HR=0. 60,95%GI:0. 44-0. 82,P=0. 001). The overall survival of the patients in the experimental group applying adjunctive therapy were longer than that in the control group,but the the difference was not statistically significant(HR =0. 74,95%GI:0. 48-1. 16,P =0. 19). The evaluation results of safety showed the following results. The incidence rates of erythra,fatigue,and anemia in the experimental group applying neoadjuvant therapy were higher than those in

  16. Combination therapy in A549 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yuan Menghui [Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an 710038 (China); Wang Jing [Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an 710038 (China)], E-mail: wangjing_fmmu@yahoo.com.cn; Deng Jinglan; Wang Zhe; Yang Weidong; Li Guoquan; Ren Bingxiu [Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2010-04-15

    Background and aim: We investigated the anti-tumor effect induced by the combination of the radiotherapeutic agent {sup 131}I-RC-160 and the prodrug 5-FC in human non-small cell lung cancer (NSCLC) A549 cells that were co-expressing the human somatostatin receptor 2 gene (hSSTR2) and E. coli cytosine deaminase gene (CD). Methods: We cloned both hSSTR2 and CD into a bicistronic mammalian expression plasmid and stably transfected it into A549 cells (pCIS-A549 cells). After antibiotic selection, SSTR expression in stable clones was determined by reverse transcription and polymerase chain reaction (RT-PCR), Western blot, flow cytometry and immunofluorescence analyses. To assess the in vivo targeting efficiency of the 'engineered' A549 cells, the cells were subcutaneously injected into nude mice and the biodistribution of {sup 99m}Tc-RC-160 was assessed at different time points. The tumor inhibitory effects of {sup 131}I-RC-160 and/or 5-FC were evaluated by measurement of tumor growth and immunohistochemical analysis. Results: Multiple analyses demonstrated the successful expression of hSSTR2 in A549 cells. In vivo radioimaging revealed specific targeting of RC-160 to the tumors derived from pCIS-A549 cells when compared to those from control A549 cells. The tumor inhibitory rate of pCIS-A549 tumors in the {sup 131}I-RC-160 plus 5-FC-treated group was significantly higher than that in the single agent-treated group, control group and control tumors. Conclusion: Co-expression of the hSSTR2 and CD genes in tumor cells can selectively sensitize these cells to the infra-additive effects of radioisotope-labeled RC-160 and 5-FC in vivo. This approach offers a potential therapeutic strategy for the treatment of lung cancer.

  17. Targets for molecular therapy of skin cancer.

    Science.gov (United States)

    Green, Cheryl L; Khavari, Paul A

    2004-02-01

    Cancers of the skin encompass the first and second most common neoplasms in the United States, epidermal basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), respectively, as well as the melanocytic malignancy, malignant melanoma (MM). Recently identified alterations in the function of specific genes in these cancers provide new potential therapeutic targets. These alterations affect conserved regulators of cellular proliferation and viability, including the Sonic Hedgehog, Ras/Raf, ARF/p53, p16(INK4A)/CDK4/Rb and NF-kappaB pathways. New modalities designed to target these specific proteins may represent promising approaches to therapy of human skin cancers.

  18. A Phase I/II Study of Combination Neoadjuvant Hormone Therapy and Weekly OGX-011 Prior to Radical to Prostatectomy in Patients With Localized Prostate Cancer

    Science.gov (United States)

    2005-08-01

    pathologic conditions including Alzheimer’s [7] and nephrotoxic injury [8]. Clusterin levels increase dramatically during castration- induced ...CHATELAIN G, NORTH S, BRUN G: Stress- induced transcription of the clusterin/apoJ gene. Biochemical Journal. (1997) 328(1): 45-50. 17. HUMPHREYS DT...apoptosis in rat prostate epithelial cells [9], in androgen dependent Shionogi tumors [10], and human prostate cancer CRW22 [11] and PC82 [12] xenografts. In

  19. Study of Combination Neoadjuvant Hormone Therapy and Weekly OGX-011 (Clusterin Antisense Oligonulceotide) Prior to Radical Prostatectomy in Patients with Localized Prostate Cancer. Phase 1 and 2

    Science.gov (United States)

    2007-08-01

    castration- induced apoptosis in rat prostate epithelial cells [9], in androgen dependent Shionogi tumors [10], and human prostate cancer CRW22 [11... Biochemical Sciences. (2000) 25(3): 95-8. 16. MICHEL D, CHATELAIN G, NORTH S, BRUN G: Stress- induced transcription of the clusterin/apoJ gene...carcinoma [6], and with various pathologic conditions including Alzheimer’s [7] and nephrotoxic injury [8]. Clusterin levels increase dramatically during

  20. The Implications of Cancer Stem Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Wenjing Jiang

    2012-12-01

    Full Text Available Surgery, radiotherapy and chemotherapy are universally recognized as the most effective anti-cancer therapies. Despite significant advances directed towards elucidating molecular mechanisms and developing clinical trials, cancer still remains a major public health issue. Recent studies have showed that cancer stem cells (CSCs, a small subpopulation of tumor cells, can generate bulk populations of nontumorigenic cancer cell progeny through the self-renewal and differentiation processes. As CSCs are proposed to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors, development of CSC-targeted therapeutic strategies holds new hope for improving survival and quality of life in patients with cancer. Therapeutic innovations will emerge from a better understanding of the biology and environment of CSCs, which, however, are largely unexplored. This review summarizes the characteristics, evidences and development of CSCs, as well as implications and challenges for cancer treatment.

  1. 中西医结合治疗晚期肺癌疗效观察%Combined therapy of traditional Chinese medicine and Western medicine for advanced lung cancer

    Institute of Scientific and Technical Information of China (English)

    刘占祥; 李艳丽; 韦安猛

    2009-01-01

    目的 观察中西医结合治疗晚期肺癌疗效.方法 将确诊的65例晚期肺癌患者按随机数字表法分为治疗组33例,对照组32例.对照组非小细胞肺癌采用CAP(环磷酰胺+阿霉素+顺铂)方案,小细胞肺癌采用EP(足叶乙苷+顺铂)方案治疗,4周重复1次,3~4次为1个疗程.治疗组在上述治疗的同时给予中药辨证施治,对痰瘀蕴结型采用六君子汤和涤痰汤加减;气阴两虚型采用人参养荣汤加减;阴阳两虚型采用资生丸加减,以上方药每日1剂水煎服.结果 治疗组临床症状明显改善,生活质量提高,明显优于对照组(P<0.05).治疗组治疗后咳嗽痰血、胸痛、气急、纳差好转,稳定率分别为81.8%(27/33)、75.8%(23/33)、69.7%(23/33)、81.8%(27/33)和69.7(25/33),对照组分别为46.9%(15/32)、31.2%(10/32)、31.2%(10/32)、34.4%(11/32)和37.5%(12/32).治疗组平均生存332 d,较对照组145 d长.治疗组治疗后Kamofsky评分稳定或增加23例(69.7%)对照组10例(31.2%),2组比较差异有统计学意义(P<0.05).结论 中药能减少放化疗产生的不良反应,对提高晚期肺癌患者生活质量和延长生存期具有较好效果.%Objective To observe the curative effect of combined therapy of traditional Chinese medicine and western medicine (TCM WM therapy)for advanced lung cancer. Methods Sixty-five patients of advanced lung cancer were randomly divided into therapy group (33 cases) and control group (32 cases). In control group, CAP schedule was used in patients with non small-cell lung cancer and EP schedule was used in patients with small cell lung cancer. A therapeutic period in two groups was four weeks and one course of treatment needed three to four pe-rieds . The therapy group was given differential treatment with herbal medicines. The phlegrm and petechia type was given Liujunzi decoction and Ditan decoction. The Qi and Yin deficiency type was given Renshenyangrong decoc-tion. The Yin and Yang deficiency type was given

  2. [Photodynamic therapy for gastric cancer].

    Science.gov (United States)

    Mimura, S; Narahara, H; Uehara, H; Otani, T; Okuda, S

    1996-01-01

    In this article, we first present our clinical data on PDT for the treatment of gastric cancer and make a comparison between a continuous wave laser and a pulsed laser. The reasons for PDT failure in certain cases are also discussed. In the fifteen years from 1981 to 1995, we have treated a total of 76 gastric cancer lesions (73 cases), which was consist of 69 early gastric cancer lesions (66 cases) and seven advanced gastric cancer lesions (seven cases) by PDT. From 1981 to 1990, we used an argon dye laser (ADL, Models 171-08 and 375-03, Spectra-Physics, Mountain View, Calif., US) as an excitation light source for PDT with HpD (Photofrin I), DHE (Photofrin II) or PHE (freeze-dried Photofrin II). From analysis of the results in terms of the depth of cancer invasion in these 44 lesions (41 cases), the rate of cure for mucosal carcinomas was 57% (13/23), that of submucosal carcinomas was 53% (10/19), and that of carcinomas invading more than the muscularis propria was 0% (0/2). These data can be interpreted to indicate that the ADL laser beam could not penetrate and supply sufficient energy to activate HpD not only in the submoucosal layer but also in the mucosal layer. In 1990, therefore, we investigated an excimer dye laser (EDL, Hamamatsu Photonics, Hamamatsu, Japan), because its pulsed beam with extremely high peak power was expected to be more efficient at exciting HpD than continuous wave lasers such as ADL and high frequency pulsed lasers such as cooper vapor dye laser (Cu VDL). From 1990 to 1995, twenty-seven early gastric cancer lesions (27 cases) and five advanced gastric cancer lesions (five cases) were treated by PDT with EDL and PHE. Of these 32 lesions, the rate of cure for mucosal carcinomas was 100% (15/15), that of submucosal carcinomas was 75% (9/12), and that of carcinomas invading more than the muscularis propria was 20% (1/5). For the purpose of determining how much energy was required for a complete cure in early gastric cancer, and to compare

  3. Drug therapy for hereditary cancers

    Directory of Open Access Journals (Sweden)

    Imyanitov Evgeny N

    2011-08-01

    Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.

  4. Postmenopausal hormone therapy and the risk of breast cancer: a contrary thought.

    Science.gov (United States)

    Speroff, Leon

    2008-01-01

    The most important unanswered question regarding postmenopausal hormone therapy and the risk of breast cancer is whether hormone therapy initiates the growth of new breast cancers or whether the epidemiologic data reflect a hormonal impact on preexisting tumors. In this perspective I review the evidence favoring hormonal effects on preexisting tumors and suggest that exposure to combined estrogen and progestin is beneficial, causing greater differentiation and earlier detection of breast cancers.

  5. Cancer therapy leading to state of cancer metabolism depression for efficient operation of small dosage cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Ponizovskiy MR

    2015-04-01

    Full Text Available “Prolonged medical starvation” as the method of cancer therapy was borrowed from folk healers Omelchenko A and Breuss R. Author was convinced in efficiency of this method of cancer treatment via examination of cured patients and on own experience. The mechanism of this method of cancer therapy operates via Warburg effect targeting that promotes efficient cancer treatment with small cytotoxic drugs. Just it was described the mechanism of Warburg effect as well as mechanism transmutation of mitochondrial function in cancer metabolism which are exhibited in connection with operation of described method cancer therapy. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission which occur sometimes as result of treatment with great dosage of cytotoxic drugs. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The significance of this work that it was substantiated the mechanism operation of combination “Prolonged medical starvation” with small dosages cytotoxic drugs of cancer treatment, which mechanism leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs in cancer therapy. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments.

  6. Breast cancer stem-like cells and breast cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Niansong Qian; Nobuko Kawaguchi-Sakita; Masakazu Toi

    2010-01-01

    @@ Until the early 1990s, human cancers were considered a morphologically heterogeneous population of cells. In 1997, Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone was organized as a hierarchy; this was subsequently denoted as cancer stem like cells (CSCs). CSCs are cancer cells that possess characteristics associated with normal stem cells and have the specific ability to give rise to all cell types found in a particular cancer. One reason for the failure of traditional anti tumor therapies might be their inability to eradicate CSCs. Therefore, therapies must identify and destroy CSCs in both primary and metastatic tumors.

  7. The Clinical and Cost Effectiveness of Aflibercept in Combination with Irinotecan and Fluorouracil-Based Therapy (FOLFIRI) for the Treatment of Metastatic Colorectal Cancer Which has Progressed Following Prior Oxaliplatin-Based Chemotherapy: a Critique of the Evidence.

    Science.gov (United States)

    Wade, Ros; Duarte, Ana; Simmonds, Mark; Rodriguez-Lopez, Rocio; Duffy, Steven; Woolacott, Nerys; Spackman, Eldon

    2015-05-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of aflibercept (Sanofi) to submit clinical and cost-effectiveness evidence for aflibercept in combination with irinotecan and fluorouracil-based therapy [irinotecan/5-fluorouracil/folinic acid (FOLFIRI)] for the treatment of metastatic colorectal cancer which has progressed following prior oxaliplatin-based chemotherapy, as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA307 issued in March 2014. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The clinical effectiveness data were derived from one good-quality double-blind randomised controlled trial (RCT), the VELOUR trial, which compared aflibercept plus FOLFIRI with placebo plus FOLFIRI. This RCT found a small but statistically significant increase in overall survival (OS); the difference in median OS was 1.44 months (13.5 months in the aflibercept group and 12.06 months in the placebo group). There was also a statistically significant increase in progression-free survival (PFS) with aflibercept; the difference in median PFS was 2.23 months (6.9 months in the aflibercept group and 4.67 months in the placebo group). However, grade 3-4 adverse events were more frequent in the aflibercept group than the placebo group: 83.5% compared with 62.5%. Treatment-emergent adverse events led to permanent discontinuation of treatment in 26.8% of patients in the aflibercept group and 12.1% of patients in the placebo group. The manufacturer's submission included an estimation of mean OS benefit based on extrapolation

  8. Photodynamic therapy for lung cancer and malignant pleural mesothelioma.

    Science.gov (United States)

    Simone, Charles B; Cengel, Keith A

    2014-12-01

    Photodynamic therapy (PDT) is a form of non-ionizing radiation therapy that uses a drug, called a photosensitizer, combined with light to produce singlet oxygen ((1)O2) that can exert anti-cancer activity through apoptotic, necrotic, or autophagic tumor cell death. PDT is increasingly being used to treat thoracic malignancies. For early-stage non-small cell lung cancer (NSCLC), PDT is primarily employed as an endobronchial therapy to definitively treat endobronchial or roentgenographically occult tumors. Similarly, patients with multiple primary lung cancers may be definitively treated with PDT. For advanced or metastatic NSCLC and small cell lung cancer (SCLC), PDT is primarily employed to palliate symptoms from obstructing endobronchial lesions causing airway compromise or hemoptysis. PDT can be used in advanced NSCLC to attempt to increase operability or to reduce the extent of operation intervention required, and selectively to treat pleural dissemination intraoperatively following macroscopically complete surgical resection. Intraoperative PDT can be safely combined with macroscopically complete surgical resection and other treatment modalities for malignant pleural mesothelioma (MPM) to improve local control and prolong survival. This report reviews the mechanism of and rationale for using PDT to treat thoracic malignancies, details prospective and major retrospectives studies of PDT to treat NSCLC, SCLC, and MPM, and describes improvements in and future roles and directions of PDT.

  9. Cancer therapy and cardiotoxicity: The need of serial Doppler echocardiography

    Directory of Open Access Journals (Sweden)

    Pardo Moira

    2007-01-01

    Full Text Available Abstract Cancer therapy has shown terrific progress leading to important reduction of morbidity and mortality of several kinds of cancer. The therapeutic management of oncologic patients includes combinations of drugs, radiation therapy and surgery. Many of these therapies produce adverse cardiovascular complications which may negatively affect both the quality of life and the prognosis. For several years the most common noninvasive method of monitoring cardiotoxicity has been represented by radionuclide ventriculography while other tests as effort EKG and stress myocardial perfusion imaging may detect ischemic complications, and 24-hour Holter monitoring unmask suspected arrhythmias. Also biomarkers such as troponine I and T and B-type natriuretic peptide may be useful for early detection of cardiotoxicity. Today, the widely used non-invasive method of monitoring cardiotoxicity of cancer therapy is, however, represented by Doppler-echocardiography which allows to identify the main forms of cardiac complications of cancer therapy: left ventricular (systolic and diastolic dysfunction, valve heart disease, pericarditis and pericardial effusion, carotid artery lesions. Advanced ultrasound tools, as Integrated Backscatter and Tissue Doppler, but also simple ultrasound detection of "lung comet" on the anterior and lateral chest can be helpful for early, subclinical diagnosis of cardiac involvement. Serial Doppler echocardiographic evaluation has to be encouraged in the oncologic patients, before, during and even late after therapy completion. This is crucial when using anthracyclines, which have early but, most importantly, late, cumulative cardiac toxicity. The echocardiographic monitoring appears even indispensable after radiation therapy, whose detrimental effects may appear several years after the end of irradiation.

  10. An overview of gene therapy in head and neck cancer

    OpenAIRE

    2013-01-01

    Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction...

  11. Photothermal ablation therapy for cancer based on metal nanostructures

    Institute of Scientific and Technical Information of China (English)

    ROZANOVA; Nadejda

    2009-01-01

    Besides conventional surgery, radiation therapy, and chemotherapy, which all tend to have side-effects and damage normal tissues, new medical strategies, such as photothermal sensitization and photo-thermal ablation therapy (PTA) with near-IR laser light, have been explored for treating cancer. Much of the current excitement surrounding nanoscience is directly connected to the promise of new nanotechnology for cancer diagnosis and therapy. The basic principle behind PTA is that heat generated from light can be used to destroy cancer cells. Strong optical absorption and high efficiency of photothermal conversion at the cancer sites are critical to the success of PTA. Because of their unique optical properties, e.g., strong surface plasmon resonance (SPR) absorption, noble metal nanomaterials, such as gold and silver, have been found to significantly enhance photothermal conversion for PTA applications. Substantial effort has been made to develop metal nanostructures with optimal structural and photothermal properties. Ideal metal nanostructures should have strong and tunable SPR, be easy to deliver, have low toxicity, and be convenient for bioconjugation for actively targeting specific cancer cells. This review would highlight some gold nanostructures with various shapes and properties, including nanoparticles (NPs), nanorods (NRs), nanoshells, nanocages, and hollow nanospheres, which have been studied for PTA applications. Among these structures, hollow gold nanospheres (HGNs) exhibit arguably the best combined properties because of their small size (30―50 nm), spherical shape, and strong, narrow, and tunable SPR absorption.

  12. Photothermal ablation therapy for cancer based on metal nanostructures

    Institute of Scientific and Technical Information of China (English)

    ROZANOVA Nadejda; ZHANG JinZhong

    2009-01-01

    Besides conventional surgery, radiation therapy, and chemotherapy, which all tend to have side-effects and damage normal tissues, new medical strategies, such as photothermal sensitization and photothermal ablation therapy (PTA) with near-IR laser light, have been explored for treating cancer. Much of the current excitement surrounding nanoscience is directly connected to the promise of new nanotechnology for cancer diagnosis and therapy. The basic principle behind PTA is that heat generated from light can be used to destroy cancer cells. Strong optical absorption and high efficiency of photothermal conversion at the cancer sites are critical to the success of PTA. Because of their unique optical properties, e.g., strong surface plasmon resonance (SPR) absorption, noble metal nanomaterials, such as gold and silver, have been found to significantly enhance photothermal conversion for PTA applications. Substantial effort has been made to develop metal nanostructures with optimal structural and photothermal properties. Ideal metal nanostructures should have strong and tunable SPR, be easy to deliver, have low toxicity, and be convenient for bioconjugation for actively targeting specific cancer cells. This review would highlight some gold nanostructures with various shapes and properties, including nanoparticles (NPs), nanorods (NRs), nanoshells, nanocages, and hollow nanospheres, which have been studied for PTA applications. Among these structures, hollow gold nanospheres (HGNs) exhibit arguably the best combined properties because of their small size (30-50 nm), spherical shape, and strong, narrow, and tunable SPR absorption.

  13. [Systemic therapy for colorectal cancer].

    Science.gov (United States)

    Pestalozzi, B C; Jäger, D; Knuth, A

    2005-06-01

    Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to the traditional 5-fluorouracil, newer anticancer drugs are available including irinotecan and oxaliplatin. Monoclonal antibodies like bevacizumab and cetuximab have been integrated into modern treatment regimens. Based on randomized clinical trials we can formulate rational treatment strategies as outlined in this article.

  14. Apoptosis : Target of cancer therapy

    NARCIS (Netherlands)

    Ferreira, CG; Epping, M; Kruyt, FAE; Giaccone, G

    2002-01-01

    Recent knowledge on apoptosis has made it possible to devise novel approaches, which exploit this process to treat cancer. In this review, we discuss in detail approaches to induce tumor cell apoptosis, their mechanism of action, stage of development, and possible drawbacks. Finally, the obstacles y

  15. Targeted Therapies for Kidney Cancer

    Science.gov (United States)

    ... The most common side effects seen with this drug include fatigue, rash, diarrhea, increases in blood pressure, and redness, pain, swelling, ... other targets that help cancer cells grow. This drug is taken as a ... effects are nausea, diarrhea, changes in skin or hair color, mouth sores, ...

  16. Reovirus: viral therapy for cancer 'as nature intended'.

    Science.gov (United States)

    Comins, C; Heinemann, L; Harrington, K; Melcher, A; De Bono, J; Pandha, H

    2008-09-01

    Oncolytic viruses are tumour selective and able to lyse cancer cells after infection. Reovirus is an example of a wild-type oncolytic virus and is currently being investigated as a potential novel therapy for cancer. This overview gives a brief description of what is known about reovirus biology and summarises the preclinical data related to its oncolytic ability. The completed and ongoing clinical trials involving reovirus, both as a single agent and in combination with chemotherapy and radiotherapy, will be reviewed and their results discussed. Many of these clinical studies are being conducted by centres in the UK.

  17. Development of drug delivery systems for radionuclide therapy using a combination therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, On Hee; Choi, Sun Ju [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2005-07-01

    For the development of new controlled drug delivery systems, the application of combination therapy using angiogenesis inhibitor and tumor static agents has drawn great attention. This approach would be very beneficial for cancer treatment especially when a new drug deliver system utilizing biodegradable polymers is developed. Therefore, the present study for the combination therapy of angiogenesis inhibitor and chemotherapeutic agents was to carry out prior to the development of the novel drug delivery. In present study, the ability of inhibition on cell growth was investigated with treatment of anti-angiogenetic agent and anticancer agent. Thalidomide was used as an antivasculatory agents and Doxorubicine was treated as a chemotherapeutic agent. To demonstrate apoptotic process in in-vitro study, TUNEL assay was carried out. Also, the alteration of p53 level was examined by using western blotting. For the cell lines, NIH:OVCAR3, MKN45, SNU719, C6, L929, T98G, Hep3B and Calu6 were applied. Results showed that Thalidomide inhibited cell growth in tumor cell lines in a dose-dependent manner and Doxorubicin as well. A significant synergistic effect on the apoptotic was noticed in the combination treatment of Thalidomide and Doxorubicin compared to a single treatment of either drug. Therefore, it can be concluded that the mechanism of cytotoxicity was due to the enhancement of apoptosis in early cell death with combination treatment in tumor cell lines.

  18. Chinese Consensus on Combination Therapy of Chronic Hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    In May 2011,editorial boards of Chinese Journal of Experimental and Clinical Infectious Diseases (Electronic Edition),Chinese Journal of Liver Diseases (Electronic Edition) and Infection International (Electronic Edition) organized an expert committee to form an expert consensus on antiviral combination therapy of chronic hepatitis B (CHB).The consensus publication promoted and standardized the combination therapy concept of chronic hepatitis B.Clinical evidence of combination therapy for CHB is incomplete.The concept of combination therapy is gradually extended,from combination of antiviral drugs plus antiviral drugs,to antiviral drugs plus hepatoprotective drugs,and antiviral drugs plus immunomodulatory drugs.Therefore,editorial boards once again asked experts to analyze the new clinical evidence,and form the expert consensus on combination therapy of chronic hepatitis B.The formulation of this consensus is according to the principles of evidence-based medicine.Large number of clinical studies of combination therapy is still in progress.This consensus can not fully answer all the problems encountered in the combination therapy of CHB.With the progress of clinical practice of antiviral therapy,and the accumulation of evidence in combination therapy,the expert committee will update the consensus timely.

  19. Photothermal combined gene therapy achieved by polyethyleneimine-grafted oxidized mesoporous carbon nanospheres.

    Science.gov (United States)

    Meng, Ying; Wang, Shanshan; Li, Chengyi; Qian, Min; Yan, Xueying; Yao, Shuangchao; Peng, Xiyue; Wang, Yi; Huang, Rongqin

    2016-09-01

    Combining controllable photothermal therapy and efficacious gene therapy in a single platform holds great promise in cancer therapy due to the enhanced combined therapeutic effects. Herein, polyethyleneimine-grafted oxidized mesoporous carbon nanospheres (OP) were developed for combined photothermal combined gene therapy in vitro and in vivo. The synthesized OP was characterized to have three dimensional spherical structure with uniformed diameter, ordered mesopores with graphitic domains, high water dispersion with zeta potential of +22 mV, and good biocompatibility. Consequently, OP was exploited as the photothermal convertor with strong NIR absorption and the gene vector via electrostatic interaction, which therefore cannot only deliver the therapeutic gene (pING4) to tumors for gene therapy, but also can eliminate the tumors by photothermal ablation. Moreover, the improved gene therapy accompanied by the NIR photothermally enhanced gene release was also well achieved based on OP. The excellent combined therapeutic effects demonstrated in vitro and in vivo suggested the OP's potential for cancer therapy.

  20. Quantifying and reducing uncertainties in cancer therapy

    Science.gov (United States)

    Barrett, Harrison H.; Alberts, David S.; Woolfenden, James M.; Liu, Zhonglin; Caucci, Luca; Hoppin, John W.

    2015-03-01

    There are two basic sources of uncertainty in cancer chemotherapy: how much of the therapeutic agent reaches the cancer cells, and how effective it is in reducing or controlling the tumor when it gets there. There is also a concern about adverse effects of the therapy drug. Similarly in external-beam radiation therapy or radionuclide therapy, there are two sources of uncertainty: delivery and efficacy of the radiation absorbed dose, and again there is a concern about radiation damage to normal tissues. The therapy operating characteristic (TOC) curve, developed in the context of radiation therapy, is a plot of the probability of tumor control vs. the probability of normal-tissue complications as the overall radiation dose level is varied, e.g. by varying the beam current in external-beam radiotherapy or the total injected activity in radionuclide therapy. The TOC can be applied to chemotherapy with the administered drug dosage as the variable. The area under a TOC curve (AUTOC) can be used as a figure of merit for therapeutic efficacy, analogous to the area under an ROC curve (AUROC), which is a figure of merit for diagnostic efficacy. In radiation therapy AUTOC can be computed for a single patient by using image data along with radiobiological models for tumor response and adverse side effects. In this paper we discuss the potential of using mathematical models of drug delivery and tumor response with imaging data to estimate AUTOC for chemotherapy, again for a single patient. This approach provides a basis for truly personalized therapy and for rigorously assessing and optimizing the therapy regimen for the particular patient. A key role is played by Emission Computed Tomography (PET or SPECT) of radiolabeled chemotherapy drugs.

  1. Recent progress in target therapy in colorectal cancer.

    Science.gov (United States)

    Pasetto, Lara Maria; Bortolami, Alberto; Falci, Cristina; Sinigaglia, Giulietta; Monfardini, Silvio

    2006-01-01

    Monoclonal antibodies are a new class of agents targeting at specific receptors on cancer cells. In addition to having direct cellular effects, antibodies can cany substances, such as radioactive isotopes, toxins and antineoplastic agents, to the targeted cells. Two of them, cetuximab (Erbitux) and bevacizumab (Avastin), seem to have acquired a significant role in the management of patients with radically resected and advanced colorectal carcinoma. Cetuximab plus irinotecan has been approved as second-line therapy in irinotecan-resistant colorectal cancer patients; bevacizumab plus 5FU/LV has resulted in higher response and longer survival than 5FU/LV alone in first line metastatic colorectal cancer; its combination with oxaliplatin has recently doubled results. The superior therapeutic efficacy of these molecular targeting agents over traditional chemotherapy has been shown by the survival benefit achieved by patients with advanced or recurrent cancers. Although the precise molecular mechanism by which these agents produce or enhance an antitumour effect, alone or in combination with anticancer drugs, is unknown, the specific inhibition of target genes critically involved in tumour progression and metastasis is clear. Further studies to determine which patient groups and anticancer drugs are more appropriate for combination therapy with these agents are needed. All the most important data obtained through recent studies are discussed, emphasizing their mechanisms of action, safety profiles and clinical applications.

  2. Polo-like kinase 1 as target for cancer therapy

    Directory of Open Access Journals (Sweden)

    Weiß Lily

    2012-12-01

    Full Text Available Abstract Polo-like kinase 1 (Plk1 is an interesting molecule both as a biomarker and as a target for highly specific cancer therapy for several reasons. Firstly, it is over-expressed in many cancers and can serve as a biomarker to monitor treatment efficacy of Plk1 inhibitors. Furthermore, the Plk1 enzyme is expressed only in dividing cells and is a major regulator of the cell cycle. It controls entry into mitosis and regulates the spindle checkpoint. The expression of Plk1 in normal cells is not nearly as strong as that in cancer cells, which makes Plk1 a discriminating tartget for the development of cancer-specific small molecule drugs. RNA interference experiments in vitro and in vivo have indicated that downregulation of Plk1 expression represents an attractive concept for cancer therapy. Over the years, a number of Plk1 inhibitors have been discovered. Many of these inhibitors are substances that compete with ATP for the substrate binding site. The ATP-competitive inhibitor BI 6727 is currently being clinically tested in cancer patients. Another drug in development, poloxin, is the first Polo-box domain inhibitor of Plk1. This compound is a derivative of the natural product, thymoquinone, derived from Nigella sativa. A novel and promising strategy is to synthesize bifunctional inhibitors that combine the high binding affinity of ATP inhibitors with the specificity of competitive inhibitors.

  3. Kundalini yoga as a support therapy for cancer patients

    OpenAIRE

    Kröneck, Mia

    2016-01-01

    This study was designed to describe cancer patient’s experience of kundalini yoga and its effect on their internal coping resources. The intention of this study is to put forward kundalini yoga as a support therapy for cancer patients for improving their wellbeing during active cancer treatment. This is a descriptive study. An academic literature review was conducted for cancer, cancer treatment, internal coping resources and yoga as therapy topics. Four voluntary female cancer patients (...

  4. The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

    Energy Technology Data Exchange (ETDEWEB)

    Ataman, Ozlem U., E-mail: ouataman@hotmail.com [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Sambrook, Sally J. [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Wilks, Chris [Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Lloyd, Andrew [Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom); Taylor, Amanda E. [Yellow Delaney Communications Ltd, Wilmslow, Cheshire (United Kingdom); Wedge, Stephen R. [Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom)

    2012-11-15

    Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that

  5. Cancer therapies in HIV cure research

    DEFF Research Database (Denmark)

    Rasmussen, Thomas A; Anderson, Jenny L; Wightman, Fiona;

    2016-01-01

    PURPOSE OF REVIEW: This article provides an overview of anticancer therapies in various stages of clinical development as potential interventions to target HIV persistence. RECENT FINDINGS: Epigenetic drugs developed for cancer have been investigated in vitro, ex vivo and in clinical trials...... as interventions aimed at reversing HIV latency and depleting the amount of virus that persists on antiretroviral therapy. Treatment with histone deacetylase inhibitors induced HIV expression in patients on antiretroviral therapy but did not reduce the frequency of infected cells. Other interventions that may...... accelerate the decay of latently infected cells, in the presence or absence of latency-reversing therapy, are now being explored. These include apoptosis-promoting agents, nonhistone deacetylase inhibitor compounds to reverse HIV latency and immunotherapy interventions to enhance antiviral immunity...

  6. Risk of Second Cancers According to Radiation Therapy Technique and Modality in Prostate Cancer Survivors

    Energy Technology Data Exchange (ETDEWEB)

    Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Wong, Jeannette; Kleinerman, Ruth; Kim, Clara; Morton, Lindsay [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Bekelman, Justin E. [Department of Radiation Oncology, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2015-02-01

    Purpose: Radiation therapy (RT) techniques for prostate cancer are evolving rapidly, but the impact of these changes on risk of second cancers, which are an uncommon but serious consequence of RT, are uncertain. We conducted a comprehensive assessment of risks of second cancer according to RT technique (>10 MV vs ≤10 MV and 3-dimensional [3D] vs 2D RT) and modality (external beam RT, brachytherapy, and combined modes) in a large cohort of prostate cancer patients. Methods and Materials: The cohort was constructed using the Surveillance Epidemiology and End Results-Medicare database. We included cases of prostate cancer diagnosed in patients 66 to 84 years of age from 1992 to 2004 and followed through 2009. We used Poisson regression analysis to compare rates of second cancer across RT groups with adjustment for age, follow-up, chemotherapy, hormone therapy, and comorbidities. Analyses of second solid cancers were based on the number of 5-year survivors (n=38,733), and analyses of leukemia were based on number of 2-year survivors (n=52,515) to account for the minimum latency period for radiation-related cancer. Results: During an average of 4.4 years' follow-up among 5-year prostate cancer survivors (2DRT = 5.5 years; 3DRT = 3.9 years; and brachytherapy = 2.7 years), 2933 second solid cancers were diagnosed. There were no significant differences in second solid cancer rates overall between 3DRT and 2DRT patients (relative risk [RR] = 1.00, 95% confidence interval [CI]: 0.91-1.09), but second rectal cancer rates were significantly lower after 3DRT (RR = 0.59, 95% CI: 0.40-0.88). Rates of second solid cancers for higher- and lower-energy RT were similar overall (RR = 0.97, 95% CI: 0.89-1.06), as were rates for site-specific cancers. There were significant reductions in colon cancer and leukemia rates in the first decade after brachytherapy compared to those after external beam RT. Conclusions: Advanced treatment planning may have reduced rectal

  7. Targeted Therapy in Nonmelanoma Skin Cancers

    Directory of Open Access Journals (Sweden)

    Giulia Spallone

    2011-05-01

    Full Text Available Nonmelanoma skin cancer (NMSC is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC, representing around 75% of NMSC and Squamous Cell Carcinomas (SCC. The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.

  8. Targeted Therapy in Nonmelanoma Skin Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Spallone, Giulia; Botti, Elisabetta; Costanzo, Antonio, E-mail: antonio.costanzo@uniroma2.it [Department of Dermatology, University of Rome “Tor Vergata”, Via Montpellier 1, 00199, Rome (Italy)

    2011-05-03

    Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.

  9. An overview of gene therapy in head and neck cancer.

    Science.gov (United States)

    Bali, Amit; Bali, Deepika; Sharma, Ashutosh

    2013-07-01

    Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction and expression, mediation of apoptosis and clinical response including pathological complete responses. The objective of this article is to provide an overview of the current available gene therapies for head and neck cancer.

  10. Carfilzomib boosted combination therapy for relapsed multiple myeloma

    Directory of Open Access Journals (Sweden)

    Steiner RE

    2017-02-01

    Full Text Available Raphael E Steiner, Elisabet E Manasanch Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Carfilzomib is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome, the proteolytic core particle within the 26S proteasome, resulting in the accumulation of proteasome substrates and ultimately growth arrest and apoptosis of tumor cells. The development and ultimate approval of this medication by regulatory agencies has been an important step toward improving clinical outcomes in multiple myeloma. Although initially approved as a single agent for the treatment of multiply relapsed and/or refractory myeloma, in the USA, it is now widely used in the early relapse setting in combination with lenalidomide and dexamethasone. Carfilzomib has also been studied in combination with second-generation immunomodulatory drugs, histone deacetylase inhibitors, alkylating agents and other novel medications. In this review article, we will discuss the efficacy, safety, tolerability and quality of life of carfilzomib-based combination therapies, as well as novel agents, for relapsed multiple myeloma. Keywords: multiple myeloma, relapsed and refractory myeloma, carfilzomib, novel drugs, salvage chemotherapy

  11. Prodrug applications for targeted cancer therapy.

    Science.gov (United States)

    Giang, Irene; Boland, Erin L; Poon, Gregory M K

    2014-09-01

    Prodrugs are widely used in the targeted delivery of cytotoxic compounds to cancer cells. To date, targeted prodrugs for cancer therapy have achieved great diversity in terms of target selection, activation chemistry, as well as size and physicochemical nature of the prodrug. Macromolecular prodrugs such as antibody-drug conjugates, targeted polymer-drug conjugates and other conjugates that self-assemble to form liposomal and micellar nanoparticles currently represent a major trend in prodrug development for cancer therapy. In this review, we explore a unified view of cancer-targeted prodrugs and highlight several examples from recombinant technology that exemplify the prodrug concept but are not identified as such. Recombinant "prodrugs" such as engineered anthrax toxin show promise in biological specificity through the conditionally targeting of multiple cellular markers. Conditional targeting is achieved by structural complementation, the spontaneous assembly of engineered inactive subunits or fragments to reconstitute functional activity. These complementing systems can be readily adapted to achieve conditionally bispecific targeting of enzymes that are used to activate low-molecular weight prodrugs. By leveraging strengths from medicinal chemistry, polymer science, and recombinant technology, prodrugs are poised to remain a core component of highly focused and tailored strategies aimed at conditionally attacking complex molecular phenotypes in clinically relevant cancer.

  12. Progress of Photodynamic Therapy in Gastric Cancer

    OpenAIRE

    Seishiro Mimura; Hiroyuki Narahara; Toru Otani; Shigeru Okuda

    1999-01-01

    Progress of photodynamic therapy (PDT) in gastric cancer and the clinical outcome are described in this paper. (1) We included the whole lesion and a 5 mm margin in the field for irradiation. Marking by injection of India-ink showing the irradiation field was performed beforehand. (2) We established the standard light dose to be 90 J/cm2 for an argon dye laser and 60 J/cm2 for a pulse wave laser. (3) The size of cancerous lesion curable by PDT was expanded from 3 cm in diameter, i.e. 7 cm2 in...

  13. CAR T Cell Therapy: A Game Changer in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Hilde Almåsbak

    2016-01-01

    Full Text Available The development of novel targeted therapies with acceptable safety profiles is critical to successful cancer outcomes with better survival rates. Immunotherapy offers promising opportunities with the potential to induce sustained remissions in patients with refractory disease. Recent dramatic clinical responses in trials with gene modified T cells expressing chimeric antigen receptors (CARs in B-cell malignancies have generated great enthusiasm. This therapy might pave the way for a potential paradigm shift in the way we treat refractory or relapsed cancers. CARs are genetically engineered receptors that combine the specific binding domains from a tumor targeting antibody with T cell signaling domains to allow specifically targeted antibody redirected T cell activation. Despite current successes in hematological cancers, we are only in the beginning of exploring the powerful potential of CAR redirected T cells in the control and elimination of resistant, metastatic, or recurrent nonhematological cancers. This review discusses the application of the CAR T cell therapy, its challenges, and strategies for successful clinical and commercial translation.

  14. The use of biofield therapies in cancer care.

    Science.gov (United States)

    Pierce, Beverly

    2007-04-01

    Biofield therapies form a subcategory of the domain of energy therapies, as defined by the National Center for Complementary and Alternative Medicine. Specific biofield therapies addressed in this article include Therapeutic Touch, Healing Touch, Polarity Therapy, Reiki, and Qigong. This article will identify core concepts in biofield therapies, review controlled trials of the use of biofield therapies with patients with cancer, describe the process of biofield therapies implementation in one cancer center, and suggest research to benefit not only patients with cancer but also family members and oncology professionals.

  15. Novel Therapies in Development for Metastatic Colorectal Cancer

    OpenAIRE

    Lee, Michael S.; Kopetz, Scott

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer mortality in the United States. Despite advances in therapy, metastatic CRC remains lethal, and further improvements in therapy are needed. Growing understanding of cancer biology, particularly in growth factor signaling, angiogenesis, and cancer immunology, has translated into many novel therapies under investigation. Patients are increasingly selected for clinical trials rationally on the basis of integral biomarkers. This re...

  16. Hadrontherapy - macrobenefit in cancer therapy?

    Science.gov (United States)

    Habrand, J. L.; Baron, E.; Bourhis, J.; Datchary, J.; Mazal, A.; Meflah, K.

    2012-07-01

    Hadrontherapy is one of the most promising radiotherapeutical innovations that deal with accelerated heavy charged particles, mainly proton and carbon ions. Their salient features include an original dose-distribution, based on the Bragg curve, and in some of them an increased RBE at the range-end. Approximately 100 000 patients have been treated so far in approximately 40 centers worldwide. Outstanding outcomes have been substantiated in rare neoplasms using protons, such as ocular melanomas, skull base sarcomas, and pediatric malignancies, while only promising evidences have emerged using carbons. Assessing their place in more common tumor-sites, such as lung, pancreas, prostate, esophagus remains to be determined, and justifies the expansion of future particle therapy programs.

  17. 盐酸羟考酮联合音乐疗法在中重度癌痛患者中的应用%Application of oxycodone hydrochloride combined with music therapy in patients with moderate to severe cancer pain

    Institute of Scientific and Technical Information of China (English)

    田会斌; 杨常清; 吴大芝; 魏利军

    2015-01-01

    Objective To investigate the effect of oxycodone hydrochloride combined the music therapy for im‐proving pain in the patients with cancer .Methods The patients with moderate to severe cancer pain admitted to our hospital were included in the study and randomly divided into two groups according to the order of admission .The two groups were respectively given different treatment methods .The group A was given oxycodone hydrochloride as the control group and the group B received the therapy of oxycodone hydrochloride combined with the music therapy as the experimental group .The clinical efficacy ,dosage ,KPS score ,QOL score and adverse drug reactions were ana‐lyzed statistically .Results The pain degree after treatment in the two groups was significantly reduced compared with before treatment ,the difference was statistically significant(P0 .05) .Conclusion In clinical treatment of the patients with moderate to severe cancer pain ,oxycodone hydrochloride combined with the music therapy has definite analgesic effect ,easy op‐eration ,few adverse reactions and high security in alleviating cancer pain ,can effectively improve the live quality of patients ,provides a new elective mode for the clinical tumor analgesia and deserves to be clinically promoted and ap‐plied .%目的:探讨盐酸羟考酮联合音乐疗法对改善癌症患者疼痛的疗效。方法将该院肿瘤科收治的中重度癌痛患者纳入研究范围,按入院先后顺序随机分为两组,分别给予不同的治疗方法,A组给予盐酸羟考酮作为对照组,B组给予盐酸羟考酮联合音乐疗法作为试验组,对其临床疗效、用药剂量、功能状态评分、生活质量评分、药物不良反应进行统计学分析。结果两组患者疼痛程度均较治疗前显著减轻,两组比较差异有统计学意义(P<0.05);A组用药剂量大于B组,两组比较差异有统计学意义(P<0.05);两组患者治疗后功能状态评分

  18. Photothermal cancer therapy and imaging based on gold nanorods.

    Science.gov (United States)

    Choi, Won Il; Sahu, Abhishek; Kim, Young Ha; Tae, Giyoong

    2012-02-01

    Gold nanorods (GNRs), which strongly absorb near-infrared (NIR) light, have shown great potential in fields of biomedical application. These include photothermal therapy, molecular imaging, biosensing, and gene delivery, especially for the treatment of diseased tissues such as cancer. These biomedical applications of GNRs arise from their various useful properties; photothermal (nanoheater) properties, efficient large scale synthesis, easy functionalization, and colloidal stability. In addition, GNRs do not decompose and have an enhanced scattering signal and tunable longitudinal plasmon absorption which allow them to be used as a stable contrast agent. Therefore, GNRs are also promising theranostic agents, combining both tumor diagnosis and treatment. In this review, we discuss the recent progress of in vitro and in vivo explorations of the diagnostic and therapeutic applications of GNRs as a component of cancer therapy.

  19. Combination therapy for pain in musculoskeletal diseases

    OpenAIRE

    Andrei Evgenyevich Karateev

    2012-01-01

    When managing patients with locomotor pathology, serious attention is paid to symptomatic therapy aimed at eliminating the unpleasant manifestations of the disease. At the same time, rational analgesia is of the greatest importance. If acute pain should be arrested, parenteral or tableted formulations of fast-acting analgesics are used for days. Longer analgesic therapy especially for clinically relevant inflammation is based on the use of nonsteroidal anti-inflammatory drugs (NSAID) having a...

  20. Combination treatment of human umbilical cord matrix stem cell-based interferon-beta gene therapy and 5-fluorouracil significantly reduces growth of metastatic human breast cancer in SCID mouse lungs.

    Science.gov (United States)

    Rachakatla, Raja Shekar; Pyle, Marla M; Ayuzawa, Rie; Edwards, Sarah M; Marini, Frank C; Weiss, Mark L; Tamura, Masaaki; Troyer, Deryl

    2008-08-01

    Umbilical cord matrix stem (UCMS) cells that were engineered to express interferon-beta (IFN-beta) were transplanted weekly for three weeks into MDA 231 breast cancer xenografts bearing SCID mice in combination with 5-fluorouracil (5-FU). The UCMS cells were found within lung tumors but not in other tissues. Although both treatments significantly reduced MDA 231 tumor area in the SCID mouse lungs, the combined treatment resulted in a greater reduction in tumor area than by either treatment used alone. These results indicate that a combination treatment of UCMS-IFN-beta cells and 5-FU is a potentially effective therapeutic procedure for breast cancer.

  1. Harnessing Endogenous Systems for Cancer Therapy

    DEFF Research Database (Denmark)

    Klauber, Thomas Christopher Bogh

    In the recent decade, two strategies in particular have attracted attention due to the prospect of significantly improving cancer treatment: Gene silencing therapy and immunotherapy. Both strategies work by manipulating endogenous mechanisms and theoretically promise very strong effect...... immunotherapy is starting to produce positive results in the clinic. A major target in cancer immunotherapy is the immunosuppressive tumor microenvironment generated directly or indirectly by the tumor. Tumor tissues have been shown to be heavily infiltrated by macrophages and DCs but due...... immunotherapy (Project II). Transfer into the clinic of therapies based on gene silencing by siRNA delivered by synthetic vectors has yet to happen. A major reason is the lack of efficiency in the delivery process, partly due to insufficient understanding of cellular uptake and processing of the si...

  2. Adenoviral gene therapy in gastric cancer: A review

    Institute of Scientific and Technical Information of China (English)

    Nima Khalighinejad; Hesammodin Hariri; Omid Behnamfar; Arash Yousefi; Amir Momeni

    2008-01-01

    Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most common cause of death in cancer related deaths. Gastric cancer like almost all other cancers has a molecular genetic basis which relies on disruption in normal cellular regulatory mechanisms regarding cell growth, apoptosis and cell division. Thus novel therapeutic approaches such as gene therapy promise to become the alternative choice of treatment in gastric cancer. In gene therapy, suicide genes, tumor suppressor genes and anti-angiogenesis genes among many others are introduced to cancer cells via vectors.Some of the vectors widely used in gene therapy are Adenoviral vectors. This review provides an update of the new developments in adenoviral cancer gene therapy including strategies for inducing apoptosis, inhibiting metastasis and targeting the cancer cells.

  3. Immune-Mediated Therapies for Liver Cancer

    OpenAIRE

    Aravalli, Rajagopal N; Steer, Clifford J.

    2017-01-01

    In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion ...

  4. A Variable Energy CW Compact Accelerator for Ion Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Johnstone, Carol J. [Fermilab; Taylor, J. [Huddersfield U.; Edgecock, R. [Huddersfield U.; Schulte, R. [Loma Linda U.

    2016-03-10

    Cancer is the second-largest cause of death in the U.S. and approximately two-thirds of all cancer patients will receive radiation therapy with the majority of the radiation treatments performed using x-rays produced by electron linacs. Charged particle beam radiation therapy, both protons and light ions, however, offers advantageous physical-dose distributions over conventional photon radiotherapy, and, for particles heavier than protons, a significant biological advantage. Despite recognition of potential advantages, there is almost no research activity in this field in the U.S. due to the lack of clinical accelerator facilities offering light ion therapy in the States. In January, 2013, a joint DOE/NCI workshop was convened to address the challenges of light ion therapy [1], inviting more than 60 experts from diverse fields related to radiation therapy. This paper reports on the conclusions of the workshop, then translates the clinical requirements into accelerat or and beam-delivery technical specifications. A comparison of available or feasible accelerator technologies is compared, including a new concept for a compact, CW, and variable energy light ion accelerator currently under development. This new light ion accelerator is based on advances in nonscaling Fixed-Field Alternating gradient (FFAG) accelerator design. The new design concepts combine isochronous orbits with long (up to 4m) straight sections in a compact racetrack format allowing inner circulating orbits to be energy selected for low-loss, CW extraction, effectively eliminating the high-loss energy degrader in conventional CW cyclotron designs.

  5. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

    Science.gov (United States)

    Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

    2015-12-01

    The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events.

  6. Employment of Salmonella in Cancer Gene Therapy.

    Science.gov (United States)

    Lee, Che-Hsin

    2016-01-01

    One of the primary limitations of cancer gene therapy is lack of selectivity of the therapeutic gene to tumor cells. Current efforts are focused on discovering and developing tumor-targeting vectors that selectively target only cancer cells but spare normal cells to improve the therapeutic index. The use of preferentially tumor-targeting bacteria as vectors is one of the innovative approaches for the treatment of cancer. This is based on the observation that some obligate or facultative-anaerobic bacteria are capable of multiplying selectively in tumors and inhibiting their growth. In this study, we exploited attenuated Salmonella as a tumoricidal agent and a vector to deliver genes for tumor-targeted gene therapy. Attenuated Salmonella, carrying a eukaryotic expression plasmid encoding an anti-angiogenic gene, was used to evaluate its' ability for tumor targeting and gene delivery in murine tumor models. We also investigated the use of a polymer to modify or shield Salmonella from the pre-existing immune response in the host in order to improve gene delivery to the tumor. These results suggest that tumor-targeted gene therapy using Salmonella carrying a therapeutic gene, which exerts tumoricidal and anti-angiogenic activities, represents a promising strategy for the treatment of tumors.

  7. Molecular targeted treatment and radiation therapy for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marquardt, Friederike; Roedel, Franz; Capalbo, Gianni; Weiss, Christian; Roedel, Claus [Dept. of Radiation Therapy, Univ. of Frankfurt/Main (Germany)

    2009-06-15

    Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations. Conclusion: longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches. (orig.)

  8. Epigallocatechin Gallate Nanodelivery Systems for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Andreia Granja

    2016-05-01

    Full Text Available Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (−-Epigallocatechin-3-gallate (EGCG is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG’s properties and potentiate its anti-tumoral activity.

  9. Combination antifungal therapy: a critical review of the evidence.

    Science.gov (United States)

    Ostrosky-Zeichner, L

    2008-05-01

    Invasive fungal infections have extremely high rates of morbidity and mortality, particularly in immunocompromised hosts. Combination antifungal therapy is conceptually attractive as a life-saving measure. However, in-vitro and in-vivo evidence is often conflicting and clinical trials in this area are limited. Most clinical studies show similar outcomes for combination antifungal therapy when compared to monotherapy, although secondary endpoints and sub-analyses often show advantages for the combinations in endpoints such as culture sterilisation. The logistics of large clinical trials of combination therapy are highly complex. Combination of antifungals with immune modulators is an exciting new research area. Until more data are available, clinicians should approach combination antifungal therapy with caution.

  10. Combination therapy for erectile dysfunction: an update review

    Institute of Scientific and Technical Information of China (English)

    Rohit R Dhir; Hao-Cheng Lin; Steven E Canfield; Run Wang

    2011-01-01

    The introduction of oral phosphodiesterase-5 inhibitors (PDE5ls) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE5ls are currently first-line monotherapy for erectile dysfunction (ED). However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE5I monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE5I therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE5I plus vacuum erectile device (VED), intraurethral medication, intracavernosal injection (ICI), androgen supplement, a-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.

  11. Targeting hypoxic response for cancer therapy

    Science.gov (United States)

    Paolicchi, Elisa; Gemignani, Federica; Krstic-Demonacos, Marija; Dedhar, Shoukat; Mutti, Luciano; Landi, Stefano

    2016-01-01

    Hypoxic tumor microenvironment (HTM) is considered to promote metabolic changes, oncogene activation and epithelial mesenchymal transition, and resistance to chemo- and radio-therapy, all of which are hallmarks of aggressive tumor behavior. Cancer cells within the HTM acquire phenotypic properties that allow them to overcome the lack of energy and nutrients supply within this niche. These phenotypic properties include activation of genes regulating glycolysis, glucose transport, acidosis regulators, angiogenesis, all of which are orchestrated through the activation of the transcription factor, HIF1A, which is an independent marker of poor prognosis. Moreover, during the adaptation to a HTM cancer cells undergo deep changes in mitochondrial functions such as “Warburg effect” and the “reverse Warburg effect”. This review aims to provide an overview of the characteristics of the HTM, with particular focus on novel therapeutic strategies currently in clinical trials, targeting the adaptive response to hypoxia of cancer cells. PMID:26859576

  12. “Smart”nanomaterials for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    LE; GUYADER; Laurent

    2010-01-01

    Recent development in nanotechnology has provided new tools for cancer therapy and diagnostics.Because of their small size,nanoscale devices readily interact with biomolecules both on the cell surface and inside the cell.Nanomaterials,such as fullerenes and their derivatives,are effective in terms of interactions with the immune system and have great potential as anticancer drugs.Comparatively,other nanomaterials are able to load active drugs to cancer cells by selectively using the unique tumor environment,such as their enhanced permeability,retention effect and the specific acidic microenvironment.Multifunctional and multiplexed nanoparticles,as the next generation of nanoparticles,are now being extensively investigated and are promising tools to achieve personalized and tailored cancer treatments.

  13. Digital pathology in personalized cancer therapy

    Directory of Open Access Journals (Sweden)

    Marcial Garcia Rojo

    2012-01-01

    Full Text Available The development of small molecule inhibitors of growth factor receptors, and the discovery of somatic mutations of the thyrosine kinase domain, have resulted in new paradigms for cancer therapy. Digital microscopy is an important tool for surgical pathologists. The achievements in the digital pathology field have modified the workflow of pathomorphology labs, enhanced the pathologist’s role in diagnostics, and increased their contribution to personalized targeted medicine. Digital image analysis is now available in a variety of platforms to improve quantification performance of diagnostic pathology. We here describe the state of digital microscopy as it applies to the field of quantitative immunohistochemistry of biomarkers related to the clinical personalized targeted therapy of breast cancer, non-small lung cancer and colorectal cancer: HER-2, EGFR, KRAS and BRAF genes. The information is derived from the experience of the authors and a review of the literature. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 570–578

  14. Bladder cancer: molecular determinants of personalized therapy.

    Science.gov (United States)

    Lopez-Beltran, Antonio; Santoni, Matteo; Massari, Francesco; Ciccarese, Chiara; Tortora, Giampaolo; Cheng, Liang; Moch, Holger; Scarpelli, Marina; Reymundo, Carlos; Montironi, Rodolfo

    2015-01-01

    Several molecular and genetic studies have provided new perspectives on the histologic classification of bladder tumors. Recent developments in the field of molecular mutational pathway analyses based on next generation sequencing technology together with classic data derived from the description of mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, mutations on TP53 gene, and cDNA technology profiling data gives support to a differentiated taxonomy of bladder cancer. All these changes are behind the use of non-traditional approach to therapy of bladder cancer patients and are ready to change our daily practice of uro-oncology. The observed correlation of some molecular alterations with tumor behavior and the identification of their targets at cellular level might support the use of molecular changes together with morphological data to develop new clinical and biological strategies to manage patients with urothelial cancer. The current review provides comprehensive data to support personalized therapy for bladder cancer based on an integrated approach including pathologic and clinical features and molecular biology.

  15. Neoadjuvant Therapy in Differentiated Thyroid Cancer

    Science.gov (United States)

    Le, Valerie H.; Camille, Nadia; Miles, Brett A.; Teng, Marita S.; Genden, Eric M.; Misiukiewicz, Krzysztof J.

    2016-01-01

    Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC.

  16. Neoadjuvant Therapy in Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Rajan P. Dang

    2016-01-01

    Full Text Available Objectives. Invasion of differentiated thyroid cancer (DTC into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs hold promise for use in the neoadjuvant setting in DTC.

  17. Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo-Hyun; Nam, Jae-Kyung; Jang, Junho; Lee, Hae-June, E-mail: hjlee@kcch.re.kr; Lee, Yoon-Jin, E-mail: yjlee8@kcch.re.kr

    2015-06-26

    Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm{sup 3} increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versus radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. • Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors.

  18. Rationale for combination therapy as initial treatment for hypertension.

    Science.gov (United States)

    Giles, Thomas D

    2003-01-01

    Recent hypertension guidelines recommend initiating antihypertensive therapy with a combination of two or more agents in patients whose blood pressure exceeds their appropriate blood pressure goal by 20/10 mm Hg. This recommendation is based on the knowledge that the majority of patients with blood pressures of this magnitude will not achieve sufficient blood pressure reduction with monotherapy. Further, compared with high-dose monotherapy, combination therapy is often associated with fewer adverse effects and, for this reason, may improve patient adherence. Bringing patients to blood pressure goal quickly is likely to improve clinical outcomes. This article discusses the rationale for using combination antihypertensive therapy as initial therapy for high blood pressure in selected patients and reviews data from a study of 364 high-risk patients with Stage 2 hypertension in which a fixed-dose combination product (amlodipine besylate/benazepril HCl) proved more successful as initial therapy than high-dose monotherapy (amlodipine besylate) in reducing blood pressure.

  19. Facile preparation of hybrid core-shell nanorods for photothermal and radiation combined therapy

    Science.gov (United States)

    Deng, Yaoyao; Li, Erdong; Cheng, Xiaju; Zhu, Jing; Lu, Shuanglong; Ge, Cuicui; Gu, Hongwei; Pan, Yue

    2016-02-01

    The hybrid platinum@iron oxide core-shell nanorods with high biocompatibility were synthesized and applied for combined therapy. These hybrid nanorods exhibit a good photothermal effect on cancer cells upon irradiation with a NIR laser. Furthermore, due to the presence of a high atomic number element (platinum core), the hybrid nanorods show a synergistic effect between photothermal and radiation therapy. Therefore, the as-prepared core-shell nanorods could play an important role in facilitating synergistic therapy between photothermal and radiation therapy to achieve better therapeutic efficacy.The hybrid platinum@iron oxide core-shell nanorods with high biocompatibility were synthesized and applied for combined therapy. These hybrid nanorods exhibit a good photothermal effect on cancer cells upon irradiation with a NIR laser. Furthermore, due to the presence of a high atomic number element (platinum core), the hybrid nanorods show a synergistic effect between photothermal and radiation therapy. Therefore, the as-prepared core-shell nanorods could play an important role in facilitating synergistic therapy between photothermal and radiation therapy to achieve better therapeutic efficacy. Electronic supplementary information (ESI) available: Details of general experimental procedures. See DOI: 10.1039/c5nr09102k

  20. Role of receptor tyrosine kinases in gastric cancer: New targets for a selective therapy

    Institute of Scientific and Technical Information of China (English)

    JC Becker; C Müller-Tidow; H Serve; W Domschke; T Pohle

    2006-01-01

    Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor family participate in several steps of tumor formation including proliferation and metastatic spread. Several known RTKs are upregulated in gastric cancer being prime targets of a tailored therapy. Only preliminary data exist, however, on the use of the currently clinically available drugs such as trastuzumab,cetuximab, bevacizumab, gefitinib, erlotinib, and imatinib in the setting of gastric cancer. Preclinical data suggest a potential benefit of their use, especially in combination with "conventional" cytostatic therapy. This review summarizes the current knowledge about their use in cancer therapy as well as new approaches and drugs to optimize treatment success.

  1. Combination Therapy for Advanced Kaposi Sarcoma

    Science.gov (United States)

    In this clinical trial, adult patients with any form of advanced Kaposi sarcoma will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments.  Patients who respond to this therapy or have stable disease will rec

  2. Hyperbilirubinemia without Transaminitis during Combined Therapy with Daclatasvir and Asunaprevir

    Directory of Open Access Journals (Sweden)

    Hayato Baba

    2016-07-01

    Full Text Available Daclatasvir (DCV and asunaprevir (ASV are direct-acting antivirals (DAAs used in the treatment of chronic hepatitis C virus (HCV infection. Combined therapy with DCV and ASV shows high efficacy and safety even in patients with cirrhosis. We encountered a patient exhibiting severe hyperbilirubinemia during combined therapy, which is an unreported side effect of DCV and ASV. A 78-year-old woman with cirrhosis developed hyperbilirubinemia >10 mg/dl without transaminitis 3 weeks after starting combined therapy. We suspected DAAs-induced liver disorder and discontinued treatment, which resulted in the improvement of hyperbilirubinemia. Caution is required in the use of DAAs for patients with advanced cirrhosis.

  3. Current concepts in combination antibiotic therapy for critically ill patients

    Directory of Open Access Journals (Sweden)

    Armin Ahmed

    2014-01-01

    Full Text Available Widespread emergence of multidrug resistant (MDR bacterial pathogens is a problem of global dimension. MDR infections are difficult to treat and frequently associated with high mortality. More than one antibiotic is commonly used to treat such infections, but scientific evidence does not favor use of combination therapy in most cases. However, there are certain subgroups where combination therapy may be beneficial, e.g. sepsis due to carbapenem-resistant Enterobacteriaceae (CRE, bacteremic pneumococcal pneumonia, and patients with multiple organ failure. Well-designed prospective studies are needed to clearly define the role of combination therapy in these subgroups.

  4. Cancer Epigenetics: New Therapies and New Challenges

    Directory of Open Access Journals (Sweden)

    Eleftheria Hatzimichael

    2013-01-01

    Full Text Available Cancer is nowadays considered to be both a genetic and an epigenetic disease. The most well studied epigenetic modification in humans is DNA methylation; however it becomes increasingly acknowledged that DNA methylation does not work alone, but rather is linked to other modifications, such as histone modifications. Epigenetic abnormalities are reversible and as a result novel therapies that work by reversing epigenetic effects are being increasingly explored. The biggest clinical impact of epigenetic modifying agents in neoplastic disorders thus far has been in haematological malignancies, and the efficacy of DNMT inhibitors and HDAC inhibitors in blood cancers clearly attests to the principle that therapeutic modification of the cancer cell epigenome can produce clinical benefit. This paper will discuss the most well studied epigenetic modifications and how these are linked to cancer, will give a brief overview of the clinical use of epigenetics as biomarkers, and will focus in more detail on epigenetic drugs and their use in solid and blood cancers.

  5. L-Tryptophan depletion bioreactor, a possible cancer therapy

    Directory of Open Access Journals (Sweden)

    Rolf Bambauer

    2015-04-01

    Full Text Available The cancer therapeutic strategies knownto date are not adequate for all cancer patients. Most of them are followed by a high rate of side effects and complications. The L-tryptophan depletion bioreactor is described as a possible new method of cancer therapy. L-tryptophan is an essential amino acid which has been recognized as an important cancer nutrient and its removal can lead to destruction of the tumour. Normal human cells or tumor cells cannot synthesize L-tryptophan and therefore tumor resistance is unlikely to develop. L-tryptophan is also a constituent for different bio-molecules such as Serotonin, Melatonin, and is needed for other synthesis processes in the cell growth. L-tryptophan degrading enzymes with 3 iso-enzymes called tryptophan side chain oxydase (TSO I, II, III were isolated. The 3 iso-enzymes can be differentiated by tryptic digestion. They have different molecular weights with different effectivenesses. All the TSO enzymes have heme that can catalyze essentially similar reactions involving L-tryptophan as a substrate. The most effective TSO is the type TSO III. A column which contained TSO as a bioreactor was integrated in a plasmapheresis unit and tested it in different animals. In sheep and rabbits L-tryptophan depletion in plasma was shown at 95% and 100% rates respectively by a single pass through the bioreactor. The results in immune supprimized rats with tumors were impressive, too. In 20 different tumor cell lines there were different efficacies. Brest cancer and medulloblastoma showed the greatest efficacy of L-tryptophan degrading. The gene technology of TSO production from Pseudomonas is associated with formation of endotoxins. This disadvantage can be prevented by different washing procedures or by using fungal sources for the TSO production. TSO III is developed to treat cancer diseases successfully, and has low side effects. A combination of L-tryptophan depletion with all available cancer therapies is

  6. Particle therapy and treatment of cancer.

    Science.gov (United States)

    Halperin, Edward C

    2006-08-01

    The desire of radiation oncologists and medical physicists to maximise the radiation dose to the tumour while minimising that to healthy tissues has led to attempts to improve the dose distributions and biological effects achievable with photons and electrons. Protons, neutrons, pions, boron-neutron capture therapy, and charged-nuclei therapy (with argon, carbon, helium [alpha particles], neon, nitrogen, and silicon) have been assessed for their physical, biological, and clinical effects. In the 90 years since protons and neutrons were discovered, investigations of particle therapy for cancer have helped to elucidate many fundamental radiobiological ideas, such as linear energy transfer, relative biological effectiveness, oxygen effect, and oxygen enhancement. Particle therapy has contributed to our understanding of medical ethics when neutron therapy became intertwined with the debate over standards of informed consent in radiation experiments in humans during the cold war era. Particle teletherapy and brachytherapy continue to show promise in some clinical situations. In the future, the insights of molecular biology might clarify the ideal particles for clinical situations.

  7. Autophagy in 5-Fluorouracil Therapy in Gastrointestinal Cancer: Trends and Challenges

    OpenAIRE

    Jia-Cheng Tang; Yi-Li Feng; Xiao Liang; Xiu-Jun Cai

    2016-01-01

    Objective: 5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system. Data Sources: All articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-...

  8. New Approaches for Prostate Cancer Combination Therapy

    Science.gov (United States)

    2009-04-01

    ADDRESS. 1. REPORT DATE 01-04-2009 2. REPORT TYPE Final 3. DATES COVERED 20 MAR 2006 - 19 MAR 2009 4. TITLE AND SUBTITLE New Approaches for... ola r Di clo fen ac 20 Di clo fen ac 10 Di clo fen ac 5 Su lin da c S ulf on e 2 00 Su lin da c S ulf on e 1 00 Su lin da c S ulf on e 5 0 Su

  9. Computed Tomography–Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non–Small Cell Lung Cancer: A Phase 1 Clinical Trial

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Li; Zhang, Jian-wen; Lin, Sheng; Luo, Hui-Qun; Wen, Qing-Lian; He, Li-Jia; Shang, Chang-Ling; Ren, Pei-Rong; Yang, Hong-Ru; Pang, Hao-Wen; Yang, Bo; He, Huai-Lin [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Chen, Yue, E-mail: chenyue5523@126.com [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Wu, Jing-Bo, E-mail: wjb6147@163.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China)

    2015-08-01

    Purpose: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non–small cell lung cancer (NSCLC). Methods and Materials: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planning target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. Results: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. Conclusion: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.

  10. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Byeong Mo Kim

    2015-11-01

    Full Text Available Ionizing radiation (IR, such as X-rays and gamma (γ-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.

  11. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy.

    Science.gov (United States)

    Kim, Byeong Mo; Hong, Yunkyung; Lee, Seunghoon; Liu, Pengda; Lim, Ji Hong; Lee, Yong Heon; Lee, Tae Ho; Chang, Kyu Tae; Hong, Yonggeun

    2015-11-10

    Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR.

  12. Prostate Specific Antigen (PSA as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT in Combination with Additional External Beam Radiation Therapy (EBRT for High Risk Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Thorsten H. Ecke

    2016-11-01

    Full Text Available High-dose-rate brachytherapy (HDR-BT with external beam radiation therapy (EBRT is a common treatment option for locally advanced prostate cancer (PCa. Seventy-nine male patients (median age 71 years, range 50 to 79 with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index, Gleason score, D’Amico risk classification for PCa, digital rectal examination (DRE, PSA value after one/three/five year(s follow-up (FU, time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis (p = 0.009, PSA on date of first HDR-BT (p = 0.033, and PSA on date of first follow-up after one year (p = 0.025 have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

  13. Pancreatic cancer: optimizing treatment options, new, and emerging targeted therapies

    Directory of Open Access Journals (Sweden)

    Chiorean EG

    2015-07-01

    Full Text Available Elena Gabriela Chiorean, Andrew L Coveler Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA Abstract: Pancreatic cancer is the fourth leading cause of cancer death in the US and is expected to become the second leading cause of cancer-related deaths in the next decade. Despite 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX and gemcitabine/nab-paclitaxel significantly improving outcomes for metastatic cancer, refractory disease still poses significant challenges. Difficulties with early detection and the inherent chemo- and radio-resistant nature of this malignancy led to attempts to define the sequential biology of pancreatic cancer in order to improve survival outcomes. Pancreatic adenocarcinoma is characterized by several germline or acquired genetic mutations, the most common being KRAS (90%, CDK2NA (90%, TP53 (75%–90%, DPC4/SMAD4 (50%. In addition, the tumor microenvironment, chemoresistant cancer stem cells, and the desmoplastic stroma have been the target of some promising clinical investigations. Among the core pathways reproducibly shown to lead the development and progression of this disease, DNA repair, apoptosis, G1/S cell cycle transition, KRAS, Wnt, Notch, Hedgehog, TGF-beta, and other cell invasion pathways, have been the target of “precision therapeutics”. No single molecularly targeted therapeutic though has been uniformly successful, probably due to the tumor heterogeneity, but biomarker research is evolving and it hopes to select more patients likely to benefit. Recent reports note activity with immunotherapies such as CD40 agonists, CCR2 inhibitors, cancer vaccines, and novel combinations against the immunosuppressive tumor milieu are ongoing. While many obstacles still exist, clearly we are making progress in deciphering the heterogeneity within pancreatic cancers. Integrating conventional and immunological targeting will be the key to effective treatment of

  14. Transcriptionally regulated, prostate-targeted gene therapy for prostate cancer.

    Science.gov (United States)

    Lu, Yi

    2009-07-02

    Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in American males today. Novel and effective treatment such as gene therapy is greatly desired. The early viral based gene therapy uses tissue-nonspecific promoters, which causes unintended toxicity to other normal tissues. In this chapter, we will review the transcriptionally regulated gene therapy strategy for prostate cancer treatment. We will describe the development of transcriptionally regulated prostate cancer gene therapy in the following areas: (1) Comparison of different routes for best viral delivery to the prostate; (2) Study of transcriptionally regulated, prostate-targeted viral vectors: specificity and activity of the transgene under several different prostate-specific promoters were compared in vitro and in vivo; (3) Selection of therapeutic transgenes and strategies for prostate cancer gene therapy (4) Oncolytic virotherapy for prostate cancer. In addition, the current challenges and future directions in this field are also discussed.

  15. Targeted Cancer Therapy Using Engineered Salmonella typhimurium.

    Science.gov (United States)

    Zheng, Jin Hai; Min, Jung-Joon

    2016-09-01

    Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy.

  16. Lipid Metabolism, Apoptosis and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Chunfa Huang

    2015-01-01

    Full Text Available Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

  17. Targeted Cancer Therapy Using Engineered Salmonella typhimurium

    Science.gov (United States)

    Zheng, Jin Hai

    2016-01-01

    Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy. PMID:27689027

  18. Immunotherapy and gene therapy of thyroid cancer.

    Science.gov (United States)

    Schott, M; Scherbaum, W A

    2004-12-01

    Most forms of thyroid cancer have a good prognosis. Some tumours, however, dedifferentiate and may finally develop into highly malignant anaplastic thyroid carcinomas with a low survival time. Due to their dedifferentiation these tumours are inaccessible to classical therapeutic options as radioiodide treatment or thyrotropin-suppression. Radical surgical revision of the tumour masses is the therapy of choice of patients with limited disease stages including patients with medullary thyroid carcinomas. Despite progress in radiation and chemotherapy regimes, many metastatic forms remain, however, incurable by conventional therapies. During the past few years new developments in immunology have revealed increasing information about the molecular basis of tumour-host interactions. The multitude of information resulting from basic science in cellular immunology, together with the availability of biologic reagents in pharmacological amounts, has opened new venues for the development of immunotherapy approaches for patients with different kind of cancers including thyroid malignancies. This review describes some most important developments in cellular immunotherapies e.g. dendritic cells-based protocols and gene therapy. It also provides a brief overview on the role of cytokines and antibodies in the treatment of advanced thyroid malignancies.

  19. Synergistic anti-proliferative and pro-apoptotic activity of combined therapy with bortezomib, a proteasome inhibitor, with anti-epidermal growth factor receptor (EGFR) drugs in human cancer cells.

    Science.gov (United States)

    Cascone, Tina; Morelli, Maria Pia; Morgillo, Floriana; Kim, Woo-Young; Rodolico, Gabriella; Pepe, Stefano; Tortora, Giampaolo; Berrino, Liberato; Lee, Ho-Young; Heymach, John V; Ciardiello, Fortunato

    2008-09-01

    The proteasome plays a pivotal role in the turnover of regulatory transduction proteins induced by activated cell membrane growth factor receptors. The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. Proteasome inhibition may sensitize human cancer cell lines to EGFR inhibitors. We investigated the growth inhibitory and pro-apoptotic effects of the proteasome inhibitor bortezomib in combination with anti-EGFR drugs, such as gefitinib, vandetanib, and cetuximab in EGFR-expressing human cancer cell lines. Bortezomib determined dose-dependent growth inhibition in a nine cancer cell line panel (IC(50) values, range 6-42 nM). A significant synergistic growth inhibitory effect was observed with the combination of bortezomib and each EGFR inhibitor in all cell lines (combination index, CI, range 0.10-0.55), which was accompanied by a significant induction in apoptosis by the combined treatment with bortezomib, cetuximab and vandetanib. In HCT-116 colon cancer and A549 lung adenocarcinoma cells, bortezomib plus EGFR inhibitor treatment induced a more effective inhibition of EGFR-activated down-stream signals, including a marked suppression in activated, phosphorylated Akt (P-Akt). In contrast, overexpression of a constitutively active P-Akt protected A549 cells by cell growth inhibition and apoptosis following treatment with bortezomib and EGFR inhibitors. The combined treatment with bortezomib and EGFR inhibitors has a synergistic growth inhibitory and pro-apoptotic activity in different human cancer cells which possess a functional EGFR-dependent autocrine growth pathway through to a more efficient and sustained inhibition of Akt.

  20. Nanomaterial-based drug delivery carriers for cancer therapy

    CERN Document Server

    Feng, Tao

    2017-01-01

    This brief summarizes different types of organic and inorganic nanomaterials for drug delivery in cancer therapy. It highlights that precisely designed nanomaterials will be the next-generation therapeutic agents for cancer treatment.

  1. Radiation Therapy and You: Support for People with Cancer

    Science.gov (United States)

    ... Terms Blogs and Newsletters Health Communications Publications Reports Radiation Therapy and You: Support for People With Cancer ... Copy This booklet covers: Questions and Answers About Radiation Therapy. Answers common questions, such as what radiation ...

  2. Effect of Combination Therapy on Joint Destruction in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Graudal, N.; Hubeck-Graudal, T.; Tarp, S.

    2014-01-01

    on progression of radiographic joint erosions in patients with rheumatoid arthritis (RA). Methods and Findings: The following combination drug therapies compared versus single DMARD were investigated: Double DMARD: 2 DMARDs (methotrexate, sulfasalazine, leflunomide, injectable gold, cyclosporine, chloroquine...

  3. Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma.

    Science.gov (United States)

    Richter, Joshua; Neparidze, Natalia; Zhang, Lin; Nair, Shiny; Monesmith, Tamara; Sundaram, Ranjini; Miesowicz, Fred; Dhodapkar, Kavita M; Dhodapkar, Madhav V

    2013-01-17

    Natural killer T (iNKT) cells can help mediate immune surveillance against tumors in mice. Prior studies targeting human iNKT cells were limited to therapy of advanced cancer and led to only modest activation of innate immunity. Clinical myeloma is preceded by an asymptomatic precursor phase. Lenalidomide was shown to mediate antigen-specific costimulation of human iNKT cells. We treated 6 patients with asymptomatic myeloma with 3 cycles of combination of α-galactosylceramide-loaded monocyte-derived dendritic cells and low-dose lenalidomide. Therapy was well tolerated and led to reduction in tumor-associated monoclonal immunoglobulin in 3 of 4 patients with measurable disease. Combination therapy led to activation-induced decline in measurable iNKT cells and activation of NK cells with an increase in NKG2D and CD56 expression. Treatment also led to activation of monocytes with an increase in CD16 expression. Each cycle of therapy was associated with induction of eosinophilia as well as an increase in serum soluble IL2 receptor. Clinical responses correlated with pre-existing or treatment-induced antitumor T-cell immunity. These data demonstrate synergistic activation of several innate immune cells by this combination and the capacity to mediate tumor regression. Combination therapies targeting iNKT cells may be of benefit toward prevention of cancer in humans.

  4. Current concepts in combination antibiotic therapy for critically ill patients

    OpenAIRE

    Armin Ahmed; Afzal Azim; Mohan Gurjar; Arvind Kumar Baronia

    2014-01-01

    Widespread emergence of multidrug resistant (MDR) bacterial pathogens is a problem of global dimension. MDR infections are difficult to treat and frequently associated with high mortality. More than one antibiotic is commonly used to treat such infections, but scientific evidence does not favor use of combination therapy in most cases. However, there are certain subgroups where combination therapy may be beneficial, e.g. sepsis due to carbapenem-resistant Enterobacteriaceae (CRE), bacteremic ...

  5. Phase I dose-finding study of S1 in combination with docetaxel and oxaliplatin (DOS) as first-line therapy in patients with advanced gastro-esophageal cancer

    DEFF Research Database (Denmark)

    Weber Vestermark, Lene; Jensen, H. A.; Schoennemann, K. R.

    2015-01-01

    Background: S-1 (Teysuno) was developed to provide more efficacious and safer oral delivery of 5-FU (F) or capecitabine. Recently S-1 in combination with cisplatin (C) was approved in Europe for the treatment of advanced gastro-esophageal cancer (aGEC). Addition of docetaxel (D) to F or CF has...

  6. Carbon materials for drug delivery & cancer therapy

    Directory of Open Access Journals (Sweden)

    Zhuang Liu

    2011-07-01

    Full Text Available Carbon nanotubes and graphene are both low-dimensional sp2 carbon nanomaterials exhibiting many unique physical and chemical properties that are interesting in a wide range of areas including nanomedicine. Since 2004, carbon nanotubes have been extensively explored as drug delivery carriers for the intracellular transport of chemotherapy drugs, proteins, and genes. In vivo cancer treatment with carbon nanotubes has been demonstrated in animal experiments by several different groups. Recently, graphene, another allotrope of carbon, has also shown promise in various biomedical applications. In this article, we will highlight recent research on these two categories of closely related carbon nanomaterials for applications in drug delivery and cancer therapy, and discuss the opportunities and challenges in this rapidly growing field.

  7. Thermohydrogel Containing Melanin for Photothermal Cancer Therapy.

    Science.gov (United States)

    Kim, Miri; Kim, Hyun Soo; Kim, Min Ah; Ryu, Hyanghwa; Jeong, Hwan-Jeong; Lee, Chang-Moon

    2016-12-01

    Melanin is an effective absorber of light and can extend to near infrared (NIR) regions. In this study, a natural melanin is presented as a photothermal therapeutic agent (PTA) because it provides a good photothermal conversion efficiency, shows biodegradability, and does not induce long-term toxicity during retention in vivo. Poloxamer solution containing melanin (Pol-Mel) does not show any precipitation and shows sol-gel transition at body temperature. After irradiation from 808 nm NIR laser at 1.5 W cm(-2) for 3 min, the photothermal conversion efficiency of Pol-Mel is enough to kill cancer cells in vitro and in vivo. The tumor growth of mice bearing CT26 tumors treated with Pol-Mel injection and laser irradiation is suppressed completely without recurrence postirradiation. All these results indicate that Pol-Mel can become an attractive PTA for photothermal cancer therapy.

  8. Advanced strategies in liposomal cancer therapy

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Jensen, Simon Skøde; Jørgensen, Kent

    2005-01-01

    , none of them have yet led to marketed drugs and are still far from achieving this goal. The most advanced and prospective technologies are probably the prodrug strategies where nontoxic drugs are carried and activated specifically in the malignant tissue by overexpressed enzymes. In the second part......Tumor specific drug delivery has become increasingly interesting in cancer therapy, as the use of chemotherapeutics is often limited due to severe side effects. Conventional drug delivery systems have shown low efficiency and a continuous search for more advanced drug delivery principles...... is therefore of great importance. In the first part of this review, we present current strategies in the drug delivery field, focusing on site-specific triggered drug release from liposomes in cancerous tissue. Currently marketed drug delivery systems lack the ability to actively release the carried drug...

  9. Alphavirus vectors for cancer gene therapy (review).

    Science.gov (United States)

    Yamanaka, Ryuya

    2004-04-01

    Alphaviruses have several characteristics that make them attractive as gene therapy vectors such as transient and high-level expression of a heterologous gene. Alphavirus vectors, Semliki Forest virus (SFV), Sindbis virus (SIN) and Venezuelan equine encephalitis virus (VEE) have been developed as gene expression vectors. Alphaviruses are positive-strand RNA viruses that can mediate efficient cytoplasmic gene expression in mammalian cells. The alphavirus RNA replication machinery has been engineered for high level heterologous gene expression. Since an RNA virus vector cannot integrate into chromosomal DNA, concerns about cell transformation are reduced. Alphavirus vectors demonstrate promise for the safe tumor-killing and tumor-specific immune responses. Recombinant alphavirus RNA replicons may facilitate gene therapy of cancer.

  10. Gold Nanoconstructs for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

    Science.gov (United States)

    Coughlin, Andrew James

    Cancer accounts for nearly 1 out of every 4 deaths in the United States, and because conventional treatments are limited by morbidity and off-target toxicities, improvements in cancer management are needed. This thesis further develops nanoparticle-assisted photothermal therapy (NAPT) as a viable treatment option for cancer patients. NAPT enables localized ablation of disease because heat generation only occurs where tissue permissive near-infrared (NIR) light and absorbing nanoparticles are combined, leaving surrounding normal tissue unharmed. Two principle approaches were investigated to improve the specificity of this technique: multimodal imaging and molecular targeting. Multimodal imaging affords the ability to guide NIR laser application for site-specific NAPT and more holistic characterization of disease by combining the advantages of several diagnostic technologies. Towards the goal of image-guided NAPT, gadolinium-conjugated gold-silica nanoshells were engineered and demonstrated to enhance imaging contrast across a range of diagnostic modes, including T1-weighted magnetic resonance imaging, X-Ray, optical coherence tomography, reflective confocal microscopy, and two-photon luminescence in vitro as well as within an animal tumor model. Additionally, the nanoparticle conjugates were shown to effectively convert NIR light to heat for applications in photothermal therapy. Therefore, the broad utility of gadolinium-nanoshells for anatomic localization of tissue lesions, molecular characterization of malignancy, and mediators of ablation was established. Molecular targeting strategies may also improve NAPT by promoting nanoparticle uptake and retention within tumors and enhancing specificity when malignant and normal tissue interdigitate. Here, ephrinA1 protein ligands were conjugated to nanoshell surfaces for particle homing to overexpressed EphA2 receptors on prostate cancer cells. In vitro, successful targeting and subsequent photothermal ablation of

  11. Recent advances of sonodynamic therapy in cancer treatment

    Science.gov (United States)

    Wan, Guo-Yun; Liu, Yang; Chen, Bo-Wei; Liu, Yuan-Yuan; Wang, Yin-Song; Zhang, Ning

    2016-01-01

    Sonodynamic therapy (SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner. In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment.

  12. Application of gold nanoparticles in cancer therapy.

    Science.gov (United States)

    Zhao, Chuan-tong; Liu, Zhen-bao

    2014-06-01

    With their unique physicochemical properties including excellent stability and biocompatibility, large specific surface area, and easy surface modification, gold nanoparticles (AuNPs) can be used as delivery vectors for drugs, genes, proteins, etc. In addition, AuNPs have excellent photothermal effects and radiosensitization characteristics, and therefore can be widely applied in the photothermal therapy and radiotherapy of cancers. This article reviews the construction, cellular uptake, and drug release of AuNPs drug-delivery systems and their applications in the treatment of tumors.

  13. Potential role of tetrandrine in cancer therapy

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-Jen

    2002-01-01

    Tetrandrine, a bisbenylisoquinoline alkaloid isolated from the dried root of Stephenia tetrandra S Moore, exhibits very broad pharmacological actions, including anti-tumor activity. The beneficial effects of tetrandrine on tumor cell cytotoxicity and radiosensitization, multidrug resistance, normal tissue radioprotection, and angiogenesis are most promising and deserve great attention. Tetrandrine has potential either as a tumoricidal agent or as an adjunct to chemotherapy and radiotherapy. To evaluate the potential clinical efficacy of tetrandrine for cancer therapy,more mechanism-based pharmacological, pharmacokinetic, and pharmacodynamic studies are required.

  14. Novel therapies in genitourinary cancer: an update

    Directory of Open Access Journals (Sweden)

    Wu Shenhong

    2008-08-01

    Full Text Available Abstract In recent years, new treatment for renal cell carcinoma (RCC has been a spotlight in the field of cancer therapeutics. With several emerging agents branded as 'targeted therapy' now available, both medical oncologists and urologists are progressively more hopeful for better outcomes. The new remedies may provide patients with improved survival and at the same time less toxicity when compared to traditional cytotoxic agents. This article will center on current and emerging treatment strategies for advanced RCC and other GU malignancies with updates from 2008 annual ASCO meeting.

  15. Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients.

    Science.gov (United States)

    Garland, Sheila N; Johnson, Jillian A; Savard, Josee; Gehrman, Philip; Perlis, Michael; Carlson, Linda; Campbell, Tavis

    2014-01-01

    Individuals with cancer are disproportionately affected by sleep disturbance and insomnia relative to the general population. These problems can be a consequence of the psychological, behavioral, and physical effects of a cancer diagnosis and treatment. Insomnia often persists for years and, when combined with already high levels of cancer-related distress, may place cancer survivors at a higher risk of future physical and mental health problems and poorer quality of life. The recommended first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBT-I), a non-pharmacological treatment that incorporates cognitive and behavior-change techniques and targets dysfunctional attitudes, beliefs, and habits involving sleep. This article presents a comprehensive review of the literature examining the efficacy of CBT-I on sleep and psychological outcomes in cancer patients and survivors. The search revealed 12 studies (four uncontrolled, eight controlled) that evaluated the effects of CBT-I in cancer patients or survivors. Results suggest that CBT-I is associated with statistically and clinically significant improvements in subjective sleep outcomes in patients with cancer. CBT-I may also improve mood, fatigue, and overall quality of life, and can be successfully delivered through a variety of treatment modalities, making it possible to reach a broader range of patients who may not have access to more traditional programs. Future research in this area should focus on the translation of evidence into clinical practice in order to increase awareness and access to effective insomnia treatment in cancer care.

  16. [Indications for and limitations of HpD photodynamic therapy for esophageal cancer and gastric cancer].

    Science.gov (United States)

    Mimura, S; Ichii, M; Imanishi, K; Otani, T; Okuda, S

    1988-04-01

    HpD photodynamic therapy (PDT) was performed on 4 patients with superficial esophageal cancer, 20 patients with 22 early gastric cancer lesions and one patient with advanced gastric cancer. About 50 h before irradiation, 3 mg/kg of HpD or 1.3-2.5 mg/kg of Photofrin II was injected intravenously. The entire lesion including a 5-mm border of normal surrounding mucosa, was irradiated with an argon dye laser at 630nm wavelength with an output of 100-400mW at the tip of the fiber. Complete response (CR) to HpD-PDT was obtained in 2 of 2 mucosal esophageal cancers, and one of 2 submucosal lesions, totalling 3 of 4, and in 13 of 13 mucosal gastric cancers and 7 of 9 submucosal lesions totalling 20 of 22. The depths of cancer involvement were determined endoscopically. In Borrmann 1 lesion with muscularis externa involvement, in spite of two trials with HpD-PDT, only partial response (PR) was obtained. Tumor laser dose had to be more than 90 J/cm2, and in several cases combined hot biopsy with electrodiathermy and/or repeated HpD-PDT was needed to obtain CR. HpD-PDT is indicated for superficial esophageal cancer and depressed and/or assembled protuberant-type of early gastric cancer with poor risk.

  17. Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

    Science.gov (United States)

    Halasa, Salaheldin; Dickinson, Eva

    2014-02-01

    From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

  18. Chimeric antigen receptor (CAR)-directed adoptive immunotherapy: a new era in targeted cancer therapy

    OpenAIRE

    Chen, Yamei; Liu, Delong

    2014-01-01

    As a result of the recent advances in molecular immunology, virology, genetics, and cell processing, chimeric antigen receptor (CAR)-directed cancer therapy has finally arrived for clinical application. CAR-directed adoptive immunotherapy represents a novel form of gene therapy, cellular therapy, and immunotherapy, a combination of three in one. Early phase clinical trial was reported in patients with refractory chronic lymphoid leukemia with 17p deletion. Accompanying the cyto...

  19. Combined aspirin and anticoagulant therapy in patients with atrial fibrillation.

    Science.gov (United States)

    So, Charlotte H; Eckman, Mark H

    2017-01-01

    The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Of 948 patients receiving OAC, 430 (45 %) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49 and 42 % of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27 % had a diagnosis of CAD and 14 % had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn't discontinued. A surprisingly large proportion of patients (22.8 %) had no obvious indication for dual therapy. Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events.

  20. A prospective randomized trial: a comparison of the analgesic effect and toxicity of 153Sm radioisotope treatment in monotherapy and combined therapy including local external beam radiotherapy (EBRT) among metastatic castrate resistance prostate cancer (mCRPC) patients with painful bone metastases.

    Science.gov (United States)

    Baczyk, M; Milecki, P; Pisarek, M; Gut, P; Antczak, A; Hrab, M

    2013-01-01

    Bone metastases in prostate cancer constitute the most frequent cause of systemic failure in treatment, which results in numerous complications and finally leads to patient's death. Pain is one of the first and most important clinical symptoms of bone metastases and can be found among more than 80% of patients. Therefore, the most analgetic effective and simultaneously the least toxic treatment is an important point of therapeutic management in this group of patients. The aim of this prospective clinical trial was a comparison of analgetic effectiveness and toxicity of monotherapy with 153Sm isotope to combined therapy (153Sm + EBRT) among patients diagnosed with multiple painful bone metastases due to CRPC (mCRPC). 177 patients with mCRPC were included into the prospective randomised clinical trial in which 89 patients were assigned to the 153Sm isotope monotherapy, while 88 patients were assigned to the combined therapy including 153Sm isotope therapy and EBRT. All patients were diagnosed (bone scan and X-ray or/and CT or/and MRI) with painful bone metastases (bone pain intensity >= 6 according to VAS classification). The following additional inclusion criteria were established: histologically confirmed adenocarcinoma of prostate, multifocal bone metastases, no prior chemotherapy or palliative radiotherapy to bone. All patients signed informed consent.The combination of the isotope therapy with EBRT was more effective analgetic treatment than isotope therapy alone. The highest pain decline was noticed in the first weeks after treatment termination. In the whole group, a total or partial analgesic effect was observed among 154 (87%) patients while among 23 (13%) patients there was a lack of analgesic effect or even pain intensification. The results of this clinical trial demonstrated that for patients with multiple mCRPC it is recommended to combine the 153Sm isotope therapy with local EBRT because of a greater analgetic effect. It is important to note that

  1. Emerging targeted therapies for castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Vincenzo eAdamo

    2012-05-01

    Full Text Available Until recently, few therapeutic options were available for patients with castration-resistant prostate cancer (CRPC. Since 2010, four new molecules with a demonstrated benefit (sipuleucel-T, cabazitaxel, abiraterone and denosumab have been approved in this setting, and to-date several other agents are under investigation in clinical trials. The purpose of this review is to present an update of targeted therapies for CRPC. Presented data are obtained from literature and congress reports updated until December 2011. Targeted therapies in advanced phases of clinical development include novel hormone-therapeutic, intracellular molecular pathways inhibiting, anti-angiogenic, bone microenvironment targeting and immunotherapeutic agents. Radium-223 and MDV3100 demonstrated a survival advantage in phase III trials and the road for their introduction in clinical practice is rapidly ongoing. Results are also awaited for phase III studies currently underway or planned with new drugs given as monotherapy (TAK-700, cabozantinib, tasquinimod, PROSTVAC-VF, ipilimumab or in combination with docetaxel (custirsen, aflibercept, dasatinib, zibotentan. Optimal timing, right combination and/or sequencing of emerging therapies as well as use of more sensitive biological markers to individualize therapies for CRPC remain challenging and studies to investigate these aspects are needed.

  2. Combining targeted therapy and immune checkpoint inhibitors in the treatment of metastatic melanoma

    Institute of Scientific and Technical Information of China (English)

    Teresa Kim; Rodabe N Amaria; Christine Spencer; Alexandre Reuben; Zachary A Cooper; Jennifer A Wargo

    2014-01-01

    Melanoma is the deadliest form of skin cancer and has an incidence that is rising faster than any other solid tumor. Metastatic melanoma treatment has considerably progressed in the past ifve years with the introduction of targeted therapy (BARF and MEK inhibitors) and immune checkpoint blockade (anti-CTLA4, anti-PD-1, and anti-PD-L1). However, each treatment modality has limitations. Treatment with targeted therapy has been associated with a high response rate, but with short-term responses. Conversely, treatment with immune checkpoint blockade has a lower response rate, but with long-term responses. Targeted therapy affects antitumor immunity, and synergy may exist when targeted therapy is combined with immunotherapy. hTis article presents a brief review of the rationale and evidence for the potential synergy between targeted therapy and immune checkpoint blockade. Challenges and directions for future studies are also proposed.

  3. Combination therapy for carbapenem-resistant Gram-negative bacteria.

    Science.gov (United States)

    Paul, Mical; Carmeli, Yehuda; Durante-Mangoni, Emanuele; Mouton, Johan W; Tacconelli, Evelina; Theuretzbacher, Ursula; Mussini, Cristina; Leibovici, Leonard

    2014-09-01

    Carbapenem-resistant Gram-negative bacteria (CR-GNB) represent an increasing hazard in healthcare settings. A central question concerning the treatment of invasive infections caused by CR-GNB involves the use of combination therapy. Potential advantages of combination therapy include improved efficacy due to synergy, while the disadvantages include advers